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Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients. This article is protected by copyright. All rights reserved.Several encouraging pre-clinical results highlight the melanin-concentrating hormone receptor 1 (MCHR1) as promising target for anti-obesity drug development. Currently however, experimentally resolved structures of MCHR1 are not available, which complicates rational drug design campaigns. check details In this study, we aimed at developing accurate, homologymodel-based 3D pharmacophores against MCHR1. We show that traditional approaches involving docking of known active small molecules are hindered by the flexibility of binding pocket residues. Instead, we derived three-dimensional pharmacophores from molecular dynamics simulations by employing our novel open-source software PyRod. In a retrospective evaluation, the generated 3D pharmacophores were highly predictive returning up to 35 % of active molecules and showing an early enrichment (EF1) of up to 27.6. Furthermore, PyRod pharmacophores demonstrate higher sensitivity than ligand-based pharmacophores and deliver structural insights, which are key to rational lead optimization. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.BACKGROUND To review the performance of noninvasive prenatal screening (NIPS) using targeted single-nucleotide polymorphisms (SNPs) approach in mixed-risk Thai women. METHODS Retrospective analysis of data for detection of trisomy 21 (T21), 18 (T18), 13 (T13), monosomy X (XO), other sex chromosome aneuploidies (SCA), and triploidy/vanishing twins (VT) from a single commercial laboratory. RESULTS Mean (±SD) gestational age and maternal weight were 13.2 (±2.1) weeks and 125.7 (±22.4) pounds, respectively (n = 8,572). From 462/8,572 (5.4%) no-calls; 1/462 (0.2%) was uninformative SNPs, and 1/462 chose amniocentesis. Redraw settled 323/460 (70%) samples with low fetal fraction (FF); and 8,434/8,572 (98.4%) were finally reportable, with 131 high risks (1.6%). The median (min-max) FF of reportable (n = 8,434) and unreportable samples (n = 137) samples were 10.5% (2.6-37.9) and 3.8% (1-14.1), respectively (p  less then  .05). Fetal karyotypes were available in 106/131 (80.9%) and 52/138 (37.7%) high risk and repeated no-calls, respectively. The positive predictive values (PPVs) for T21 (n = 47), T18 (n = 15), T13 (n = 7), XO (n = 8), other SCA (n = 7), and triploidy/VT were 94%, 100%, 58.3%, 66.7%, 70%, and 57.1%, respectively. None of repeated no-calls had aneuploidies. CONCLUSION SNP-based NIPS has high PPVs for T21 and T18. Although the proprietary SNPs library is not population-specific, uninformative SNPs are uncommon. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.BACKGROUND Anhydramnios results from the poor development of the placenta or problems with intrauterine development of the kidneys or urinary tract. Complete lack of amniotic fluid indicates a severe problem with the organs of the urinary system. The genes associated with anhydramnios show very diversity and are not yet well defined. METHODS Whole-exome sequencing (WES) was used for an aborted male case around the 20th week of gestation diagnosed with anhydramnios. The resulted deleterious variants were verified by Sanger sequencing. Pathogenicity of deleterious variants was explored by in silico analysis. RESULTS A maternally inherited deleterious frameshift variant, c.1454_1455insC, p.(S486Ffs29) in exon 9 and two paternally inherited missense variants c.1037C > G, p.(Ser346Trp) in exon 7 and c.1465A > G, p.(Asn489Asp) in exon 9 of Angiotensin-I-Converting Enzyme (ACE) gene were found and confirmed by Sanger sequencing. c.1454_1455insC, p.(S486Ffs29) and c.1037C > G, p.(Ser346Trp) were identified as two novel compound heterozygous deleterious variants. The pathogenicity of these deleterious variants was determined by in silico analysis and both the deleterious variants disrupt the structure of the ACE protein. CONCLUSION Two novel compound heterozygous variants were identified in the case with anhydramnios, which may be associated with pathogenicity of anhydramnios. Our data also revealed that the WES approach may provide helpful information for genetic counseling of the families with anhydramnios. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.OBJECTIVES This research aimed to explain how the Safe Recovery Programme (SRP) may best work to reduce falls in older adults undergoing rehabilitation in four wards in an older person's health and rehabilitation service. METHODS Qualitative realist methods were used, including surveys completed by patients and staff, and qualitative interviews or focus groups exploring views of patients, ward staff and SRP educators. RESULTS Emphasising different types of information for patients with different pre-existing understandings may facilitate their responses to SRP messaging. Consistency and coherence of SRP messaging within ward routines varied in response to staff SRP training and ongoing feedback mechanisms from SRP educators. CONCLUSIONS Tailored individualised approaches for patients with specific characteristics may lead to patients being less likely to engage in risky behaviours. Staff training and processes for facilitating ongoing feedback between patients, SRP and ward staff are required to ensure consistency and coherence of SRP messaging. © 2020 AJA Inc.Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR activation in cognitive deficits of rodent developmental models of schizophrenia, we show that chronic administration of ∆9-tetrahydrocannabinol (THC) to mice during adolescence induces a long-lasting activation of mTOR in prefrontal cortex (PFC), alterations of excitatory/inhibitory balance, intrinsic properties of layer V pyramidal neurons, and long-term depression, as well as cognitive deficits in adulthood. All are prevented by administrating a 5-HT6 receptor antagonist or rapamycin, during adolescence. In contrast, they are still present 2 weeks after the same treatments delivered at the adult stage. Collectively, these findings suggest a role of 5-HT6 receptor-operated mTOR signaling in abnormalities of cortical network wiring elicited by THC at a critical period of PFC maturation and highlight the potential of 5-HT6 receptor antagonists as early therapy to prevent cognitive symptom onset in adolescent cannabis abusers.