Why older adults spend time sedentary and break their sedentary behavior: a mixed methods approach using life-logging equipment

Older adults are recommended to reduce their sedentary time to promote healthy ageing. To develop effective interventions identifying when, why, and how older adults are able to change their sitting habits is important. The aim of this mixed-method study was to improve our understanding of reasons for (breaking) sedentary behavior in older adults. Thirty older adults (74.0 [+/- 5.3] years old, 73% women) were asked about their believed reasons for (breaking) sedentary behavior, and about their actual reasons when looking at a personal storyboard with objective records of activPAL monitor data and time-lapse camera pictures showing all their periods of sedentary time in a day. The most often mentioned believed reason for remaining sedentary was television/radio (mentioned by 48.3%), while eating/drinking was most often mentioned as actual reason (96.6%). Only 17.2% believed that food/tea preparation was a reason to break up sitting, while this was an actual reason for 82.8% of the study sample. Results of this study show that there is a discrepancy between believed and actual reasons for (breaking) sedentary behavior. These findings suggest developing interventions utilizing the actual reasons for breaking sedentary behavior to reduce sedentary time in older adults

The aminoguanidine carboxylate BVT.12777 activates ATP-sensitive K(+ )channels in the rat insulinoma cell line, CRI-G1

BACKGROUND: 3-guanidinopropionic acid derivatives reduce body weight in obese, diabetic mice. We have assessed whether one of these analogues, the aminoguanidine carboxylate BVT.12777, opens K(ATP )channels in rat insulinoma cells, by the same mechanism as leptin. RESULTS: BVT.12777 hyperpolarized CRI-G1 rat insulinoma cells by activation of K(ATP )channels. In contrast, BVT.12777 did not activate heterologously expressed pancreatic β-cell K(ATP )subunits directly. Although BVT.12777 stimulated phosphorylation of MAPK and STAT3, there was no effect on enzymes downstream of PI3K. Activation of K(ATP )in CRI-G1 cells by BVT.12777 was not dependent on MAPK or PI3K activity. Confocal imaging showed that BVT.12777 induced a re-organization of cellular actin. Furthermore, the activation of K(ATP )by BVT.12777 in CRI-G1 cells was demonstrated to be dependent on actin cytoskeletal dynamics, similar to that observed for leptin. CONCLUSIONS: This study shows that BVT.12777, like leptin, activates K(ATP )channels in insulinoma cells. Unlike leptin, BVT.12777 activates K(ATP )channels in a PI3K-independent manner, but, like leptin, channel activation is dependent on actin cytoskeleton remodelling. Thus, BVT.12777 appears to act as a leptin mimetic, at least with respect to K(ATP )channel activation, and may bypass up-stream signalling components of the leptin pathway

Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension

Background: Disruption of cyclic nucleotide signaling in sympathetic postganglionic neurons contributes to impaired intracellular calcium handling (Ca2+) and the development of dysautonomia during the early stages of hypertension, although how this occurs is poorly understood. Emerging evidence supports the uncoupling of signalosomes in distinct cellular compartments involving cyclic nucleotide-sensitive PDEs (phosphodiesterases), which may underpin the autonomic phenotype in stellate neurons. Methods: Using a combination of single-cell RNA sequencing together with Forster resonance energy transfer-based sensors to monitor cyclic adenosine 3',5'-monophosphate, PKA (protein kinase A)-dependent phosphorylation and cGMP (cyclic guanosine 3',5'-monophosphate), we tested the hypothesis that dysregulation occurs in a sub-family of PDEs in the cytosol and outer mitochondrial membrane of neurons from the stellate ganglion. Results: PDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6. Conclusions: When taken together, these results suggest that site-specific inhibition of PDE2A and PDE6D at the outer mitochondrial membrane may provide a therapeutic target to ameliorate cardiac sympathetic impairment during the onset of hypertension

Exploring the context of sedentary behaviour in older adults (what, where, why, when and with whom)

BACKGROUND: Older adults are the most sedentary segment of the population. Little information is available about the context of sedentary behaviour to inform guidelines and intervention. There is a dearth of information about when, where to intervene and which specific behaviours intervention should target. The aim of this exploratory study was to obtain objective information about what older adults do when sedentary, where and when they are sedentary and in what social context. METHODS: The study was a cross-sectional data collection. Older adults (Mean age = 73.25, SD ± 5.48, median = 72, IQR = 11) volunteers wore activPAL monitors and a Vicon Revue timelapse camera between 1 and 7 days. Periods of sedentary behaviour were identified using the activPAL and the context extracted from the pictures taken during these periods. Analysis of context was conducted using the Sedentary Behaviour International Taxonomy classification system. RESULTS: In total, 52 days from 36 participants were available for analysis. Participants spent 70.1 % of sedentary time at home, 56.9 % of sedentary time on their own and 46.8 % occurred in the afternoon. Seated social activities were infrequent (6.9 % of sedentary bouts) but prolonged (18 % of sedentary time). Participants appeared to frequently have vacant sitting time (41 % of non-screen sedentary time) and screen sitting was prevalent (36 % of total sedentary time). CONCLUSIONS: This study provides valuable information to inform future interventions to reduce sedentary behaviour. Interventions should consider targeting the home environment and focus on the afternoon sitting time, though this needs confirmation in a larger study. Tackling social isolation may also be a target to reduce sedentary time

Reproducibility of optical coherence tomography airway imaging

Optical coherence tomography (OCT) is a promising imaging technique to evaluate small airway remodeling. However, the short-term insertion-reinsertion reproducibility of OCT for evaluating the same bronchial pathway has yet to be established. We evaluated 74 OCT data sets from 38 current or former smokers twice within a single imaging session. Although the overall insertion-reinsertion airway wall thickness (WT) measurement coefficient of variation (CV) was moderate at 12%, much of the variability between repeat imaging was attributed to the observer; CV for repeated measurements of the same airway (intra-observer CV) was 9%. Therefore, reproducibility may be improved by introduction of automated analysis approaches suggesting that OCT has potential to be an in-vivo method for evaluating airway remodeling in future longitudinal and intervention studies. (C) 2015 Optical Society of Americ

Country reviews of social assistance in crises: A compendium of rapid assessments of the nexus between social protection and humanitarian assistance in crisis settings

© 2021 Institute of Development Studies. This is an open access report available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://opendocs.ids.ac.uk/opendocs/handle/20.500.12413/16675This collection brings together brief overviews of the social assistance landscape in eight fragile and conflict-affected settings in sub-Saharan Africa and the Middle East: Iraq, Jordan, Lebanon, Mali, Niger, Nigeria, Somalia and Yemen. These overviews were prepared as part of Better Assistance in Crises (BASIC) Research, a multi-year programme (2020–24) supported by the Foreign, Commonwealth and Development Office (FCDO) of the UK government. BASIC Research aims to inform policy and programming on effective social assistance in situations of crisis, including for those who are experiencing climate-related shocks and stressors, protracted conflict and forced displacement.UKAi

Unbiased metabolome screen leads to personalized medicine strategy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disease that affects 1/350 individuals in the United Kingdom. The cause of amyotrophic lateral sclerosis is unknown in the majority of cases. Two-sample Mendelian randomization enables causal inference between an exposure, such as the serum concentration of a specific metabolite, and disease risk. We obtained genome-wide association study summary statistics for serum concentrations of 566 metabolites which were population matched with a genome-wide association study of amyotrophic lateral sclerosis. For each metabolite, we performed Mendelian randomization using an inverse variance weighted estimate for significance testing. After stringent Bonferroni multiple testing correction, our unbiased screen revealed three metabolites that were significantly linked to the risk of amyotrophic lateral sclerosis: Estrone-3-sulphate and bradykinin were protective, which is consistent with literature describing a male preponderance of amyotrophic lateral sclerosis and a preventive effect of angiotensin-converting enzyme inhibitors which inhibit the breakdown of bradykinin. Serum isoleucine was positively associated with amyotrophic lateral sclerosis risk. All three metabolites were supported by robust Mendelian randomization measures and sensitivity analyses; estrone-3-sulphate and isoleucine were confirmed in a validation amyotrophic lateral sclerosis genome-wide association study. Estrone-3-sulphate is metabolized to the more active estradiol by the enzyme 17β-hydroxysteroid dehydrogenase 1; further, Mendelian randomization demonstrated a protective effect of estradiol and rare variant analysis showed that missense variants within HSD17B1, the gene encoding 17β-hydroxysteroid dehydrogenase 1, modify risk for amyotrophic lateral sclerosis. Finally, in a zebrafish model of C9ORF72-amyotrophic lateral sclerosis, we present evidence that estradiol is neuroprotective. Isoleucine is metabolized via methylmalonyl-CoA mutase encoded by the gene MMUT in a reaction that consumes vitamin B12. Multivariable Mendelian randomization revealed that the toxic effect of isoleucine is dependent on the depletion of vitamin B12; consistent with this, rare variants which reduce the function of MMUT are protective against amyotrophic lateral sclerosis. We propose that amyotrophic lateral sclerosis patients and family members with high serum isoleucine levels should be offered supplementation with vitamin B12

Contextualising the pervasive impact of macroeconomic austerity on prison health in England: A qualitative study among international policymakers

Background: Prisons offer the state the opportunity to gain access to a population that is at particularly high risk of ill-health. Despite the supportive legal and policy structures surrounding prison rehabilitation, the oppressive nature of the austerity policy in England threatens its advanced improvement.Methods: Using grounded theory methodology, this is the first interdisciplinary qualitative study to explore the impact of macroeconomic austerity on prison health in England from the perspective of 29 international prison policymakers.Results: The far-reaching impact of austerity in England has established a regressive political system that shapes the societal attitude towards social issues, which has exacerbated the existing poor health of the prisoners. Austerity has undermined the notion of social collectivism, imposed a culture of acceptance among prison bureaucrats and the wider community, and normalised the devastating impacts of prison instability. These developments are evidenced by the increasing levels of suicide, violence, radicalisation and prison gangs among prisoners, as well as the imposition of long working hours and the high levels of absenteeism among prison staff.Conclusions: This study underscores an important and yet unarticulated phenomenon that despite being the fifth largest economy in the world, England’s poorest, marginalised and excluded population continues to bear the brunt of austerity. Reducing the prison population, using international obligations as minimum standards to protect prisoners’ right to health and providing greater resources would create a more positive and inclusive system, in line with England’s international and domestic commitments to the humane treatment of all people

Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication

New therapeutic targets are a valuable resource for treatment of SARS-CoV-2 viral infection. Genome-wide association studies have identified risk loci associated with COVID-19, but many loci are associated with comorbidities and are not specifictohost–virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of the 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins. Aggregating COVID-19 genome-wide association studies statistics for genespecific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19. EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. EXOSC2 is a component of the RNA exosome, and here, LC-MS/MS analysis of protein pulldowns demonstrated interaction between the SARS-CoV-2 RNA polymerase and most of the human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expressionandimpededSARS-CoV-2replicationwithoutimpacting cellular viability. Targeted depletion of EXOSC2 may be a safe and effective strategy to protect against clinical COVID-19