The Fast Component of hERG Gating Charge: An Interaction between D411 in the S1 and S4 Residues.

Kv11.1 (hERG) is a voltage-gated potassium channel that shows very slow ionic current activation kinetics, and an unusual underlying biphasic gating charge movement with fast and slow components that differ greatly in time course. The structural basis and role of the fast component of gating charge (Q) is unclear, and its relationship to the slow activation of hERG channels is not understood.

Exploring interprofessional, interagency multimorbidity care: case study based observational research.

Background: The increase in multimorbidity or co-occurring chronic illnesses is a leading healthcare concern. Patients with multimorbidity require ongoing care from many different professionals and agencies, and often report a lack of integrated care.

Objective: To explore the daily help-seeking behaviours of patients with multimorbidity, including which health professionals they seek help from, how professionals work together, and perceptions and characteristics of effective interprofessional, interagency multimorbidity care.

Humanized mouse model supports development, function, and tissue residency of human natural killer cells.

Immunodeficient mice reconstituted with a human immune system represent a promising tool for translational research as they may allow modeling and therapy of human diseases in vivo. However, insufficient development and function of human natural killer (NK) cells and T cell subsets limit the applicability of humanized mice for studying cancer biology and therapy. Here, we describe a human interleukin 15 () and human signal regulatory protein alpha () knock-in mouse on a background (SRG-15).

"I can't bend it and it hurts like mad": direct observation of gout consultations in routine primary health care.

Background: Gout is the most common form of inflammatory arthritis and is associated with considerable co-morbidity. It is usually managed in the primary care setting with a combination of lifestyle modification and pharmacological therapy. This study describes patterns of communication about gout observed in interactions between patients and primary care practitioners during routine consultations.

Changes over time in population level transport satisfaction and mode of travel: A 13 year repeat cross-sectional study, UK.

Aim: The aim of the study was to examine changes over time in satisfaction with usual transport mode, explore individual and area level characteristics as mediators in the likelihood of transport satisfaction, and whether any changes in transport satisfaction varied by these factors over time.

Methods: Adults from West Central Scotland, United Kingdom, who participated at both waves of the repeat cross-sectional 'Transport, Health and Well-being Study' conducted in 1997 (n=2735) and 2010 (n=2024) were assessed. Individuals completed a detailed postal questionnaire at both time points including self-rated satisfaction with usual transport mode (using a seven point scale subsequently dichotomised to a binary outcome of satisfied (1-2) and other (3-7)).

The Role of Occupation in Explaining Cognitive Functioning in Later Life: Education and Occupational Complexity in a U.S. National Sample of Black and White Men and Women.

Objective: Positive associations between education and late-life cognition have been widely reported. This study examines whether occupational complexity mediates the relationship between education and late-life cognition, and whether the magnitude of mediation differs by race, gender, or education level.

Methods: Data were from a population-based cohort of non-Hispanic Blacks and Whites aged ≥45 years (n = 7,357).

Type III hypersensitivity reactions to a B cell epitope antigen are abrogated using a depot forming vaccine platform.

Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen.

Long-Term Outcomes of Patent Foramen Ovale Closure or Medical Therapy after Stroke.

Background: Whether closure of a patent foramen ovale reduces the risk of recurrence of ischemic stroke in patients who have had a cryptogenic ischemic stroke is unknown.

Methods: In a multicenter, randomized, open-label trial, with blinded adjudication of end-point events, we randomly assigned patients 18 to 60 years of age who had a patent foramen ovale (PFO) and had had a cryptogenic ischemic stroke to undergo closure of the PFO (PFO closure group) or to receive medical therapy alone (aspirin, warfarin, clopidogrel, or aspirin combined with extended-release dipyridamole; medical-therapy group). The primary efficacy end point was a composite of recurrent nonfatal ischemic stroke, fatal ischemic stroke, or early death after randomization.

Participation in a US community-based cardiovascular health study: investigating nonrandom selection effects related to employment, perceived stress, work-related stress, and family caregiving.

Purpose: Participation in health studies may be inversely associated with employment and stress. We investigated whether employment, perceived stress, work-related stress, and family caregiving were related to participation in a longitudinal US community-based health study of black and white men and women aged ≥45 years.

Methods: Prevalence ratios and confidence intervals were estimated for completion of the second stage (S2) of a two-stage enrollment process by employment (status, type), and stress (perceived stress, work-related stress, caregiving), adjusting for age, sex, race, region, income, and education.

Drusen in patient-derived hiPSC-RPE models of macular dystrophies.

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology.

Household Exposure to Livestock and Health in the CHILILAB HDSS Cohort, Vietnam.

In Vietnam, pigs and poultry are predominantly produced by small-scale farmers, creating challenges for zoonotic disease management. The objective of this study was to characterize practices related to livestock and manure management and to measure association with 3 self-reported health symptoms (coughing, fever, and diarrhea/nausea/vomiting) in a region currently undergoing health transitions. We analyzed cross-sectional survey data collected from a subset (N = 5520) of the Chi Linh Health and Demographic Surveillance System cohort in Chi Linh district, Vietnam.

The Effect of Changes in Cervical Cancer Screening Guidelines on Chlamydia Testing.

Purpose: Many chlamydia infections are identified through screening, which is frequently offered to females concomitantly with cervical cancer screening. Recent cervical cancer screening guidelines recommend screening less frequently and starting later. We sought to evaluate the impact of the May 2012 Ontario, Canada, cervical cancer screening guideline change on Papanicolaou (Pap) and chlamydia trachomatis (chlamydia) testing and incidence.

Combination of poly I:C and Pam3CSK4 enhances activation of B cells in vitro and boosts antibody responses to protein vaccines in vivo.

Vaccines that can rapidly induce strong and robust antibody-mediated immunity could improve protection from certain infectious diseases for which current vaccine formulations are inefficient. For indications such as anthrax and influenza, antibody production in vivo is a correlate of efficacy. Toll-like receptor (TLR) agonists are frequently studied for their role as vaccine adjuvants, largely because of their ability to enhance initiation of immune responses to antigens by activating dendritic cells.

The experiences of pregnant women in an interventional clinical trial: Research In Pregnancy Ethics (RIPE) study.

There is increasing global pressure to ensure that pregnant women are responsibly and safely included in clinical research in order to improve the evidence base that underpins healthcare delivery during pregnancy. One supposed barrier to inclusion is the assumption that pregnant women will be reluctant to participate in research. There is however very little empirical research investigating the views of pregnant women.

Patients' Perioperative Experience of Awake Deep-Brain Stimulation for Parkinson Disease.

Background: Awake craniotomy for tumor resection and epilepsy surgery is a well-tolerated procedure. Qualitative data on patients' experience of awake deep-brain stimulation (DBS) are, however, lacking. We collected qualitative data on patients' experience of awake DBS with a view to identifying areas for improvement.

The Influence of Neighbourhoods and the Social Environment on Sedentary Behaviour in Older Adults in Three Prospective Cohorts.

Sedentary behaviour is an emerging risk factor for poor health. This study aimed to identify ecological determinants of sedentary behaviour, for which evidence is currently scarce. The study participants were community dwelling adults from, respectively, the Lothian Birth Cohort 1936 (n = 271, mean age 79) and the 1930s (n = 119, mean age 83) and 1950s (n = 310, mean age 64) cohorts of the West of Scotland Twenty-07 study.

Return on investment from fuel treatments to reduce severe wildfire and erosion in a watershed investment program in Colorado.

A small but growing number of watershed investment programs in the western United States focus on wildfire risk reduction to municipal water supplies. This paper used return on investment (ROI) analysis to quantify how the amounts and placement of fuel treatment interventions would reduce sediment loading to the Strontia Springs Reservoir in the Upper South Platte River watershed southwest of Denver, Colorado following an extreme fire event. We simulated various extents of fuel mitigation activities under two placement strategies: (a) a strategic treatment prioritization map and (b) accessibility.

Physical and Organizational Job Stressors in Pregnancy and Associations With Primary Cesarean Deliveries.

Objective: The aim of this study was to assess the relationship between exposure to physical and organizational job stressors during pregnancy and cesarean delivery.

Methods: We sampled 580 employed women in California who participated in a nested population-based case-control study of birth outcomes. Adjusted multivariate regression analyses estimated associations between heavy lifting, frequent bending, high noise, extreme temperature, prolonged standing and organizational stressors (shift work, inflexible schedules, effort-reward ratio), and primary cesarean (vs vaginal) delivery, controlling for covariates.

Underreporting of high-risk water and sanitation practices undermines progress on global targets.

Water and sanitation indicators under the Millennium Development Goals failed to capture high-risk practices undertaken on a regular basis. In conjunction with local partners, fourteen rounds of household surveys using mobile phones with a customized open-source application were conducted across nine study geographies in Asia and Africa. In addition to the main water and sanitation facilities, interviewees (n = 245,054) identified all water and sanitation options regularly used for at least one season of the year.

Expertise in Everyday Nurse-Patient Conversations: The Importance of Small Talk.

A great deal of nursing activity is embedded in what is considered to be everyday conversation. These conversations are important to health professionals because communication can affect health outcomes, and they are important to patients who want to know they are being heard and cared for. How do nurses talk with patients and what are the features of effective communication in practice? In this exploratory study, two expert nurses recorded conversations with patients during domiciliary visits.

Prevalence of Cardiovascular Health by Occupation: A Cross-Sectional Analysis Among U.S. Workers Aged ≥45 Years.

Introduction: Identification of groups with poor cardiovascular health (CVH) can inform where and how to target public health efforts. National prevalence estimates of CVH were derived for clinical (blood glucose, total cholesterol, blood pressure) and behavioral (BMI, diet quality, physical activity, smoking) factors among U.S.

The role of packaged water in meeting global targets on improved water access.

Packaged water (as either refill, bottled, or sachet water) has become an important element of water security in many low- and middle-income countries, owing to poor reliability and lack of piped water infrastructure. However, over time and across countries, the Demographic and Health Surveys monitoring program has inconsistently classified packaged water components as either improved or unimproved. Using data collected as part of the Performance Monitoring and Accountability 2020 (PMA2020) surveys on water options in nine study geographies across eight countries, we identified five geographies where packaged water constituted one of several options for 5% or more of users.

Mindfulness training attenuates the increase in salivary cortisol concentration associated with competition in highly trained wheelchair-basketball players.

This study determined the effect of 8 wk of mindfulness training (MT) on salivary cortisol (sCort) and rate of salivary Immunoglobulin-A (sIgA) secretion in wheelchair-basketball players during a competition period. The mindful group completed 8 weeks of MT in addition to training and competition. sCort and rate of sIgA secretion were measured at baseline, at 2-week intervals, the end and 2 weeks following the intervention.

Evaluation of Cross-Calibrated Ge/Ga Phantoms for Assessing PET/CT Measurement Bias in Oncology Imaging for Single- and Multicenter Trials.

Quantitative PET imaging is an important tool for clinical trials evaluating the response of cancers to investigational therapies. The standardized uptake value, used as a quantitative imaging biomarker, is dependent on multiple parameters that may contribute bias and variability. The use of long-lived, sealed PET calibration phantoms offers the advantages of known radioactivity activity concentration and simpler use than aqueous phantoms.