Association between person-centred care quality and advance care planning participation in haemodialysis.

OBJECTIVE: Person-centred care (PCC), which incorporates patients' preferences and values for medical care and their life, has been proposed in decision-making for promoting advance care planning (ACP) among patients with kidney failure. Therefore, we aimed to examine variations in PCC across facilities and the association between PCC and ACP participation. METHODS: This multicentre cross-sectional study included Japanese adults undergoing outpatient haemodialysis at six dialysis centres. The main exposure was PCC, measured using the 13-item Japanese version of the Primary Care Assessment Tool-short form. The main outcome was ACP participation as defined by discussion with the attending physician or written documentation or notes regarding treatment preferences. A general linear model was used to examine the covariates of the quality of PCC. Modified Poisson regression models were used to examine the associations of ACP participation. RESULTS: A total of 453 individuals were analysed; 26.3% of them participated in ACP. Higher PCC was associated with greater ACP participation in a dose-response manner (adjusted prevalence ratios for the first to fourth quartiles: 1.36, 2.31, 2.64 and 3.10, respectively) in respondents with usual source of care (USC) than in those without USC. Among the PCC subdomains, first contact, longitudinality, comprehensiveness (services provided) and community orientation were particularly associated with ACP participation. A maximum of 12.0 points of facility variation was noted in the quality of PCC. CONCLUSIONS: High quality of PCC was associated with ACP participation. The substantial disparity in PCC between facilities provides an opportunity to revisit the quality improvement in PCC.

Relapsing Peritoneal Dialysis-Associated Peritonitis due to Kocuria rhizophila: A Case Report.

Introduction: The Kocuria genus, encompassing gram-positive coccoid actinobacteria belonging to the Micrococcaceae family, has recently been discovered residing on the human skin and oral flora. Reports of Kocuria-associated infections in humans have been scarce. Herein, we present the first case of relapsing peritoneal dialysis (PD)-associated peritonitis caused by Kocuria rhizophila. Case Presentation: The patient, a 78-year-old male, presented with turbid effluent PD fluid, accompanied by an elevated white blood cell count of 253 cells/µL, of which 59% were neutrophils. A diagnosis of PD-associated peritonitis was established, leading to the initiation of intraperitoneal administration of ceftazidime and vancomycin. Subsequently, Kocuria rhizophila was identified through the bacterial culture of the dialysate. On the seventh day of initial treatment, the antibiotic regimen was changed to penicillin G, and the patient underwent a 3-week course of antibiotics. However, 1 week after discharge, the patient's dialysis fluid became cloudy once again, with subsequent detection of Kocuria rhizophila in the fluid culture. Ultimately, the decision was made to remove the patient's PD catheter and transition to hemodialysis. Conclusion: PD-associated peritonitis attributed to Kocuria species may be considered a potential risk for recurrence.

Trust, Multidimensional Health Literacy, and Medication Adherence among Patients Undergoing Long-Term Hemodialysis.

BACKGROUND: Basic health literacy and trust in physicians can influence medication adherence in patients receiving dialysis. However, how high-order health literacy is associated with medication adherence and how trust in physicians mediates this association remain unclear. We assessed the inter-relationships between health literacy, trust in physicians, and medication adherence. We investigated the mediating role of trust in physicians in the relationship between health literacy and medication adherence. METHODS: This multicenter cross-sectional study included Japanese adults receiving outpatient hemodialysis at six dialysis centers. Multidimensional health literacy was measured using the 14-item Functional, Communicative, and Critical Health Literacy scale. Trust in physicians was measured using the five-item Wake Forest Physician Trust scale. Medication adherence was measured using the 12-item Adherence Starts with Knowledge scale. A series of general linear models were created to analyze the associations between health literacy and Adherence Starts Knowledge scores with and without trust in physicians. Mediation analysis was performed to determine whether trust in physicians mediated this association. RESULTS: In total, 455 patients were analyzed. Higher functional and communicative health literacies were associated with less adherence difficulties (per 1-point higher: -1.79 [95% confidence interval (CI): -2.59 to -0.99] and -2.21 [95% CI: -3.45 to -0.96], respectively), whereas higher critical health literacy was associated with greater adherence difficulties (per 1-point higher: 1.69 [95% CI: 0.44 to 2.94]). After controlling for trust in physicians, the magnitude of the association between health literacies and medication adherence decreased. Trust in physicians partially mediated the association between functional or communicative health literacy and medication adherence (especially beliefs) and completely mediated the association between critical health literacy and medication adherence (especially behaviors). CONCLUSIONS: Functional and communicative health literacies were positively associated with medication adherence, whereas critical health literacy was negatively associated with it. Each association was mediated by trust in physicians.

Kidney Biopsy Proven Thrombotic Microangiopathy Induced by Methamphetamine: A Case Report.

A 47-year-old man was admitted to our hospital with acute kidney injury, severe hypertension, heart failure, thrombocytopenia, and elevated lactate dehydrogenase. Renal biopsy revealed fibrin thrombi within the glomerular capillaries and moderate fibrotic intimal thickening in the interlobular arteries. The histological diagnosis was thrombotic microangiopathy (TMA). Regarding cardiac involvement, we found marked stenosis in the left anterior descending artery on coronary angiography and cardiomyopathy on myocardial biopsy. Blood concentrations of amphetamine and methamphetamine were high (14.1 ng/mL and 333 ng/mL, respectively). It is important to consider methamphetamine as a cause of renal TMA and multi-organ dysfunction.

Natural Selection Signatures in the Hondo and Ryukyu Japanese Subpopulations.

Natural selection signatures across Japanese subpopulations are under-explored. Here we conducted genome-wide selection scans with 622,926 single nucleotide polymorphisms for 20,366 Japanese individuals, who were recruited from the main-islands of Japanese Archipelago (Hondo) and the Ryukyu Archipelago (Ryukyu), representing two major Japanese subpopulations. The integrated haplotype score (iHS) analysis identified several signals in one or both subpopulations. We found a novel candidate locus at IKZF2, especially in Ryukyu. Significant signals were observed in the major histocompatibility complex region in both subpopulations. The lead variants differed and demonstrated substantial allele frequency differences between Hondo and Ryukyu. The lead variant in Hondo tags HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01, a haplotype specific to Japanese and Korean. While in Ryukyu, the lead variant tags DRB1*15:01-DQB1*06:02, which had been recognized as a genetic risk factor for narcolepsy. In contrast, it is reported to confer protective effects against type 1 diabetes and human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. The FastSMC analysis identified 8 loci potentially affected by selection within the past 20-150 generations, including 2 novel candidate loci. The analysis also showed differences in selection patterns of ALDH2 between Hondo and Ryukyu, a gene recognized to be specifically targeted by selection in East Asian. In summary, our study provided insights into the selection signatures within the Japanese and nominated potential sources of selection pressure.

Demographic history of Ryukyu islanders at the southern part of the Japanese Archipelago inferred from whole-genome resequencing data.

The Ryukyu Islands are located in the southernmost part of the Japanese Archipelago and consist of several island groups. Each island group has its own history and culture, which differ from those of mainland Japan. People of the Ryukyu Islands are genetically subdivided; however, their detailed demographic history remains unclear. We report the results of a whole-genome sequencing analysis of a total of 50 Ryukyu islanders, focusing on genetic differentiation between Miyako and Okinawa islanders. We confirmed that Miyako and Okinawa islanders cluster differently in principal component analysis and ADMIXTURE analysis and that there is a population structure among Miyako islanders. The present study supports the hypothesis that population differentiation is primarily caused by genetic drift rather than by differences in the rate of migration from surrounding regions, such as the Japanese main islands or Taiwan. In addition, the genetic cline observed among Miyako and Okinawa islanders can be explained by recurrent migration beyond the bounds of these islands. Our analysis also suggested that the presence of multiple subpopulations during the Neolithic Ryukyu Jomon period is not crucial to explain the modern Ryukyu populations. However, the assumption of multiple subpopulations during the time of admixture with mainland Japanese is necessary to explain the modern Ryukyu populations. Our findings add insights that could help clarify the complex history of populations in the Ryukyu Islands.

Infection-Related Cryoglobulinemic Glomerulonephritis with Serum Anti-Factor B Antibodies Identified and Staining for NAPlr/Plasmin Activity Due to Infective Endocarditis.

In this rare case of infection-related cryoglobulinemic glomerulonephritis with infective endocarditis, a 78-year-old male presented with an acute onset of fever and rapidly progressive glomerulonephritis. His blood culture results were positive for Cutibacterium modestum, and transesophageal echocardiography showed vegetation. He was diagnosed with endocarditis. His serum immunoglobulin M, IgM-cryoglobulin, and proteinase-3-anti-neutrophil cytoplasmic antibody levels were elevated, and his serum complement 3 (C3) and C4 levels were decreased. Renal biopsy results showed endocapillary proliferation, mesangial cell proliferation, and no necrotizing lesions on light microscopy, with strong positive staining for IgM, C3, and C1q in the capillary wall. Electron microscopy showed deposits in the mesangial area in the form of fibrous structures without any humps. Histological examination confirmed a diagnosis of cryoglobulinemic glomerulonephritis. Further examination showed the presence of serum anti-factor B antibodies and positive staining for nephritis-associated plasmin receptor and plasmin activity in the glomeruli, suggesting infective endocarditis-induced cryoglobulinemic glomerulonephritis.

Selective Bcl-2 inhibition promotes hematopoietic chimerism and allograft tolerance without myelosuppression in nonhuman primates.

Hematopoietic stem cell transplantation (HSCT) has many potential applications beyond current standard indications, including treatment of autoimmune disease, gene therapy, and transplant tolerance induction. However, severe myelosuppression and other toxicities after myeloablative conditioning regimens have hampered wider clinical use. To achieve donor hematopoietic stem cell (HSC) engraftment, it appears essential to establish niches for the donor HSCs by depleting the host HSCs. To date, this has been achievable only by nonselective treatments such as irradiation or chemotherapeutic drugs. An approach that is capable of more selectively depleting host HSCs is needed to widen the clinical application of HSCT. Here, we show in a clinically relevant nonhuman primate model that selective inhibition of B cell lymphoma 2 (Bcl-2) promoted hematopoietic chimerism and renal allograft tolerance after partial deletion of HSCs and effective peripheral lymphocyte deletion while preserving myeloid cells and regulatory T cells. Although Bcl-2 inhibition alone was insufficient to induce hematopoietic chimerism, the addition of a Bcl-2 inhibitor resulted in promotion of hematopoietic chimerism and renal allograft tolerance despite using only half of the dose of total body irradiation previously required. Selective inhibition of Bcl-2 is therefore a promising approach to induce hematopoietic chimerism without myelosuppression and has the potential to render HSCT more feasible for a variety of clinical indications.

Transcriptome Analysis in a Scleractinian Coral, Acropora tenuis, during the Spawning Season With Reference to the Gonadal Condition.

Synchronous spawning is a striking feature of coral. Although it is important for reproductive success, corals reallocate energy for reproduction to growth when they are damaged by external stimuli. To assess the transcriptome before and after spawning in the scleractinian coral Acropora tenuis, we tagged three colonies (one bleached and two unbleached) in the field around Sesoko Island (Okinawa, Japan) in November 2016, sampled them monthly from May to July 2017, and performed RNA sequencing (RNA-Seq) analysis. Histological analysis revealed that the previously bleached colony possessed gametes in June, by which time the other two colonies had already spawned. In RNA-Seq analyses, multi-dimensional scaling based on gene expression similarity among the samples reflected the differences between colonies and between months except for the sample of a non-spawned colony in May, which was similar to the samples in June. The similarity of the non-spawned colony sample in May to the samples in June was also shown in hierarchical clustering based on the expression patterns of the genes that were differentially expressed between months in the spawned colonies. These results suggest that non-spawning was already decided in May, and that the physiological condition in a non-spawned colony in May was advanced to June. RNA-Seq analysis also showed that genes related to gametogenesis and those related to apoptosis were upregulated before and after spawning, respectively.

Impact of ABO Compatibility/Incompatibility on the Perioperative Anti-SARS-CoV-2 Immunoglobulin G Levels in 2 Preoperatively Vaccinated Patients Undergoing Kidney Transplant: A Case Report.

Herein, we monitored the perioperative anti-SARS-CoV-2 spike immunoglobulin G titers in patients who were preoperatively vaccinated with 2 doses of a COVID-19 messenger RNA vaccine. Additionally, we compared the clinical settings between ABO-incompatible and ABO-compatible pre-emptive kidney transplant (KTx). Case 1 was of a 45-year-old man who was an ABO-incompatible KTx recipient. Before transplant, his serum antibody titers decreased from 278 U/mL at baseline to 41.9 U/mL after desensitization therapy (84.9% lower) and 54.7 U/mL (80.3% lower) at day 8; it is now maintained at 4.1 U/mL at 6 months posttransplant (98.5% lower). Case 2 was of a 50-year-old man who was an ABO-compatible KTx recipient. His serum antibody titer level decreased from 786 U/mL at baseline to 386 U/mL on day 8 (50.8% lower) and is now maintained at 156 U/mL at 6 months posttransplant (80.1% lower). We suggest that anti-SARS-CoV-2 spike immunoglobulin G titers should be monitored during the perioperative period to determine the optimal timing of COVID-19 vaccine booster doses for the maintenance of protective immunity, particularly in ABO-incompatible KTx recipients who require desensitization therapy.

Evaluation of the Correlation Between Responders and Non-Responders to the Second Coronavirus Disease Vaccination In Kidney Transplant Recipients: A Retrospective Single-Center Cohort Study.

BACKGROUND: The immune response to COVID-19 vaccination in kidney transplant (KTx) recipients is significantly lower than that in healthy controls. We evaluated immune responses after the COVID-19 vaccine and their possible relationship with other cofactors in KTx recipients. METHODS: This retrospective single-center cohort study included 29 KTx recipients 2-8 weeks after receiving 2 doses of the Pfizer-BioNTech SARS-CoV-2 messenger RNA vaccine. Anti-SARS-CoV-2 spike (S) immunoglobulin (Ig)-G levels were evaluated to define cofactors influencing the immune response between the responder (anti-SARS-CoV-2 IgG level ≥0.8 U/mL) (n = 16) and nonresponder groups (anti-SARS-CoV-2 IgG level <0.8 U/mL) (n = 13). The kinetics of antibodies between 2 and 6 months after the second vaccination was also compared between the groups. RESULTS: KTx recipients with IgG levels ≥0.8 U/mL were younger (54 [interquartile range {IQR}, 46.5-61] years vs 65 [IQR, 55-71.5] years; P = .01), had been transplanted for a longer median time (1588 [IQR, 1382-4751] days vs 1034 [IQR, 548.5-1833] days; P = .02), and were more often treated with a lower mycophenolate mofetil dosage (765.6 ± 119.6 vs 1077 ± 76.9 mg; P = .04) than KTx recipients with IgG levels <0.8 U/mL. There was no significant difference in antibody titers between time periods after the second dose in the responder group. At the 6-month follow-up, a serologic response against the SARS-CoV-2 S was observed in 44.4% of KTx recipients in the nonresponder group. CONCLUSIONS: More than 50% of KTx recipients developed a higher antibody response after the second dose of COVID-19 vaccination.

Comparison of antibody response following the second dose of SARS-CoV-2 mRNA vaccine in elderly patients with late-stage chronic kidney disease.

Background: Currently, it is unclear whether the progression of chronic kidney disease (CKD) could be an independent predictor of antibody response after administration of a COVID-19 vaccine. This study aimed to investigate the immune response to COVID-19 vaccination in patients with CKD stage G4 to G5 without renal replacement therapy and G5D using the recommended dose and schedule. Methods: This retrospective single-center cohort study evaluated immunogenicity regarding antibody response after COVID-19 vaccination in our hospital for late-stage CKD patients aged ≥ 60 years. We evaluated antibody responses in 48 patients with CKD G4, 35 patients with CKD G5, and 70 patients undergoing hemodialysis (HD; CKD G5D). Results: After the second vaccination, anti-SARS-CoV-2-S (Spike) IgG levels were found to be positive (> 0.8 U/mL) in all CKD G4 and G5 patients (100%), and 69 of 70 HD patients (98.5%). The median (interquartile range [IQR] S-IgG level (Ab titers) was 358 [130.2-639.2], 218 [117-377], and 185.5 [95.1-323.5] U/mL in the CKD G4, G5, and HD groups, respectively. The median S-IgG levels were significantly lower in the HD group than in the CKD G4 group (p < 0.01). However, there was no significant difference in the antibody titers between the CKD G4 and G5 groups. To further analyze the decline in S-IgG levels after 6 months, we additionally assessed and compared antibody titers at 1 month and 6 months after the second vaccination in the HD group. Compared with the median S-IgG levels of 185.5 [95.1-323.5] U/mL 1 month after the second dose, the median S-IgG level 6 months thereafter was significantly decreased at 97.4 [62.5-205.5] U/mL (p < 0.05). Conclusions: We highlight two major factors of variability in the vaccine response. First, in elderly patients with late-stage CKD, antibody titers tended to be lower in the G5D group than in the G4 and G5 groups despite the shorter time since vaccination; therefore, CKD stage progression might cause a decline in antibody titers. Second, waning immune responses were observed 6 months after second dose administration in HD patients advocating a potential need for a third booster dose vaccine after 6 months.

Genomic and transcriptomic analyses of the subterranean termite Reticulitermes speratus: Gene duplication facilitates social evolution.

Termites are model social organisms characterized by a polyphenic caste system. Subterranean termites (Rhinotermitidae) are ecologically and economically important species, including acting as destructive pests. Rhinotermitidae occupies an important evolutionary position within the clade representing a transitional taxon between the higher (Termitidae) and lower (other families) termites. Here, we report the genome, transcriptome, and methylome of the Japanese subterranean termite Reticulitermes speratus Our analyses highlight the significance of gene duplication in social evolution in this termite. Gene duplication associated with caste-biased gene expression was prevalent in the R. speratus genome. The duplicated genes comprised diverse categories related to social functions, including lipocalins (chemical communication), cellulases (wood digestion and social interaction), lysozymes (social immunity), geranylgeranyl diphosphate synthase (social defense), and a novel class of termite lineage-specific genes with unknown functions. Paralogous genes were often observed in tandem in the genome, but their expression patterns were highly variable, exhibiting caste biases. Some of the assayed duplicated genes were expressed in caste-specific organs, such as the accessory glands of the queen ovary and the frontal glands of soldier heads. We propose that gene duplication facilitates social evolution through regulatory diversification, leading to caste-biased expression and subfunctionalization and/or neofunctionalization conferring caste-specialized functions.

Species divergence and repeated ancient hybridization in a Sulawesian lake system.

An increasing volume of empirical studies demonstrated that hybridization between distant lineages may have promoted speciation in various taxa. However, the timing, extent and direction of introgressive hybridization remain unknown in many cases. Here, we report a possible case in which repeated hybridization promoted divergence of Oryzias ricefishes (Adrianichthyidae) on Sulawesi, an island of Wallacea. Four Oryzias species are endemic to the Malili Lake system in central Sulawesi, which is composed of five tectonic lakes; of these, one lake is inhabited by two species. Morphological and population genomic analyses of genome-wide single-nucleotide polymorphisms revealed that these two sympatric species are phylogenetically sister to but substantially reproductively isolated from each other. Analyses of admixture and comparison of demographic models revealed that the two sympatric species experienced several substantial introgressions from outgroup populations that probably occurred soon after they had secondary contact with each other in the lake. However, the ratio of migrants from the outgroups was estimated to be different between the two species, which is consistent with the hypothesis that these introgressions aided their divergence or prevented them from forming a hybrid swarm. Repeated lake fragmentations and fusions may have promoted diversification of this freshwater fish species complex that is endemic to this ancient lake system.

Coevolution between MHC Class I and Antigen-Processing Genes in Salamanders.

Proteins encoded by antigen-processing genes (APGs) provide major histocompatibility complex (MHC) class I (MHC-I) with antigenic peptides. In mammals, polymorphic multigenic MHC-I family is served by monomorphic APGs, whereas in certain nonmammalian species both MHC-I and APGs are polymorphic and coevolve within stable haplotypes. Coevolution was suggested as an ancestral gnathostome feature, presumably enabling only a single highly expressed classical MHC-I gene. In this view coevolution, while optimizing some aspects of adaptive immunity, would also limit its flexibility by preventing the expansion of classical MHC-I into a multigene family. However, some nonmammalian taxa, such as salamanders, have multiple highly expressed MHC-I genes, suggesting either that coevolution is relaxed or that it does not prevent the establishment of multigene MHC-I. To distinguish between these two alternatives, we use salamanders (30 species from 16 genera representing six families) to test, within a comparative framework, a major prediction of the coevolution hypothesis: the positive correlation between MHC-I and APG diversity. We found that MHC-I diversity explained both within-individual and species-wide diversity of two APGs, TAP1 and TAP2, supporting their coevolution with MHC-I, whereas no consistent effect was detected for the other three APGs (PSMB8, PSMB9, and TAPBP). Our results imply that although coevolution occurs in salamanders, it does not preclude the expansion of the MHC-I gene family. Contrary to the previous suggestions, nonmammalian vertebrates thus may be able to accommodate diverse selection pressures with flexibility granted by rapid expansion or contraction of the MHC-I family, while retaining the benefits of coevolution between MHC-I and TAPs.