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Here, the authors identify interleukin-11 as a mediator of bone-adipose crosstalk during mechanical loading of the bone. Interleukin-11 secreted by the bone acts as a hormone to regulate fat metabolism, in addition to having an autocrine-paracrine effect on bone itself.

Abstract Traumatic brain injury (TBI) is associated with coagulation/fibrinolysis disorders. We retrospectively evaluated 61 TBI cases transported to hospital within 1 h post-injury. Levels of thrombin-antithrombin III complex (TAT), D-dimer, and plasminogen activator inhibitor-1 (PAI-1) were measured on arrival and 3 h, 6 h, 12 h, 1 day, 3 days and 7 days after injury. Multivariate logistic regression analysis was performed to identify prognostic factors for coagulation and fibrinolysis. Plasma TAT levels peaked at admission and decreased until 1 day after injury. Plasma D-dimer levels increased, peaking up to 3 h after injury, and decreasing up to 3 days after injury. Plasma PAI-1 levels increased up to 3 h after injury, the upward trend continuing until 6 h after injury, followed by a decrease until 3 days after injury. TAT, D-dimer, and PAI-1 were elevated in the acute phase of TBI in cases with poor outcome. Multivariate logistic regression analysis showed that D-dimer elevation from admission to 3 h after injury and PAI-1 elevation from 6 h to 1 day after injury were significant negative prognostic indicators. Post-TBI hypercoagulation, fibrinolysis, and fibrinolysis shutdown were activated consecutively. Hyperfibrinolysis immediately after injury and subsequent fibrinolysis shutdown were associated with poor outcome.

Land cover changes in mountainous regions are potential precursors to landslide disasters. However, the effects of past long-term land cover changes on the characteristics of recent landslides remains underexplored. We studied land cover evolution over a 56-year period on Omishima Island in western Japan to examine the spatial relations of landslides in the July 2018 storm event based on rainfall, land cover trajectories, and topography. We generated land cover maps for 1962, 1981, and 2018 by aerial photo interpretation. We also identified 512 new landslides. Based on 47-year precipitation records, we estimated the return periods of 1- to 264-h rainfalls during the storm using the generalised extreme value (GEV) distributions. Return periods showed wide variation when the derived GEV distributions were applied to 1-km grid rainfall distributions. Despite such pronounced spatial variations in rainfall, we did not observe a clear correlation between rainfall intensity and landslide distribution. In contrast, land cover trajectories had a pronounced effect on landslide occurrence. Landslides were more concentrated on slopes that experienced land cover changes after 1962. A comparison of slopes on farmland developed between 1962 and 1981 (mainly citrus orchards) indicated that landslide density and area ratio were significantly lower on slopes that had reverted to forests than on those remaining as farmland. However, the values of the reforested slopes exceeded those of forests and farmlands that remained since before 1962. Our geospatial analysis revealed that even if the field had shifted to forests, the effects of reduced slope stability due to orchard development had remained for at least 37 years. This suggested that the impacts of converting forests to orchards last longer than harvesting in managed plantation forests.

Abstract Background Studies have demonstrated the efficacy of oxygen delivery-guided perfusion (ODGP) in preventing postoperative acute kidney injury, but the benefit of ODGP for delirium has not been confirmed. We retrospectively investigated the risk factors for postoperative delirium in patients who underwent ODGP (with oxygen delivery index [DO2i] > 300 mL/min/m2). Methods Consecutive patients who underwent on-pump cardiovascular surgery with ODGP from January 2018 to December 2020 were retrospectively analyzed. In addition to examining patients’ DO2i during cardiopulmonary bypass (CPB), we quantified the two primary DO2 components-hematocrit (Hct) and pump flow. Delirium was defined based on the Intensive Care Delirium Screening Checklist (ICDSC). Patients were divided into three groups: no delirium (ICDSC score = 0), subsyndromal delirium (ICDSC score = 1–3), and clinical delirium (ICDSC score ≥ 4). Results Multivariate analysis identified only the number of red blood cell (RBC) units transfused, intubation time, and the cumulative time below the Hct threshold of 25% as predictive factors of postoperative delirium. Although patients with higher ICDSC scores had greater hemodilution during CPB, ODGP resulted in a higher pump flow, and DO2i was maintained above 300 mL/min/m2, with no significant difference between the three groups. Conclusions A low Hct level during CPB with ODGP, the number of RBC units transfused, and intubation time were associated with postoperative delirium. Further investigations are needed to determine the ability of ODGP to prevent low Hct during CPB.

Abstract Background The alcohol-metabolizing enzyme aldehyde dehydrogenase 2 (ALDH2) is a carcinogenic acetaldehyde-degrading enzyme, and its low activity is a genetic constitution peculiar to East Asians. People with low alcohol dehydrogenase 1B activity (ADH1B*1/*1 genotype) have a high risk of developing head and neck cancer and alcoholism. The study aims to evaluate the effectiveness of brief interventions for excessive drinking among college students and adults in their 20s, including information on five constitutions that combine the ALDH2 and ADH1B genotypes. Methods Participants comprised university students and staff aged 20–30 years who had consumed ≥40 g (males) or ≥20 g (females) of pure alcohol; they were classified into intervention and control groups using a simple randomization method. Participants anonymously filled out questionnaires linked to identification numbers and recorded the drinking days and amounts on the drinking calendar. The intervention group will then be tested for genotype testing using saliva (5 types of combinations of ALDH2 and ADH1B enzyme activities); the result report will arrive approximately 1 month later. We will conduct a 30-min face-to-face or online intervention. The control group will be merely given the conventional materials, and genetic testing will be performed voluntarily after 6 months (end of study). The intervention group will undergo questionnaire surveys 1 month after the intervention and 3 and 6 months after baseline. Questionnaire surveys will be conducted 1, 3, and 6 months after baseline for the control group. The average amount of drinking before and after the intervention, attribute/baseline data between the two groups, and time-series data were compared using various analysis tools. For interventions, we engaged in dialog based on intervention materials that added genotyping content to the existing materials, result reports, baseline data, and drinking calendar records. Participants’ ingenuity is respected to support their drinking behavior and goal setting. Discussion Individual information on the genetic makeup of alcohol-metabolizing enzymes provided during the intervention is more personal and objective than general health information, especially in Japan, where the ALDH2 low activity rate is high. This information may be useful for health care and precautionary measures. Trial registration R000050379, UMIN000044148, Registered on June 1, 2021. Scientific Title: Examination of simple intervention using genetic polymorphism information for excessive drinking.

Upregulation of transcription factor OASIS in podocytes contributes to podocyte and/or tubular injury through decreased PRKCi expression and is a critical event for the disturbance of kidney homeostasis.

Abstract Background Coronavirus disease (COVID-19) has induced an urgent need to train medical students not only in infection prevention control but also in the treatment of infectious diseases, including COVID-19. This study evaluates the impact of simulated clinical practice with peer role-plays and a lecture on clinical education for COVID-19. Methods The sample for the study included 82 fourth- and fifth-year medical students undergoing clinical clerkship in respiratory medicine. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages of simulated clinical practice with peer role-plays and lectures on clinical education for COVID-19. Results A total of 75 students participated in the COVID-19 education program between January and November 2021. The responses to the questionnaire revealed that the satisfaction level of students with COVID-19 education was high. No significant change was found among students concerning fear of COVID-19 before and after the program. The degree of burden of handling information on COVID-19 reduced significantly, while the degree with respect to the use of personal protective equipment (PPE), including appropriate wearing and removing of PPE, and care of patients with confirmed COVID-19 while taking steps to prevent infection, exhibited a decreasing trend. Nine FGIs were conducted (n = 74). The advantages of simulated clinical practice were segregated into five categories (infection prevention control, educational methods, burden on healthcare providers, self-reflection, and fear of COVID-19); and that of the lecture were segregated into four categories (information literacy, knowledge of COVID-19, educational methods, and self-reflection). Conclusions Simulated clinical practice with peer role-plays and the lecture pertaining to COVID-19 can prove to be efficient and safe methods for learning about COVID-19 infection and prevention control for medical students. They can reduce the burden of COVID-19 patients’ care. Moreover, they can also provide an opportunity for self-reflection, realize the burden of medical care, and acquire relevant information.

Hepatitis delta virus (HDV), a satellite virus of HBV, is regarded as the most severe type of hepatitis virus because of the substantial morbidity and mortality. The IFN system is the first line of defense against viral infections and an essential element of antiviral immunity; however, the role of the hepatic IFN system in controlling HBV-HDV infection remains poorly understood. Herein, we showed that HDV infection of human hepatocytes induced a potent and persistent activation of the IFN system whereas HBV was inert in triggering hepatic antiviral response. Moreover, we demonstrated that HDV-induced constitutive activation of the hepatic IFN system resulted in a potent suppression of HBV while modestly inhibiting HDV. Thus, these pathogens are equipped with distinctive immunogenicity and varying sensitivity to the antiviral effectors of IFN, leading to the establishment of a paradoxical mode of viral interference wherein HDV, the superinfectant, outcompetes HBV, the primary pathogen. Furthermore, our study revealed that HDV-induced constitutive IFN system activation led to a state of IFN refractoriness, rendering therapeutic IFNs ineffective. The present study provides potentially novel insights into the role of the hepatic IFN system in regulating HBV-HDV infection dynamics and its therapeutic implications through elucidating the molecular basis underlying the inefficacy of IFN-based antiviral strategies against HBV-HDV infection.

The study of nuclei in the region around the N = Z doubly-magic nucleus 100Sn has been of long standing interest for the nuclear structure and nuclear astrophysics. Recently, Park et al. have reported on properties of -decaying isomers and isomeric ratios in the vicinity of 100Sn. That experiment was performed at the Radioactive Ion Beam Factory (RIBF) of the RIKEN Nishina Center in Japan as a part of the EURICA campaign. Neutron-deficient nuclei were produced in a fragmentation reaction of a 124Xe primary beam on a 9Be target at an energy of 345 MeV/A. Secondary ions were separated and identified in the BigRIPS fragment separator and implanted in the silicon detector array WAS3ABi. The data presented here were obtained in another experiment performed at the RIBF using the same reaction but slightly different separator settings. New results of ratios of isomeric population and half-lives of -decaying isomers populated in the experiment are presented. [ABSTRACT FROM AUTHOR]

Abstract Background Heat shock protein (HSP) 90 functions as a molecular chaperone and is constitutively expressed and induced in response to stress in many cell types. We have previously demonstrated that transforming growth factor-β (TGF-β), the most abundant cytokine in bone cells, induces the expression of HSP27 through Smad2, p44/p42 mitogen-activated protein kinase (MAPK), p38 MAPK, and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in mouse osteoblastic MC3T3-E1 cells. This study investigated the effects of HSP90 on the TGF-β-induced HSP27 expression and the underlying mechanism in mouse osteoblastic MC3T3-E1 cells. Methods Clonal osteoblastic MC3T3-E1 cells were treated with the HSP90 inhibitors and then stimulated with TGF-β. HSP27 expression and the phosphorylation of Smad2, p44/p42 MAPK, p38 MAPK, and SAPK/JNK were evaluated by western blot analysis. Result HSP90 inhibitors 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib significantly enhanced the TGF-β-induced HSP27 expression. TGF-β inhibitor SB431542 reduced the enhancement by 17-DMAG or onalespib of the TGF-β-induced HSP27 expression levels. HSP90 inhibitors, geldanamycin, onalespib, and 17-DMAG did not affect the TGF-β-stimulated phosphorylation of Smad2. Geldanamycin did not affect the TGF-β-stimulated phosphorylation of p44/p42 MAPK or p38 MAPK but significantly enhanced the TGF-β-stimulated phosphorylation of SAPK/JNK. Onalespib also increased the TGF-β-stimulated phosphorylation of SAPK/JNK. Furthermore, SP600125, a specific inhibitor for SAPK/JNK, significantly suppressed onalespib or geldanamycin’s enhancing effect of the TGF-β-induced HSP27 expression levels. Conclusion Our results strongly suggest that HSP90 inhibitors upregulated the TGF-β-induced HSP27 expression and that these effects of HSP90 inhibitors were mediated through SAPK/JNK pathway in osteoblasts.

Abstract Background Scleractinian corals of the genus Montipora (Anthozoa, Cnidaria) possess some unusual biological traits, such as vertical transmission of algal symbionts; however, the genetic bases for those traits remain unknown. We performed extensive comparative genomic analyses among members of the family Acroporidae (Montipora, Acropora, and Astreopora) to explore genomic novelties that might explain unique biological traits of Montipora using improved genome assemblies and gene predictions for M. cactus, M. efflorescens and Astreopora myriophthalma. Results We obtained genomic data for the three species of comparable high quality to other published coral genomes. Comparative genomic analyses revealed that the gene families restricted to Montipora are significantly more numerous than those of Acropora and Astreopora, but their functions are largely unknown. The number of gene families specifically expanded in Montipora was much lower than the number specifically expanded in Acropora. In addition, we found that evolutionary rates of the Montipora-specific gene families were significantly higher than other gene families shared with Acropora and/or Astreopora. Of 40 gene families under positive selection (Ka/Ks ratio > 1) in Montipora, 30 were specifically detected in Montipora-specific gene families. Comparative transcriptomic analysis of early life stages of Montipora, which possesses maternally inherited symbionts, and Acropora, which lacks them, revealed that most gene families continuously expressed in Montipora, but not expressed in Acropora do not have orthologs in Acropora. Among the 30 Montipora-specific gene families under positive selection, 27 are expressed in early life stages. Conclusions Lineage-specific gene families were important to establish the genus Montipora, particularly genes expressed throughout early life stages, which under positive selection, gave rise to biological traits unique to Montipora. Our findings highlight evolutionarily acquired genomic bases that may support symbiosis in these stony corals and provide novel insights into mechanisms of coral-algal symbiosis, the physiological foundation of coral reefs.

Abstract Although numerous dinoflagellate species (Family Symbiodiniaceae) are present in coral reef environments, Acropora corals tend to select a single species, Symbiodinium microadriaticum, in early life stages, even though this species is rarely found in mature colonies. In order to identify molecular mechanisms involved in initial contact with native symbionts, we analyzed transcriptomic responses of Acropora tenuis larvae at 1, 3, 6, 12, and 24 h after their first contact with S. microadriaticum, as well as with non-native symbionts, including the non-symbiotic S. natans and the occasional symbiont, S. tridacnidorum. Some gene expression changes were detected in larvae inoculated with non-native symbionts at 1 h post-inoculation, but those returned to baseline levels afterward. In contrast, when larvae were exposed to native symbionts, we found that the number of differentially expressed genes gradually increased in relation to inoculation time. As a specific response to native symbionts, upregulation of pattern recognition receptor-like and transporter genes, and suppression of cellular function genes related to immunity and apoptosis, were exclusively observed. These findings indicate that coral larvae recognize differences between symbionts, and when the appropriate symbionts infect, they coordinate gene expression to establish stable mutualism.

Background and objectivesPatients with benign paroxysmal positional vertigo of the posterior canal (pc-BPPV) exhibit BPPV fatigue, where the positional nystagmus diminishes with the repeated performance of the Dix–Hallpike test (DHt). BPPV fatigue is thought to be caused by the disintegration of lumps of otoconial debris into smaller parts and can eliminate positional nystagmus within a few minutes [similar to the immediate effect of the Epley maneuver (EM)]. In this study, we aimed to show the non-inferiority of the repeated DHt to the EM for eliminating positional nystagmus after 1 week.MethodsThis multicenter, randomized controlled clinical trial was designed based on the CONSORT 2010 guidelines. Patients who had pc-BPPV were recruited and randomly allocated to Group A or Group B. Patients in Group A were treated using the EM, and patients in Group B were treated using repeated DHt. For both groups, head movements were repeated until the positional nystagmus had been eliminated (a maximum of three repetitions). After 1 week, the patients were examined to determine whether the positional nystagmus was still present. The groups were compared in terms of the percentage of patients whose positional nystagmus had been eliminated, with the non-inferiority margin set at 15%.ResultsData for a total of 180 patients were analyzed (90 patients per group). Positional nystagmus had been eliminated in 50.0% of the patients in Group A compared with 47.8% in Group B. The upper limit of the 95% confidence interval for the difference was 14.5%, which was lower than the non-inferiority margin.DiscussionThis study showed the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week in patients with pc-BPPV and that even the disintegration of otoconial debris alone has a therapeutic effect for pc-BPPV. Disintegrated otoconial debris disappears from the posterior canal because it can be dissolved in the endolymph or returned to the vestibule via activities of daily living.Classification of evidenceThis study provides Class II evidence of the non-inferiority of repeated DHt to the EM for eliminating positional nystagmus after 1 week.Registration numberUMIN000016421.