Proximity of the neurovascular structures during all-inside lateral meniscal repair in children: a cadaveric study.

Purpose: Meniscal repair has become increasingly common in a pediatric and adolescent population. All-inside repair techniques are utilized more often given their ease of insertion and decreased operative time required. However, there are possible risks including damage to adjacent neurovascular structures.

Human immunodeficiency virus-related cerebral white matter disease in children.

The human immunodeficiency virus (HIV) epidemic seems largely controlled by anti-retroviral treatment with resultant large numbers of children growing up with the disease on long-term treatment, placing them at higher risk to develop HIV-related brain injury, ongoing cognitive impairment and treatment-related neurological complications. Cerebral white matter involvement is a common radiologic finding in HIV infection and the causes of this have overlapping appearances, ranging from diffuse widespread involvement to focal lesions. The varied pathophysiology is broadly grouped into primary effects of HIV, opportunistic infection, vascular disease and neoplasms.

Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study.

Background: Paediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS.

Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies.

Background: Fetal atrioventricular block (AVB) occurs in 2% to 4% of anti-Ro antibody-positive pregnancies and can develop in <24 h. Only rarely has standard fetal heart rate surveillance detected AVB in time for effective treatment.

Objectives: Outcome of anti-Ro pregnancies was surveilled with twice-daily home fetal heart rate and rhythm monitoring (FHRM) and surveillance echocardiography.

The genetic landscape of severe combined immunodeficiency in the United States and Canada in the current era (2010-2018).

In a 250 patient cohort from the US and Canada in the current era (2010–2018), we show that over 90% of patients with severe combined immunodeficiency (SCID) can be genetically-characterized.

Identification of p38 MAPK as a novel therapeutic target for Friedreich's ataxia.

Friedreich ataxia (FRDA) is an autosomal recessive neuro- and cardio-degenerative disorder caused by decreased expression of frataxin, a protein that localizes to mitochondria and is critical for iron-sulfur-cluster (ISC) assembly. There are no proven effective treatments for FRDA. We previously screened a random shRNA library and identified a synthetic shRNA (gFA11) that reverses the growth defect of FRDA cells in culture.

Heart sounds at home: feasibility of an ambulatory fetal heart rhythm surveillance program for anti-SSA-positive pregnancies.

Objective: Fetuses exposed to anti-SSA (Sjögren's) antibodies are at risk of developing irreversible complete atrioventricular block (CAVB), resulting in death or permanent cardiac pacing. Anti-inflammatory treatment during the transition period from normal heart rhythm (fetal heart rhythm (FHR)) to CAVB (emergent CAVB) can restore sinus rhythm, but detection of emergent CAVB is challenging, because it can develop in ⩽24 h. We tested the feasibility of a new technique that relies on home FHR monitoring by the mother, to surveil for emergent CAVB.

Systemic onset juvenile idiopathic arthritis and exposure to fine particulate air pollution.

Objectives: Fine particulate matter (PM2.5) is a measurable component of ambient pollution, and positive associations of short-term PM2.5 exposure with the clinical presentation of systemic onset juvenile idiopathic arthritis (SJIA) in young children have been described in a regional cohort.

Autism Spectrum Disorder, Developmental and Psychiatric Features in 16p11.2 Duplication.

The 16p11.2 duplication (BP4-BP5) is associated with Autism Spectrum Disorder (ASD), although significant heterogeneity exists. Quantitative ASD, behavioral and neuropsychological measures and DSM-IV diagnoses in child and adult carriers were compared with familial non-carrier controls, and to published results from deletion carriers.

Evaluation of Pre-Hematopoietic Cell Transplantation (HCT) Brain MRI and Neurologic Complications of Pediatric Patients Undergoing HCT for Hematologic Malignancies.

Adverse neurologic complications (NC) occur commonly in pediatric patients with hematologic malignancies both pre- and post-allogeneic hematopoietic cell transplant (HCT). Given this known risk, we previously obtained pre-HCT brain magnetic resonance imaging (MRI) to document baseline abnormalities but utility of this and findings are not well described. This study aimed to ( a) determine the prevalence and risk factors for abnormal brain MRI and ( b) determine prevalence and risk factors for development of new NC during and 2 years post-HCT.

Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity.

Eosinophilic esophagitis (EoE) is a chronic disease characterized clinically by symptoms of esophageal dysfunction and histologically by eosinophil-predominant inflammation. EoE is frequently associated with concomitant atopic diseases and immunoglobulin E (IgE) sensitization to food allergens in children as well as to aeroallergens and cross-reactive plant allergen components in adults. Patients with EoE respond well to elemental and empirical food elimination diets.

Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications.

Transfusion complications in thalassemia patients: a report from the Centers for Disease Control and Prevention (CME).

Background: Transfusions are the primary therapy for thalassemia but have significant cumulative risks. In 2004, the Centers for Disease Control and Prevention (CDC) established a national blood safety monitoring program for thalassemia. This report summarizes the population and their previous nonimmune and immune transfusion complications.

Developmental origins of diabetes: The role of oxidative stress.

The 'thrifty phenotype' hypothesis proposes that the fetus adapts to an adverse intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure survival, but by favoring the development of certain organs over that of others, this leads to persistent alterations in the growth and function of developing tissues. This concept has been somewhat controversial, however recent epidemiological, clinical, and animal studies provide support for the developmental origins of disease hypothesis. Underlying mechanisms include reprogramming of the hypothalamic-pituitary-adrenal axis, islet development, and insulin signaling pathways.

A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci.

Diabetes impacts approximately 200 million people worldwide, of whom approximately 10% are affected by type 1 diabetes (T1D). The application of genome-wide association studies (GWAS) has robustly revealed dozens of genetic contributors to the pathogenesis of T1D, with the most recent meta-analysis identifying in excess of 40 loci. To identify additional genetic loci for T1D susceptibility, we examined associations in the largest meta-analysis to date between the disease and ∼2.

Incidence of and risk factors for community acquired pneumonia in US HIV-infected children, 2000-2005.

The incidence of and risk factors for community-acquired pneumonia (CAP) are described from 2000 to 2005 in a multicenter US cohort of HIV-infected children. In 736 patients, 87 episodes of CAP (33.2 events/1000 person-years) had a mean CD4% of 23% (controls: 30%) and mean CD4 cell count of 668 cells/μl (controls: 870 cells/μl).

Epigenetics and maternal nutrition: nature v. nurture.

Under- and over-nutrition during pregnancy has been linked to the later development of diseases such as diabetes and obesity. Epigenetic modifications may be one mechanism by which exposure to an altered intrauterine milieu or metabolic perturbation may influence the phenotype of the organism much later in life. Epigenetic modifications of the genome provide a mechanism that allows the stable propagation of gene expression from one generation of cells to the next.

Epigenetic mechanisms in the development of type 2 diabetes.

Type 2 diabetes (T2D) is a disorder of complex genetics influenced by interactions between susceptible genetic loci and environmental perturbations. Intrauterine growth retardation is one such environmental perturbation linked to the development of T2D in adulthood. An abnormal metabolic intrauterine milieu affects fetal development by permanently modifying expression of key genes regulating beta-cell development (Pdx1) and glucose transport (Glut4) in muscle.

Perinatal programming of obesity.

Obesity is a growing threat worldwide, and the prevalence has risen dramatically over the last decade. A number of epidemiological studies have shown that there is a direct relationship between birth weight and BMI in childhood and in adult life. A number of factors influence the development of childhood and adult obesity and birth weight as a proxy for the intrauterine environment may be one of the many.

Developmental origins of diabetes: the role of epigenetic mechanisms.

Purpose Of Review: Intrauterine growth retardation has been linked to later development of type 2 diabetes. An abnormal intrauterine milieu affects the development of the fetus by permanently modifying gene expression of susceptible cells. Altered gene expression persists after birth suggesting that an epigenetic mechanism may be responsible for changes in transcription.

Role of metabolic programming in the pathogenesis of beta-cell failure in postnatal life.

Intrauterine growth retardation (IUGR) has been linked to later development of type 2 diabetes in adulthood. Human studies indicate that individuals who were growth retarded at birth have impaired insulin secretion and insulin resistance. Multiple animal models of IUGR demonstrate impaired beta-cell function and development.

Developmental origins of beta-cell failure in type 2 diabetes: the role of epigenetic mechanisms.

Intrauterine growth retardation (IUGR) has been linked to later development of type 2 diabetes in adulthood. An abnormal metabolic intrauterine milieu affects the development of the fetus by permanently modifying gene expression of susceptible cells. Altered gene expression persists after birth, suggesting that an epigenetic mechanism may be responsible for changes in transcription.

Developmental origins of diabetes: the role of oxidative stress.

The "thrifty phenotype" hypothesis proposes that the fetus adapts to an adverse intrauterine milieu by optimizing the use of a reduced nutrient supply to ensure survival, but, by favoring the development of certain organs over that of others, this leads to persistent alterations in the growth and function of developing tissues. This concept has been somewhat controversial; however, recent epidemiological, clinical, and animal studies provide support for the developmental origins of disease hypothesis. Underlying mechanisms include reprogramming of the hypothalamic-pituitary-adrenal axis, islet development, and insulin signaling pathways.