November-December 2011

2012-01-19T05:15:00.001-08:00

(1)Acharya A, Hans CP, Koenig SN, Nichols HA, Galindo CL, Garner HR,<br />Merrill WH, Hinton RB and Garg V

(1)Acharya A, Hans CP, Koenig SN, Nichols
HA, Galindo CL, Garner HR, Merrill WH, Hinton RB and Garg V

INHIBITORY ROLE OF Notch1 IN CALCIFIC AORTIC VALVE DISEASE

2011; 6:e27743

Aortic valve calcification is the most common form of valvular heart disease,
but the mechanisms of calcific aortic valve disease (CAVD) are unknown. NOTCH1
mutations are associated with aortic valve malformations and adult-onset
calcification in families with inherited disease. The Notch signaling pathway
is critical for multiple cell differentiation processes, but its role in the
development of CAVD is not well understood. The aim of this study was to
investigate the molecular changes that occur with inhibition of Notch signaling
in the aortic valve. Notch signaling pathway members are expressed in adult
aortic valve cusps, and examination of diseased human aortic valves revealed
decreased expression of NOTCH1 in areas of calcium deposition. To identify
downstream mediators of Notch1, we examined gene expression changes that occur
with chemical inhibition of Notch signaling in rat aortic valve interstitial
cells (AVICs). We found significant downregulation of Sox9 along with several
cartilage-specific genes that were direct targets of the transcription factor,
Sox9. Loss of Sox9 expression has been published to be associated with aortic
valve calcification. Utilizing an in vitro porcine aortic valve calcification
model system, inhibition of Notch activity resulted in accelerated
calcification while stimulation of Notch signaling attenuated the calcific
process. Finally, the addition of Sox9 was able to prevent the calcification of
porcine AVICs that occurs with Notch inhibition. In conclusion, loss of Notch
signaling contributes to aortic valve calcification via a Sox9-dependent mechanism.

Department of Pediatrics, University of Texas Southwestern Medical Center,
Dallas, Texas, United States of America.

10.1371/journal.pone.0027743

http://www.ncbi.nlm.nih.gov/pubmed/22110751

(2)Adamczak R, Pillardy J, Vallat BK and
Meller J

FAST GEOMETRIC CONSENSUS APPROACH FOR PROTEIN MODEL QUALITY ASSESSMENT

2011; 18:1807-1818

Model quality assessment (MQA) is an integral part of protein structure
prediction methods that typically generate multiple candidate models. The
challenge lies in ranking and selecting the best models using a variety of
physical, knowledge-based, and geometric consensus (GC)-based scoring
functions. In particular, 3D-Jury and related GC methods assume that well-predicted
(sub-)structures are more likely to occur frequently in a population of
candidate models, compared to incorrectly folded fragments. While this approach
is very successful in the context of diversified sets of models, identifying
similar substructures is computationally expensive since all pairs of models
need to be superimposed using MaxSub or related heuristics for
structure-to-structure alignment. Here, we consider a fast alternative, in
which structural similarity is assessed using 1D profiles, e.g., consisting of
relative solvent accessibilities and secondary structures of equivalent amino
acid residues in the respective models. We show that the new approach, dubbed
1D-Jury, allows to implicitly compare and rank N models in O(N) time, as opposed
to quadratic complexity of 3D-Jury and related clustering-based methods. In
addition, 1D-Jury avoids computationally expensive 3D superposition of pairs of
models. At the same time, structural similarity scores based on 1D profiles are
shown to correlate strongly with those obtained using MaxSub. In terms of the
ability to select the best models as top candidates 1D-Jury performs on par
with other GC methods. Other potential applications of the new approach,
including fast clustering of large numbers of intermediate structures generated
by folding simulations, are discussed as well.

Department of Environmental Health, University of Cincinnati College of
Medicine, Cincinnati, Ohio 45226, USA.

10.1089/cmb.2010.0170

http://www.ncbi.nlm.nih.gov/pubmed/21244273

(3)Adams RE, Santo JB and Bukowski WM

THE PRESENCE OF a BEST FRIEND BUFFERS THE EFFECTS OF NEGATIVE EXPERIENCES

2011; 47:1786-1791

The goal of the current study was to examine how the presence of a best friend
might serve as protection against the effect of negative experiences on global
self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A
total of 103 English-speaking male (n = 55) and female (n = 48) participants
from Grade 5 (M = 10.27 years) and Grade 6 (M = 11.30 years) completed booklets
about their experiences that occurred 20 min previously and how they felt about
themselves at the moment, and they provided saliva multiple times per day over
the course of 4 consecutive days. Having a best friend present during an
experience significantly buffered the effect of the negativity of the
experience on cortisol and global self-worth. When a best friend was not
present, there was a significant increase in cortisol and a significant
decrease in global self-worth as the negativity of the experience increased.
When a best friend was present, there was less change in cortisol and global
self-worth due to the negativity of the experience.

Division of Developmental and Behavioral Pediatrics, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH 45229-3039, USA. ryan.adams@cchmc.org

10.1037/a0025401

http://www.ncbi.nlm.nih.gov/pubmed/21895364

(4)Alder MNandTimm NL

A "RARE" CASE OF MELENA IN a 3-YEAR-OLD

2011; 27:1084

Melena is a potential sign of life-threatening upper gastrointestinal bleeding;
however, there are numerous substances ingested resulting in a stool appearance
similar to melena. Examples of such substances include black licorice, bismuth
subsalicylate, and iron supplements. We report a case of a well-appearing
3-year-old Vietnamese girl presenting to our emergency department after 2
episodes of "black, sticky" stool. The cause of her
"melena" was determined after father revealed that she had ingested 2
bowls of pork blood soup during the preceding 12 hours. This case highlights
the need for a careful dietary history and cultural considerations in children
presenting with what may appear to be melena.

Pediatric Residency Training Program, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH 45229, USA.

10.1097/PEC.0b013e31823606b5

http://www.ncbi.nlm.nih.gov/pubmed/22068076

(5)Allred NJ, Poehling KA, Szilagyi PG,
Zhang F, Edwards KM, Staat MA, Donauer S, Prill MM and Fairbrother G

THE IMPACT OF MISSED OPPORTUNITIES ON SEASONAL INFLUENZA VACCINATION
COVERAGE FOR HEALTHY YOUNG CHILDREN

2011; 17:560-564

OBJECTIVE: To estimate the impact of missed opportunities on influenza
vaccination coverage among 6- through 23-month-old children who sought medical
care during the 2004-2005 influenza season. DESIGN: Retrospective cohort study.
SETTING: Fifty-two primary care practice sites located in Rochester, New York,
Nashville, Tennessee, and Cincinnati, Ohio. PARTICIPANTS: Children 6 through 23
months of age. METHODS/OUTCOME MEASURE: Charts were reviewed and data collected
on influenza vaccinations, type of health care visit (well child or other), and
presence of illness symptoms. Missed opportunity was defined as a practice
visit by an eligible child during influenza season, when vaccine was available,
but during which the child did not receive an influenza vaccination. Vaccine
was assumed to be available between the first and last dates influenza
vaccination was recorded at that practice. Each child was classified as fully
vaccinated, partially vaccinated, or unvaccinated. RESULTS: Data were analyzed
for 1724 children, 6 through 23 months of age. Most children (62.0%) had at
least 1 missed opportunity during this period. Among children with any missed
opportunities, 12.8% were fully and 29.8% were partially vaccinated. Overall,
33.6% of the missed opportunities occurred during well child visits and 66.4%
during other types of visits; 75% occurred when no other vaccines were given.
Eliminating all missed opportunities would have increased full vaccination
coverage from 30.3% to 49.9%. CONCLUSIONS: Missed opportunities for influenza
vaccination are frequent. Reducing missed opportunities could significantly
increase influenza vaccination rates and should be a goal in each practice.

National Center for Immunization and Respiratory Diseases, Centers for Disease
Control and Prevention, Atlanta, Georgia, USA. nallred@cdc.gov

10.1097/PHH.0b013e31821831c3

http://www.ncbi.nlm.nih.gov/pubmed/21964369

(6)Ammerman RT, Putnam FW, Stevens J, Bosse
NR, Short JA, Bodley AL and Van Ginkel JB

AN OPEN TRIAL OF IN-HOME CBT FOR DEPRESSED MOTHERS IN HOME VISITATION

2011; 15:1333-1341

Research has demonstrated that low income mothers participating in home
visitation programs have high rates of depression. This study used an open
trial design to evaluate In-Home Cognitive Behavioral Therapy (IH-CBT), an
evidence-based treatment for depression that is delivered in the home setting
and has been adapted to address the needs of low income mothers participating
in home visitation. 64 depressed mothers recruited from a home visitation
program and who had completed IH-CBT were compared to 241 mothers from the same
setting who met identical screening criteria at enrollment but did not receive
the treatment. In addition, pre- and post-treatment measures of depression and
related clinical features were contrasted in the 64 mothers receiving IH-CBT.
There was a significantly greater reduction in depressive symptoms in the
IH-CBT group relative to their counterparts who did not receive the treatment.
Results from pre-post comparisons showed that treated mothers had decreased
diagnosis of major depression, lower reported stress, increased coping and
social support, and increased positive views of motherhood at post-treatment.
Findings suggest that IH-CBT is a promising approach to addressing maternal
depression in the context of home visitation and warrants further study. Public
health implications for home visiting programs are discussed.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
University of Cincinnati College of Medicine, 3333 Burnet Avenue, ML 3015,
Cincinnati, OH 45229, USA. robert.ammerman@cchmc.org

10.1007/s10995-010-0691-7

http://www.ncbi.nlm.nih.gov/pubmed/20936338

(7)Anderson JB, Iyer SB, Beekman RH,
Jenkins KJ, Klitzner TS, Kugler JD, Martin GR, Neish SR, Rosenthal GL and
Lannon CM

NATIONAL PEDIATRIC CARDIOLOGY QUALITY IMPROVEMENT COLLABORATIVE: LESSONS
FROM DEVELOPMENT AND EARLY YEARS

2011; 32:103-109

The National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC)
was established by the Joint Council on Congenital Heart Disease to
dramatically improve the outcomes of care for children with congenital heart
disease (CHD) through a national collaborative network of multidisciplinary
clinical teams and families, working together to collect longitudinal data, use
improvement science methods and conduct research intended to accelerate the
development and translation of new knowledge into practice. The initial project
selected for this learning network is focused on care processes and outcomes of
the initial interstage period for infants with hypoplastic left heart syndrome.
A practice-based registry is being used to understand variation in care and
outcomes of infants and children with complex CHD. The NPC-QIC has effectively
recruited and engaged a large number of U.S. centers caring for infants with
complex CHD and provides the infrastructure needed to support the
implementation of practice changes across the collaborative that will
ultimately improve outcomes in this high-risk group of patients. We describe
here the development and early years of NPC-QIC as well as the challenges this
collaborative faces moving forward. Â© 2011 Elsevier Ireland Ltd.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
Boston Children's Hospital, Boston, MA, United States Mattel Children's
Hospital, UCLA, Los Angeles, CA, United States Children's Hospital and Medical
Center, Omaha, NE, United States Children's National Medical Center,
Washington, DC, United States University of Texas Health Center, San Antonio,
TX, United States University of Maryland, Baltimore, MD, United States

10.1016/j.ppedcard.2011.10.008

(8)Askenazi DJ, Montesanti A, Hunley H,
Koralkar R, Pawar P, Shuaib F, Liwo A, Devarajan P and Ambalavanan N

URINE BIOMARKERS PREDICT ACUTE KIDNEY INJURY AND MORTALITY IN VERY LOW BIRTH
WEIGHT INFANTS

2011; 159:907-12 e1

OBJECTIVES: To test the hypothesis that noninvasive urinary biomarkers may
improve early identification, differentiate causes, and predict outcomes of
acute kidney injury (AKI) in very low birth weight subjects. STUDY DESIGN: We
performed 2 nested case-control studies to compare the ability of 6 urine
biomarkers to predict AKI (rise in serum creatinine of at least 0.3 mg/dL) and
mortality (death before 36 weeks postmenstrual age). RESULTS: Compared to
subjects without AKI (n = 21), those with AKI (n = 9) had higher maximum
neutrophil gelatinase-associated lipocalin (OR = 1.2 [1.0, 1.6]; P < .01;
receiver operator characteristics [ROC] area under the curve [AUC] = .80) and
higher maximum osteopontin (OR = 3.2 [1.5, 9.9]; P < .01; ROC AUC = 0.83).
Compared with survivors (n = 100), nonsurvivors (n = 23) had higher maximum
kidney injury molecule 1 (OR = 1.1 [1.0, 1.2]; P < .02; ROC AUC = 0.64) and
higher maximum osteopontin (OR = 1.8 (1.2, 2.7); P < .001; AUC of ROC =
0.78). The combination of biomarkers improved predictability for both AKI and
mortality. Controlling for gestational age and birth weight did not affect
results considerably. CONCLUSIONS: Urinary biomarkers can predict AKI and
mortality in very low birth weight infants independent of gestational age and
birth weight.

Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
35233, USA. daskenazi@peds.uab.edu

10.1016/j.jpeds.2011.05.045

http://www.ncbi.nlm.nih.gov/pubmed/21784446

(9)Assa'ad AH, Gupta SK, Collins MH,
Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG and Aceves
SS

AN ANTIBODY AGAINST IL-5 REDUCES NUMBERS OF ESOPHAGEAL INTRAEPITHELIAL
EOSINOPHILS IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS

2011; 141:1593-1604

BACKGROUND & AIMS: The role of interleukin (IL)-5 in the pathogenesis of
eosinophilic esophagitis (EoE) has been established in animal models; anti-IL-5
therapy has been reported to be effective in adults. We investigated whether
IL-5 has a role in accumulation of esophageal eosinophils in children with EoE
and whether therapy with mepolizumab, an antibody against IL-5, reduces the
number of esophageal intraepithelial eosinophils in children with EoE. METHODS:
We performed an international, multicenter, double-blind, randomized,
prospective study of 59 children with EoE, defined as baseline peak count of
esophageal intraepithelial eosinophils of >/= 20 in at least 1 high-power
field (hpf). Patients received an infusion every 4 weeks (a total of 3
infusions) of 0.55, 2.5, or 10 mg/kg mepolizumab. No placebo group was used.
RESULTS: Baseline peak and mean esophageal intraepithelial eosinophil counts
were (mean +/- SE) 122.5 +/- 8.78 and 39.1 +/- 3.63 per hpf, respectively. Four
weeks after the third infusion, peak eosinophil counts were <5 per hpf in 5 of
57 children (8.8%); we did not observe differences among groups given different
doses of mepolizumab. Reduced peak and mean eosinophil counts, to <20 per
hpf, were observed in 18 of 57 (31.6%) and 51 of 57 (89.5%) children,
respectively. Peak and mean esophageal intraepithelial eosinophil counts
decreased significantly to 40.2 +/- 5.17 and 9.3 +/- 1.25 per hpf, respectively
(P < .0001). An analysis to evaluate predictors of response associated a
higher mean baseline esophageal intraepithelial eosinophil count with a greater
reduction in mean count (P < .0001). CONCLUSIONS: IL-5 is involved in the
pathogenesis of EoE in children. Mepolizumab, an antibody against IL-5, reduces
esophageal eosinophilic inflammation in these patients.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical
Center, Cincinnati, Ohio 45229, USA. amal.assa'ad@cchmc.org

10.1053/j.gastro.2011.07.044

http://www.ncbi.nlm.nih.gov/pubmed/21835135

(10)Atzinger C, Melvin A and Heald B

PRESENTED ABSTRACTS FROM THE THIRTIETH ANNUAL EDUCATION CONFERENCE OF THE
NATIONAL SOCIETY OF GENETIC COUNSELORS (SAN DIEGO, CA, OCTOBER 2011)

2011; 20:690-771

Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, ML 4006
Cincinnati 45229 USA National Society of Genetic Counselors Executive Office,
Chicago USA Cleveland Clinic, Cleveland USA

10.1007/s10897-011-9404-7

(11)Basu RK, Standage SW, Cvijanovich NZ, Allen
GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Shanley TP,
Bigham MT, Wheeler DS, Devarajan P, Goldstein SL and Wong HR

IDENTIFICATION OF CANDIDATE SERUM BIOMARKERS FOR SEVERE SEPTIC
SHOCK-ASSOCIATED KIDNEY INJURY VIA MICROARRAY

2011; 15:R273

ABSTRACT: INTRODUCTION: Septic-shock-associated acute kidney injury (SSAKI)
carries high morbidity in the pediatric population. Effective treatment
strategies are lacking, in part due to poor detection and prediction. There is
a need to identify novel candidate biomarkers of SSAKI. The objective of our
study was to determine whether microarray data from children with septic shock
could be used to derive a panel of candidate biomarkers for predicting SSAKI.
METHODS: A retrospective cohort study compared microarray data representing the
first 24 hours of admission for 179 children with septic shock with those of 53
age-matched normal controls. SSAKI was defined as a >200% increase of
baseline serum creatinine, persistent to 7 days after admission. RESULTS:
Patients with SSAKI (n = 31) and patients without SSAKI (n = 148) were
clinically similar, but SSAKI carried a higher mortality (45% vs. 10%).
Twenty-one unique gene probes were upregulated in SSAKI patients versus
patients without SSAKI. Using leave-one-out cross-validation and class
prediction modeling, these probes predicted SSAKI with a sensitivity of 98%
(95% confidence interval (CI) = 81 to 100) and a specificity of 80% (95% CI =
72 to 86). Serum protein levels of two specific genes showed high sensitivity
for predicting SSAKI: matrix metalloproteinase-8 (89%, 95% CI = 64 to 98) and
elastase-2 (83%, 95% CI = 58 to 96). Both biomarkers carried a negative
predictive value of 95%. When applied to a validation cohort, although both
biomarkers carried low specificity (matrix metalloproteinase-8: 41%, 95% CI =
28 to 50; and elastase-2: 49%, 95% CI = 36 to 62), they carried high
sensitivity (100%, 95% CI = 68 to 100 for both). CONCLUSIONS: Gene probes
upregulated in critically ill pediatric patients with septic shock may allow
for the identification of novel candidate serum biomarkers for SSAKI
prediction.

Cincinnati Children's Hospital Medical Center and Cincinnati Children's
Research Foundation, Department of Pediatrics, University of Cincinnati College
of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45223, USA. hector.wong@cchmc.org.

10.1186/cc10554

http://www.ncbi.nlm.nih.gov/pubmed/22098946

(12)Becker PM, Tran TS, Delannoy MJ, He C,
Shannon JM and McGrath-Morrow S

SEMAPHORIN 3A CONTRIBUTES TO DISTAL PULMONARY EPITHELIAL CELL
DIFFERENTIATION AND LUNG MORPHOGENESIS

2011; 6:e27449

RATIONALE: Semaphorin 3A (Sema3A) is a neural guidance cue that also mediates
cell migration, proliferation and apoptosis, and inhibits branching
morphogenesis. Because we have shown that genetic deletion of neuropilin-1,
which encodes an obligatory Sema3A co-receptor, influences airspace remodeling in
the smoke-exposed adult lung, we sought to determine whether genetic deletion
of Sema3A altered distal lung structure. METHODS: To determine whether loss of
Sema3A signaling influenced distal lung morphology, we compared pulmonary
histology, distal epithelial cell morphology and maturation, and the balance
between lung cell proliferation and death, in lungs from mice with a targeted
genetic deletion of Sema3A (Sema3A(-/-)) and wild-type (Sema3A(+/+)) littermate
controls. RESULTS: Genetic deletion of Sema3A resulted in significant perinatal
lethality. At E17.5, lungs from Sema3A(-/-) mice had thickened septae and
reduced airspace size. Distal lung epithelial cells had increased intracellular
glycogen pools and small multivesicular and lamellar bodies with atypical
ultrastructure, as well as reduced expression of type I alveolar epithelial
cell markers. Alveolarization was markedly attenuated in lungs from the rare
Sema3A(-/-) mice that survived the immediate perinatal period. Furthermore,
Sema3A deletion was linked with enhanced postnatal alveolar septal cell death.
CONCLUSIONS: These data suggest that Sema3A modulates distal pulmonary
epithelial cell development and alveolar septation. Defining how Sema3A
influences structural plasticity of the developing lung is a critical first
step for determining if this pathway can be exploited to develop innovative
strategies for repair after acute or chronic lung injury.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns
Hopkins University School of Medicine, Baltimore, Maryland, United States of
America. Patrice.Becker@questcor.com

10.1371/journal.pone.0027449

http://www.ncbi.nlm.nih.gov/pubmed/22096573

(13)Bernstein DI, Bravo FJ, Clark JR,
Earwood JD, Rahman A, Glazer R and Cardin RD

N-METHANOCARBATHYMIDINE IS MORE EFFECTIVE THAN ACYCLOVIR FOR TREATING
NEONATAL HERPES SIMPLEX VIRUS INFECTION IN GUINEA PIGS

2011; 92:386-388

The outcome of neonatal herpes simplex (HSV) infection, even after therapy with
high dose acyclovir (ACV), is not optimum. We therefore evaluated
N-Methanocarbathymidine ((N)-MCT) using the guinea pig model of neonatal
herpes. Treatment with ACV (60 mg/kg/day) was compared to doses of 1, 5, and 25
mg/kg/day of (N)-MCT initiated 1, 2, or 3 days postinoculation (dpi). Both ACV
and (N)-MCT significantly improved survival, but only (N)-MCT significantly
reduced the number of animals with symptoms when begun at 1 dpi. When therapy
was begun at 2 dpi, only (N)-MCT (1, 5, or 25 mg/kg/day) significantly
increased survival. In fact, (N)-MCT improved survival up to 3 dpi, the last
time point evaluated. (N)-MCT was highly effective and superior to high dose
ACV therapy for the treatment of neonatal herpes in the guinea pig model.

Cincinnati Children's Hospital Medical Center, University of Cincinnati,
Cincinnati, OH, United States. David.Bernstein@cchmc.org

10.1016/j.antiviral.2011.08.021

http://www.ncbi.nlm.nih.gov/pubmed/21924293

(14)Berry CA, Nitsos I, Hillman NH, Pillow
JJ, Polglase GR, Kramer BW, Kemp MW, Newnham JP, Jobe AH and Kallapur SG

INTERLEUKIN-1 IN LIPOPOLYSACCHARIDE INDUCED CHORIOAMNIONITIS IN THE FETAL
SHEEP

2011; 18:1092-1102

We tested the hypothesis that interleukin 1 (IL-1) mediates intra-amniotic
lipopolysaccharide (LPS)-induced chorioamnionitis in preterm fetal sheep.
Time-mated Merino ewes with singleton fetuses received IL-1alpha, LPS, or
saline (control) by intra-amniotic injection 1 to 2 days before operative
delivery at 124 +/- 1 days gestational age (N = 5-9/group; term = 150 days).
Recombinant human IL-1 receptor antagonist (rhIL-1ra) was given into the
amniotic fluid 3 hours before intra-amniotic LPS or saline to block IL-1
signaling. Inflammation in the chorioamnion was determined by histology,
cytokine messenger RNA (mRNA), protein expression, and by quantitation of
activated inflammatory cells. Intra-amniotic IL-1 and LPS both induced
chorioamnionitis. However, IL-1 blockade with IL-1ra did not decrease
intra-amniotic LPS-induced increases in pro-inflammatory cytokine mRNAs,
numbers of inflammatory cells, myeloperoxidase, or monocyte chemotactic
protein-1-expressing cells in the chorioamnion. We conclude that IL-1 and LPS
both can cause chorioamnionitis, but IL-1 is not an important mediator of
LPS-induced chorioamnionitis in fetal sheep.

Division of Pulmonary Biology/Neonatology, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH 45229, USA.

10.1177/1933719111404609

http://www.ncbi.nlm.nih.gov/pubmed/21493953

(15)Besnard V, Wert SE, Ikegami M, Xu Y,
Heffner C, Murray SA, Donahue LR and Whitsett JA

MATERNAL SYNCHRONIZATION OF GESTATIONAL LENGTH AND LUNG MATURATION

2011; 6:e26682

Among all mammals, fetal growth and organ maturation must be precisely
synchronized with gestational length to optimize survival at birth. Lack of
pulmonary maturation is the major cause of infant mortality in preterm birth.
Whether fetal or maternal genotypes influence the close relationship between
the length of gestation and lung function at birth is unknown. Structural and
biochemical indicators of pulmonary maturity were measured in two mouse strains
whose gestational length differed by one day. Shorter gestation in C57BL/6J
mice was associated with advanced morphological and biochemical pulmonary
development and better perinatal survival when compared to A/J pups born
prematurely. After ovarian transplantation, A/J pups were born early in
C57BL/6J dams and survived after birth, consistent with maternal control
gestational length. Expression of genes critical for perinatal lung function
was assessed in A/J pups born after ovarian transfer. A subset of mRNAs
important for perinatal respiratory adaptation was selectively induced in the
A/J pups born after ovarian transfer. mRNAs precociously induced after ovarian
transfer indicated an important role for the transcription factors C/EBPalpha
and CREB in maternally induced lung maturation. We conclude that fetal lung
maturation is determined by both fetal and maternal genotypes. Ovarian transfer
experiments demonstrated that maternal genotype determines the timing of birth
and can influence fetal lung growth and maturation to ensure perinatal
survival.

The Perinatal Institute and Section of Neonatology, Perinatal and Pulmonary
Biology, Cincinnati Children's Hospital Medical Center, the Department of
Pediatrics and The University of Cincinnati College of Medicine, Cincinnati,
Ohio, United States of America.

10.1371/journal.pone.0026682

internal-pdf://Besnard-2011-Maternal synchroniza-2258188032/Besnard-2011-Maternal
synchroniza.pdf; http://www.ncbi.nlm.nih.gov/pubmed/22096492

(16)Birkemeier KL, Podberesky DJ, Salisbury
S and Serai S

BREATHE IN... BREATHE OUT... STOP BREATHING: DOES PHASE OF RESPIRATION
AFFECT THE HALLER INDEX IN PATIENTS WITH PECTUS EXCAVATUM?

2011; 197:W934-9

OBJECTIVE: The purpose of this article is to determine whether the phase of
respiration at the time of imaging affects chest wall measurements and compression
of internal structures in patients with pectus excavatum. MATERIALS AND
METHODS: Forty-seven patients (median age, 14 years) imaged for preoperative
pectus excavatum underwent limited axial balanced steady-state free precession
MRI of the chest at inspiration, expiration, and stop quiet breathing. Two
radiologists, who were blinded to prior measurements, independently calculated
the Haller index, asymmetry index, and sternal tilt in each phase of
respiration. Compression of internal structures was recorded. Statistical
comparison was performed. RESULTS: The Haller index was significantly lower at
inspiration, compared with stop quiet breathing and expiration, with medians
(interquartile ranges) of 3.96 (3.27-4.61), 5.16 (4.02-6.48), and 5.09
(4.14-6.63), respectively (p < 0.0001 for both). No significant difference
in Haller indexes was observed between expiration and stop quiet breathing (p =
0.1171). Of 11 patients with a Haller index less than 3.25 at inspiration,
eight (72.7%) had an index greater than 3.25 on expiration and stop quiet
breathing, which accounted for 17% (8/47) of all patients imaged. Compression
of the liver or vascular structures was present in 24 (51%) patients. There was
no significant difference in the asymmetry index, sternal tilt, or right heart
compression between phases of respiration. CONCLUSION: Obtaining the Haller
Index at inspiration may result in a value significantly lower than that at
expiration, potentially affecting surgical and financial decision making.
Compression of the liver and vascular structures was observed in 51% of
patients, but additional research is needed to determine the clinical
significance of this finding.

Department of Radiology, Cincinnati Children's Hospital Medical Center, OH
45229-3039, USA. Krista.Birkemeier@cchmc.org

10.2214/AJR.11.6430

http://www.ncbi.nlm.nih.gov/pubmed/22021545

(17)Black S, Nicolay U, Vesikari T, Knuf M,
Del Giudice G, Della Cioppa G, Tsai T, Clemens R and Rappuoli R

HEMAGGLUTINATION INHIBITION ANTIBODY TITERS AS a CORRELATE OF PROTECTION FOR
INACTIVATED INFLUENZA VACCINES IN CHILDREN

2011; 30:1081-1085

INTRODUCTION: The hemagglutination inhibition (HI) titer of 1:40, which has
been recognized as an immunologic correlate corresponding to a 50% reduction in
the risk of contracting influenza, is based on studies in adults. Neither
seasonal nor challenge-based correlates have been evaluated in children.
METHODS: A total of 4707 influenza vaccine-naive healthy children 6 to 72
months old were randomized in a ratio of 2:2:1 to receive 2 doses of
MF-59-adjuvanted influenza vaccine (Novartis Vaccines), trivalent inactivated
influenza vaccine subunit (trivalent inactivated influenza vaccine control,
GSK), or a saline placebo during the 2007 to 2008 and 2008 to 2009 influenza
seasons. The second dose was given 30 days after dose 1. Clinical
influenza-like illnesses cases identified by active surveillance were confirmed
by reverse transcription polymerase chain reaction testing for influenza.
Vaccine immunogenicity 50 days after dose 1 was evaluated in a subset of 777
children. RESULTS: Immunogenicity and efficacy results for H3N2 were evaluated
against the Prentice criteria, which confirmed that the immunogenicity results
warranted estimation of an immunologic correlate. We then used the Dunning
model fitting the H3N2 antibody titers at day 50 and the influenza cases
observed in the immunogenicity subset to estimate a correlate of protection.
This analysis revealed that a cutoff HI titer of 1:110 was associated with the
conventional 50% clinical protection rate against infection during the entire
season, and titers of 1:215, 1:330, and 1:629 predicated protection rates of
70%, 80%, and 90%, respectively. The conventional adult HI titer of 1:40 was
only associated with 22% protection. CONCLUSIONS: The use of the 1:40 HI adult
correlate of protection is not appropriate when evaluating influenza vaccines
in children. Although a cutoff of 1:110 may be used to predict the conventional
50% clinical protection rate, a titer of 1:330 would predict an 80% protective
level, which would seem to be more desirable from a public health perspective.

Center for Global Health, University of Cincinnati Children's Hospital,
Cincinnati, OH 45229, USA. stevblack@gmail.com

10.1097/INF.0b013e3182367662

http://www.ncbi.nlm.nih.gov/pubmed/21983214

(18)Braun JM, Kalkbrenner AE, Calafat AM,
Yolton K, Ye X, Dietrich KN and Lanphear BP

IMPACT OF EARLY-LIFE BISPHENOL A EXPOSURE ON BEHAVIOR AND EXECUTIVE FUNCTION
IN CHILDREN

2011; 128:873-882

OBJECTIVES: To estimate the impact of gestational and childhood bisphenol A
(BPA) exposures on behavior and executive function at 3 years of age and to
determine whether child gender modified those associations. METHODS: We used a
prospective birth cohort of 244 mothers and their 3-year-old children from the
greater Cincinnati, Ohio, area. We characterized gestational and childhood BPA
exposures by using the mean BPA concentrations in maternal (16 and 26 weeks of
gestation and birth) and child (1, 2, and 3 years of age) urine samples,
respectively. Behavior and executive function were measured by using the
Behavior Assessment System for Children 2 (BASC-2) and the Behavior Rating
Inventory of Executive Function-Preschool (BRIEF-P). RESULTS: BPA was detected
in >97% of the gestational (median: 2.0 mug/L) and childhood (median: 4.1
mug/L) urine samples. With adjustment for confounders, each 10-fold increase in
gestational BPA concentrations was associated with more anxious and depressed
behavior on the BASC-2 and poorer emotional control and inhibition on the
BRIEF-P. The magnitude of the gestational BPA associations differed according
to child gender; BASC-2 and BRIEF-P scores increased 9 to 12 points among
girls, but changes were null or negative among boys. Associations between childhood
BPA exposure and neurobehavior were largely null and not modified by child
gender. CONCLUSIONS: In this study, gestational BPA exposure affected
behavioral and emotional regulation domains at 3 years of age, especially among
girls. Clinicians may advise concerned patients to reduce their exposure to
certain consumer products, but the benefits of such reductions are unclear.

Department of Environmental Health, Harvard School of Public Health, Harvard
University, Boston, MA 02130, USA. jbraun@hsph.harvard.edu

10.1542/peds.2011-1335

http://www.ncbi.nlm.nih.gov/pubmed/22025598

(19)Brinkman WB, Hartl J, Rawe LM, Sucharew
H, Britto MT and Epstein JN

PHYSICIANS' SHARED DECISION-MAKING BEHAVIORS IN ATTENTION-DEFICIT/
HYPERACTIVITY DISORDER CARE

2011; 165:1013-1019

Objectives: To describe the amount of shared decisionmaking (SDM) behavior
exhibited during treatmentplanning encounters for children newly diagnosed as
having attention-deficit/hyperactivity disorder and to explore relationships
between participant characteristics and the amount of SDM. Design: Prospective
cohort study. Setting: Seven community-based primary care pediatric practices
in the Cincinnati, Ohio; northern Kentucky; and southeast Indiana regions from
October 5, 2009, through August 9, 2010. Participants: Ten pediatricians and 26
families with a 6- to 10-year-old child newly diagnosed as having attention-
deficit/hyperactivity disorder. Outcome Measure: The amount of SDM behavior
exhibited during videorecorded encounters, as coded by 2 independent raters
using the validated Observing Patient Involvement (OPTION) scale, which was
adapted for use in pediatric settings and produces a score ranging from 0 (no
parental involvement) to 100 (maximal parental involvement). Results:
Treatmentdecisions focusedoninitiationofmedication treatment. The mean (SD)
total OPTION score was 28.5 (11.7). More SDM was observed during encounters
involving families with white vs nonwhite children (adjusted mean difference
score, 14.9; 95% confidence interval [CI], 10.2-19.6;P<.001), private vs
public health insurance coverage (adjusted mean difference score, 15.1;
11.2-19.0; P<.001), mothers with at least some college education vs
highschoolgraduateor less (adjustedmeandifference score, 12.3; 7.2-17.4;
P<.001), and parents who did not screen positive for seriousmentalillness vs
thosewhodid (adjusted mean difference score, 15.0; 11.9-18.1; P<.001).
Conclusions: Low levels of SDM were observed. Exploratory analyses identified
potential disparities and barriers. Interventions may be needed to foster SDM
with all parents, especially those of nonwhite race, of lower socioeconomic
status, of lower educational level, and with serious mental illness. Â©2011
American Medical Association. All rights reserved.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Cincinnati Pediatric Research Group, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH, United States Center for
Innovation in Chronic Disease Care, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States Center for
Attention-Deficit/Hyperactivity Disorder, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, OH, United States

10.1001/archpediatrics.2011.154 10.1542/peds.114.1.e23; Leslie, L.K., Stallone,
K.A., Weckerly, J., McDaniel, A.L., Monn, A., Implementing ADHD guidelines in
primary care: Does one size fit all? (2006) Journal of Health Care for the Poor
and Und(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/22065181

(20)Bronson PG, Goldstein BA, Ramsay PP,
Beckman KB, Noble JA, Lane JA, Seldin MF, Kelly JA, Harley JB, Moser KL,
Gaffney PM, Behrens TW, Criswell LA and Barcellos LF

THE rs4774 CIITA MISSENSE VARIANT IS ASSOCIATED WITH RISK OF SYSTEMIC LUPUS
ERYTHEMATOSUS

2011; 12:667-671

The major histocompatibility complex (MHC) class II transactivator gene (CIITA)
encodes an important transcription factor required for human leukocyte antigens
(HLA) class II MHC-restricted antigen presentation. MHC genes, including the
HLA class II DRB1*03:01 allele, are strongly associated with systemic lupus
erythematosus (SLE). Recently the rs4774 CIITA missense variant (+1632G/C) was
reported to be associated with susceptibility to multiple sclerosis. In the
current study, we investigated CIITA, DRB1*03:01 and risk of SLE using a
multi-stage analysis. In stage 1, 9 CIITA variants were tested in 658 cases and
1363 controls (N=2021). In stage 2, rs4774 was tested in 684 cases and 2938
controls (N=3622). We also performed a meta-analysis of the pooled 1342 cases
and 4301 controls (N=5643). In stage 1, rs4774*C was associated with SLE (odds
ratio (OR)=1.24, 95% confidence interval (95% CI)=1.07-1.44, P=4.2Ã—10-3).
Similar results were observed in stage 2 (OR=1.16, 95% CI=1.02-1.33,
P=8.5Ã—10-3) and the meta-analysis of the combined data set (OR=1.20, 95%
CI=1.09-1.33, P meta=2.5Ã—10-4). In all three analyses, the strongest evidence
for association between rs4774*C and SLE was present in individuals who carried
at least one copy of DRB1*03:01 (P meta=1.9Ã—10-3). Results support a role for
CIITA in SLE, which appears to be stronger in the presence of DRB1*03:01. Â©
2011 Macmillan Publishers Limited All rights reserved.

Division of Epidemiology, Genetic Epidemiology, School of Public Health,
University of California, 209 Hildebrand Hall, Berkeley, CA 94720-7356, United
States Division of Biostatistics, School of Public Health, University of
California, Berkeley, CA, United States Biomedical Genomics Center, University
of Minnesota, Minneapolis, MN, United States Children's Hospital Oakland
Research Institute, Oakland, CA, United States Department of Biochemistry and
Molecular Medicine, School of Medicine, University of California, Davis, CA,
United States Oklahoma Medical Research Foundation, Oklahoma City, OK, United
States Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United
States US Department of Veterans Affairs Medical Center, Cincinnati, OH, United
States Immunology Diagnostics and Biomarkers, Genentech, South San Francisco,
CA, United States Rosalind Russell Medical Research Center for Arthritis,
Department of Medicine, University of California, San Francisco, CA, United
States

10.1038/gene.2011.36

http://www.ncbi.nlm.nih.gov/pubmed/21614020

(21)Brown C, Clayton-Boswell H, Chaves SS,
Prill MM, Iwane MK, Szilagyi PG, Edwards KM, Staat MA, Weinberg GA, Fairbrother
G, Hall CB, Zhu Y and Bridges CB

VALIDITY OF PARENTAL REPORT OF INFLUENZA VACCINATION IN YOUNG CHILDREN
SEEKING MEDICAL CARE

2011; 29:9488-9492

Background: Despite frequent use of self-reported information to determine
pediatric influenza vaccination coverage, little data are available on the
validity of parental reporting of their child's influenza vaccination status
and on factors affecting its accuracy. Methods: We compared parent reported
influenza vaccination of children to documented reports of vaccination
collected from medical records (the criterion standard) among children aged
6-59 months who presented to selected hospitals, emergency departments, and
clinics in three U.S. counties with acute respiratory illness during three
influenza seasons (November through May of 2004-2007). Demographic and
epidemiologic data were collected from chart reviews and parental surveys.
Results: Among 3072 children aged 6-59 months, 47.5% were reported by the
parent to have received influenza vaccine and 39.5% of children had medical
record verification of influenza vaccination. Sensitivity and specificity of
parental reporting was 92.1% and 82.3%, respectively, when compared to the
immunization record. However, 17.7% of children whose parents reported
vaccination had no influenza vaccination documented in their medical records,
and this proportion was even higher at 28.6%, among children with an underlying
high-risk medical condition. Greater reporting accuracy was associated with
younger age of child (6-23 months vs. 24-59 months), white non-Hispanic
race/ethnicity, having health insurance, and having a mother with a college
education. Conclusions: Our findings indicate that although parental report of
influenza vaccination is fairly reliable (âˆ¼76-96%), over reporting by parents
often occurs and immunization record review remains the preferable method for
determining vaccination status in children. Â© 2011.

National Center for Immunization and Respiratory Diseases, Center for Disease
Control and Prevention, Atlanta, GA, United States Vanderbilt Institute for
Clinical and Translational Research (VICTR), Vanderbilt University Medical
Center, Nashville, TN, United States Departments of Pediatrics, University of
Rochester School of Medicine and Dentistry, Rochester, NY, United States
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN,
United States Department of Pediatrics, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States

10.1016/j.vaccine.2011.10.023

http://www.ncbi.nlm.nih.gov/pubmed/22015394

(22)Brunskill EW, Sequeira-Lopez M, Pentz
ES, Lin E, Yu J, Aronow BJ, Potter SS and Gomez RA

GENES THAT CONFER THE IDENTITY OF THE RENIN CELL

2011; 22:2213-2225

Renin-expressing cells modulate BP, fluid-electrolyte homeostasis, and kidney
development, but remarkably little is known regarding the genetic regulatory
network that governs the identity of these cells. Here we compared the gene
expression profiles of renin cells with most cells in the kidney at various
stages of development as well as after a physiologic challenge known to induce
the transformation of arteriolar smooth muscle cells into renin-expressing
cells. At all stages, renin cells expressed a distinct set of genes
characteristic of the renin phenotype, which was vastly different from other
cell types in the kidney. For example, cells programmed to exhibit the renin
phenotype expressed Akr1b7, and maturing cells expressed angiogenic factors
necessary for the development of the kidney vasculature and RGS (regulator of
G-protein signaling) genes, suggesting a potential relationship between renin
cells and pericytes. Contrary to the plasticity of arteriolar smooth muscle
cells upstream from the glomerulus, which can transiently acquire the embryonic
phenotype in the adult under physiologic stress, the adult juxtaglomerular cell
always possessed characteristics of both smooth muscle and renin cells. Taken
together, these results identify the gene expression profile of
renin-expressing cells at various stages of maturity, and suggest that
juxtaglomerular cells maintain properties of both smooth muscle and
renin-expressing cells, likely to allow the rapid control of body fluids and BP
through both contractile and endocrine functions. Copyright Â© 2011 by the American
Society of Nephrology.

Department of Pediatrics, Cincinnati Children's Hospital, Cincinnati, OH,
United States Department of Cell and Developmental Biology, Cincinnati
Children's Hospital, Cincinnati, OH, United States Department of Pediatrics,
University of Virginia School of Medicine, Charlottesville, VA, United States
Department of Cell Biology, University of Virginia School of Medicine,
Charlottesville, VA, United States

10.1681/asn.2011040401

http://www.ncbi.nlm.nih.gov/pubmed/22034642

(23)Burks AW, Jones SM, Boyce JA, Sicherer
SH, Wood RA, Assa'ad A and Sampson HA

NIAID-SPONSORED 2010 GUIDELINES FOR MANAGING FOOD ALLERGY: APPLICATIONS IN
THE PEDIATRIC POPULATION

2011; 128:955-965

Data from many studies have suggested a rise in the prevalence of food
allergies during the past 10 to 20 years. Currently, no curative treatments for
food allergy exist, and there are no effective means of preventing the disease.
Management of food allergy involves strict avoidance of the allergen in the
patient's diet and treatment of symptoms as they arise. Because diagnosis and
management of the disease can vary between clinical practice settings, the
National Institute of Allergy and Infectious Diseases (NIAID) sponsored
development of clinical guidelines for the diagnosis and management of food
allergy. The guidelines establish consensus and consistency in definitions,
diagnostic criteria, and management practices. They also provide concise recommendations
on how to diagnose and manage food allergy and treat acute food allergy
reactions. The original guidelines encompass practices relevant to patients of
all ages, but food allergy presents unique and specific concerns for infants,
children, and teenagers. To focus on those concerns, we describe here the
guidelines most pertinent to the pediatric population.

Division of Allergy and Immunology, Department of Pediatrics, Duke University
Medical Center, Durham, NC 27710, USA. wesley.burks@duke.edu

10.1542/peds.2011-0539

http://www.ncbi.nlm.nih.gov/pubmed/21987705

(24)Cancelas JA

ON HOW RAC CONTROLS HEMATOPOIETIC STEM CELL ACTIVITY

2011; 51 Suppl 4:153S-159S

Rac GTPases form part of the family of Rho small GTPases. Rac GTPases, like
other Rho family GTPases, are key molecular switches controlling the
transduction of external signals to cytoplasmic and nuclear effectors. The
development of genetic and pharmacological tools has allowed a more precise
definition of the specific roles of Rac GTPases in hematopoietic stem cells
(HSCs). Our current knowledge has enabled dissection of their specific and
redundant roles. Rac GTPases are now known to be crucial in the response of
HSCs to the hematopoietic microenvironment cues. This review will briefly
summarize the known HSC functions that are regulated by Rac GTPases, focusing
on adhesion, migration, retention, proliferation, and survival, and how Rac
relates to the physiological functions of HSC. The development of small
molecule inhibitors with the ability to interfere with Rac GTPase activation
offers new therapeutic strategies to manipulate the function of HSC in vivo and
ex vivo.

Hoxworth Blood Center, University of Cincinnati Academic Health Center, and
Stem Cell Program, Division of Experimental Hematology and Cancer Biology,
Cincinnati Children's Hospital Medical Center, University of Cincinnati Medical
Center, Cincinnati, Ohio, USA. Jose.Cancelas@uc.edu

10.1111/j.1537-2995.2011.03378.x

http://www.ncbi.nlm.nih.gov/pubmed/22074626

(25)Carle AC, Cella D, Cai L, Choi SW,
Crane PK, Curtis SM, Gruhl J, Lai JS, Mukherjee S, Reise SP, Teresi JA, Thissen
D, Wu EJ and Hays RD

ADVANCING PROMIS's METHODOLOGY: RESULTS OF THE THIRD PATIENT-REPORTED
OUTCOMES MEASUREMENT INFORMATION SYSTEM (PROMIS((R))) PSYCHOMETRIC SUMMIT

2011; 11:677-684

In 2002, the NIH launched the 'Roadmap for Medical Research'. The
Patient-Reported Outcomes Measurement Information System (PROMIS((R))) is one
of the Roadmap's key aspects. To create the next generation of patient-reported
outcome measures, PROMIS utilizes item response theory (IRT) and computerized
adaptive testing. In 2009, the NIH funded the second wave of PROMIS studies
(PROMIS II). PROMIS II studies continue PROMIS's agenda, but also include new
features, including longitudinal analyses and more sociodemographically diverse
samples. PROMIS II also includes increased emphasis on pediatric populations
and evaluation of PROMIS item banks for clinical research and population
science. These aspects bring new psychometric challenges. To address this,
investigators associated with PROMIS gathered at the Third Psychometric Summit
in September 2010 to identify, describe and discuss pressing psychometric
issues and new developments in the field, as well as make analytic
recommendations for PROMIS. The summit addressed five general themes: linking,
differential item functioning, dimensionality, IRT models for longitudinal
applications and new IRT software. In this article, we review the discussions
and presentations that occurred at the Third PROMIS Psychometric Summit.

University of Cincinnati School of Medicine, James M Anderson Center for Health
Systems Excellence, Cincinnati Children's Hospital Medical Center, 3333 Burnet
Avenue, MLC 7014, Cincinnati, OH 45229, USA. adam.carle.cchmc@gmail.com

10.1586/erp.11.74

http://www.ncbi.nlm.nih.gov/pubmed/22098283

(26)Carle AC, Dewitt EM and Seid M

PATIENT OUTCOMES IN RHEUMATOLOGY, 2011: a REVIEW OF MEASURES. MEASURES OF
HEALTH STATUS AND QUALITY OF LIFE IN JUVENILE RHEUMATOID ARTHRITIS

2011; 63:S438-45

Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati,
OH 45226

(27)Carle AC, Dewitt EM and Seid M

MEASURES OF HEALTH STATUS AND QUALITY OF LIFE IN JUVENILE RHEUMATOID
ARTHRITIS: PEDIATRIC QUALITY OF LIFE INVENTORY (PedsQL) RHEUMATOLOGY MODULE
3.0, JUVENILE ARTHRITIS QUALITY OF LIFE QUESTIONNAIRE (JAQQ), PAEDIATRIC
RHEUMATOLOGY QUALITY OF LIFE SCALE (PRQL), AND CHILDHOOD ARTHRITIS HEALTH
PROFILE (CAHP)

2011; 63:S438-S445

Cincinnati Children's Hospital, Medical Center, Cincinnati, OH, United States

10.1002/acr.20560

(28)Case-Smith J, Holland T and Bishop B

EFFECTIVENESS OF AN INTEGRATED HANDWRITING PROGRAM FOR FIRST-GRADE STUDENTS:
a PILOT STUDY

2011; 65:670-678

We developed and piloted a program for first-grade students to promote
development of legible handwriting and writing fluency. The Write Start program
uses a coteaching model in which occupational therapists and teachers
collaborate to develop and implement a handwriting-writing program. The
small-group format with embedded individualized supports allows the therapist
to guide and monitor student performance and provide immediate feedback. The
12-wk program was implemented with 1 class of 19 students. We administered the
Evaluation of Children's Handwriting Test, Minnesota Handwriting Assessment,
and Woodcock-Johnson Fluency and Writing Samples test at baseline, immediately
after the Write Start program, and at the end of the school year. Students made
large, significant gains in handwriting legibility and speed and in writing
fluency that were maintained at 6-mo follow-up. The Write Start program appears
to promote handwriting and writing skills in first-grade students and is ready
for further study in controlled trials.

Occupational Therapy Division, School of Allied Medical Professions, Ohio State
University, Columbus, OH 43210, USA. Jane.case-smith@osumc.edu

10.5014/ajot.2011.000984

http://www.ncbi.nlm.nih.gov/pubmed/22214111

(29)Chambers PL, Mahabee-Gittens E and
Leonard AC

VULNERABLE CHILD SYNDROME, PARENTAL PERCEPTION OF CHILD VULNERABILITY, AND
EMERGENCY DEPARTMENT USAGE

2011; 27:1009-1013

BACKGROUND: Vulnerable child syndrome (VCS) describes children perceived to be
at risk for behavioral, developmental, or medical problems. Families with the
dynamics of VCS overuse health care resources with frequent visits to doctors'
offices. OBJECTIVE: The objective of the study was to explore the relationship
between VCS, parental perception of child vulnerability (PPCV), and frequency
of emergency department (ED) visits. DESIGN/METHODS: Parents of patients 1 to
15 years old presenting with nonurgent complaints to a pediatric ED were
eligible. Participants completed questionnaires in which the Vulnerable Child
Scale was used to generate a measure of PPCV. Primary outcomes included number
of ED visits and PPCV assignment. Children were divided into 2 PPCV groups by
Vulnerable Child Scale score: less than 40 (high PPCV) versus 40 or greater
(low PPCV). The cutoff point was chosen as 1 SD (7.3) from the sample mean
(46.8) on the vulnerable end of the scale (low scores). RESULTS: The mean ages
of the 351 parents and children were 30 (SD, 7.7) years and 5 (SD, 3.9) years,
respectively; 17% of children had high PPCV. Eleven variables differed
statistically between subjects with high and low PPCV including number of ED
visits and hospital admissions, excellent reported child health, pregnancy
problems, delivery problems, child mental health problems, parent mental health
problems, and child developmental problems. CONCLUSIONS: Our results reveal
that children with higher PPCV had an increased number of ED visits, and risk
factors for higher perceived vulnerability scores were identified. Future
investigation on ways to intervene with families with the dynamics of VCS may
be warranted.

Division of Emergency Medicine, Department of Pediatrics, Cincinnati Children's
Hospital Medical Center, University of Cincinnati College of Medicine,
Cincinnati, OH, USA. patricia.chambers@cchmc.org

10.1097/PEC.0b013e318235bb4f

http://www.ncbi.nlm.nih.gov/pubmed/22068058

(30)Charlton BM, Corliss HL, Missmer SA,
Frazier AL, Rosario M, Kahn JA and Austin SB

REPRODUCTIVE HEALTH SCREENING DISPARITIES AND SEXUAL ORIENTATION IN a COHORT
STUDY OF U.S. ADOLESCENT AND YOUNG ADULT FEMALES

2011; 49:505-510

PURPOSE: To examine sexual orientation group disparities in the Papanicolaou
(Pap) and sexually transmitted infection (STI)/human papillomavirus (HPV) tests
among adolescents and young adult females. METHODS: Survey data from 4,224
adolescents and young adults aged 17-25 years who responded to the 2005 wave
questionnaire of the Growing Up Today Study were cross-sectionally examined with
multivariate generalized estimating equations regression. We examined
associations between sexual orientation and reproductive healthcare utilization
as well as abnormal results with completely heterosexual as the referent group,
controlling for age, race/ethnicity, geographic region, and sexual history.
RESULTS: After accounting for sociodemographics and sexual history, mostly
heterosexual/bisexual females had 30% lower odds of having a Pap test within
the last year and almost 40% higher odds of being diagnosed with an STI, as
compared with the completely heterosexual group. Additionally, lesbians had
very low odds of having a Pap test in their lifetime (odds ratio = .13, p
</= .0001) and having a Pap test within the last year (odds ratio = .25, p =
.0002), as compared with completely heterosexuals. CONCLUSIONS: Our study
demonstrates that sexual minority adolescent and young adult women underutilize
routine reproductive health screenings, including Pap smears and STI tests.
Providers and health educators should be aware of these disparities so that
they can provide appropriate care to young women and their families and ensure
that all young women receive reproductive health screening. Further research is
needed to explore reasons sexual minority females are not accessing care as
recommended because this may suggest opportunities to improve reproductive
health screenings as well as broader healthcare access issues.

Department of Epidemiology, Harvard School of Public Health, Boston,
Massachusetts 02115, USA. bcharlto@hsph.harvard.edu

10.1016/j.jadohealth.2011.03.013

http://www.ncbi.nlm.nih.gov/pubmed/22018565

(31)Chauhan BK, Lou M, Zheng Y and Lang RA

BALANCED Rac1 AND RhoA ACTIVITIES REGULATE CELL SHAPE AND DRIVE INVAGINATION
MORPHOGENESIS IN EPITHELIA

2011; 108:18289-18294

Epithelial bending is a central feature of morphogenesis in animals. Here we
show that mutual antagonism by the small Rho GTPases Rac1 and RhoA determines
cell shape, tissue curvature, and invagination activity in the model epithelium
of the developing mouse lens. The epithelial cells of the invaginating lens
placode normally elongate and change from a cylindrical to an apically
constricted, conical shape. RhoA mutant lens placode cells are both longer and
less apically constricted than control cells, thereby reducing epithelial
curvature and invagination. By contrast, Rac1 mutant lens placode cells are
shorter and more apically restricted than controls, resulting in increased
epithelial curvature and precocious lens vesicle closure. Quantification of
RhoA- and Rac1-dependent pathway markers over the apical-basal axis of lens pit
cells showed that in RhoA mutant epithelial cells there was a Rac1 pathway gain
of function and vice versa. These findings suggest that mutual antagonism
produces balanced activities of RhoA-generated apical constriction and
Rac1-dependent cell elongation that controls cell shape and thus curvature of
the invaginating epithelium. The ubiquity of the Rho family GTPases suggests
that these mechanisms are likely to apply generally where epithelial
morphogenesis occurs.

Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH 45229, USA.

10.1073/pnas.1108993108

http://www.ncbi.nlm.nih.gov/pubmed/22021442

(32)Chung TK, Lynch ER, Fiser CJ, Nelson
DA, Agricola K, Tudor C, Franz DN and Krueger DA

PSYCHIATRIC COMORBIDITY AND TREATMENT RESPONSE IN PATIENTS WITH TUBEROUS
SCLEROSIS COMPLEX

2011; 23:263-269

BACKGROUND: Behavioral and psychiatric comorbidity are common in tuberous
sclerosis complex (TSC), but information regarding psychopharmacologic
management is lacking. METHODS: We reviewed clinical records of patients
evaluated over a 20-month period at a large, quaternary referral center
specializing in the comprehensive management of patients with TSC. Data were
collected regarding psychiatric diagnoses, psychopharmacologic medications used
to treat these disorders, and clinical response to treatment at follow-up.
RESULTS: There were 113 encounters by 62 pediatric and adult patients with TSC,
which were included in the present analysis. Behavioral and anxiety disorders
were most prevalent, as were autism spectrum disorders and
attention-deficit/hyperactivity disorder. Antipsychotics, antidepressants, and
anticonvulsants with mood-stabilizing properties were the most often prescribed
psychoactive medications and were associated with an overall improvement or
stabilization of psychiatric symptoms 65% of the time. CONCLUSIONS: Psychiatric
comorbidity, especially behavioral disorders, is very common among patients
with TSC. Pharmacologic treatment can be very effective and should be
considered for optimal disease management in affected individuals.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, OH
45229, USA.

http://www.ncbi.nlm.nih.gov/pubmed/22073383

(33)Cnota JF, Gupta R, Michelfelder EC and
Ittenbach RF

CONGENITAL HEART DISEASE INFANT DEATH RATES DECREASE AS GESTATIONAL AGE
ADVANCES FROM 34 TO 40 WEEKS

2011; 159:761-765

OBJECTIVES: To describe congenital heart disease death rates in infants born
between 34 and 40 weeks, estimate the relationship between gestational age and
congenital heart disease infant death rates, and compare congenital heart
disease death rates across 1- and 2-week intervals in gestational age. STUDY
DESIGN: The 2000 to 2003 national linked birth/infant death cohort datasets
were obtained. Congenital heart disease deaths were identified by using
International Statistical Classification of Diseases, 10th Revision codes. Proportional
death rates were calculated by using congenital heart disease deaths and all
live births. The relationship between congenital heart disease death rates and
gestational age was determined. Death rates were compared across intervals.
RESULTS: A total of 14.9 million records were analyzed. Congenital heart
disease deaths occurred in 4736 infants (0.04%) born between 34 and 40 weeks.
There was a significant, negative linear relationship between congenital heart
disease death rate and gestational age (R(2) = 0.97). Comparisons across 1-week
intervals varied (P = .02-.23). All 2-week intervals were statistically
significant (P < .01). CONCLUSIONS: Congenital heart disease death rates
decrease as gestational age approaches 40 weeks. These results should be considered
before elective delivery for the sole indication of prenatally diagnosed
congenital heart disease.

The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH, USA. james.cnota@cchmc.org

10.1016/j.jpeds.2011.04.020

http://www.ncbi.nlm.nih.gov/pubmed/21676411

(34)Conway PHandBerwick DM

IMPROVING THE RULES FOR HOSPITAL PARTICIPATION IN MEDICARE AND MEDICAID

2011; 306:2256-2257

Centers for Medicare and Medicaid Services, Mailstop S3-02-01, 7500 Security
Blvd, Baltimore, MD 21244, United States Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States

10.1001/jama.2011.1611

http://www.ncbi.nlm.nih.gov/pubmed/22008181

(35)Cousino M, Hazen R, Yamokoski A, Miller
V, Zyzanski S, Drotar D and Kodish E

PARENT PARTICIPATION AND PHYSICIAN-PARENT COMMUNICATION DURING INFORMED
CONSENT IN CHILD LEUKEMIA

2011; 128:e1544-e1551

OBJECTIVE: In this study we evaluated the effectiveness of a physician-directed
intervention at enhancing positive physician behaviors and communication
strategies during informed consent conferences (ICCs) for pediatric acute
leukemia clinical trials. PATIENTS AND METHODS: Physicians at 2 large pediatric
hospitals were recruited to participate in a physician-directed intervention
(PDI), which included 1 full-day seminar and successive half-day booster sessions.
ICCs were then observed, audiotaped, coded, and analyzed to evaluate the
effectiveness of the intervention. Data also were collected at 2 control sites.
Between 2003 and 2007, 59 ICCs were observed and analyzed. RESULTS: Significant
group differences were found in physician rapport-building behaviors.
Physicians in the PDI + booster session group engaged in greater
rapport-building than did physicians in the PDI group who did not attend
booster sessions and physicians in the control group. No group differences were
detected for physician partnership-building. In addition, parents in the PDI +
booster session group engaged in more general communication and study-related
communication, and mothers in the PDI groups asked significantly more questions
per minute than did mothers in the control group. CONCLUSIONS: These results
provide support for the effectiveness of the PDI at enhancing positive
physician behaviors. Booster-session attendance is a critical component of
physician-directed interventions to improve parental participation and
physician-parent communication during ICCs. Copyright Â© 2011 by the American
Academy of Pediatrics.

Department of Psychology, Case Western Reserve University, Cleveland, OH,
United States Division of Developmental/Behavioral Pediatrics and Psychology,
Rainbow Babies and Children's Hospital, Cleveland, OH, United States Department
of Pediatrics, Case Western Reserve University, Cleveland, OH, United States
Department of Bioethics, Cleveland Clinic, 9500 Euclid Ave JJ60, Cleveland, OH
44195, United States Department of Anesthesiology and Critical Care Medicine,
Children's Hospital of Philadelphia, Philadelphia, PA, United States Department
of Family Medicine, Case Western Reserve University, Cleveland, OH, United
States Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States

10.1542/peds.2010-3542

http://www.ncbi.nlm.nih.gov/pubmed/22065265

(36)Czech KA, Bennett M and Devarajan P

DISTINCT METALLOPROTEINASE EXCRETION PATTERNS IN FOCAL SEGMENTAL
GLOMERULOSCLEROSIS

2011; 26:2179-2184

Metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) degrade type IV
collagen, and represent important tissue remodeling enzymes in several kidney
disorders. In this study, we measured urinary levels of MMP-2, MMP-9, and the
tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in patients with
steroid-sensitive nephrotic syndrome (SSNS, n = 18, median age 5) and focal
segmental glomerulosclerosis (FSGS, n = 16, median age 15). We found that
urinary concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly
elevated in FSGS patients as compared to SSNS in both relapse and remission (p
< 0.002). Furthermore, urinary levels of these enzymes are increased early
on in the FSGS disease process (chronic kidney disease stages 1 and 2). The
findings from this pilot study suggest that MMPs and TIMPs have the potential
to represent candidate, early non-invasive biomarkers for diagnosis and/or
response to therapy. In addition, they may represent therapeutic targets for
preventing chronic kidney disease progression in FSGS.

Division of Nephrology & Hypertension, Cincinnati Children's Hospital and
Medical Center, 3333 Burnet Ave, MLC 7022, Cincinnati, OH 45229, USA. kimberly.czech@cchmc.org

10.1007/s00467-011-1897-7

http://www.ncbi.nlm.nih.gov/pubmed/21720805

(37)Daikoku T, Cha J, Sun X, Tranguch S,
Xie H, Fujita T, Hirota Y, Lydon J, Demayo F, Maxson R and Dey SK

CONDITIONAL DELETION OF MSX HOMEOBOX GENES IN THE UTERUS INHIBITS BLASTOCYST
IMPLANTATION BY ALTERING UTERINE RECEPTIVITY

2011; 21:1014-1025

An effective bidirectional communication between an implantation-competent
blastocyst and the receptive uterus is a prerequisite for mammalian
reproduction. The blastocyst will implant only when this molecular cross-talk
is established. Here we show that the muscle segment homeobox gene (Msh) family
members Msx1 and Msx2, which are two highly conserved genes critical for
epithelial-mesenchymal interactions during development, also play crucial roles
in embryo implantation. Loss of Msx1/Msx2 expression correlates with altered
uterine luminal epithelial cell polarity and affects E-cadherin/beta-catenin
complex formation through the control of Wnt5a expression. Application of Wnt5a
in vitro compromised blastocyst invasion and trophoblast outgrowth on cultured
uterine epithelial cells. The finding that Msx1/Msx2 genes are critical for
conferring uterine receptivity and readiness to implantation could have
clinical significance, because compromised uterine receptivity is a major cause
of pregnancy failure in IVF programs.

Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's
Hospital Medical Center, University of Cincinnati College of Medicine,
Cincinnati, OH 45229, USA.

10.1016/j.devcel.2011.09.010

http://www.ncbi.nlm.nih.gov/pubmed/22100262

(38)Dawodu A

WHAT's NEW IN MOTHER-INFANT VITAMIN D DEFICIENCY: A 21st CENTURY PERSPECTIVE

2012; 21:2-3

Global Health Center, Cincinnati Children's Hospital Medical Center, 3333
Burnet Avenue, MLC 2048 Cincinnati, OH 45229-3039, United States

10.1159/000331904

http://www.ncbi.nlm.nih.gov/pubmed/22025133

(39)Day SB, Ledford JR, Zhou P, Lewkowich
IP and Page K

GERMAN COCKROACH PROTEASES AND PROTEASE-ACTIVATED RECEPTOR-2 REGULATE
CHEMOKINE PRODUCTION AND DENDRITIC CELL RECRUITMENT

2012; 4:100-110

We recently showed that serine proteases in German cockroach (GC) feces (frass)
decreased experimental asthma through the activation of protease-activated
receptor (PAR)-2. Since dendritic cells (DCs) play an important role in the
initiation of asthma, we queried the role of GC frass proteases in modulating
CCL20 (chemokine C-C motif ligand 20) and granulocyte macrophage
colony-stimulating factor (GM-CSF) production, factors that regulate pulmonary
DCs. A single exposure to GC frass resulted in a rapid, but transient, increase
in GM-CSF and a steady increase in CCL20 in the airways of mice. Instillation
of protease-depleted GC frass or instillation of GC frass in PAR-2-deficient
mice significantly decreased chemokine release. A specific PAR-2-activating
peptide was also sufficient to induce CCL20 production. To directly assess the
role of the GC frass protease in chemokine release, we enriched the protease
from GC frass and confirmed that the protease was sufficient to induce both
GM-CSF and CCL20 production in vivo. Primary airway epithelial cells produced
both GM-CSF and CCL20 in a protease- and PAR-2-dependent manner. Finally, we
show a decreased percentage of myeloid DCs in the lung following allergen
exposure in PAR-2-deficient mice compared to wild-type mice. However, there was
no difference in GC frass uptake. Our data indicate that, through the
activation of PAR-2, allergen-derived proteases are sufficient to induce CCL20
and GM-CSF production in the airways. This leads to increased recruitment
and/or differentiation of myeloid DC populations in the lungs and likely plays
an important role in the initiation of allergic airway responses. Copyright Â©
2011 S. Karger AG, Basel.

Division of Critical Care Medicine, Cincinnati Children's Hospital Medical
Center, Cincinnati Children's Research Foundation, 3333 Burnet Ave, ML 7006,
Cincinnati, OH 45229, United States Division of Immunobiology, Cincinnati
Children's Hospital Medical Center, Cincinnati Children's Research Foundation,
Cincinnati, OH, United States Department of Pediatrics, University of
Cincinnati, Cincinnati, OH, United States

Cited By (since 1996) 1 Export Date 11 January 2012 Source Scopus doi
10.1159/000329132 Language of Original Document English Correspondence Address
Page, K.; Division of Critical Care Medicine, Cincinnati Children's Hospital
Medical Center, Cin(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/21876326

(40)Dehmer JJ, Garrison AP, Speck KE,
Dekaney CM, Landeghem LV, Sun X, Henning SJ and Helmrath MA

EXPANSION OF INTESTINAL EPITHELIAL STEM CELLS DURING MURINE DEVELOPMENT

2011; 6:e27070

Murine small intestinal crypt development is initiated during the first
postnatal week. Soon after formation, overall increases in the number of crypts
occurs through a bifurcating process called crypt fission, which is believed to
be driven by developmental increases in the number of intestinal stem cells
(ISCs). Recent evidence suggests that a heterogeneous population of ISCs exists
within the adult intestine. Actively cycling ISCs are labeled by Lgr5, Ascl2
and Olfm4; whereas slowly cycling or quiescent ISC are marked by Bmi1 and
mTert. The goal of this study was to correlate the expression of these markers
with indirect measures of ISC expansion during development, including
quantification of crypt fission and side population (SP) sorting. Significant
changes were observed in the percent of crypt fission and SP cells consistent
with ISC expansion between postnatal day 14 and 21. Quantitative real-time
polymerase chain reaction (RT-PCR) for the various ISC marker mRNAs
demonstrated divergent patterns of expression. mTert surged earliest, during
the first week of life as crypts are initially being formed, whereas Lgr5 and
Bmi1 peaked on day 14. Olfm4 and Ascl2 had variable expression patterns. To
assess the number and location of Lgr5-expressing cells during this period,
histologic sections from intestines of Lgr5-EGFP mice were subjected to
quantitative analysis. There was attenuated Lgr5-EGFP expression at birth and
through the first week of life. Once crypts were formed, the overall number and
percent of Lgr5-EGFP positive cells per crypt remain stable throughout
development and into adulthood. These data were supported by Lgr5 in situ
hybridization in wild-type mice. We conclude that heterogeneous populations of
ISCs are expanding as measured by SP sorting and mRNA expression at distinct
developmental time points.

Department of Surgery, University of North Carolina, Chapel Hill, North
Carolina, United States of America.

10.1371/journal.pone.0027070

http://www.ncbi.nlm.nih.gov/pubmed/22102874

(41)Dorn LD, Pabst S, Sontag LM, Kalkwarf
HJ, Hillman JB and Susman EJ

BONE MASS, DEPRESSIVE, AND ANXIETY SYMPTOMS IN ADOLESCENT GIRLS: VARIATION
BY SMOKING AND ALCOHOL USE

2011; 49:498-504

PURPOSE: The purpose of the study was to examine (a) the association between
depressive and anxiety symptoms with bone health, (b) the association of
smoking or alcohol use with bone health, and, in turn (c) whether the
association between depressive and anxiety symptoms with bone health varied by
smoking or alcohol use individually or by combined use. Bone health included
total body bone mineral content (TB BMC) and bone mineral density (BMD) of the
lumbar spine, total hip, and femoral neck. Previously published data have not
examined these issues in adolescence, a period when more than 50% of bone mass
is accrued. METHODS: An observational study enrolled 262 healthy adolescent
girls by age cohort (11, 13, 15, and 17 years). Participants completed questionnaires
and interviews on substance use, depressive symptoms, and anxiety. BMC and BMD
were measured by dual-energy X-ray absorptiometry. RESULTS: Higher depressive
symptoms were associated with lower TB BMC and BMD (total hip, femoral neck).
Those with the lowest level of smoking had higher BMD of the hip and femoral
neck, whereas no main effect differences were noted by alcohol use. Regular
users of both cigarettes and alcohol demonstrated a stronger negative
association between depressive symptoms and TB BMC as compared with
nonusers/experimental users and regular alcohol users. Findings were parallel
for anxiety symptoms. CONCLUSION: Depressive and anxiety symptoms may
negatively influence bone health in adolescent girls. Consideration of multiple
substances, rather than cigarettes or alcohol separately, may be particularly
informative with respect to the association of depression with bone health.

Division of Adolescent Medicine, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio 45226, USA. lorah.dorn@cchmc.org

10.1016/j.jadohealth.2011.03.008

http://www.ncbi.nlm.nih.gov/pubmed/22018564

(42)Drissi R, Wu J, Hu Y, Bockhold C and
Dome JS

TELOMERE SHORTENING ALTERS THE KINETICS OF THE DNA DAMAGE RESPONSE AFTER
IONIZING RADIATION IN HUMAN CELLS

2011; 4:1973-1981

Studies of telomerase-deficient mice and human cell lines have showed that
telomere shortening enhances sensitivity to ionizing radiation (IR). The
molecular basis for this observation remains unclear. To better understand the
connection between telomere shortening and radiation sensitivity, we evaluated
components of the DNA damage response pathway in normal human fibroblasts with
short and long telomeres. Late-passage cells with short telomeres showed
enhanced sensitivity to IR compared with early-passage cells with longer
telomeres. Compared with early-passage cells, late-passage cells had a higher
baseline level of phosphorylated H2AX protein (gammaH2AX) before IR but
diminished peak levels of H2AX phosphorylation after treatment with IR. Both
the appearance and disappearance of gammaH2AX foci were delayed in late-passage
cells, indicative of delayed DNA repair. In contrast to the situation with
H2AX, ATM and p53 phosphorylation kinetics were similar in early- and
late-passage cells, but phosphorylation of the chromatin-bound ATM targets SMC1
and NBS1 was delayed in late-passage cells. Because impaired phosphorylation
associated with short telomeres was restricted to chromatin-bound ATM targets,
chromatin structure was assessed. DNA from cells with short telomeres was more
resistant to digestion with micrococcal nuclease, indicative of compacted
chromatin. Moreover, cells with short telomeres showed histone acetylation and
methylation profiles consistent with heterochromatin. Together our data suggest
a model in which short telomeres induce chromatin structure changes that limit
access of activated ATM to its downstream targets on the chromatin, thereby
providing a potential explanation for the increased radiation sensitivity seen
with telomere shortening. Cancer Prev Res; 4(12); 1973-81. (c)2011 AACR.

Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC
20010. Phone: 202-476-3656; Fax: 1-202-476-5648; jdome@cnmc.org; and Rachid Drissi, Division of Oncology,
Cincinnati Children's Hospital Medical Center, MLC 7013, 3333 Burnet Avenue,
Cincinnati, OH 45229. rachid.drissi@cchmc.org.

10.1158/1940-6207.CAPR-11-0069

http://www.ncbi.nlm.nih.gov/pubmed/21930799

(43)Drotar D

CONTEMPORARY DIRECTIONS IN RESEARCH ETHICS IN PEDIATRIC PSYCHOLOGY:
INTRODUCTION TO THE SPECIAL SECTION

2011; 36:1063-1070

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333
Burnet Avenue MLC 7039, Cincinnati, OH, 45229-3039, USA. Dennis.Drotar@cchmc.org.

10.1093/jpepsy/jsr077

http://www.ncbi.nlm.nih.gov/pubmed/21933810

(44)D'Souza S, Del Prete D, Jin S, Sun Q,
Huston AJ, Kostov FE, Sammut B, Hong CS, Anderson JL, Patrene KD, Yu S, Velu
CS, Xiao G, Grimes HL, Roodman GD and Galson DL

Gfi1 EXPRESSED IN BONE MARROW STROMAL CELLS IS a NOVEL OSTEOBLAST SUPPRESSOR
IN PATIENTS WITH MULTIPLE MYELOMA BONE DISEASE

2011; 118:6871-6880

Protracted inhibition of osteoblast (OB) differentiation characterizes multiple
myeloma (MM) bone disease and persists even when patients are in long-term
remission. However, the underlying pathophysiology for this prolonged OB suppression
is unknown. Therefore, we developed a mouse MM model in which the bone marrow
stromal cells (BMSCs) remained unresponsive to OB differentiation signals after
removal of MM cells. We found that BMSCs from both MM-bearing mice and MM
patients had increased levels of the transcriptional repressor Gfi1 compared
with controls and that Gfi1 was a novel transcriptional repressor of the
critical OB transcription factor Runx2. Trichostatin-A blocked the effects of
Gfi1, suggesting that it induces epigenetic changes in the Runx2 promoter.
MM-BMSC cell-cell contact was not required for MM cells to increase Gfi1 and
repress Runx2 levels in MC-4 before OBs or naive primary BMSCs, and Gfi1
induction was blocked by anti-TNF-Î± and anti-IL-7 antibodies. Importantly,
BMSCs isolated from Gfi1-/- mice were significantly resistant to MMinduced OB
suppression. Strikingly, siRNA knockdown of Gfi1 in BMSCs from MMpatients
significantly restored expression of Runx2 and OB differentiation markers.
Thus, Gfi1 may have an important role in prolonged MM-induced OB suppression
and provide a new therapeutic target for MM bone disease. Â© 2011 by The
American Society of Hematology.

Department of Medicine, Division of Hematology/Oncology, University of
Pittsburgh, Pittsburgh, PA, United States Center for Bone Biology of UPMC,
University of Pittsburgh, Pittsburgh, PA, United States University of
Pittsburgh, Veterans Administration Pittsburgh Healthcare System Research and
Development, University Dr C, Pittsburgh, PA 15240, United States Division of
Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
United States

Export Date 11 January 2012 Source Scopus CODEN BLOOA doi
10.1182/blood-2011-04-346775 Language of Original Document English
Correspondence Address Galson, D.L.; University of Pittsburgh, Veterans
Administration Pittsburgh Healthcare System Rese(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/22042697

(45)Epstein JN, Langberg JM, Lichtenstein
PK, Kolb R, Altaye M and Simon JO

USE OF AN INTERNET PORTAL TO IMPROVE COMMUNITY-BASED PEDIATRIC ADHD CARE: A
CLUSTER RANDOMIZED TRIAL

2011; 128:e1201-e1208

OBJECTIVE: To determine the effectiveness of a quality improvement program to
improve pediatricians' adherence to existing, evidence-based,
attention-deficit/hyperactivity disorder (ADHD) practice guidelines. METHODS:
Forty-nine community-based pediatricians at 8 practices participated in a
cluster-randomized trial. Practices were matched according to the numbers of
pediatricians and the proportions of patients receiving Medicaid. The medical
charts for a random sample of patients with ADHD for each of the participating
pediatricians were examined at baseline and 6 months. All practices participated
in 4 sessions of training, including didactic lectures and office flow
modification workshops. Practices were then given access to an ADHD Internet
portal that allowed parents, teachers, and pediatricians to input information
(eg, rating scales) about patients, after which information was scored,
interpreted, and formatted in a report style that was helpful for assessment
and treatment of patients with ADHD. Physicians evaluated their practice
behaviors quarterly and addressed under-performing areas. RESULTS:
Pediatricians in the intervention group, compared with those in the control
group, demonstrated significantly higher rates of many American Academy of
Pediatrics-recommended ADHD care practices, including collection of parent
(Cohen's d = 0.69) and teacher (d = 0.68) rating scales for assessment of
children with ADHD, use of Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition, criteria (d = 0.85), and use of teacher rating
scales to monitor treatment responses (d = 1.01). CONCLUSION: A quality
improvement intervention that can be widely disseminated by using
Internet-based information technology significantly improved the quality of
ADHD care in community-based pediatric settings. Copyright Â© 2011 by the
American Academy of Pediatrics.

Department of Pediatrics, College of Medicine, University of Cincinnati,
Cincinnati, OH, United States Department of Pediatrics, Cincinnati Children's
Hospital Medical Center, ML 10006, 3333 Burnet Ave, Cincinnati, OH 45229-3039,
United States

10.1542/peds.2011-0872

http://www.ncbi.nlm.nih.gov/pubmed/22007005

(46)Eshelman-Kent D, Kinahan KE, Hobbie W,
Landier W, Teal S, Friedman D, Nagarajan R and Freyer DR

CANCER SURVIVORSHIP PRACTICES, SERVICES, AND DELIVERY: a REPORT FROM THE
CHILDREN's ONCOLOGY GROUP (COG) NURSING DISCIPLINE, adolescent/young ADULT, AND
LATE EFFECTS COMMITTEES

2011; 5:345-357

PURPOSE: To describe survivorship services provided by the Children's Oncology
Group (COG), an assessment of services was undertaken. Our overall aims were
(1) to describe survivorship services, including the extent of services
provided, resources (personnel, philanthropy, and research funding), billing
practices, and barriers to care and 2) to describe models of care that are in
use for childhood cancer survivors and adult survivors of childhood cancer.
METHODS: One hundred seventy-nine of 220 COG institutions (81%) completed an
Internet survey in 2007. RESULTS: One hundred fifty-five (87%) reported
providing survivorship care. Fifty-nine percent of institutions provide care
for their pediatric population in specialized late effects programs. For adult
survivors, 47% of institutions chose models of care, which included
transitioning to adult providers for risk-based health care, while 44% of
institutions keep survivors indefinitely at the treating institution (Cancer
Center Based Model without Community Referral). Sixty-eight percent provide
survivors with a copy of their survivorship care plan. Only 31% of institutions
provide a detailed summary of results after each clinic visit, and 41% have a
database to track survivor health outcomes. Minimal time required for initial
and annual survivorship visits is estimated to be approximately 120 and 90 min,
respectively. The most prevalent barriers to care were the lack of dedicated
time for program development and a perceived insufficient knowledge on the part
of the clinician receiving the transition referral. CONCLUSIONS: Not all COG
institutions provide dedicated survivorship care, care plans, or have databases
for tracking outcomes. Transitioning to adult providers is occurring within the
COG. Survivorship care is time intensive.

Division of Hematology-Oncology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229-3039, USA. Debra.kent@cchmc.org

10.1007/s11764-011-0192-8

http://www.ncbi.nlm.nih.gov/pubmed/21894490

(47)Faigenbaum AD, Stracciolini A and Myer
GD

EXERCISE DEFICIT DISORDER IN YOUTH: A HIDDEN TRUTH

2011; 100:1423-1425

Department of Health and Exercise Science, College of New Jersey, 2000
Pennington Road, Ewing, NJ, United States Division of Sports Medicine,
Children's Hospital Boston, Harvard Medical School, Boston, MA, United States
Cincinnati Children's Hospital Medical Center, Sports Medicine Biodynamics
Center, Human Performance Laboratory, Cincinnati, OH, United States Departments
of Pediatrics and Orthopaedic Surgery, College of Medicine, University of
Cincinnati, Cincinnati, OH, United States Athletic Training Division, School of
Allied Medical Professions, Ohio State University, Columbus, OH, United States
Department of Athletic Training, Sports Orthopaedics, and Pediatric Science,
Rocky Mountain University of Health Professions, Provo, UT, United States

10.1111/j.1651-2227.2011.02461.x

http://www.ncbi.nlm.nih.gov/pubmed/21895766

(48)Ferrand Y, Magazine M, Rao US and Glass
TF

BUILDING CYCLIC SCHEDULES FOR EMERGENCY DEPARTMENT PHYSICIANS

2011; 41:521-533

Physicians at a branch of the emergency department at Cincinnati Children's
Hospital Medical Center complained that their schedules were too erratic
because of the multitude of operating requirements, regulatory constraints,
physician preferences, and holiday requests. We addressed this issue by using
integer programming to build cyclic schedules that can be repeated throughout
the year. These schedules are flexible enough o handle incorporating holidays,
work assignments, and vacation requests ex post. After we rolled out the
calendar-year-based cyclic schedule, we captured statistics to assess the
viability and the quality of the yearly schedule generated. Surveys of the
physicians and the scheduler after implementation showed that the new schedule
provides predictability and well-balanced work patterns. Â© 2011.INFORMS.

Cincinnati Children's Hospital Medical Center, Liberty Campus, Cincinnati, OH
45229, United States Department of Operations and Business Analytics,
University of Cincinnati, Cincinnati, OH 45221, United States

org/10.1287/inte.1110.0563

(49)Filipovich AH

THE EXPANDING SPECTRUM OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

2011; 11:512-516

PURPOSE OF REVIEW: Hemophagocytic lymphohistiocytosis (HLH) is more widely
recognized by clinicians. No longer viewed as a disorder of young children,
adult patients are now being identified and treated. In this review, I summarize
clinical features of patients with recently identified genetic causes, discuss
a new paradigm for understanding the clinical evolution of HLH, and update
current results with hematopoietic cell transplantation. RECENT FINDINGS: The
list of genetic defects underlying HLH continues to grow. Among the autosomal
recessive defects underlying HLH, we add STX11 (Syntaxin 11) - a snare protein,
and MUNC18-2 (also known as STXBP2 - Syntaxin-binding protein). These two
proteins now join MUNC 13-4 as components of the degranulation machinery in
cytotoxic lymphocytes, responsible for the delivery of Perforin and Granzyme B
to selectively kill target cells. The mechanism of action in the newest
X-linked disorder associated with HLH, XIAP deficiency (also termed XLP 2), is
currently unknown. Treatment of HLH has also improved in recent years, at least
in experienced centers where a significant number of patients are seen.
Clinicians who are familiar with the dynamic evolution of the disease are
learning how to modify treatment when initial or continuation therapy fails to
achieve a stable clinical status, preferably clinical remission. Use of reduced
intensity conditioning protocols pretransplant has resulted in superior
short-term and long-term survival rates of greater than 85%. SUMMARY:
Substantial progress continues to be made in exploring the complex cause and
pathophysiology of HLH. Hand in hand, a greater recognition of the condition
has led to improved treatments.

Cincinnati Children's Hospital Medical Center, University of Cincinnati,
Cincinnati, Ohio, USA. lisa.filipovich@cchmc.org

10.1097/ACI.0b013e32834c22f5

http://www.ncbi.nlm.nih.gov/pubmed/21971331

(50)Flowers SRandKashikar-Zuck S

MEASURES OF JUVENILE FIBROMYALGIA: FUNCTIONAL DISABILITY INVENTORY (FDI),
MODIFIED FIBROMYALGIA IMPACT QUESTIONNAIRE-CHILD VERSION (MFIQ-C), AND
PEDIATRIC QUALITY OF LIFE INVENTORY (PedsQL) 3.0 RHEUMATOLOGY MODULE PAIN AND
HURT SCALE

2011; 63:S431-S437

Children's Medical Center of Dayton, Dayton, OH, United States Division of
Behavioral Medicine and Clinical Psychology, MLC 3015, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH 45229, United States University of
Cincinnati College of Medicine, Cincinnati, OH, United States

10.1002/acr.20639

(51)Foster MT, Shi H, Softic S, Kohli R,
Seeley RJ and Woods SC

TRANSPLANTATION OF NON-VISCERAL FAT TO THE VISCERAL CAVITY IMPROVES GLUCOSE
TOLERANCE IN MICE: INVESTIGATION OF HEPATIC LIPIDS AND INSULIN SENSITIVITY

2011; 54:2890-2899

Aims/hypothesis: Intra-abdominal transplantation of non-visceral adipose tissue
in rodents, simulating increased abdominal fat in obesity, paradoxically
improves glucose tolerance and insulin sensitivity. We hypothesised that this
improvement is due to transplant-induced enhanced uptake of fatty acids by
adipose tissue, thus reducing fatty acid flux into, and triacylglycerol storage
in, the liver. Methods: In Experiment 1, mice were sham-operated or received
heterologous epididymal white adipose tissue (WAT; EWAT) or visceral WAT (VWAT)
transplantation to the portal and splanchnic circulation regions in the
visceral cavity. In Experiment 2, inguinal WAT (IWAT) or EWAT was removed and
subsequently transplanted to the visceral cavity of the same mouse
(autotransplant). IWAT and EWAT autotransplants were repeated in Experiment 3
and compared with heterotransplants. Results: Heterotransplantation of VWAT did
not alter glucose tolerance, whereas auto- or hetero-transplantation of EWAT or
IWAT significantly improved glucose tolerance. Transplantation-induced
improvements in glucose tolerance 4 weeks after surgery coincided with
decreased liver triacylglycerol, decreased portal plasma lipids and increased
hepatic insulin sensitivity. By 8 weeks, these changes were apparent only in
mice with autotransplantation. Heterologous EWAT transplantation-induced
glucose improvement persisted without altered liver metabolism. Conclusions/
interpretation: Increases in visceral fat, via transplantation of visceral or
non-visceral adipose tissue, is not a major risk factor for glucose
intolerance. In fact, there are dynamic metabolic improvements following
transplantation that include decreased portal lipids and improved liver
metabolism, but these improvements are transient under certain circumstances.
Â© 2011 Springer-Verlag.

Obesity Research Center, Department of Psychiatry, University of Cincinnati,
2170 E. Galbraith Road, Cincinnati, OH 45237, United States Department of
Zoology, Miami University, Oxford, OH, United States Division of
Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,
Cincinnati Childrens Hospital Medical Center, Cincinnati, OH, United States
Department of Internal Medicine, University of Cincinnati, Cincinnati, OH,
United States

10.1007/s00125-011-2259-5

http://www.ncbi.nlm.nih.gov/pubmed/21805228

(52)Fountain-Capal J, Holland KD, Gilbert
DL and Hallinan BE

WHEN SHOULD CLINICIANS ORDER GENETIC TESTING FOR DRAVET SYNDROME?

2011; 45:319-323

The role of neuronal voltage-gated sodium channel, alpha-1 subunit (SCN1A) gene
mutations in Dravet syndrome is well-established. With a broader phenotype than
initially described, some patients lack features of Dravet syndrome as defined
by the International League Against Epilepsy. We evaluated the predictive value
of International League Against Epilepsy criteria for a positive mutation in a
cohort of consecutively tested children. Mutations of SCN1A were evident in 16
of 69 children. Exhibiting >/=4 International League Against Epilepsy
criteria demonstrated 100% sensitivity. Seven criteria (resistance to multiple
antiepileptic drugs, multiple seizure types, abnormal electroencephalogram
features, exacerbation with hyperthermia, normal development before seizure
onset, seizures beginning before age 1 year, and psychomotor retardation) were
present in >/=85% of mutation-positive cases. The three criteria that best
predicted a mutation in SCN1A included exacerbation with hyperthermia, normal
development before seizure onset, and the appearance of ataxia, pyramidal
signs, or interictal myoclonus. We have demonstrated a high-sensitivity testing
strategy for detecting mutations of SCN1A in children with suspected Dravet
syndrome.

Division of Pediatric Neurology, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio 45229-3039, USA. jamiekcapal@gmail.com

10.1016/j.pediatrneurol.2011.08.001

http://www.ncbi.nlm.nih.gov/pubmed/22000312

(53)Franciosi JP, Hommel KA, DeBrosse CW,
Greenberg AB, Greenler AJ, Abonia JP, Rothenberg ME and Varni JW

DEVELOPMENT OF a VALIDATED PATIENT-REPORTED SYMPTOM METRIC FOR PEDIATRIC
EOSINOPHILIC ESOPHAGITIS: QUALITATIVE METHODS

2011; 11Background: Previous attempts to measure symptoms in pediatric
Eosinophilic Esophagitis (EoE) have not fully included patients and parents in
the item development process. We sought to identify and validate key patient
self-reported and parent proxy-reported outcomes (PROs) specific to
EoE.Methods: We developed methodology for focus and cognitive interviews based
on the Food and Drug Administration (FDA) guidelines for PROs, the validated
generic PedsQLâ„¢ guidelines, and the consolidated criteria for reporting
qualitative research (COREQ). Both child (ages 8-12 and 13-18) and parent-proxy
(ages 2-4, 5-7, 8-12, and 13-18) interviews were conducted.Results: We
conducted 75 interviews to construct the new instrument. Items were identified
and developed from individual focus interviews, followed by cognitive
interviews for face and content validation. Initial domains of symptom
frequency and severity were developed, and open-ended questions were used to
generate specific items during the focus interviews. Once developed, the
instrument construct, instructions, timeframe, scoring, and specific items were
systematically reviewed with a separate group of patients and their parents
during the cognitive interviews.Conclusions: To capture the full impact of
pediatric EoE, both histologic findings and PROs need to be included as equally
important outcome measures. We have developed the face and content validated
Pediatric Eosinophilic Esophagitis Symptom Score (PEESSâ„¢ v2.0). The PEESSâ„¢
v2.0 metric is now undergoing multisite national field testing as the next
iterative instrument development phase. Â© 2011 Franciosi et al; licensee
BioMed Central Ltd.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH, United States Center for the Promotion
of Treatment Adherence and Self-Management, Division of Behavioral Medicine and
Clinical Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH, United States Division of Allergy and Immunology, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH, United States Clinical Trials Office,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
Department of Pediatrics, College of Medicine, Department of Landscape
Architecture and Urban Planning, College of Architecture, Texas A and M
University, College Station, TX, United States

10.1186/1471-230x-11-126

http://www.ncbi.nlm.nih.gov/pubmed/22099448

(54)Frawley KJ, Anton CG, Zbojniewicz AM
and Cornwall R

CT EVALUATION OF EXTENSOR TENDON ENTRAPMENT AS a COMPLICATION OF a DISTAL
RADIAL FRACTURE IN a CHILD

2011; 41:1472-1475

Extensor indicis proprius (EIP) entrapment is a rare complication of a distal
radial fracture. We report an 11-year-old with limited flexion of her index
finger 1 year after a distal radial fracture. The utility of cross-sectional
imaging in the diagnosis and preoperative planning of this complication is
presented.

Department of Radiology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, USA. kieran_frawley@health.qld.gov.au

10.1007/s00247-011-2029-z

http://www.ncbi.nlm.nih.gov/pubmed/21487674

(55)Frenck R, J., Thompson A, Yeh SH,
London A, Sidhu MS, Patterson S, Gruber WC, Emini EA, Scott DA, Gurtman A and
Study G

IMMUNOGENICITY AND SAFETY OF 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN
CHILDREN PREVIOUSLY IMMUNIZED WITH 7-VALENT PNEUMOCOCCAL CONJUGATE VACCINE

2011; 30:1086-1091

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) has proven
highly effective in preventing diseases caused by Streptococcus pneumoniae;
however, in some regions, serotype coverage is limited. A recently licensed
13-valent PCV (PCV13) was developed to provide additional coverage globally.
Children previously vaccinated with PCV7 could benefit from supplemental
vaccination with PCV13 to provide protection against the 6 additional serotypes
in PCV13. This open-label study evaluated the immunogenicity and safety of administering
PCV13 to healthy children previously vaccinated with PCV7. METHODS: Children
between 15 months and 2 years of age (group 1) received 2 doses of PCV13;
children between 2 and 5 years (group 2) received 1 dose. Antibodies
(immunoglobulin G) against the polysaccharide antigens in PCV13 were measured
before vaccination and 1 month after the final dose. Solicited local and
systemic adverse events (AEs) were collected for 7 days postvaccination.
Unsolicited and serious AEs were collected throughout. RESULTS: A total of 284
subjects (group 1: n = 109; group 2: n = 175) had blood available for testing.
Antipneumococcal immunoglobulin G geometric mean fold rises ranged from 2- to
19-fold for the PCV7 serotypes and from approximately 2- to 124-fold for the 6
additional serotypes. Additionally, postvaccination titers in excess of 0.35
mug/mL, the serologic correlate of immunity against pneumococcus for children,
occurred in >/=98% of subjects in both groups for 12 of the 13 serotypes in
PCV13. Slightly lower percentage of subjects, 94.5% and 92% of subjects in
group 1 and group 2, respectively, had postvaccine titers for serotype 3
exceeding the serologic correlate of immunity. Reactogenicity was typically
mild and self-limited, and unsolicited AEs reported were generally consistent
with common childhood illnesses. CONCLUSION: PCV13 was safe and immunogenic
when administered to children who had previously received PCV7, and can be used
for supplemental vaccination to provide additional protection against the 6 additional
serotypes.

Cincinnati Children's Hospital Medical Center, Department of Pediatrics,
Cincinnati, OH 45229, USA. Robert.Frenck@cchmc.org

10.1097/INF.0b013e3182372c6a

http://www.ncbi.nlm.nih.gov/pubmed/21983216

(56)Froehlich TE, Epstein JN, Nick TG,
Melguizo Castro MS, Stein MA, Brinkman WB, Graham AJ, Langberg JM and Kahn RS

PHARMACOGENETIC PREDICTORS OF METHYLPHENIDATE DOSE-RESPONSE IN
ATTENTION-deficit/hyperactivity DISORDER

2011; 50:1129-1139 e2

OBJECTIVE: Because of significant individual variability in
attention-deficit/hyperactivity disorder (ADHD) medication response, there is
increasing interest in identifying genetic predictors of treatment effects.
This study examined the role of four catecholamine-related candidate genes in
moderating methylphenidate (MPH) dose-response. METHOD: Eighty-nine
stimulant-naive children with ADHD 7 to 11 years old participated in a
randomized, double-blind, crossover trial of long-acting MPH. Parents and
teachers assessed each child's response on placebo and three MPH dosage levels
using the Vanderbilt ADHD rating scales. Children were genotyped for
polymorphisms in the 3' untranslated region of dopamine transporter (DAT), exon
3 on dopamine receptor D(4) (DRD4), codon 158 on catechol-O-methyltransferase,
and the adrenergic alpha(2A)-receptor promoter. Linear mixed models evaluated
gene, dose (milligrams per kilogram per day), and gene-by-dose effects on
inattentive and hyperactive-impulsive domain outcomes. RESULTS: The most
statistically significant gene-by-dose interactions were observed on
hyperactive-impulsive symptoms for DRD4 and DAT polymorphisms, with
participants lacking the DAT 10-repeat allele showing greater improvements in
symptoms with increasing dose compared with 10-repeat carriers (p = .008) and
those lacking the DRD4 4-repeat allele showing less improvement across MPH
doses compared with 4-repeat carriers (p = 0.02). CONCLUSIONS: This study
suggests that DAT and DRD4 polymorphisms may be associated with individual
variability in MPH dose-response, although further research in larger samples
is required to confirm these findings and their clinical utility. CLINICAL TRIAL
REGISTRATION INFORMATION: Response Variability in Children with
Attention-Deficit/Hyperactivity Disorder (ADHD); http://www.clinicaltrials.gov;
NCT01238822.

University of Cincinnati College of Medicine and Cincinnati Children's Hospital
Medical Center, Cincinnati, OH 45229, USA. tanya.froehlich@cchmc.org

10.1016/j.jaac.2011.08.002

http://www.ncbi.nlm.nih.gov/pubmed/22024001

(57)Fusakio ME, Mohammed JP, Laumonnier Y,
Hoebe K, Kohl J and Mattner J

C5a REGULATES NKT AND NK CELL FUNCTIONS IN SEPSIS

2011; 187:5805-5812

Complement, NKT, and NK cells play critical roles in the first line defense
against pathogens. Functional roles for both C5a receptors, that is, complement
receptor C5a (C5aR) and C5a receptor-like 2 (C5L2), in sepsis have been
demonstrated. However, the role of C5a in innate lymphocyte activation during sepsis
remains elusive. In this article, we show that naive NKT and NK cells already
express high levels of C5aR and minor levels of C5L2 mRNA, but no protein. Upon
Escherichia coli-induced sepsis, we found C5aR surface expression on
subpopulations of NKT and NK cells, suggesting rapid translation into C5aR
protein on bacterial encounter. Importantly, significantly increased survival
in the absence of C5aR, NKT, and NK cells, but not of C5L2, was associated with
reduced IFN-gamma and TNF-alpha serum levels. Sepsis induction in
C5aR(+)/C5aR(-) mixed bone marrow chimeras identified cognate engagement of
C5aR on NKT cells as an important factor for the recruitment of NKT cells.
Furthermore, we found synergistic interaction between C5aR and TLRs enhancing
the production of TNF-alpha and IFN-gamma from NKT and NK cells in cocultures
with dendritic cells. Our results identify C5aR activation as a novel pathway
driving detrimental effects of NKT and NK cells during early experimental
sepsis.

Division of Immunobiology, Cincinnati Children's Hospital, Cincinnati, OH
45229, USA.

10.4049/jimmunol.1100338

http://www.ncbi.nlm.nih.gov/pubmed/22058413

(58)Gamis AS, Alonzo TA, Gerbing RB, Hilden
JM, Sorrell AD, Sharma M, Loew TW, Arceci RJ, Barnard D, Doyle J, Massey G,
Perentesis J, Ravindranath Y, Taub J and Smith FO

NATURAL HISTORY OF TRANSIENT MYELOPROLIFERATIVE DISORDER CLINICALLY
DIAGNOSED IN DOWN SYNDROME NEONATES: A REPORT FROM THE CHILDREN's ONCOLOGY
GROUP STUDY A2971

2011; 118:6752-6759

Transient myeloproliferative disorder (TMD), restricted to newborns with
trisomy 21, is a megakaryocytic leukemia that although lethal in some is
distinguished by its spontaneous resolution. Later development of acute myeloid
leukemia (AML) occurs in some. Prospective enrollment (n = 135) elucidated the
natural history in Down syndrome (DS) patients diagnosed with TMD via the use
of uniform monitoring and intervention guidelines. Prevalent at diagnosis were
leukocytosis, peripheral blast exceeding marrow blast percentage, and
hepatomegaly. Among those with life-threatening symptoms, most (n = 29/38; 76%)
received intervention therapy until symptoms abated and then were monitored
similarly. Organomegaly with cardiopulmonary compromise most frequently led to
intervention (43%). Death occurred in 21% but only 10% were attributable to TMD
(intervention vs observation patients: 13/14 vs 1/15 because of TMD). Among
those solely observed, peripheral blasts and all other TMD symptoms cleared at
a median of 36 and 49 days from diagnosis, respectively. On the basis of the
diagnostic clinical findings of hepatomegaly with or without life-threatening
symptoms, 3 groups were identified with differing survival: low risk with
neither finding (38%), intermediate risk with hepatomegaly alone (40%), and
high risk with both (21%; overall survival: 92% Â± 8%, 77% Â± 12%, and 51% Â±
19%, respectively; P â‰¤ .001). Among all, AML subsequently occurred in 16% at
a median of 441 days (range, 118-1085 days). The trial is registered at http://www.clinicaltrials.gov
as NCT00003593. Â© 2011 by The American Society of Hematology.

Children's Mercy Hospitals and Clinics, 2401 Gillham Rd, Kansas City, MO 64108,
United States University of Southern California, Los Angeles, CA, United States
Childrens Oncology Group, Arcadia, CA, United States Children's Hospital
Colorado, Denver, CO, United States City of Hope, Duarte, CA, United States
University of Missouri, Columbia, MO, United States Johns Hopkins University,
Baltimore, MD, United States IWK Health Center, Halifax, NS, Canada Hospital
for Sick Children, Toronto, ON, Canada Virginia Commonwealth University,
Richmond, VA, United States Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Children's Hospital of Michigan, Detroit, MI,
United States

Cited By (since 1996) 1 Export Date 11 January 2012 Source Scopus CODEN BLOOA
doi 10.1182/blood-2011-04-350017 Language of Original Document English
Correspondence Address Gamis, A.S.; Children's Mercy Hospitals and Clinics,
2401 Gillham Rd, Kan(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/21849481

(59)Garza JM, Nylund CM and Kaul A

TIME TO STOP BLAMING GASTROESOPHAGEAL REFLUX

2011; 50:1110-1115

OBJECTIVES. Cough, pain, and desaturation episodes in infants are often
ascribed to gastroesophageal reflux, and many are empirically treated with acid
suppression medications. The authors hypothesize that most of these symptoms
are not related to gastroesophageal reflux. METHODS. Retrospective review of
186 combined pH-multichannel intraluminal impedance studies performed in
infants at Cincinnati Children's Hospital. RESULTS. Of 4159 symptoms reported
1504 (36%) were associated with reflux events (27% nonacid and 9% acid). When
total number of symptoms and reflux events were taken into consideration,
nonacid reflux events were as likely to be associated with a symptom as acid
reflux events (P = .66). CONCLUSION. The extra-esophageal symptoms commonly
attributed to gastroesophageal reflux in infants are most often not associated
with a reflux event. Even though causality cannot be definitively proven, in
the minority in whom a symptom association is observed, nonacid events are as
likely as acid events to cause symptoms.

Cincinnati Children's Hospital Medical Center, OH, USA. jose.garza@cchmc.org

10.1177/0009922811412585

http://www.ncbi.nlm.nih.gov/pubmed/21685210

(60)Geraghty SR

PHOTO ALBUM OF PUMPED BREASTMILK

2011; 6:433-434

Center for Breastfeeding Medicine, Cincinnati Children's Hospital Medical
Center , Cincinnati, Ohio.

10.1089/bfm.2010.0058

http://www.ncbi.nlm.nih.gov/pubmed/21133763

(61)Greiner HM, Park YD, Holland K, Horn
PS, Byars AW, Mangano FT, Smith JR, Lee MR and Lee KH

SCALP EEG DOES NOT PREDICT HEMISPHERECTOMY OUTCOME

2011; 20:758-763

BACKGROUND: Functional hemispherectomy is effective in carefully selected
patients, resulting in a reduction of seizure burden up to complete resolution,
improvement of intellectual development, and developmental benefit despite
possible additional neurological deficit. Despite apparent hemispheric
pathology on brain magnetic resonance imaging (MRI) or other imaging tests,
scalp electroencephalography (EEG) could be suggestive of bilateral ictal onset
or even ictal onset contralateral to the dominant imaging abnormality. We aimed
to investigate the role of scalp EEG lateralization pre-operatively in
predicting outcome. METHODS: We retrospectively reviewed 54 patients who
underwent hemispherectomy between 1991 and 2009 at Medical College of Georgia
(1991-2006) and Cincinnati Children's Hospital Medical Center (2006-2009) and
had at least one year post-operative follow-up. All preoperative EEGs were
reviewed, and classified as either lateralizing or nonlateralizing, for both
ictal and interictal EEG recordings. RESULTS: Of 54 patients, 42 (78%) became
seizure free. Twenty-four (44%) of 54 had a nonlateralizing ictal or interictal
EEG. Further analysis was based on etiology of epilepsy, including malformation
of cortical development (MCD), Rasmussen syndrome (RS), and stroke (CVA). EEG
nonlateralization did not predict poor outcome in any of the etiology groups
evaluated. CONCLUSION: Scalp EEG abnormalities in contralateral or bilateral hemispheres
do not, in isolation, predict a poor outcome from hemispherectomy. Results of
other non-invasive and invasive evaluations should be used to determine
candidacy.

Department of Pediatrics, Division of Child Neurology, Cincinnati Children's,
Hospital Medical Center, 3333 Burnet Avenue, MLC 2015, Cincinnati, OH, United
States.

10.1016/j.seizure.2011.07.006

http://www.ncbi.nlm.nih.gov/pubmed/21813300

(62)Hammill AM, Wentzel M, Gupta A, Nelson
S, Lucky A, Elluru R, Dasgupta R, Azizkhan RG and Adams DM

SIROLIMUS FOR THE TREATMENT OF COMPLICATED VASCULAR ANOMALIES IN CHILDREN

2011; 57:1018-1024

BACKGROUND: Vascular anomalies comprise a diverse group of diagnoses. While
infantile hemangiomas are common, the majority of these conditions are quite
rare and have not been widely studied. Some of these lesions, though benign,
can impair vital structures, be deforming, or even become life-threatening.
Vascular tumors such as kaposiform hemangioendotheliomas (KHE) and complicated
vascular malformations have proven particularly difficult to treat. PROCEDURE:
Here we retrospectively evaluate a series of six patients with complicated,
life-threatening vascular anomalies who were treated with the mTOR inhibitor
sirolimus for compassionate use at two centers after failing multiple other
therapies. RESULTS: These patients showed significant improvement in clinical
status with tolerable side effects. CONCLUSIONS: Sirolimus appears to be
effective and safe in patients with life-threatening vascular anomalies and
represents an important tool in treating these diseases. These findings are
currently being further evaluated in a Phase II safety and efficacy trial.

Hemangioma and Vascular Malformation Center, Cincinnati Children's Hospital
Medical Center, Cincinnati, Ohio, USA. adrienne.hammill@cchmc.org

10.1002/pbc.23124

http://www.ncbi.nlm.nih.gov/pubmed/21445948

(63)Hilliard MEandHood KK

TAKING EVIDENCE-BASED COPING SKILLS TRAINING TO THE INTERNET

2011; 11:464-466

Center for Treatment Adherence, Division of Behavioral Medicine and Clinical
Psychology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
45229, USA.

10.1007/s11892-011-0221-z

http://www.ncbi.nlm.nih.gov/pubmed/21842262

(64)Hillman NH, Nitsos I, Berry C, Pillow
JJ, Kallapur SG and Jobe AH

POSITIVE END-EXPIRATORY PRESSURE AND SURFACTANT DECREASE LUNG INJURY DURING
INITIATION OF VENTILATION IN FETAL SHEEP

2011; 301:L712-20

The initiation of ventilation in preterm, surfactant-deficient sheep without
positive end-expiratory pressure (PEEP) causes airway injury and lung
inflammation. We hypothesized that PEEP and surfactant treatment would decrease
the lung injury from initiation of ventilation with high tidal volumes. Fetal
sheep at 128-day gestational age were randomized to ventilation with: 1) no
PEEP, no surfactant; 2) 8-cmH(2)O PEEP, no surfactant; 3) no PEEP + surfactant;
4) 8-cmH(2)O PEEP + surfactant; or 5) control (2-cmH(2)O continuous positive
airway pressure) (n = 6-7/group). After maternal anesthesia and hysterotomy,
the head and chest were exteriorized, and the fetus was intubated. While
maintaining placental circulation, the fetus was ventilated for 15 min with a
tidal volume escalating to 15 ml/kg using heated, humidified, 100% nitrogen.
The fetus then was returned to the uterus, and tissue was collected after 30
min for evaluation of early markers of lung injury. Lambs receiving both
surfactant and PEEP had increased dynamic compliance, increased static lung
volumes, and decreased total protein and heat shock proteins 70 and 60 in
bronchoalveolar lavage fluid compared with other groups. Ventilation,
independent of PEEP or surfactant, increased mRNA expression of acute phase
response genes and proinflammatory cytokine mRNA in the lung tissue compared
with controls. PEEP decreased mRNA for cytokines (2-fold) compared with groups
receiving no PEEP. Surfactant administration further decreased some cytokine
mRNAs and changed the distribution of early growth response protein-1
expression. The use of PEEP during initiation of ventilation at birth decreased
early mediators of lung injury. Surfactant administration changed the
distribution of injury and had a moderate additive protective effect.

Cincinnati Children's Hospital Medical Center, Division of Pulmonary Biology,
3333 Burnet Ave., Cincinnati, OH 45229-3039, USA. Noah.Hillman@cchmc.org

10.1152/ajplung.00157.2011

http://www.ncbi.nlm.nih.gov/pubmed/21856815

(65)Hinton RB

GENETIC CONTRIBUTION TO BICUSPID AORTIC VALVE MORPHOLOGY

2011; 155:2899-2900

Division of Cardiology, The Heart Institute, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States

10.1002/ajmg.a.34277

(66)Hirota Y, Cha J, Yoshie M, Daikoku T
and Dey SK

HEIGHTENED UTERINE MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1 (mTORC1)
SIGNALING PROVOKES PRETERM BIRTH IN MICE

2011; 108:18073-18078

Although preterm delivery is a major global health issue, its causes and
underlying mechanism remain elusive. Using mutant mice, mimicking aspects of
human preterm birth, we show here that uterine decidual senescence early in
pregnancy via heightened mammalian target of rapamycin complex 1 (mTORC1)
signaling is a significant contributor of preterm birth and fetal death, and
that these adverse phenotypes are rescued by a low dose of rapamycin, an
inhibitor of mTORC1 signaling. This role of mTORC1 signaling in determining the
timing of birth in mice may help us better understand the mechanism of the
timing of birth in humans and develop new and improved strategies to combat the
global problem of preterm birth.

Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children's
Research Foundation, Cincinnati, OH 45229, USA.

10.1073/pnas.1108180108

http://www.ncbi.nlm.nih.gov/pubmed/22025690

(67)Hobson MJandWong HR

FINDING NEW THERAPIES FOR SEPSIS: THE NEED FOR PATIENT STRATIFICATION AND
THE USE OF GENETIC BIOMARKERS

2011; 15:1009

ABSTRACT: Reversing the immunoparalysis associated with septic shock remains a
priority for improving the outcome of patients suffering from sepsis. The
efficacy of future therapies may be better studied under an effective system of
patient stratification. Gene expression biomarkers offer a mechanism by which
patients may be appropriately stratified in such clinical trials.

Division of Critical Care Medicine, Cincinnati Children's Hospital Medical
Center and Cincinnati Children's Research Foundation, Department of Pediatrics,
University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA. hector.wong@cchmc.org.

10.1186/cc10527

http://www.ncbi.nlm.nih.gov/pubmed/22169064

(68)Hood KK, Rausch JR and Dolan LM

DEPRESSIVE SYMPTOMS PREDICT CHANGE IN GLYCEMIC CONTROL IN ADOLESCENTS WITH
TYPE 1 DIABETES: RATES, MAGNITUDE, AND MODERATORS OF CHANGE

2011; 12:718-723

OBJECTIVE: To determine whether depressive symptoms in adolescents with type 1
diabetes predict change in glycemic control over time. RESEARCH DESIGN AND
METHODS: A total of 145 adolescents (aged 13-18 yr) participated in two study
visits (baseline and 6 months). They completed a measure of depressive symptoms
(Children's Depression Inventory; CDI) and had their A1c values and adherence
to blood glucose monitoring (BGM) documented. RESULTS: Three variables
predicted A1c change over 6 months: CDI change score (B = 0.11; p < 0.001),
BGM frequency at baseline (B = -0.21; p = 0.03), and A1c at baseline (B =
-0.23; p = 0.002). A three-way interaction among these variables was
significant (p < 0.01) and showed that adolescents with high adherence to
BGM who were achieving optimal glycemic control (</=7.5%) at baseline were
resistant to increasing A1c values, even if depressive symptoms worsened.
However, as adherence to BGM declines, there is a synergistic effect with
depressive symptoms to accelerate the increase of A1c values over time, making
it more difficult to bring A1c back to optimal levels. CONCLUSIONS: Results
suggest that depressive symptoms are important predictors of A1c change by
themselves as well as when considered with adherence to BGM. There is a need to
screen for depressive symptoms and expand and develop prevention and
intervention strategies in order to put adolescents with type 1 diabetes in the
best position for optimal glycemic control.

Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH 45229, USA. korey.hood@cchmc.org

10.1111/j.1399-5448.2011.00771.x

http://www.ncbi.nlm.nih.gov/pubmed/21564454

(69)Howell JCandWells JM

GENERATING INTESTINAL TISSUE FROM STEM CELLS: POTENTIAL FOR RESEARCH AND
THERAPY

2011; 6:743-755

Intestinal resection and malformations in adult and pediatric patients result
in devastating consequences. Unfortunately, allogeneic transplantation of
intestinal tissue into patients has not been met with the same measure of
success as the transplantation of other organs. Attempts to engineer intestinal
tissue in vitro include disaggregation of adult rat intestine into subunits
called organoids, harvesting native adult stem cells from mouse intestine and
spontaneous generation of intestinal tissue from embryoid bodies. Recently, by
utilizing principles gained from the study of developmental biology, human
pluripotent stem cells have been demonstrated to be capable of directed
differentiation into intestinal tissue in vitro. Pluripotent stem cells offer a
unique and promising means to generate intestinal tissue for the purposes of
modeling intestinal disease, understanding embryonic development and providing
a source of material for therapeutic transplantation.

Division of Endocrinology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229-3039, USA.

10.2217/rme.11.90

http://www.ncbi.nlm.nih.gov/pubmed/22050526

(70)Huang G, Zhao X, Wang L, Elf S, Xu H,
Sashida G, Zhang Y, Liu Y, Lee J, Menendez S, Yang Y, Yan X, Zhang P, Tenen DG,
Osato M, Hsieh JJD and Nimer SD

THE ABILITY OF MLL TO BIND RUNX1 AND METHYLATE H3K4 AT PU.1 REGULATORY
REGIONS IS IMPAIRED BY MDS/AML-ASSOCIATED RUNX1/AML1 MUTATIONS

2011; 118:6544-6552

The mixed-lineage leukemia (MLL) H3K4 methyltransferase protein, and the
heterodimeric RUNX1/CBFÎ² transcription factor complex, are critical for
definitive and adult hematopoiesis, and both are frequently targeted in human
acute leukemia. We identified a physical and functional interaction between
RUNX1 (AML1) and MLL and show that both are required to maintain the histone
lysine 4 trimethyl mark (H3K4me3) at 2 critical regulatory regions of the AML1
target gene PU.1. Similar to CBFÎ², we show that MLL binds to AML1 abrogating
its proteasome-dependent degradation. Furthermore, a subset of previously uncharacterized
frame-shift and missense mutations at the N terminus of AML1, found in MDS and
AML patients, impairs its interaction with MLL, resulting in loss of the
H3K4me3 mark within PU.1 regulatory regions, and decreased PU.1 expression. The
interaction between MLL and AML1 provides a mechanism for the sequence-specific
binding of MLL to DNA, and identifies RUNX1 target genes as potential effectors
of MLL function. Â© 2011 by The American Society of Hematology.

Molecular Pharmacology and Chemistry Program, Sloan-Kettering Institute,
Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Box 575, New York, NY
10065, United States Divisions of Experimental Hematology and Cancer Biology,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, United States
Cancer Science Institute, National University of Singapore, Singapore,
Singapore Department of Medicine, Washington University School of Medicine, St
Louis, MO, United States

10.1182/blood-2010-11-317909

http://www.ncbi.nlm.nih.gov/pubmed/22012064

(71)Ida JB, Stark MW, Xiang Z and
Fazekas-May M

LARYNGEAL CANCER INVOLVING a BRANCHIAL CLEFT CYST

2011; 33:1796-1799

BACKGROUND: Benign secondary neck lesions in the setting of laryngeal cancer
have been described, but not with branchial cleft cysts. This article describes
a branchial cleft cyst in a laryngectomy/neck dissection specimen. METHODS AND
RESULTS: A 44-year-old woman presented to our emergency department with an
obstructing laryngeal tumor that was staged as a T4N0M0 squamous cell cancer on
the basis of clinical and radiographic findings. After laryngectomy with
bilateral neck dissections, the neck specimen contained a right-sided branchial
cleft cyst, which was directly invaded by tumor. In addition, the location of
the cyst relative to the larynx suggested that this was a third branchial cleft
cyst. CONCLUSION: This is the first report of a laryngeal carcinoma invading a
branchial cleft cyst. Staging discrepancies may result from concurrent head and
neck lesions, altering treatment plans, or changing the prognosis for the
patient. Lesions such as this are nearly impossible to diagnose preoperatively,
and a high index of suspicion for advanced cancer should be maintained.

Department of Otolaryngology-Head and Neck Surgery, Cincinnati Children's
Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio, USA. jonathan.ida@cchmc.org

10.1002/hed.21476

http://www.ncbi.nlm.nih.gov/pubmed/20629072

(72)Istaphanous GK, McAuliffe JJ and Loepke
AW

IN REPLY

2011; 115:1133-1135

*Cincinnati Children's Hospital Medical Center, University of Cincinnati
College of Medicine, Cincinnati, Ohio. pedsanesthesia@gmail.com.

(73)Iwane MK, Prill MM, Lu X, Miller EK,
Edwards KM, Hall CB, Griffin MR, Staat MA, Anderson LJ, Williams JV, Weinberg
GA, Ali A, Szilagyi PG, Zhu Y and Erdman DD

HUMAN RHINOVIRUS SPECIES ASSOCIATED WITH HOSPITALIZATIONS FOR ACUTE
RESPIRATORY ILLNESS IN YOUNG US CHILDREN

2011; 204:1702-1710

Background.The contribution of human rhinovirus (HRV) to severe acute
respiratory illness (ARI) is unclear.Objective.To assess the association
between HRV species detection and ARI hospitalizations.Methods.Children <5
years old hospitalized for ARI were prospectively enrolled between December
2003 and April 2005 in 3 US counties. Asymptomatic controls were enrolled
between December 2003 and March 2004 and between October 2004 and April 2005 in
clinics. Nasal and throat swab samples were tested for HRV and other viruses
(ie, respiratory syncytial virus, human metapneumovirus, parainfluenza virus,
and influenza virus) by reverse-transcription-polymerase chain reaction, and
genetic sequencing identified HRV species and types. HRV species detection was
compared between controls and patients hospitalized during months in which
controls were enrolled.Results.A total of 1867 children with 1947 ARI
hospitalizations and 784 controls with 790 clinic visits were enrolled and
tested for HRV. The HRV-A detection rate among participants â‰¥24 months old
was 8.1% in the hospitalized group and 2.2% in the control group (P =. 009),
and the HRV-C detection rates among those â‰¥6 months old were 8.2% and 3.9%,
respectively (P =. 002); among younger children, the detection rates for both
species were similar between groups. The HRV-B detection rate was â‰¤1%. A
broad diversity of HRV types was observed in both groups. Clinical
presentations were similar among HRV species. Compared with children infected
with other viruses, children with HRV detected were similar for severe hospital
outcomes and more commonly had histories or diagnoses of asthma or wheezing. Â©
Published by Oxford University Press on behalf of the Infectious Diseases
Society of America 2011.

National Center for Immunization and Respiratory Diseases, Centers for Disease
Control and Prevention, 1600 Clifton Rd, Atlanta, GA 30333, United States
Department of Pediatrics, Emory University, School of Medicine, Atlanta, GA,
United States Departments of Pediatrics, United States Preventive Medicine, United
States Biostatistics, Vanderbilt University, Medical Center, Nashville, TN,
United States Department of Pediatrics, University of Rochester, School of
Medicine and Dentistry, NY, United States Department of Pediatrics, Cincinnati
Children's Hospital, Medical Center, OH, United States

10.1093/infdis/jir634

http://www.ncbi.nlm.nih.gov/pubmed/22013207

(74)Johnson K, Brehm SB, Weinrich B,
Meinzen-Derr J and de Alarcon A

COMPARISON OF THE PEDIATRIC VOICE HANDICAP INDEX WITH PERCEPTUAL VOICE
ANALYSIS IN PEDIATRIC PATIENTS WITH VOCAL FOLD LESIONS

2011; 137:1258-1262

OBJECTIVE: To compare a subjective patient/family-derived voice handicap survey
with an expert observer-derived method of evaluating voice disturbance in
pediatric patients with vocal fold lesions (VFLs). DESIGN: Retrospective
review. SETTING: Tertiary care referral center. PATIENTS: Thirty-eight children
with VFLs referred for voice evaluation. MAIN OUTCOME MEASURES: Pediatric Voice
Handicap Index (pVHI) scores and Consensus Auditory-Perceptual Evaluation of
Voice (CAPE-V) scores. Percentages for CAPE-V (100-point scale) and pVHI
(92-point scale) were calculated for direct comparisons. Relationships between
pVHI scores and CAPE-V scores were investigated using the Spearman rank
correlation. RESULTS: Thirty-eight patients with VFLs (median age, 8.3 years;
age range, 4.2-17.2 years; 63% males) were included from a database of more
than 600 children and evaluated between November 15, 2005, and June 15, 2010.
The median CAPE-V overall score was 30.3 (range, 1-67), and the normalized
total pVHI score was 29.3 (range, 0-73) (P = .90). The Spearman rank
correlation showed significant fair correlations between CAPE-V overall and
functional pVHI and between CAPE-V strain and breathiness, and the pVHI total,
functional, but none higher than rho = 0.44 (P </= .03). The correlation was
higher in males for CAPE-V loudness to total pVHI (rho = 0.40, P = .04) and in
females for CAPE-V breathiness (rho = 0.58, P = .03) and strain (rho = 0.55, P
= .04) to total pVHI. CONCLUSIONS: The CAPE-V and the pVHI are useful tools in
the measurement of voice outcomes in children with VFLs. There are fair
correlations between the CAPE-V and the pVHI, and they likely evaluate
important yet different aspects of voice disturbance. Significant gender
differences in these correlations should be further evaluated in future
studies.

Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 2018,
Cincinnati, OH 45229-3039. alessandro.dealarcon@cchmc.org.

10.1001/archoto.2011.193

http://www.ncbi.nlm.nih.gov/pubmed/22183908

(75)Kamani NR, Kumar S, Hassebroek A, Eapen
M, LeRademacher J, Casper J, Cowan M, SÃ¡nchez dT, Ferster A, Szabolcs P,
Wingard JR, Horwitz E and Filipovich AH

MALIGNANCIES AFTER HEMATOPOIETIC CELL TRANSPLANTATION FOR PRIMARY IMMUNE
DEFICIENCIES: A REPORT FROM theÂ center FOR INTERNATIONAL BLOOD AND MARROW
TRANSPLANT RESEARCH

2011; 17:1783-1789

We describe the incidence of malignancy in patients with primary
immunodeficiency disorders (PIDD) following hematopoietic cell transplantation
(HCT). From the Center for International Blood and Marrow Transplant Research,
2266 PIDD patients who had undergone allogeneic HCT between 1968 and 2003 were
identified. Patient, disease, and transplant factors for development of
malignancy were examined and pathology reports for reported malignancies
reviewed independently by a pathologist for confirmation. The incidence of
malignancy was highest for Wiskott-Aldrich syndrome (3.3%), with an overall
incidence of 2.3% for PIDD. Post-HCT malignancy was confirmed for 52 of 63
reported cases. Forty-five of 52 patients developed posttransplant
lymphoproliferative disorders (PTLD) at a median of 3 months post-HCT. Of
these, 26 had received T cell-depleted (TCD) bone marrow. Three patients who
developed myelodysplastic syndrome had received TCD marrow and total body
irradiation. Three patients developed a solid tumor. Patients with PIDD are at
a relatively low risk of developing malignancies post-HCT compared with their
historic risk of cancer. The most frequent malignancy or lymphoproliferative
disorder was early-onset PTLD. As in other HCT recipients, TCD appears to
correlate with PTLD development. Our results lend support to the hypothesis
that immune reconstitution in PIDD following HCT leads to a decrease in cancer
risk. Â© 2011 American Society for Blood and Marrow Transplantation.

Children's National Medical Center, Washington, DC, United States Center for
International Blood and Marrow Transplant Research, Minneapolis, MN, United
States Center for International Blood and Marrow Transplant Research,
Milwaukee, WI, United States Medical College of Wisconsin, Milwaukee, WI,
United States Children's Hospital of Wisconsin, Milwaukee, WI, United States
University of California, San Francisco, CA, United States Hospital
Universitario Materno-Infantil Vall d'Hebron, Barcelona, Spain HÃ´pital
Universitaire des Enfants Reine Fabiola, Brussels, Belgium Duke University
Medical Center, Durham, NC, United States Shands HealthCare at the University
of Florida, Gainesville, FL, United States Children's Hospital of Philadelphia,
Philadelphia, PA, United States Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States

10.1016/j.bbmt.2011.05.008

http://www.ncbi.nlm.nih.gov/pubmed/21658461

(76)Kennebeck SS, Timm NL, Kurowski EM,
Byczkowski TL and Reeves SD

THE ASSOCIATION OF EMERGENCY DEPARTMENT CROWDING AND TIME TO ANTIBIOTICS IN
FEBRILE NEONATES

2011; 18:1380-1385

ACADEMIC EMERGENCY MEDICINE 2011; 18:1380-1385 (c) 2011 by the Society for
Academic Emergency Medicine ABSTRACT: Objectives: The objective was to assess
the relationship between emergency department (ED) crowding and timeliness of
antibiotic administration to neonates presenting with fever in a pediatric ED.
Methods: This was a retrospective cohort study of febrile neonates (aged 0-30
days) evaluated for serious bacterial infections (SBIs) in a pediatric ED from
January 2006 to January 2008. General linear models were used to evaluate the
association of five measures of ED crowding with timeliness of antibiotic
administration, controlling for patient characteristics. A secondary analysis
was conducted to determine which part of the ED visit for this population was
most affected by crowding. Results: A total of 190 patients met inclusion
criteria. Mean time to first antibiotic was 181.7 minutes (range = 18-397
minutes). At the time of case presentation, the number of patients waiting in
the waiting area, total number of hours spent in the ED by current ED patients,
number of ED patients awaiting admission, and hourly boarding time were all
positively associated with longer times to antibiotic. The time from patient
arrival to room placement exhibited the strongest association with measures of
crowding. Conclusions: Emergency department crowding is associated with delays
in antibiotic administration to the febrile neonate despite rapid recognition
of this patient population as a high-risk group. Each component of ED crowding,
in terms of input, throughput, and output factors, was associated with delays.
Further work is required to develop processes that foster a more rapid
treatment protocol for these high-risk patients, regardless of ED crowding
pressures.

From the Division of Pediatric Emergency Medicine, Department of Pediatrics,
Cincinnati Children's Hospital Medical Center (SSK, NLT, EMK, TLB, SDR), and
the Department of Clinical Pediatrics, University of Cincinnati College of
Medicine (SSK, NLT, SDR), Cincinnati, OH.

10.1111/j.1553-2712.2011.01221.x

http://www.ncbi.nlm.nih.gov/pubmed/22168202

(77)Kevan EN, Simmons JR, Kocoshis SA,
Cohen MB and Rudolph JA

sTREM-1 AND LBP IN CENTRAL VENOUS CATHETER-ASSOCIATED BLOODSTREAM INFECTIONS
IN PEDIATRIC INTESTINAL FAILURE

2011; 53:627-633

OBJECTIVE: Central venous catheter-associated bloodstream infections (CVC-BSIs)
are a major cause of morbidity and mortality in the pediatric intestinal
failure (IF) population. We assessed plasma lipopolysaccharide-binding protein
(LBP) and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as
biomarkers for CVC-BSI. We hypothesized that sTREM-1 and LBP rise with BSI and
decline following treatment, and that baseline LBP is higher in the IF population
than in controls. PATIENTS AND METHODS: Patients younger than 4 years were
recruited from the IF registry at Cincinnati Children's Hospital. LBP and
sTREM-1 levels were measured on 22 patients with IF at baseline, 17 patients
with IF with BSIs, and 11 healthy controls. RESULTS: Mean sTREM-1 level (pg/mL)
and LBP level (mug/mL) rose with CVC-BSI over baseline (115.0 +/- 51.2 vs 85.9
+/- 27.6, P = 0.011 and 79.8 +/- 45.4 vs 20.5 +/- 11.3, P < 0.001,
respectively) and declined following antibiotic therapy (115.0 +/- 51.2 vs 77.9
+/- 29.8, P = 0.003 and 79.8 +/- 45.4 vs 26.2 +/- 10.8, P < 0.001,
respectively). Receiver operating characteristic curves showed that neither
sTREM-1 nor LBP is sufficient to predict bacteremia versus fever without
bacteremia (area under these curves = 0.57 and 0.82, respectively). Baseline
LBP was higher in hospitalized patients than in outpatients (27.5 +/- 8.7 vs
13.5 +/- 9.2, P = 0.002), patients with previous BSIs versus those without
(23.5 +/- 10.4 vs 10.1 +/- 8.3, P = 0.016), and those listed for
transplantation versus those not listed (29.6 +/- 9.8 vs 16.2 +/- 9.5, P =
0.033). CONCLUSIONS: sTREM-1 and LBP rise with CVC-BSI in IF and decline after
treatment; however, neither distinguishes infection from nonbacteremic febrile
episodes. Baseline LBP may be a marker of disease severity in IF.

Division of Gastroenterology, Hepatology, and Nutrition, Department of
Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
ekevan@ghs.org

10.1097/MPG.0b013e3182294fcc

http://www.ncbi.nlm.nih.gov/pubmed/21701408

(78)Khanna D, Krishnan E, Dewitt EM, Khanna
PP, Spiegel B and Hays RD

THE FUTURE OF MEASURING PATIENT-REPORTED OUTCOMES IN RHEUMATOLOGY:
PATIENT-REPORTED OUTCOMES MEASUREMENT INFORMATION SYSTEM (PROMIS)

2011; 63:S486-S490

University of Michigan School of Medicine, Ann Arbor, United States Stanford
University, Palo Alto, CA, United States Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States University of California, Los Angeles,
United States

10.1002/acr.20581

(79)Khanna D, Krishnan E, Dewitt EM, Khanna
PP, Spiegel B and Hays RD

PATIENT OUTCOMES IN RHEUMATOLOGY, 2011: a REVIEW OF MEASURES. THE FUTURE OF
MEASURING PATIENT-REPORTED OUTCOMES IN RHEUMATOLOGY

2011; 63:S486-90

Associate Professor of Medicine and Director, Scleroderma Program, School of
Medicine, University of Michigan, 24 Frank Lloyd Wright Drive, PO Box 481, Ann
Arbor, MI 48106 Stanford University, Palo Alto, CA Cincinnati Children's
Hospital Medical Center, Cincinnati, OH University of California, Los Angeles

(80)Kim HK, Kim SM, Lee SH, Racadio JM and
Shin MJ

SUBCUTANEOUS EPIDERMAL INCLUSION CYSTS: ULTRASOUND (US) AND MR IMAGING
FINDINGS

2011; 40:1415-1419

Objective: To describe the characteristic US and MR findings of subcutaneous
epidermal inclusion cysts. Materials and methods: Seventy-nine patients with
subcutaneous epidermal inclusion cysts underwent US (n = 70), MR (n = 7), or
both (n = 2). On US, the margin, shape, echogenicity, through-transmission,
wall, internal debris and vascularity were evaluated. On MR, the shape, wall,
signal intensity, internal debris, and enhancement pattern were evaluated. Results:
On US, characteristic findings were well circumscribed (n = 69, 96%),
ovoid-shaped (n = 56, 78%), heterogeneously and mildly echogenic (n = 66, 92%),
increased through-transmission (n = 66, 92%) and low echoic rim (n = 48, 67%).
Internal debris was seen in 31 cases (43%) and often contained linear echogenic
reflections (n = 12, 17%), dark clefts (n = 13, 18%), or a mixture (n = 5, 7%).
Most masses showed no Doppler flow (n = 70, 97%). On MR, all cases demonstrated
a well-demarcated oval-shaped mass with a surrounding rim. On T1-weighted image
(WI), the mass showed slightly high T1 signal in 4/9 (44%) and iso-signal in
5/9 (56%). On T2WI, the mass showed high signal in 6/9 (67%), intermediate in
2/9 (22%), and a target appearance in 1/9 (11%). Internal linear dark T2 signal
debris was observed in 4/9 (44%). All lesions showed peripheral rim enhancement
without central enhancement. Conclusions: On US, subcutaneous epidermal
inclusion cysts are usually well-circumscribed, oval-shaped, mildly echogenic masses
with occasional linear anechoic and/or echogenic reflections, increased
through-transmission, hypoechoic rim and no Doppler flow. On MR, an
intermediate to high T2 signal mass with occasional low signal debris and no
central enhancement can strengthen the diagnosis. Â© 2010 ISS.

Department of Radiology and Research Institute, University of Ulsan, Asan
Medical Center, 86, Asanbyeongwon-gil, Songpa-gu, Seoul, South Korea Department
of Radiology, Cincinnati Children's Hospital, Medical Center, 3333 Burnet Avenue,
Cincinnati, OH 45229, United States Department of Radiology, University of
Michigan Hospitals, 1500 E Medical Center Dr., Ann Arbor, MI 48109, United
States

10.1007/s00256-010-1072-4

http://www.ncbi.nlm.nih.gov/pubmed/21132291

(81)King BA, Boyd JT and Kingma PS

PULMONARY MATURATIONAL ARREST AND DEATH IN a PATIENT WITH PULMONARY
INTERSTITIAL GLYCOGENOSIS

2011; 46:1142-1145

We present the clinical presentation and pathological findings from a term
infant with atypical neonatal lung disease. A full term Caucasian male
presented at birth with signs of respiratory distress. The respiratory
condition continued to deteriorate despite maximum intervention and the patient
was placed on ECMO for further cardiorespiratory assistance. An open lung
biopsy demonstrated findings consistent with severe lung growth abnormality
with non-uniform pulmonary interstitial glycogenosis. The patient consequently
developed a pulmonary hemorrhage that required discontinuation of ECMO. The
patient died shortly after decannulation. Most literature suggests that PIG is
one of the few pediatric interstitial lung diseases that has a favorable
prognosis with rare mortality in the absence of co-morbidities. However, the
current case suggests prognosis may depend more on the underlying diagnosis
than on the histological finding of PIG. In addition, this case may provide
insight into the pathogenesis and potential modifiers of this idiopathic
disorder.

The Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary
Biology, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH45229-3039, USA. paul.kingma@cchmc.org

10.1002/ppul.21486

http://www.ncbi.nlm.nih.gov/pubmed/21618718

(82)Kingma PS

IS PREMEDICATION FOR INTUBATION OF PRETERM INFANTS THE RIGHT CHOICE?

2011; 159:883-884

Perinatal Institute, Section of Neonatology, Perinatal and Pulmonary Biology,
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

http://www.ncbi.nlm.nih.gov/pubmed/21880330

(83)Kramer EL, Hardie WD, Mushaben EM,
Acciani TH, Pastura PA, Korfhagen TR, Hershey GK, Whitsett JA and Le Cras TD

RAPAMYCIN DECREASES AIRWAY REMODELING AND HYPERREACTIVITY IN a TRANSGENIC
MODEL OF NONINFLAMMATORY LUNG DISEASE

2011; 111:1760-1767

Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and
chronic obstructive pulmonary disease. New therapeutic targets are needed as
some patients are refractory to current therapies and develop progressive
airway remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is
a key regulator of cellular proliferation and survival. Treatment with the mTOR
inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models,
but it is unclear if rapamycin can directly inhibit airway remodeling and AHR,
or whether its therapeutic effects are entirely mediated through
immunosuppression. To address this question, we utilized transforming growth
factor-alpha (TGF-alpha) transgenic mice null for the transcription factor
early growth response-1 (Egr-1) (TGF-alpha Tg/Egr-1(ko/ko) mice). These mice
develop airway smooth muscle thickening and AHR in the absence of altered lung
inflammation, as previously reported. In this study, TGF-alpha Tg/Egr-1(ko/ko)
mice lost body weight and developed severe AHR after 3 wk of lung-specific TGF-alpha
induction. Rapamycin treatment prevented body weight loss, airway wall
thickening, abnormal lung mechanics, and increases in airway resistance to
methacholine after 3 wk of TGF-alpha induction. Increases in tissue damping and
airway elastance were also attenuated in transgenic mice treated with
rapamycin. TGF-alpha/Egr-1(ko/ko) mice on doxycycline for 8 wk developed severe
airway remodeling. Immunostaining for alpha-smooth muscle actin and
morphometric analysis showed that rapamycin treatment prevented airway smooth
muscle thickening around small airways. Pentachrome staining, assessments of
lung collagen and fibronectin mRNA levels, indicated that rapamycin also
attenuated fibrotic pathways induced by TGF-alpha expression for 8 wk. Thus
rapamycin reduced airway remodeling and AHR, demonstrating an important role
for mTOR signaling in TGF-alpha-induced/EGF receptor-mediated reactive airway
disease.

Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center,
3333 Burnet Ave., Cincinnati, Ohio 45229-3039. tim.lecras@cchmc.org.

10.1152/japplphysiol.00737.2011

http://www.ncbi.nlm.nih.gov/pubmed/21903885

(84)Krawczeski CD, Goldstein SL, Woo JG,
Wang Y, Piyaphanee N, Ma Q, Bennett M and Devarajan P

TEMPORAL RELATIONSHIP AND PREDICTIVE VALUE OF URINARY ACUTE KIDNEY INJURY
BIOMARKERS AFTER PEDIATRIC CARDIOPULMONARY BYPASS

2011; 58:2301-2309

OBJECTIVES: We investigated the temporal pattern and predictive value (alone
and in combination) of 4 urinary biomarkers (neutrophil gelatinase-associated
lipocalin [NGAL], interleukin [IL]-18, liver fatty acid-binding protein
[L-FABP], and kidney injury molecule [KIM]-1) for cardiac surgery-associated
acute kidney injury (AKI). BACKGROUND: Serum creatinine (S(Cr)) is a delayed
marker for AKI after cardiopulmonary bypass (CPB). Rapidly detectable AKI
biomarkers could allow early intervention and improve outcomes. METHODS: Data
from 220 pediatric patients were analyzed. Urine samples were obtained before
and at intervals after CPB initiation. AKI was defined as a >/=50% increase
in S(Cr) from baseline within 48 h after CPB. The temporal pattern of biomarker
elevation was established, and biomarker elevations were correlated with AKI
severity and clinical outcomes. Biomarker predictive abilities were evaluated
by area under the curve (AUC), net reclassification improvement, and integrated
discrimination improvement. RESULTS: AKI occurred in 27% of patients. Urine
NGAL significantly increased in AKI patients at 2 h after CPB initiation. IL-18
and L-FABP increased at 6 h, and KIM-1 increased at 12 h. Biomarker elevations
were correlated with AKI severity and clinical outcomes and improved AKI
prediction above a clinical model. At 2 h, addition of NGAL increased the AUC
from 0.74 to 0.85 (p < 0.0001). At 6 h, NGAL, IL-18, and L-FABP each
improved the AUC from 0.72 to 0.91, 0.84, and 0.77, respectively (all p <
0.05). The added predictive ability of the biomarkers was supported by net
reclassification improvement and integrated discrimination improvement.
Biomarker combinations further improved AKI prediction. CONCLUSIONS: Urine
NGAL, IL-18, L-FABP, and KIM-1 are sequential predictive biomarkers for AKI and
are correlated with disease severity and clinical outcomes after pediatric CPB.
These biomarkers, particularly in combination, may help establish the timing of
injury and allow earlier intervention in AKI.

The Heart Institute, Cincinnati Children's Hospital Medical Center, University
of Cincinnati College of Medicine, Cincinnati, OH, USA.

10.1016/j.jacc.2011.08.017

http://www.ncbi.nlm.nih.gov/pubmed/22093507

(85)Kuhn BRandMezoff AG

PEDIATRIC LYMPHOCYTIC COLITIS PRESENTING WITH INTRACTABLE DIARRHEA

2011; 53:579-581

Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. benkuhn@hotmail.com

10.1097/MPG.0b013e3182214ac6

http://www.ncbi.nlm.nih.gov/pubmed/21543998

(86)Kumaravel SN, Tabangin ME, Sebera KE
and Warren NS

ENRICHING THE GENETIC COUNSELING RECRUITMENT PIPELINE: a NATIONAL
CROSS-SECTIONAL STUDY OF PUBLIC HIGH SCHOOL COUNSELORS

2011; 20:559-571

Early awareness of careers is helpful in recruiting students into a career
pipeline. School counselors are among the top resources that students turn to
when seeking advice about choosing their career. Studies show that high school
is the ideal time to generate interest in the genetic counseling career,
especially for minorities. This novel study of 291 high school counselors
working in ethnically diverse public school districts in the United States
examined to what extent members of this important group discuss genetic
counseling as a career option with their students. The findings indicate that
the majority of school counselors in this study (83%) did not discuss genetic
counseling with their students, citing a lack of resources and lack of student
interest as the major barriers. Suggestions of ways to increase high school
counselors' awareness of the genetic counseling career in order to enhance the
goal of enriching recruitment of ethnic minorities into the genetic counseling
pipeline are presented.

Cancer Risk and Prevention, Long Beach Memorial Medical Center, Long Beach, CA,
USA. sharanyakumaravel@gmail.com

10.1007/s10897-011-9386-5

http://www.ncbi.nlm.nih.gov/pubmed/21769571

(87)Kummer AWandTurner J

ETHICS IN THE PRACTICE OF SPEECH-LANGUAGE PATHOLOGY IN HEALTH CARE SETTINGS

2011; 32:330-337

ETHICS refers to a moral philosophy or a set of moral principles that determine
appropriate behavior in a society. Medical ethics includes a set of specific
values that are considered in determining appropriate conduct in the practice
of medicine or health care. Because the practice of medicine and medical
speech-language pathology affects the health, well-being, and quality of life
of individuals served, adherence to a code of ethical conduct is critically
important in the health care environment. When ethical dilemmas arise,
consultation with a bioethics committee can be helpful in determining the best
course of action. This article will help to define medical ethics and to
discuss the six basic values that are commonly considered in discussions of
medical ethics. Common ethical mistakes in the practice of speech-language
pathology will be described. Finally, the value of a bioethics consultation for
help in resolving complex ethical issues will be discussed.

Division of Speech Pathology, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio.

10.1055/s-0031-1292758

http://www.ncbi.nlm.nih.gov/pubmed/22144083

(88)Kunzmann S, Collins JJP, Yang Y, Uhlig
S, Kallapur SG, Speer CP, Jobe AH and Kramer BW

ANTENATAL INFLAMMATION REDUCES EXPRESSION OF CAVEOLIN-1 AND INFLUENCES
MULTIPLE SIGNALING PATHWAYS IN PRETERM FETAL LUNGS

2011; 45:969-976

Bronchopulmonary dysplasia (BPD), associated with chorioamnionitis, results
from the simultaneous effects of disrupted lung development, lung injury, and
repair superimposed on the developing lung. Caveolins (Cavs) are implicated as
major modulators of lung injury and remodeling by multiple signaling pathways,
although Cavs have been minimally studied in the injured developing lung. We
hypothesized that chorioamnionitis-associated antenatal lung inflammation would
decrease the expression of Cav-1 in preterm fetal lungs.Wetested whether
changes occurred in the transcription factors Smad2/3, Smad1/5, Stat3, and
Stat1, andwealso studied the activation of acid-sphingomyelinase (a-SMase) with
the generation of ceramide, along with changes in the expression of heme
oxygenase - 1 (HO-1) as indicators of possible Cav-1 - mediated effects. Fetal
sheep were exposed to 10 mg of intra-amniotic endotoxin or saline for 2, 7, or
2 + 7 days before preterm delivery at 124 days of gestation. The expression of
Cav-1 and HO-1 and the phosphorylation of Smad and Stat were evaluated by
real-time PCR, Western blotting, and/or immunohistochemistry. The activity of
a-SMase and the concentrations of ceramide were measured. Intra-amniotic
endotoxin decreased Cav-1 mRNA and protein expression in the lungs, with a
maximum reduction of Cav-1 mRNA to 50% Â± 7% of the control value (P<0.05),
and of Cav-1 protein expression to20%Â±5%of the control value (P < 0.05).
Decreased concentrations of Cav-1 were associated with the elevated
phosphorylation of Smad2/3, Stat3, and Stat1, but not of Smad1/5. The
expression of HO-1, a-SMase activity, and ceramide increased. Antenatal
inflammation decreased the expression of Cav-1 in the preterm fetal lung. The
decreased expression of Cav-1 was associated with the activation of the
Smad2/3, Stat, anda-SMase/ ceramidepathways, andwiththe increasedexpression of
HO-1. The decreased concentrations of Cav-1 and changes in other signaling
pathways may contribute to BPD.

University Children's Hospital, University of WÃ¼rzburg, WÃ¼rzburg, Germany
School of Mental Health and Neuroscience, Department of Pediatrics, School for
Oncology and Developmental Biology, Maastricht, Netherlands Institute of
Pharmacology and Toxicology, Medical Faculty, Rheinisch-WestfÃ¤lische
Technische Hochschule Aachen University, Aachen, Germany Division of Pulmonary
Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United
States School of Women's and Infants' Health, University of Western Australia,
Perth, WA, Australia

10.1165/rcmb.2010-0519OC

http://www.ncbi.nlm.nih.gov/pubmed/21562314

(89)Kuppala VS, Meinzen-Derr J, Morrow AL
and Schibler KR

PROLONGED INITIAL EMPIRICAL ANTIBIOTIC TREATMENT IS ASSOCIATED WITH ADVERSE
OUTCOMES IN PREMATURE INFANTS

2011; 159:720-725

OBJECTIVE: To investigate the outcomes after prolonged empirical antibiotic
administration to premature infants in the first week of life, and concluding
subsequent late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death.
STUDY DESIGN: Study infants were /= 5 days) and study outcomes that control for
birth weight, gestational age, race, prolonged premature rupture of membranes,
days on high-frequency ventilation in 7 days, and the amount of breast milk
received in the first 14 days of life. RESULTS: Of the 365 premature infants
who survived 7 days free of sepsis or NEC, 36% received prolonged initial
empirical antibiotics, which was independently associated with subsequent
outcomes: LOS (OR, 2.45 [95% CI, 1.28-4.67]) and the combination of LOS, NEC,
or death (OR, 2.66 [95% CI, 1.12-6.3]). CONCLUSIONS: Prolonged administration
of empirical antibiotics to premature infants with sterile cultures in the
first week of life is associated with subsequent severe outcomes. Judicious
restriction of antibiotic use should be investigated as a strategy to reduce
severe outcomes for premature infants.

Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH, USA.

10.1016/j.jpeds.2011.05.033

http://www.ncbi.nlm.nih.gov/pubmed/21784435

(90)Kurth M, Puetz J, Kouides P, Sanders J,
Sexauer C, Bernstein J, Gruppo R, Manco-Johnson M, Neufeld EJ, Rodriguez N,
Wicklund B, Quon D and Aledort L

THE USE OF a SINGLE VON WILLEBRAND FACTOR-CONTAINING, PLASMA-DERIVED FVIII
PRODUCT IN HEMOPHILIA A IMMUNE TOLERANCE INDUCTION: THE US EXPERIENCE

2011; 9:2229-2234

Background:Inhibitors are a serious complication for patients with severe
hemophilia A. Immune tolerance induction (ITI) is the primary method for
eradicating these inhibitors. The role of type of concentrate and in particular
the use of von Willebrand factor-containing, plasma-derived factor VIII
(VWF/pd-FVIII) concentrate in primary or rescue ITI remains unclear.
Objectives:To report retrospective collection of data on the use of a single
VWF/pd-FVIII concentrate in primary and rescue ITI. Methods:Retrospective chart
review of hemophilia A inhibitor patients at 11 US institutions who received
VWF/pd-FVIII concentrate in primary or rescue ITI. Results:Primary ITI was
carried out in eight inhibitor patients with a 75% complete and partial
success. Secondary ITI was carried out in 25 inhibitor patients, with 52%
attaining complete or partial success. Conclusions:This report represents the
largest group of primarily pediatric, high-titer inhibitor patients treated
with a single VWF/pd-FVIII concentrate. It adds retrospective data to the use
of VWF-containing plasma-derived factor VIII concentrate in primary and rescue
ITI, particularly in those patients with characteristics of poor response to
ITI. Â© 2011 International Society on Thrombosis and Haemostasis.

Department of Pediatrics, Children's Hospitals and Clinics of Minnesota,
Minneapolis, MN, United States Department of Pediatrics, Cardinal Glennon
Children's Medical Center, St Louis, MO, United States Department of Medicine,
University of Rochester Medical Center, Rochester, NY, United States Department
of Pediatrics, Cook Children's Hospital, Fort Worth, TX, United States
Department of Pediatrics, Oklahoma University Health Science Center, Oklahoma
City, OK, United States Children's Center for Cancer and Blood Diseases, Las
Vegas, NV, United States Department of Pediatrics, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States Department of Pediatrics,
University of Colorado and Health Sciences Center, Children's Hospital
Colorado, Aurora, CO, United States Department of Pediatrics, Children's
Hospital of Boston, Boston, MA, United States Department of Pediatrics,
University of Texas-Texas Medical Center, Houston, TX, United States Department
of Pediatrics, Children's Mercy Hospital, Kansas City, MO, United States
Department of Medicine, Orthapedic Hospital, Los Angeles, CA, United States
Department of Medicine, Mount Sinai Medical Center, New York City, NY, United
States

10.1111/j.1538-7836.2011.04493.x

http://www.ncbi.nlm.nih.gov/pubmed/21883884

(91)Ladage D, Tilemann L, Ishikawa K,
Correll RN, Kawase Y, Houser SR, Molkentin JD and Hajjar RJ

INHIBITION OF PKCalpha/beta WITH RUBOXISTAURIN ANTAGONIZES HEART FAILURE IN
PIGS AFTER MYOCARDIAL INFARCTION INJURY

2011; 109:1396-1400

Rationale: Protein kinase Calpha (PKCalpha) activity and protein level are
induced during cardiac disease where it controls myocardial contractility and
propensity to heart failure in mice and rats. For example, mice lacking the
gene for PKCalpha have enhanced cardiac contractility and reduced
susceptibility to heart failure after long-term pressure overload or after
myocardial infarction injury. Pharmacological inhibition of PKCalpha/beta with
Ro-32-0432, Ro-31-8220 or ruboxistaurin (LY333531) similarly enhances cardiac
function and antagonizes heart failure in multiple models of disease in both
mice and rats. Objective: Large and small mammals differ in several key indexes
of heart function and biochemistry, lending uncertainty as to how PKCalpha/beta
inhibition might affect or protect a large animal model of heart failure.
Methods and Results: We demonstrate that ruboxistaurin administration to a pig
model of myocardial infarction-induced heart failure was protective.
Twenty-kilogram pigs underwent left anterior descending artery occlusion resulting
in myocardial infarctions and were then divided into vehicle or ruboxistaurin
feed groups, after which they were monitored monthly for the next 3 months.
Ruboxistaurin administered pigs showed significantly better recovery of
myocardial contractility 3 months after infarction injury, greater ejection
fraction, and greater cardiac output compared with vehicle-treated pigs.
Conclusions: These results provide additional evidence in a large animal model
of disease that PKCalpha/beta inhibition (with ruboxistaurin) represents a
tenable and novel therapeutic approach for treating human heart failure.

Howard Hughes Medical Institute, Cincinnati Children's Hospital Medical Center,
240 Albert Sabin Way, Cincinnati, OH 45229-3039. Jeff.Molkentin@cchmc.org.

10.1161/CIRCRESAHA.111.255687

http://www.ncbi.nlm.nih.gov/pubmed/21998327

(92)Ladow K, Schumann BL, Luse N,
Warshawsky D, Pickens WL, Hoath SB and Talaska G

ACUTE TREATMENT WITH KEROSENE DAMAGES THE DERMAL BARRIER AND ALTERS THE
DISTRIBUTION OF TOPICALLY APPLIED BENZO(a)PYRENE IN MICE

2011; 8:701-708

The dermal route is important in many occupational exposures. Some materials may
reduce the barrier function of the skin to enhance absorption and effect on
internal organs. We have reported previously that kerosene cleaning following
treatment with used engine oil increased DNA adduct levels in the lungs of mice
compared with animals treated with used oil alone. To investigate what other
physiological parameters might be affected by kerosene, we conducted in vitro
and in vivo measurements of skin barrier function. We also topically applied
3H-BAP(100 nM in 25 L acetone) and washed half the mice with 25 L kerosene 1 hr
after carcinogen application. Groups of four mice were euthanized from 1 to 72
hr after treatment. Skin, lungs, and livers were harvested from each animal and
stored separately. Kerosene application reduced the barrier function of the
skin in vitro beyond the effect of the acetone vehicle and the vehicle plus
BAP. In vivo studies indicated that kerosene treatment reduced the barrier
function at 4 and 8 hr post application and that the barrier function recovered
at 24 hr after a single treatment. The fraction of the radiolabel remaining in
the skin of animals treated with 3H-BAP and washed with kerosene was
significantly less than those not washed, beginning at 24 hr (p 0.05).
Fractional distribution to the lungs and livers of these animals became
significantly elevated at this time. Kerosene treatment compromises dermal
barrier function and the ability of the skin to retain water, enhances
carcinogen absorption, and alters organ distribution. This appears to
contribute to the increase in BAP DNA adducts we reported earlier. Â© 2011
JOEH, LLC.

Department of Environmental Health, University of Cincinnati Medical School,
3223 Eden Ave., Cincinnati, OH 45267, United States Department of Pediatrics,
Children's Hospital Research Center, Cincinnati, OH, United States

10.1080/15459624.2011.626732

http://www.ncbi.nlm.nih.gov/pubmed/22059855

(93)Lehman LL, Gilbert DL, Leach JL, Wu SW
and Standridge SM

VERTEBRAL ARTERY DISSECTION LEADING TO STROKE CAUSED BY VIOLENT NECK TICS OF
TOURETTE SYNDROME

2011; 77:1706-1708

Division of Neurology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, USA. Laura.Lehman@childrens.harvard.edu

10.1212/WNL.0b013e318238253c

http://www.ncbi.nlm.nih.gov/pubmed/21975212

(94)LeMaster T, Pendergrass T and Manos J

IT TAKES MORE THAN MAGIC: 1100 SAFE DAYS AND COUNTING

2011; 7:e256-7

Cincinnati Children's Center for Simulation and Research, 3333 Burnet Avenue ML
12000, Cincinnati, Ohio 45229

10.1016/j.ecns.2011.09.046

(95)Li J, Bessho K, Shivakumar P, Mourya R,
Mohanty SK, Dos Santos JL, Miura IK, Porta G and Bezerra JA

Th2 SIGNALS INDUCE EPITHELIAL INJURY IN MICE AND ARE COMPATIBLE WITH THE
BILIARY ATRESIA PHENOTYPE

2011; 121:4244-4256

Biliary atresia (BA) is a destructive cholangiopathy of childhood in which Th1
immunity has been mechanistically linked to the bile duct inflammation and
obstruction that culminate in liver injury. Based on reports of decreased Th1
cytokines in some patients and the development of BA in mice lacking CD4+ T
cells, we hypothesized that Th1-independent mechanisms can also activate
effector cells and induce BA. Here, we tested this hypothesis using Stat1-/-
mice, which lack the ability to mount Th1 immune responses. Infection of
Stat1-/- mice with rhesus rotavirus type A (RRV) on postnatal day 1 induced a
prominent Th2 response, duct epithelial injury and obstruction within 7 days,
and atresia shortly thereafter. A high degree of phosphorylation of the Th2
transcription factor Stat6 was observed; however, concurrent inactivation of
Stat1 and Stat6 in mice did not prevent BA after RRV infection. In contrast,
depletion of macrophages or combined loss of Il13 and Stat1 reduced tissue
infiltration by lymphocytes and myeloid cells, maintained epithelial integrity,
and prevented duct obstruction. In concordance with our mouse model, humans at
the time of BA diagnosis exhibited differential hepatic expression of Th2 genes
and serum Th2 cytokines. These findings demonstrate compatibility between Th2
commitment and the pathogenesis of BA, and suggest that patient subgrouping in future
clinical trials should account for differences in Th2 status.

Cincinnati Children's Hospital Medical Center and the Department of Pediatrics
of the University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

10.1172/JCI57728

http://www.ncbi.nlm.nih.gov/pubmed/22005305

(96)Liu T, Patek K and Schneider KW

DIVERSITY AND GENERAL STUDENT SCHOLARSHIP RECIPIENT ESSAYS: 2010 NATIONAL
SOCIETY OF GENETIC COUNSELORS MEMBERSHIP COMMITTEE

2011; 20:556-558

In an effort to increase the diversity of the membership of the National
Society of Genetic Counselors (NSGC), the Membership Committee provided two
$500 scholarships to genetic counseling students planning to attend the NSGC
AEC meeting in Dallas, Texas in October 2010. Requirements for applicants of
both scholarships included enrollment in the fall of 2010, good standing at an
accredited genetic counseling training program, and NSGC membership or plans to
join in 2011. Students who are from communities underrepresented in the NSGC,
including, but not limited to, those of minority cultural/ethnic backgrounds
and those with disabilities were eligible to apply for the
"Diversity" scholarship. Students from all backgrounds who have an interest
in diversity issues were eligible to apply for the "General"
scholarship. Applicants wrote essays 1000 words or less answering the following
questions: How has your identity as a member of a group underrepresented in the
genetic counseling profession affected your pursuit of this career? What do you
feel is lacking in genetic counseling to address the issues of underrepresented
groups? What strategies do you recommend for addressing these issues and/or
increasing diversity? Why do you think diversity is an important issue for the
field of genetic counseling? What strategies do you recommend to attract and
retain students, especially those from underrepresented populations, into the
field of genetic counseling? How do you envision contributing to these
strategies? The essays by the award recipients elucidated interesting
perspectives and ideas for increasing diversity in the genetic counseling
profession.

Department of Biological Sciences, College of Natural Sciences, Turlock, CA
95382, USA.

10.1007/s10897-011-9380-y

http://www.ncbi.nlm.nih.gov/pubmed/21717287

(97)Lo MM, Salisbury S, Scherer PE, Furth
SL, Warady BA and Mitsnefes MM

SERUM ADIPONECTIN COMPLEXES AND CARDIOVASCULAR RISK IN CHILDREN WITH CHRONIC
KIDNEY DISEASE

2011; 26:2009-2017

In contrast to the general population, patients with chronic kidney disease
(CKD) experience increased total adiponectin levels despite an increased
prevalence of cardiovascular disease. Adiponectin circulates as trimer, low
molecular weight (LMW), and high molecular weight (HMW) complexes. The
distribution and role of each subfraction in CKD is unknown. This
cross-sectional analysis examined the association of serum adiponectin and its
subfractions with known cardiovascular risk factors in 105 children (median age
12 years; 56% male) enrolled into the Chronic Kidney Disease in Children (CKiD)
study, an observational cohort study of children with CKD stage 2-4.HMW
accounted for 46% of total adiponectin, followed by LMW (34%) and trimer (20%).
In multivariable analysis, LMW was independently associated with iohexol
glomerular filtration rate (GFR) (p = 0.004) and was higher in pubertal versus
prepubertal children (p = 0.005). HMW/LMW ratio was independently associated
with age and iohexol GFR (all p < 0.001). Unexpectedly, systolic blood
pressure was positively correlated with HMW (p = 0.01), and HMW/LMW ratio (p =
0.007) and inversely correlated with LMW (p = 0.009). Among subfractions, only
LMW was significantly correlated with left ventricular mass (LVM) index (p =
0.05). In multivariable analysis, decreased LMW was independently associated
with higher LVM index [beta= -0.25, 95% confidence interval (CI) -0.50, -0.03,
p=0.04) after adjustment for body mass index (BMI), age, and blood pressure.The
higher total adiponectin levels in children with CKD are associated with higher
HMW and lower LMW. This imbalance may be an important biomarker for increased
cardiovascular risk despite higher levels of total adiponectin in children with
CKD.

Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical
Center, MLC: 7022, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.

10.1007/s00467-011-1906-x

http://www.ncbi.nlm.nih.gov/pubmed/21553321

(98)Lu Z, Chen H, Meng Y, Wang Y, Xue L,
Zhi S, Qiu Q, Yang L, Mo JQ and Guan MX

THE tRNA MET 4435A>G MUTATION IN THE MITOCHONDRIAL HAPLOGROUP G2a1 IS
RESPONSIBLE FOR MATERNALLY INHERITED HYPERTENSION IN a CHINESE PEDIGREE

2011; 19:1181-1186

Mutations in mitochondrial DNA (mtDNA) have been associated with hypertension
in several pedigrees with maternal inheritance. However, the pathophysiology of
maternally inherited hypertension remains poorly understood. We reported here
clinical, genetic evaluations and molecular analysis of mtDNA in a
three-generation Han Chinese family with essential hypertension. Eight of 17
matrilineal relatives exhibited a wide range of severity in essential hypertension,
whereas none of the offsprings of the affected father had hypertension. The
age-at-onset of hypertension in the maternal kindred varied from 31 to 65
years, with an average of 52 years. Sequence analysis of mtDNA in this pedigree
identified the known homoplasmic 4435A>G mutation, which is located at
immediately 3â€² end to the anticodon, corresponding to the conventional
position 37 of tRNA Met, and 41 variants belonging to the Asian haplogroup
G2a1. In contrast, the 4435A>G mutation occurred among mtDNA haplogroups
B5a, D, M7a2 and J. The adenine (A37) at this position of tRNA Met is
extraordinarily conserved from bacteria to human mitochondria. This modified
A37 was shown to contribute to the high fidelity of codon recognition,
structural formation and stabilization of functional tRNAs. However, 41 other
mtDNA variants in this pedigree were the known polymorphisms. The occurrence of
the 4435AG mutation in two genetically unrelated families affected by
hypertension indicates that this mutation is involved in hypertension. Our
present investigations further supported our previous findings that the 4435AG
mutation acted as an inherited risk factor for the development of hypertension.
Our findings will be helpful for counseling families of maternally inherited
hypertension. Â© 2011 Macmillan Publishers Limited All rights reserved.

Emergercy Medical Department, First Affiliated Hospital of Wenzhou Medical
College, Zhejiang, China Attardi Institute of Mitochondrial Biomedicine,
Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical
College, Wenzhou, Zhejiang, China Division of Human Genetics, Cincinnati
Childrens Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH
45229-3039, United States Division of Pathology, Cincinnati Childrens Hospital
Medical Center, Cincinnati, OH, United States Deparment of Genetics, College of
Life Sciences, Zhejiang University, Zhejiang, China

10.1038/ejhg.2011.111

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3198143/

(99)Ma J

TRANSCRIPTIONAL ACTIVATORS AND ACTIVATION MECHANISMS

2011; 2:879-888

Transcriptional activators are required to turn on the expression of genes in a
eukaryotic cell. Activators bound to the enhancer can facilitate either the
recruitment of RNA polymerase II to the promoter or its elongation. This
article examines a few selected issues in understanding activator functions and
activation mechanisms.

Division of Biomedical Informatics, Division of Developmental Biology,
Cincinnati Children's Research Foundation, University of Cincinnati College of
Medicine, Cincinnati, OH, 45229, USA, jun.ma@cchmc.org.

10.1007/s13238-011-1101-7

http://www.ncbi.nlm.nih.gov/pubmed/22180087

(100)MÃ¼ller DandGoldstein SL

HEMODIALYSIS IN CHILDREN WITH END-STAGE RENAL DISEASE

2011; 7:650-658

Although renal transplantation remains the most common treatment for children
with end-stage renal disease (ESRD), the majority of children incident to ESRD
receive dialytic therapy before receiving a renal allograft. Advances in the
past decade have led to improved outcomes for children receiving maintenance
hemodialysis, the majority of whom survive into adulthood. Medical, surgical,
nutritional and psychosocial factors must be considered to provide optimal
maintenance hemodialysis for children. In this Review, we discuss the various
aspects of providing optimal hemodialysis to children, including vascular
access, nutritional status, clearance targets, medications and assessment of
health-related quality of life. Â© 2011 Macmillan Publishers Limited. All
rights reserved.

Department of Pediatric Nephrology, CharitÃ© University Hospital,
Augustenburger Platz 1, 13353 Berlin, Germany Division of Nephrology and
Hypertension, Cincinnati Children's Hospital Medical Center, MLC 7022, 3333
Burnet Avenue, Cincinnati, OH 45229, United States

10.1038/nrneph.2011.124

http://www.ncbi.nlm.nih.gov/pubmed/21894181

(101)MacK EH, Wheeler DS and Hirsch R

ENDOVASCULAR TREATMENT OF NEAR-FATAL NEONATAL SUPERIOR VENA CAVA SYNDROME

2011; 12:e410-e412

Objective: We describe the endovascular management of an 8-wk-old previously
healthy female who developed superior vena cava syndrome secondary to
Pseudomonas septic shock and disseminated intravascular coagulation. Doppler
ultrasound confirmed near-total thrombotic occlusion of the superior vena cava
and right internal jugular vein. She was taken emergently for cardiac
catheterization, which confirmed the large superior vena cava thrombus
extending into the right internal jugular vein and innominate vein with almost
complete occlusion of the innominate vein. The superior vena cava to right
atrium gradient was 14 mm Hg with very little antegrade flow into the right
atrium, right femoral artery occlusion, and branch pulmonary artery emboli.
Intervention involved serial balloon dilation inflations across the superior
vena cava and innominate vein with improvement in the superior vena cava to
right atrium gradient to 5 mm Hg and significant improvement in left
ventricular function. Anticoagulation included heparin infusion for 48 hrs followed
by enoxaparin for 1 month, alteplase for 48 hrs, eptifibatide (glycoprotein
IIb/IIIa inhibitor) for 9 days followed by aspirin. Data Sources: Chart review.
Case reports are exempt from approval of our Institutional Review Board. Study
Selection: None. Data Extraction: None. Data Synthesis: None. Conclusions:
Daily head ultrasounds were performed without evidence of intracranial
hemorrhage. All thromboses resolved within 3 wks. Her organ function recovered
and she was discharged to home. The etiology of her colitis is still unknown.
At 9-month follow-up, she was doing well with no residual organ dysfunction. Â©
2011 by the Society of Critical Care Medicine and the World Federation of
Pediatric Intensive and Critical Care Societies.

Division of Pediatric Critical Care, University of South Carolina, Palmetto
Health Children's Hospital, Columbia, SC, United States Department of
Pediatrics, University of Cincinnati, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States Cardiac Catheterization Laboratory, Heart
Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH,
United States

10.1097/PCC.0b013e3181fe44a6

http://www.ncbi.nlm.nih.gov/pubmed/21116206

(102)Mahnke YD, Saqr A, Hazenfeld S, Brady
RC, Roederer M and Subbramanian RA

AGE-RELATED CHANGES IN DURABILITY AND FUNCTION OF VACCINE-ELICITED
INFLUENZA-SPECIFIC CD4+ T-CELL RESPONSES

2011; 29:8606-8614

The major antigenic component of licensed influenza vaccines, hemagglutinin
(HA), elicits predominantly type-specific antibody responses, thus
necessitating frequent antigenic updates to the annual vaccine. However,
accumulating evidence suggests that influenza vaccines can also induce
significant cross-reactive T-cell responses to highly divergent, heterosubtypic
HA antigens not included in the vaccine. Influenza vaccines are less effective
among the elderly and studies that characterize cross-reactive T-cell immunity
in this vulnerable population are much needed. Here, we systematically compare
the ex vivo frequency, cytokine profile and phenotype of vaccine-elicited
HA-specific T-cell responses among a cohort of young (18-49 years old) and
elderly (â‰¥70 years old) vaccinees, as well as the maturation and activation
phenotype of total CD4+ and CD8+ T-cells. IFN-Î³ production after in vitro
expansion and HA-specific Ab titers were also determined. We find that
vaccine-elicited ex vivo frequencies of CD4+ T-cells elicited by vaccination
reactive to any given homo- or heterosubtypic Ag were comparable across the two
age groups. While, no differences were observed between age groups in the
phenotype of Ag-specific or total CD4+ T-cells, PBMC from young adults were
superior at producing IFN-Î³ after short-term Ag-specific culture.
Significantly, while vaccine-elicited T-cell responses were durable among the
younger vaccinees, they were short-lived among the elderly. These results have
important ramifications for our understanding of vaccine-induced changes in the
magnitude and functionality of HA-specific CD4+ T-cells, as well as age-related
alterations in response kinetics. Â© 2011 Elsevier Ltd.

ImmunoTechnology Section, Vaccine Research Center, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD,
United States Division of Infectious Diseases, Department of Pediatrics,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

10.1016/j.vaccine.2011.09.019

http://www.ncbi.nlm.nih.gov/pubmed/21939709

(103)Manos J, Pendergrass T and LeMaster T

DEMYSTIFYING CODES: SIMULATION TO IMPROVE CODE RESPONSE OUTSIDE OF THE ICU

2011; 7:e257-e257

Cincinnati Children's Center for Simulation and Research, 3333 Burnet Avenue ML
12000, Cincinnati, Ohio 45229

10.1016/j.ecns.2011.09.048

(104)Marsh RAandFilipovich AH

FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS AND X-LINKED LYMPHOPROLIFERATIVE
DISEASE

2011; 1238:106-121

Familial hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative
disease are rare, fatal, inherited immune deficiency disorders. Both diagnoses
are used to describe patients who are affected by several known or presumed
genetic mutations that, in common, predispose patients to the development of
hemophagocytic lymphohistiocytosis. Many pivotal advances have been made in
recent years with regard to our understanding and treatment of these diseases.
Here, we will describe the genetic and functional bases of these diseases,
highlight their clinical manifestations, and discuss current diagnostic and
therapeutic strategies.

Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood
Diseases Institute, Cincinnati Children's Hospital Medical Center, Ohio 45229,
USA. Rebecca.Marsh@cchmc.org

10.1111/j.1749-6632.2011.06265.x

http://www.ncbi.nlm.nih.gov/pubmed/22129058

(105)Martinez HR, Niu MC, Sutton VR,
Pignatelli R, Vatta M and Jefferies JL

COFFIN-LOWRY SYNDROME AND LEFT VENTRICULAR NONCOMPACTION CARDIOMYOPATHY WITH
a RESTRICTIVE PATTERN

2011; 155:3030-3034

Coffin-Lowry syndrome (CLS) is an X-linked dominant condition characterized by
moderate to severe mental retardation, characteristic facies, and hand and
skeletal malformations. The syndrome is due to mutations in the gene that
encodes the ribosomal protein S6 kinase-2, a growth factor-regulating protein
kinase located on Xp22.2. Cardiac anomalies are known to be associated with
CLS. Left ventricular noncompaction (LVNC) is a clinically heterogeneous
disorder characterized by left ventricular (LV) myocardial trabeculations and
intertrabecular recesses that communicate with the LV cavity. Patients may
present with a variety of clinical phenotypes, ranging from a complete absence
of symptoms to a rapid, progressive decline in LV systolic and diastolic
function, resulting in congestive heart failure, malignant ventricular
tachyarrhythmias, and systemic thromboembolic events. Restrictive
cardiomyopathy is an uncommon primary cardiomyopathy characterized by biatrial
enlargement, normal or decreased biventricular volume, impaired ventricular
filling, and normal or near-normal systolic function. We describe a patient
with CLS and LVNC with a restrictive pattern, as documented by echocardiography
and cardiac catheterization. To our knowledge, there have been no previous
reports of concomitant CLS and LVNC. On the basis of our case, we suggest that
patients with CLS be screened not only for congenital structural heart defects
but also for LVNC cardiomyopathy. Â© 2011 Wiley Periodicals, Inc. Â© 2011 Wiley
Periodicals, Inc.

The Section of Pediatric Cardiology, Texas Children's Hospital, Houston, TX,
United States The Department of Human and Molecular Genetics, Baylor College of
Medicine, Houston, TX, United States The Texas Heart Institute at St. Luke's
Episcopal Hospital, Houston, TX, United States Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States

10.1002/ajmg.a.33856

http://www.ncbi.nlm.nih.gov/pubmed/22009732

(106)Mathew P, Gerbing R, Alonzo TA, Wallas
T, Gong JZ, Jasty R, Jorstad DT, Raimondi SC, Chavez CM, Eisenberg NL, Hirsch
B, Gamis A, Smith FO and Arceci RJ

A PHASE II STUDY OF AMIFOSTINE IN CHILDREN WITH MYELODYSPLASTIC SYNDROME: a
REPORT FROM THE CHILDREN's ONCOLOGY GROUP STUDY (AAML0121)

2011; 57:1230-1232

Based on its potential role in adult myelodysplastic syndrome (MDS), the
Children's Oncology Group (COG) embarked on a phase II study using amifostine
in pediatric MDS (WHO 2001 criteria) patients. Responses were evaluated after
two cycles. Ten patients were enrolled; five were deemed ineligible, and four
withdrew after the first course. Only one patient completed two courses, and
was found to be in complete remission. The study was closed after being open
for 2 years due to slow accrual. Studying a rare disease like MDS may pose
insurmountable obstacles even in a large clinical trials group such as COG, in
part because of the changing definitions of MDS and the rarity of adult type
MDS in children. The role of amifostine in pediatric MDS was not known at the
time of study.

Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico
87131-0001, USA. pmathew@salud.unm.edu

10.1002/pbc.23164

http://www.ncbi.nlm.nih.gov/pubmed/21681928

(107)McCracken KW, Howell JC, Wells JM and
Spence JR

GENERATING HUMAN INTESTINAL TISSUE FROM PLURIPOTENT STEM CELLS IN VITRO

2011; 6:1920-1928

Here we describe a protocol for generating 3D human intestinal tissues (called
organoids) in vitro from human pluripotent stem cells (hPSCs). To generate
intestinal organoids, pluripotent stem cells are first differentiated into
FOXA2(+)SOX17(+) endoderm by treating the cells with activin A for 3 d. After
endoderm induction, the pluripotent stem cells are patterned into CDX2(+) mid-
and hindgut tissue using FGF4 and WNT3a. During this patterning step, 3D mid-
or hindgut spheroids bud from the monolayer epithelium attached to the tissue
culture dish. The 3D spheroids are further cultured in Matrigel along with
prointestinal growth factors, and they proliferate and expand over 1-3 months
to give rise to intestinal tissue, complete with intestinal mesenchyme and
epithelium comprising all of the major intestinal cell types. To date, this is
the only method for efficiently directing the differentiation of hPSCs into 3D
human intestinal tissue in vitro.

Division of Developmental Biology, Cincinnati, Ohio, USA.

10.1038/nprot.2011.410

http://www.ncbi.nlm.nih.gov/pubmed/22082986

(108)Melvin A, Litsky A, Mayerson J,
Stringer K, Melvin D and Juncosa-Melvin N

AN ARTIFICIAL TENDON TO CONNECT THE QUADRICEPS MUSCLE TO THE TIBIA

2011; 29:1775-1782

No permanent, reliable artificial tendon exists clinically. Our group developed
the OrthoCouplerâ„¢ device as a versatile connector, fixed at one end to a
muscle, and adaptable at the other end to inert implants such as prosthetic
bones or to bone anchors. The objective of this study was to evaluate four
configurations of the device to replace the extensor mechanism of the knee in
goats. Within muscle, the four groups had: (A) needle-drawn uncoated bundles,
(B) needle-drawn coated bundles, (C) barbed uncoated bundles, and (D) barbed
coated bundles. The quadriceps tendon, patella, and patellar tendon were
removed from the right hind limb in 24 goats. The four groups (n = 6 for each)
were randomly assigned to connect the quadriceps muscle to the tibia (with a
bone plate). Specimens were collected from each operated leg and contralateral
unoperated controls both for mechanical testing and histology at 90 days
post-surgery. In strength testing, maximum forces in the operated leg (vs.
unoperated control) were 1,288 Â± 123 N (vs. 1,387 Â± 118 N) for group A, 1,323
Â± 144 N (vs. 1,396 Â± 779 N) for group B, 930 Â± 125 N (vs. 1,337 Â± 126 N)
for group C, and 968 Â± 109 N (vs. 1,528 Â± 146 N) for group D (mean Â± SEM).
The strengths of the OrthoCouplerâ„¢ legs in the needled device groups were
equivalent to unoperated controls (p = 0.6), while both barbed device groups
had maximum forces significantly lower than their controls (p = 0.001). We
believe this technology will yield improved procedures for clinical challenges
in orthopaedic oncology, revision arthroplasty, tendon transfer, and tendon
injury reconstruction. Copyright Â© 2011 Orthopaedic Research Society.

Surgical Energetics LLC, Covington, KY, United States Ohio State University,
Columbus, OH, United States Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States University of Cincinnati, Cincinnati, OH, United
States

10.1002/jor.21419

http://www.ncbi.nlm.nih.gov/pubmed/21520259

(109)Merchant TE, Rose SR, Bosley C, Wu S,
Xiong X and Lustig RH

GROWTH HORMONE SECRETION AFTER CONFORMAL RADIATION THERAPY IN PEDIATRIC
PATIENTS WITH LOCALIZED BRAIN TUMORS

2011; 29:4776-4780

Purpose: Growth hormone deficiency (GHD) after radiation therapy negatively
affects growth and development and quality of life in children with brain
tumors. Patients and Materials: Between 1997 and 2008, 192 pediatric patients
with localized primary brain tumors (ependymoma, n = 88; low-grade glioma, n =
51; craniopharyngioma, n = 28; high-grade glioma, n = 23; and other tumor
types, n = 2) underwent provocative testing of GH secretion by using the
secretogogues arginine and L-dopa before and after (6, 12, 36, and 60 months)
conformal radiation therapy (CRT). A total of 664 arginine/L-dopa test
procedures were performed. Results: Baseline testing revealed preirradiation
GHD in 22.9% of tested patients. On the basis of data from 118 patients, peak
GH was modeled as an exponential function of time after CRT and mean radiation
dose to the hypothalamus. The average patient was predicted to develop GHD with
the following combinations of the time after CRT and mean dose to the
hypothalamus: 12 months and more than 60 Gy; 36 months and 25 to 30 Gy; and 60
months and 15 to 20 Gy. A cumulative dose of 16.1 Gy to the hypothalamus would
be considered the mean radiation dose required to achieve a 50% risk of GHD at
5 years (TD50/5). Conclusion: GH secretion after CRT can be predicted on the
basis of dose and time after irradiation in pediatric patients with localized
brain tumors. These findings provide an objective radiation dose constraint for
the hypothalamus. Â© 2011 by American Society of Clinical Oncology.

St Jude Children's Research Hospital, Mail Stop 220, 262 Danny Thomas Place,
Memphis, TN 38015-3678, United States Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States University of California at San
Francisco, San Francisco, CA, United States

10.1200/jco.2011.37.9453

http://www.ncbi.nlm.nih.gov/pubmed/22042949

(110)Merhar S

BIOMARKERS IN NEONATAL POSTHEMORRHAGIC HYDROCEPHALUS

2012; 101:1-7

Posthemorrhagic hydrocephalus (PHH) is a rare but serious outcome among
premature babies in the NICU, with consequences including mortality and severe
neurodevelopmental disabilities. The causes of PHH are still not entirely
understood, and its prevention and treatment are controversial. Various
cerebrospinal fluid biomarkers have been studied in infants with PHH in order
to recognize the causes, diagnose brain injury, and predict neurodevelopmental
outcomes. This systematic review summarizes studies on biomarkers of
extracellular matrix activity, fibrinolysis/coagulation, hypoxia/cell death,
and inflammation in the cerebrospinal fluid of infants with PHH. Copyright Â©
2011 S. Karger AG, Basel.

Division of Neonatology, Cincinnati Children's Hospital, 3333 Burnet Ave ML
7009, Cincinnati, OH 45229, United States

10.1159/000323498

http://www.ncbi.nlm.nih.gov/pubmed/21791933

(111)Miller CK

ASPIRATION AND SWALLOWING DYSFUNCTION IN PEDIATRIC PATIENTS

2011; 3:336-343

Early identification and management of aspiration associated with oral intake
will help contribute to the best possible outcome for infants and children who
have airway protection issues with swallowing. Though the incidence and
prevalence of aspiration specifically related to swallowing dysfunction across
medical conditions in the pediatric population is unknown, there is
accumulating evidence of swallowing-related aspiration in infants and children
with diagnoses that include structural abnormalities of the upper airway,
central nervous system abnormalities, and progressive neurological disease. Chronic
aspiration is associated with compromised respiratory health, progressive lung
disease, bronchiectasis, and respiratory failure; thus, early detection and
appropriate management is crucial. Determining the etiology and effect of
aspiration is complex, and multiple evaluations are often required. This
article will focus on instrumental studies of swallowing physiology used in the
diagnosis and management of swallowing dysfunction and aspiration. Therapeutic
strategies to improve airway protection during swallowing will also be
described. Â© 2011 The Author(s).

Cincinnati Children's Hospital Medical Center, Aerodigestive and Sleep Center,
Interdisciplinary Feeding Team, ML 11002, 3333 Burnet Avenue, Cincinnati, OH
45229, United States

10.1177/1941406411423967

(112)Mina R, Melson P, Powell S, Rao M,
Hinze C, Passo M, Graham TB and Brunner HI

EFFECTIVENESS OF DEXAMETHASONE IONTOPHORESIS FOR TEMPOROMANDIBULAR JOINT
INVOLVEMENT IN JUVENILE IDIOPATHIC ARTHRITIS

2011; 63:1511-1516

OBJECTIVE: Temporomandibular joint (TMJ) involvement is common in juvenile
idiopathic arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade
electric currents for transdermal dexamethasone delivery into deeper anatomic
structures. The purpose of this study was to assess the safety and
effectiveness of DIP for the treatment of TMJ involvement in JIA, and to
delineate variables that are associated with improvement after DIP. METHODS:
Medical records of all JIA patients who underwent DIP for TMJ involvement at a
larger tertiary pediatric rheumatology center from 1997-2011 were reviewed. DIP
was performed using a standard protocol. The effectiveness of DIP was assessed
by comparing the maximal interincisor opening (MIO(TMJ) ) and the maximal
lateral excursion (MLE(TMJ) ) before and after treatment. RESULTS: Twenty-eight
patients (ages 2-21 years) who received an average of 8 DIP treatment sessions
per involved TMJ were included in the analysis. Statistically significant
improvement in the median MIO(TMJ) (P < 0.0001) was observed in 68%. The
median MLE(TMJ) (P = 0.03) improved in 69%, and resolution of TMJ pain occurred
in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were
transient site erythema (86%), skin blister (4%), and metallic taste (4%).
Improvement in TMJ range of motion from DIP is associated with lower MIO(TMJ) ,
lower MLE(TMJ) , and absence of TMJ crepitus at baseline. CONCLUSION: In this
pilot study, DIP appeared to be an effective and safe initial treatment of TMJ
involvement in JIA, especially among patients with decreased TMJ measurements.
Prospective controlled studies are needed.

Cincinnati Children's Hospital Medical Center, Ohio 45229-3039, USA. minara@ucmail.uc.edu

10.1002/acr.20600

http://www.ncbi.nlm.nih.gov/pubmed/22034112

(113)Mizukawa B, Wei J, Shrestha M,
Wunderlich M, Chou FS, Griesinger A, Harris CE, Kumar AR, Zheng Y, Williams DA
and Mulloy JC

INHIBITION OF RAC GTPase SIGNALING AND DOWNSTREAM PROSURVIVAL BCL-2 PROTEINS
AS COMBINATION TARGETED THERAPY IN MLL-AF9 LEUKEMIA

2011; 118:5235-5245

The Rac family of small Rho GTPases coordinates diverse cellular functions in
hematopoietic cells including adhesion, migration, cytoskeleton rearrangements,
gene transcription, proliferation, and survival. The integrity of Rac signaling
has also been found to critically regulate cellular functions in the initiation
and maintenance of hematopoietic malignancies. Using an in vivo gene targeting
approach, we demonstrate that Rac2, but not Rac1, is critical to the initiation
of acute myeloid leukemia in a retroviral expression model of MLL-AF9
leukemogenesis. However, loss of either Rac1 or Rac2 is sufficient to impair survival
and growth of the transformed MLL-AF9 leukemia. Rac2 is known to positively
regulate expression of Bcl-2 family proteins toward a prosurvival balance. We
demonstrate that disruption of downstream survival signaling through
antiapoptotic Bcl-2 proteins is implicated in mediating the effects of Rac2
deficiency in MLL-AF9 leukemia. Indeed, overexpression of Bcl-xL is able to
rescue the effects of Rac2 deficiency and MLL-AF9 cells are exquisitely
sensitive to direct inhibition of Bcl-2 family proteins by the BH3-mimetic,
ABT-737. Furthermore, concurrent exposure to NSC23766, a small-molecule
inhibitor of Rac activation, increases the apoptotic effect of ABT-737,
indicating the Rac/Bcl-2 survival pathway may be targeted synergistically.

Division of Oncology, Cancer and Blood Diseases Institute, Cincinnati
Children's Hospital Medical Center, OH 45229, USA.

10.1182/blood-2011-04-351817

http://www.ncbi.nlm.nih.gov/pubmed/21940819

(114)Morgan CI, Ledford JR, Zhou P and Page
K

ZINC SUPPLEMENTATION ALTERS AIRWAY INFLAMMATION AND AIRWAY
HYPERRESPONSIVENESS TO a COMMON ALLERGEN

2011; 8:36

ABSTRACT: BACKGROUND: Zinc supplementation can modulate immunity through
inhibition of NF-kappaB, a transcription factor that controls many immune
response genes. Thus, we sought to examine the mechanism by which zinc
supplementation tempers the response to a common allergen and determine its
effect on allergic airway inflammation. METHODS: Mice were injected with zinc
gluconate prior to German cockroach (GC) feces (frass) exposure and airway
inflammation was assessed. Primary bone marrow-derived neutrophils and
DMSO-differentiated HL-60 cells were used to assess the role of zinc gluconate
on tumor necrosis factor (TNF)alpha expression. NF-kappaB:DNA binding and IKK
activity were assessed by EMSA and in vitro kinase assay. Protein levels of
A20, RIP1 and TRAF6 were assessed by Western blot analysis. Establishment of
allergic airway inflammation with GC frass was followed by administration of
zinc gluconate. Airway hyperresponsiveness, serum IgE levels, eosinophilia and
Th2 cytokine production were assessed. RESULTS: Administration of zinc
gluconate prior to allergen exposure resulted in significantly decreased neutrophil
infiltration and TNFalpha cytokine release into the airways. This correlated
with decreased NF-kappaB activity in the whole lung. Treatment with zinc
gluconate significantly decreased GC frass-mediated TNFalpha production from
bone-marrow derived neutrophils and HL-60 cells. We confirmed zinc-mediated
decreases in NF-kappaB:DNA binding and IKK activity in HL-60 cells. A20, a
natural inhibitor of NF-kappaB and a zinc-fingered protein, is a potential
target of zinc. Zinc treatment did not alter A20 levels in the short term, but
resulted in the degradation of RIP1, an important upstream activator of IKK.
TRAF6 protein levels were unaffected. To determine the application for zinc as
a therapeutic for asthma, we administered zinc following the establishment of
allergic airway inflammation in a murine model. Zinc supplementation decreased
airway hyperresponsiveness and serum IgE levels, but had no effect on Th2
cytokine expression. CONCLUSIONS: This report suggests that the mechanism by
which zinc supplementation alters NF-kappaB activity is via the alteration of
A20 activity. In addition, this study provides evidence that supplementation of
zinc to asthmatics may alter airway reactivity and serum IgE levels, suggesting
zinc supplementation as a potential treatment for asthmatics.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, USA. kristen.page@cchmc.org.

10.1186/1476-9255-8-36

internal-pdf://Morgan-2011-Zinc supplementation-0379149312/Morgan-2011-Zinc
supplementation.pdf; http://www.ncbi.nlm.nih.gov/pubmed/22151973

(115)Mushaben EM, Kramer EL, Brandt EB,
Khurana Hershey GK and Le Cras TD

RAPAMYCIN ATTENUATES AIRWAY HYPERREACTIVITY, GOBLET CELLS, AND IgE IN
EXPERIMENTAL ALLERGIC ASTHMA

2011; 187:5756-5763

The mammalian target of rapamycin (mTOR) signaling pathway integrates
environmental cues, promotes cell growth/differentiation, and regulates immune
responses. Although inhibition of mTOR with rapamycin has potent
immunosuppressive activity, mixed effects have been reported in OVA-induced
models of allergic asthma. We investigated the impact of two rapamycin
treatment protocols on the major characteristics of allergic asthma induced by
the clinically relevant allergen, house dust mite (HDM). In protocol 1, BALB/c
mice were exposed to 10 intranasal HDM doses over a period of 24 d and treated
with rapamycin simultaneously during the sensitization/exposure period. In
protocol 2, rapamycin was administered after the mice had been sensitized to
HDM (i.p. injection) and prior to initiation of two intranasal HDM challenges
over 4 d. Airway hyperreactivity (AHR), IgE, inflammatory cells, cytokines, leukotrienes,
goblet cells, and activated T cells were assessed. In protocol 1, rapamycin
blocked HDM-induced increases in AHR, inflammatory cell counts, and IgE, as
well as attenuated goblet cell metaplasia. In protocol 2, rapamycin blocked
increases in AHR, IgE, and T cell activation and reduced goblet cell
metaplasia, but it had no effect on inflammatory cell counts. Increases in
IL-13 and leukotrienes were also blocked by rapamycin, although increases in
IL-4 were unaffected. These data demonstrated that rapamycin can inhibit
cardinal features of allergic asthma, including increases in AHR, IgE, and
goblet cells, most likely as a result of its ability to reduce the production
of two key mediators of asthma: IL-13 and leukotrienes. These findings
highlight the importance of the mTOR pathway in allergic airway disease.

Division of Pulmonary Biology, Cincinnati Children's Hospital, Cincinnati, OH
45229, USA. tim.lecras@cchmc.org

10.4049/jimmunol.1102133

http://www.ncbi.nlm.nih.gov/pubmed/22021618

(116)Nathan PC, Schiffman JD, Huang S,
Landier W, Bhatia S, Eshelman-Kent D, Wright J, Oeffinger KC and Hudson MM

CHILDHOOD CANCER SURVIVORSHIP EDUCATIONAL RESOURCES IN NORTH AMERICAN
PEDIATRIC hematology/oncology FELLOWSHIP TRAINING PROGRAMS: a SURVEY STUDY

2011; 57:1186-1190

BACKGROUND: Childhood cancer survivors require life-long care by clinicians
with an understanding of the specific risks arising from the prior cancer and
its therapy. We surveyed North American pediatric hematology/oncology training
programs to evaluate their resources and capacity for educating medical
trainees about survivorship. PROCEDURE: An Internet survey was sent to training
program directors and long-term follow-up clinic (LTFU) directors at the 56 US
and Canadian centers with pediatric hematology/oncology fellowship programs.
Perceptions regarding barriers to and optimal methods of delivering
survivorship education were compared among training program and LTFU clinic
directors. RESULTS: Responses were received from 45/56 institutions of which
37/45 (82%) programs require that pediatric hematology/oncology fellows
complete a mandatory rotation focused on survivorship. The rotation is 4 weeks
or less in 21 programs. Most (36/45; 80%) offer didactic lectures on
survivorship as part of their training curriculum, and these are considered
mandatory for pediatric hematology/oncology fellows at 26/36 (72.2%). Only 10
programs (22%) provide training to medical specialty trainees other than
pediatric hematology/oncology fellows. Respondents identified lack of time for
trainees to spend learning about late effects as the most significant barrier
to providing survivorship teaching. LTFU clinic directors were more likely than
training program directors to identify lack of interest in survivorship among
trainees and survivorship not being a formal or expected part of the fellowship
training program as barriers. CONCLUSIONS: The results of this survey highlight
the need to establish standard training requirements to promote the achievement
of basic survivorship competencies by pediatric hematology/oncology fellows.

The Hospital for Sick Children, Toronto, ON, Canada. paul.nathan@sickkids.ca

10.1002/pbc.23214

http://www.ncbi.nlm.nih.gov/pubmed/21674761

(117)Nemecek ER, Ellis K, He W, Bunin NJ,
Bajwa RS, Cheerva A, Cairo MS, Dvorak C, Duval M, Davies S, Eapen M, Gross TG,
Hussein AA, MacMillan ML, Mehta PA, Pulsipher MA, Seber A, Woolfrey AE,
Frangoul HA and Carpenter PA

OUTCOME OF MYELOABLATIVE CONDITIONING AND UNRELATED DONOR HEMATOPOIETIC CELL
TRANSPLANTATION FOR CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA IN THIRD REMISSION

2011; 17:1833-1840

We conducted a retrospective study of 155 children who underwent unrelated
donor hematopoietic cell transplantation (HCT) between 1990 and 2005 for acute
lymphoblastic leukemia in third remission. The median patient age was 11 years,
the median time from diagnosis to first relapse was 36 months, and the median
time from first relapse to second relapse was 26 months. Stem cell sources were
bone marrow (n = 115), peripheral blood (n = 11), and cord blood (n = 29). All
patients received a myeloablative pretransplantation conditioning regimen. The
5-year estimates of leukemia-free survival, relapse, and nonrelapse mortality
were 30%, 25%, and 45%, respectively. In multivariate analysis, the only risk
factor associated with relapse was the interval between the first relapse and
the second relapse. Second relapses occurring >26 months from the first
relapse were associated with lower risk for post-HCT relapse compared with second
relapses occurring at â‰¤26 months (relative risk, 0.4; P =.01). Relapse risk
was lowest when late second relapse was preceded by late first relapse (>36
months from diagnosis), as demonstrated by a 3-year relapse rate of 9% (P
=.0009). Our data indicate that long-term leukemia-free survival can be
achieved in children with acute lymphoblastic leukemia in third remission using
unrelated donor HCT, especially when the second relapse occurs late. Â© 2011
American Society for Blood and Marrow Transplantation.

Pediatric Blood and Marrow Transplant Program, Doernbecher Children's Hospital,
Portland, OR, United States Center for International Blood and Marrow
Transplant Research, Milwaukee, WI, United States Children's Hospital of
Philadelphia, Philadelphia, PA, United States Nationwide Children's Hospital,
Columbus, OH, United States Kosair Children's Hospital, Louisville, KY, United
States Morgan Stanley Children's Hospital of New York, Presbyterian Columbia
Univ. Medical Center, New York, NY, United States University of California San
Francisco Medical Center, San Francisco, CA, United States Sainte Justine
Hospital, Montreal, QC, Canada Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States King Hussein Cancer Center, Amman, Jordan University
of Minnesota Medical Center, Minneapolis, MN, United States Primary Children's
Medical Center, Salt Lake City, UT, United States Institute of Pediatric
Oncology, Sao Paulo, Brazil Fred Hutchinson Cancer Research Center, Seattle,
WA, United States Vanderbilt University Medical Center, Nashville, TN, United
States

10.1016/j.bbmt.2011.05.014

http://www.ncbi.nlm.nih.gov/pubmed/21683798

(118)Ng KP, Ebrahem Q, Negrotto S, Mahfouz
RZ, Link KA, Hu Z, Gu X, Advani A, Kalaycio M, Sobecks R, Sekeres M, Copelan E,
Radivoyevitch T, MacIejewski J, Mulloy JC and Saunthararajah Y

P53 INDEPENDENT EPIGENETIC-DIFFERENTIATION TREATMENT IN XENOTRANSPLANT
MODELS OF ACUTE MYELOID LEUKEMIA

2011; 25:1739-1750

Suppression of apoptosis by TP53 mutation contributes to resistance of acute
myeloid leukemia (AML) to conventional cytotoxic treatment. Using
differentiation to induce irreversible cell cycle exit in AML cells could be a
p53-independent treatment alternative, however, this possibility requires
evaluation. In vitro and in vivo regimens of the deoxycytidine analogue
decitabine that deplete the chromatin-modifying enzyme DNA methyl-transferase 1
without phosphorylating p53 or inducing early apoptosis were determined. These
decitabine regimens but not equimolar DNA-damaging cytarabine upregulated the
key late differentiation factors CCAAT enhancer-binding protein and p27/cyclin
dependent kinase inhibitor 1B (CDKN1B), induced cellular differentiation and
terminated AML cell cycle, even in cytarabine-resistant p53-and p16/CDKN2A-null
AML cells. Leukemia initiation by xenotransplanted AML cells was abrogated but
normal hematopoietic stem cell engraftment was preserved. In vivo, the low
toxicity allowed frequent drug administration to increase exposure, an
important consideration for S phase specific decitabine therapy. In
xenotransplant models of p53-null and relapsed/refractory AML, the
non-cytotoxic regimen significantly extended survival compared with conventional
cytotoxic cytarabine. Modifying in vivo dose and schedule to emphasize this
pathway of decitabine action can bypass a mechanism of resistance to standard
therapy. Â© 2011 Macmillan Publishers Limited All rights reserved.

Department of Translational Hematology and Oncology Research, Taussig Cancer
Institute, Cleveland Clinic, 9500 Euclid Avenue R40, Cleveland, OH 44195,
United States Experimental Hematology and Cancer Biology, Cincinnati Children's
Hospital, Cleveland, OH, United States Department of Hematologic Oncology and
Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH,
United States Department of Epidemiology and Biostatistics, Case Western
Reserve University, Cleveland, OH, United States

10.1038/leu.2011.159

http://www.ncbi.nlm.nih.gov/pubmed/21701495

(119)Noah TK, Donahue B and Shroyer NF

INTESTINAL DEVELOPMENT AND DIFFERENTIATION

2011; 317:2702-2710

In this review, we present an overview of intestinal development and cellular
differentiation of the intestinal epithelium. The review is separated into two
sections: Section one summarizes organogenesis of the small and large
intestines, including endoderm and gut tube formation in early embryogenesis,
villus morphogenesis, and crypt formation. Section two reviews cell fate
specification and differentiation of each cell type within the intestinal
epithelium. Growth factor and transcriptional networks that regulate these
developmental processes are summarized.

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's
Hospital Medical Center, Cincinnati, OH, USA.

10.1016/j.yexcr.2011.09.006

http://www.ncbi.nlm.nih.gov/pubmed/21978911

(120)Noh PH, Defoor WR and Reddy PP

PERCUTANEOUS ANTEGRADE URETERAL STENT PLACEMENT DURING PEDIATRIC
ROBOT-ASSISTED LAPAROSCOPIC PYELOPLASTY

2011; 25:1847-1851

BACKGROUND AND PURPOSE: Robot-assisted laparoscopic pyeloplasty has become more
widely used. Intraoperative placement and confirmation of ureteral stent
position can be cumbersome with the robotic arms in place. We present a
technique of percutaneous antegrade stent placement that is reliable with
minimal morbidity. PATIENTS AND METHODS: A retrospective cohort study was
performed. Patient demographics, radiographic imaging, intraoperative details,
and surgical outcomes were abstracted from the medical record. A 14-gauge
angiocatheter was placed through the abdominal wall. A ureteral stent was
guided over a wire down the dismembered ureter. Stent position was confirmed by
retrograde reflux of methylene blue. A urethral catheter was left in place for
12 to 36 hours. RESULTS: Twenty-nine patients (15 male, 14 female) were
identified. Average age was 10 years. Average follow-up was 14 months. Fifteen
left- and 14 right-sided procedures were performed. Two patients needed
retrograde stent placement. Mean time to correctly position the stent was less
than 5 minutes. Postoperatively, one patient had a urine leak managed by an
indwelling urethral catheter and did not need percutaneous drainage. All stents
were removed approximately 4 to 6 weeks postoperatively. One patient had
retrograde migration of the stent managed by ureteroscopy at the time of stent
retrieval. CONCLUSIONS: Antegrade ureteral stent placement through a
percutaneous angiocatheter, during robot-assisted laparoscopic pyeloplasty, is
a rapid and effective technique. Intraoperative confirmation of stent position
can be obtained, using methylene blue bladder distention, without repositioning
the patient or undocking the surgical robot.

Division of Pediatric Urology, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio 45229-3039, USA. paul.noh@cchmc.org

10.1089/end.2011.0168

http://www.ncbi.nlm.nih.gov/pubmed/21967318

(121)O'Flaherty T, Santoro K and Pentiuk S

CALCULATING AND PREPARING a PUREED-BY-GASTROSTOMY-TUBE (PBGT) DIET FOR
PEDIATRIC PATIENTS WITH RETCHING AND GAGGING POSTFUNDOPLICATION

2011; 3:361-364

Children with feeding disorders often require gastrostomy feedings and may
experience episodes of retching and gagging. The pureed-by-gastrostomy-tube
(PBGT) diet was developed to reduce episodes of retching and gagging, provide a
complete source of the child's nutrition and fluid needs as an alternative to
commercialized formulas, and promote oral intake. This article is a follow-up
to the authors' original report. The authors' intention is to now provide
guidelines for other dietitians to calculate and analyze this specialized
formula. It also describes feeding guidelines, family education, and ongoing
patient follow-up and monitoring. Â© 2011 The Author(s).

Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati,
OH, United States

10.1177/1941406411423702

(122)Palencia-Desai S, Kohli V, Kang J, Chi
NC, Black BL and Sumanas S

VASCULAR ENDOTHELIAL AND ENDOCARDIAL PROGENITORS DIFFERENTIATE AS
CARDIOMYOCYTES IN THE ABSENCE OF Etsrp/Etv2 FUNCTION

2011; 138:4721-4732

Previous studies have suggested that embryonic vascular endothelial,
endocardial and myocardial lineages originate from multipotential
cardiovascular progenitors. However, their existence in vivo has been debated
and molecular mechanisms that regulate specification of different
cardiovascular lineages are poorly understood. An ETS domain transcription
factor Etv2/Etsrp/ER71 has been recently established as a crucial regulator of
vascular endothelial differentiation in zebrafish and mouse embryos. In this
study, we show that etsrp-expressing vascular endothelial/endocardial
progenitors differentiate as cardiomyocytes in the absence of Etsrp function
during zebrafish embryonic development. Expression of multiple endocardial
specific markers is absent or greatly reduced in Etsrp knockdown or mutant
embryos. We show that Etsrp regulates endocardial differentiation by directly
inducing endocardial nfatc1 expression. In addition, Etsrp function is required
to inhibit myocardial differentiation. In the absence of Etsrp function,
etsrp-expressing endothelial and endocardial progenitors initiate myocardial
marker hand2 and cmlc2 expression. Furthermore, Foxc1a function and interaction
between Foxc1a and Etsrp is required to initiate endocardial development, but
is dispensable for the inhibition of myocardial differentiation. These results
argue that Etsrp initiates endothelial and endocardial, and inhibits
myocardial, differentiation by two distinct mechanisms. Our findings are
important for the understanding of genetic pathways that control cardiovascular
differentiation during normal vertebrate development and will also greatly
contribute to the stem cell research aimed at regenerating heart tissues.

Division of Developmental Biology, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH 45229, USA.

10.1242/dev.064998

http://www.ncbi.nlm.nih.gov/pubmed/21989916

(123)Pardo AC, Do T, Ryder T, Meyer A,
Miles L and Wong BL

COMBINATION OF STEROIDS AND ISCHIAL WEIGHT-BEARING KNEE ANKLE FOOT ORTHOSES
IN DUCHENNE's MUSCULAR DYSTROPHY PROLONGS AMBULATION PAST 20 YEARS OF AGE--a
CASE REPORT

2011; 21:800-802

Patients with Duchenne muscular dystrophy (DMD) lose ambulation by age 12.
Long-term steroids have lengthened ambulation by 2-5 years. Ischial
weight-bearing knee ankle foot orthoses prolong ambulation for 2-3 years. We
report the outcome of the ambulatory status of a patient with DMD treated with
daily steroid therapy and orthoses. This male patient was diagnosed with DMD at
age of 2. He has been treated with daily steroids since age 7 years. He lost
the ability to arise from the floor and walk up steps at age 14 and lost
ambulation by age 16. He was fitted with orthoses at age 16 following surgical
correction of his lower extremity contractures and regained independent
ambulation. At age 20, he was able to stand independently in his orthoses and
take steps with moderate support. We conclude that a combination of daily
steroids and orthoses prolongs ambulation beyond that of the natural history
DMD.

Department of Pediatric Neurology, Cincinnati Children's Hospital Medical
Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. andrea.pardo@cchmc.org

10.1016/j.nmd.2011.06.006

http://www.ncbi.nlm.nih.gov/pubmed/21784636

(124)Parikh SN, Bonnaig N and Zbojniewicz A

INTRACAPSULAR ORIGIN OF THE LONG HEAD OF THE BICEPS TENDON WITH GLENOID
AVULSION OF THE GLENOHUMERAL LIGAMENTS

2011; 34:e781-4

An 18-year-old woman presented with a history of recurrent glenohumeral
dislocations involving her right dominant shoulder. Physical examination
suggested physiologic hyperlaxity and anterior instability. Magnetic resonance
arthrography demonstrated an anomalous intracapsular origin of the long head of
the biceps tendon (LHBT), with normal-appearing LHBT in the intertubercular
groove. Diagnostic arthroscopy confirmed the absence of the LHBT attachment on
the superior labrum. Instead, the LHBT originated from the capsule of the
shoulder joint. Diagnostic arthroscopy also revealed glenoid avulsion of the
glenohumeral ligaments (GAGL) lesion as a tear in the anterior-inferior capsule
near its insertion on the glenoid and labrum. An arthroscopic anterior
capsulolabral repair was performed with rotator interval closure by imbrication
of superior and middle glenohumeral ligaments. A retrospective review of the
magnetic resonance arthrogram identified irregularity and interposition of
contrast between the capsule and the anterior-inferior labrum that was
reproduced in the abduction-external rotation view corresponding with the GAGL
lesion seen at arthroscopy. At 12 months postoperatively, the patient
demonstrated full range of motion and no signs of instability. This case report
helps to raise awareness about 2 rare shoulder lesions: the anomalous origin of
LHBT and the GAGL lesion. Diagnosing such lesions on preoperative magnetic
resonance imaging may aid in operative planning and avoid unexpected
intraoperative findings.

Division of Pediatric Orthopaedic Surgery, Cincinnati Children's Hospital
Medical Center, Cincinnati, Ohio, USA. shital.parikh@cchmc.org

10.3928/01477447-20110922-26

http://www.ncbi.nlm.nih.gov/pubmed/22049965

(125)PeÃ±a A, Bischoff A and Levitt MA

THE TRANSPUBIC APPROACH FOR THE CORRECTION OF COMPLEX ANORECTAL AND
UROGENITAL MALFORMATIONS

2011; 46:2316-2320

Background: The transpubic approach has been used mainly to treat urethral
injuries and prostate cancer. There are no reports describing this approach in
anorectal malformations. Methods: Forty-two patients who underwent a transpubic
approach for their genitourinary/colorectal reconstruction were reviewed.
Indications, complications, and follow-up were analyzed. A midline
infraumbilical incision was used. The pubic cartilage was divided with needle
cautery. Institutional review board approval was obtained (IRB# 2008-1317).
Results: The cases included complex malformations (16), covered exstrophy (15),
long urogenital sinus with normal rectum (6), and reoperations in cloacas which
had been left with persistent fistulae between vagina and urinary tract with
normal rectum (5). Excellent exposure was achieved in all cases, allowing
successful anatomical reconstruction. Functional results varied depending on
the specific type of defect but were not expected to be good due to severe
congenital or acquired anatomic defects. There were 3 complications related to
the transpubic approach: pubic dehiscence, suspected osteomyelitis, and
bleeding. Conclusion: The transpubic approach should be considered for the
repair of complex anorectal and urogenital malformations, especially when
adequate exposure cannot be achieved with an abdominal, perineal, or posterior
sagittal approach. Another ideal indication is in patients with a normal rectum
who were born with a complex urogenital sinus or underwent a failed attempted
repair but were left with problems requiring reoperation in a scarred and
fibrotic pelvis. Â© 2011 Elsevier Inc.

Colorectal Center for Children, Division of Pediatric Surgery, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH 45229, United States

10.1016/j.jpedsurg.2011.09.023

http://www.ncbi.nlm.nih.gov/pubmed/22152873

(126)Pendergrass T, Manos J and LeMaster T

AS SEEN ON TV: POPULAR MEDIA TO HELP LEARNERS DISCOVER THE MAGIC OF
SIMULATION

2011; 7:e259-e259

Cincinnati Children's Center for Simulation and Research, 3333 Burnet Avenue ML
12000, Cincinnati, Ohio 45229

10.1016/j.ecns.2011.09.054

(127)Plageman TF, J., Chauhan BK, Yang C,
Jaudon F, Shang X, Zheng Y, Lou M, Debant A, Hildebrand JD and Lang RA

A TRIO-RhoA-Shroom3 PATHWAY IS REQUIRED FOR APICAL CONSTRICTION AND
EPITHELIAL INVAGINATION

2011; 138:5177-5188

Epithelial invagination is a common feature of embryogenesis. An example of
invagination morphogenesis occurs during development of the early eye when the
lens placode forms the lens pit. This morphogenesis is accompanied by a
columnar-to-conical cell shape change (apical constriction or AC) and is known
to be dependent on the cytoskeletal protein Shroom3. Because Shroom3-induced AC
can be Rock1/2 dependent, we hypothesized that during lens invagination, RhoA,
Rock and a RhoA guanine nucleotide exchange factor (RhoA-GEF) would also be
required. In this study, we show that Rock activity is required for lens pit
invagination and that RhoA activity is required for Shroom3-induced AC. We
demonstrate that RhoA, when activated and targeted apically, is sufficient to
induce AC and that RhoA plays a key role in Shroom3 apical localization.
Furthermore, we identify Trio as a RhoA-GEF required for Shroom3-dependent AC
in MDCK cells and in the lens pit. Collectively, these data indicate that a
Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.

The Visual Systems Group, Cincinnati Children's Hospital Medical Center,
University of Cincinnati, Cincinnati, OH 45229, USA.

10.1242/dev.067868

http://www.ncbi.nlm.nih.gov/pubmed/22031541

(128)Potter JL, Wade SL, Walz NC, Cassedy
A, Stevens MH, Yeates KO and Taylor HG

PARENTING STYLE IS RELATED TO EXECUTIVE DYSFUNCTION AFTER BRAIN INJURY IN
CHILDREN

2011; 56:351-358

OBJECTIVE: The goal of this study was to examine how parenting style
(authoritarian, authoritative, permissive) and family functioning are related
to behavioral aspects of executive function following traumatic brain injury
(TBI) in young children. METHOD: Participants included 75 children with TBI and
97 children with orthopedic injuries (OI), ages 3-7 years at injury. Pre-injury
parenting behavior and family functioning were assessed shortly after injury,
and postinjury executive functions were assessed using the Behavior Rating
Inventory of Executive Functioning (BRIEF; Gioia & Isquith, 2004) at 6, 12,
and 18 months postinjury. Mixed model analyses, using pre-injury executive
functioning (assessed by the BRIEF at baseline) as a covariate, examined the relationship
of parenting style and family characteristics to executive functioning in
children with moderate and severe TBI compared to OI. RESULTS: Among children
with moderate TBI, higher levels of authoritarian parenting were associated
with greater executive difficulties at 12 and 18 months following injury.
Permissive and authoritative parenting styles were not significantly associated
with postinjury executive skills. Finally, fewer family resources predicted
more executive deficits across all of the groups, regardless of injury type.
CONCLUSION: These findings provide additional evidence regarding the role of
the social and familial environment in emerging behavior problems following
childhood TBI.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, USA. jennifer.potter@cchmc.org

10.1037/a0025445

http://www.ncbi.nlm.nih.gov/pubmed/21928918

(129)Prada CE, Al Jasmi F, Kirk EP, Hopp M,
Jones O, Leslie ND and Burrow TA

CARDIAC DISEASE IN METHYLMALONIC ACIDEMIA

2011; 159:862-864

Methylmalonic acidemia (MMA) is a heterogeneous disorder, with onset from
infancy to adulthood and varying degrees of organ involvement and severity.
Cardiac disease is a known lethal complication of other organic acidemias, but
has not been associated with MMA. We identified 3 patients with MMA and cardiac
disease.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center,
University of Cincinnati College of Medicine, Cincinnati, OH, USA.

10.1016/j.jpeds.2011.06.005

http://www.ncbi.nlm.nih.gov/pubmed/21784454

(130)Prada CE, Sellars EA, Spaeth CG,
Kline-Fath B, Crombleholme TM and Hopkin RJ

SEVERE CERVICAL SCOLIOSIS IN THE FETUS

2011; 31:1198-1202

OBJECTIVE: This study provides prenatal characteristics and postnatal outcomes
of patients with severe cervical scoliosis. METHODS: A retrospective analysis
of clinical information from cases prenatally diagnosed with severe cervical
scoliosis (>90 degrees angulation) in the Fetal Care Center at Cincinnati
Children's Hospital Medical Center between 2007 and 2010 was performed. We excluded
iniencephaly and tumors of the head or neck. RESULTS: We identified five
patients with severe cervical scoliosis. The fetal spine abnormality was
diagnosed between 18 and 27 weeks of gestation. Classical cesarean section was
recommended in all patients. There were no immediate airway or neurological
complications in the delivery room. Extravertebral anomalies were present in
four of the five patients. These patients had a more complicated clinical
course and three separate syndromes including a complex collagenopathy,
heterotaxy, and Klippel-Feil syndrome were identified. One patient had an
isolated cervical deformation secondary to a large uterine fibroid with a
benign clinical course. None of the infants have required spinal surgery.
CONCLUSION: Our patients suggest that connective tissue diseases or heterotaxy
may be important risk factors for the development of severe cervical scoliosis.
There were no significant long-term complications directly related to cervical
scoliosis.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, USA.

10.1002/pd.2898

http://www.ncbi.nlm.nih.gov/pubmed/22031186

(131)Presicce P, Orsborn K, King E, Pratt
J, Fichtenbaum CJ and Chougnet CA

FREQUENCY OF CIRCULATING REGULATORY T CELLS INCREASES DURING CHRONIC HIV
INFECTION AND IS LARGELY CONTROLLED BY HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

2011; 6:e28118

Regulatory T cells (Tregs) act by suppressing the activation and effector
functions of innate and adaptive immune responses. HIV infection impacts Treg
proportion and phenotype, although discrepant results have been reported
depending on the patient population and the way Tregs were characterized. The
effects of highly active antiretroviral therapy (HAART) on Treg frequency have
not been thoroughly documented. We performed a detailed longitudinal analysis
of Treg frequency and phenotype in 11 HIV-infected individuals enrolled in a
single, prospective clinical trial, in which all patients underwent the same
treatment protocol and were sampled at the same time points. Tregs were
characterized for their expression of molecules associated with activation,
cell cycle, apoptosis, or function, and compared to circulating Tregs from a group
of age-matched healthy individuals.Our results revealed increased proportions,
but reduced absolute numbers of circulating CD3(+)CD4(+)FOXP3(+) Tregs in
chronically infected HIV-infected patients. Treg frequency was largely
normalized by HAART. Importantly, we show that similar conclusions were drawn
regardless of the combination of markers used to define Tregs. Our results also
showed increased expression of cell cycle markers (Ki67 and cyclin B) in Tregs
from untreated infected individuals, which were decreased by HAART. However,
the Treg phenotype in untreated patients was not consistent with a higher level
of generalized activation, as they expressed very low levels of CD69, slightly
elevated levels of HLA-DR and similar levels of GARP compared to Tregs from
uninfected donors. Moreover, none of these markers was significantly changed by
HAART. Treg expression of CTLA-4 and cytotoxic molecules was identical between
patients and controls. The most striking difference in terms of functional
molecules was the high expression of CD39 by Tregs in untreated patients, which
HAART only partially controlled.

Division of Molecular Immunology, Cincinnati Children's Hospital Research
Foundation, Department of Pediatrics, University of Cincinnati College of
Medicine, Cincinnati, Ohio, United States of America.

10.1371/journal.pone.0028118

internal-pdf://Presicce-2011-Frequency of
Circula-2644062464/Presicce-2011-Frequency of Circula.pdf; http://www.ncbi.nlm.nih.gov/pubmed/22162758

(132)Putnam FW

SAFE AT HOME?

2011; 159:710-711

Cincinnati Children's Hospital, Center for Safe and Healthy Children,
Cincinnati, Ohio.

http://www.ncbi.nlm.nih.gov/pubmed/21890148

(133)Qian Y, Zhou X, Liang M, Qu J and Guan
MX

THE ALTERED ACTIVITY OF COMPLEX III MAY CONTRIBUTE TO THE HIGH PENETRANCE OF
LEBER's HEREDITARY OPTIC NEUROPATHY IN a CHINESE FAMILY CARRYING THE ND4
G11778A MUTATION

2011; 11:871-877

The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading
to Leber's hereditary optic neuropathy (LHON). Despite considerable clinical
evidences, the modifier role of nuclear background and mitochondrial haplotypes
in phenotypic manifestation of LHON remains poorly understood. We investigated
the effect of these modifiers on bioenergetics in lymphoblastoid cell lines
derived from five affected subjects of one Chinese family carrying the G11778A
mutation and five Chinese controls. Significant reductions in the activities of
complexes I and III were observed in mutant cell lines from the Chinese family,
whereas the mutant cell lines from other families carrying the same mutation
exhibited only reduced activity of complex I. The reduced activities of
complexes I and III caused remarkably higher reductions of ATP synthesis in
mutant cell lines from the Chinese family than those from other families. The
deficient respiration increased generation of reactive oxygen species. The defect
in complex III activity, likely resulting from the mitochondrial haplotype or
nuclear gene alteration, worsens mitochondrial dysfunction caused by the
G11778A mutation, thereby causing extremely high penetrance and expressivity of
optic neuropathy in this Chinese family. Our data provide the first
experimental evidence that altered activity of complex III modulates the
phenotypic manifestation of LHON-associated G11778A mutation. Thus, our
findings may provide new insights into the pathophysiology of LHON.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio, USA.

10.1016/j.mito.2011.06.006

http://www.ncbi.nlm.nih.gov/pubmed/21742061

(134)Rappuoli R, Mandl CW, Black S and De
Gregorio E

VACCINES FOR THE TWENTY-FIRST CENTURY SOCIETY

2011; 11:865-872

Vaccines have been one of the major revolutions in the history of mankind and,
during the twentieth century, they eliminated most of the childhood diseases
that used to cause millions of deaths. In the twenty-first century, vaccines
will also play a major part in safeguarding people's health. Supported by the
innovations derived from new technologies, vaccines will address the new needs
of a twenty-first century society characterized by increased life expectancy,
emerging infections and poverty in low-income countries. Â© 2011 Macmillan
Publishers Limited. All rights reserved.

Novartis Vaccines and Diagnostics Srl, Via Fiorentina 5, 53100 Siena, Italy
Novartis Vaccines and Diagnostics Inc., 45 Sydney Street, Cambridge, MA 02139,
United States Center for Global Health, University of Cincinnati Children's
Hospital, Cincinnati, OH 45229, United States

10.1038/nri3085 10.1056/NEJMoa1102287; The 2010 scientific strategic plan of
the Global HIV Vaccine Enterprise (2010) Nature Med., 16, pp. 981-989. ,
Council of the Global HIV Vaccine Enterprise et al; Kaufmann, S., Is the
development of a new t(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/22051890

(135)Ravi S

AUTOIMMUNE INNER EAR DISEASE

2011; 32:299-307

Autoimmune inner ear disease (AIED), first reported by McCabe in 1979,
describes a disease process in which cochleovestibular is compromised by one's
own immune system. Only indirect laboratory evidence exists regarding the
underlying immune reaction, which can only be confirmed histopathologically in
postmortem studies. Diagnosis involves a thorough history and complete head and
neck, otomicroscopic, and audiometric evaluation. AIED classically presents
with bilateral, fluctuating, or rapidly progressive asymmetric sensorineural
hearing loss (SNHL), which typically occurs over weeks to months but can occur
suddenly over a period of a few hours or days. Fifty percent of patients have
vestibular symptoms as well, which can be unilateral or bilateral. A lengthy
serological workup is unwarranted given the absence of a reliable diagnostic
laboratory test. Antibodies to the 68-kDa protein (heat shock protein-70) is
marker-specific but not sensitive for AIED and may correlate with steroid
responsiveness. In cases where the diagnosis remains unclear, a prolonged
course of steroids, with repeat audiometric testing at 1 month, can be
undertaken. Treatment aims to inhibit the detrimental immune response using
immunosuppressant drugs; however, no standardized treatment regimen has been
found. Cochlear implantation remains a viable last resort for patients with
progressive SNHL.

Department of Otolaryngology, University of Cincinnati/Cincinnati Children's
Hospital, UC Neuroscience Institute, Cincinnati, Ohio

(136)Redline S, Amin R, Beebe D, Chervin
RD, Garetz SL, Giordani B, Marcus CL, Moore RH, Rosen CL, Arens R, Gozal D,
Katz ES, Mitchell RB, Muzumdar H, Taylor HG, Thomas N and Ellenberg S

THE CHILDHOOD ADENOTONSILLECTOMY TRIAL (CHAT): RATIONALE, DESIGN, AND
CHALLENGES OF a RANDOMIZED CONTROLLED TRIAL EVALUATING a STANDARD SURGICAL
PROCEDURE IN a PEDIATRIC POPULATION

2011; 34:1509-1517

Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of
pediatric obstructive sleep apnea (OSA) are performed in the US in children
under 15 years of age. No definitive study, however, has been yet conducted
that has rigorously evaluated the effectiveness of AT for not only improving
sleep disordered breathing, but also for improving clinically relevant
outcomes, such as neurocognitive function, behavior, and quality of life. The
Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological
and health outcomes in children randomized to receive early AT (eAT) as
compared to Watchful Waiting with Supportive Care (WWSC). Important secondary
goals of the study are to evaluate outcomes in subgroups defined by obesity and
race. This paper addresses key elements in the design and implementation of a
controlled trial for a widely used "standard practice" surgical
intervention in a pediatric population, that include establishment of
standardized data collection procedures across sites for a wide variety of data
types, establishment of equipoise, and approaches for minimizing unblinding of
selected key personnel. The study framework that was established should provide
a useful template for other pediatric controlled studies or other studies that evaluate
surgical interventions.

Harvard Medical School, Division of Sleep Medicine, Brigham and Women's
Hospital, 221 Longwood Avenue, Boston, MA 02115, United States Children's
Hospital Medical Center, Cincinnati, OH, United States Sleep Disorders Center and
Department of Neurology, University of Michigan, Ann Arbor, MI, United States
Department of Otolaryngology/Head and Neck Surgery, University of Michigan
Health System, Ann Arbor, MI, United States Neuropsychology Section,
Departments of Psychiatry, Neurology, and Psychology, University of Michigan,
Ann Arbor, MI, United States Sleep Center, Children's Hospital of Philadelphia,
University of Pennsylvania, Philadelphia, PA, United States Department of
Biostatistics and Epidemiology, University of Pennsylvania School of Medicine,
Philadelphia, PA, United States Department of Pediatrics, University
Hospitals-Case Medical Center, Rainbow Babies and Children's Hospital,
Cleveland, OH, United States Children's Hospital at Montefiore, Albert Einstein
College of Medicine, Bronx, NY, United States Department of Pediatrics,
Pritzker School of Medicine, University of Chicago, Chicago, IL, United States
Division of Respiratory Diseases, Harvard Medical School, Children's Hospital,
Boston, Boston, MA, United States Pediatric Otolaryngology, Saint Louis
University School of Medicine, Cardinal Glennon Children's Medical Center, St
Louis, MO, United States Neuropsychology and Assessment, Department of Child
and Adolescent Psychiatry and Behavioral Science, Children's Hospital of
Philadelphia, Philadelphia, PA, United States

10.5665/sleep.1388

http://www.ncbi.nlm.nih.gov/pubmed/22043122

(137)Reed CA, Baker RS, Lam CT, Hilshorst
JL, Ferguson R, Lombardi J and Eghtesady P

APPLICATION OF NEAR-INFRARED SPECTROSCOPY DURING FETAL CARDIAC SURGERY

2011; 171:159-163

BACKGROUND: Near-infrared spectroscopy (NIRS) has been shown to provide
reliable noninvasive monitoring of regional oxygenation in a variety of clinical
settings. We set out to test its feasibility as a monitor of fetal and
placental oxygenation during fetal cardiac surgery. MATERIALS AND METHODS: Six
ovine fetuses from 98-110 ds gestation were placed on fetal bypass for 30 min
and followed post-bypass for 2 h. A NIRS probe (MI INVOS 5100B; Somanetics,
Troy, MI) was placed on the pregnant uterine horn during and after fetal
surgery. NIRS values were compared with blood gas values obtained by direct
sampling from umbilical circulation. RESULTS: NIRS values positively correlated
with umbilical venous oxygen saturation (R(2)=0.891, P<0.01) and partial
oxygen pressure values (R(2)=0.810, P<0.01). NIRS values also correlated to
a lesser extent with umbilical venous pH and pCO(2), and fetal arterial pH,
pO(2), and oxygen saturation. CONCLUSIONS: This is the first report of
application of NIRS in the setting of fetal surgery. NIRS permits noninvasive
assessment of placental oxygen saturation and pO(2). This technology is a
simple and useful tool for real-time monitoring of oxygen delivery to the fetus
during maternal-fetal cardiac interventions and of overall well-being of the
fetal-placental unit.

Division of Cardiothoracic Surgery, Cincinnati Children's Hospital Medical
Center, Cincinnati, Ohio 45229-3032, USA.

10.1016/j.jss.2009.11.012

http://www.ncbi.nlm.nih.gov/pubmed/20189599

(138)Rehman AU, Gul K, Morell RJ, Lee K,
Ahmed ZM, Riazuddin S, Ali RA, Shahzad M, Jaleel AU, Andrade PB, Khan SN, Khan
S, Brewer CC, Ahmad W, Leal SM and Friedman TB

MUTATIONS OF GIPC3 CAUSE NONSYNDROMIC HEARING LOSS DFNB72 BUT NOT DFNB81
THAT ALSO MAPS TO CHROMOSOME 19p

2011; 130:759-765

A missense mutation of Gipc3 was previously reported to cause age-related hearing
loss in mice. Point mutations of human GIPC3 were found in two small families,
but association with hearing loss was not statistically significant. Here, we
describe one frameshift and six missense mutations in GIPC3 cosegregating with
DFNB72 hearing loss in six large families that support statistically
significant evidence for genetic linkage. However, GIPC3 is not the only
nonsyndromic hearing impairment gene in this region; no GIPC3 mutations were
found in a family cosegregating hearing loss with markers of chromosome 19p.
Haplotype analysis excluded GIPC3 from the obligate linkage interval in this
family and defined a novel locus spanning 4.08 Mb and 104 genes. This closely
linked but distinct nonsyndromic hearing loss locus was designated DFNB81. Â©
2011 Springer-Verlag (outside the USA).

Laboratory of Molecular Genetics, National Institute on Deafness and Other
Communication Disorders, National Institutes of Health, Rockville, MD 20850,
United States National Centre of Excellence in Molecular Biology, Punjab
University, Lahore, Pakistan Department of Molecular and Human Genetics, Baylor
College of Medicine, Houston, TX 77030, United States Division of Pediatric
Ophthalmology, Cincinnati Children's Hospital Research Foundation, Cincinnati,
OH 45229, United States Division of Otolaryngology, Head and Neck Surgery,
Cincinnati Children's Hospital Research Foundation, Cincinnati, OH 45229,
United States Department of Biochemistry, Faculty of Biological Sciences,
Quaid-I-Azam University, Islamabad 45320, Pakistan Otolaryngology Branch,
National Institute on Deafness and Other Communication Disorders, National
Institutes of Health, Bethesda, MD 20850, United States Allama Iqbal Medical
College, Jinnah Hospital Complex, University of Health Sciences, Lahore 54550,
Pakistan

10.1007/s00439-011-1018-5

http://www.ncbi.nlm.nih.gov/pubmed/21660509

(139)Rohan JM, Delamater A, Pendley JS,
Dolan L, Reeves G and Drotar D

IDENTIFICATION OF SELF-MANAGEMENT PATTERNS IN PEDIATRIC TYPE 1 DIABETES
USING CLUSTER ANALYSIS

2011; 12:611-618

OBJECTIVES: This study identified three distinct patterns of self-management
groups for a sample of 239 youth (9-11 years) with type 1 diabetes and their
maternal and paternal caregivers, and assessed their relationship to glycemic
control (HbA1c). METHODS: Youth and their maternal and paternal caregivers were
administered the diabetes self-management profile (DSMP) to assess
self-management. Glycemic control was based on hemoglobin A1c. RESULTS:
Two-step cluster analysis identified three different self-management groups
based on youth, maternal, and paternal reports. Analysis of variance indicated
that the pattern of less optimal diabetes self-management was associated with worse
glycemic control. CONCLUSION: Our results objectively describe differences in
patterns of self-management in youth with type 1 diabetes, that relate to
glycemic control. Interventions based on these specific patterns of
self-management may improve diabetes management and enhance glycemic control in
children and adolescents with type 1 diabetes.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, USA. Jennifer.Rohan@cchmc.org

10.1111/j.1399-5448.2010.00752.x

http://www.ncbi.nlm.nih.gov/pubmed/21446925

(140)Rose SR, Rutter MM, Mueller R, Harris
M, Hamon B, Bulluck AF and Smith FO

BONE MINERAL DENSITY IS NORMAL IN CHILDREN WITH FANCONI ANEMIA

2011; 57:1034-1038

BACKGROUND: Conflicting data exist regarding whether low bone mineral density
(BMD) is associated with Fanconi anemia (FA). The current study identified the
frequency of low BMD in FA, expecting low BMD even in childhood and before HCT.
PROCEDURE: Thirty-seven FA patients (18 prior HCT, 19 no prior HCT),
participating in an IRB-approved database, had clinical assessment of DXA of
lumbar spine BMD. Four had used androgens, one later underwent HCT. Most had
used glucocorticoids after HCT (prolonged in five), and one more with no HCT.
BMD [in standard deviation units from mean for age (SD), gender, and ethnicity
(BMD Z-score)] was then adjusted for height age, and separately for bone
maturation (BA). Data were collected for height SD, pubertal stage, and
duration since HCT. RESULTS: BMD Z-score (without adjustment) was <-1 SD in
half of FA children. BA-adjusted BMD Z-score was similar. (BA was not usually
delayed, although most patients were short.) In contrast, height age-adjusted
BMD Z-score was normal in most with FA (only below -2.0 in one child after
prolonged glucocorticoids). Mean duration after HCT until DXA test was 6.2
years (median 4.2 years, range 1-18 years). CONCLUSIONS: Children and
adolescents with FA have normal BMD prior to and after HCT, when DXA results
are adjusted for bone size/height age. In contrast, BA-adjustment of BMD was
not useful in this population. Individual BMD results may be influenced by
gonadal function, transplantation status, and prolonged glucocorticoid therapy.

Division of Endocrinology, Cincinnati Children's Hospital Medical Center,
University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. Susan.Rose@cchmc.org

10.1002/pbc.22956

http://www.ncbi.nlm.nih.gov/pubmed/21480470

(141)Rothenberg ME, Wen T, Shik D, Cole ET,
Mingler MM and Munitz A

IL-13 RECEPTOR Î±1 DIFFERENTIALLY REGULATES AEROALLERGEN-INDUCED LUNG
RESPONSES

2011; 187:4873-4880

IL-13 and IL-4 are hallmark cytokines of Th2-associated diseases including
asthma. Recent studies revealed that IL-13RÎ±1 regulates asthma pathogenesis by
mediating both IL-4- and IL-13-mediated responses. Nonetheless, the relative
contribution of each cytokine in response to aeroallergen challenge and the
degree of functional dichotomy between IL-4 and IL-13 in asthma remains
unclear. Consistent with prior publications, we demonstrate that IL-13RÎ±1
regulates aeroallergen-induced airway resistance and mucus production but not
IgE and Th2 cytokine production. We demonstrate that aeroallergen-induced
eosinophil recruitment and chemokine production were largely dependent on
IL-13RÎ±1 after Aspergillus but not house dust mite (HDM) challenges. Notably,
Aspergillus-challenged mice displayed increased IL-13RÎ±1- dependent
accumulation of dendritic cell subsets into lung-draining lymph nodes in
comparison with HDM-challenged mice. Comparison of IL-4 and IL-13 levels in the
different experimental models revealed increased IL-4/IL-13 ratios after HDM
challenge, likely explaining the IL-13RÎ±1-independent eosinophilia and
chemokine production. Consistently, eosinophil adoptive transfer experiments
revealed near ablation of lung eosinophilia in response to Aspergillus in
Il13ra1-/- mice, suggesting that Aspergillus-induced lung eosinophil
recruitment is regulated by IL-13-induced chemokine production rather than
altered IL-13 signaling in eosinophils. Furthermore, the near complete
protection observed in Il13ra1-/- mice in response to Aspergillus challenge was
dependent on mucosal sensitization, as alum/Aspergillus-sensitized mice that
were rechallenged with Aspergillus developed IL-13RÎ±1- independent
eosinophilia although other asthma parameters remained IL-13Ra1 dependent.
These results establish that IL-13RÎ±1 is required for aeroallergeninduced
airway resistance and that allergen-induced chemokine production and consequent
eosinophilia is dictated by the balance between IL-4 and IL-13 production in
situ. Copyright Â© 2011 by The American Association of Immunologists, Inc.

Division of Allergy and Immunology, Cincinnati Children's Hospital Medical
Center, MLC 7028, 3333 Burnet Avenue, Cincinnati, OH 45229, United States
Department of Clinical Microbiology and Immunology, Sackler Faculty of
Medicine, Tel Aviv University, Tel Aviv 69978, Israel

10.4049/jimmunol.1004159

http://www.ncbi.nlm.nih.gov/pubmed/21957151

(142)Rowe AK, Onikpo F, Lama M, Osterholt
DM and Deming MS

IMPACT OF a MALARIA-CONTROL PROJECT IN BENIN THAT INCLUDED THE INTEGRATED
MANAGEMENT OF CHILDHOOD ILLNESS STRATEGY

2011; 101:2333-2341

Objectives: To estimate the impact of the Integrated Management of Childhood
Illness (IMCI) strategy on early-childhood mortality, we evaluated a
malaria-control project in Benin that implemented IMCI and promoted
insecticide-treated nets (ITNs). Methods: We conducted a before-and-after
intervention study that included a nonrandomized comparison group. We used the
preceding birth technique to measure early-childhood mortality (risk of dying
before age 30 months), and we used health facility surveys and household
surveys to measure process indicators. Results: Most process indicators
improved in the area covered by the intervention. Notably, because ITNs were
also promoted in the comparison area children's ITN use increased by about 20
percentage points in both areas. Regarding early-childhood mortality, the trend
from baseline (1999-2001) to follow-up (2002-2004) for the intervention area
(13.0% decrease; P<.001) was 14.1% (P<.001) lower than was the trend for
the comparison area (1.3% increase; P=.46). Conclusions: Mortality decreased in
the intervention area after IMCI and ITN promotion. ITN use increased similarly
in both study areas, so the mortality impact of ITNs in the 2 areas might have
canceled each other out. Thus, the mortality reduction could have been
primarily attributable to IMCI's effect on health care quality and
care-seeking.

Division of Parasitic Diseases, Center for Disease Control and Prevention,
Mailstop F22, 4770 Buford Highway, Atlanta, GA 30341-3724, United States
Division of General and Community Pediatric Research, Cincinnati Children's
Hospital, Cincinnati, OH, United States Direction Departementale de la Sante
Publique de l'Oueme et Plateau, Ministry of Health, Porto Novo, Benin
Africare-Benin, Porto Novo, Benin

10.2105/ajph.2010.300068

http://www.ncbi.nlm.nih.gov/pubmed/21566036

(143)SÃ¡nchez E, Comeau ME, Freedman BI,
Kelly JA, Kaufman KM, Langefeld CD, Brown EE, AlarcÃ³n GS, Kimberly RP, Edberg
JC, Ramsey-Goldman R, Petri M, Reveille JD, VilÃ¡ LM, Merrill JT, Tsao BP,
Kamen DL, Gilkeson GS, James JA, Vyse TJ, Gaffney PM, Jacob CO, Niewold TB,
Richardson BC, Harley JB, AlarcÃ³n-Riquelme ME and Sawalha AH

IDENTIFICATION OF NOVEL GENETIC SUSCEPTIBILITY LOCI IN AFRICAN AMERICAN
LUPUS PATIENTS IN a CANDIDATE GENE ASSOCIATION STUDY

2011; 63:3493-3501

Objective Candidate gene and genome-wide association studies have identified
several disease susceptibility loci in lupus patients. These studies have
largely been performed in lupus patients who are Asian or of European ancestry.
This study was undertaken to examine whether some of these same susceptibility
loci increase lupus risk in African American individuals. Methods
Single-nucleotide polymorphisms tagging 15 independent lupus susceptibility
loci were genotyped in a set of 1,724 lupus patients and 2,024 healthy controls
of African American descent. The loci examined included PTPN22, FCGR2A, TNFSF4,
STAT4, CTLA4, PDCD1, PXK, BANK1, MSH5 (HLA region), CFB (HLA region),
C8orf13-BLK region, MBL2, KIAA1542, ITGAM, and MECP2/IRAK1. Results We found
the first evidence of genetic association between lupus in African American
patients and 5 susceptibility loci (C8orf13-BLK, BANK1, TNFSF4, KIAA1542, and
CTLA4; P = 8.0 Ã— 10-6, P = 1.9 Ã— 10-5, P = 5.7 Ã— 10-5, P = 0.00099, and P =
0.0045, respectively). Further, we confirmed the genetic association between
lupus and 5 additional lupus susceptibility loci (ITGAM, MSH5, CFB, STAT4, and
FCGR2A; P = 7.5 Ã— 10-11, P = 5.2 Ã— 10-8, P = 8.7 Ã— 10 -7, P = 0.0058, and P
= 0.0070, respectively), and provided evidence, for the first time, of
genome-wide significance for the association between lupus in African American
patients and ITGAM and MSH5 (HLA region). Conclusion These findings provide
evidence of novel genetic susceptibility loci for lupus in African Americans
and demonstrate that the majority of lupus susceptibility loci examined confer
lupus risk across multiple ethnicities. Â© 2011 by the American College of
Rheumatology.

Oklahoma Medical Research Foundation, MS 24, 825 NE 13th Street, Oklahoma City,
OK 73104, United States Wake Forest University Health Sciences, Winston-Salem,
NC, United States Wake Forest University, School of Medicine, Winston-Salem,
NC, United States Oklahoma Medical Research Foundation, University of Oklahoma
Health Sciences Center, Oklahoma City VA Medical Center, Oklahoma City, United
States University of Alabama, Birmingham, United States Northwestern
University, Feinberg School of Medicine, Chicago, IL, United States Johns Hopkins
University, School of Medicine, Baltimore, MD, United States University of
Texas, Health Science Center, Houston, United States University of Puerto Rico,
School of Medicine, San Juan, Puerto Rico Oklahoma Medical Research Foundation,
University of Oklahoma, Health Sciences Center, Oklahoma City, United States
University of California, Los Angeles, United States Medical University of
South Carolina, Charleston, United States King's College London, Guy's
Hospital, London, United Kingdom University of Southern California, Los
Angeles, United States University of Chicago, Chicago, IL, United States
University of Michigan, Ann Arbor VA Medical Center, Ann Arbor, United States
Cincinnati Children's Hospital Medical Center, Cincinnati VA Medical Center,
Cincinnati, OH, United States Pfizer-University of Granada-Junta de Andalucia,
Granada, Spain

10.1002/art.30563

(144)Saldana SN, Hooper DK, Froehlich TE,
Campbell KM, Prows CA, Sadhasivam S, Nick TG, Seid M, Vinks AA and Glauser TA

CHARACTERISTICS OF SUCCESSFUL RECRUITMENT IN PROSPECTIVE PEDIATRIC
PHARMACOGENETIC STUDIES

2011; 33:2072-2081

BACKGROUND: There is a need to explore feasible means of accruing an
appropriate study cohort to help fill the knowledge gap between pharmacogenetic
contributions to drug response and clinical application in the pediatric
population. OBJECTIVES: The aim of this study was to identify factors affecting
recruitment of eligible subjects in pharmacogenetic studies at a large
Midwestern pediatric academic medical center. The objectives were to evaluate
recruitment success of ongoing trials and ascertain contributors to
differential recruitment rates. We hypothesized that studies with good
recruitment of eligible subjects would share characteristics not present in
studies with lower than anticipated recruitment. The goal was to better
understand barriers to good recruitment in pharmacogenetic studies to help
inform future trial and infrastructure design. METHODS: Investigators designed
a survey with proposed elements of success, which was then completed by lead
and/or site investigators of all pharmacogenetics studies at the institution.
Results were evaluated using an investigator-developed likelihood of success
scoring system. RESULTS: Two studies recruited >95% of the approached eligible
patients; 4 studies were consistent with investigator-anticipated recruitment
(>50%), and 1 study did not meet expected recruitment. A study's total score
on the investigator-devised scoring tool correlated well with the proportion of
approached patients recruited (Pearson's correlation, r = 0.82; P < 0.001).
Multiple factors impacted successful recruitment into these pharmacogenetic
studies. Features of studies with successful recruitment included standardized
clinical care, an ongoing team-patient relationship, severe and/or
life-threatening outcome measures, study coordinator with experience in
clinical research, a study medication with few or no alternative treatment
options, and active involvement of the research team in clinical care.
CONCLUSIONS: A scoring system for study characteristics may be useful to
calculate the risk of failure for successful recruitment, allow discrimination
among characteristics contributing to the risk, and permit study design
alterations to improve likelihood of successful recruitment in pediatric
pharmacogenetic studies.

Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical
Center, Cincinnati, Ohio; Division of Pharmacy, Cincinnati Children's Hospital
Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of
Cincinnati College of Medicine, Cincinnati, Ohio.

10.1016/j.clinthera.2011.10.026

http://www.ncbi.nlm.nih.gov/pubmed/22136977

(145)Santos VR, de Castro OW, Pun RY,
Hester MS, Murphy BL, Loepke AW, Garcia-Cairasco N and Danzer SC

CONTRIBUTIONS OF MATURE GRANULE CELLS TO STRUCTURAL PLASTICITY IN TEMPORAL
LOBE EPILEPSY

2011; 197:348-357

During the development of epilepsy in adult animals, newly generated granule
cells integrate abnormally into the hippocampus. These new cells migrate to
ectopic locations in the hilus, develop aberrant basal dendrites, contribute to
mossy fiber sprouting, and exhibit changes in apical dendrite structure and
dendritic spine number. Mature granule cells do not appear to exhibit migration
defects, basal dendrites, and mossy fiber sprouting, but whether they exhibit
apical dendrite abnormalities or spine changes is not known. To address these
questions, we examined the apical dendritic structure of bromodeoxyuridine
(Brdu)-birthdated, green fluorescent protein (GFP)-expressing granule cells
born 2 months before pilocarpine-induced status epilepticus. In contrast to
immature granule cells, exposing mature granule cells to status epilepticus did
not significantly disrupt the branching structure of their apical dendrites.
Mature granule cells did, however, exhibit significant reductions in spine
density and spine number relative to age-matched cells from control animals.
These data demonstrate that while mature granule cells are resistant to
developing the gross structural abnormalities exhibited by younger granule
cells, they show similar plastic rearrangement of their dendritic spines.

Department of Anesthesia, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, USA.

10.1016/j.neuroscience.2011.09.034

http://www.ncbi.nlm.nih.gov/pubmed/21963349

(146)Schroeder JK, Kessler CA and
Handwerger S

CRITICAL ROLE FOR TWIST1 IN THE INDUCTION OF HUMAN UTERINE DECIDUALIZATION

2011; 152:4368-4376

The importance of the transcription factor TWIST1 for uterine decidualization
was examined in human uterine fibroblast (HUF) cells decidualized in vitro with
medroxyprogesterone, estradiol (E2), and prostaglandin E2. TWIST1 mRNA levels
increased by 6.0- to 6.8-fold during the first 1-2 d of decidualization and
remained above predecidualization levels for up to 15 d. Pretreatment of HUF
cells with a TWIST1 small interfering RNA (siRNA) for 3 d before the induction
of decidualization resulted in less morphologic differentiation than HUF cells
pretreated with a nonsilencing control RNA. In addition, the cells pretreated
with TWIST1 siRNA expressed 75-95% less IGF binding protein 1, LEFTY2,
fibromodulin, laminin, and several other mRNA during decidualization, including
the mRNA for the transcription factors forkhead box protein O1 and
v-ets-erythroblastosis virus E26, both of which were previously shown to be
critical for the induction of decidualization. The HUF cells pretreated with
the TWIST1 siRNA also underwent less apoptosis during decidualization than the
control cells, as evidenced by a 20% decrease in DNA fragmentation (terminal
deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling
assay) and a 43-48% decrease in caspase 3, BCL2-associated X protein, and TNF
receptor superfamily member 6 mRNA levels. Although the knockdown of TWIST1
expression markedly attenuated the induction of decidualization, overexpression
of TWIST1 alone was insufficient to induce the decidualization of HUF cells.
Taken together, these findings strongly implicate an essential role for TWIST1
in the initiation of human decidualization and uterine stromal cell apoptosis
that occurs upstream of the induction of forkhead box protein O1 and
v-ets-erythroblastosis virus E26 mRNA.

Department of Pediatrics, University of Cincinnati and Division of
Endocrinology, Cincinnati Children's Hospital Medical Center, 3333 Burnet
Avenue, Cincinnati, Ohio 45229-3039, USA.

10.1210/en.2011-1140

http://www.ncbi.nlm.nih.gov/pubmed/21914771

(147)Schultz JM, Bhatti R, Madeo AC,
Turriff A, Muskett JA, Zalewski CK, King KA, Ahmed ZM, Riazuddin S, Ahmad N,
Hussain Z, Qasim M, Kahn SN, Meltzer MR, Liu XZ, Munisamy M, Ghosh M, Rehm HL,
Tsilou ET, Griffith AJ, Zein WM, Brewer CC and Friedman TB

ALLELIC HIERARCHY OF CDH23 MUTATIONS CAUSING NON-SYNDROMIC DEAFNESS DFNB12
OR USHER SYNDROME USH1D IN COMPOUND HETEROZYGOTES

2011; 48:767-775

Background: Recessive mutant alleles of MYO7A, USH1C, CDH23, and PCDH15 cause
non-syndromic deafness or type 1 Usher syndrome (USH1) characterised by
deafness, vestibular areflexia, and vision loss due to retinitis pigmentosa.
For CDH23, encoding cadherin 23, non-syndromic DFNB12 deafness is associated
primarily with missense mutations hypothesised to have residual function. In
contrast, homozygous nonsense, frame shift, splice site, and some missense
mutations of CDH23, all of which are presumably functional null alleles, cause
USH1D. The phenotype of a CDH23 compound heterozygote for a DFNB12 allele in
trans configuration to an USH1D allele is not known and cannot be predicted
from current understanding of cadherin 23 function in the retina and vestibular
labyrinth. Methods and results: To address this issue, this study sought CDH23
compound heterozygotes by sequencing this gene in USH1 probands, and families
segregating USH1D or DFNB12. Five non-syndromic deaf individuals were
identified with normal retinal and vestibular phenotypes that segregate
compound heterozygous mutations of CDH23, where one mutation is a known or
predicted USH1 allele. Conclusions: One DFNB12 allele in trans configuration to
an USH1D allele of CDH23 preserves vision and balance in deaf individuals,
indicating that the DFNB12 allele is phenotypically dominant to an USH1D
allele. This finding has implications for genetic counselling and the
development of therapies for retinitis pigmentosa in Usher syndrome. Accession
numbers: The cDNA and protein Genbank accession numbers for CDH23 and cadherin
23 used in this paper are AY010111.2 and AAG27034.2, respectively.

Laboratory of Molecular Genetics, National Institute on Deafness and Other
Communication Disorders (NIDCD), National Institutes of Health (NIH),
Rockville, MD, United States National Centre of Excellence in Molecular
Biology, Punjab University, Lahore, Pakistan Otolaryngology Branch, NIDCD, NIH,
Rockville, MD, United States Ophthalmic Genetics and Visual Function Branch,
National Eye Institute, NIH, Bethesda, MD, United States Division of Pediatric
Otolaryngology Head and Neck Surgery, Children's Hospital Research Foundation,
Cincinnati, OH, United States Division of Ophthalmology, Children's Hospital
Research Foundation, Cincinnati, OH, United States Department of
Otolaryngology, University of Miami, Miami, FL, United States Department of
Pediatrics, Genetics Unit, All India Institute of Medical Sciences, New Delhi,
Indonesia Laboratory for Molecular Medicine, Partners HealthCare Center for
Personalized Genetic Medicine, Cambridge, MA, United States Department of
Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA,
United States Center for Research for Mothers and Children, National Institute
of Child Health and Human Development, National Institutes of Health,
Rockville, MD, United States Allama Iqbal Medical Research Centre, Allama Iqbal
Medical College, Lahore, Pakistan

10.1136/jmedgenet-2011-100262

http://www.ncbi.nlm.nih.gov/pubmed/21940737

(148)Sengupta AandCancelas JA

A CONUNDRUM IN MAMMALIAN HEMATOPOIETIC STEM CELL POLARITY

2011; 10Comment on: Sengupta A, et al. Proc Natl Acad Sci USA 2011; 108:9957-62.

Stem Cell Program; Division of Experimental Hematology and Cancer Biology;
Cincinnati Children's Hospital Medical Center; Cincinnati, OH USA; and Center
for Stem Cell Research; Christian Medical College; Vellore, Tamil Nadu, India.

http://www.ncbi.nlm.nih.gov/pubmed/22157228

(149)Setchell KD, Brown NM, Zhao X, Lindley
SL, Heubi JE, King EC and Messina MJ

SOY ISOFLAVONE PHASE II METABOLISM DIFFERS BETWEEN RODENTS AND HUMANS:
IMPLICATIONS FOR THE EFFECT ON BREAST CANCER RISK

2011; 94:1284-1294

BACKGROUND: Human and animal studies have produced conflicting results with
regard to the effect of soy isoflavones on breast cancer risk. This may be due
to differences in isoflavone metabolism. OBJECTIVE: The objective of this study
was to determine whether soy isoflavone phase II metabolism differs between
humans and rodents. DESIGN: Circulating total and unconjugated isoflavone
concentrations were determined by mass spectrometry in plasma samples from 7
separate studies: 1) in Sprague-Dawley rats and in 3 strains of mice fed
commercial soy-containing diets; 2) in Sprague-Dawley rats gavaged with
genistein; 3) in healthy adults who consumed single servings of soy nuts, soy
milk, and tempeh; 4) in healthy adults subchronically given soy milk; 5) in
healthy women orally administered 50 mg genistein; 6) in healthy women orally
administered 20 mg pure S-(-)equol; and 7) in 6-mo-old infants fed soy infant
formula and later, at age 3 y, a soy germ isoflavone supplement. RESULTS: The
proportion of unconjugated genistein in plasma from adults and infants who
consumed different soy foods, pure genistein, or an isoflavone supplement was
<1% in steady state and <2% at peak concentrations. By contrast, rodents
fed soy-containing diets conjugate isoflavones less efficiently. The plasma
percentages of unconjugated genistein concentrations in Sprague-Dawley rats and
C57BL/6, nude, and transgenic AngptL4B6 mice were 4.0 +/- 0.6%, 4.6 +/- 0.6%,
11.6 +/- 0%, and 30.1 +/- 4.3%, respectively, which represent 20, 23, 58, and
150 times that in humans. CONCLUSION: The markedly higher circulating
concentrations of biologically active (unconjugated) genistein in certain
strains of mice cast doubt on the value of the use of these rodents for gaining
insight into the effects of isoflavones in humans, especially with regard to
the effects on breast tissue.

Division of Pathology and Laboratory Medicine, Cincinnati Children's Hospital
Medical Center, OH 45229, USA. kenneth.setchell@cchmc.org

10.3945/ajcn.111.019638

http://www.ncbi.nlm.nih.gov/pubmed/21955647

(150)Sever-Chroneos Z, Murthy A, Davis J,
Florence JM, Kurdowska A, Krupa A, Tichelaar JW, White MR, Hartshorn KL, Kobzik
L, Whitsett JA and Chroneos ZC

GM-CSF MODULATES PULMONARY RESISTANCE TO INFLUENZA A INFECTION

2011; 92:319-328

Alveolar type II epithelial or other pulmonary cells secrete GM-CSF that
regulates surfactant catabolism and mucosal host defense through its capacity
to modulate the maturation and activation of alveolar macrophages. GM-CSF
enhances expression of scavenger receptors MARCO and SR-A. The alveolar
macrophage SP-R210 receptor binds the surfactant collectin SP-A mediating
clearance of respiratory pathogens. The current study determined the effects of
epithelial-derived GM-CSF in host resistance to influenza A pneumonia. The
results demonstrate that GM-CSF enhanced resistance to infection with
1.9Ã—104ffc of the mouse-adapted influenza A/Puerto Rico/8/34 (PR8) H1N1
strain, as indicated by significant differences in mortality and mean survival
of GM-CSF-deficient (GM-/-) mice compared to GM-/- mice in which GM-CSF is
expressed at increased levels. Protective effects of GM-CSF were observed both
in mice with constitutive and inducible GM-CSF expression under the control of
the pulmonary-specific SFTPC or SCGB1A1 promoters, respectively. Mice that
continuously secrete high levels of GM-CSF developed desquamative interstitial
pneumonia that impaired long-term recovery from influenza. Conditional
expression of optimal GM-CSF levels at the time of infection, however, resulted
in alveolar macrophage proliferation and focal lymphocytic inflammation of
distal airways. GM-CSF enhanced alveolar macrophage activity as indicated by
increased expression of SP-R210 and CD11c. Infection of mice lacking the
GM-CSF-regulated SR-A and MARCO receptors revealed that MARCO decreases resistance
to influenza in association with increased levels of SP-R210 in MARCO-/-
alveolar macrophages. In conclusion, GM-CSF enhances early host resistance to
influenza. Targeting of MARCO may reinforce GM-CSF-mediated host defense
against pathogenic influenza. Â© 2011 Elsevier B.V.

University of Texas Health Science Center at Tyler, Center of Biomedical
Research, 11937 US HWY 271, Tyler, TX 75708-3154, United States Medical College
of Wisconsin, Department of Pharmacology and Toxicology, 8701 Watertown Plank Rd.,
Milwaukee, WI, United States Boston University School of Medicine, Department
of Hematology and Oncology, 650 Albany St. Boston, MA, United States Cincinnati
Children's Hospital Medical Center, Division of Pulmonary Biology and
Neonatology, 3333 Burnet Ave., Cincinnati, OH, United States Department of
Environmental Health, Harvard School of Public Health, Boston, MA, United
States

10.1016/j.antiviral.2011.08.022

http://www.ncbi.nlm.nih.gov/pubmed/21925209

(151)Shah SS, Aronson PL, Mohamad Z and
Lorch SA

DELAYED ACYCLOVIR THERAPY AND DEATH AMONG NEONATES WITH HERPES SIMPLEX VIRUS
INFECTION

2011; 128:1153-1160

OBJECTIVE: To determine the association of delayed acyclovir therapy with death
among neonates with herpes simplex virus (HSV) infection. METHODS: A
multicenter, retrospective, cohort study was conducted between January 1, 2003,
and December 31, 2009, with 1086 neonates (age: 1 and </=7 days after
hospital admission. Multivariate logistic regression models determined the
association between delayed acyclovir therapy and death, with the use of
propensity scores for each neonate's likelihood of receiving delayed acyclovir
treatment to control for differences in illness severity between groups.
RESULTS: The median age was 10 days. Delayed acyclovir therapy was administered
to 262 neonates (24.1%). In most cases (86.2%) of delayed receipt, acyclovir
administration occurred on the second or third day of hospitalization. The
overall mortality rate was 7.3% (95% confidence interval: 5.8%-9.0%); 9.5% of
those who received delayed acyclovir treatment and 6.6% of those who received
early acyclovir treatment died. In a multivariate analysis, delayed acyclovir
therapy was associated with significantly greater odds of death (adjusted odds
ratio: 2.63 [95% confidence interval: 1.36-5.08]) compared with early acyclovir
therapy. CONCLUSIONS: In this multicenter observational study of neonates with
HSV infection, delayed initiation of acyclovir therapy was associated with
in-hospital death. Our data support the use of empiric acyclovir therapy for
neonates undergoing testing for HSV infection.

MSCE, Division of Infectious Diseases, Cincinnati Children's Hospital Medical
Center, 3333 Burnet Avenue, ML 7035, Cincinnati, OH 45229. ssamir.shah@cchmc.org.

10.1542/peds.2011-0177

http://www.ncbi.nlm.nih.gov/pubmed/22123868

(152)Shak JR, Sodikoff JB, Speckman RA,
Rollin FG, Chery MP, Cole CR and Suchdev PS

ANEMIA AND HELICOBACTER PYLORI SEROREACTIVITY IN a RURAL HAITIAN POPULATION

2011; 85:913-918

Anemia is a significant health concern worldwide and can be the result of
nutritional, environmental, social, and infectious etiologies. We estimated the
prevalence of anemia in 336 pre-school children and 132 adults in the rural
Central Plateau of Haiti and assessed associations with age, sex, household
size, water source, sanitation, and Helicobacter pylori seroreactivity using
logistic regression analysis; 80.1% (269/336) of children and 63.6% (84/132) of
adults were anemic. Among children, younger age was associated with increased
prevalence of anemia (adjusted odds ratio [aOR] = 4.1, 95% confidence interval
[CI] = 1.5-11.1 for children 6-11 months compared with children 48-59 months).
Among adults, 50.8% were H. pylori -seropositive, and seropositivity was
inversely associated with anemia (aOR = 0.4, 95% CI = 0.2-0.9). Anemia
prevalence in this region of Haiti is very high and not attributable to
sanitary conditions or a high prevalence of H. pylori infection. Copyright Â©
2011 by The American Society of Tropical Medicine and Hygiene.

Emory University School of Medicine, 1648 Pierce Drive, Atlanta, GA 30322,
United States Project Medishare for Haiti, Miami, FL, United States Cincinnati
Children's Hospital Medical Center, Cincinnati, OH, United States Project
Medishare, Thomonde, Haiti

10.4269/ajtmh.2011.11-0101

http://www.ncbi.nlm.nih.gov/pubmed/22049049

(153)Shepherd JA, Wang L, Fan B, Gilsanz V,
Kalkwarf HJ, Lappe J, Lu Y, Hangartner T, Zemel BS, Fredrick M, Oberfield S and
Winer KK

OPTIMAL MONITORING TIME INTERVAL BETWEEN DXA MEASURES IN CHILDREN

2011; 26:2745-2752

The monitoring time interval (MTI) is the expected time in years necessary to
identify a change between two measures that exceeds the measurement error. Our
purpose was to determine MTI values for dual-energy X-ray absorptiometry (DXA)
scans in normal healthy children, according to age, sex, and skeletal site.
2014 children were enrolled in the Bone Mineral Density in Childhood Study and
had DXA scans of the lumbar spine, total hip, nondominant forearm, and whole
body. Measurements were obtained annually for seven visits from 2002 to 2010.
Annualized rates of change were calculated by age and sex for all bone regions.
A subgroup of 155 children ages 6 to 16 years (85 boys) had duplicate scans for
calculation of scan precision. The bone mineral density (BMD) regions of
interest included the spine, total body less head (TBLH), total hip, femoral
neck, and one-third radius. Bone mineral content (BMC) was also evaluated for
the spine and TBLH. The percent coefficient of variation (%CV) and MTI were
calculated for each measure as a function of age and sex. The MTI values were
substantially less than 1 year for the TBLH and spine BMD and BMC for boys Ì‚17
years and girlsa;circcirc 15 years. The hip and one-third radius MTIs were
generally 1 year in the same group. MTI values as low as 3 months were found
during the peak growth years. However, the MTI values in late adolescence for
all regions were substantially longer and became nonsensical as each region
neared the age for peak bone density. All four DXA measurement sites had
reasonable (< 1 year) MTI values for boys Ì‚17 years and girlsa;circcirc 15
years. MTI was neither useful nor stable in late adolescence and young
adulthood. Alternative criteria to determine scan intervals must be used in
this age range. Â© 2011 American Society for Bone and Mineral Research.

Department of Radiology and Bioimaging, Bone and Breast Density Research Group,
University of California, San Francisco, CA 94143-0628, United States Children's
Hospital, Los Angeles, Los Angeles, CA, United States Division of General and
Community Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Osteoporosis Research Center, Creighton
University, Omaha, NE, United States Department of Health Research and Policy,
Stanford University, Stanford, CA, United States BioMedical Imaging Laboratory,
Wright State University, Dayton, OH, United States Division of
Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia,
Philadelphia, PA, United States Clinical Trials and Surveys Corp, Baltimore,
MD, United States St. Luke's-Roosevelt Hospital, New York, NY, United States
NIH, Endocrinology, Nutrition and Growth Branch, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, Bethesda, MD, United
States

10.1002/jbmr.473 10.1210/jc.2011-1111; Kelly, T., Specker, B., Binkley, N.,
Pediatric BMD reference database for US white children (2005) Bone., 36 (SUPPL.
1), pp. S30; Bishop, N., Braillon, P., Burnham, J., Cimaz, R., Davies, J.,
Fewtrell, M., (TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/21773995

(154)Shroff R, Weaver Jr DJ and Mitsnefes
MM

CARDIOVASCULAR COMPLICATIONS IN CHILDREN WITH CHRONIC KIDNEY DISEASE

2011; 7:642-649

The lifespan of children with advanced chronic kidney disease (CKD) remains low
compared with the general pediatric population. As in adults with CKD,
cardiovascular disease accounts for the majority of deaths in children with
CKD, as these patients have a high prevalence of traditional and uremia-related
risk factors for cardiovascular disease. The cardiovascular adaptations that
precipitate these terminal events begin in predialysis CKD. Initially, these
alterations increase left ventricular performance and vascular function to
maintain hemodynamic homeostasis. However, these modifications are unable to
sustain cardiovascular function in the long term and ultimately lead to left
ventricular failure, impaired cardiorespiratory fitness and even sudden death.
In this Review, we provide an update on the prevalence of the risk factors
associated with cardiovascular disease in pediatric patients with CKD, the
cardiac and vascular adaptations that occur in these patients and the
management of cardiovascular risk in this population. Â© 2011 Macmillan
Publishers Limited. All rights reserved.

Nephrology Unit, Great Ormond Street Hospital for Children NHS Trust, Great
Ormond Street, London WC1N 3JH, United Kingdom Division of Pediatric Nephrology
and Hypertension, Department of Pediatrics, Levine Children's Hospital at
Carolinas Medical Center, 1001 Blythe Boulevard, Charlotte, NC 28232, United
States Division of Nephrology and Hypertension, Cincinnati Children's Hospital
Medical Center, MLC 7022, 3333 Burnett Avenue, Cincinnati, OH 45229, United
States

10.1038/nrneph.2011.116 10.1002/14651858.CD008327 (; McKay, C.P., Portale, A.,
Emerging topics in pediatric bone and mineral disorders (2009) Semin. Nephrol.,
29, pp. 370-378; Schaefer, B., Long-term control of parathyroid hormone and
calcium-ph(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/21912426

(155)Siegel RM, Rich W and Khoury J

AN OFFICE-BASED LOW-CARBOHYDRATE INTERVENTION IN TEENS: ONE-YEAR FOLLOW-UP
OF a SIX-MONTH INTERVENTION

2011; 50:1062-1063

Center for Better Health and Nutrition, The Heart Institute, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Bob.Siegel@cchmc.org

10.1177/0009922810384848

http://www.ncbi.nlm.nih.gov/pubmed/21098523

(156)Sikora KAandGrom AA

UPDATE ON THE PATHOGENESIS AND TREATMENT OF SYSTEMIC IDIOPATHIC ARTHRITIS

2011; 23:640-646

PURPOSE OF REVIEW: Systemic juvenile idiopathic arthritis (SJIA) is an
inflammatory condition characterized by fever, lymphadenopathy, rash,
arthritis, and serositis. Although the ultimate cause of this disorder remains
elusive, recent work defining cytokine effector mechanisms has led to a new
treatment paradigm for this condition. In this review, we describe the recent
immunological reclassification of SJIA as an autoinflammatory disorder as well
as detailing the dramatic changes in its treatment. RECENT FINDINGS: SJIA is an
autoinflammatory disorder in which defects of innate immune system pathways
lead to significant inflammation. Recent studies of the pathophysiology, as
well as successful treatment trials, have established interleukin-1beta
(IL-1beta) and IL-6 as key cytokines in the pathogenesis of this condition. As
a result, their inhibition has become the centerpiece of the current SJIA
treatment paradigm. SUMMARY: There has been a major shift away from the
traditional treatments of SJIA towards therapeutics that inhibit IL-1beta and
IL-6. In fact, the IL-1 blocker anakinra is now regarded as standard of care
for SJIA patients with systemic symptoms, while the IL-6 inhibitor tocilizumab
shows great potential. Future research holds promise for the development of
more efficient cytokine inhibition as well a more comprehensive knowledge of
the innate cytokine networks in this disease.

William S. Rowe Division of Rheumatology, Cincinnati Children's Hospital
Medical Center, Cincinnati, Ohio, USA.

10.1097/MOP.0b013e32834cba24

http://www.ncbi.nlm.nih.gov/pubmed/22045308

(157)Simon NW, Montgomery KS, Beas BS,
Mitchell MR, LaSarge CL, Mendez IA, BaÃ±uelos C, Vokes CM, Taylor AB, Haberman
RP, Bizon JL and Setlow B

DOPAMINERGIC MODULATION OF RISKY DECISION-MAKING

2011; 31:17460-17470

Many psychiatric disorders are characterized by abnormal risky decision-making
and dysregulated dopamine receptor expression. The current study was designed
to determine how different dopamine receptor subtypes modulate risk-taking in
young adult rats, using a "Risky Decision-making Task" that involves
choices between small "safe" rewards and large "risky"
rewards accompanied by adverse consequences. Rats showed considerable, stable
individual differences in risk preference in the task, which were not related
to multiple measures of reward motivation, anxiety, or pain sensitivity.
Systemic activation of D2-like receptors robustly attenuated risk-taking,
whereas drugs acting on D1-like receptors had no effect. Systemic amphetamine
also reduced risk-taking, an effect which was attenuated by D2-like (but not
D1-like) receptor blockade. Dopamine receptor mRNA expression was evaluated in
a separate cohort of drug-naive rats characterized in the task. D1 mRNA
expression in both nucleus accumbens shell and insular cortex was positively
associated with risk-taking, while D2 mRNA expression in orbitofrontal and
medial prefrontal cortex predicted risk preference in opposing nonlinear
patterns. Additionally, lower levels ofD2mRNAin dorsal striatum were associated
with greater risk-taking. These data strongly implicate dopamine signaling in
prefrontal cortical-striatal circuitry in modulating decision-making processes
involving integration of reward information with risks of adverse consequences.
Â© 2011 the authors.

Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260,
United States Interdisciplinary Graduate Program in Biomedical Sciences,
University of Florida College of Medicine, Gainesville, FL 32610-0229, United
States Department of Anesthesia/Research, Cincinnati Children's Hospital,
Cincinnati, OH 45229-3026, United States Department of Neurobiology and
Behavior, University of California Irvine, Irvine, CA 92697, United States
Department of Psychology, Texas A and M University, College Station, TX
77843-4235, United States Department of Psychological and Brain Sciences, The
Johns Hopkins University, Baltimore, MD 21218-2686, United States Departments
of Psychiatry and Neuroscience, University of Florida College of Medicine,
Gainesville, FL 32610-0256, United States

10.1523/jneurosci.3772-11.2011

http://www.ncbi.nlm.nih.gov/pubmed/22131407

(158)Spanier AJ, Kahn RS, Xu Y, Hornung R
and Lanphear BP

COMPARISON OF BIOMARKERS AND PARENT REPORT OF TOBACCO EXPOSURE TO PREDICT
WHEEZE

2011; 159:776-782

Objective: To identify the optimal measure of active and passive prenatal
tobacco exposure to predict wheeze in early life. Study design: We conducted a
birth cohort study of 398 mother-infant dyads enrolled during the second
trimester of pregnancy and followed through age 2 years. We measured tobacco
exposure with maternal report, serum cotinine level, and meconium cotinine
level. We assessed wheeze with parent report every 6 months. We used a repeated
measures logistic regression model. Results: Of 367 children with respiratory
data, 26% percent had parent reported active or passive prenatal maternal
tobacco exposure, but cotinine was detected in 61% of mothers during pregnancy.
Compared with children of mothers in the fifth percentile of tobacco exposure,
children of mothers in the 95th percentile had increased odds of wheeze when
exposure was measured with maternal serum cotinine level (adjusted OR, 2.6; 95%
CI, 1.3-5.2; P < .006) versus meconium cotinine level (adjusted OR, 2.0; 95%
CI, 1.0-4.0; P =.04) and total parent-reported exposure (adjusted OR, 1.7; 95%
CI, 1.1-2.7; P =.01). Conclusions: Serum cotinine, a biomarker of tobacco
exposure, was more strongly associated with wheeze than parent-reported
exposure. Studies that rely on parent report of prenatal tobacco exposure may
underestimate risk of wheeze. Copyright Â© 2011 Mosby Inc. All rights reserved.

Department of Pediatrics, Penn State University, Hershey Medical Center, 500
University Dr, Hershey, PA 17033-0850, United States Division of General and
Community Pediatrics, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Child and Family Research Institute, Simon Fraser
University, British Columbia Children's Hospital, Vancouver, BC, Canada

10.1016/j.jpeds.2011.04.025

http://www.ncbi.nlm.nih.gov/pubmed/21645908

(159)Sreih A, Ezzeddine R, Leng L, LaChance
A, Yu G, Mizue Y, Subrahmanyan L, Pons-Estel B, Abelson AK, Gunnarsson I,
Svenungsson E, Cavett J, Glenn S, Zhang L, Montgomery R, Perl A, Salmon J,
Alarcon-Riquelme M, Harley JB and Bucala R

DUAL EFFECT OF THE MACROPHAGE MIGRATION INHIBITORY FACTOR GENE ON THE
DEVELOPMENT AND SEVERITY OF HUMAN SYSTEMIC LUPUS ERYTHEMATOSUS

2011; 63:3942-3951

OBJECTIVE: To study the effect of the innate cytokine macrophage migration
inhibitory factor (MIF) on the susceptibility and severity of systemic lupus
erythematosus (SLE) in a multinational population of 1,369 Caucasian and
African American patients. METHODS: Two functional polymorphisms in the MIF
gene, a -794 CATT(5-8) microsatellite repeat (rs5844572) and a -173 G/C
single-nucleotide polymorphism (rs755622), were assessed for association with
SLE in 3,195 patients and healthy controls. We also measured MIF plasma levels
in relation to genotypes and clinical phenotypes, and assessed Toll-like
receptor 7 (TLR-7)-stimulated MIF production in vitro. RESULTS: Both Caucasians
and African Americans with the high-expression MIF haplotype -794
CATT(7)/-173*C had a lower incidence of SLE (in Caucasians, odds ratio [OR]
0.63, 95% confidence interval [95% CI] 0.53-0.89, P = 0.001; in African
Americans, OR 0.46, 95% CI 0.23-0.95, P = 0.012). In contrast, among patients
with established SLE, reduced frequencies of low-expression MIF genotypes (-794
CATT(5)) were observed in those with nephritis, those with serositis, and those
with central nervous system (CNS) involvement when compared to patients without
end-organ involvement (P = 0.023, P = 0.005, and P = 0.04, respectively).
Plasma MIF levels and TLR-7-stimulated MIF production in vitro reflected the
underlying MIF genotype of the studied groups. CONCLUSION: These findings
suggest that MIF, which has both proinflammatory properties and macrophage and
B cell survival functions, exerts a dual influence on the immunopathogenesis of
SLE. High-expression MIF genotypes are associated with a reduced susceptibility
to SLE and may contribute to an enhanced clearance of infectious pathogens.
Once SLE develops, however, low-expression MIF genotypes may protect from
ensuing inflammatory end-organ damage.

Yale University School of Medicine, New Haven, Connecticut 06520, USA.

10.1002/art.30624

http://www.ncbi.nlm.nih.gov/pubmed/22127710

(160)Staat MA, Griffin MR, Donauer S,
Edwards KM, Szilagyi PG, Weinberg GA, Hall CB, Prill MM, Chaves SS, Bridges CB,
Poehling KA and Fairbrother G

VACCINE EFFECTIVENESS FOR LABORATORY-CONFIRMED INFLUENZA IN CHILDREN 6-59
MONTHS OF AGE, 2005-2007

2011; 29:9005-9011

To estimate the effectiveness of influenza vaccine against medical care visits
for laboratory-confirmed influenza in young children we conducted a matched
case-control study in children with acute respiratory illness or fever from
2005-2007. Influenza vaccine effectiveness (VE) was calculated using cases with
laboratory-confirmed influenza and controls who tested negative for influenza.
The effectiveness of influenza vaccine in fully vaccinated children 6-59 months
of age was 56% (95% CI: 25%-74%); a significant VE was not found for partial
vaccination.

Department of Pediatrics, University of Cincinnati College of Medicine,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, United
States. mary.staat@cchmc.org

10.1016/j.vaccine.2011.09.037

http://www.ncbi.nlm.nih.gov/pubmed/21945256

(161)Stefater JA, 3, Ren S, Lang RA and
Duffield JS

METCHNIKOFF's POLICEMEN: MACROPHAGES IN DEVELOPMENT, HOMEOSTASIS AND
REGENERATION

2011; 17:743-752

Over the past decade, modern genetic tools have permitted scientists to study
the function of myeloid lineage cells, including macrophages, as never before.
Macrophages were first detected more than a century ago as cells that ingested
bacteria and other microbes, but it is now known that their functional roles
are far more numerous. In this review, we focus on the prevailing functions of
macrophages beyond their role in innate immunity. We highlight examples of
macrophages acting as regulators of development, tissue homoeostasis,
remodeling (the reorganization or renovation of existing tissues) and repair.
We also detail how modern genetic tools have facilitated new insights into these
mysterious cells.

Visual Systems Group, Divisions of Pediatric Ophthalmology and Developmental
Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue,
Cincinnati, OH 45229, USA.

10.1016/j.molmed.2011.07.009

http://www.ncbi.nlm.nih.gov/pubmed/21890411

(162)Strait RT, Hicks W, Barasa N, Mahler
A, Khodoun M, Kohl J, Stringer K, Witte D, Van Rooijen N, Susskind BM and
Finkelman FD

MHC CLASS I-SPECIFIC ANTIBODY BINDING TO NONHEMATOPOIETIC CELLS DRIVES
COMPLEMENT ACTIVATION TO INDUCE TRANSFUSION-RELATED ACUTE LUNG INJURY IN MICE

2011; 208:2525-2544

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic
pulmonary edema that develops during or within 6 h after a blood transfusion,
is the most frequent cause of transfusion-associated death in the United
States. Because development of TRALI is associated with donor antibodies (Abs)
reactive with recipient major histocompatibility complex (MHC), a mouse model
has been studied in which TRALI-like disease is caused by injecting mice with
anti-MHC class I monoclonal Ab (mAb). Previous publications with this model
have concluded that disease is caused by FcR-dependent activation of
neutrophils and platelets, with production of reactive oxygen species that
damage pulmonary vascular endothelium. In this study, we confirm the role of
reactive oxygen species in the pathogenesis of this mouse model of TRALI and
show ultrastructural evidence of pulmonary vascular injury within 5 min of
anti-MHC class I mAb injection. However, we demonstrate that disease induction
in this model involves macrophages rather than neutrophils or platelets,
activation of complement and production of C5a rather than activation of
FcgammaRI, FcgammaRIII, or FcgammaRIV, and binding of anti-MHC class I mAb to
non-BM-derived cells such as pulmonary vascular endothelium. These observations
have important implications for the prevention and treatment of TRALI.

Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, USA.

10.1084/jem.20110159

http://www.ncbi.nlm.nih.gov/pubmed/22025304

(163)Strait RT, Hicks W, Barasa N, Mahler
A, Khodoun M, Kohl J, Stringer K, Witte D, Van Rooijen N, Susskind BM and
Finkelman FD

MHC CLASS I-SPECIFIC ANTIBODY BINDING TO NONHEMATOPOIETIC CELLS DRIVES
COMPLEMENT ACTIVATION TO INDUCE TRANSFUSION-RELATED ACUTE LUNG INJURY IN MICE

2011; 208:2525-2544

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic
pulmonary edema that develops during or within 6 h after a blood transfusion,
is the most frequent cause of transfusion-associated death in the United
States. Because development of TRALI is associated with donor antibodies (Abs)
reactive with recipient major histocompatibility complex (MHC), a mouse model
has been studied in which TRALI-like disease is caused by injecting mice with
anti-MHC class I monoclonal Ab (mAb). Previous publications with this model
have concluded that disease is caused by FcR-dependent activation of
neutrophils and platelets, with production of reactive oxygen species that
damage pulmonary vascular endothelium. In this study, we confirm the role of
reactive oxygen species in the pathogenesis of this mouse model of TRALI and
show ultrastructural evidence of pulmonary vascular injury within 5 min of
anti-MHC class I mAb injection. However, we demonstrate that disease induction
in this model involves macrophages rather than neutrophils or platelets,
activation of complement and production of C5a rather than activation of
FcgammaRI, FcgammaRIII, or FcgammaRIV, and binding of anti-MHC class I mAb to
non-BM-derived cells such as pulmonary vascular endothelium. These observations
have important implications for the prevention and treatment of TRALI.

Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, USA.

10.1084/jem.20110159

http://www.ncbi.nlm.nih.gov/pubmed/22025304

(164)Strawn JRandKeeshin BR

SUCCESSFUL TREATMENT OF POSTTRAUMATIC STRESS DISORDER WITH PRAZOSIN IN a
YOUNG CHILD

2011; 45:1590-1591

Department of Psychiatry, College of Medicine, University of Cincinnati,
Cincinnati, OH, United States Mayerson Center for Safe and Healthy Children,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

0.1345/aph.1Q548

http://www.ncbi.nlm.nih.gov/pubmed/22116993

(165)Summer SS, Brehm BJ, Benoit SC and
D'Alessio DA

ADIPONECTIN CHANGES IN RELATION TO THE MACRONUTRIENT COMPOSITION OF a
WEIGHT-LOSS DIET

2011; 19:2198-2204

Adiponectin is an adipose-derived protein with beneficial metabolic effects.
Low adiponectin is associated with obesity and related diseases. Significant
weight loss increases adiponectin, reducing disease risk. This study compared
the effects of two weight-loss diets with different macronutrient compositions
on adiponectin. Eighty-one obese women in two cohorts were randomized to a
low-fat (LF) or a low-carbohydrate (LC) diet. All subjects underwent equivalent
weight-loss intervention, with weight and other measures assessed at baseline
and after 6 (cohort I) or 4 (cohort II) months. Body fat was measured by dual
energy X-ray absorptiometry. Adiponectin was measured by radioimmunoassay. Diet
intake was assessed using 24-h recalls and 3-day diet records. Data were
analyzed via t-tests and repeated-measures factorial ANOVA using time, diet,
and replicate (cohort I vs. cohort II) as factors. Age, weight, body fat, BMI,
adiponectin, and diet were similar at baseline. Following intervention,
macronutrient composition of the diet was vastly different between the groups,
reflecting the assigned diet. Both groups lost weight and body fat (P <
0.001), with effect in LC dieters greater than LF dieters (-9.1 kg vs. -4.97 kg
weight, P < 0.05 and -5.45 kg vs. -2.62 kg fat, P < 0.001). Adiponectin
increased in the LC (+1.92 mcg/ml, P < 0.01), but not the LF (+0.86 mcg/ml,
P = 0.81), group. There was no correlation between weight loss and increase in
adiponectin. These results confirm that diet-induced loss of weight and body
fat is associated with increased adiponectin concentrations. This effect is
evident with weight loss of 10% or more, and may be greater with LC diets.

Cincinnati Children's Hospital Medical Center, Clinical Translational Research
Center, Cincinnati, Ohio, USA. Suzanne.summer@cchmc.org

10.1038/oby.2011.60

http://www.ncbi.nlm.nih.gov/pubmed/21455123

(166)Talbert RJ, Laor T and Yin H

PROLIFERATIVE MYOSITIS: EXPANDING THE DIFFERENTIAL DIAGNOSIS OF a SOFT
TISSUE MASS IN INFANCY

2011; 40:1623-1627

Proliferative myositis, a pseudosarcomatous lesion of skeletal muscle, is quite
rare in the pediatric population. While benign, it is not always recognized as
such, and may be treated with an extensive resection that can result in
permanent disfigurement. We report a case of an infant with the diagnosis of
proliferative myositis, who to our knowledge is the youngest patient to be
evaluated with magnetic resonance imaging (MRI). Although the MRI findings are
non-specific, we highlight the importance of considering proliferative myositis
in the differential diagnosis of a soft tissue mass, which ultimately might
prevent an overly aggressive resection in a child.

Division of Pediatric Orthopaedics, Cincinnati Children's Hospital Medical
Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. robtalbert2002@gmail.com

10.1007/s00256-011-1274-4

http://www.ncbi.nlm.nih.gov/pubmed/21912882

(167)Taylor-Haas J, Paterno MV and Shaffer
MD

FEMORAL NECK STRESS FRACTURE AND FEMOROACETABULAR IMPINGEMENT

2011; 41:905

The patient was a 34-year-old male recreational marathon runner referred to a
physical therapist with a chief complaint of worsening right lateral hip pain
of 3 months duration that was insidious in nature. Following a physical
examination, the physical therapist discussed his suspicions with the referring
physician. Magnetic resonance imaging revealed findings consistent with a
stress fracture at the inferomedial right femoral neck, a mild cam-type
deformity of the right femoral neck, and a mild degree of heterogeneity of the
right superior anterior labrum, representing a possible tear.

Division of Occupational Therapy and Physical Therapy, Sports Medicine
Biodynamics Center, Cincinnati Children's Hospital Medical Center, Cincinnati,
OH., USA.

10.2519/jospt.2011.0423

http://www.ncbi.nlm.nih.gov/pubmed/22048418

(168)Tegtmeyer K, Conway EE, J., Upperman
JS, Kissoon N and Task Force for Pediatric Emergency,Mass Critical

EDUCATION IN a PEDIATRIC EMERGENCY MASS CRITICAL CARE SETTING

2011; 12:S135-40

INTRODUCTION: An emergency mass critical care event puts significant strains on
all healthcare resources, including equipment, supplies, and manpower; it leads
to extraordinary stresses on healthcare providers, many of whom will be
expected to deliver care outside of their usual scope of practice. Education
and educational resources will be critically important for training providers
and diminishing the stress, anxiety, and chaos of delivering pediatric
emergency mass critical care. This article suggests educational tools, as well
as potential resources, that need to be developed to cope with a pediatric
emergency mass critical care event. METHODS: In May 2008, the Task Force for
Mass Critical Care published guidance on provision of mass critical care to
adults. Acknowledging that the critical care needs of children during disasters
were unaddressed by this effort, a 17-member Steering Committee, assembled by
the Oak Ridge Institute for Science and Education with guidance from members of
the American Academy of Pediatrics, convened in April 2009 to determine
priority topic areas for pediatric emergency mass critical care
recommendations.Steering Committee members established subgroups by topic area
and performed literature reviews of MEDLINE and Ovid databases. The Steering
Committee produced draft outlines through consensus-based study of the
literature and convened October 6-7, 2009, in New York, NY, to review and
revise each outline. Eight draft documents were subsequently developed from the
revised outlines as well as through searches of MEDLINE updated through March
2010.The Pediatric Emergency Mass Critical Care Task Force, composed of 36
experts from diverse public health, medical, and disaster response fields,
convened in Atlanta, GA, on March 29-30, 2010. Feedback on each manuscript was
compiled and the Steering Committee revised each document to reflect expert
input in addition to the most current medical literature. TASK FORCE
RECOMMENDATIONS: Identifying educational needs to prepare for a pediatric
emergency mass critical care event is essential for all healthcare
organizations. Educational strategies and tactics should be developed at
multiple levels for a comprehensive approach to preparing for pediatric
emergency mass critical care.

Division of Critical Care Medicine, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, USA. ken.tegtmeyer@cchmc.org

10.1097/PCC.0b013e318234a764

http://www.ncbi.nlm.nih.gov/pubmed/22067922

(169)Timm N, Bouvay K, Scheid B and Defoor
WR, J.

EVALUATION AND MANAGEMENT OF SEXUALLY TRANSMITTED INFECTIONS IN ADOLESCENT
MALES PRESENTING TO a PEDIATRIC EMERGENCY DEPARTMENT: IS THE CHIEF COMPLAINT
DIAGNOSTIC?

2011; 27:1042-1044

OBJECTIVES: The objectives of the study were to (1) describe evaluation and
treatment patterns for adolescent males presenting with a concern for sexually
transmitted infection (STI) in a pediatric emergency department, (2) assess the
rates of STIs in symptomatic males, and (3) determine the utility of urinalysis
alone in predicting STIs in adolescent males. METHODS: A retrospective cohort
study was conducted of all patients presenting to our pediatric emergency
department from January 1, 2007, to December 31, 2007. Inclusion criteria
included males, aged 15 to 21 years, with an STI or urinary chief complaint.
Exclusion criteria were referrals from pediatricians, a previous history of
urinary tract infection or preexisting urologic condition, or primary complaint
of scrotal and/or testicular pain. RESULTS: A total of 270 patients were
identified. Testing included urinalysis with microscopy (UA) (64%), urine
culture (53%), Neisseria gonorrhoeae (GC), and Chlamydia trachomatis (CT) (93%),
and Trichomonas vaginalis (5%). Sixty-four percent of males tested positive for
either GC or CT, or both. Overall, 91% of patients were treated for CT and GC,
18% for T. vaginalis, and 5% for urinary tract infection. The sensitivity and
specificity of a positive UA for presence of GC and/or CT were 86% and 82%,
respectively, whereas the positive and negative predictive values were 89% and
77%, respectively. There were no positive urine cultures in the cohort.
CONCLUSIONS: Sixty-four percent of patients were diagnosed with either GC or
CT. Although UA is helpful in predicting STI, limited use is warranted, given
the high prevalence of disease in this selected population. The urine culture
does not appear to be a necessary adjunct in the management of these patients.

Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, USA. Nathan.timm@cchmc.org

10.1097/PEC.0b013e318235e950

http://www.ncbi.nlm.nih.gov/pubmed/22068065

(170)Timm NLandGneuhs M

THE PEDIATRIC HOSPITAL INCIDENT COMMAND SYSTEM: AN INNOVATIVE APPROACH TO
HOSPITAL EMERGENCY MANAGEMENT

2011; 71:S549-54

Division of Emergency Medicine, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio 45229, USA. Nathan.timm@cchmc.org

10.1097/TA.0b013e31823a4d28

http://www.ncbi.nlm.nih.gov/pubmed/22072045

(171)Tlustos SJ, Chiu CYP, Walz NC, Taylor
HG, Yeates KO and Wade SL

EMOTION LABELING AND SOCIO-EMOTIONAL OUTCOMES 18 MONTHS AFTER EARLY
CHILDHOOD TRAUMATIC BRAIN INJURY

2011; 17:1132-1142

A growing body of literature has documented evidence for emotion labeling (EL)
deficits after traumatic brain injury (TBI); however, long-term effects of TBI
on EL abilities, particularly among young children, are unclear. We
investigated EL abilities and socio-emotional outcomes in 32 children with
moderate-severe TBI, 23 with complicated-mild TBI, and 82 children with
orthopedic injuries (OI), shortly after injury and at 18 months post-injury.
All children were between 3:0 and 6:11 years of age at the time of injury. Repeated
measures analyses indicated that all groups showed improved EL performance
between acute and 18-month assessments, but that the moderate-severe TBI group
improved at a slower rate than the OI group, so that the two groups showed
significantly different performance at 18 months. Emotion labeling ability did
not significantly contribute to the prediction of socio-emotional outcomes
after controlling for pre-injury functioning. These results provide preliminary
evidence of emerging EL deficits after early childhood TBI that are related to
injury severity but that do not predict social and behavioral outcomes. Â©
Copyright The International Neuropsychological Society 2011.

Department of Psychology, University of Cincinnati, Cincinnati, OH, United
States Department of Communication Sciences and Disorders, University of
Cincinnati, Cincinnati, OH, United States Division of Behavioral Medicine and
Clinical Psychology, Department of Pediatrics, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States University of Cincinnati College
of Medicine, Cincinnati, OH, United States Division of Developmental and
Behavioral Pediatrics and Psychology, Department of Pediatrics, Case Western
Reserve University, Cleveland, OH, United States Rainbow Babies and Children's
Hospital, University Hospitals Case Medical Center, Cleveland, OH, United
States Division of Psychology, Department of Pediatrics, Ohio State University,
United States Center for Biobehavioral Health, Research Institute at Nationwide
Children's Hospital, Columbus, OH, United States Division of Physical Medicine
and Rehabilitation, Department of Pediatrics, Cincinnati Children's Hospital
Medical Center, Cincinnati, OH, United States

10.1017/s1355617711001202 10.1177/107319110100800308; Beatty, W.W., Testa,
J.A., English, S., Winn, P., Influences of clustering and switching on the
verbal fluency performance of patients with Alzheimer's disease (1997) Aging,
Neuropsychology, (TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/21923972

(172)Tonkin E, Calzone K, Jenkins J, Lea D
and Prows C

GENOMIC EDUCATION RESOURCES FOR NURSING FACULTY

2011; 43:330-340

PURPOSE: The increasing recognition regarding the relevance of genomics across
the scope of nursing healthcare practice has resulted in the drive to integrate
appropriate genomic knowledge and skills into nurse education and training. In
this final article of the series Genetics-Genomics and Nursing Education, we
will look at genetic and genomic education resources and the factors that
influence both their creation and use. ORGANIZING CONSTRUCT: In considering
nurse education from faculty and student perspectives, four identified areas of
need have been used as the organizing constructs: guidance (what should be
taught and at what level of complexity); support and training; access to
genetics professionals and service users; and quality resources. This paper
sets out to address the following points: (a) why there is a need for quality
genomics education resources to support nurse education; (b) what is required
from a resource to make it "useful" for the user; and (c) how the
quality and impact of a resource can be measured. While not exhaustive,
information is provided to a number of globally accessible resources, along
with detailed descriptions of selected teaching or learning tools. Strategies
for evaluating the suitability of a resource and suggestions on how genomic
resources can be used within nurse education are provided. CONCLUSIONS: The use
of clinically relevant resources that link theory to professional practice and
which meet predefined learning outcomes and practice indicators for nurse
education and training will facilitate the integration of genomics into
curricula by nurse faculty. CLINICAL RELEVANCE: Providing clinically meaningful
education and training in genomics is central to enabling every nurse to
develop the appropriate knowledge and skills in genomics in order to provide
optimum care to individuals and families now, and to facilitate the integration
of new information and technology as it becomes available across mainstream
healthcare services.

National Health Service, National Genetics Education & Development Centre,
University of Glamorgan, Pontypridd, Wales, U.K. etonkin@glam.ac.uk

10.1111/j.1547-5069.2011.01415.x

http://www.ncbi.nlm.nih.gov/pubmed/22034967

(173)Trapnell BC, Strausbaugh SD, Woo MS,
Tong SY, Silber SA, Mulberg AE and Leitz G

CORRIGENDUM TO â€œEfficacy AND SAFETY OF PANCREAZEÂ® FOR TREATMENT OF
EXOCRINE PANCREATIC INSUFFICIENCY DUE TO CYSTIC FIBROSISâ€ [J CYST FIBROS, 10(2011)350-356]

2011;
10:491-492

Division of Pulmonary Medicine and Biology, Cincinnati Children's Hospital Medical
Center, Cincinnati, OH, United States Division of Pulmonary, Critical Care and
Sleep Medicine, University of Cincinnati Medical Center, 3333 Burnet Avenue,
4029 CCRF, Cincinnati, OH 45229-3039, United States Division of Pediatric
Pulmonology, Rainbow Babies and Children's Hospital and University, Hospitals
at Case, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH,
United States Division of Pulmonary, Critical Care, Sleep Medicine, Rainbow
Babies and Children's Hospital and University, Hospitals at Case, Case Western
Reserve University, 11100 Euclid Avenue, Cleveland, OH, United States UCLA
School of Nursing, Box 956917, Los Angeles, CA 90095-6917, United States
Johnson and Johnson Pharmaceutical Research and Development, 920, Route 202,
Raritan, NJ 08869, United States

10.1016/j.jcf.2011.09.004

(174)Treves ST, Parisi MT and Gelfand MJ

PEDIATRIC RADIOPHARMACEUTICAL DOSES: NEW GUIDELINES

2011; 261:347-349

Department of Radiology, Children's Hospital Boston, Harvard Medical School,
300 Longwood Ave, Boston, MA 02115, United States Department of Radiology,
Seattle Children's Hospital, Seattle, WA, United States Section of Nuclear
Medicine, Department of Radiology, Cincinnati Children's Hospital, Cincinnati,
OH, United States

10.1148/radiol.11110449

http://www.ncbi.nlm.nih.gov/pubmed/22012901

(175)Treves ST, Parisi MT and Gelfand MJ

PEDIATRIC RADIOPHARMACEUTICAL DOSES: NEW GUIDELINES

2011; 261:347-349

Department of Radiology, Children's Hospital Boston, Harvard Medical School,
300 Longwood Ave, Boston, MA 02115, United States Department of Radiology,
Seattle Children's Hospital, Seattle, WA, United States Section of Nuclear
Medicine, Department of Radiology, Cincinnati Children's Hospital, Cincinnati,
OH, United States

10.1148/radiol.11110449

http://www.ncbi.nlm.nih.gov/pubmed/22012901

(176)Uygungil B, Assa'Ad A, Khurana Hershey
GK and Risma K

IMMUNODEFICIENCY: a PROBLEM WITH THE FAUCET OR THE DRAIN?

2011; 107:547-549

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

10.1016/j.anai.2011.09.016

http://www.ncbi.nlm.nih.gov/pubmed/22123391

(177)Vadaparampil ST, Kahn JA, Salmon D,
Lee JH, Quinn GP, Roetzheim R, Bruder K, Malo TL, Proveaux T, Zhao X, Halsey N
and Giuliano AR

MISSED CLINICAL OPPORTUNITIES: PROVIDER RECOMMENDATIONS FOR HPV VACCINATION
FOR 11-12 YEAR OLD GIRLS ARE LIMITED

2011; 29:8634-8641

Objective: The purpose of this study was to determine the prevalence of
physician recommendation of human papillomavirus (HPV) vaccination in early
(ages 11-12), middle (13-17), and late adolescent/young adult (18-26) female
patients by physician specialty, and to identify factors associated with
recommendation in early adolescents. Methods: A 38-item survey was conducted
April 2009 through August 2009 among a nationally representative random sample
of 1538 Family Physicians, Pediatricians, and Obstetricians and Gynecologists
obtained from the American Medical Association Physician Masterfile. A
multivariable model was used to assess factors associated with frequency of
physician recommendation of HPV vaccination (" always" = 76-100% of
the time vs. other = 0-75%) within the past 12. months. Results: Completed
surveys were received from 1013 physicians, including 500 Family Physicians,
287 Pediatricians, and 226 Obstetricians and Gynecologists (response rate =
67.8%). Across the specialties, 34.6% of physicians reported they "
always" recommend the HPV vaccine to early adolescents, 52.7% to middle
adolescents, and 50.2% to late adolescents/young adults. The likelihood of
" always" recommending the HPV vaccine was highest among
Pediatricians for all age groups (P< 0.001). Physician specialty, age,
ethnicity, reported barriers, and Vaccines for Children provider status were
significantly associated with " always" recommending HPV vaccination
for early adolescents. Conclusions: Findings suggest missed clinical
opportunities for HPV vaccination, and perceived barriers to vaccination may
drive decisions about recommendation. Results suggest the need for age and
specialty targeted practice and policy level interventions to increase HPV
vaccination among US females. Â© 2011 Elsevier Ltd.

Department of Health Outcomes and Behavior, Moffitt Cancer Center, MRC-CANCONT,
12902 Magnolia Drive, Tampa, FL 33612, United States Cincinnati Children's
Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, United
States National Vaccine Program Office, Office of Public Health and Science,
Office of the Secretary, Department of Health and Human Services, 200
Independence Avenue SW, Washington, DC 20201, United States Biostatistics Department,
Moffitt Cancer Center, MRC-CANCONT, 12902 Magnolia Drive, Tampa, FL 33612,
United States Department of Family Medicine, College of Medicine, University of
South Florida, 2 Tampa General Circle, 6th Floor, Tampa, FL 33606, United
States Department of Obstetrics and Gynecology, College of Medicine, University
of South Florida, 5802 N. 30th Street, Tampa, FL 33610, United States Institute
for Vaccine Safety, Department of International Health, Johns Hopkins Bloomberg
School of Public Health, 615 N. Wolfe Street, Baltimore, MD 21205, United
States Department of Cancer Epidemiology, Moffitt Cancer Center, MRC-CANCONT,
12902 Magnolia Drive, Tampa, FL 33612, United States

10.1016/j.vaccine.2011.09.006

http://www.ncbi.nlm.nih.gov/pubmed/21924315

(178)Valenzuela JM, La Greca AM, Hsin O,
Taylor C and Delamater AM

PRESCRIBED REGIMEN INTENSITY IN DIVERSE YOUTH WITH TYPE 1 DIABETES: ROLE OF
FAMILY AND PROVIDER PERCEPTIONS

2011; 12:696-703

Recent literature suggests that disparities in prescribed treatments may exist
for youth with type 1 diabetes. There is limited research to date examining
factors associated with prescribed regimen intensity in this population. In
this study, we examined racial/ethnic differences in regimen intensity and
predictors of regimen intensity in youth with type 1 diabetes. We expected that
minority youth would have less intensive regimens and that caregiver and
physician perceptions would be associated with regimen intensity. This
cross-sectional study included 178 families of 10- to 17-yr-old youth at three
endocrinology clinics. Caregivers reported perceived costs and benefits of
intensive regimens. Physicians described the prescribed treatment and their
perceptions of family/child competence and self-management. Analyses included
analysis of covariance and hierarchical multiple linear regression. Findings
indicate a disparity in regimen intensity for minority youth. Caregiver
perceptions of costs associated with intensive regimens and physician
perceptions of family competence are associated with prescribed regimen
intensity. Interventions targeting disparities in prescribed regimen intensity
should be considered. Further research is needed to understand the role of family
perceptions of treatments and physician clinical decision making in addressing
health disparities in type 1 diabetes.

Division of Behavioral Medicine & Clinical Psychology, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH 45209, USA. jessica.valenzuela@cchmc.org

10.1111/j.1399-5448.2011.00766.x

http://www.ncbi.nlm.nih.gov/pubmed/21457425

(179)Vanhoutte DandHeymans S

THROMBOSPONDIN 1: A PROTECTIVE "MATRI-CELLULAR" SIGNAL IN THE
STRESSED HEART

2011; 58:770-771

Department of Cardiovascular Diseases, KU Leuven, Leuven, Belgium Molecular
Cardiovascular Biology, Cincinnati Children's Hospital Medical Center, MLC
7020, 240 Albert Sabin Way, Cincinnati, OH 45229-3039, United States Center for
Heart Failure Research, Cardiovascular Research Institute Maastricht (CARIM),
Maastricht University, Maastricht, Netherlands

10.1161/hypertensionaha.111.176933

http://www.ncbi.nlm.nih.gov/pubmed/21947464

(180)Wade SL, Oberjohn K, Conaway K,
Osinska P and Bangert L

LIVE COACHING OF PARENTING SKILLS USING THE INTERNET: IMPLICATIONS FOR
CLINICAL PRACTICE

2011; 42:487-493

Many parents who would benefit from parenting skills training via live coaching
do not receive it due to barriers such as time, distance, and the
unavailability of skilled providers. This report describes an innovative
web-based parenting skills program for families of young children with
traumatic brain injury (TBI)-Internet-Based Interacting Together Everyday,
Recovery After Childhood TBI (I-InTERACT). I-InTERACT is a web-based parenting
skills program of 10-14 sessions that combines self-guided web modules with
live coaching via videoconferencing. We describe the feasibility and utility of
this approach, as well as the unique nature of the therapeutic process,
detailing the perspectives of 13 parents of children with TBI who participated
in the program and 6 therapists who delivered the program. Nine of 13 parents
preferred the web-based coaching to traditional treatment; they cited its ease
of use and the comfort of doing it at home. Therapists uniformly liked coaching
over the web despite the need to address boundaries and troubleshoot
technological difficulties. Therapeutic alliance was comparable to traditional
therapy with nearly all families expressing a strong connection to the
therapist. Individuals with less computer experience particularly liked the
program because it gave them access to the web and a sense of empowerment.
These preliminary findings support the utility of web-based parenting skills
training for families from diverse backgrounds, while underscoring the
potential for clinical use with other underserved populations. Â© 2011 American
Psychological Association.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States
University of Cincinnati, United States

10.1037/a0025222 10.1159/000028956; Bauer, W.M., Growick, B., Rehabilitation
counseling in Appalachian America (2003) Journal of Rehabilitation, 69, pp.
18-24; Chapman, L.A., Wade, S.L., Walz, N.C., Taylor, H.G., Stancin, T.,
Yeates, K.O., Clini(TRUNCATED)

(181)Wang JandRichards DA

SPATIAL REGULATION OF EXOCYTIC SITE AND VESICLE MOBILIZATION BY THE ACTIN
CYTOSKELETON

2011; 6Numerous studies indicate a role for the actin cytoskeleton in
secretion. Here, we have used evanescent wave and widefield fluorescence
microscopy to study the involvement of the actin cytoskeleton in secretion from
PC12 cells. Secretion was assayed as loss of ANF-EmGFP in widefield mode. Under
control conditions, depolarization induced secretion showed two phases: an
initial rapid rate of loss of vesicular cargo (tau = 1.4 s), followed by a
slower, sustained drop in fluorescence (tau = 34.1 s). Pretreatment with
Latrunculin A changed the kinetics to a single exponential, slightly faster
than the fast component of control cells (1.2 s). Evanescent wave microscopy
allowed us to examine this at the level of individual events, and revealed
equivalent changes in the rates of vesicular arrival at the plasma membrane
immediately following and during the sustained phase of release.
Co-transfection of mCherry labeled Î²-actin and ANF-EmGFP demonstrated that
sites of exocytosis had an inverse relationship with sites of actin enrichment.
Disruption of visualized actin at the membrane resulted in the loss of
specificity of exocytic site. Â© 2011 Wang, Richards. This is an open-access
article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any
medium, provided the original author and source are credited.

Department of Anesthesia, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States

Export Date 11 January 2012 Source Scopus Art. No. e29162 doi
10.1371/journal.pone.0029162 Language of Original Document English
Correspondence Address Richards, D. A.; Department of Anesthesia, Cincinnati
Children's Hospital Medical Center, Cin(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/22195014

(182)Whitcomb S, Bass J and Luiselli J

EFFECTS OF a COMPUTER-BASED EARLY READING PROGRAM (HEADSPROUTÂ®) ON WORD
LIST AND TEXT READING SKILLS IN a STUDENT WITH AUTISM

2011; 23:491-499

School of Education, University of Massachusetts, Amherst USA Cincinnati
Children's Hospital Medical Center, Cincinnati USA May Institute, Randolph
02368 USA

10.1007/s10882-011-9240-6

(183)Wills-Karp MandFinkelman FD

INNATE LYMPHOID CELLS WIELD a DOUBLE-EDGED SWORD

2011; 12:1025-1027

Division of Immunobiology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Department of Medicine, Cincinnati Veterans
Affairs Medical Center, University of Cincinnati College of Medicine,
Cincinnati, OH, United States

10.1038/ni.2142

http://www.ncbi.nlm.nih.gov/pubmed/22012433

(184)Wills-Karp MandFinkelman FD

INNATE LYMPHOID CELLS WIELD a DOUBLE-EDGED SWORD

2011; 12:1025-1027

Division of Immunobiology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States Department of Medicine, Cincinnati Veterans
Affairs Medical Center, University of Cincinnati College of Medicine,
Cincinnati, OH, United States

10.1038/ni.2142

http://www.ncbi.nlm.nih.gov/pubmed/22012433

(185)Wong HR, Cvijanovich NZ, Allen GL, Thomas
NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Shanley TP, Bigham MT,
Wheeler DS, Doughty LA, Tegtmeyer K, Poynter SE, Kaplan JM, Chima RS, Stalets
E, Basu RK, Varisco BM and Barr FE

VALIDATION OF a GENE EXPRESSION-BASED SUBCLASSIFICATION STRATEGY FOR
PEDIATRIC SEPTIC SHOCK

2011; 39:2511-2517

OBJECTIVE: Septic shock heterogeneity has important implications for clinical
trial implementation and patient management. We previously addressed this
heterogeneity by identifying three putative subclasses of children with septic
shock based exclusively on a 100-gene expression signature. Here we attempted
to prospectively validate the existence of these gene expression-based
subclasses in a validation cohort. DESIGN: Prospective observational study involving
microarray-based bioinformatics. SETTING: Multiple pediatric intensive care
units in the United States. PATIENTS: Separate derivation (n = 98) and
validation (n = 82) cohorts of children with septic shock. INTERVENTIONS: None
other than standard care. MEASUREMENTS AND MAIN RESULTS: Gene expression
mosaics of the 100 class-defining genes were generated for 82 individual
patients in the validation cohort. Using computer-based image analysis,
patients were classified into one of three subclasses ("A," "B,"
or "C") based on color and pattern similarity relative to reference
mosaics generated from the original derivation cohort. After subclassification,
the clinical database was mined for phenotyping. Subclass A patients had higher
illness severity relative to subclasses B and C as measured by maximal organ
failure, fewer intensive care unit-free days, and a higher Pediatric Risk of
Mortality score. Patients in subclass A were characterized by repression of
genes corresponding to adaptive immunity and glucocorticoid receptor signaling.
Separate subclass assignments were conducted by 21 individual clinicians using
visual inspection. The consensus classification of the clinicians had modest
agreement with the computer algorithm. CONCLUSIONS: We have validated the
existence of subclasses of children with septic shock based on a biologically
relevant, 100-gene expression signature. The subclasses have relevant clinical
differences.

Department of Pediatrics, Cincinnati Children's Hospital Medical Center and
Cincinnati Children's Research Foundation, University of Cincinnati College of
Medicine, Cincinnati, OH, USA. hector.wong@cchmc.org

10.1097/CCM.0b013e3182257675

http://www.ncbi.nlm.nih.gov/pubmed/21705885

(186)Yang J, Ylipaa A, Sun Y, Zheng H, Chen
K, Nykter M, Trent J, Ratner N, Lev DC and Zhang W

GENOMIC AND MOLECULAR CHARACTERIZATION OF MALIGNANT PERIPHERAL NERVE SHEATH
TUMOR IDENTIFIES THE IGF1R PATHWAY AS a PRIMARY TARGET FOR TREATMENT

2011; 17:7563-7573

PURPOSE: Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that
lacks effective therapeutic strategies. We gain insight into the most recurrent
genetically altered pathways with the purpose of scanning possible therapeutic
targets. EXPERIMENTAL DESIGN: We conducted a microarray-based comparative
genomic hybridization profiling of two cohorts of primary MPNST tissue samples
including 25 patients treated at The University of Texas MD Anderson Cancer
Center and 26 patients from Tianjin Cancer Hospital. Immunohistochemistry (IHC)
and cell biology detection and validation were carried out on human MPNST
tissues and cell lines. RESULTS: Genomic characterization of 51 MPNST tissue
samples identified several frequently amplified regions harboring 2,599 genes
and regions of deletion including 4,901 genes. At the pathway level, we
identified a significant enrichment of copy number-altering events in the
insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent
amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a
potential target in MPNSTs, we first confirmed that high IGF1R protein
correlated with worse tumor-free survival in an independent set of samples
using IHC. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the
effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using siRNAs
or an IGF1R inhibitor, MK-0646, led to significant decreases in cell
proliferation, invasion, and migration accompanied by attenuation of the
PI3K/AKT and mitogen-activated protein kinase pathways. CONCLUSION: These
integrated genomic and molecular studies provide evidence that the IGF1R
pathway is a potential therapeutic target for patients with MPNST. Clin Cancer
Res; 17(24); 7563-73. (c)2011 AACR.

Authors' Affiliations: Departments of Bone and Soft Tissue Tumor, Pathology,
and Epidemiology and Biostatistics, Tianjin Medical University Cancer Hospital
and Institute, Tianjin, China; Departments of Pathology, Sarcoma Medical
Oncology, and Cancer Biology, The University of Texas MD Anderson Cancer
Center, Houston, Texas; Department of Signal Processing, Tampere University of
Technology, Tampere, Finland; and Division of Experimental Hematology and
Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati,
Ohio.

10.1158/1078-0432.CCR-11-1707

http://www.ncbi.nlm.nih.gov/pubmed/22042973

(187)Yaszay B, Obrien M, Shufflebarger HL,
Betz RR, Lonner B, Shah SA, Boachie-Adjei O, Crawford A, Letko L, Harms J,
Gupta MC, Sponseller PD, Abel MF, Flynn J, MacAgno A and Newton PO

EFFICACY OF HEMIVERTEBRA RESECTION FOR CONGENITAL SCOLIOSIS: A MULTICENTER
RETROSPECTIVE COMPARISON OF THREE SURGICAL TECHNIQUES

2011; 36:2052-2060

Study Design: Multicenter, retrospective study. Objective: To compare the
outcomes of three surgical treatments for congenital spinal deformity due to a
hemivertebra. Summary of Background Data: Congenital anomalies of the spine can
cause significant and progressive scoliosis and kyphosis. Their management may
be challenging and controversy remains over the "best" surgical
treatment. Methods: A multicenter retrospective study of patients with congenital
spinal deformity due to 1 or 2 level hemivertebra(e) was performed. The
surgical treatments included hemiepiphysiodesis or in situ fusion (group 1),
instrumented fusion without hemivertebra excision (group 2), or instrumented
hemivertebra excision (group 3). Results: Seventy-six patients with minimum
2-year follow-up were evaluated. The mean age was 8 years (range: 1-18). The
hemivertebra were fully segmented, nonincarcerated (67%), incarcerated (1%),
and semisegmented (32%). There were 65 patients with single hemivertebra and 11
patients with double hemivertebra. There were 14 (18.4%) group 1, 20 (26.3%)
group 2, and 42 (55.3%) group 3 patients. Group 1 (37 Â± 14Â°) and group 3 (35
Â± 26Â°) patients had smaller preoperative curves than group 2 patients (55 Â±
26Â°) (P < 0.01). Group 3 had better percent correction at 2 years than
groups 1 and 2 (P < 0.001). Group 3 had shorter fusion (P = 0.001), less
estimated blood loss (EBL, P = 0.03), and a trend toward shorter operative
times than group 2 (P = 0.10). The overall complication rate for the entire
group was 30% group 1 (23%), group 2 (17%), and group 3 (44%) (P = 0.09).
Conclusion: While hemivertebra resection for congenital scoliosis had a higher
complication rate than either hemiepiphysiodesis/in situ fusion or
instrumentated fusion without resection, posterior hemivertebra resection in
younger patients resulted in better percent correction than the other two
techniques. Â© 2011 Lippincott Williams & Wilkins.

Department of Orthopedic Surgery, Rady Childrens Hospital, San Diego, CA,
United States Department of Orthopedics, Miami Childrens Hospital, Miami, FL,
United States Department of Orthopedic Surgery, Shriners Hospitals for
Children, Philadelphia, Philadelphia, PA, United States Department of Orthopaedics,
Alfred i DuPont Hospital for Children, Wilmington, DE, United States Department
of Orthopaedic Surgery, Hospital for Special Surgery, New York, NY, United
States Department of Orthopaedic Surgery, Cincinnati Childrens Hospital Medical
Center, Cincinnati, OH, United States Department of Orthopedic Surgery,
Klinikum Karlsbad Langensteinbach, Karlsbad, Germany Department of Orthopaedic
Surgery, University of California-Davis, Sacramento, CA, United States
Department of Orthopaedics, Johns Hopkins, Baltimore, MD, United States
Department of Orthopedic Surgery, University of Virginia, Charlottesville, VA,
United States Department of Orthopedic Surgery, Childrens Hospital of
Philadelphia, Philadelphia, PA, United States

10.1097/BRS.0b013e318233f4bb

http://www.ncbi.nlm.nih.gov/pubmed/22048650

(188)Yin S

MALICIOUS USE OF NONPHARMACEUTICALS IN CHILDREN

2011; 35:924-929

OBJECTIVE: The objective of this study was to describe malicious nonpharmaceutical
exposures in children reported to US poison centers. METHODS: We performed a
retrospective study of all nonpharmaceutical exposures involving children 7
years old reported to the US National Poison Data System (NPDS) from 2000 to
2008 for which the reason for exposure was coded as "malicious". The
American Association of Poison Control Centers definition and categorization of
nonpharmaceuticals was used. Data collected for each case included age, gender,
month and year of the exposure, the exposed substance or substances, intent,
and poison center outcome designation. Fatality abstracts (summaries of the
facts reported to the poison center) were reviewed. RESULTS: Out of
approximately 21.4 million exposures reported to NPDS during the study period,
4,053 cases involving 4,232 nonpharmaceuticals were identified. The mean number
of cases per year was 450 (range 409-546) with no linear annual trend (p=0.28).
The median age was 3 years (1.5, 5) with boys constituting 57%. 4.5% of the
cases resulted in moderate or worse outcomes in which the outcome was known.
The most commonly reported major categories were household cleaning substances
(23%), cosmetics/personal care products (13%), pesticides (8%), other/unknown
nondrug substances (6%), foreign bodies/toys/miscellaneous (5%), alcohols (5%),
hydrocarbons (4%), lacrimators (4%), chemicals (4%), and deodorizers (3%). Four
children died and 18 others had lifethreatening injuries. Among these 22
children, cleaning substances (7) were the most common major category followed
by chemicals (4), alcohols (3), fumes/gases/vapors (2) and six other categories
with 1 each. In the only case where the presence or absence of associated
physical injuries was described, the child had multiple injuries consistent
with physical abuse. CONCLUSION: Malicious administration of nonpharmaceuticals
is an important component of child maltreatment with cases being reported
consistently to poison centers. PRACTICAL IMPLICATIONS: Clinicians should
consider the possibility of child abuse when presented with these exposures.

Denver Health and Hospital Authority, Rocky Mountain Poison and Drug Center,
Denver, CO, USA; Cincinnati Children's Hospital, Division of Emergency of
Medicine, University of Cincinnati School of Medicine, Department of
Pediatrics, Cincinnati, OH, USA.

10.1016/j.chiabu.2011.05.019

http://www.ncbi.nlm.nih.gov/pubmed/22074758

(189)Yonezawa S, Higashi M, Yamada N,
Yokoyama S, Kitamoto S, Kitajima S and Goto M

MUCINS IN HUMAN NEOPLASMS: CLINICAL PATHOLOGY, GENE EXPRESSION AND
DIAGNOSTIC APPLICATION

2011; 61:697-716

Mucins are high molecular weight glycoproteins that play important roles in
carcinogenesis and tumor invasion. Our immunohistochemical studies demonstrated
that MUC1 or MUC4 expression is related to the aggressive behavior and poor
outcome of human neoplasms. MUC2 is expressed in indolent pancreatobiliary
neoplasms, but these tumors sometimes show invasive growth with MUC1 expression
in invasive areas. MUC5AC shows de novo high expression in many types of
precancerous lesions of pancreatobiliary cancers and is an effective marker for
early detection of the neoplasms. The combination of MUC1, MUC2, MUC4 and
MUC5AC expression may be useful for early detection and evaluation of the
potential for malignancy of pancreatobiliary neoplasms. Regarding the mechanism
of mucin expression, we have recently reported that expression of the mucin
genes is regulated epigenetically in cancer cell lines, using quantitative
MassARRAY analysis, methylation-specific polymerase chain reaction analysis and
chromatin immunoprecipitation analysis, with confirmation by the treatment with
5-aza-2â€²-deoxycytidine and trichostatin A. We have also developed a
monoclonal antibody against the MUC1 cytoplasmic tail domain, which has many
biological roles. Based on all of the above findings, we suggest that
translational research into mucin gene expression mechanisms, including
epigenetics, may provide new tools for early and accurate detection of human
neoplasms. Â© 2011 The Authors. Pathology International Â© 2011 Japanese
Society of Pathology and Blackwell Publishing Asia Pty Ltd.

Department of Human Pathology, Field of Oncology, Kagoshima University Graduate
School of Medical and Dental Sciences, Kagoshima, Japan Department of Surgical
Pathology, Kagoshima University Hospital, Kagoshima, Japan National Sanatorium
Hoshizuka-Keiaien, Kanoya, Kagoshima, Japan Division of Reproductive Sciences,
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States

10.1111/j.1440-1827.2011.02734.x 10.1002/ijc.26187; Moniaux, N., Varshney,
G.C., Chauhan, S.C., Generation and characterization of anti-MUC4 monoclonal
antibodies reactive with normal and cancer cells in humans (2004) J Histochem
Cytochem, 52, p(TRUNCATED)

http://www.ncbi.nlm.nih.gov/pubmed/22126377

(190)Zeller MH, Reiter-Purtill J, Ratcliff
MB, Inge TH and Noll JG

TWO-YEAR TRENDS IN PSYCHOSOCIAL FUNCTIONING AFTER ADOLESCENT ROUX-EN-Y
GASTRIC BYPASS

2011; 7:727-732

BACKGROUND: Comprehensive studies of adolescent bariatric surgery outcomes are
in their infancy and are critically needed. The present study examined the rate
of change in the body mass index (BMI), health-related quality of life (HRQOL),
depressive symptoms, and self-concept in adolescents undergoing Roux-en-Y
gastric bypass (RYGB) during the first 24 postoperative months using a
prospective longitudinal design at a pediatric medical center. METHODS: A total
of 16 adolescents (mean age 16.2 yr; 62.5% female, mean BMI 59.9 kg/m2; 97% of
eligible, consecutive patients) completed the Impact of Weight on Quality of
Life-Kids, Pediatric Quality of Life Inventory, Beck Depression Inventory,
Self-Perception Profile for Adolescents, and height and weight measurements at
baseline and 6, 12, 18, and 24 months after RYGB. A total of 75% participated
at all follow-up points. RESULTS: Before RYGB, global psychosocial impairments
were documented. Hierarchical linear modeling was used to examine the growth
trajectories. Several quadratic (nonlinear) trends were revealed. A substantial
reduction in weight and depressive symptoms, as well as improved HRQOL and
self-concept were identified across the first postoperative year, followed by
decelerations in year 2, including weight regain (P < .0001) and slight
increases in depressive symptoms (P = .004) and decreases in HRQOL (Social, P =
.002; Body Esteem, P = .0007; Physical Comfort, P < .0001; and Total, P <
.0001), and self-concept (Social, P = .02; Appearance, P = .002; and Close
Friendship, P = .008). CONCLUSION: During the first 24 months after RYGB,
preliminary evidence suggests adolescents experience significant weight loss as
well as psychosocial and HRQOL improvements. A deceleration in these gains
occurred in the second postoperative year. Longer term follow-up with larger
samples is critical to determine the weight and psychosocial trajectories, and
what role psychosocial status plays in adolescents' weight change and
maintenance.

Division of Behavioral Medicine and Clinical Psychology, Cincinnati Children's
Hospital Medical Center, Cincinnati, Ohio 45229, USA. meg.zeller@cchmc.org

10.1016/j.soard.2011.01.034

http://www.ncbi.nlm.nih.gov/pubmed/21497142

(191)Zhang G, Karns R, Sun G, Indugula SR,
Cheng H, Havas-Augustin D, Novokmet N, Rudan D, Durakovic Z, Missoni S,
Chakraborty R, Rudan P and Deka R

EXTENT OF HEIGHT VARIABILITY EXPLAINED BY KNOWN HEIGHT-ASSOCIATED GENETIC
VARIANTS IN AN ISOLATED POPULATION OF THE ADRIATIC COAST OF CROATIA

2011; 6:e29475

BACKGROUND: Human height is a classical example of a polygenic quantitative
trait. Recent large-scale genome-wide association studies (GWAS) have
identified more than 200 height-associated loci, though these variants explain
only 2 approximately 10% of overall variability of normal height. The objective
of this study was to investigate the variance explained by these loci in a
relatively isolated population of European descent with limited admixture and
homogeneous genetic background from the Adriatic coast of Croatia.
METHODOLOGY/PRINCIPAL FINDINGS: In a sample of 1304 individuals from the island
population of Hvar, Croatia, we performed genome-wide SNP typing and assessed
the variance explained by genetic scores constructed from different panels of
height-associated SNPs extracted from five published studies. The combined
information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of
phenotypic variation in our sample. Genetic scores based on 20 approximately 50
SNPs reported by the remaining individual GWA studies explained 3 approximately
5% of height variance. These percentages of variance explained were within
ranges comparable to the original studies and heterogeneity tests did not detect
significant differences in effect size estimates between our study and the
original reports, if the estimates were obtained from populations of European
descent. CONCLUSIONS/SIGNIFICANCE: We have evaluated the portability of
height-associated loci and the overall fitting of estimated effect sizes
reported in large cohorts to an isolated population. We found proportions of
explained height variability were comparable to multiple reference GWAS in
cohorts of European descent. These results indicate similar genetic
architecture and comparable effect sizes of height loci among populations of
European descent.

Human Genetics Division, Cincinnati Children's Hospital, Cincinnati, Ohio,
United States of America.

10.1371/journal.pone.0029475

internal-pdf://Zhang-2011-Extent of height var-3197728000/Zhang-2011-Extent of
height var.pdf; http://www.ncbi.nlm.nih.gov/pubmed/22216288

(192)Zhang P, Wu Y, Belenkaya TY and Lin X

SNX3 CONTROLS Wingless/Wnt SECRETION THROUGH REGULATING RETROMER-DEPENDENT
RECYCLING OF WNTLESS

2011; 21:1677-1690

Drosophila Wingless (Wg) acts as a morphogen during development. Wg secretion
is controlled by a seven-pass transmembrane cargo Wntless (Wls). We have
recently identified retromer as a key regulator involved in Wls trafficking. As
sorting nexin (SNX) molecules are essential components of the retromer complex,
we hypothesized that specific SNX(s) is required for retromer-mediated Wnt
secretion. Here, we generated Drosophila mutants for all of the eight snx
members, and identified Drosophila SNX3 (DSNX3) as an essential molecule
required for Wg secretion. We show that Wg secretion and its signaling activity
are defective in Dsnx3 mutant clones in wing discs. Wg levels in the culture
medium of Dsnx3-depleted S2 cells are also markedly reduced. Importantly, Wls
levels are strikingly reduced in Dsnx3 mutant cells, and overexpression of Wls
can rescue the Wg secretion defect observed in Dsnx3 mutant cells. Moreover, DSNX3
can interact with the retromer component Vps35, and co-localize with Vps35 in
early endosomes. These data indicate that DSNX3 regulates Wg secretion via
retromer-dependent Wls recycling. In contrast, we found that Wg secretion is
not defective in cells mutant for Drosophila snx1 and snx6, two components of
the classical retromer complex. Ectopic expression of DSNX1 or DSNX6 fails to
rescue the Wg secretion defect in Dsnx3 mutant wing discs and in Dsnx3
dsRNA-treated S2 cells. These data demonstrate the specificity of the
DSNX3-retromer complex in Wls recycling. Together, our findings suggest that
DSNX3 acts as a cargo-specific component of retromer, which is required for
endocytic recycling of Wls and Wg/Wnt secretion. Â© 2011 IBCB, SIBS, CAS All
rights reserved.

State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of
Zoology, Chinese Academy of Sciences, Beijing 100101, China Division of
Developmental Biology, Cincinnati Children's Hospital Medical Center,
Cincinnati, OH 45229, United States

10.1038/cr.2011.167

http://www.ncbi.nlm.nih.gov/pubmed/22041890

(193)Zhang R, Wu T, Wang Y, Liu H, Zou Y,
Liu W, Xiang J, Xiao C, Yang L and Fu Z

INTERICTAL MAGNETOENCEPHALOGRAPHIC FINDINGS RELATED WITH SURGICAL OUTCOMES
IN LESIONAL AND NONLESIONAL NEOCORTICAL EPILEPSY

2011; 20:692-700

Purpose: To investigate whether interictal magnetoencephalography (MEG)
concordant with other techniques can predict surgical outcome in patients with
lesional and nonlesional refractory neocortical epilepsy (NE). Methods: 23
Patients with lesional NE and 20 patients with nonlesional NE were studied. MEG
was recorded for all patients with a 275 channel whole-head system. Synthetic
aperture magnetometry (SAM) with excess kurtosis (g2) and conventional
Equivalent Current Dipole (ECD) were used for MEG data analysis. 27 Patients
underwent long-term extraoperative intracranial video electroencephalography
(iVEEG) monitoring. Surgical outcomes were assessed based on more than 1-year
of post-surgical follow-up using Engel classification system. Results: As we
expected, both favorable outcomes (Engel class I or II) and seizure freedom
outcomes (Engel class IA) were higher for the concordance condition (MEG findings
are concordant with MRI or iVEEG findings) versus the discordance condition.
Also the seizure free rate was significantly higher (Ï‡2 = 5.24, P < 0.05)
for the patients with lesional NE than for the patients with nonlesional NE. In
30% of the patients with nonlesional NE, the MEG findings proved to be valuable
for intracranial electrode implantation. Conclusions: This study demonstrates
that a favorable post-surgical outcome can be obtained in most patients with
concordant MEG and MRI results even without extraoperative iVEEG monitoring,
which indicates that the concordance among different modalities could indicate
a likelihood of better postsurgical outcomes. However, extraoperative iVEEG
monitoring remains prerequisite to the patients with discordant MEG and MRI
findings. For nonlesional cases, our results showed that MEG could provide
critical information in the placement of intracranial electrodes. Â© 2011
British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Department of Neurosurgery, Brain Hospital Affiliated, Nanjing Medical
University, Nanjing, China MEG Center, Brain Hospital Affiliated, Nanjing
Medical University, Nanjing, China Department of Radiology, Brain Hospital
Affiliated, Nanjing Medical University, Nanjing, China MEG Center, Cincinnati
Children's Hospital Medical Center, Cincinnati, OH, United States Department of
Biomedical Engineering, University of Cincinnati, OH, United States Department
of Neurosurgery, First Hospital Affiliated, Nanjing Medical University, Nanjing
210029, China

10.1016/j.seizure.2011.06.021

http://www.ncbi.nlm.nih.gov/pubmed/21782477

(194)Zhou B, Wu Y and Lin X

RETROMER REGULATES APICAL-BASAL POLARITY THROUGH RECYCLING CRUMBS

2011; 360:87-95

Epithelial cells are characterized by an "apical-basal" polarization.
The transmembrane protein Crumbs (Crb) is an essential apical determinant which
confers apical membrane identity. Previous studies indicated that Crb did not constantly
reside on the apical membrane, but was actively recycled. However, the cellular
mechanism(s) underlying this process was unclear. Here we showed that in
Drosophila, retromer, which was a retrograde complex recycling certain
transmembrane proteins from endosomes to trans-Golgi network (TGN), regulated
Crb in epithelial cells. In the absence of retromer, Crb was mis-targeted into
lysosomes and degraded, causing a disruption of the apical-basal polarity. We
further showed that Crb co-localized and interacted with retromer, suggesting
that retromer regulated the retrograde recycling of Crb. Our data presented
here uncover the role of retromer in regulating apical-basal polarity in
epithelial cells and identify retromer as a novel regulator of Crb recycling.

Division of Developmental Biology, Cincinnati Children's Hospital Medical
Center, and the Graduate Program in Molecular and Developmental Biology,
University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

10.1016/j.ydbio.2011.09.009

http://www.ncbi.nlm.nih.gov/pubmed/21958744

CCHMC Authors' Publications

November-December 2011