Gait Speed and Mood, Cognition, and Quality of Life in Older Adults With Atrial Fibrillation

Background: Low gait speed has been linked with impaired mood, cognition, and quality of life (QOL) in older adults. We examined whether low gait speed was associated with impaired mood, cognition, and QOL among older adults with atrial fibrillation (AF). Methods and Results: Participants (n=1185) had a diagnosis of AF, aged \u3e /=65 years, CHA2DS2VASc \u3e /=2 and had no contraindications to anticoagulation. Participants completed a 15-foot walk test, and low gait speed was categorized using cutoffs from the Fried Frailty Index. Participants self-reported measures of depressive symptoms (Patient Health Questionnaire 9 \u3e /=10), anxiety symptoms (Generalized Anxiety Disorder 7 \u3e /=10), cognitive impairment (Montreal Cognitive Assessment \u3c /=23), and potentially impaired Atrial Fibrillation Effect Quality-of-Life Questionnaire \u3c 80. Participants were on average aged 75.3 (SD: 7.0) years, 48.0% were women, and 85.5% were non-Hispanic white; 85.6% were taking an oral anticoagulant, 26.1% had low gait speed, 8.4% had elevated depressive symptoms, 5.7% had elevated anxiety symptoms, 41.1% were cognitively impaired, and 41.6% had potentially impaired AF-related QOL. Participants with low gait speed were significantly more likely to have elevated depressive symptoms (adjusted odds ratio: 2.1, 95% CI: 1.3-3.4), elevated anxiety symptoms (adjusted odds ratio: 2.2, 95% CI: 1.2-3.9), and cognitive impairment (adjusted odds ratio: 1.5, 95% CI: 1.1-2.1). Impaired AF-related QOL did not differ by gait speed after adjustment for clinical characteristics (adjusted odds ratio: 1.1, 95% CI: 0.8-1.5). Conclusions: Twenty-six percent of older adults with AF had low gait speed, and low gait speed was associated with impaired mood and cognition. Further research is needed to determine whether declines in gait speed lead to impaired mood and cognition or whether these conditions develop concurrently

Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.

Activated macrophages undergo metabolic reprogramming, which drives their pro-inflammatory phenotype, but the mechanistic basis for this remains obscure. Here, we demonstrate that upon lipopolysaccharide (LPS) stimulation, macrophages shift from producing ATP by oxidative phosphorylation to glycolysis while also increasing succinate levels. We show that increased mitochondrial oxidation of succinate via succinate dehydrogenase (SDH) and an elevation of mitochondrial membrane potential combine to drive mitochondrial reactive oxygen species (ROS) production. RNA sequencing reveals that this combination induces a pro-inflammatory gene expression profile, while an inhibitor of succinate oxidation, dimethyl malonate (DMM), promotes an anti-inflammatory outcome. Blocking ROS production with rotenone by uncoupling mitochondria or by expressing the alternative oxidase (AOX) inhibits this inflammatory phenotype, with AOX protecting mice from LPS lethality. The metabolic alterations that occur upon activation of macrophages therefore repurpose mitochondria from ATP synthesis to ROS production in order to promote a pro-inflammatory state

Cohort Profile: The United Kingdom Research study into Ethnicity and COVID-19 outcomes in Healthcare workers (UK-REACH)

The UK-REACH cohort was established to understand why ethnic minority healthcare workers (HCWs) are at risk of poorer outcomes from COVID-19 when compared with their White ethnic counterparts in the UK. Through study design, it contains a uniquely high percentage of participants from ethnic minority backgrounds about whom a wide range of qualitative and quantitative data have been collected. A total of 17 891 HCWs aged 16–89 years (mean age: 44) have been recruited from across the UK via all major healthcare regulators, individual National Health Service hospital trusts and UK HCW membership bodies who advertised the study to their registrants/staff to encourage participation in the study. Data available include linked healthcare records for 25 years from the date of consent and consent to obtain genomic sequencing data collected via saliva. Online questionnaires include information on demographics, COVID-19 exposures at work and home, redeployment in the workforce due to COVID-19, mental health measures, workforce attrition and opinions on COVID-19 vaccines, with baseline (n = 15 119), 6 (n = 5632) and 12-month follow-up (n = 6535) data captured. Request data access and collaborations by following documentation found at https://www.uk-reach.org/main/data_sharing

Healthcare workers’ views on mandatory SARS-CoV-2 vaccination in the UK: A cross-sectional, mixed-methods analysis from the UK-REACH study

Background: Several countries now have mandatory SARS-CoV-2 vaccination for healthcare workers (HCWs) or the general population. HCWs’ views on this are largely unknown. Using data from the nationwide UK-REACH study we aimed to understand UK HCW's views on improving SARS-CoV-2 vaccination coverage, including mandatory vaccination. // Methods: Between 21st April and 26th June 2021, we administered an online questionnaire via email to 17 891 UK HCWs recruited as part of a longitudinal cohort from across the UK who had previously responded to a baseline questionnaire (primarily recruited through email) as part of the United Kingdom Research study into Ethnicity And COVID-19 outcomes in Healthcare workers (UK-REACH) nationwide prospective cohort study. We categorised responses to a free-text question “What should society do if people do not get vaccinated against COVID-19?” using qualitative content analysis. We collapsed categories into a binary variable: favours mandatory vaccination or not, using logistic regression to calculate its demographic predictors, and its occupational, health, and attitudinal predictors adjusted for demographics. // Findings: Of 5633 questionnaire respondents, 3235 answered the free text question. Median age of free text responders was 47 years (IQR 36–56) and 2705 (74.3%) were female. 18% (n = 578) favoured mandatory vaccination (201 [6%] participants for HCWs and others working with vulnerable populations; 377 [12%] for the general population), but the most frequent suggestion was education (32%, n = 1047). Older HCWs (OR 1.84; 95% CI 1.44–2.34 [≥55 years vs 16 years to <40 years]), HCWs vaccinated against influenza (OR 1.49; 95% CI 1.11–2.01 [2 vaccines vs none]), and with more positive vaccination attitudes generally (OR 1.10; 95% CI 1.06–1.15) were more likely to favour mandatory vaccination, whereas female HCWs (OR= 0.79, 95% CI 0.63–0.96, vs male HCWs) and Black HCWs (OR=0.46, 95% CI 0.25–0.85, vs white HCWs) were less likely to. // Interpretation: Only one in six of the HCWs in this large, diverse, UK-wide sample favoured mandatory vaccination. Building trust, educating, and supporting HCWs who are hesitant about vaccination may be more acceptable, effective, and equitable

Access to personal protective equipment in healthcare workers during the COVID-19 pandemic in the United Kingdom: results from a nationwide cohort study (UK-REACH)

BACKGROUND: Healthcare workers (HCWs) are at high risk of SARS-CoV-2 infection. Effective use of personal protective equipment (PPE) reduces this risk. We sought to determine the prevalence and predictors of self-reported access to appropriate PPE (aPPE) for HCWs in the UK during the COVID-19 pandemic. METHODS: We conducted cross sectional analyses using data from a nationwide questionnaire-based cohort study administered between December 2020-February 2021. The outcome was a binary measure of self-reported aPPE (access all of the time vs access most of the time or less frequently) at two timepoints: the first national lockdown in the UK in March 2020 (primary analysis) and at the time of questionnaire response (secondary analysis). RESULTS: Ten thousand five hundred eight HCWs were included in the primary analysis, and 12,252 in the secondary analysis. 35.2% of HCWs reported aPPE at all times in the primary analysis; 83.9% reported aPPE at all times in the secondary analysis. In the primary analysis, after adjustment (for age, sex, ethnicity, migration status, occupation, aerosol generating procedure exposure, work sector and region, working hours, night shift frequency and trust in employing organisation), older HCWs and those working in Intensive Care Units were more likely to report aPPE at all times. Asian HCWs (aOR:0.77, 95%CI 0.67-0.89 [vs White]), those in allied health professional and dental roles (vs those in medical roles), and those who saw a higher number of COVID-19 patients compared to those who saw none (≥ 21 patients/week 0.74, 0.61-0.90) were less likely to report aPPE at all times. Those who trusted their employing organisation to deal with concerns about unsafe clinical practice, compared to those who did not, were twice as likely to report aPPE at all times. Significant predictors were largely unchanged in the secondary analysis. CONCLUSIONS: Only a third of HCWs in the UK reported aPPE at all times during the first lockdown and that aPPE had improved later in the pandemic. We also identified key determinants of aPPE during the first UK lockdown, which have mostly persisted since lockdown was eased. These findings have important implications for the safe delivery of healthcare during the pandemic

The Structure and Origin of Switchbacks: Parker Solar Probe Observations

Switchbacks are rapid magnetic field reversals that last from seconds to hours. Current Parker Solar Probe (PSP) observations pose many open questions in regards to the nature of switchbacks. For example, are they stable as they propagate through the inner heliosphere, and how are they formed? In this work, we aim to investigate the structure and origin of switchbacks. In order to study the stability of switchbacks, we suppose the small scale current sheets therein may work to braid and stabilize the switchbacks. Thus, we use the partial variance of increments method to identify the small scale current sheets, and then compare their distributions in switchbacks. With more than one thousand switchbacks identified with PSP observations in seven encounters, we find many more current sheets inside than outside switchbacks, indicating that these micro-structures should work to stabilize the S-shape structures of switchbacks. Additionally, with the helium measurements, we study the variations of helium abundance ratios and alpha-proton differential speeds to trace switchbacks to their origins. We find both helium-rich and helium-poor populations in switchbacks, implying the switchbacks could originate from both closed and open magnetic field regions in the Sun. Moreover, we observe that the alpha-proton differential speeds also show complex variations as compared to the local Alfv\'en speed. The joint distributions of both parameters show that low helium abundance together with low differential speed is the dominant state in switchbacks. The presence of small scale current sheets in switchbacks along with the helium features are in line with the hypothesis that switchbacks could originate from the Sun via interchange reconnection process. However, other formation mechanisms are not excluded

Impact of stratospheric air and surface emissions on tropospheric nitrous oxide during ATom

We measured the global distribution of tropospheric N2O mixing ratios during the NASA airborne Atmospheric Tomography (ATom) mission. ATom measured concentrations of ∼ 300 gas species and aerosol properties in 647 vertical profiles spanning the Pacific, Atlantic, Arctic, and much of the Southern Ocean basins, nearly from pole to pole, over four seasons (2016–2018). We measured N2O concentrations at 1 Hz using a quantum cascade laser spectrometer (QCLS). We introduced a new spectral retrieval method to account for the pressure and temperature sensitivity of the instrument when deployed on aircraft. This retrieval strategy improved the precision of our ATom QCLS N2O measurements by a factor of three (based on the standard deviation of calibration measurements). Our measurements show that most of the variance of N2O mixing ratios in the troposphere is driven by the influence of N2O-depleted stratospheric air, especially at mid- and high latitudes. We observe the downward propagation of lower N2O mixing ratios (compared to surface stations) that tracks the influence of stratosphere–troposphere exchange through the tropospheric column down to the surface. The highest N2O mixing ratios occur close to the Equator, extending through the boundary layer and free troposphere. We observed influences from a complex and diverse mixture of N2O sources, with emission source types identified using the rich suite of chemical species measured on ATom and the geographical origin calculated using an atmospheric transport model. Although ATom flights were mostly over the oceans, the most prominent N2O enhancements were associated with anthropogenic emissions, including from industry (e.g., oil and gas), urban sources, and biomass burning, especially in the tropical Atlantic outflow from Africa. Enhanced N2O mixing ratios are mostly associated with pollution-related tracers arriving from the coastal area of Nigeria. Peaks of N2O are often associated with indicators of photochemical processing, suggesting possible unexpected source processes. In most cases, the results show how difficult it is to separate the mixture of different sources in the atmosphere, which may contribute to uncertainties in the N2O global budget. The extensive data set from ATom will help improve the understanding of N2O emission processes and their representation in global models.This research has been supported by the National Aeronautics and Space Administration (grant nos. NNX15AJ23G, NNX17AF54G, NNX15AG58A, NNX15AH33A, and 80NSSC19K0124) and the National Science Foundation (grant nos. 1852977, AGS-1547626, and AGS-1623745)

Transcriptional Changes in Schistosoma mansoni during Early Schistosomula Development and in the Presence of Erythrocytes

Schistosome blood flukes cause more mortality and morbidity than any other human worm infection, but current control methods primarily rely on a single drug. There is a desperate need for new approaches to control this parasite, including vaccines. People become infected when the free-swimming larva, the cercaria, enters through the skin and becomes the schistosomulum. Schistosomula are susceptible to immune responses during their first few days in the host before they become adult parasites. We characterised the genes that these newly transformed parasites switch on when they enter the host to identify molecules that are critical for survival in the human host. Some of these highly up-regulated genes can be targeted for future development of new vaccines and drugs