Locomotor Training in the Pediatric Spinal Cord Injury Population: A Systematic Review of the Literature

Purpose: The aim of this review was to investigate the effects of locomotor training on pediatric SCI and develop recommendations for pediatric LT guidelines.https://jdc.jefferson.edu/dptcapstones/1002/thumbnail.jp

Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features

SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and consequently which of the three major SOX5 protein isoforms are affected. One intragenic deletion involving only untranslated exons was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene

High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide.

A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota

Mutations in the Human UBR1 Gene and the Associated Phenotypic Spectrum

Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n=29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. the review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. for all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.German Research FoundationUniv Hosp Magdeburg, Inst Human Genet, D-39120 Magdeburg, GermanyUniv Hosp Erlangen, Inst Human Genet, Erlangen, GermanyHosp Nacl Ninos Dr Carlos Saenz Herrera, Dept Med, San Jose, Costa RicaKlinikum Bremen Mitte, Bremen, GermanyCHU Vaudois, Dept Med Genet, CH-1011 Lausanne, SwitzerlandUniv Hosp, Dept Pediat Surg, Poitiers, FranceHosp La Fe, Dept Pediat, E-46009 Valencia, SpainAMC Univ Hosp, Dept Pediat Genet, Amsterdam, NetherlandsVanderbilt Univ, Monroe Carell Jr Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Nashville, TN 37235 USACleveland Clin, Genom Med Inst, Cleveland, OH 44106 USAGuys Hosp, London SE1 9RT, EnglandKariminejad Najmabadi Pathol & Genet Ctr, Tehran, IranGreenwood Genet Ctr, Greenwood, SC 29646 USAUmea Univ, Dept Med Biosci Med & Clin Genet, Umea, SwedenWomens & Childrens Hosp, SA Clin Genet Serv, Adelaide, SA, AustraliaStiftung Deutsch Klin Diagnost GmbH, Fachbereich Kinder & Jugendmed, Wiesbaden, GermanyUniv São Paulo, Dept Pediat, São Paulo, BrazilUniv British Columbia, Dept Pediat, Div Biochem Dis, BC Childrens Hosp, Vancouver, BC V6T 1W5, CanadaCtr Human Genet, Ingelheim, GermanyNanjing Med Univ, Nanjing Childrens Hosp, Dept Digest Dis, Nanjing, Jiangsu, Peoples R ChinaUniv Klinikum Bonn, Zentrum Kinderheilkunde, Bonn, GermanyUniv Tehran Med Sci, Childrens Med Ctr, Res Ctr Immunodeficiencies, Tehran, IranUniv Tehran Med Sci, Dept Immunol, Tehran, IranKing Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi ArabiaOndokuz Mayis Univ, Dept Med, Samsun, TurkeyOndokuz Mayis Univ, Dept Pediat Genet, Samsun, TurkeyAl Thawra Teaching Hosp, Dept Pediat, Sanaa, YemenHosp Gen Mexico City, Fac Med, Dept Human Genet, Mexico City, DF, MexicoUniv Med Ctr Utrecht, Dept Med Genet, Utrecht, NetherlandsNatl Childrens Hosp, San Jose, Costa RicaSisli Etfal Res Hosp, Dept Med Genet, Istanbul, TurkeyNizams Inst Med Sci, Dept Med Genet, Hyderabad, Andhra Pradesh, IndiaMaulana Azad Med Coll, Dept Pediat, New Delhi, IndiaDeenanath Mangeshkar Hosp & Res Ctr, Dept Genet, Erandawane, IndiaMinist Hlth, Dept Pediat, Manama, BahrainUniv Fed Bahia, Fac Med, Hosp Univ Prof Edgar Santos, Pediat Endocrinol Unit, Salvador, BA, BrazilErnst Moritz Arndt Univ Greifswald, Univ Med, Dept Med A, Greifswald, GermanyTech Univ Munich, Else Kroner Fresenius Zentrum Ernahrungsmed, Freising Weihenstephan, GermanyTech Univ Munich, Zent Inst Ernahrungs & Lebensmittelforsch, Freising Weihenstephan, GermanyTech Univ Munich, Klinikum Rechts Isar, Dept Pediat, D-80290 Munich, GermanyGerman Research Foundation: DFG ZE 524/2-3Web of Scienc