Acrofacial Dysostosis, Cincinnati Type, a Mandibulofacial Dysostosis Syndrome with Limb Anomalies, Is Caused by POLR1A Dysfunction.

We report three individuals with a cranioskeletal malformation syndrome that we define as acrofacial dysostosis, Cincinnati type. Each individual has a heterozygous mutation in POLR1A, which encodes a core component of RNA polymerase 1. All three individuals exhibit varying degrees of mandibulofacial dysostosis, and two additionally have limb anomalies.

Definitions of cardiovascular insufficiency and relation to outcomes in critically ill newborn infants.

Background: We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants.

Objective: This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death.

The Warburg effect in mycobacterial granulomas is dependent on the recruitment and activation of macrophages by interferon-γ.

Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-γ (IFN-γ). Mycobacterium avium-infected mice lacking IFN-γ signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG).

Genome-wide characterisation of Foxa1 binding sites reveals several mechanisms for regulating neuronal differentiation in midbrain dopamine cells.

Midbrain dopamine neuronal progenitors develop into heterogeneous subgroups of neurons, such as substantia nigra pars compacta, ventral tegmental area and retrorubal field, that regulate motor control, motivated and addictive behaviours. The development of midbrain dopamine neurons has been extensively studied, and these studies indicate that complex cross-regulatory interactions between extrinsic and intrinsic molecules regulate a precise temporal and spatial programme of neurogenesis in midbrain dopamine progenitors. To elucidate direct molecular interactions between multiple regulatory factors during neuronal differentiation in mice, we characterised genome-wide binding sites of the forkhead/winged helix transcription factor Foxa1, which functions redundantly with Foxa2 to regulate the differentiation of mDA neurons.

Long-Term Behavioral Outcomes after a Randomized, Clinical Trial of Counselor-Assisted Problem Solving for Adolescents with Complicated Mild-to-Severe Traumatic Brain Injury.

Family problem-solving therapy (FPST) has been shown to reduce behavior problems after pediatric traumatic brain injury (TBI). It is unclear whether treatment gains are maintained. We sought to evaluate the maintenance of improvements in behavior problems after a Web-based counselor-assisted FPST (CAPS) intervention compared to an Internet resource comparison (IRC) intervention provided to adolescents within the initial year post-TBI.

Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction.

Intrauterine growth restriction (IUGR) due to placental insufficiency is a leading cause of perinatal complications for which there is no effective prenatal therapy. We have previously demonstrated that intraplacental injection of adenovirus-mediated insulin-like growth factor-1 (Ad-IGF-1) corrects fetal weight in a murine IUGR model induced by mesenteric uterine artery branch ligation. This study investigated the effect of intraplacental Ad-IGF-1 gene therapy in a rabbit model of naturally occurring IUGR (runt) due to placental insufficiency, which is similar to the human IUGR condition with onset in the early third trimester, brain sparing, and a reduction in liver weight.

Randomized, double-blind, dose-escalation trial of triptorelin for ovary protection in childhood-onset systemic lupus erythematosus.

Objective: To determine the dose of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy, to determine the length of time needed to achieve ovarian suppression after initiation of triptorelin treatment, and to investigate the safety of triptorelin.

Methods: In this randomized, double-blind, placebo-controlled, dose-escalation study, female patients ages <21 years were randomized 4:1 to receive triptorelin (n = 25) or placebo (n = 6). The starting doses of triptorelin were 25, 50, 75, and 100 μg/kg, and the dose was escalated until complete ovarian suppression was maintained.

Online problem-solving therapy after traumatic brain injury: a randomized controlled trial.

Background: Pediatric traumatic brain injury (TBI) contributes to impairments in functioning in everyday settings. Evidence suggests that online family problem-solving therapy (FPST) may be effective in reducing adolescent behavioral morbidity. This article examines the efficacy of Counselor-Assisted Problem Solving (CAPS), a form of online FPST in improving long-term functional outcomes of adolescents with TBI relative to Internet resources only.

NK cells and their ability to modulate T cells during virus infections.

Natural killer (NK) cells are important in protection against virus infections, and many viruses have evolved mechanisms to thwart NK cell activity. NK cells respond to inflammatory signals at an early stage of virus infection, resulting in proliferation, cytokine production, and cytolytic activity that can reduce virus loads. Moreover, the rapid kinetics of the NK cell response enables NK cells to influence other populations of innate immune cells, affect the inflammatory milieu, and guide adaptive immune responses to infection.

CNS, lung, and lymph node involvement in Gaucher disease type 3 after 11 years of therapy: clinical, histopathologic, and biochemical findings.

A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at an age of 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs.

C5a and bradykinin receptor cross-talk regulates innate and adaptive immunity in Trypanosoma cruzi infection.

Complement and the kallikrein-kinin cascade system are both activated in injured tissues. Little is known about their partnership in the immunopathogenesis of Chagas disease, the chronic infection caused by the intracellular protozoan Trypanosoma cruzi. In this study, we show that pharmacological targeting of the C5a receptor (C5aR) or the bradykinin B2 receptor (B2R) inhibited plasma leakage in hamster cheek pouch topically exposed to tissue culture trypomastigotes (TCTs).

Vasculopathy in the young Turner syndrome population.

Context: Turner syndrome (TS) carries an increased risk for vascular disease, or vasculopathy.

Objective: Vasculopathy can be detected in young TS patients.

Design And Patients: Vasculopathy was prospectively assessed by measuring vascular function and structure in TS patients (n = 49) and lean (L) (n = 76) and obese (O) controls (n = 52) through noninvasive techniques.

Long-term benefits of an early online problem-solving intervention for executive dysfunction after traumatic brain injury in children: a randomized clinical trial.

Importance: Executive dysfunction after traumatic brain injury (TBI) in children is common and leads to significant short- and long-term problems in functioning across multiple settings. We hypothesized that improvements in short-term executive function would be maintained to 24 months after injury and that improvements would increase over time in a counselor-assisted problem-solving (CAPS) intervention.

Objective: To evaluate the efficacy of a CAPS intervention administered within 7 months of complicated mild to severe TBI compared with an Internet resource condition in improving long-term executive dysfunction.

Interventions for attention problems after pediatric traumatic brain injury: what is the evidence?

Objective: To gain an understanding of the current state of the evidence for management of attention problems after traumatic brain injury (TBI) in children, determine gaps in the literature, and make recommendations for future research. TYPE: Focused systematic review.

Literature Survey: PubMed/Medline and PsychINFO databases were searched for relevant articles published in English during the last 20 years.

Thrombin drives tumorigenesis in colitis-associated colon cancer.

The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/- mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge.

Single-session motivational intervention to decrease alcohol use during pregnancy.

This randomized clinical trial tested the effectiveness of a single-session of motivational interviewing (MI) to decrease alcohol use during pregnancy, while examining theory-based mechanisms of the intervention. Eligible pregnant women who drank any amount of alcohol in the previous year (n=122) were randomized to an intervention or comparison group. Drinking behaviors, basic psychological need satisfaction, and autonomous motivation to decrease prenatal alcohol use were measured at baseline, 30 day postbaseline, and 30 day postpartum follow-ups.

Behavioral predictors of outpatient mental health service utilization within 6 months after traumatic brain injury in adolescents.

Objectives: To characterize utilization of mental health services and determine the ability of a behavior problem and clinical functioning assessment to predict utilization of such services within the first 6 months after moderate and severe traumatic brain injury in a large cohort of adolescents.

Design: Multicenter cross-sectional study.

Setting: Outpatient setting of 4 tertiary pediatric hospitals, 2 tertiary general medical centers, and 1 specialized children's hospital.

Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis.

Objective: To determine the long-term safety and efficacy of rilonacept, an anti-interleukin-1 fusion protein, in patients with active systemic juvenile idiopathic arthritis (JIA).

Methods: In patients with systemic JIA, ages 4-20 years, the efficacy of rilonacept was evaluated using 30%, 50%, and 70% levels of improvement according to the adapted American College of Rheumatology (ACR) Pediatric 30, 50, and 70 response criteria, respectively. Efficacy and safety were evaluated during 23 months of open-label treatment (3 phases) after a 4-week, double-blind, placebo-controlled phase.

Online problem-solving therapy for executive dysfunction after child traumatic brain injury.

Objective: Executive dysfunction after traumatic brain injury (TBI) in children is common and leads to significant problems in functioning across multiple settings. The objective of this study was to evaluate the efficacy of a web-based counselor-assisted problem solving (CAPS) intervention compared with an Internet resource comparison (IRC) for treatment of executive dysfunction within 12 months after complicated mild to severe TBI in adolescents. We hypothesized that CAPS would significantly improve parent ratings of executive dysfunction compared with an IRC.

Impact of Depression and Childhood Trauma in Mothers Receiving Home Visitation.

Research has documented the deleterious effects of maternal depression and childhood trauma on parenting and child development. There are high rates of both depression and childhood trauma in new mothers participating in home visitation programs, a prevention approach designed to optimize mother and child outcomes. Little is known about the impacts of maternal depression and childhood trauma on parenting in the context of home visitation.

A multicenter study of the risk of intra-abdominal injury in children after normal abdominal computed tomography scan results in the emergency department.

Study Objective: We determine whether intra-abdominal injury is rarely diagnosed after a normal abdominal computed tomography (CT) scan result in a large, generalizable sample of children evaluated in the emergency department (ED) after blunt torso trauma.

Methods: This was a planned analysis of data collected during a prospective study of children evaluated in one of 20 EDs in the Pediatric Emergency Care Applied Research Network. The study sample consisted of patients with normal results for abdominal CT scans performed in the ED.

DTI values in key white matter tracts from infancy through adolescence.

Background And Purpose: DTI is an advanced neuroimaging technique that allows in vivo quantification of water diffusion properties as surrogate markers of the integrity of WM microstructure. In our study, we investigated normative data from a large number of pediatric and adolescent participants to examine the developmental trends in DTI during this conspicuous WM maturation period.

Materials And Methods: DTI data in 202 healthy pediatric and adolescent participants were analyzed retrospectively.

Foxm1 transcription factor is required for lung fibrosis and epithelial-to-mesenchymal transition.

Alveolar epithelial cells (AECs) participate in the pathogenesis of pulmonary fibrosis, producing pro-inflammatory mediators and undergoing epithelial-to-mesenchymal transition (EMT). Herein, we demonstrated the critical role of Forkhead Box M1 (Foxm1) transcription factor in radiation-induced pulmonary fibrosis. Foxm1 was induced in AECs following lung irradiation.