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Severe health proteins insufficiency induces hepatic term and wide spread level of FGF21 yet inhibits its hypothalamic expression inside developing test subjects.
CONTEXT Immune checkpoint inhibitors (ICIs), as anti-programmed cell death protein-1 (PD-1), anti-programmed cell death protein-ligand 1 (PD-L1), and anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some types of advanced cancer. Their main treatment-related side-effects are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Hypoparathyroidism, on the contrary, is an extremely rare irAE. OBJECTIVES The aim of the study was to investigate the etiology of autoimmune hypoparathyroidism in a lung cancer patient treated with pembrolizumab, an anti-PD-1. METHODS Calcium-sensing receptor (CaSR) autoantibodies, their functional activity, Ig subclasses and epitopes involved in the pathogenesis of autoimmune hypoparathyroidism were tested. RESULTS The patient developed hypocalcemia after 15 cycles of pembrolizumab. Calcium levels normalised with oral calcium carbonate and calcitriol and no remission of hypocalcemia was demonstrated during a nine-month follow-up. The patient was found to be positive for CaSR-stimulating antibodies, of IgG1 and IgG3 subclasses, that were able to recognize functional epitopes on the receptor, thus causing hypocalcemia. CONCLUSION The finding confirms that ICIs therapy can trigger, amongst other endocrinopathies, hypoparathyroidism which can be caused by pathogenic autoantibodies. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail [email protected] control strategies recommended by the World Health Organization are threatened by resistance of Anopheles mosquitoes to insecticides. Information on the distribution of resistant genotypes of malaria vectors is increasingly needed to address the problem. Ten years of published and unpublished data on malaria vector susceptibility/resistance and resistance genes have been collected across Togo. Relationships between the spatial distribution of resistance status and environmental, socio-economic, and landscape features were tested using randomization tests, and calculating Spearman rank and Pearson correlation coefficients between mosquito mortality and different gridded values. Anopheles gambiae sensu lato was resistant to DDT, pyrethroids, and the majority of carbamates and organophosphates. Three sibling species were found (i.e., An. gambiae, Anopheles coluzzii, and Anopheles arabiensis) with four resistance genes, including kdr (L1014F, L1014S, and N1575Y) and ace1 (G119S). The most frequent resistance gene was L1014F. Overall, no association was found between the susceptibility/resistance status and environmental features, suggesting that evolution of resistance may be most closely related to extreme selection from local insecticide use. Nevertheless, further research is necessary for firm conclusions about this lack of association, and the potential role of landscape characteristics such as presence of crops and percentage of tree cover. © The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America.All rights reserved. For permissions, please e-mail [email protected] management of laryngotracheal stenosis (LTS) in the pediatric burn patient is complex and requires a multi-disciplinary approach. The mainstay of treatment for LTS is laryngotracheal reconstruction (LTR), however, limited reports of burn-specific laryngotracheal reconstruction techniques exist. Here, we provide insight into the initial airway evaluation, surgical decision-making, anesthetic challenges, and incision modifications based on our experience in treating patients with this pathology. The initial airway evaluation can be complicated by microstomia, trismus and neck contractures - the authors recommend treatment of these complications prior to initial airway evaluation to optimize safety. The surgical decision-making regarding pursuing single-stage LTR, double-stage LTR, and 1.5 stage LTR can be challenging - the authors recommend 1.5 stage LTR when possible due to the extra safety of rescue tracheostomy and the decreased risk of granuloma, which is especially important in pro-inflammatory burn physiology. Anesthetic challenges include obtaining intravenous access, securing the airway, and intravenous induction - the authors recommend peripherally inserted central catheter (PICC) when appropriate, utilizing information from the initial airway evaluation to secure the airway, and avoidance of succinylcholine upon induction. Neck and chest incisions are often within the total body surface (TBSA) covered by the burn injury - the authors recommend modifying typical incisions to cover unaffected skin whenever possible in order to limit infection and prevent wound healing complications. Pediatric laryngotracheal reconstruction in the burn patient is challenging, but can be safe when the surgeon is thoughtful in their decision-making. © The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail [email protected] Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. check details However, Fst and activin A's implication in metabolic regulation is unclear. OBJECTIVE To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon. METHODS Plasma Fst and activin A levels were analyzed in obese T2D patients (N=10) closely matched to glucose-tolerant lean (N=12) and obese (N=10) individuals in the fasted state and following a 4-hour hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry. RESULTS Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese non-diabetic individuals (p0.47; p less then 0.05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose).
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