The Norwegian School of Sport Sciences (Norwegian: Norges idrettshøgskole, NIH) is a public university located at Sognsvann in Oslo, Norway. It has the national responsibility for education and research related within sport sciences. It provides education at the Bachelor, Master and Doctorate levels.
Background: Levothyroxine (LT4) is among the most frequently prescribed medications worldwide and the leading cause of thyrotoxicosis, a known risk factor for lower bone density and fracture. However, the skeletal consequences of LT4 use in biochemically euthyroid individuals remain poorly characterized. Methods: Data are from the Baltimore Longitudinal Study of Aging (BLSA). Eligible participants were euthyroid at all study visits and either consistently or never used LT4 throughout follow-up. Sex-stratified propensity score matching (1:3 ratio) balanced LT4-users and non-users on demographic, physiologic, medical and sex-specific factors. BMD was measured by dual-energy X-ray absorptiometry and linear mixed-effects models with piece-wise linear age splines were used to estimate age-specific BMD trajectories. Results: We included 108 men (31 LT4-users, 77 non-users) and 202 women (53 LT4-users, 149 non-users) analyzed in four age-strata: (<60, 60-69, 70-79, >= 80). Among men, annual BMD change was similar between LT4-users and non-users across all age strata. Among women, LT4-users experienced significantly greater BMD decline than non-users in two age groups: <60 (difference:-0.010 g/cm2/year; 95% CI-0.015 to-0.006) and 70-79 (difference:-0.003 g/cm2/year; 95% CI-0.005 to-0.001). Conclusions: Findings raise the possibility that LT4 therapy may be a factor in bone loss, particularly among women in late-middle and early old-age. Even the potential for a deleterious effect should be included in a pragmatic assessment of LT4 treatment indications and monitoring to avoid overtreatment in vulnerable populations.
INTRODUCTION: Hypertension represents a worldwide public health challenge related to chronic illnesses. This study set out to examine gender-based variations in prevalence and associated factors of hypertension in Malaysia. MATERIALS AND METHODS: We conducted a secondary data analysis based on the National Health and Morbidity Survey 2019, which was a nationwide cross-sectional study employing a two-stage stratified random sampling approach. Hypertension was defined as systolic BP >= 140 or diastolic BP? 90 mm Hg, told to have hypertension by medical personal previously. Multiple logistic regression analysis was applied. RESULTS: The prevalence of hypertension among adults in Malaysia was 30.0% (95% CI: 28.57, 31.50), men 30.3% (95% CI: 28.2, 32.5), and women 29.7% (95% CI: 28.0, 31.5). For both genders, increasing age, adults with higher BMI, other Bumiputras, unemployed and those with diabetes and high cholesterol had higher odds of hypertension. Among men, alcohol consumption showed higher odds [AOR: 1.31 (95% CI: 1.02, 1.68)], meanwhile, active smokers [AOR: 0.74 (95% CI: 0.64, 0.86)] and married men [AOR: 0.74 (95% CI: 0.57, 0.94)] showed lower odds of hypertension. Among women, Chinese [AOR: 0.62 (95% CI: 0.49, 0.77)], Indian [AOR: 0.65 (95% CI: 0.49, 0.86)], and tertiary education [AOR: 0.49 (95% CI: 0.35, 0.69)] showed lower odds and physically inactive women [AOR: 1.31 (95% CI: 1.1, 1.55)] showed higher odds of hypertension. CONCLUSION: Prevalence and the factors associated with hypertension differ between the two genders. Intervention strategies related to hypertension should consider the gender differences particularly among young men and elderly women.
Background Technological advances have recently made possible the estimation of maximal oxygen consumption ( V O 2max ) by consumer wearables. However, the validity of such estimations has not been systematically summarized using meta-analytic methods and there are no standards guiding the validation protocols. Objective The aim was to (1) quantitatively summarize previous studies investigating the validity of the V O 2max estimated by consumer wearables and (2) provide best-practice recommendations for future validation studies. Methods First, we conducted a systematic review and meta-analysis of studies validating the estimation of V O 2max by wearables. Second, based on the state of knowledge (derived from the systematic review) combined with the expert discussion between the members of the Towards Intelligent Health and Well-Being Network of Physical Activity Assessment (INTERLIVE) consortium, we provided a set of best-practice recommendations for validation protocols. Results Fourteen validation studies were included in the systematic review and meta-analysis. Meta-analysis results revealed that wearables using resting condition information in their algorithms significantly overestimated V O 2max (bias 2.17 ml·kg −1 ·min −1 ; limits of agreement − 13.07 to 17.41 ml·kg −1 ·min −1 ), while devices using exercise-based information in their algorithms showed a lower systematic and random error (bias − 0.09 ml·kg −1 ·min −1 ; limits of agreement − 9.92 to 9.74 ml·kg −1 ·min −1 ). The INTERLIVE consortium proposed six key domains to be considered for validating wearable devices estimating V O 2max , concerning the following: the target population, reference standard, index measure, testing conditions, data processing, and statistical analysis. Conclusions Our meta-analysis suggests that the estimations of V O 2max by wearables that use exercise-based algorithms provide higher accuracy than those based on resting conditions. The exercise-based estimation seems to be optimal for measuring V O 2max at the population level, yet the estimation error at the individual level is large, and, therefore, for sport/clinical purposes these methods still need improvement. The INTERLIVE network hereby provides best-practice recommendations to be used in future protocols to move towards a more accurate, transparent and comparable validation of V O 2max derived from wearables. PROSPERO ID CRD42021246192.
The mycobacterial membrane exporter MmpL3 transports trehalose monomycolates (TMM) from the cytosol to the outer membrane of Mycobacterium tuberculosis, making it a potential drug target. Proton influx is believed to drive TMM efflux, suggesting that disrupting proton transfer (PT) could be therapeutic. However, the PT mechanism and its relation to function remain unclear. Recent MmpL3 structures reveal a potential proton channel in its hydrophobic core, which also binds potential antituberculosis compounds. We investigated the PT process using hybrid quantum-mechanical/molecular-mechanical and classical molecular dynamics simulations. We show that transient water chains form in two connected transmembrane cavities that act as proton conduits. Four consecutive PT events are necessary to alter the protonation states of acidic residues in the protein core, triggering conformational changes that affect the TMM binding site. The process begins with the tandem movement of two protons through an upper cavity, protonating two aspartate residues via a classical hydronium migration. After conformational shifts, PT proceeds through a lower cavity, protonating two glutamate residues near the cytosolic opening and inducing further conformational shifts; here, PT occurs sequentially via hydronium and proton-hole migration. The cycle ends with the release of protons into the cytosol. Based on the observed conformational changes, we propose a mechanism for TMM efflux.
Causal inference from a randomized trial becomes challenging when interest focuses on a specific subpopulation and when the causal effect involves both the randomized binary treatment and a non-randomized continuous exposure. This study is motivated by a clinical trial conducted among women of childbearing potential to evaluate the effectiveness of a malaria vaccine during pregnancy within the subpopulation of women who would have become pregnant under placebo conditions. Although the primary policy-relevant contrast concerns the binary randomized treatment-vaccine versus placebo-there also exists a continuous post-randomization exposure-exposure to pregnancy-characterized by the timing of conception. Given the seasonality of malaria transmission and waning of vaccine-induced immunity, vaccine effectiveness during pregnancy may vary with conception timing, motivating causal evaluations that consider both exposures. We propose methodological approaches for causal inference in this setting, study their large-sample and finite-sample properties, and apply them to the malaria vaccine trial to provide a comprehensive assessment of vaccine effectiveness against pregnancy malaria in the target subpopulation while accounting for temporal variation in disease transmission.
