With high circulating aldosterone, intercalated cell mineralocorticoid receptor gene ablation directly reduced pendrin's relative abundance in the apical membrane region and pendrin abundance per cell whether serum potassium was high or low. Intercalated cell mineralocorticoid receptor ablation blunted, but did not eliminate, aldosterone's effect on pendrin total and apical abundance and subcellular distribution. CONCLUSIONS With high circulating aldosterone, intercalated cell mineralocorticoid receptor ablation reduces chloride absorption in the CCD and indirectly reduces principal cell epithelial sodium channel abundance and function. This receptor directly regulates pendrin's total abundance and its relative abundance in the apical membrane region over a wide range in serum potassium concentration. Aldosterone regulates pendrin through mechanisms both dependent and independent of the IC MR receptor. Copyright © 2020 by the American Society of Nephrology.BACKGROUND Like other cancer epidemiological cohorts, the California Teachers Study (CTS) has experienced declining participation to follow-up questionnaires; neither the reasons for these declines nor the steps that could be taken to mitigate these trends are fully understood. METHODS The CTS offered their 6th study questionnaire (Q6) in the fall of 2017 using an integrated, online system. The team delivered a web and mobile-adaptive questionnaire to 45,239 participants via email using marketing automation technology. The study's integrated platform captured data on recruitment activities that may influence overall response, including the date and time invitations and reminders were emailed and the date and time questionnaires were started and submitted. RESULTS The overall response rate was 43%. Participants ages 65 - 69 were 25% more likely to participate than their younger counterparts (OR=1.25, 95% CI, 1.18-1.32) and non-white participants were 28% less likely to participate than non-Hispanic white cohort members (OR=0.72, 95% CI, 0.68-0.76). Previous questionnaire participation was strongly associated with response (OR=6.07, 95% CI, 5.50-6.70). Invitations sent after 2 PM had the highest response (OR=1.75, 95% CI, 1.65-1.84), as did invitations sent on Saturdays (OR=1.48, 95% CI, 1.36-1.60). CONCLUSIONS An integrated system that captures paradata about questionnaire recruitment and response can enable studies to quantify the engagement patterns and communication desires of cohort members. IMPACT As cohorts continue to collect scientific data, it is imperative to collect and analyze information on how participants engage with the study. Copyright ©2020, American Association for Cancer Research.BACKGROUND We aimed to identify rare (minor allele frequency ≤1%), potentially pathogenic non-synonymous variants in a well-characterised cohort with a clinical history of exertional heat illness (EHI) or exertional rhabdomyolysis (ER). The genetic link between malignant hyperthermia (MH) and EHI was investigated due to their phenotypic overlap. METHODS The coding regions of 38 genes relating to skeletal muscle calcium homeostasis or exercise intolerance were sequenced in 64 patients (mostly military personnel) with a history of EHI, or ER and who were phenotyped using skeletal muscle in vitro contracture tests. We assessed the pathogenicity of variants using prevalence data, in silico analysis, phenotype and segregation evidence and by review of the literature. RESULTS We found 51 non-polymorphic, potentially pathogenic variants in 20 genes in 38 patients. Our data indicate that RYR1 p.T3711M (previously shown to be likely pathogenic for MH susceptibility) and RYR1 p.I3253T are likely pathogenic for EHI. PYGM p.A193S was found in 3 patients with EHI, which is significantly greater than the control prevalence (p=0.000025). We report the second case of EHI in which a missense variant at CACNA1S p.R498 has been found. Combinations of rare variants in the same or different genes are implicated in EHI. CONCLUSION We confirm a role of RYR1 in the heritability of EHI as well as ER but highlight the likely genetic heterogeneity of these complex conditions. We propose defects, or combinations of defects, in skeletal muscle calcium homeostasis, oxidative metabolism and membrane excitability are associated with EHI. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2IG-DMR) on 11p15.5 and 5%-10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS. METHODS A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped. RESULTS The median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤-2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS. CONCLUSION Historical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Caspofungin nmr Published by BMJ.