Boston Children's Hospital

About: Boston Children's Hospital is a healthcare organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 165409 authors who have published 215589 publications receiving 6885627 citations.

Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome

Abstract: Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.

The mental health of young people in Australia: key findings from the child and adolescent component of the national survey of mental health and well‐being

Abstract: Objective: To identify the prevalence of three mental disorders (Depressive Disorder, Conduct Disorder and Attention-Deficit/Hyperactivity Disorder), the prevalence of mental health problems, the health-related quality of life of those with problems, and patterns of service utilisation of those with and without mental health problems, among 4–17-year-olds in Australia. To identify rates of health-risk behaviours among adolescents with mental health problems.Method: The mental disorders were assessed using the parent-version of the Diagnostic Interview Schedule for Children Version IV. Parents completed the Child Behaviour Checklist to identify mental health problems and standard questionnaires to assess healthrelated quality of life and service use. The Youth Risk Behaviour Questionnaire completed by adolescents was employed to identify health-risk behaviours.Results: Fourteen percent of children and adolescents were identified as having mental health problems. Many of those with mental health problems ha...

The new neurometabolic cascade of concussion

Abstract: Objective: To review the underlying pathophysiologic processes of concussive brain injury and relate these neurometabolic changes to clinical sports-related issues such as injury to the developing brain, overuse injury, and repeated concussion. Data Sources: Over 100 articles from both basic science and clinical medical literature selected for relevance to concussive brain injury, postinjury pathophysiology, and recovery of function. Data Synthesis: The primary elements of the pathophysiologic cascade following concussive brain injury include abrupt neuronal depolarization, release of excitatory neurotransmitters, ionic shifts, changes in glucose metabolism, altered cerebral blood flow, and impaired axonal function. These alterations can be correlated with periods of postconcussion vulnerability and with neurobehavioral abnormalities. While the time course of these changes is well understood in experimental animal models, it is only beginning to be characterized following human concussion. Conclusions/Recommendations: Following concussion, cerebral pathophysiology can be adversely affected for days in animals and weeks in humans. Significant changes in cerebral glucose metabolism can exist even in head-injured patients with normal Glasgow Coma Scores, underscoring the need for indepth clinical assessment in an effort to uncover neurocognitive correlates of altered cerebral physiology. Improved guidelines for clinical management of concussion may be formulated as the functional significance and duration of these postinjury neurometabolic derangements are better delineated.

A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis

Abstract: The progressive familial intrahepatic cholestases (PFIC) are a group of inherited disorders with severe cholestatic liver disease from early infancy. A subgroup characterized by normal serum cholesterol and gamma-glutamyltranspeptidase (gammaGT) levels is genetically heterogeneous with loci on chromosomes 2q (PFIC2) and 18q. The phenotype of the PFIC2-linked group is consistent with defective bile acid transport at the hepatocyte canalicular membrane. The PFIC2 gene has now been identified by mutations in a positional candidate, BSEP, which encodes a liver-specific ATP-binding cassette (ABC) transporter, sister of p-glycoprotein (SPGP). The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP).