Developmental and epileptic encephalopathies (DEEs) are a group of epilepsies with early onset and severe symptoms that sometimes lead to death. Although previous work successfully discovered several genes implicated in disease outcomes, it remains challenging to identify causative mutations within these genes from the background variation present in all individuals due to disease heterogeneity...

Robust, affordable plasma proteomic biomarker workflows are needed for large-scale clinical studies. We evaluated aspects of sample preparation to allow liquid chromatography-mass spectrometry (LC-MS) analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes.Using LC-MS with data-independent acquisition we ev...

Social distancing measures designed to contain the COVID-19 pandemic can restrict physical activity, a particular concern for high-risk patient groups. We assessed rheumatoid arthritis patients' physical activity and sedentary behavior level, pain, fatigue, and health-related quality of life prior to and during the social distancing measures implemented in Sao Paulo, Brazil.Post-menopausal fema...

Nutrients are conventionally classified as macronutrients (carbohydrates, fat and protein), and micronutrients (vitamins, minerals, electrolytes). This classification is based upon the quantity required to maintain health, and also, perhaps, the caloric value of the concerned nutrient. We support the use of the descriptor meganutrient for fibre and water. The latter is required in significantly...

This communication discusses the physiology and pathology of the insulin glucagon ratio, with respect to obesity. Though high insulin levels are associated with obesity in this manuscript the authors specifically highlight its role in the causation and clinical management of obesity. It suggests that the term insulin glucagon ratio be used in preference to glucagon insulin ratio, and shares ins...

The South African Diabetes Prevention Programme (SA-DPP) is a lifestyle intervention targeting individuals at high risk of developing type 2 diabetes mellitus (T2DM). In this paper we describe the mixed-method staged approach that was used to develop and refine the SA-DPP intervention curriculum and the appropriate tools for local resource-poor communities. During the preparation phase, existin...

Background In patients with aortic stenosis (AS), the presence of mitral regurgitation (MR) can lead to underestimation of AS severity and worse clinical outcomes. The objective of this study was to characterize the magnitude of the effects of concomitant MR on hemodynamic indicators of AS severity using clinical data and a computational cardiovascular simulation. Methods and Results Echocardio...

Renal fibrosis is a hallmark of chronic kidney disease, while efficient therapy against renal fibrosis is still lacking. In this study, we investigated the role of a novel small-molecule compound VCP979 on renal fibrosis and inflammation in a rat model of unilateral ureteral obstruction (UUO). One week after the UUO surgery, rats were administered VCP979 by gavage for one week, and after treatm...

Atherosclerotic plaque rupture leading to myocardial infarction is a major global health burden. Applying the tandem stenosis (TS) mouse model, which distinctively exhibits the characteristics of human plaque instability/rupture, we use quantitative proteomics to understand and directly compare unstable and stable atherosclerosis. Our data highlight the disparate natures and define unique prote...

We aimed to evaluate the microcirculatory resistance (MR) and myocardial metabolic adaptations at rest and in response to increased cardiac workload in patients with suspected coronary microvascular dysfunction (CMD).Patients with objective ischaemia and/or myocardial injury and non-obstructive coronary artery disease underwent thermodilution-derived microcirculatory assessment and transcardiac...

To compare the cost-effectiveness of coronary artery calcium (CAC) score-guided statin therapy criteria and American College of Cardiology/American Heart Association (ACC/AHA) guidelines (10-year pooled cohort equation [PCE] risk ≥ 7.5%) with selection according to Australian guidelines (5-year absolute cardiovascular disease risk [ACVDR] ≥ 10%), for people with family histories of premature co...

Pain perception can be modulated by several factors. Phenomena like temporal summation leads to increased perceived pain, whereas behavioral conditioning can result in analgesic responses. Furthermore, during repeated, identical noxious stimuli, pain intensity can vary greatly in some individuals. Understanding these variations is important, given the increase in investigations that assume stab...

It is well-known that secondhand smoke exposure in childhood or adolescence is positively associated with morbidity and mortality. However, less is known about the current status of and most recent trends in secondhand smoke exposure among adolescents in China.We aimed to assess recent changes in the prevalence of secondhand smoke exposure among adolescents in China using nationally representat...

The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life's Essential 8. We examined the association of total and individual CVH metrics according to Life's Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in  life.Data were from the National Health and Nutrition Examination Survey (NHANES) 2005...

The frequency and significance of cytomegalovirus (CMV) infection in seropositive (R+) heart transplant recipients (HTR) is unclear, with preventative recommendations mostly extrapolated from other groups. We evaluated the incidence and severity of CMV infection in R+ HTR, to identify risk factors and describe outcomes.R+ HTR from 2010 to 2019 were included. Antiviral prophylaxis was not routin...

Coronary microvascular dysfunction (CMD) is associated with cardiac dysfunction and predictive of cardiac mortality in obesity, especially in females. Clinical data further support that CMD associates with development of heart failure with preserved ejection fraction and that mineralocorticoid receptor (MR) antagonism may be more efficacious in obese female, versus male, HFpEF patients. Accordi...

Cardiovascular ailments are a major cause of mortality where over 1.3 billion people suffer from hypertension leading to heart-disease related deaths. Snake venoms possess a broad repertoire of natriuretic peptides with therapeutic potential for treating hypertension, congestive heart failure, and related cardiovascular disease. We now describe several taipan () natriuretic peptides TNPa-e whic...

Cardiometabolic diseases encompass a range of interrelated conditions that arise from underlying metabolic perturbations precipitated by genetic, environmental, and lifestyle factors. While obesity, dyslipidaemia, smoking, and insulin resistance are major risk factors for cardiometabolic diseases, individuals still present in the absence of such traditional risk factors, making it difficult to ...

Investigating modifiable risk factors for the early stages of the development of type 2 diabetes is essential for effective prevention. Some studies show protective associations between dairy and prediabetes; however, associations are heterogeneous by the type and fat content of dairy foods.To examine the relationship between the consumption of dairy, including different types of dairy products...