Single-nucleotide polymorphisms (SNPs) in FSHB and FSHR genes have been described, some of them impacting testicular volume and sperm output. The FSHR p.N680S and the FSHB -211G>T variants could be genetic marker to predict FSH response. CONCLUSIONS FSH may be helpful to increase sperm production in infertile men, even if the evidence to recommend the use of FSH in this setting is weak. Placebo-controlled clinical trials, considering FSHB-FSHR haplotype, are needed to define the most effective dosage, the best treatment length and the criteria to select candidate responder patients. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding with obvious reasons are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that impact the biosynthesis of active vitamin K-dependent (VKD) coagulation factors with possible off-target effects. The NIH Clinical Collection (NCC) library containing 727 drugs was screened and 9 drugs, including the most commonly prescribed anticoagulant warfarin, were identified. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), while idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other three drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs targeting VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants. Copyright © 2020 American Society of Hematology.CONTEXT The Effect of physiological changes in nighttime cortisol and glucagon on endogenous glucose production (EGP) and nocturnal glycemia are unknown. OBJECTIVE To determine the effects of changes in cortisol and glucagon on EGP during the night. DESIGN Two overnight protocols were conducted. In Protocol 1, endogenous cortisol was blocked with metyrapone and hydrocortisone infused either at constant (constant) or increasing (variable) rates to mimic basal or physiological nocturnal cortisol concentrations. In Protocol 2, endogenous glucagon was blocked with somatostatin and exogenous glucagon was infused at either 'basal' or 'elevated' rates to mimic nocturnal glucagon concentrations observed in ND and T2D individuals. EGP was measured using [3-3H] glucose and gluconeogenesis estimated with 2H2O in all studies. SETTING Mayo Clinic Clinical Research Trials Unit, Rochester, MN, USA. PARTICIPANTS In Protocol 1, 34 subjects [17 non-diabetic (ND) and 17 T2D] and in Protocol 2, 39 subjects [21 ND and 18 T2D] were studied. MAIN OUTCOME MEASURES EGP. RESULTS EGP, gluconeogenesis and glycogenolysis were higher with variable than constant cortisol at 7 AM in T2D subjects. In contrast, nocturnal EGP did not differ in ND subjects between variable vs. constant cortisol. https://www.selleckchem.com/products/taurocholic-acid-sodium-salt-hydrate.html While elevated glucagon increased EGP, glycogenolysis and gluconeogenesis in ND, the data in T2D subjects indicated that EGP and gluconeogenesis, but not glycogenolysis were higher during the early part of the night. CONCLUSION Nocturnal hyperglucagonemia but not physiological rise in cortisol, contributes to nocturnal hyperglycemia in T2D due to increased gluconeogenesis. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.In this issue, Wang and colleagues solve an important puzzle in the understanding of schizophrenia. Previous work has linked NMDA receptor hypofunction to schizophrenia and shown that individuals with schizophrenia have a suppressed steady-state cortical response to 40-Hz repetitive auditory stimulation. However, systemic application of NMDA antagonists paradoxically increases this cortical response in rodents. Here, by specifically applying NMDA receptor blockade in the auditory thalamus while measuring the acoustically-driven response in two cortical regions simultaneously, Wang and colleagues found the drop in the steady-state response that is seen in schizophrenia. These findings solve an important paradox in the field and suggest that specific thalamic neurochemical alterations may occur in the brain of individuals with schizophrenia. In addition, this work suggests that suppression of NMDA receptors in the thalamus may serve as a potential animal model for the disease. © The Author(s) 2020. Published by Oxford University Press on behalf of CINP.MOTIVATION The outbreak of COVID-2019 initiated at Wuhan, China has become a global threat by rapid transmission and severe fatalities. Recent studies have uncovered whole genome sequence of SARS-CoV-2 (causing COVID-2019). In addition, lung metagenomic studies on infected patients revealed overrepresented Prevotella spp. producing certain proteins in abundance. We performed host-pathogen protein-protein interaction analysis between SARS-CoV-2 and overrepresented Prevotella proteins with human proteome. We also performed functional overrepresentation analysis of interacting proteins to understand their role in COVID-2019 severity. RESULTS It was found that over-expressed Prevotella proteins can promote viral infection. As per the results, Prevotella proteins, but not viral proteins are involved in multiple interactions with NF-kB, which is involved in increasing clinical severity of COVID-2019. Prevotella may have role in COVID-2019 outbreak and should be given importance for understanding disease mechanisms and improving treatment outcomes.