Aims: ZSF1 obese rats harbouring two mutant leptin receptor alleles (Lepr and Lepr) develop metabolic syndrome and heart failure with preserved ejection fraction (HFpEF), making them a widely used animal model in cardiometabolic research. Studies using ZSF1 rats have contributed significantly to the elucidation of pathophysiological mechanisms underlying HFpEF and therapeutic strategies against this multi-organ syndrome. In contrast, hybrid, lean ZSF1 rats (L-ZSF1) do not develop HFpEF and generally serve as controls, disregarding the possibility that the presence of one mutant Lepr allele might affect left ventricular ejection fraction (LVEF), diastolic dysfunction and other relevant HFpEF parameters, such as N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and cardiac inflammation, which could increase during disease manifestation.
View Article and Find Full Text PDFDiseases caused by Streptococcus pneumoniae (pneumococcus) produce a great impact on public health, killing about one million people annually despite available vaccines. Recent research has revealed that the pneumococcus produces extracellular vesicles (pEVs), which display selective cargo and hold potential for vaccine development. Here, we evaluated the immunogenicity and protective potential of pEVs derived from a non-encapsulated pneumococcal strain (R6) using murine models of pneumococcal colonization and invasive pneumonia.
View Article and Find Full Text PDFAbuse of amphetamine-type stimulants is linked to cardiovascular adverse effects like arrhythmias, accelerated atherosclerosis, acute coronary syndromes and sudden cardiac death. Excessive catecholamine release following amphetamine use causes vasoconstriction and vasospasms, over time leading to hypertension, endothelial dysfunction or even cardiotoxicity. However, immediate vascular pathomechanisms related to amphetamine exposure, especially endothelial function, remain incompletely understood and were analyzed in this study.
View Article and Find Full Text PDFA restoration of low homoarginine (hArg) levels in obese ZSF1 rats (O-ZSF1) before (S1-ZSF1) and after (S2-ZSF1) the manifestation of heart failure with preserved ejection fraction (HFpEF) did not affect the worsening of cardiac HFpEF characteristics. Here, potential regulation of key enzymes of arginine metabolism in other organs was analyzed. Arginase 2 (ARG2) was reduced >35% in the kidney and small intestine of hArg-supplemented rats compared to O-ZSF1.
View Article and Find Full Text PDFIntroduction: Fibro-calcific aortic valve disease has high prevalence and is associated with significant mortality. Fibrotic extracellular matrix (ECM) remodeling and calcific mineral deposition change the valvular microarchitecture and deteriorate valvular function. Valvular interstitial cells (VICs) in profibrotic or procalcifying environment are frequently used in vitro models.
View Article and Find Full Text PDFBackground: Risk-reducing bilateral salpingo-oophorectomy reduces mortality from high-grade serous carcinoma in patients with hereditary breast and ovarian cancer associated gene mutations. Ideal surgical management includes 5 steps outlined in 2005 by the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists. In addition, it is recommended that pathologic examination include serial sectioning of specimens.
View Article and Find Full Text PDFThromboembolic events (TEEs) can be classified into two types: venous TEEs (vTEEs), such as pulmonary embolism (PE) and deep vein thrombosis (DVT), and arterial TEEs (ATEs), such as acute myocardial infarction and cerebral infarction. Ovarian cancer has a high incidence of venous thromboembolism, with the clear cell subtype carrying the highest risk. However, the incidence of ATEs, especially cerebral infarction, in patients with ovarian carcinoma, of all subtypes, is much lower.
View Article and Find Full Text PDFAcute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms, generally referred to as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing.
View Article and Find Full Text PDFDiastolic dysfunction in heart failure with preserved ejection fraction (HFpEF) is characterised by increased left ventricular stiffness and impaired active relaxation. Underpinning pathomechanisms are incompletely understood. Cardiac hypertrophy and end stage heart disease are associated with alterations in the cardiac microtubule (MT) network.
View Article and Find Full Text PDFAim: Heart failure with preserved ejection fraction (HFpEF) is associated with left ventricular stiffness, impaired diastolic relaxation, and severe exercise intolerance. Decreased homoarginine (hArg) levels are an independent predictor of mortality in cardiovascular disease and correlate with impaired exercise performance. We recently reported alterations in arginine, hArg, and related amino acids in obese ZSF1 rats (O-ZSF1), with a HFpEF phenotype.
View Article and Find Full Text PDFBackground: There is a little empirical evidence of the impact of pooling randomized controlled trials (RCTs) and cohort studies (CSs) on the certainty-of-evidence. To evaluate the hypothetical-scenario of pooling bodies-of-evidence from RCTs with matched bodies-of-evidence from CSs on the certainty-of-evidence.
Methods: We extracted GRADE ratings of bodies-of-evidence from RCTs in Cochrane reviews, and rated the certainty-of-evidence from matched bodies-of-evidence from CSs.
Only very few Cochrane nutrition reviews include cohort studies (CSs), but most evidence in nutrition research comes from CSs. We aimed to pool bodies of evidence (BoE) from randomized controlled trials (RCTs) derived from Cochrane reviews with matched BoE from CSs. The Cochrane Database of Systematic Reviews and MEDLINE were searched for systematic reviews (SRs) of RCTs and SRs of CSs.
View Article and Find Full Text PDFEndothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF.
View Article and Find Full Text PDFBackground: Heart failure (HF) is the leading cause of death in western countries. Cardiac dysfunction is accompanied by skeletal alterations resulting in muscle weakness and fatigue. Exercise is an accepted interventional approach correcting cardiac and skeletal dysfunction, thereby improving mortality, re-hospitalization and quality of life.
View Article and Find Full Text PDFBackground: To improve health planning at primary health care (PHC) level, Business Plans were introduced in Tajikistan by the Enhancing Primary Health Care (EPHC) Services Project.
Objective: To describe the history and process of implementation of Business Plans and to identify barriers, facilitators and lessons learnt from scaling up Business Plans.
Methods: Set in a qualitative research design, we conducted a desk review of project and official documents and seventeen semi-structured interviews with key stakeholders at national and sub-national levels between May and July 2020.
Extracellular vesicles (EVs) have recently garnered attention for their participation in host-microbe interactions in pneumococcal infections. However, the effect of EVs on the host immune system remain poorly understood. Our studies focus on EVs produced by (pEVs), and reveal that pEVs are internalized by macrophages, T cells, and epithelial cells.
View Article and Find Full Text PDFHeart failure with preserved ejection fraction (HFpEF) is associated with high mortality and has an increasing prevalence associated with the demographic change and limited therapeutic options. Underlying mechanisms are largely elusive and need to be explored to identify specific biomarkers and new targets, which mirror disease progression and intervention success. Obese ZSF1 (O-ZSF1) rats are a useful animal model, as they spontaneously develop hypertension, hyperlipidemia and glucose intolerance and finally HFpEF.
View Article and Find Full Text PDFIntroduction: We conducted a scoping review of dietary guidelines with the intent of developing a position paper by the "IUNS Task force on Dietary Fat Quality" tasked to summarize the available evidence and provide the basis for dietary recommendations.
Methods: We systematically searched several databases and Web sites for relevant documents published between 2015 and 2019.
Results: Twenty documents were included.
Introduction: We conducted a scoping review of systematic reviews (SRs) on dietary fat intake and health outcomes in human adults within the context of a position paper by the "International Union of Nutritional Sciences Task force on Dietary Fat Quality" tasked to summarize the available evidence and provide dietary recommendations.
Methods: We systematically searched several databases for relevant SRs of randomized controlled trials (RCTs) and/or prospective cohort studies published between 2015 and 2019 assessing the association between dietary fat and health outcomes.
Results: Fifty-nine SRs were included.
Objective: To identify and describe the use of the GRADE approach for rating the certainty of evidence in nutrition systematic reviews (SRs).
Study Design And Setting: We systematically searched for SRs using GRADE that were published between 2015 and 2019 in the 10 "nutrition" journals with the highest impact factor according to the JCR 2018.
Results: Out of 800 SRs, 55 SRs of randomized control trials (RCTs) and/or nonrandomized studies (NRSs) used GRADE.
Opioid use has emerged as a leading cause of death in the US. Given that 1 in 300 opioid-naive patients exposed to opioids after cesarean birth will become persistent users, hospitals should strive to limit exposure to these medications. We set out to evaluate whether transitioning to a standardized order set based on multimodal combination analgesic therapy decreases the exposure to opioids after cesarean delivery.
View Article and Find Full Text PDFOvarian cysts and specifically ovarian teratomas are a common finding in young patients. These cysts display histological cell types from all three cells lines: endodermal, ectodermal and mesodermal origins. A 22-year-old woman who displayed classic signs of cortisol excess - excessive weight gain, difficultly losing weight and abdominal striae - was found to have a 10 cm mature teratoma cyst.
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