Practice patterns of kidney stone management across European and non-European centers: an in-depth investigation from the European Renal Stone Network (ERSN).

Kidney stones are a common condition in the general population, however, high-quality evidence for its management is scarce. We propose the creation of an international network with the aim of sharing practice patterns and patient data towards an improvement of our knowledge of the disease. Cross-sectional survey. An online survey was circulated through several scientific societies. Items were grouped into six domains. Each center's overall score (OS) was also calculated. Chi square and Mann-Whitney tests were performed for differences across centers. The countries that contributed most were Italy (8.6%), Turkey (6.6%), France and Spain (6.1%). Some type of nutritional work-up was implemented in 62% of centers. A DEXA scan was performed by 46% of centers, whereas some kind of acidification test was performed by 25% of centers. Most centers (80%) implemented blood investigations at least at baseline. With regard to 24-h urine exams, 7 out of 16 were performed by at least 50% of centers. Information on stone composition was collected by 58% of centers. The OS was significantly higher among higher-volume centers compared with lower-volume centers (p = 0.002). Significant differences between EU and non-EU centers were found. Cross-sectional design; no validation on information. Our survey highlights the potential for the creation of a network of centers that could share information in a common database for observational research and for enrollment of patients in interventional trials

Liquid-vapor oscillations of water in hydrophobic nanopores

Water plays a key role in biological membrane transport. In ion channels and water-conducting pores (aquaporins), one dimensional confinement in conjunction with strong surface effects changes the physical behavior of water. In molecular dynamics simulations of water in short (0.8 nm) hydrophobic pores the water density in the pore fluctuates on a nanosecond time scale. In long simulations (460 ns in total) at pore radii ranging from 0.35 nm to 1.0 nm we quantify the kinetics of oscillations between a liquid-filled and a vapor-filled pore. This behavior can be explained as capillary evaporation alternating with capillary condensation, driven by pressure fluctuations in the water outside the pore. The free energy difference between the two states depends linearly on the radius. The free energy landscape shows how a metastable liquid state gradually develops with increasing radius. For radii larger than ca. 0.55 nm it becomes the globally stable state and the vapor state vanishes. One dimensional confinement affects the dynamic behavior of the water molecules and increases the self diffusion by a factor of two to three compared to bulk water. Permeabilities for the narrow pores are of the same order of magnitude as for biological water pores. Water flow is not continuous but occurs in bursts. Our results suggest that simulations aimed at collective phenomena such as hydrophobic effects may require simulation times longer than 50 ns. For water in confined geometries, it is not possible to extrapolate from bulk or short time behavior to longer time scales.Comment: 20 pages, 4 figures, 3 tables; to be published in Proc. Natl. Acad. Sci. US

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp

The Barbados Insulin Matters (BIM) study: Barriers to insulin therapy among a population-based sample of people with type 2 diabetes in the Caribbean island of Barbados.

AIM: The purpose of this study was to document in people with type 2 diabetes (T2DM) in Barbados, attitudes and beliefs that may result in psychological insulin resistance. METHODS: A representative, population-based, sample of 175 eligible people with T2DM 25 years of age and over was surveyed by telephone. The 20-item insulin treatment appraisal scale (ITAS) was administered (score range 20 to 100 for positive to negative perceptions). RESULTS: 117 people participated (67% response rate, 32% male, mean age 66 years, 90% Black, 22% on insulin). Of non-responders, 52 were not contactable and 6 were difficult to communicate with. Negative perceptions about insulin use included - meant a worsening of diabetes (68%), would worry family (63%), feared self-injection (58%), meant a failure in self-management (57%), injections were painful (54%), would be seen as being sicker (46%), increased hypoglycaemia risk (38%), required effort (34%), causes weight gain (27%), causes a deterioration in health (14%), and would have to give up enjoyable activities (10%). Positive perceptions were - helps good glycaemic control (78%), would prevent complications (61%) and improves health (58%). Mean total ITAS score (61.6, SD = 7.7) was lower for those on insulin compared to those not on insulin (53.7 vs. 63.8, p < 0.0001). Sex, age and diabetes diagnosis duration were not significant predictors of ITAS score. CONCLUSIONS: Multiple factors related to patient beliefs and attitudes need to be considered and addressed when initiating insulin in order to minimise psychological insulin resistance and delay. Patients using insulin had less negative perceptions than those not on insulin

Low levels of cardiovascular risk factors and coronary heart disease in a UK Chinese population.

OBJECTIVE: To compare the prevalence of cardiovascular risk factors and coronary heart disease in Chinese and Europid adults. DESIGN: Population based, cross sectional survey. SETTING: Newcastle upon Tyne, UK, 1991-93. SUBJECTS: Altogether 380 Chinese and 625 Europid adults, aged 25-64 years. MAIN OUTCOME MEASURES: Fasting lipid levels, blood pressure, body mass index (BMI), the proportions who smoked, and the prevalence of coronary heart disease based on the Rose angina questionnaire and major electrocardiographic abnormalities on resting 12 lead electrocardiogram (Minnesota codes 1.1-1.2). All figures were age adjusted to the 1991 England and Wales population. RESULTS: Altogether 183 and 197 Chinese, and 310 and 315 Europid men and women respectively were seen. Compared with Europid men, Chinese men had a lower mean total cholesterol concentration (5.1 versus 5.6 mmol/l, p 0.05) and diastolic (75 versus 68 mmHg, p < 0.001) blood pressures. The prevalence of coronary heart disease was significantly lower in Chinese than Europid men (4.9% versus 16.6%, p < 0.001) but not significantly different in women (7.3% versus 11.1%, p = 0.16). CONCLUSION: Strategies for UK Chinese are needed to maintain this favourable risk factor profile and prevent any potential increase in the risk of coronary heart disease associated with increasing acculturation

Anthropometric cut-offs to identify hyperglycemia in an Afro-Caribbean population: a cross-sectional population-based study from Barbados.

INTRODUCTION: Body mass index (BMI) and waist circumference (WC) cut-offs associated with hyperglycemia may differ by ethnicity. We investigated the optimal BMI and WC cut-offs for identifying hyperglycemia in the predominantly Afro-Caribbean population of Barbados. RESEARCH DESIGN AND METHODS: A cross-sectional study of 865 individuals aged ≥25 years without known diabetes or cardiovascular disease was conducted. Hyperglycemia was defined as fasting plasma glucose ≥5.6 mmol/L or hemoglobin A1c ≥5.7% (39 mmol/mol). The Youden index was used to identify the optimal cut-offs from the receiver operating characteristic (ROC) curves. Further ROC analysis and multivariable log binomial regression were used to compare standard and data-derived cut-offs. RESULTS: The prevalence of hyperglycemia was 58.9% (95% CI 54.7% to 63.0%). In women, optimal BMI and WC cut-offs (27 kg/m2 and 87 cm, respectively) performed similarly to standard cut-offs. In men, sensitivities of the optimal cut-offs of BMI ≥24 kg/m2 (72.0%) and WC ≥86 cm (74.0%) were higher than those for standard BMI and WC obesity cut-offs (30.0% and 25%-46%, respectively), although with lower specificity. Hyperglycemia was 70% higher in men above the data-derived WC cut-off (prevalence ratio 95% CI 1.2 to 2.3). CONCLUSIONS: While BMI and WC cut-offs in Afro-Caribbean women approximate international standards, our findings, consistent with other studies, suggest lowering cut-offs in men may be warranted to improve detection of hyperglycemia. Our findings do, however, require replication in a new data set.The project was supported by the Ministry of Health of the Government of Barbados. ANW is supported by the Fogarty International Center of the National Institutes of Health under Award Number K43TW010698. This paper describes the views of the authors and does not necessarily represent the official views of the National Institutes of Health (USA)

Assessment of COVID-19 as the underlying cause of death among children and young people aged 0 to 19 years in the US.

IMPORTANCE: COVID-19 was the underlying cause of death for more than 940 000 individuals in the US, including at least 1289 children and young people (CYP) aged 0 to 19 years, with at least 821 CYP deaths occurring in the 1-year period from August 1, 2021, to July 31, 2022. Because deaths among US CYP are rare, the mortality burden of COVID-19 in CYP is best understood in the context of all other causes of CYP death. OBJECTIVE: To determine whether COVID-19 is a leading (top 10) cause of death in CYP in the US. DESIGN, SETTING, AND PARTICIPANTS: This national population-level cross-sectional epidemiological analysis for the years 2019 to 2022 used data from the US Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (WONDER) database on underlying cause of death in the US to identify the ranking of COVID-19 relative to other causes of death among individuals aged 0 to 19 years. COVID-19 deaths were considered in 12-month periods between April 1, 2020, and August 31, 2022, compared with deaths from leading non-COVID-19 causes in 2019, 2020, and 2021. MAIN OUTCOMES AND MEASURES: Cause of death rankings by total number of deaths, crude rates per 100 000 population, and percentage of all causes of death, using the National Center for Health Statistics 113 Selected Causes of Death, for ages 0 to 19 and by age groupings (<1 year, 1-4 years, 5-9 years, 10-14 years, 15-19 years). RESULTS: There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100 000 population overall; 4.3 per 100 000 for those younger than 1 year; 0.6 per 100 000 for those aged 1 to 4 years; 0.4 per 100 000 for those aged 5 to 9 years; 0.5 per 100 000 for those aged 10 to 14 years; and 1.8 per 100 000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group. CONCLUSIONS AND RELEVANCE: The findings of this study suggest that COVID-19 was a leading cause of death in CYP. It caused substantially more deaths in CYP annually than any vaccine-preventable disease historically in the recent period before vaccines became available. Various factors, including underreporting and not accounting for COVID-19's role as a contributing cause of death from other diseases, mean that these estimates may understate the true mortality burden of COVID-19. The findings of this study underscore the public health relevance of COVID-19 to CYP. In the likely future context of sustained SARS-CoV-2 circulation, appropriate pharmaceutical and nonpharmaceutical interventions (eg, vaccines, ventilation, air cleaning) will continue to play an important role in limiting transmission of the virus and mitigating severe disease in CYP

Vacuum stability and the Cholesky decomposition

We discuss how the Cholesky decomposition may be used to ascertain whether a critical point of the field theory scalar potential provides a stable vacuum configuration. We then use this method to derive the stability conditions in a specific example.Comment: 7 page