The calcium-sensing receptor (CaSR) is essential to maintain a stable calcium concentration in serum. Spermatozoa are exposed to immense changes in concentrations of CaSR ligands such as calcium, magnesium, and spermine during epididymal maturation, in the ejaculate, and in the female reproductive environment. However, the role of CaSR in human spermatozoa is unknown.
 
  This work aimed to investigate the role of CaSR in human spermatozoa.
 
  We identified CaSR in human spermatozoa and characterized the response to CaSR agonists on intracellular calcium, acrosome reaction, and 3',5'-cyclic adenosine 5'-monophosphate (cAMP) in spermatozoa from men with either loss-of-function or gain-of-function mutations in CASR and healthy donors.
 
  CaSR is expressed in human spermatozoa and is essential for sensing extracellular free ionized calcium (Ca2+) and Mg2+. Activators of CaSR augmented the effect of sperm-activating signals such as the response to HCO3- and the acrosome reaction, whereas spermatozoa from men with a loss-of-function mutation in CASR had a diminished response to HCO3-, lower progesterone-mediated calcium influx, and were less likely to undergo the acrosome reaction in response to progesterone or Ca2+. CaSR activation increased cAMP through soluble adenylyl cyclase (sAC) activity and increased calcium influx through CatSper. Moreover, external Ca2+ or Mg2+ was indispensable for HCO3- activation of sAC. Two male patients with a CASR loss-of-function mutation in exon 3 presented with normal sperm counts and motility, whereas a patient with a loss-of-function mutation in exon 7 had low sperm count, motility, and morphology.
 
  CaSR is important for the sensing of Ca2+, Mg2+, and HCO3- in spermatozoa, and loss-of-function may impair male sperm function.
 CaSR is important for the sensing of Ca2+, Mg2+, and HCO3- in spermatozoa, and loss-of-function may impair male sperm function.The objective of this study was to evaluate wool (Dorset and Rambouillet) and hair (Dorper, Katahdin, and White Dorper) breeds for their ability to complement Romanov germplasm in an annual fall lambing system by estimating direct maternal grandsire and sire breed effects on economically important lamb and ewe traits. After 3 yr of evaluation under spring lambing, ewes of the five F1 types were transitioned to spring mating, exposed to composite terminal sires, and evaluated under a barn lambing system at 4, 5, and 6 yr of age. A total of 527 first generation crossbred (F1) ewes produced 1,151 litters and 2,248 lambs from 1,378 May exposures. After accounting for differences in dam age, birth type, and sex, lamb survival to weaning was unaffected by maternal grandsire breed (P = 0.30). However, lambs born to 50% Dorset (16.8 ± 0.21 kg) or 50% White Dorper ewes (16.8 ± 0.28 kg) were heavier at weaning than those born to 50% Katahdin dams (13.8 ± 0.32 kg; P less then 0.001). Additionally, lambs born to 50% Dored ewes (17.8 ± 0.94 kg; P = 0.05), but no other sire breed differences were detected (P ≥ 0.07). Results demonstrated that incorporating the Romanov into a crossbreeding system is a practical means of improving out-of-season ewe productivity.Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death [adjusted hazard ratio (aHR) 0.89], but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR  less then 30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31-1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
  The influenza vaccine is one of the best ways to prevent influenza infection, but little is known about influenza vaccine failure.
 
  This study evaluated patients admitted for an acute respiratory illness during the 2015-2019 influenza seasons to compare vaccinated, influenza-negative patients to vaccinated, influenza-positive patients. Statistical analyses were performed with STATA and R using Pearson's chi-squared, Kruskal-Wallis, Wilcoxon rank-sum tests and multivariate logistic regression.
 
  1236 patients vaccinated for influenza were enrolled, of which 235 (19%) tested positive for influenza. Demographics, vaccines and comorbidities were similar between the groups except for morbid obesity (13% in the influenza negative vs. 8%, p=0.04), and immunosuppression (63% in the influenza positive vs. 54%, p=0.01). Logistic regression analysis demonstrated older patients (OR 1.47, 95%CI 1.03-2.10) and immunosuppressed patients (OR 1.56, 1.15-2.12) were at increased risk for influenza despite immunization. When evaluated by influenza subtype, immunosuppression was found to increase the risk for influenza A/H3N2 (OR 1.86, 95%CI 1.25-2.75).
 
  Our study demonstrated increased risk of influenza vaccine failure in older patients and immunosuppressed patients.  https://www.selleckchem.com/products/gw4869.html  These groups are also at increased risk for influenza complications. To improve protection of patients against future influenza illnesses, more effective vaccines and strategies are needed.
 Our study demonstrated increased risk of influenza vaccine failure in older patients and immunosuppressed patients. These groups are also at increased risk for influenza complications. To improve protection of patients against future influenza illnesses, more effective vaccines and strategies are needed.