Comparison of Psychological Distress between Type 2 Diabetes Patients with and without Proteinuria

We investigated the link between proteinuria and psychological distress among patients with type 2 diabetes mellitus (T2DM). A total of 130 patients with T2DM aged 69.1±10.3 years were enrolled in this cross-sectional study. Urine and blood parameters, age, height, body weight, and medications were analyzed, and each patient’s psychological distress was measured using the six-item Kessler Psychological Distress Scale (K6). We compared the K6 scores between the patients with and without proteinuria. Forty-two patients (32.3%) had proteinuria (≥±) and the level of HbA1c was 7.5±1.3%. The K6 scores of the patients with proteinuria were significantly higher than those of the patients without proteinuria even after adjusting for age and sex. The clinical impact of proteinuria rather than age, sex and HbA1c was demonstrated by a multiple regression analysis. Proteinuria was closely associated with higher psychological distress. Preventing and improving proteinuria may reduce psychological distress in patients with T2DM

Relationship between self-esteem and suicidal ideation before and during COVID-19 in a non-clinical sample: mediating effects of psychological distress and hopelessness

IntroductionSeveral studies have highlighted the impact of the novel coronavirus disease (COVID-19) pandemic on suicide. Accordingly, investigating the risk factors of suicide during this crisis is important. Based on the escape theory of suicide, the current study examined the serial mediating roles of psychological distress and hopelessness in the relationship between self-esteem and suicidal ideation. It also aimed to explore whether or not the COVID-19 pandemic changed the mediation effect in any way.MethodsData were collected from 645 university students before and during the pandemic. The study employed mediation and multi-group analyses to test the hypotheses.ResultsThe results demonstrated that individuals with low self-esteem reported high psychological distress, which further lead to hopelessness and eventually heightened suicidal ideation. Multi-group analysis revealed that psychological distress exerted a greater impact on suicidal ideation during COVID-19.DiscussionThe finding suggested that self-esteem, hopelessness, and psychological distress could help elucidate the development of suicidal ideation. Clinicians may target these factors in suicide prevention programs, particularly in the settings of the COVID-19 pandemic or future crisis

Summary of the 3rd IAEA technicalmeeting on divertor concepts

This report summarizes the contributions presented at the 3rd IAEA technical meeting on divertor concepts, held in Vienna, Austria, 4–7 November 2019. The meeting brought together more than 70 experts from nuclear fusion research sites worldwide to discuss the different aspects that the divertor design and fusion machine operation involve, from ITER divertor developments to innovative technologies for future DEMO divertor. The main topics of the meeting were: divertor and confinement; radiative power exhaust; scrape-off layer (SOL) and divertor physics; steady state operation and transient heat loads; plasma facing components materials and heat exhaust for steady state operation; and divertors for DEMO and future power reactors

Subaru Hyper Suprime-Cam Survey for An Optical Counterpart of GW170817

We perform a $z$-band survey for an optical counterpart of a binary neutron star coalescence GW170817 with Subaru/Hyper Suprime-Cam. Our untargeted transient search covers $23.6$ deg$^2$ corresponding to the $56.6\%$ credible region of GW170817 and reaches the $50\%$ completeness magnitude of $20.6$ mag on average. As a result, we find 60 candidates of extragalactic transients, including J-GEM17btc (a.k.a. SSS17a/DLT17ck). While J-GEM17btc is associated with NGC 4993 that is firmly located inside the 3D skymap of GW170817, the other 59 candidates do not have distance information in the GLADE v2 catalog or NASA/IPAC Extragalactic Database (NED). Among 59 candidates, 58 are located at the center of extended objects in the Pan-STARRS1 catalog, while one candidate has an offset. We present location, $z$-band apparent magnitude, and time variability of the candidates and evaluate the probabilities that they are located inside of the 3D skymap of GW170817. The probability for J-GEM17btc is $64\%$ being much higher than those for the other 59 candidates ($9.3\times10^{-3}-2.1\times10^{-1}\%$). Furthermore, the possibility, that at least one of the other 59 candidates is located within the 3D skymap, is only $3.2\%$. Therefore, we conclude that J-GEM17btc is the most-likely and distinguished candidate as the optical counterpart of GW170817.Comment: 14 pages, 9 figures. Accepted for publication in PASJ (Publications of the Astronomical Society of Japan

Low-Dose Intravenous Alteplase in Wake-Up Stroke

Background and Purpose—We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods—This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results—Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P=0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P>0.999), respectively. Conclusions—No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions

Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung

BackgroundAldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined.MethodsWe examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 −/− mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 −/− mice.ResultsIn humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 −/− and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 −/− mice. Aldh2 −/− tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 −/− mice than in WT mice.ConclusionsALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect

Power Exhaust Concepts and Divertor Designs for Japanese and European DEMO Fusion Reactors

Concepts of the power exhaust and divertor design have been developed, with a high priority in the pre-conceptual design phase of the Japan-Europe Broader Approach DEMO Design Activity. A common critical issue is the large power exhaust and its fraction in the main plasma and divertor by the radiative cooling. Different exhaust concepts in the main plasma and divertor have been developed for JA and EU DEMOs. JA proposed a conventional closed divertor geometry to challenge large Psep/Rp handling of 30-35 MWm-1 in order to maintain the radiation fraction in the main plasma at the ITER-level (fradmain = Pradmain/Pheat ~0.4) and higher plasma performance. EU challenged both increasing fradmain to ~0.65 and handling the ITER-level Psep/Rp in the open divertor geometry. Power exhaust simulations have been performed by SONIC (JA) and SOLPS5.1 (EU) with corresponding Psep = 250-300 MW and 150-200 MW, respectively. Both results showed that large divertor radiation fraction (Praddiv/Psep 0.8) was required to reduce both peak qtarget ( 10MWm-2) and Te,idiv. In addition, the JA divertor performance with EU-reference Psep of 150MW showed benefit of the closed geometry to reduce the peak qtarget and Te,idiv near the separatrix, and to produce the partial detachment. Integrated designs of the water cooled divertor target, cassette and coolant pipe routing have been developed in both EU and JA, based on the tungsten (W) monoblock concept with Cu-alloy pipe. For year-long operation, DEMO-specific risks such as radiation embrittlement of Cu-interlayers and Cu-alloy cooling pipe were recognized, and both foresee higher water temperature (130-200 °C) compared to that for ITER. At the same time, several improved technologies of high heat flux components have been developed in EU, and different heat sink design, i.e. Cu-alloy cooling pipes for targets and RAFM steel ones for the baffle, dome and cassette, was proposed in JA. The two approaches provide important case-studies of the DEMO divertor, and will significantly contribute to both DEMO designs

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

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