Aortic reservoir-excess pressure parameters are associated with worse cognitive function in people with untreated stage II/III hypertension.

Objective: Hypertension is a recognized risk factor for the development of cognitive impairment and dementia in older adults. Aortic stiffness and altered haemodynamics could promote the transmission of detrimental high pressure pulsatility into the cerebral circulation, potentially damaging brain microvasculature and leading to cognitive impairment. We determined whether reservoir-excess pressure parameters were associated with cognitive function in people with hypertension (HT) and normotension (NT).

Reservoir-excess pressure parameters are independently associated with NT-proBNP in older adults.

Aims: Parameters derived from reservoir-excess pressure analysis have been demonstrated to predict cardiovascular events. Thus, altered reservoir-excess pressure parameters could have a detrimental effect on highly-perfused organs like the heart. We aimed to cross-sectionally determine whether reservoir-excess pressure parameters were associated with N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in older adults.

Type 2 diabetes exacerbates changes in blood pressure-independent arterial stiffness: cross-sectional and longitudinal evidence from the SUMMIT study.

Greater central artery stiffness is observed in people with type 2 diabetes (T2DM). Elevated blood pressure (BP) and altered arterial wall structure/composition in T2DM are generally considered as main drivers for this alteration. However, because conventional arterial stiffness measures are BP-dependent and as such an influence of BP remains in a measure, it is unclear if greater central artery stiffness is a function of greater BP, or due to changes in the structure and composition of the arterial wall.

Genome-wide mRNA profiling in urinary extracellular vesicles reveals stress gene signature for diabetic kidney disease.

Urinary extracellular vesicles (uEV) are a largely unexplored source of kidney-derived mRNAs with potential to serve as a liquid kidney biopsy. We assessed ∼200 uEV mRNA samples from clinical studies by genome-wide sequencing to discover mechanisms and candidate biomarkers of diabetic kidney disease (DKD) in Type 1 diabetes (T1D) with replication in Type 1 and 2 diabetes. Sequencing reproducibly showed >10,000 mRNAs with similarity to kidney transcriptome.

Community health workers and Covid-19: Cross-country evidence on their roles, experiences, challenges and adaptive strategies.

Community health workers (CHWs) are a key part of the health workforce, with particular importance for reaching the most marginalised. CHWs' contributions during pandemics have received growing attention, including for COVID-19. This paper contributes to learning about CHWs' experiences during COVID-19, based on evidence from India, Bangladesh, Pakistan, Sierra Leone, Kenya and Ethiopia.

Facilitating high quality acute care in resource-constrained environments: Perspectives of patients recovering from sepsis, their caregivers and healthcare workers in Uganda and Malawi.

Sepsis is a major global health problem, especially in sub-Saharan Africa. Improving patient care requires that healthcare providers understand patients' priorities and provide quality care within the confines of the context they work. We report the perspectives of patients, caregivers and healthcare workers regarding care quality for patients admitted for sepsis to public hospitals in Uganda and Malawi.

How can we strengthen partnership and coordination for health system emergency preparedness and response? Findings from a synthesis of experience across countries facing shocks.

Background: Discussions of health system resilience and emergency management often highlight the importance of coordination and partnership across government and with other stakeholders. However, both coordination and partnership have been identified as areas requiring further research. This paper identifies characteristics and enablers of effective coordination for emergency preparedness and response, drawing on experience from different countries with a range of shocks, including floods, drought, and COVID-19.

Reservoir Pressure Integral Is Independently Associated With the Reduction in Renal Function in Older Adults.

Background: Arterial hemodynamic parameters derived from reservoir-excess pressure analysis exhibit prognostic utility. Reservoir-excess pressure analysis may provide useful information about an influence of altered hemodynamics on target organ such as the kidneys. We determined whether the parameters derived from the reservoir-excess pressure analysis were associated with the reduction in estimated glomerular filtration rate in 542 older adults (69.

Plaque characteristics and biomarkers predicting regression and progression of carotid atherosclerosis.

The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb.

Carotid-femoral pulse wave velocity acquisition methods and their associations with cardiovascular risk factors and subclinical biomarkers of vascular health.

Background: Different methods to measure carotid-femoral pulse wave velocity (CFPWV) may affect the measurements obtained and influence the association between CFPWV, cardiovascular risk factors and biomarkers of subclinical vascular health. The estimation of distance between the carotid and femoral artery measurement sites (the arterial path length) is particularly problematic.

Method: We determined if CFPWV and equation-based estimates of CFPWV were influenced by arterial path length and if this affected the association of CFPWV with cardiovascular risk factors and subclinical vascular biomarkers.

Cerebral small vessel disease, systemic vascular characteristics and potential therapeutic targets.

Introduction: Cerebral small vessel disease (SVD) is prevalent in the elderly population and is associated with increased risk of dementia, stroke and disability. Currently there are no clear targets or strategies for the treatment of cerebral SVD. We set out to identify modifiable vascular treatment targets.

Reservoir-Excess Pressure Parameters Independently Predict Cardiovascular Events in Individuals With Type 2 Diabetes.

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Structure-based, multi-targeted drug discovery approach to eicosanoid inhibition: Dual inhibitors of mPGES-1 and 5-lipoxygenase activating protein (FLAP).

Background: Due to the importance of both prostaglandins (PGs) and leukotrienes (LTs) as pro-inflammatory mediators, and the potential for eicosanoid shunting in the presence of pathway target inhibitors, we have investigated an approach to inhibiting the formation of both PGs and LTs as part of a multi-targeted drug discovery effort.

Methods: We generated ligand-protein X-ray crystal structures of known inhibitors of microsomal prostaglandin E2 synthase-1 (mPGES-1) and the 5-Lipoxygenase Activating Protein (FLAP), with their respective proteins, to understand the overlapping pharmacophores. We subsequently used molecular modeling and structure-based drug design (SBDD) to identify hybrid structures intended to inhibit both targets.

"Are we getting the biometric bioethics right?" - the use of biometrics within the healthcare system in Malawi.

Biometrics is the science of establishing the identity of an individual based on their physical attributes. Ethical concerns surrounding the appropriate use of biometrics have been raised, especially in resource-poor settings. A qualitative investigation was conducted to explore biometrics clients (= 14), implementers (= 12) and policy makers as well as bioethicists (= 4) perceptions of the ethical aspects of implementing biometrics within the healthcare system in Malawi.

A qualitative study exploring stakeholder perspectives on the use of biological samples for future unspecified research in Malawi.

Background: There is growing interest in the collection, storage and reuse of biological samples for future research. Storage and future use of biological samples raise ethical concerns and questions about approaches that safeguard the interests of participants. The situation is further complicated in Africa where there is a general lack of governing ethical frameworks that could guide the research community on appropriate approaches for sample storage and use.

Prognostic imaging biomarkers for diabetic kidney disease (iBEAt): study protocol.

Background: Diabetic kidney disease (DKD) remains one of the leading causes of premature death in diabetes. DKD is classified on albuminuria and reduced kidney function (estimated glomerular filtration rate (eGFR)) but these have modest value for predicting future renal status. There is an unmet need for biomarkers that can be used in clinical settings which also improve prediction of renal decline on top of routinely available data, particularly in the early stages.

Weight change and sulfonylurea therapy are related to 3 year change in microvascular function in people with type 2 diabetes.

Aims/hypothesis: Although cardiovascular disease is the biggest cause of death in people with diabetes, microvascular complications have a significant impact on quality of life and financial burden of the disease. Little is known about the progression of microvascular dysfunction in the early stages of type 2 diabetes before the occurrence of clinically apparent complications. We aimed to explore the determinants of endothelial-dependent and -independent microvascular function progression over a 3 year period, in people with and without both diabetes and few clinical microvascular complications.

Stakeholder views on the acceptability of human infection studies in Malawi.

Background: Human infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMICs) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design.

A Mendelian Randomization Study Provides Evidence That Adiposity and Dyslipidemia Lead to Lower Urinary Albumin-to-Creatinine Ratio, a Marker of Microvascular Function.

Urinary albumin-to-creatinine ratio (ACR) is a marker of diabetic nephropathy and microvascular damage. Metabolic-related traits are observationally associated with ACR, but their causal role is uncertain. Here, we confirmed ACR as a marker of microvascular damage and tested whether metabolic-related traits have causal relationships with ACR.

A Formative Qualitative Study on the Acceptability of Deferred Consent in Adult Emergency Care Research in Malawi.

Research in emergency medical care is challenging due to a limited therapeutic window for intervention, which may compromise informed consent. "Deferred consent" allows initiation of study procedures before full consent is recorded. We conducted a formative qualitative study exploring perspectives on deferred consent in Malawi among research ethics committee members, health care professionals, and lay representatives.

Locally delivered GLP-1 analogues liraglutide and exenatide enhance microvascular perfusion in individuals with and without type 2 diabetes.

Aims/hypothesis: Glucagon-like peptide-1 (GLP-1) analogues reduce the risk of macrovascular disease in diabetes; however, little is known about their microvascular effects. This research examined the microvascular actions of the GLP-1 analogues liraglutide and exenatide in individuals with and without type 2 diabetes (study 1). It also explored the involvement of the GLP-1 receptor (study 2) and the nitric oxide pathway in mediating the microvascular effects of the analogues.