Brief bouts of device-measured intermittent lifestyle physical activity and its association with major adverse cardiovascular events and mortality in people who do not exercise: a prospective cohort study

BACKGROUND: Guidelines emphasise the health benefits of bouts of physical activity of any duration. However, the associations of intermittent lifestyle physical activity accumulated through non-exercise with mortality and major adverse cardiovascular events (MACE) remain unclear. We aimed to examine the associations of bouts of moderate-to-vigorous intermittent lifestyle physical activity (MV-ILPA) and the proportion of vigorous activity contributing within these bouts with mortality and MACE. METHODS: In this prospective cohort study, we used data from the UK Biobank on adults who do not exercise (ie, those who did not report leisure-time exercise) who had wrist-worn accelerometry data available. Participants were followed up until Nov 30, 2022, with the outcome of interest of all-cause mortality obtained through linkage with NHS Digital of England and Wales, and the NHS Central Register and National Records of Scotland, and MACE obtained from inpatient hospitalisation data provided by the Hospital Episode Statistics for England, the Patient Episode Database for Wales, and the Scottish Morbidity Record for Scotland. MV-ILPA bouts were derived using a two-level Random Forest classifier and grouped as short (<1 min), medium (1 to <3 min; 3 to <5 min), and long (5 to <10 min). We further examined the dose-response relationship of the proportion of vigorous physical activity contributing to the MV-ILPA bout. FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 684 Biobank participants wore an accelerometer on their wrist. 25 241 adults (mean age 61·8 years [SD 7·6]), of whom 14 178 (56·2%) were women, were included in our analysis of all-cause mortality. During a mean follow-up duration of 7·9 years (SD 0·9), 824 MACE and 1111 deaths occurred. Compared with bouts of less than 1 min, mortality risk was lower for bouts of 1 min to less than 3 min (hazard ratio [HR] 0·66 [0·53-0·81]), 3 min to less than 5 min (HR 0·56 [0·46-0·69]), and 5 to less than 10 min (HR 0·48 [0·39-0·59]). Similarly, compared with bouts of less than 1 min, risk of MACE was lower for bouts of 1 min to less than 3 min (HR 0·71 [0·54-0·93]), 3 min to less than 5 min (0·62 [0·48-0·81]), and 5 min to less than 10 min (0·59 [0·46-0·76]). Short bouts (<1 min) were associated with lower MACE risk only when bouts were comprised of at least 15% vigorous activity. INTERPRETATION: Intermittent non-exercise physical activity was associated with lower mortality and MACE. Our results support the promotion of short intermittent bouts of non-exercise physical activity of moderate-to-vigorous intensity to improve longevity and cardiovascular health among adults who do not habitually exercise in their leisure time. FUNDING: Australian National Health, Medical Research Council, and Wellcome Trust

Qualitative study of practices and attitudes towards physical activity among prediabetic men and women in urban and rural Malawi.

OBJECTIVES: Given the decline in physical activity levels in Malawi, like other sub-Saharan African countries, and its implication for non-communicable disease (NCD) prevention, this study aimed to compare and contrast accounts of practices and attitudes towards physical activity among Malawian men and women (previously identified as having pre-diabetes) in urban and rural settings. SETTING: Two communities: one urban (Lilongwe) and one rural (Karonga). PARTICIPANTS: 14 men (urban N=6, rural N=8) and 18 women (urban N=9, rural N=9) classified as prediabetic during their participation in an NCD survey 3-5 years previously. DESIGN: A qualitative focus group study (N=4) and thematic analysis, with the ecological model used as a framework to characterise the types of physical activity people engaged in and potential ways to support them to exercise more. RESULTS: Participants reported undertaking different types of physical activity across all ecological model domains (household, occupational, transport, recreational). Rural participants reported more vigorous physical activities than urban participants, and women reported more household activities than men. Many participants recognised a need to promote physical activity in Malawi, and the health benefits of doing so, including the importance of physical activity in helping them stay strong to maintain physical functioning. Barriers to physical activity included competing priorities (especially urban men), societal expectations around wealth, use of motorised transport, lack of accessible facilities for women, ageing and ill health. CONCLUSIONS: Physical activity is declining in Malawi as working and transport practices change in response to economic development, making promotion of alternative forms of physical activity a public health priority. Multilevel interventions emphasising the personal benefits/value of physical activity for all ages, and routine and group-based exercising, as well as investment in accessible recreational facilities (including for women) and active travel infrastructure should be considered to improve physical activity levels in Malawi

Gender differences in the association between adiposity and probable major depression: a cross-sectional study of 140,564 UK Biobank participants

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Previous studies on the association between adiposity and mood disorder have produced contradictory results, and few have used measurements other than body mass index (BMI). We examined the association between probable major depression and several measurements of adiposity: BMI, waist circumference (WC), waist-hip-ratio (WHR), and body fat percentage (BF%).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; We conducted a cross-sectional study using baseline data on the sub-group of UK Biobank participants who were assessed for mood disorder. Multivariate logistic regression models were used, adjusting for potential confounders including: demographic and life-style factors, comorbidity and psychotropic medication.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Of the 140,564 eligible participants, evidence of probable major depression was reported by 30,145 (21.5%). The fully adjusted odds ratios (OR) for obese participants were 1.16 (95% confidence interval (CI) 1.12, 1.20) using BMI, 1.15 (95% CI 1.11, 1.19) using WC, 1.09 (95% CI 1.05, 1.13) using WHR and 1.18 (95% CI 1.12, 1.25) using BF% (all p &#60;0.001). There was a significant interaction between adiposity and gender (p = 0.001). Overweight women were at increased risk of depression with a dose response relationship across the overweight (25.0-29.9 kg/m2), obese I (30.0-34.9 kg/m2), II (35.0-39.9 kg/m2) and III (≥40.0 kg/m2) categories; fully adjusted ORs 1.14, 1.20, 1.29 and 1.48, respectively (all p &#60; 0.001). In contrast, only obese III men had significantly increased risk of depression (OR 1.29, 95% CI 1.08, 1.54, p = 0.006).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Adiposity was associated with probable major depression, irrespective of the measurement used. The association was stronger in women than men. Physicians managing overweight and obese women should be alert to this increased risk

Dysglycaemia and South Asian ethnicity: a proteomic discovery and confirmation analysis highlights differences in ZAG

Aims To (1) explore and verify differences in the plasma proteome of white European (WE) and South Asian (SA) adults with normal glycaemic control (NGC) or non-diabetic hyperglycaemia (NDH) and to (2) validate these findings using a separate WE and SA cohort at a high risk of NDH. Methods Mass spectrometry analysis was performed on fasted samples from 72 WE or SA men with NGC or NDH. These results were verified using specific biochemical assays and validated by repeating the analysis in an additional cohort of 30 WE and 30 SA adults. Proteomic results were analysed using independent samples t test and univariate analysis. The targeted assay results were analysed using generalised linear models with adjustment for appropriate covariates including age, BMI, fasting plasma glucose, high-density lipoprotein-cholesterol, triglycerides and sex. Results Only zinc-alpha-2-glycoprotein (ZAG) significantly differed between both ethnicities and glycaemic control groups. ZAG-specific biochemical assays verified the lower circulating ZAG in SAs (41.09 versus 37.07 (mg L−1); p = 0.014), but not the difference between NGC and NDH groups (p = 0.539). Validation of the ethnicity difference in a separate cohort confirmed that, after adjustment for covariates, ZAG was lower in SAs (p = 0.018). There was no association between ZAG and glycaemic control in the validation cohort. Conclusions Our analyses identified that ZAG is lower in SAs compared to WEs, but its difference between glycaemic control statuses was uncertain. Further research is needed to establish whether lower ZAG in SAs is associated with, or prognostic of, health outcomes, particularly regarding the risk of dysglycaemia

“I see salt everywhere”: A qualitative examination of the utility of arts-based participatory workshops to study noncommunicable diseases in Tanzania and Malawi.

The burden of noncommunicable diseases (NCDs) including hypertension, diabetes, and cancer, is rising in Sub-Saharan African countries like Tanzania and Malawi. This increase reflects complex interactions between diverse social, environmental, biological, and political factors. To intervene successfully, new approaches are therefore needed to understand how local knowledges and attitudes towards common NCDs influence health behaviours. This study compares the utility of using a novel arts-based participatory method and more traditional focus groups to generate new understandings of local knowledges, attitudes, and behaviours towards NCDs and their risk factors. Single-gender arts-based participatory workshops and focus group discussions were conducted with local communities in Tanzania and Malawi. Thematic analysis compared workshop and focus group transcripts for depth of content and researcher-participant hierarchies. In addition, semiotic analysis examined the contribution of photographs of workshop activities to understanding participants’ experiences and beliefs about NCD risk factors. The arts-based participatory workshops produced in-depth, vivid, emotive narratives of participants’ beliefs about NCDs and their impact (e.g., “… it spreads all over your body and kills you—snake’s poison is similar to diabetes poison”), while the focus groups provided more basic accounts (e.g., “diabetes is a fast killer”). The workshops also empowered participants to navigate activities with autonomy, revealing their almost overwhelmingly negative beliefs about NCDs. However, enabling participants to direct the focus of workshop activities led to challenges, including the perpetuation of stigma (e.g., comparing smells associated with diabetes symptoms with sewage). Semiotic analysis of workshop photographs provided little additional insight beyond that gained from the transcripts. Arts-based participatory workshops are promising as a novel method to inform development of culturally relevant approaches to NCD prevention in Tanzania and Malawi. Future research should incorporate more structured opportunities for participant reflection during the workshops to minimise harm from any emerging stigma

Nitrogen limitation constrains sustainability of ecosystem response to CO2

Enhanced plant biomass accumulation in response to elevated atmospheric CO2 concentration could dampen the future rate of increase in CO2 levels and associated climate warming. However, it is unknown whether CO2-induced stimulation of plant growth and biomass accumulation will be sustained or whether limited nitrogen (N) availability constrains greater plant growth in a CO2-enriched world(1-9). Here we show, after a six-year field study of perennial grassland species grown under ambient and elevated levels of CO2 and N, that low availability of N progressively suppresses the positive response of plant biomass to elevated CO2. Initially, the stimulation of total plant biomass by elevated CO2 was no greater at enriched than at ambient N supply. After four to six years, however, elevated CO2 stimulated plant biomass much less under ambient than enriched N supply. This response was consistent with the temporally divergent effects of elevated CO2 on soil and plant N dynamics at differing levels of N supply. Our results indicate that variability in availability of soil N and deposition of atmospheric N are both likely to influence the response of plant biomass accumulation to elevated atmospheric CO2. Given that limitations to productivity resulting from the insufficient availability of N are widespread in both unmanaged and managed vegetation(5,7-9), soil N supply is probably an important constraint on global terrestrial responses to elevated CO2.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62769/1/nature04486.pd

The Liberation of Embryonic Stem Cells

Mouse embryonic stem (ES) cells are defined by their capacity to self-renew and their ability to differentiate into all adult tissues including the germ line. Along with efficient clonal propagation, these properties have made them an unparalleled tool for manipulation of the mouse genome. Traditionally, mouse ES (mES) cells have been isolated and cultured in complex, poorly defined conditions that only permit efficient derivation from the 129 mouse strain; genuine ES cells have not been isolated from another species in these conditions. Recently, use of small molecule inhibitors of glycogen synthase kinase 3 (Gsk3) and the Fgf-MAPK signaling cascade has permitted efficient derivation of ES cells from all tested mouse strains. Subsequently, the first verified ES cells were established from a non-mouse species, Rattus norvegicus. Here, we summarize the advances in our understanding of the signaling pathways regulating mES cell self-renewal that led to the first derivation of rat ES cells and highlight the new opportunities presented for transgenic modeling on diverse genetic backgrounds. We also comment on the implications of this work for our understanding of pluripotent stem cells across mammalian species

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention