Committee report : Questionnaire survey on the treatment of COVID-19 in patients receiving dialysis therapy

Background: Patients with coronavirus disease 2019 (COVID-19) who receive dialysis therapy develop more severe disease and have a poorer prognosis than patients who do not. Although various data on the treatment of patients not receiving dialysis therapy have been reported, clinical practice for patients on dialysis is challenging as data is limited. The Infection Control Committee of the Japanese Society for Dialysis Therapy decided to clarify the status of treatment in COVID-19 patients on dialysis. Methods: A questionnaire survey of 105 centers that had treated at least five COVID-19 patients on dialysis was conducted in August 2021. Results: Sixty-six centers (62.9%) responded to the questionnaire. Antivirals were administered in 27.7% of facilities treating mild disease (most patients received favipiravir) and 66.7% of facilities treating moderate disease (most patients with moderate or more severe conditions received remdesivir). Whether and how remdesivir is administered varies between centers. Steroids were initiated most frequently in moderate II disease (50.8%), while 43.1% of the facilities initiated steroids in mild or moderate I disease. The type of steroid, dose, and the duration of administration were generally consistent, with most facilities administering dexamethasone 6 mg orally or 6.6 mg intravenously for 10 days. Steroid pulse therapy was administered in 48.5% of the facilities, and tocilizumab was administered in 25.8% of the facilities, mainly to patients on ventilators or equivalent medications, or to the cases of exacerbations. Furthermore, some facilities used a polymethylmethacrylate membrane during dialysis, nafamostat as an anticoagulant, and continuous hemodiafiltration in severe cases. There was limited experience of polymyxin B-immobilized fiber column-direct hemoperfusion and extracorporeal membrane oxygenation. The discharge criteria for patients receiving dialysis therapy were longer than those set by the Ministry of Health, Labor and Welfare in 22.7% of the facilities. Conclusions: Our survey revealed a variety of treatment practices in each facility. Further evidence and innovations are required to improve the prognosis of patients with COVID-19 receiving dialysis therapy

Investigation for the efficacy of COVID-19 vaccine in Japanese CKD patients treated with hemodialysis

Background: Dialysis patients are predisposed to severe disease and have a high mortality rate in coronavirus disease 2019 (COVID-19) due to their comorbidities and immunocompromised conditions. Therefore, dialysis patients should be prioritized for vaccination. This study aimed to examine how long the effects of the vaccine are maintained and what factors affect antibody titers. Methods: Hemodialysis patients (HD group) and age- and sex-matched non-dialysis individuals (Control group), receiving two doses of BNT162b2 vaccine, were recruited through the Japanese Society for Dialysis Therapy (JSDT) Web site in July 2021. Anti-SARS-CoV-2 immunoglobulin (IgG) (SARS-CoV-2 IgG titers) was measured before vaccination, 3 weeks after the first vaccination, 2 weeks after the second vaccination, and 3 months after the second vaccination, and was compared between Control group and HD group. Factors affecting SARS-CoV-2 IgG titers were also examined using multivariable regression analysis and stepwise regression analysis (least AIC). In addition, we compared adverse reactions in Control and HD groups and examined the relationship between adverse reactions and SARS-CoV-2 IgG titers. Results: Our study enrolled 123 participants in the Control group (62.6% men, median age 67.0 years) and 206 patients in the HD group (64.1% men, median age 66.4 years). HD group had significantly lower SARS-CoV-2 IgG titers at 3 weeks after the first vaccination (p < 0.0001), 2 weeks after second vaccination (p = 0.0002), and 3 months after the second vaccination (p = 0.045) than Control group. However, the reduction rate of SARS-CoV-2 IgG titers between 2 weeks and 3 months after the second vaccination was significantly smaller in HD group than in Control (p = 0.048). Stepwise regression analysis revealed that dialysis time was identified as the significant independent factors for SARS-CoV-2 IgG titers at 2 weeks after the second vaccination in HD group (p = 0.002) and longer dialysis time resulted in higher maximum antibody titers. The incidences of fever and nausea after the second vaccination were significantly higher in the HD group (p = 0.039 and p = 0.020). Antibody titers in those with fever were significantly higher than those without fever in both groups (HD: p = 0.0383, Control: p = 0.0096). Conclusion: HD patients had significantly lower antibody titers than age- and sex-matched non-dialysis individuals over 3 months after vaccination. Dialysis time was identified as a factor affecting SARS-CoV-2 IgG titers in HD group, with longer dialysis time resulting in higher maximum SARS-CoV-2 IgG titers

T-Cell Response and Antibody Production Induced by the COVID-19 Booster Vaccine in Japanese Chronic Kidney Disease Patients Treated with Hemodialysis

Humoral and cellular responses are critical in understanding immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Here, we evaluated these responses in hemodialysis (HD) patients after the booster vaccination. SARS-CoV-2 immunoglobulin (IgG) levels, neutralizing antibody titers, and the T-SPOT®.COVID test (T-SPOT) were measured prior to, three weeks after, and three months after the booster administration. The HD group had significantly higher SARS-CoV-2 IgG levels and neutralizing antibody titers against the original strain at three weeks and three months after the booster vaccination compared to the control group, albeit the HD group had lower SARS-CoV-2 IgG levels and neutralizing antibody titers before the booster administration. Moreover, the HD group had significantly higher T-SPOT levels at all three time points compared to the control group. The HD group also had significantly higher local and systemic adverse reaction rates than the control group. By booster vaccination, HD patients could acquire more effective SARS-CoV-2-specific humoral and cellular immunity than the control group

Transient suppression of transplanted spermatogonial stem cell differentiation restores fertility in mice.

A remarkable feature of tissue stem cells is their ability to regenerate the structure and function of host tissue following transplantation. However, the dynamics of donor stem cells during regeneration remains largely unknown. Here we conducted quantitative clonal fate studies of transplanted mouse spermatogonial stem cells in host seminiferous tubules. We found that, after a large population of donor spermatogonia settle in host testes, through stochastic fate choice, only a small fraction persist and regenerate over the long term, and the rest are lost through differentiation and cell death. Further, based on these insights, we showed how repopulation efficiency can be increased to a level where the fertility of infertile hosts is restored by transiently suppressing differentiation using a chemical inhibitor of retinoic acid synthesis. These findings unlock a range of potential applications of spermatogonial transplantation, from fertility restoration in individuals with cancer to conservation of biological diversity.Wellcome Trust MRC Royal Societ

Reworking of Hadean crust in the Acasta gneisses, northwestern Canada: Evidence from in-situ Lu-Hf isotope analysis of zircon

The Acasta Gneiss Complex of northwestern Canada comprises early Archean orthogneisses and includes the oldest known terrestrial rocks (3.94-4.03 Ga). Previous zircon geochronological studies revealed the presence of zircon xenocrysts with ages up to 4.

Oxidation States of Fe in Constituent Minerals of a Spinel Lherzolite Xenolith from the Tariat Depression, Mongolia: The Significance of Fe3+ in Olivine

The oxidation states of Fe within olivine, orthopyroxene, clinopyroxene, and spinel in a spinel lherzolite xenolith from the Tariat Depression, Mongolia were investigated using 57Fe Mössbauer spectroscopy to evaluate the redox condition of the upper mantle from which the Tariat spinel lherzolite xenolith was derived. The purity of separated minerals for the Mössbauer spectroscopic analysis was examined using X-ray powder diffraction, Raman spectroscopy, and transmission electron microscopy. Average Fo and Fe contents of olivine at the core part of the xenolith are 89.9(4) mol % and 0.195(3) atoms per formula unit, respectively. The Fe3+/ΣFe values of the olivine, orthopyroxene, clinopyroxene, and spinel, determined by Mössbauer spectroscopic analysis, are 0.027(2), 0.15(1), 0.26(3), and 0.34(5), respectively. The Mössbauer spectrum of olivine consists of two doublets assigned to Fe2+ at the octahedral sites and one doublet, with I.S. of 0.40(2) mm/s and Q.S. of 0.69(3) mm/s assigned to Fe3+ at the octahedral site. Since the Tariat spinel lherzolite xenolith in this study shows no evidence of metasomatism or thermal alteration, the existence of a small amount of Fe3+ in olivine and the fairly high Fe3+ contents of clinopyroxene, orthopyroxene, and spinel imply that the upper mantle under the Tariat area was in a rather oxidized condition

Effect of Acoustic Emission Sensor Location on the Detection of Grinding Wheel Deterioration in Cylindrical Grinding

The acoustic emission (AE) technique is an effective method for monitoring grinding wheels, and numerous studies have been published on applying an AE to monitor grinding wheels. However, there are few studies on the effect of the location of the AE sensor in stably acquiring the AE signals generated during deterioration in cylindrical grinding wheels. In this study, we propose a stable method for detecting the deterioration of a cubic boron nitride (cBN) grinding wheel during cylindrical grinding using AE. We compared the AE signals acquired during grinding from an AE sensor located on the hydrostatic bearing, which supports the grinding wheel shaft, with those from the tailstock spindle. Although positioning the AE sensor on the hydrostatic bearing was found to reduce the AE signal intensity, the AE signal variations were smaller at the same grinding position, and the effect of the grinding position was less than that for the tailstock spindle. Moreover, positioning an AE sensor on the hydrostatic bearing is considered to provide the characteristics of AE signals specifically focused on the changes in cBN on the grinding wheel surface allowing the surface roughness of the workpiece to be estimated during grinding