4,158 research outputs found

    Objectively measured physical activity and kidney function in older men; a cross-sectional population-based study.

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    Background: kidney function declines in older adults and physical activity levels are low. We investigated whether higher levels of physical activity and lower levels of sedentary behaviour were associated with lower odds of low kidney function in older men. Methods: cross-sectional study of 1,352 men from the British Regional Heart Study, mean (standard deviation) age 78.5 (4.6) year. Physical activity and sedentary behaviour were measured using Actigraph GT3X accelerometers. Kidney function was measured by estimated Glomerular filtration rate (eGFR) using the chronic kidney disease-EPI creatinine-cystatin equation. Associations between physical (in)activity and kidney function were investigated using regression models. Results: higher levels of physical activity and lower levels of sedentary behaviour were associated with reduced odds ratios (ORs) for lower eGFR (<45 versus β‰₯45 ml/min per 1.73 m2) after adjustment for covariates. Each additional 1,000 steps, 30 min of light physical activity and 10 min of moderate/vigorous physical activity per day were associated with a lower odds (95% confidence interval (CI)) of a low eGFR; OR 0.81 (0.73, 0.91), OR 0.87 (0.78, 0.97) and OR 0.84 (0.76, 0.92), respectively. Each additional 30 min of sedentary behaviour per day was associated with a higher odds of a low eGFR (1.16 95% CI 1.06, 1.27). Associations between moderate/vigorous physical activity and lower kidney function persisted after adjustment for light physical activity or sedentary behaviour. Conclusion: physical activity is associated with kidney function in older men and could be of public health importance in this group who are at increased risk of poor kidney function and low physical activity. More evidence is needed on whether the association is causal

    Does total volume of physical activity matter more than pattern for onset of CVD? A prospective cohort study of older British men.

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    AIMS: With increasing age, physical inactivity and sedentary behaviour levels increase, as does cardiovascular disease (CVD) incidence. We investigate how device-measured sedentary behaviour and physical activity (PA) are related to CVD onset in men aged 70+; whether the total volume of activity is more important than pattern. METHODS AND RESULTS: Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978-80. In 2010-12, 3137 survivors were invited to complete questionnaires and wear an Actigraph GT3x accelerometer for 7β€―days. PA intensity was categorised as sedentary, light and moderate to vigorous (MVPA). Men were followed up for Myocardial Infarction, stroke and heart failure (ICD9 410-414, 430-438 and 428) morbidity and mortality from 2010 to 12 to June 2016. Hazard Ratios (HRs) for incident Cardiovascular Disease (CVD) were estimated. 1528/3137 (49%) men had sufficient accelerometer data. 254 men with pre-existing CVD were excluded. Participants' mean age was 78.4 (range 71-92)β€―years. After median 4.9β€―years follow-up, 122 first CVD events occurred in 1181 men (22.7/1000β€―person-years) with complete data. For each additional 30β€―min in sedentary behaviour, light PA,10β€―min in MVPA, or 1000 steps/day, HRs for CVD were 1.09(95%CI 1.00, 1.19), 0.94(0.85, 1.04), 0.88(0.81, 0.96) and 0.86(0.78 to 0.95) respectively, adjusted for measurement-related factors, socio-demographics, health behaviours and disability. HRs for accumulating 150β€―min/week MVPA in bouts β‰₯1β€―min and bouts β‰₯10β€―min were 0.47(0.32 to 0.69), and 0.49(0.25, 0.98). CONCLUSIONS: In older men, high volume of steps or MVPA rather than MVPA bouts was associated with reduced CVD risk

    Adherence to physical activity guidelines in older adults, using objectively measured physical activity in a population-based study.

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    BACKGROUND: Physical activity (PA) levels in older adults decline with age. The prevalence and correlates of adherence to current UK PA guidelines in older adults has not been studied using objectively measured PA, which can examine precisely whether PA is carried out in bouts of specified length and intensity. METHODS: Free living men and women aged 70-93 years from 25 towns in the United Kingdom, participating in parallel on-going population based cohort studies were invited (by post) to wear a GT3x accelerometer over the hip for one week in 2010-12. Adherence to UK PA guidelines was defined as β‰₯150 minutes/week of moderate or vigorous PA (MVPA) in bouts of β‰₯10 minutes; the effect of different intensities and durations were examined. RESULTS: 1593 men and 857 women participated (responses 51% and 29% respectively). 15% men and 10% women achieved β‰₯150 minutes/week of MVPA (defined as >1040 cpm) in bouts lasting β‰₯10 minutes. With MVPA defined as >1952 cpm, prevalences were 7% and 3% respectively. Those adhering to guidelines were younger, had fewer chronic health conditions, less depression, less severe mobility limitations, but higher exercise self-efficacy and exercise outcomes expectations. They rated their local environment more highly for social activities and leisure facilities, having somewhere nice to go for a walk and feeling safe after dark, They left the house on more days per week, were more likely to use active transport (cycle or walk) and to walk a dog regularly. CONCLUSIONS: Few older adults attain current PA guidelines. Health promotion to extend the duration of moderate-intensity activity episodes to 10 minutes or more could yield important health gains among older adults. However future studies will need to clarify whether attaining guideline amounts of PA in spells lasting 10 minutes or more is critical for reducing chronic disease risks as well as improving cardiometabolic risk factors

    Drop Traffic in Microfluidic Ladder Networks with Fore-Aft Structural Asymmetry

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    We investigate the dynamics of pairs of drops in microfluidic ladder networks with slanted bypasses, which break the fore-aft structural symmetry. Our analytical results indicate that unlike symmetric ladder networks, structural asymmetry introduced by a single slanted bypass can be used to modulate the relative drop spacing, enabling them to contract, synchronize, expand, or even flip at the ladder exit. Our experiments confirm all these behaviors predicted by theory. Numerical analysis further shows that while ladder networks containing several identical bypasses are limited to nearly linear transformation of input delay between drops, mixed combination of bypasses can cause significant non-linear transformation enabling coding and decoding of input delays.Comment: 4 pages, 5 figure

    Structure of the hDmc1-ssDNA filament reveals the principles of its architecture

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    In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination

    Feasibility and acceptability of NIDUS-professional, a training and support intervention for homecare workers caring for clients living with dementia: a cluster-randomised feasibility trial.

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    INTRODUCTION: In the first randomised controlled trial of a dementia training and support intervention in UK homecare agencies, we aimed to assess: acceptability of our co-designed, manualised training, delivered by non-clinical facilitators; outcome completion feasibility; and costs for a future trial. METHODS: This cluster-randomised (2:1) single-blind, feasibility trial involved English homecare agencies. Intervention arm agency staff were offered group videocall sessions: 6 over 3 months, then monthly for 3 months (NIDUS-professional). Family carers (henceforth carers) and clients with dementia (dyads) were offered six to eight complementary, individual intervention sessions (NIDUS-Family). We collected potential trial measures as secondary outcomes remotely at baseline and 6 months: HCW (homecare worker) Work-related Strain Inventory (WRSI), Sense of Competence (SoC); proxy-rated Quality of Life (QOL), Disability Assessment for Dementia scale (DAD), Neuropsychiatric Inventory (NPI) and Homecare Satisfaction (HCS). RESULTS: From December 2021 to September 2022, we met agency (4 intervention, 2 control) and HCWs (n = 62) recruitment targets and recruited 16 carers and 16/60 planned clients. We met a priori progression criteria for adherence (β‰₯4/6 sessions: 29/44 [65.9%,95% confidence interval (CI): 50.1,79.5]), HCW or carer proxy-outcome completion (15/16 (93.8% [69.8,99.8]) and proceeding with adaptation for HCWs outcome completion (46/63 (73.0% [CI: 60.3,83.4]). Delivery of NIDUS-Professional costs was Β£6,423 (Β£137 per eligible client). WRSI scores decreased and SoC increased at follow-up, with no significant between-group differences. For intervention arm proxy-rated outcomes, carer-rated QOL increased, HCW-rated was unchanged; carer and HCW-rated NPI decreased; DAD decreased (greater disability) and HCS was unchanged. CONCLUSION: A pragmatic trial is warranted; we will consider using aggregated, agency-level client outcomes, including neuropsychiatric symptoms

    Protective effect of wild Corni fructus methanolic extract against acute alcoholic liver injury in mice

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    Background: In Chinese folk medicine, Corni fructus (C. fructus) has traditionally been used to improve liver function, although the mechanism underlying its activity remains unclear. The aim of the present study was to evaluate the protective effects of wild C. fructus methanolic extract against acute alcoholic liver injury.Methods: Alcohol was administered to mice for three consecutive days, either alone or in combination with C. fructus methanolic extract (50, 100, or 200mg/kg body weight/d). Serum and liver tissue were collected from the animals and subjected to biochemical and histopathological analyses.Results:C. fructus significantly alleviated alcohol-induced liver injury by reducing serum alanine aminotransferase, aspartate aminotransferase, and thiobarbituric acid reactive species, inhibiting hydroxyl radicals (center dot OH), and increasing total superoxide dismutase, glutathione peroxidase, and glutathione in the liver (P<0.05). In addition, the C. fructus treatment inhibited the expression and activity of cytochrome P450 2E1 (P<0.05)Conclusions:C. fructus could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury.- This work was supported by the Construction Project of Shaanxi Collaborative Innovation Center (2015, Shaanxi Sci-tech University); High-End Foreign Experts Recruitment Program [Grant GDW20146100228]; and Key Construction Program of International Cooperation Base in S&T Shaanxi Province, China [Grant 2015SD0018].info:eu-repo/semantics/publishedVersio

    The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

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    p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate
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