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To establish trajectories of cognitive and motor function, and to determine the sequence of change across individual tests in community-dwelling individuals aged 45-90 years.
Between 1997 and 2016, we repeatedly assessed cognitive function with 5 tests in 9514 participants aged 45-90 years from the population-based Rotterdam Study. Between 1999 and 2016, we measured motor function with 3 tests in 8297 participants. All participants were free from dementia, stroke, and parkinsonism. We assessed overall and education-specific cognitive and motor trajectories using linear mixed models with age as time scale. Next, we determined the sequence of change across individual tests.
The number of assessments per participant ranged between 1 and 6 (mean interval, years [SD] 5.1 [1.4]) for cognitive function, and 1 and 4 (5.4 [1.4]) for motor function. Cognitive and motor trajectories declined linearly between ages 45 and 65 years, followed by steeper declines after ages 65-70 years. Lower educated participants had indings benefit the understanding of the natural course of cognitive and motor function during aging, and highlight the role of education in the preservation of cognitive but not motor function.The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world. Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system. In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm. This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19. There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19. Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address. We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients. A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.
Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in up to 50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW).
Urine was collected from NGU cases (129 MSM; 121 MSW) and controls (70 MSM; 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had <5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU, and to select bacteria for targeted quantitative PCR (qPCR).
Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared to 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs. 2%) and MP (21% vs. 1%) (both p≤0.001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs. 3%, p=0.036) and MSW (17% vs. 1%, p<0.001), but MP was associated with NGU only among MSM (13% vs. 1%, p=0.004). Associations were stronger in men with idiopathic NGU.
HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis.
HI and MP are potential causes of male urethritis. this website MP was more often detected among MSM than MSW with urethritis.
Impaired lymphatic drainage of the arterial wall results in intimal lipid accumulation and atherosclerosis. However, the mechanisms regulating lymphangiogenesis in atherosclerotic arteries are not well understood. Our studies identified elevated levels of matrix protein R-Spondin 2 (RSPO2) in atherosclerotic arteries. In this study, we investigated the role of RSPO2 in lymphangiogenesis, arterial cholesterol efflux into lesion-draining lymph nodes and development of atherosclerosis.
The effect of RSPO2 on lymphangiogenesis was investigated using human lymphatic endothelial cells in vitro and implanted Matrigel plugs in vivo. Cellular and molecular approaches, pharmacological agents, and siRNA silencing of RSPO2 receptor LGR4 were used to investigate RSPO2-mediated signaling in lymphatic endothelial cells. In vivo LDL tracking and perivascular blockade of RSPO2-LGR4 signaling using LGR4-ECD pluronic gel in hypercholesterolemic mice were utilized to investigate the role of RSPO2 in arterial reverse cholesteion and prevention of its cardiovascular complications is an urgent medical need. The findings of the present study that inhibition of LGR4-mediated signaling increases arterial lymphangiogenesis, improves lymphatic drainage from the vessel wall and attenuates atherosclerosis, provide a framework from which novel therapeutic strategies to augment lymphatic vessel density and reduce atherosclerotic lesion formation can be developed and used for the treatment of patients with atherosclerosis. This pathway may also have important implications in other pathological conditions associated with lymphatic dysfunction, such as lymphedema, obesity, hypertension, and impaired wound healing.
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