Survey of Period Variations of Superhumps in SU UMa-Type Dwarf Novae

We systematically surveyed period variations of superhumps in SU UMa-type dwarf novae based on newly obtained data and past publications. In many systems, the evolution of superhump period are found to be composed of three distinct stages: early evolutionary stage with a longer superhump period, middle stage with systematically varying periods, final stage with a shorter, stable superhump period. During the middle stage, many systems with superhump periods less than 0.08 d show positive period derivatives. Contrary to the earlier claim, we found no clear evidence for variation of period derivatives between superoutburst of the same object. We present an interpretation that the lengthening of the superhump period is a result of outward propagation of the eccentricity wave and is limited by the radius near the tidal truncation. We interpret that late stage superhumps are rejuvenized excitation of 3:1 resonance when the superhumps in the outer disk is effectively quenched. Many of WZ Sge-type dwarf novae showed long-enduring superhumps during the post-superoutburst stage having periods longer than those during the main superoutburst. The period derivatives in WZ Sge-type dwarf novae are found to be strongly correlated with the fractional superhump excess, or consequently, mass ratio. WZ Sge-type dwarf novae with a long-lasting rebrightening or with multiple rebrightenings tend to have smaller period derivatives and are excellent candidate for the systems around or after the period minimum of evolution of cataclysmic variables (abridged).Comment: 239 pages, 225 figures, PASJ accepte

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

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

Impact of the 3% Oxygen Desaturation Index via Overnight Pulse Oximetry on Cardiovascular Events and Death in Patients Undergoing Hemodialysis: A Retrospective Cohort Study

It is unclear whether the severity of sleep-disordered breathing (SDB) affects the risk of cardiovascular events and mortality in patients undergoing hemodialysis (HD). We determined the severity of SDB with the 3% oxygen desaturation index (ODI) via overnight pulse oximetry. This study was a retrospective cohort, observational study of 134 patients on maintenance HD at a single center. They were divided into four groups according to SDB severity (normal, mild, moderate, and severe), and were followed. The baseline characteristics of all patients were as follows: the median age was 67 (interquartile range, 59–75) years, 64.2% were men, 37.3% were diabetic, and the median duration of HD was 69 (29–132) months. During follow-up, major adverse cardiovascular events (MACEs) occurred in 71 patients and deaths in 60 (including 32 cardiovascular deaths). Severe SDB was an independent risk factor for MACEs (hazard ratio [HR] = 4.66, 95% confidence interval [CI] = 1.87–11.61, p = 0.001) and all-cause death (HR = 5.74, 95% CI = 1.92–16.70, p = 0.001). Severe SDB had a statistically significant impact on the risk of MACEs and mortality in patients undergoing HD. The severity of the 3% ODI via overnight pulse oximetry may be a useful marker as a risk factor for cardiovascular outcomes and mortality in these patients

Correlation of hippocampal atrophy with hyperhomocysteinemia in hemodialysis patients: An exploratory pilot study.

BACKGROUND:Cognitive impairment is one of the important critical issues in hemodialysis (HD) patients. However, the associating factors of brain atrophy in HD patients have not been fully elucidated. PURPOSE AND METHODS:Brain magnetic resonance imaging (MRI) was performed in 34 of total 72 HD outpatients in our dialysis center. These MRI images were analyzed by an application software; Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD). VSRAD quantitatively calculates the extent of brain atrophy (percent of volume reduction) comparing with a MRI imaging database of 80 age-matched healthy controls. The extent of both hippocampal and whole-brain atrophy was evaluated with possible contributing factors. RESULTS:In all patients, the mean extent of hippocampal atrophy was 27.3%, and the mean extent of whole-brain atrophy was 11.2%. The extent of hippocampal atrophy was significantly correlated with low body mass index (BMI), total serum homocysteine (tHcy) levels, and brachial-ankle pulse wave velocity (baPWV). The extent of whole-brain atrophy showed significant correlations with age, hypoalbuminemia, and baPWV. Based on the multiple regression analysis, tHcy was an independent determinant of hippocampal atrophy (β = 0.460, R2 = 0.189, P<0.01); while age was an independent determinant of whole-brain atrophy (β = 0.594, R2 = 0.333, P<0.01). CONCLUSIONS:In this exploratory pilot study, hippocampal atrophy was significantly correlated with hyperhomocysteinemia in HD patients

High prevalence of peripheral arterial disease (PAD) in incident hemodialysis patients: screening by ankle-brachial index (ABI) and skin perfusion pressure (SPP) measurement

Abstract Background Peripheral arterial disease (PAD) has much impact on mortality in hemodialysis (HD) patients. Ankle-brachial index (ABI) and skin perfusion pressure (SPP) are useful tools to detect PAD in HD patients. However, the prevalence of PAD in incident HD patients by ABI and SPP measurement has not been fully elucidated. Methods We examined both ABI and SPP in 185 consecutive patients with end-stage renal failure at the initiation of HD therapy. PAD was diagnosed by previous history, clinical symptoms, histories of endovascular peripheral intervention, bypass surgery, amputation due to PAD, and values of ABI and SPP. Cut-off value of ABI and SPP for diagnosing PAD was set at < 0.9 and < 50 mmHg, respectively. Results The percentage of limbs with ABI < 0.9 and SPP value < 50 mmHg among total limbs were 10.8 and 21.1%, respectively. Among 185 patients in incident HD patients, 45 patients were diagnosed as having PAD. ABI and SPP positively correlated (r = 0.311, p = 0.006). However, discrepancy between ABI and SPP values (normal or high ABI with low SPP, or low ABI with normal SPP) was also found. Among 45 incident HD patients with PAD, only 14 patients (31.1%) showed low ABI and low SPP values. Conclusion Measurement of both ABI and SPP might be necessary to improve the diagnostic accuracy of PAD. Prevalence of PAD in incident HD patients was proved to be very high

Aliskiren, a Direct Renin Inhibitor, Improves Vascular Endothelial Function in Patients on Hemodialysis Independent of Antihypertensive Effect ~ a Pilot Study~

Aims: Aliskiren inhibits the first step in the renin-angiotensin system (RAS) and recently has been shown to modulate vascular diseases via RAS-dependent and independent pathways. This study aimed to determine the effect of aliskiren-associated direct renin inhibition on endothelial function in patients on hemodialysis via flow-mediated dilatation (FMD) and platelet-derived microparticles (PDMP), as biomarkers of atherosclerosis. Methods: A 12-week prospective study was performed with 24 patients on hemodialysis who were administered 150 mg orally aliskiren once daily for 12 weeks. Results: No significant difference were observed between pre-dialysis, home, and weekly averaged blood pressure at baseline and at 12 weeks (151.5 ± 8.5/80.9 ± 12.9 mmHg vs 150.3 ± 15.3/78.9 ± 21.2 mmHg, 151.4 ± 9.7/82.3 ± 14.7 mmHg vs 151.2 ± 17.7/81.4 ± 10.6 mmHg, and 156.0 ± 18.3/81.9 ± 9.4 mmHg vs 152.5 ± 18.9/81.7 ± 12.3 mmHg, respectively). FMD significantly increased from 2.54% ± 1.45% at baseline to 3.11% ± 1.37% at 12 weeks (P = 0.0267), and PDMP significantly decreased from 13.9 ± 5.8 U/mL at baseline to 10.9 ± 4.5 U/mL at 12 weeks (P = 0.0002). Conclusion: Aliskiren improved vascular endothelial function and platelet-endothelium activation in patients on hemodialysis independent of antihypertensive effect

Association between zinc deficiency and aorta stiffness in non-diabetic hemodialysis patients.

ObjectivesZinc deficiency (Zn MethodsOf 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn ResultsThe zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (pConclusionThe study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation