Ion permeation through a narrow cavity constriction in KCNQ1 channels: Mechanism and implications for pathogenic variants.

KCNQ1 potassium channels play a pivotal role in the physiology and pathophysiology of several human excitable and epithelial tissues. The latest cryo-electron microscopy (cryo-EM) structures provide unique insights into channel function and pharmacology, opening avenues for different therapeutic strategies against human diseases associated with KCNQ1 mutations. However, these structures also raise fundamental questions about the mechanisms of ion permeation.

Dataset on extreme thunderstorm ground enhancements registered on Aragats in 2023.

To advance high-energy atmospheric physics, studying atmospheric electric fields (AEF) and cosmic ray fluxes as an interconnected system is crucial. At Mt. Argats, simultaneous measurements of particle fluxes, electric fields, weather conditions, and lightning locations have significantly enhanced the validation of models that describe the charge structures of thunderclouds and the mechanics of internal electron accelerators.

[The present-day medical demographic situation in the Republic of Karelia].

The analysis of basic medical and demographic indicators (primary morbidity and disability of adult population, mortality, age structure and life expectancy) and provision of medical care in the Republic of Karelia in 2011-2020 was carried out. It established consistently high level of primary morbidity of population with respiratory diseases; injuries, poisoning and other consequences of external causes; diseases of genitourinary system. Diseases of cardiovascular system and malignant neoplasms occupy leading positions in the structure of causes of disability and mortality of population during period under review.

[The nature of the actual nutrition of elderly residents of the European North of Russia who had community-acquired pneumonia, not associated with the COVID-19 virus, from the standpoint of the possibility of the microelement state disorder.].

An increasing number of elderly and senile people characterises the structure of modern society. With ageing, a violation of the microelement homeostasis of the human body occurs. The natural biogeochemical conditions of the North initiate a metabolic restructuring of the body, accompanied by changes in the microelement state, which disrupts the functions of protective systems and increases the risk of developing diseases.

Mechanism of external K+ sensitivity of KCNQ1 channels.

KCNQ1 voltage-gated K+ channels are involved in a wide variety of fundamental physiological processes and exhibit the unique feature of being markedly inhibited by external K+. Despite the potential role of this regulatory mechanism in distinct physiological and pathological processes, its exact underpinnings are not well understood. In this study, using extensive mutagenesis, molecular dynamics simulations, and single-channel recordings, we delineate the molecular mechanism of KCNQ1 modulation by external K+.

Development of an Integrated Platform Using Multidisciplinary Real-World Data to Facilitate Biomarker Discovery for Medical Products.

Translational multidisciplinary research is important for the Center for Devices and Radiological Health's efforts for utilizing real-world data (RWD) to enhance predictive evaluation of medical device performance in patient subpopulations. As part of our efforts for developing new RWD-based evidentiary approaches, including in silico discovery of device-related risk predictors and biomarkers, this study aims to characterize the sex/race-related trends in hip replacement outcomes and identify corresponding candidate single nucleotide polymorphisms (SNPs). Adverse outcomes were assessed by deriving RWD from a retrospective analysis of hip replacement hospital discharge data from the National Inpatient Sample (NIS).

On the initiation of lightning in thunderclouds.

The relationship of lightning and elementary particle fluxes in the thunderclouds is not fully understood to date. Using the particle beams (the so-called Thunderstorm Ground Enhancements - TGEs) as a probe we investigate the characteristics of the interrelated atmospheric processes. The well-known effect of the TGE dynamics is the abrupt termination of the particle flux by the lightning flash.

Excess mortality after hip fracture in elderly persons from Europe and the USA: the CHANCES project.

Background: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.

Objective: All-cause mortality after hip fracture was investigated to assess its magnitude.

Methods: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.

Role of innate immunity in pregnant patients with vulvovaginal infections in the development of intrauterine infection in the newborn.

A total of 115 pregnant women were examined: 59 patients with opportunistic vulvovaginal infections and 56 without infection. Congenital immunity parameters (TLR-2, NF-κB, and IL-2 receptors in placental tissue) were studied by immunohistochemical methods. Realization of congenital infection was associated with activation of IL-6 receptors and TLR-2 in the placenta and an increase of NF-κB level.

Prospective study on physical activity and risk of in situ breast cancer.

Background: Physical activity has been identified as protective factor for invasive breast cancer risk, whereas comparable studies on in situ carcinoma are rare.

Methods: The study included data from 283,827 women of the multinational European Prospective Investigation into C7ancer and Nutrition (EPIC)-cohort study. Detailed information on different types of physical activity conducted during the prior year, such as occupational, recreational, and household activity, as well as on important cofactors, was assessed at baseline.

Physical activity and risk of breast cancer overall and by hormone receptor status: the European prospective investigation into cancer and nutrition.

Physical activity is associated with reduced risks of invasive breast cancer. However, whether this holds true for breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status is controversial. The study included 257,805 women from the multinational EPIC-cohort study with detailed information on occupational, recreational and household physical activity and important cofactors assessed at baseline.

Prediagnostic concentrations of plasma genistein and prostate cancer risk in 1,605 men with prostate cancer and 1,697 matched control participants in EPIC.

Purpose: Data from prospective epidemiological studies in Asian populations and from experimental studies in animals and cell lines suggest a possible protective association between dietary isoflavones and the development of prostate cancer. We examined the association between circulating concentrations of genistein and prostate cancer risk in a case-control study nested in the European Prospective Investigation into Cancer and Nutrition.

Methods: Concentrations of the isoflavone genistein were measured in prediagnostic plasma samples for 1,605 prostate cancer cases and 1,697 matched control participants.

Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition.

Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake.

Fruit and vegetable intake and the risk of gastric adenocarcinoma: a reanalysis of the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST) study after a longer follow-up.

In a previous European prospective investigation into cancer and nutrition (EPIC) analysis, we found an inverse association between total intake of vegetables, onion and garlic, and risk of intestinal gastric cancer (GC) and between citrus fruit and risk of cardia GC. The aim of this study is to reanalyze the effect of fruit and vegetables (F&V), based on a longer follow-up and twice the number of GC cases. Subjects are 477,312 men and women mostly aged 35 to 70 years participating in the EPIC cohort, including 683 gastric adenocarcinomas with 11 years of follow-up.

Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

Background: Epidemiologic data suggest that diet is a risk factor in the etiology of gastric cancer. However, the role of dietary fatty acids, a modifiable risk factor, remains relatively unexplored.

Objective: The objective of this study was to determine the association of plasma phospholipid fatty acid concentrations, as biomarkers of exogenous and endogenously derived fatty acids, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition-Europe Gastric Cancer (EPIC-EURGAST).

Genetic variability of the forkhead box O3 and prostate cancer risk in the European Prospective Investigation on Cancer.

Forkhead box O3 (FOXO3) has a wide range of functions: it promotes tumor suppression, cell cycle arrest, repair of damaged DNA, detoxification of reactive oxygen species, apoptosis and plays a pivotal role in promoting longevity. FOXO3 is a key downstream target of the PI3K-Akt pathway in response to cellular stimulation by growth factors or insulin and has been proposed as a bridge between ageing and tumor suppression. Three SNPs in the FOXO3 gene (rs3800231, rs9400239 and rs479744) that have been shown to be strongly and consistently associated with longevity, were examined in relation to PC risk in a case control study of 1571 incident PC cases and 1840 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC).