Joint modeling of correlated binary outcomes using multivariate logistic regression: contraception and HIV knowledge in Sri Lanka.

Reproductive health significantly contributes to the overall well-being and social welfare of women. Within the spectrum of modern and traditional contraceptive methods in use, condoms have been strongly advocated by numerous HIV programs as a primary means of preventing HIV infection in Sri Lanka. Given the intrinsic relationship between contraceptive utilization and HIV awareness, our study aims to concurrently analyze the patterns of contraceptive usage and HIV knowledge, while accounting for their potential correlation.

α-Synuclein Regulates Peripheral Insulin Secretion and Glucose Transport.

Aim: Population based studies indicate a positive association between type 2 diabetes (T2D) and Parkinson's disease (PD) where there is an increased risk of developing PD in patients with T2D. PD is characterized by the abnormal accumulation of intraneuronal aggregated α-synuclein (α-syn) in Lewy bodies, which negatively impact neuronal viability. α-syn is also expressed in both pancreatic islets and skeletal muscle, key players in glucose regulation.

Assessment of current status and geospatial analysis of compliance to bacteriological parameters: Tools to ensure access to safe water in Sri Lanka.

Compliance of drinking-water to bacteriological parameters serves as a surrogate measure of the risk of water-borne diseases. Understanding the risk of water-borne diseases could help promote healthy behaviors such as household water treatment and safe water storage practices and advocacy to increase access to centrally-managed piped water. The objective of this research was to assess the current status of compliance and to geospatially analyze the probability of compliance to bacteriological parameters in the Western Province of Sri Lanka.

Pancreatic β cell-selective zinc transporter 8 insufficiency accelerates diabetes associated with islet amyloidosis.

GWAS have shown that the common R325W variant of SLC30A8 (ZnT8) increases the risk of type 2 diabetes (T2D). However, ZnT8 haploinsufficiency is protective against T2D in humans, counterintuitive to earlier work in humans and mouse models. Therefore, whether decreasing ZnT8 activity is beneficial or detrimental to β cell function, especially under conditions of metabolic stress, remains unknown.

Predictive modelling for COVID-19 outbreak control: lessons from the navy cluster in Sri Lanka.

In response to an outbreak of coronavirus disease 2019 (COVID-19) within a cluster of Navy personnel in Sri Lanka commencing from 22nd April 2020, an aggressive outbreak management program was launched by the Epidemiology Unit of the Ministry of Health. To predict the possible number of cases within the susceptible population under four social distancing scenarios, the COVID-19 Hospital Impact Model for Epidemics (CHIME) was used. With increasing social distancing, the epidemiological curve flattened, and its peak shifted to the right.

Combination of human tau and islet amyloid polypeptide exacerbates metabolic dysfunction in transgenic mice.

Amyloid plaques and neurofibrillary tangles composed of hyperphosphorylated tau are important contributors to Alzheimer's disease (AD). Tau also impacts pancreatic beta cell function and glucose homeostasis. Amyloid deposits composed of islet amyloid polypeptide (IAPP) are a pathological feature of type 2 diabetes (T2D).

Assessment of drought resilience of hospitals in Sri Lanka: a cross-sectional survey.

Background: Drought is an extreme weather event. Drought-related health effects can increase demands on hospitals while restricting their functional capacity. In July 2017, Sri Lanka had been experiencing prolonged drought for around a year and data on the resilience of hospitals were required.

Behavioral Abnormalities in Knockout and Humanized Tau Mice.

Microtubule-associated protein tau assists in stabilizing microtubules and has been particularly implicated in Alzheimer's disease (AD). Given the importance of tau to AD pathogenesis and therapies, it is important to understand non-classic physiological functions for this protein inside and outside the central nervous system (CNS). Our group has previously shown that tau ablation triggers glucose intolerance and pancreatic dysfunction in mice, suggesting that tau plays a role in peripheral metabolic regulation.

The Link Between Tau and Insulin Signaling: Implications for Alzheimer's Disease and Other Tauopathies.

The microtubule-associated protein tau (MAPT) is mainly identified as a tubulin binding protein essential for microtubule dynamics and assembly and for neurite outgrowth. However, several other possible functions for Tau remains to be investigated. Insulin signaling is important for synaptic plasticity and memory formation and therefore is essential for proper brain function.

Tau ablation in mice leads to pancreatic β cell dysfunction and glucose intolerance.

The microtubule-associated protein tau is highly expressed in pancreatic islets. Abnormally phosphorylated tau aggregates assemble into neurofibrillary tangles linked to Alzheimer's disease pathology and has also been found in islets of patients with type 2 diabetes. However, the significance of tau in islet function remains relatively unexplored.

Impaired peripheral glucose homeostasis and Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia. Recent studies suggest that metabolic disturbances, particularly type 2 diabetes (T2D) increase the risk of cognitive decline and AD. AD is also a risk factor for T2D, and a growing body of evidence indicates that these diseases are connected both at clinical and molecular levels.

Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults.

Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear.

Amyloid-β and islet amyloid pathologies link Alzheimer's disease and type 2 diabetes in a transgenic model.

Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-β (Aβ) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases.

The Link between Type 2 Diabetes and Neurodegeneration: Roles for Amyloid-β, Amylin, and Tau Proteins.

A wealth of evidence indicates a strong link between type 2 diabetes (T2D) and neurodegenerative diseases such as Alzheimer's disease (AD). Although the precise mechanism remains unclear, T2D can exacerbate neurodegenerative processes. Brain atrophy, reduced cerebral glucose metabolism, and central nervous system insulin resistance are features of both AD and T2D.

ABCA1 deficiency and cellular cholesterol accumulation increases islet amyloidogenesis in mice.

Aims/hypothesis: Islet amyloid, a pathological feature of type 2 diabetes, forms from the aggregation of islet amyloid polypeptide (IAPP), a beta cell peptide that is produced and co-secreted with insulin. Cholesterol regulates amyloid-β processing, deposition and clearance, promoting amyloidogenesis in the brain. ATP-binding cassette transporter 1 (ABCA1) is a cholesterol efflux transporter that when absent increases and when overexpressed reduces brain amyloid-β deposition in mouse models of Alzheimer's disease.

Inflammation and Oxidative Stress: The Molecular Connectivity between Insulin Resistance, Obesity, and Alzheimer's Disease.

Type 2 diabetes (T2DM), Alzheimer's disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer's disease (AD) is the most common subtype of dementia.

A shortened verbal autopsy instrument for use in routine mortality surveillance systems.

Background: Verbal autopsy (VA) is recognized as the only feasible alternative to comprehensive medical certification of deaths in settings with no or unreliable vital registration systems. However, a barrier to its use by national registration systems has been the amount of time and cost needed for data collection. Therefore, a short VA instrument (VAI) is needed.

Islet amyloid inhibitors improve glucose homeostasis in a transgenic mouse model of type 2 diabetes.

Increasing evidence points to the cytotoxicity of islet amyloid polypeptide (IAPP) aggregates as a major contributor to the loss of β-cell mass in type 2 diabetes. Prevention of IAPP formation represents a potential treatment to increase β-cell survival and function. The IAPP inhibitory peptide, D-ANFLVH, has been previously shown to prevent islet amyloid accumulation in cultured human islets.

Loss of Cyp8b1 improves glucose homeostasis by increasing GLP-1.

Besides their role in facilitating lipid absorption, bile acids are increasingly being recognized as signaling molecules that activate cell-signaling receptors. Targeted disruption of the sterol 12α-hydroxylase gene (Cyp8b1) results in complete absence of cholic acid (CA) and its derivatives. Here we investigate the effect of Cyp8b1 deletion on glucose homeostasis.

Regulation of ABCA1 protein expression and function in hepatic and pancreatic islet cells by miR-145.

Objective: The ATP-binding cassette transporter A1 (ABCA1) protein maintains cellular cholesterol homeostasis in several different tissues. In the liver, ABCA1 is crucial for high-density lipoprotein biogenesis, and in the pancreas ABCA1 can regulate insulin secretion. In this study, our aim was to identify novel microRNAs that regulate ABCA1 expression in these tissues.

Effects of high-fat diet feeding on Znt8-null mice: differences between β-cell and global knockout of Znt8.

Genomewide association studies have linked a polymorphism in the zinc transporter 8 (Znt8) gene to higher risk of developing type 2 diabetes. Znt8 is highly expressed in pancreatic β-cells where it is involved in the regulation of zinc transport into granules. However, Znt8 is also expressed in other tissues including α-cells, where its function is as yet unknown.

miR-33a modulates ABCA1 expression, cholesterol accumulation, and insulin secretion in pancreatic islets.

Changes in cellular cholesterol affect insulin secretion, and β-cell-specific deletion or loss-of-function mutations in the cholesterol efflux transporter ATP-binding cassette transporter A1 (ABCA1) result in impaired glucose tolerance and β-cell dysfunction. Upregulation of ABCA1 expression may therefore be beneficial for the maintenance of normal islet function in diabetes. Studies suggest that microRNA-33a (miR-33a) expression inversely correlates with ABCA1 expression in hepatocytes and macrophages.

Loss of both ABCA1 and ABCG1 results in increased disturbances in islet sterol homeostasis, inflammation, and impaired β-cell function.

Cellular cholesterol homeostasis is important for normal β-cell function. Disruption of cholesterol transport by decreased function of the ATP-binding cassette (ABC) transporter ABCA1 results in impaired insulin secretion. Mice lacking β-cell ABCA1 have increased islet expression of ABCG1, another cholesterol transporter implicated in β-cell function.

Islet cholesterol accumulation due to loss of ABCA1 leads to impaired exocytosis of insulin granules.

Objective: The ATP-binding cassette transporter A1 (ABCA1) is essential for normal insulin secretion from β-cells. The aim of this study was to elucidate the mechanisms underlying the impaired insulin secretion in islets lacking β-cell ABCA1.

Research Design And Methods: Calcium imaging, patch clamp, and membrane capacitance were used to assess the effect of ABCA1 deficiency on calcium flux, ion channel function, and exocytosis in islet cells.