Men on the Move: A Randomized Controlled Feasibility Trial of a Scalable, Choice-Based, Physical Activity and Active Transportation Intervention for Older Men.

We conducted Men on the Move, a 12-week randomized controlled feasibility trial of a scalable, choice-based, physical activity (PA) and active transportation intervention. Participants were community-dwelling men aged 60 years and older (n = 29 intervention [INT] and n = 29 waitlist control [CON]). Trained activity coaches delivered: (a) one-on-one participant consultations to develop personal action plans for PA and active transportation, (b) monthly group-based motivational meetings, (c) weekly telephone support, (d) complimentary recreation and transit passes, and (e) pedometers and diaries for self-monitoring. Men on the Move demonstrated high rates of recruitment, retention, and intervention adherence. INT chose a variety of group-based and individual PAs and destinations for their personal action plans. At 12 weeks, INT achieved more steps, moderate-vigorous PA, and energy expenditure than CON. INT was also more likely to take transit and meet national guideline levels of PA. At 24 weeks follow-up, INT benefits were sustained for moderate-vigorous PA and energy expenditure.

Determining the optimal diagnostic and risk stratification approaches for people with hypertension in two rural populations in Kenya and The Gambia: a study protocol for IHCoR-Africa Work Package 2.

Background: Sub-Saharan Africa (SSA) has one of the highest prevalences of hypertension worldwide. The impact of hypertension is of particular concern in rural SSA, where access to clinics and hospitals is limited. Improvements in the management of people with hypertension in rural SSA could be achieved by sharing diagnosis and care tasks between the clinic and the community. To develop such a community-centred programme we need optimal approaches to identify and risk stratify patients with elevated blood pressure. The aim of the study is to improve the evidence base for diagnosis and risk estimation for a community-centred hypertension programme in two rural settings in SSA. Methods: We will conduct a cross-sectional study of 1250 adult participants in Kilifi, Kenya and Kiang West, The Gambia. The study has five objectives which will determine the: (1) accuracy of three blood pressure (BP) measurement methods performed by community health workers in identifying people with hypertension in rural SSA, compared to the reference standard method; (2) relationship between systolic BP and cardiovascular risk factors; (3) prevalence of hypertension-mediated organ damage (HMOD); (4) accuracy of innovative point-of-care (POC) technologies to identify patients with HMOD; and (5) cost-effectiveness of different combinations of BP and HMOD measurements for directing hypertension treatment initiation. Expected findings: This study will determine the accuracy of three methods for community BP measurement and POC technologies for HMOD assessment. Using the optimal methods in this setting it will estimate the prevalence of hypertension and provide the best estimate to date of HMOD prevalence in SSA populations. The cost-effectiveness of decision-making approaches for initiating treatment of hypertension will be modelled. These results will inform the development of a community-centred programme to improve care for hypertensive patients living in rural SSA. Existing community engagement networks will be used to disseminated within the research setting.

Many people live with high blood pressure in sub-Saharan Africa. In this region, the proportion of people with high blood pressure is one of the highest in the world. However, few people with high blood pressure are treated and this can lead to serious medical issues and even death. This is particularly true in rural areas where treatment and understanding of blood pressure is lower than in cities. There are many reasons why high blood pressure is a major health problem in rural sub-Saharan Africa, such as a lack of clear symptoms; less access to healthcare; and limited time to travel to clinics for care. One option for improving the management of blood pressure is to use a community-centred approach, where care is brought into the community making it easier to access. To bring care into the community, we need to find out what is the best way for community health workers to identify who needs to be treated. Standard techniques may not be useful in a rural community and could require too many resources to make them practical. This study aims to determine what is the best way to identify high blood pressure and related health complications in a community setting. The study will take place across two sites: one in Kilifi, Kenya and the other in Kiang West, The Gambia. We will enrol 1250 participants, with 625 in each country. The people living in these areas have been involved in the design of this study through community engagement and have helped identify the need for improving how blood pressure is treated in a rural areas. Throughout this study, we will continue to meet with the communities. Once the study is completed, we will use our strong links with the communities, healthcare providers and policymakers to share the results.

Analysis of integrin turnover in fly myotendinous junctions.

Transient (short-term) cell adhesion underlies dynamic processes such as cell migration, whereas stable (long-term) cell adhesion maintains tissue architecture. Ongoing adhesion complex turnover is essential for transient cell adhesion, but it is not known whether turnover is also required for maintenance of long-term adhesion. We used fluorescence recovery after photobleaching to analyze the dynamics of an integrin adhesion complex (IAC) in a model of long-term cell-ECM adhesion, myotendinous junctions (MTJs), in fly embryos and larvae. We found that the IAC undergoes turnover in MTJs and that this process is mediated by clathrin-dependent endocytosis. Moreover, the small GTPase Rab5 can regulate the proportion of IAC components that undergo turnover. Also, altering Rab5 activity weakened MTJs, resulting in muscle defects. In addition, growth of MTJs was concomitant with a decrease in the proportion of IAC components undergoing turnover. We propose that IAC turnover is tightly regulated in long-term cell-ECM adhesions to allow normal tissue growth and maintenance.

Integrin-mediated adhesion maintains sarcomeric integrity.

Integrin-mediated adhesion to the ECM is essential for normal development of animal tissues. During muscle development, integrins provide the structural stability required to construct such a highly tensile, force generating tissue. Mutations that disrupt integrin-mediated adhesion in skeletal muscles give rise to a myopathy in humans and mice. To determine if this is due to defects in formation or defects in maintenance of muscle tissue, we used an inducible, targeted RNAi based approach to disrupt integrin-mediated adhesion in fully formed adult fly muscles. A decrease in integrin-mediated adhesion in adult muscles led to a progressive loss of muscle function due to a failure to maintain normal sarcomeric cytoarchitecture. This defect was due to a gradual, age dependent disorganization of the sarcomeric actin, Z-line, and M-line. Electron microscopic analysis showed that reduction in integrin-mediated adhesion resulted in detachment of actin filaments from the Z-lines, separation of the Z-lines from the membrane, and eventually to disintegration of the Z-lines. Our results show that integrin-mediated adhesion is essential for maintaining sarcomeric integrity and illustrate that the seemingly stable adhesive contacts underlying sarcomeric architecture are inherently dynamic.

An ongoing role for structural sarcomeric components in maintaining Drosophila melanogaster muscle function and structure.

Animal muscles must maintain their function while bearing substantial mechanical loads. How muscles withstand persistent mechanical strain is presently not well understood. The basic unit of muscle is the sarcomere, which is primarily composed of cytoskeletal proteins. We hypothesized that cytoskeletal protein turnover is required to maintain muscle function. Using the flight muscles of Drosophila melanogaster, we confirmed that the sarcomeric cytoskeleton undergoes turnover throughout adult life. To uncover which cytoskeletal components are required to maintain adult muscle function, we performed an RNAi-mediated knockdown screen targeting the entire fly cytoskeleton and associated proteins. Gene knockdown was restricted to adult flies and muscle function was analyzed with behavioural assays. Here we analyze the results of that screen and characterize the specific muscle maintenance role for several hits. The screen identified 46 genes required for muscle maintenance: 40 of which had no previously known role in this process. Bioinformatic analysis highlighted the structural sarcomeric proteins as a candidate group for further analysis. Detailed confocal and electron microscopic analysis showed that while muscle architecture was maintained after candidate gene knockdown, sarcomere length was disrupted. Specifically, we found that ongoing synthesis and turnover of the key sarcomere structural components Projectin, Myosin and Actin are required to maintain correct sarcomere length and thin filament length. Our results provide in vivo evidence of adult muscle protein turnover and uncover specific functional defects associated with reduced expression of a subset of cytoskeletal proteins in the adult animal.

The systematic identification of cytoskeletal genes required for Drosophila melanogaster muscle maintenance.

Animal muscles must maintain their function and structure while bearing substantial mechanical loads. How muscles withstand persistent mechanical strain is presently not well understood. Understanding the mechanisms by which tissues maintain their complex architecture is a key goal of cell biology. This dataset represents a systematic screen through the Drosophila melanogaster cytoskeleton to identify genes that are required to maintain tissue, specifically muscle, architecture. Using RNA interference (RNAi), we knocked down 238 genes in Drosophila and assayed for climbing ability with a robust behavioural assay. Here we present the summary of the screen and provide the complete results of the assays. We have uncovered a number of novel hits that would reward further study. The data are easy to use: the raw data are provided to allow researchers to perform their own analysis and analysed results are given indicating whether or not the genes are required for muscle maintenance. This dataset will allow other researchers to identify candidate genes for more detailed study and lead to better understanding of muscle maintenance.