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

Is ‘activist’ a dirty word? Place identity, activism and unconventional gas development across three continents

Communities respond to unconventional gas in a variety of ways. In some communities, industry has held a social license, while in other areas, industrial development has been slowed, halted, or prevented by social resistance. Repeatedly, across multiple nations and communities, we have observed that social identities that either incorporate or eschew activism intersect with perceptions of this development's effect on place identity to either foster or discourage opposition. Particularly interesting are cases in which fracking is perceived to threaten local place identity, but where activism conflicts with social identity. To mobilise different sectors of the population, it often appears important for local residents to be perceived as ‘regular citizens’ and not as activists. We explore how intersection of social identities and place identity shaped the different ways in which communities in Australia, Canada, the Netherlands, and the United States have responded to unconventional gas development. Communities resisting development often see ‘activism’ as something that ‘outsiders’ do and that must be rejected as insufficiently objective and neutral. This view of activism and activists produces specific forms of resistance that differ from typical ‘activist’ actions, in which ‘knowledge’, ‘information’, neutrality, and objectivity are particularly important.</p

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

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

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

Tissue Specific Profiling of Females of Schistosoma japonicum by Integrated Laser Microdissection Microscopy and Microarray Analysis

Schistosomes are parasitic worms responsible for important human diseases in tropical and developing nations. There is urgent need to develop new drugs and vaccines to augment current treatments for this disease. In recent years, concerted efforts by many laboratories have led to extensive genetic sequencing of the parasites, and the publication of genome sequence for two agents of schistosomiasis appears imminent. This genetic information has revealed many molecules expressed by the schistosome parasites for which no functional information is available. This lack of information extends to ignorance of where in the complex multicellular schistosome parasites the genes are expressed. We integrated two molecular and cellular techniques to address these knowledge gaps. We used laser microdissection microscopy to dissect small but highly important tissues involved in nutrition and reproduction from sections of female Schistosoma japonicum. From these dissected tissues we then used a broad molecular biology method to identify the multiple genes active in these tissues. Our approach has allowed us to formulate the basis of a “gene atlas” for schistosome parasites, defining the expression repertoire of specific tissues. The better understanding of the roles of tissues in parasite biology, especially in development, reproduction and interactions with its human hosts, should promote future investigations into pathogenesis and control of these significant parasites

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