Participatory learning and action to address type 2 diabetes in rural Bangladesh: a qualitative process evaluation

BACKGROUND: Diabetes is 7th largest cause of death worldwide, and prevalence is increasing rapidly in low-and middle-income countries. There is an urgent need to develop and test interventions to prevent and control diabetes and develop the theory about how such interventions can be effective. We conducted a participatory learning and action (PLA) intervention with community groups in rural Bangladesh which was evaluated through a cluster randomised controlled trial. There was a large reduction in the combined prevalence of type 2 diabetes and intermediate hyperglycaemia in the PLA group compared with the control group. We present findings from qualitative process evaluation research to explore how this intervention was effective. // METHODS: We conducted group interviews and focus group discussions using photovoice with purposively sampled group attenders and non-attenders, and intervention implementers. Data were collected before the trial analysis. We used inductive content analysis to generate theory from the data. // RESULTS: The intervention increased the health literacy of individuals and communities - developing their knowledge, capacity and self-confidence to enact healthy behaviours. Community, household and individual capacity increased through social support and social networks, which then created an enabling community context, further strengthening agency and enabling community action. This increased opportunities for healthy behaviour. Community actions addressed lack of awareness about diabetes, gendered barriers to physical activity and lack of access to blood glucose testing. The interaction between the individual, household, and community contexts amplified change, and yet there was limited engagement with macro level, or ‘state’, barriers to healthy behaviour. // CONCLUSIONS: The participatory approach enabled groups to analyse how context affected their ability to have healthy behaviours and participants engaged with issues as a community in the ways that they felt comfortable. We suggest measuring health literacy and social networks in future interventions and recommend specific capacity strengthening to develop public accountability mechanisms and health systems strengthening to complement community-based interventions

Community participatory learning and action cycle groups to reduce type 2 diabetes in Bangladesh (D:Clare trial): study protocol for a stepped-wedge cluster randomised controlled trial.

BACKGROUND: An estimated 463 million people globally have diabetes, with the prevalence growing in low-and middle-income settings, such as Bangladesh. Given the need for context-appropriate interventions to prevent type 2 diabetes mellitus (T2DM), the 'Diabetes: Community-led Awareness, Response and Evaluation' (D:Clare) trial will rigorously evaluate the replication and scale-up of a participatory learning and action (PLA) cycle intervention in Bangladesh, to inform policy on population-level T2DM prevention and control. METHODS: This is a stepped-wedge cluster randomised controlled trial, with integrated process and economic evaluations, conducted from March 2020 to September 2022. The trial will evaluate a community-based four-phase PLA cycle intervention focused on prevention and control of T2DM implemented over 18 months, against a control of usual care. Twelve clusters will be randomly allocated (1:1) to implement the intervention at project month 1 or 12. The intervention will be evaluated through three cross-sectional surveys at months 1, 12 and 24. The trial will be conducted in Alfadanga Upazila, Faridpur district, with an estimated population of 120,000. Clusters are defined as administrative geographical areas, with approximately equal populations. Each of the six unions in Alfadanga will be divided into two clusters, forming 12 clusters in total. Given the risk of inter-cluster contamination, evaluation surveys will exclude villages in border areas. Participants will be randomly sampled, independently for each survey, from a population census conducted in January 2020. The primary outcome is the combined prevalence of intermediate hyperglycaemia and T2DM, measured through fasting and 2-h post-glucose load blood tests. A total of 4680 participants provide 84% power to detect a 30% reduction in the primary outcome, assuming a baseline of 30% and an ICC of 0.07. The analysis will be by intention-to-treat, comparing intervention and control periods across all clusters, adjusting for geographical clustering. DISCUSSION: This study will provide further evidence of effectiveness for community-based PLA to prevent T2DM at scale in a rural Bangladesh setting. However, we encountered several challenges in applying the stepped-wedge design to our research context, with particular consideration given to balancing seasonality, timing and number of steps and estimation of partial versus full effect. TRIAL REGISTRATION: ISRCTN: ISRCTN42219712 . Registered on 31 October 2019

Participatory learning and action cycles with women s groups to prevent neonatal death in low-resource settings: A multi-country comparison of cost-effectiveness and affordability.

WHO recommends participatory learning and action cycles with women's groups as a cost-effective strategy to reduce neonatal deaths. Coverage is a determinant of intervention effectiveness, but little is known about why cost-effectiveness estimates vary significantly. This article reanalyses primary cost data from six trials in India, Nepal, Bangladesh and Malawi to describe resource use, explore reasons for differences in costs and cost-effectiveness ratios, and model the cost of scale-up. Primary cost data were collated, and costing methods harmonized. Effectiveness was extracted from a meta-analysis and converted to neonatal life-years saved. Cost-effectiveness ratios were calculated from the provider perspective compared with current practice. Associations between unit costs and cost-effectiveness ratios with coverage, scale and intensity were explored. Scale-up costs and outcomes were modelled using local unit costs and the meta-analysis effect estimate for neonatal mortality. Results were expressed in 2016 international dollars. The average cost was $203 (range:$61-$537) per live birth. Start-up costs were large, and spending on staff was the main cost component. The cost per neonatal life-year saved ranged from$135 to $1627. The intervention was highly cost-effective when using income-based thresholds. Variation in cost-effectiveness across trials was strongly correlated with costs. Removing discounting of costs and life-years substantially reduced all cost-effectiveness ratios. The cost of rolling out the intervention to rural populations ranges from 1.2% to 6.3% of government health expenditure in the four countries. Our analyses demonstrate the challenges faced by economic evaluations of community-based interventions evaluated using a cluster randomized controlled trial design. Our results confirm that women's groups are a cost-effective and potentially affordable strategy for improving birth outcomes among rural populations

Distribution of diabetes, hypertension and non-communicable disease risk factors among adults in rural Bangladesh: a cross-sectional survey

Background: Non-communicable diseases (NCDs) are increasing in low-income settings. We conducted a survey of risk factors, blood pressure and blood glucose in rural Bangladesh and assessed variations by age, sex and wealth. Methods: We surveyed a random sample of 12 280 adults aged >30 years in 96 villages in rural Bangladesh. Fieldworkers measured blood glucose and conducted an insulin tolerance test with a repeat blood test 120 min post glucose ingestion. Blood pressure, anthropometric, socioeconomic, lifestyle and behavioural risk factors data were also collected. Data were analysed to describe the prevalence of diabetes, intermediate hyperglycaemia, hypertension and NCD risk factors by age, sex and wealth. Results: Women had higher levels of overweight or obesity and lower levels of physical activity and fruit and vegetable consumption than men; 63% of men used tobacco compared with 41.3% of women. Overweight or obesity and abdominal obesity (waist to hip ratio) increased with socioeconomic status (least poor vs most poor: OR (95% CI) 3.21 (2.51 to 4.11) for men and 2.83 (2.28 to 3.52) for women). Tobacco use, passive smoke exposure and salt consumption fell with increasing socioeconomic status in both sexes. Clustering of risk factors showed more than 70% of men and women reported at least three risk factors. Women in the least poor group were 33% more likely to have three or more risk factors compared with women in the most poor group (1.33 (95% CI 1.17 to 1.58)). The combined prevalence of impaired fasting glucose, impaired glucose tolerance and diabetes was 26.1% among men and 34.9% among women, and increased with age. The prevalence of prehypertension and hypertension was 30.7% and 15.9% among men and 27.2% and 22.5% among women, with similar rising prevalence with age. Conclusion: NCD risk factors, hyperglycaemia and raised blood pressure are an immediate health threat in rural Bangladesh. Initiatives to improve detection, treatment and prevention strategies are needed

Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis

Earlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination

Expression of Tas1 Taste Receptors in Mammalian Spermatozoa: Functional Role of Tas1r1 in Regulating Basal Ca2+ and cAMP Concentrations in Spermatozoa

Background: During their transit through the female genital tract, sperm have to recognize and discriminate numerous chemical compounds. However, our current knowledge of the molecular identity of appropriate chemosensory receptor proteins in sperm is still rudimentary. Considering that members of the Tas1r family of taste receptors are able to discriminate between a broad diversity of hydrophilic chemosensory substances, the expression of taste receptors in mammalian spermatozoa was examined. Methodology/Principal Findings: The present manuscript documents that Tas1r1 and Tas1r3, which form the functional receptor for monosodium glutamate (umami) in taste buds on the tongue, are expressed in murine and human spermatozoa, where their localization is restricted to distinct segments of the flagellum and the acrosomal cap of the sperm head. Employing a Tas1r1-deficient mCherry reporter mouse strain, we found that Tas1r1 gene deletion resulted in spermatogenic abnormalities. In addition, a significant increase in spontaneous acrosomal reaction was observed in Tas1r1 null mutant sperm whereas acrosomal secretion triggered by isolated zona pellucida or the Ca2+ ionophore A23187 was not different from wild-type spermatozoa. Remarkably, cytosolic Ca2+ levels in freshly isolated Tas1r1-deficient sperm were significantly higher compared to wild-type cells. Moreover, a significantly higher basal cAMP concentration was detected in freshly isolated Tas1r1-deficient epididymal spermatozoa, whereas upon inhibition of phosphodiesterase or sperm capacitation, the amount of cAMP was not different between both genotypes. Conclusions/Significance: Since Ca2+ and cAMP control fundamental processes during the sequential process of fertilization, we propose that the identified taste receptors and coupled signaling cascades keep sperm in a chronically quiescent state until they arrive in the vicinity of the egg - either by constitutive receptor activity and/or by tonic receptor activation by gradients of diverse chemical compounds in different compartments of the female reproductive tract

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

HSP70-binding protein HSPBP1 regulates chaperone expression at a posttranslational level and is essential for spermatogenesis

Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate and analyze transgenic mice that lack the cochaperone HSPBP1, a nucleotide-exchange factor of HSP70 proteins and inhibitor of chaperone-assisted protein degradation. Male HSPBP1(−/−) mice are sterile because of impaired meiosis and massive apoptosis of spermatocytes. HSPBP1 deficiency in testes strongly reduces the expression of the inducible, antiapoptotic HSP70 family members HSPA1L and HSPA2, the latter of which is essential for synaptonemal complex disassembly during meiosis. We demonstrate that HSPBP1 affects chaperone expression at a posttranslational level by inhibiting the ubiquitylation and proteasomal degradation of inducible HSP70 proteins. We further provide evidence that the cochaperone BAG2 contributes to HSP70 stabilization in tissues other than testes. Our findings reveal that chaperone expression is determined not only by regulated transcription, but also by controlled degradation, with degradation-inhibiting cochaperones exerting essential prosurvival functions

High Temperature Fatigue Behaviour of Secondary AlSi7Cu3Mg Alloys

none3siThe high temperature fatigue behaviour of secondary AlSi7Cu3Mg alloys has been investigated. The alloy has been solubilized and aged for different times to obtain the age-hardening profile. The peak hardness is reached at 180 °C after 4 h ageing treatment. Further, the hardness stabilizes showing a plateau in the range between 5 and 10 hours of ageing treatment. The heat treatment leads to a complete dissolution of Cu-rich phases, spheroidization of eutectic Si particles and precipitation inside the α-Al matrix. Several fatigue tests have been carried out on selected heat-treated specimens both at room and elevated temperatures (200 and 300 °C). The obtained results show how the fatigue strength decreases with increasing the testing temperaturenoneDe Mori, Alessandro; Timelli, Giulio; Berto, FilippoDe Mori, Alessandro; Timelli, Giulio; Berto, Filipp