Search

Context: Many adrenal adenomas exhibit mild autonomous cortisol secretion (MACS). Although MACS is associated with increased cardiovascular mortality, the underlying mechanisms are not fully defined., Objective: To investigate mechanisms that may link MACS and cardiovascular mortality in adults with adrenal adenoma., Design: Cross-sectional study., Patients: Twenty adults with adrenal adenoma and MACS and 20 controls with nonfunctioning adrenal adenoma., Methods: Reactive hyperemia index (RHI) was measured by peripheral artery tonometry and 24-hour ambulatory blood pressure monitoring (24h AMBP) was performed. Indices of insulin secretion and sensitivity were estimated by measuring glucose and insulin fasting and following a mixed meal., Main Outcome Measure: The primary outcome was the difference in RHI between participants with MACS vs nonfunctioning adrenal adenoma., Results: The average cortisol after 1-mg dexamethasone and urinary free cortisol were higher in patients with MACS. There was no significant difference in fasting RHI (2.0 [interquartile range (IQR) 1.6-2.4] vs 2.0 [IQR 1.7-2.2, P = .72), but postprandial RHI was higher in patients with MACS (2.2 [1.8-2.7] vs 1.8 [1.5-2.2], P = .04). 24-hour ambulatory blood pressure monitoring and Matsuda index were not significantly different in the groups. Fasting glucose and glucose area under the curve after the mixed meal were higher and insulinogenic index was lower in participants with MACS., Conclusion: Adults with adrenal adenoma and MACS do not have fasting endothelial dysfunction and postprandial endothelial function may be better. These patients have fasting and postprandial hyperglycemia with lower insulin secretion, which may underlie the association between MACS and increased cardiovascular mortality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Currently, there is no validated and available method internationally to determine the contents of nicotine and aerosolizing agents, namely glycerol and propylene glycol, added onto the heatsticks for use in heated smoking devices., Objective: To determine the concentrations of nicotine, propylene glycol, glycerol and triacetin in heated tobacco products (HTPs) which is essential to understanding their health effects on smokers as well as secondhand smokers., Methods: A simple methodology was developed and validated to simultaneously determine nicotine, propylene glycol, glycerol, and triacetin concentrations present in heatsticks. The tobacco material was extracted with a mixture of methanol-acetonitrile (7 + 3, by volume) with 1,3-butanediol and n-heptadecane as internal standards and analyzed with gas chromatography with flame-ionization detection (GC-FID)., Results: Good linearity was achieved over the following concentration ranges: 0.1-1.0 mg/mL for nicotine, 0.03-2.0 mg/mL for propylene glycol, 0.5-10.0 mg/mL for glycerol, and 0.1-4.0 mg/mL triacetin, with a coefficient of determination ≥0.995. The limits of detection and quantification were 0.0009 and 0.003 mg/mL for nicotine, 0.02 and 0.02 mg/mL for propylene glycol, 0.03 and 0.09 mg/mL for glycerol, and 0.005 and 0.02 mg/mL for triacetin, respectively. Good recoveries were obtained for nicotine at 89.8-102.0%, propylene glycol at 95.5-102.5%, glycerol at 95.2-102.6%, and triacetin at 90.6-103.1%., Conclusion: This method provides an affordable and reliable technique for routine analysis of nicotine and aerosolizing chemicals present in HTPs which is necessary to assess their impact to public health., Highlights: Many gaps remain in research on HTPs, in particular, country levels information on the content of the products are limited. This article contains information on a newly developed method to simultaneously determine nicotine, propylene glycol, glycerol and triacetin present in the tobacco material and butts of heatsticks for HTPs., (© AOAC INTERNATIONAL 2021. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Context: Lower sodium intake is paradoxically associated with higher mortality in type 2 diabetes (T2D)., Objective: To determine whether sympathetic nervous system (SNS) activation and endothelial dysfunction contribute to these observations, we examined the effect of salt supplementation on these systems in people with T2D with habitual low sodium. We hypothesized that salt supplementation would lower SNS activity and improve endothelial function compared to placebo., Design: We conducted a randomized, double-blinded, placebo-controlled crossover trial., Setting: The study took place in a tertiary referral diabetes outpatient clinic., Participants: Twenty-two people with T2D with habitual low sodium intake (24-hour urine sodium <150 mmol/24h) were included., Intervention: Salt supplementation (100 mmol NaCl/24h) or placebo for 3 weeks was administered., Main Outcome Measures: The primary outcome of SNS activity and endothelial function was assessed as follows: Microneurography assessed muscle sympathetic nerve activity (MSNA), pulse amplitude tonometry assessed endothelial function via reactive hyperemic index (RHI), and arterial stiffness was assessed via augmentation index (AI). Secondary outcomes included cardiac baroreflex, serum aldosterone, ambulatory blood pressure monitoring (ABPM), heart rate variability (HRV), and salt sensitivity., Results: Compared to placebo, salt supplementation increased MSNA (burst frequency P = .047, burst incidence P = .016); however, RHI (P = .24), AI (P = .201), ABPM (systolic P = .09, diastolic P = .14), and HRV were unaffected. Salt supplementation improved baroreflex (slope P = .026) and lowered aldosterone (P = .004), and in salt-resistant individuals there was a trend toward improved RHI (P = .07)., Conclusions: In people with T2D and low habitual sodium intake, salt supplementation increased SNS activity without altering endothelial function or blood pressure but improved baroreflex function, a predictor of cardiac mortality. Salt-resistant individuals trended toward improved endothelial function with salt supplementation., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Neutron generators are an excellent tool that can be effectively utilized in educational institutions for applications such as neutron activation analysis, neutron radiography, and profiling and irradiation effects. For safety purposes, it is imperative that appropriate measures are taken in order to minimize the radiation dose from such devices to the operators, students and the public. This work presents the simulation and measurement results for the neutron and photon dose rates in the vicinity of the neutron generator installed at the University of Sharjah. A very good agreement is found between the simulated and measured dose rates. All of the public dose constraints were found to be met. The occupational dose constraint was also met after imposing a 200 cm no entry zone around the generator room., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The molecular clock is a valuable and widely used tool for estimating evolutionary rates and timescales in biological research. There has been considerable progress in the theory and practice of molecular clocks over the past five decades. Although the idea of a molecular clock was originally put forward in the context of protein evolution and advanced using various biochemical techniques, it is now primarily applied to analyses of DNA sequences. An interesting but very underappreciated aspect of molecular clocks is that they can be based on genetic data other than DNA or protein sequences. For example, evolutionary timescales can be estimated using microsatellites, protein folds, and even the extent of recombination. These genome features hold great potential for molecular dating, particularly in cases where nucleotide sequences might be uninformative or unreliable. Here we present an outline of the different genetic data types that have been used for molecular dating, and we describe the features that good molecular clocks should possess. We hope that our article inspires further work on the genome as an evolutionary timepiece., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Context: The use of next-generation sequencing has resulted in the identification of recurrent somatic mutations underlying primary aldosteronism (PA). However, significant gaps remain in our understanding of the relationship between tumor aldosterone synthase (CYP11B2) expression and somatic mutation status., Objective: The objective of the study was to investigate tumor CYP11B2 expression and somatic aldosterone-driver gene mutation heterogeneity., Methods: Fifty-one adrenals from 51 PA patients were studied. Immunohistochemistry for CYP11B2 was performed. Aldosterone-producing adenomas with intratumor CYP11B2 heterogeneity were analyzed for mutation status using targeted next-generation sequencing. DNA was isolated from CYP11B2-positive, CYP11B2-negative, and adjacent normal areas from formalin-fixed, paraffin-embedded sections., Results: Of 51 adrenals, seven (14 %) showed distinct heterogeneity in CYP11B2 by immunohistochemistry, including six adenomas with intratumor heterogeneity and one multinodular hyperplastic adrenal with both CYP11B2-positive and -negative nodules. Of the six adrenocortical adenomas with CYP11B2 heterogeneity, three had aldosterone-regulating mutations (CACNA1D p.F747C, KCNJ5 p.L168R, ATP1A1 p.L104R) only in CYP11B2-positive regions, and one had two different mutations localized to two histologically distinct CYP11B2-positive regions (ATP2B3 p.L424&#95;V425del, KCNJ5 p.G151R). Lastly, one adrenal with multiple CYP11B2-expressing nodules showed different mutations in each (CACNA1D p.F747V and ATP1A1 p.L104R), and no mutations were identified in CYP11B2-negative nodule or adjacent normal adrenal., Conclusions: Adrenal tumors in patients with PA can demonstrate clear heterogeneity in CYP11B2 expression and somatic mutations in driver genes for aldosterone production. These findings suggest that aldosterone-producing adenoma tumorigenesis can occur within preexisting nodules through the acquisition of somatic mutations that drive aldosterone production.