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Acyanotic CHD constituted 96.3% of detected cases. Two children diagnosed with CHD (Tetralogy of Fallot and severe pulmonary valve stenosis respectively) had successful intervention. The prevalence of previously undiagnosed CHD among school children in Lagos Nigeria is substantial and highlights gaps in the health care system and school health programs. Echocardiographic screening of school children provides an opportunity for missed early diagnosis and treatment of CHD and reduces the prevalence of first-diagnosed CHD in adulthood. Therefore, focused clinical examination of school children followed by echocardiography is a strategy that could bridge this diagnostic and treatment gap in CHD. © 2020 Wiley Periodicals, Inc.BACKGROUND Exposure to ethanol during pregnancy is the cause of fetal alcohol spectrum disorder. The function of L1 cell adhesion molecule (L1), critical for proper brain development, is dependent on detergent-resistant membrane microdomains (DRM). Ethanol at low concentrations disrupts L1 function measured by inhibition of downstream signaling and alterations in L1-DRM distribution in cerebellum in vivo and in cerebellar granule neurons (CGN) in vitro. We have previously shown that choline pretreatment of CGN partially prevents ethanol toxicity through improving L1 function in vitro. Here we show that choline supplementation reduces the impact of ethanol on L1 in cerebellum in vivo. METHODS Pregnant rat dams were placed on choline free diet on gestational Day 5 (G5). Pups were treated with saline or choline from postnatal day (P) 1-5. On P5, pups were intubated twice 2 hr apart with ethanol or Intralipid® for a total dose of 6 g/kg/d and sacrificed 1 hr after the last intubation. The cerebella were harvested and L1 phosphorylation/dephosphorylation status and distribution in DRM were analyzed. RESULTS Ethanol reduced L1 tyrosine phosphorylation and L1-Y1176 dephosphorylation in cerebella, and caused an increase in the percent of L1 in DRM. Choline supplementation of pups reduced the ethanol-induced changes in L1 phosphorylation status and ameliorated ethanol-induced redistribution of L1 into DRM. CONCLUSION Choline supplementation before an acute dose of ethanol ameliorates changes in L1 in vivo. © 2020 Wiley Periodicals, Inc.The global burden of chronic kidney disease (CKD) is increasing with a projection of becoming the fifth leading cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the entire annual healthcare budget in high-income countries. Crucially, however, both the onset and progression of CKD is potentially preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions-be it primary, i.e. to prevent de novo CKD, or secondary or tertiary, i.e. prevention of worsening early CKD or progression of more advanced CKD to end-stage kidney disease, respectively. Primary prevention should focus on the modification of CKD risk factors and address the structural abnormalities of the kidney and urinary tracts, and exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization, glycemic control and avoiding high-protein high-sodium diet should be the main goal of education and clinical interventions. ZCL278 in vivo In patients with moderate to advanced CKD, the management of comorbidities such as uremia and cardiovascular disease along with low-protein diet are among the recommended preventative interventions to avoid or delay dialysis or kidney transplantation. Whereas national policies and strategies for noncommunicable diseases may exist in a country, specific policies directed toward education and awareness about CKD screening, prevention and treatment are often lacking. There is an urgent need to increase awareness for preventive measures throughout populations, professionals and policy makers. © 2020 European Dialysis and Transplant Nurses Association/European Renal Care Association.Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of β-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Cerebro-oculo-facio-skeletal syndrome (COFS) is a rare autosomal recessive neurodegenerative disease belonging to the family of DNA repair disorders, characterized by microcephaly, congenital cataracts, facial dysmorphism and arthrogryposis. Here, we describe the detailed morphological and microscopic phenotype of three fetuses from two families harboring ERCC5/XPG likely pathogenic variants, and review the five previously reported fetal cases. In addition to the classical features of COFS, the fetuses display thymus hyperplasia, splenomegaly and increased hematopoiesis. Microencephaly is present in the three fetuses with delayed development of the gyri, but normal microscopic anatomy at the supratentorial level. Microscopic anomalies reminiscent of pontocerebellar hypoplasia are present at the infratentorial level. In conclusion, COFS syndrome should be considered in fetuses when intrauterine growth retardation is associated with microcephaly, arthrogryposis and ocular anomalies. Further studies are needed to better understand XPG functions during human development.
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