Bicuspid aortic valves undergo excessive strain during opening: A simulation study

ObjectiveThe objective of this study was to examine the influence of the morphologic characteristics of the bicuspid aortic valve on its disease progression by comparing the motion, stress/strain distribution, and blood flow of normal and stenotic tricuspid valves using simulation models.MethodsBicuspid, stenotic tricuspid with commissural fusion or thickened leaflet, and normal aortic valves were modeled with internal blood flow. Blood flow and the motion of aortic valve leaflets were studied using fluid–structure interaction finite element analysis, and stress/strain (curvature) distributions were calculated during the cardiac cycle. To mimic disease progression, we modified the local thickness of the leaflet where the bending stress was above a threshold.ResultsTransvalvular pressure gradient was greater in the bicuspid valve compared with the stenotic tricuspid valve with a similar valvular area. The bending strain (curvature) increased in both stenotic tricuspid and bicuspid valves, but a greater increase was observed in the bicuspid valve, and this was concentrated on the midline of the fused leaflets. During disease progression analysis, severity of the stenosis increased only in the bicuspid aortic valve model in terms of valvular area and pressure gradient.ConclusionsThe characteristic morphology of the bicuspid valve creates excessive bending strain on the leaflets during ventricular ejection. Such mechanical stress may be responsible for the rapid progression of this disease

Dietary Salt Intake is a Significant Determinant of Impaired Kidney Function in the General Population

Background/Aims: Kidney dysfunction is an important risk factor for cardiovascular disease and end-stage renal disease. This study investigated whether dietary salt intake predicts deterioration of kidney function in the general population. Methods: In all, 12 126 subjects with a normal estimated glomerular filtration rate (eGFR ≥60 mL/min per 1.73m2) attending an annual check-up were enrolled in the study and were followed-up for a median of 1754 days; the endpoint was the development of impaired kidney function (eGFR < 60 mL/min per 1.73m2). Individual salt intake was estimated using spot urine analysis. Results: At baseline, mean (± SD) salt intake and eGFR were 10.6 ± 3.4 g/day and 80.8 ± 12.9 mL/min per 1.73m2, respectively. During the follow-up period, 1384 subjects (25.2 per 1000 person-years) developed impaired kidney function. Multivariate Cox hazard regression analysis revealed salt intake as a significant predictor of the new onset of kidney impairment (hazard ratio 1.045; 95% confidence interval 1.025–1.065). Subjects were divided into two groups based on salt intake; the incidence of impaired kidney function was higher in the group with high than low salt intake (P < 0.001, log-rank test). Multivariate Cox hazard regression analysis indicated a 29% increased risk of developing impaired kidney function in the high-salt group. Multivariate linear regression analysis showed a significant correlation between salt intake and yearly decline in eGFR (β = 0.060, P < 0.001). Conclusion: Salt intake is associated with the development of impaired kidney function in the general population, independent of its effects on blood pressure. Salt restriction may help prevent the development of impaired kidney function

The New School Absentees Reporting System for Pandemic Influenza A/H1N1 2009 Infection in Japan

Objective: To evaluate the new Japanese School Absentees Reporting System for Infectious Disease (SARSID) for pandemic influenza A/H1N1 2009 infection in comparison with the National epidemiological Surveillance of Infectious Disease (NESID). Methods:We used data of 53,223 students (97.7%) in Takamatsu city Japan. Data regarding school absentees in SARSID was compared with that in NESID from Oct 13, 2009 to Jan 12, 2010. Results: Similar trends were observed both in SARSID and NESID. However, the epidemic trend for influenza in SARSID was thought to be more sensitive than that in NESID. Conclusion: The epidemic trend for influenza among school-aged children could be easily and rapidly assessed by SARSID compared to NESID. SARSID might be useful for detecting the epidemic trend of influenza

Automatic Analysis of Composite Physical Signals Using Non-Negative Factorization and Information Criterion

In time-resolved spectroscopy, composite signal sequences representing energy transfer in fluorescence materials are measured, and the physical characteristics of the materials are analyzed. Each signal sequence is represented by a sum of non-negative signal components, which are expressed by model functions. For analyzing the physical characteristics of a measured signal sequence, the parameters of the model functions are estimated. Furthermore, in order to quantitatively analyze real measurement data and to reduce the risk of improper decisions, it is necessary to obtain the statistical characteristics from several sequences rather than just a single sequence. In the present paper, we propose an automatic method by which to analyze composite signals using non-negative factorization and an information criterion. The proposed method decomposes the composite signal sequences using non-negative factorization subjected to parametric base functions. The number of components (i.e., rank) is also estimated using Akaike's information criterion. Experiments using simulated and real data reveal that the proposed method automatically estimates the acceptable ranks and parameters

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

BACKGROUND: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study\u27s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p\u3c0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p\u3c0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target