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Summary: Akabane virus (AKAV) is teratogenic to the foetus of domestic ruminants and causes a significant reproduction loss in cattle in Japan. In several past epizootics in cattle, AKAV was also associated with post‐natal encephalomyelitis, mainly in calves and young stock. Previously analysed AKAV isolates in East Asia form two major clusters, genogroups I and II, with isolates involved in encephalomyelitis belonging mainly to the former. Between 2007 and 2013, AKAV epizootics were regularly observed in Japan during the summer/autumn season, and abnormal deliveries and post‐natal encephalomyelitis caused by the virus in cattle were reported. During this period, 30 AKAV isolates were obtained from diseased and sentinel cattle, a piglet and Culicoides biting midges throughout Japan and were subjected to genetic comparison and phylogenetic analysis with previous isolates. In 2007, 2011 and 2013, AKAV belonging to genogroup I was identified in the central nervous systems of calves showing neurological disorders. Notably, a total of 165 cases of bovine encephalomyelitis were reported in 2011 and the isolated viruses from affected animals shared high genetic identities with a South Korean isolate that was associated with a large outbreak in 2010, suggesting some epidemiological linkage between these epizootics. Epizootics of genogroup II were observed in 2008 and 2010, but bovine post‐natal encephalomyelitis cases rarely occurred. Our findings suggest that the frequent incursion of genogroup I isolates has increased the frequency of post‐natal encephalomyelitis cases in Japan in recent years. Infection by genogroup I virus was also identified in piglets with neurological disorders or congenital malformations in 2011 and 2013. The aetiological role of AKAV in pigs should be elucidated in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Although several attempts have been made to control enzootic bovine leukosis (EBL) at the local level, a nationwide control program has not been implemented in Japan, except for passive surveillance. Effective control of EBL requires that the transmission routes of bovine leukemia virus (BLV) infection should be identified and intercepted based on scientific evidence. In this cross-sectional study, we examined the risk factors associated with within-herd transmission of BLV on infected dairy farms in Japan. Blood samples taken from 30 randomly selected adult cows at each of 139 dairy farms were tested by enzyme-linked immunosorbent assay (ELISA). Information on herd management was collected using a structured questionnaire. Results Infected farms were defined as those with more than one ELISA-positive animal and accounted for 110 (79.1%) of the 139 farms in the study. Completed questionnaires obtained from 90 of these 110 farms were used for statistical analysis. Seroprevalence, which was defined as the proportions of animals that tested positive out of all animals tested on the farm, was 17.1%, 48.1%, and 68.5% for the 25th, 50th, and 75th percentiles, respectively. A mixed logistic regression analysis implicated a loose housing system, dehorning, and a large number of horseflies in summer as risk factors (coefficient = 0.71, 1.11, and 0.82; p = 0.03, < 0.01, and 0.01, respectively) and feeding of colostrum to newborn calves from their dams as a protective factor (coefficient = -1.11, p = 0.03) against within-farm transmission of BLV on infected farms. Conclusion Control of EBL in infected dairy farms in Japan will be improved by focusing particularly on these risk and protective factors.

Introduction: Human alveolar echinococcosis caused by Echinococcus multilocularis is an important zoonotic disease in the northern hemisphere. The life cycle of E. multilocularis is maintained primarily in wild animals and requires an intermediate host (mainly small mammals). Human can become an intermediate host through accidental ingestion of E. multilocularis eggs. Hokkaido Prefecture is the only area of Japan in which human alveolar echinococcosis is endemic. The purposes of this study were to elucidate the land use ecological factors associated with the density of red fox feces along paved roads and the relationship between the distributions of red fox ( Vulpes vulpes ) populations and fox feces, which determine the level of hazard from eggs., Methods: A series of surveys was conducted in the central part of the Nemuro Peninsula of Hokkaido, excluding urban areas, over a total of 4 years in May-June in 2014 and 2016-2018 when red foxes remain with their cubs around the dens. Transects of 500 m were set up on paved roads, and feces within the transects were counted. Univariable and multivariable analyses were performed to examine ecological factors including the principal components (PCs) of five land use-type occupancy proportions within 500 m and 1 km, respectively, as explanatory fixed-effect variables. The number of feces in each transect was examined as the response variable using integrated nested Laplace approximation with negative binomial errors with a spatio-temporal autocorrelations structure to separate the effects of similarities of neighboring locations and annual variation. The multivariable models with the lowest widely applicable information criterion values were selected., Results: The feces density was explained by the PC of the 500- m buffer (-0.27, 2.5th and 97.5th percentiles: -0.44, -0.10) characterized by mixed forests (-0.82) and scarcity of residential areas (0.29) and the proximity to the nearest livestock farm house (-0.35, 2.5th and 97.5th percentiles: -0.53, -0.17). This suggested that foxes defecate in the areas where prey is abundant, avoiding humans., Discussion: Policy discussions regarding bait distribution design targeting these conditions should be initiated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fukui, Uraguchi, Numa, Suzuki, Karasawa, Maita, Yokozawa, Hayama and Makita.)

This study aimed to develop a screening method to identify Japanese Black (JB) cattle farms at high risk of bovine leukemia virus (BLV) transmission. We introduced a recently established lymphocyte count (LC) cut-off to detect cattle with persistent lymphocytosis (PL). To identify high-risk farms, we examined the relationship between the proportion of cattle with PL and the mean blood proviral loads (PVL) per farm. The results showed a strong correlation between the proportion of cattle with high LC, higher than the LC cut-off values for JB cattle, and the mean blood PVL per farm. This indicates that the mean blood PVL on a herd basis of JB cattle can be estimated from the proportion of cattle with high LC. Specifically, the mean blood PVL on farms with >30 % cattle having high LC was estimated to be greater than 100 copies/10 ng DNA. The higher the proportion of cattle with high LC per farm, the higher the proportion of cattle at risk as sources of BLV infection. The study demonstrated that the proportion of cattle with high LC, based on the new LC cut-off, serves as a practical index for screening high-risk farms with PL cattle that have high PVL. This finding is meaningful for prioritizing farms with a high proportion of cattle with high LC, necessitating BLV infection prevention measures, such as voluntary culling and segregation, in order to develop a regional, stepwise BLV eradication strategy., Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Aldosterone and the MR (mineralocorticoid receptor) are important therapeutic targets for hypertension and cardiovascular diseases. However, biomarkers of tissue MR signaling are not fully established. Extracellular vesicles released from eukaryotic cells can provide information on tissue signaling. Using samples from patients with primary aldosteronism (PA), we explored the potential of urinary extracellular vesicles (uEVs) as a noninvasive indicator of MR signaling to guide treatment., Methods: We analyzed proteins contained in PA uEVs by liquid chromatography tandem mass spectrometry. We narrowed down candidate biomarkers by referring to an existing database of urinary exosomes. The results were validated through Western blot analysis involving 63 patients with PA and 11 healthy volunteers., Results: We identified a total of 1940 proteins in PA uEVs. Comparative analysis with the existing database narrowed down the pathways enriched in PA uEVs, which were related to diabetic complications, Rac1 signaling, and aldosterone-regulated sodium reabsorption. A closer look at the identified proteins revealed ENaCγ (epithelial Na + channel γ) peptides near the proteolytic cleavage sites, and Western blot analysis confirmed the predominant presence of cleaved ENaCγ, a marker of aldosterone signaling in renal tubules. In PA uEVs, cleaved ENaCγ showed a 4.8-fold increase compared with healthy volunteers and was significantly correlated with the aldosterone-to-renin ratio, aldosterone levels, and fractional excretion of K + . Targeted treatment in PA reduced the abundance of cleaved ENaCγ, suggesting a causal role for MR in its induction., Conclusions: This study provides a list of proteins contained in PA uEVs and suggests that ENaCγ in uEVs is a promising biomarker for renal MR signaling., Competing Interests: S. Shibata received research funding from the Daiichi Sankyo Foundation of Life Science. The funder had no role in the study design, execution of experiments, data collection and analysis, decision to publish, or preparation of the article. The other authors report no conflicts.

In Japan, outbreaks of H5N8 highly pathogenic avian influenza (HPAI) were reported between November 2020 and March 2021 in 52 poultry farms. Understanding HPAI epidemiology would help poultry industries improve their awareness of the disease and enhance the immediate implementation of biosecurity measures. This study was a simulation-based matched case-control study to elucidate the risk factors associated with HPAI outbreaks in chicken farms in Japan. Data were collected from 42 HPAI-affected farms and 463 control farms that were within a 5-km radius of each case farm but remained uninfected. When infected farms were detected as clusters, one farm was randomly selected from each cluster, considering the possibility that the cluster was formed by farm-to-farm transmission within an epidemic area. For each case farm, up to three control farms were selected within a 5-km radius. Overall, 26 case farms (16 layer and 10 broiler farms) and 75 control farms (45 layer and 30 broiler farms) were resampled 1000 times for the conditional logistic regression model with explanatory variables comprising geographical factors and farm flock size. A larger flock size and shorter distance to water bodies from the farm were found to increase infection risk in layer farms. Similarly, in broiler farms, a shorter distance to water bodies increased infection risk. On larger farms, frequent access of farm staff and instrument carriages to premises could lead to increased infection risk. Waterfowl visiting water bodies around farms may also be associated with infection risk., Competing Interests: Declaration of competing interest none., (Copyright © 2023. Published by Elsevier Ltd.)

Geographical wildlife patterns reflect historical range expansion and connectivity and provide insights into wildlife population management. In our large-scale phylogeographic population analysis of wild boars (Sus scrofa leucomystax) in Japan, we identified 15 clusters using 29 microsatellite markers, each structured within a range of approximately 200 km. This suggests that evolution was essentially driven by isolation by distance, and that the range of gene flow was limited. One cluster contained subpopulations located approximately 900 km apart, indicating the occurrence of past anthropogenic introductions. Moreover, we estimated effective migration to visualize the geographic genetic population diversity. This analysis identified six potential barriers, one of which involved large plains and mountainous areas in the Kanto region of eastern Japan. This barrier likely persisted in the two eastern clusters for an extended period, restricting migration to the neighboring areas. Overall, our study sheds light on the demographic history of wild boar in Japan, provides evidence of past anthropogenic introductions from distant areas, and highlights the importance of geographic barriers in shaping genetic diversity and population dynamics. This knowledge will be beneficial for forming informed wildlife management strategies toward the conservation of genetic integrity and ecological balance of wild boar populations in Japan., (© 2023. The Author(s).)

Classical swine fever (CSF) re-emerged in Gifu Prefecture, central Japan, in September 2018 and is currently widespread in wild boar populations. Due to its widespread in wild boars, an oral mass vaccination strategy was initiated in March 2019, employing a commercial bait vaccine that is a live attenuated vaccine. To enhance the effectiveness of oral vaccination, it is crucial to determine the vaccine's effective spatial range. This understanding is essential for devising a comprehensive vaccination strategy, which should also include a preliminary investigation of wild boar habitats before vaccination. This study aimed to estimate the effective range of oral vaccination for wild boars against CSF by analyzing the geographical relationship between immune wild boars and vaccination points within the vaccination areas in Gifu Prefecture. This study utilized oral vaccination data from April 2021 to March 2022. The prevalence of CSF infections in wild boars remained below 5% in this period, suggesting limited disease transmission and immune wild boars were considered to be induced by the effect of vaccination. Two vaccination campaigns were conducted during this period, with almost 2000 vaccination points each. To investigate the factors associated with the intensity (i.e., density) of immune wild boar, the nearest distances to a vaccination point and to a susceptible wild boar were evaluated as explanatory variables. The Rhohat procedure and point process model were utilized to analyze the relationship between the intensity of immune wild boars and the explanatory variables. The point process model revealed a significant decrease in the intensity of immune wild boars when the distance from the nearest vaccination point exceeded 500 m, indicating that the effective spatial range of bait vaccination is within 500 m of the vaccination point. Although the distance to the nearest susceptible animal did not show significance in the model, Rhohat plots indicated that the intensity of immune wild boars decreased at distances greater than 1200 m from the nearest susceptible wild boar. This finding highlights the importance of investigating susceptible wild boar populations within a range of at least 1200 m from a vaccination point before implementation. The present study revealed the effective range of oral vaccination for wild boars against CSF and indicated the importance of investigating susceptible wild boar habitats around vaccination points before the implementation of vaccination. These findings may help improve the effectiveness of oral vaccinations., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: There are approximately 13 million patients with osteoporosis in Japan; however, only 20% of them receive treatment. This study compared the 4-year continuation rates of osteoporosis drugs at different dosing intervals across throughout Japan., Materials and Methods: Receipt data were analyzed to determine the continuation of osteoporosis medication in patients who began treatment at 210 hospitals throughout Japan between October 2016 and September 2017. Continuation rates were compared using Kaplan-Meier curves and log-rank tests., Results: The 4-year continuation rates of daily, weekly, monthly, semi-annual, and yearly medications nationwide were 8.6%, 16.5%, 13.5%, 31.0%, and 26.0%, respectively. The 4-year continuation rates for semi-annual and yearly drugs were significantly higher than daily, weekly, monthly drugs., Conclusion: Throughout Japan, the 4-year treatment continuation rates of daily, weekly, monthly, semi-annual, and yearly osteoporosis drugs all decreased over time. However, the continuation rates of semi-annual and yearly drugs in the fourth year were significantly higher than those for the other dosing regimens. Therefore, injectable drugs with dosing intervals ≥6 months may improve continuation rates of osteoporosis drugs. Geriatr Gerontol Int 2023; 23: 665-670., (© 2023 Japan Geriatrics Society.)

Objectives: Animal movement is an important factor in the transmission of infectious diseases among livestock. A better understanding of animal movement characteristics provides a more reliable estimation of disease spread and promotes modeling studies. In Japan, all the cattle movement information is recorded in a national database called the Individual Cattle Identification Register (ICIR)." Our previous studies using this information demonstrated heterogeneity in the movement of dairy and beef cows according to location, season, and age. The present study describes the probability distributions of the movement of Japanese dairy and beef cows in the following month on a regional basis., Data Description: This publication contains four probability distribution datasets for the predicted locations of dairy and beef cows in Japan in the following month, which were developed using individual cattle movement information obtained from the ICIR. These datasets provide information on cattle movement in the following month on a regional basis, given properties such as birth region, location, time, and age., (© 2023. The Author(s).)

Background: Aujeszky's disease virus (ADV) primarily infects domestic pigs and wild boars, causing the abortion and death of young piglets due to central nervous system disorders. In Japan, the national eradication program for ADV in domestic pigs has been successful in most prefectures; however, concern has been raised regarding ADV-infected wild boars as a source of transmission to domestic pigs., Results: We assessed the nationwide seroprevalence of ADV among wild boars (Sus scrofa) in Japan. Moreover, we determined the sex-based differences in the spatial clustering of seropositive animals. Serum samples were obtained from a total of 1383 wild boars acquired by hunting in 41 prefectures in three fiscal years (April-March in 2014, 2015, and 2017). Seropositivity tests for ADV using enzyme-linked immunosorbent assay, the latex agglutination and neutralization tests showed 29 boars seropositive for ADV (29/1383, 2.1% [95% confidence interval, CI: 1.4-3.0%]), with 28 of these boars originating from three prefectures in the Kii Peninsula (28/121, 23.1% [95% CI: 16.0-31.7%]). The degree of spatial clustering of these ADV-seropositive adult boars in the Kii Peninsula was evaluated using the K-function and data from sera samples of 46 (14 seropositive) male and 54 (12 seropositive) female boars. The degree of clustering among females was significantly higher in seropositive animals than in tested animals; however, such a difference was not observed for seropositive males., Conclusions: The spatial dynamics of ADV among adult wild boars may be characterized based on sex, and is likely due to sex-based differences in behavioral patterns including dispersal among wild boars., (© 2023. The Author(s).)

Purpose: Prostate cancer (PC) treatment causes sexual dysfunction (SD) and alters fertility, male identity, and intimate relationships with partners. In Japan, little attention has been paid to the importance of providing care for SD associated with PC treatment. This study is aimed at clarifying the care needs of Japanese men regarding SD associated with PC treatment., Methods: One-to-one semi-structured interviews were conducted with 44 PC patients to identify their care needs. Data were analyzed using thematic analysis., Results: Four core categories emerged from the analysis. (1) "Need for empathy from medical staff regarding fear of SD": patients had difficulty confiding in others about their sexual problems, and medical staff involvement in their SD issues was lacking. (2) "Need for information that provides an accurate understanding of SD and coping strategies before deciding on treatment": lack of information about SD in daily life and difficulty understanding information from medical institutions, caused men to regret their treatment. (3) "Need for professional care for individuals and couples affected by SD": men faced loss of intimacy because of their partners' unwillingness to understand their SD issues or tolerate non-sexual relationships. (4) "Need for an environment that facilitates interaction among men to resolve SD issues": men felt lonely and wanted to interact with other patients about their SD concerns., Conclusion: These findings may help form care strategies tailored to these needs and applicable to other societies with strong traditional gender norms., (© 2023. The Author(s).)

Animal movement is an important factor in the transmission of animal infectious diseases. A better understanding of movement patterns is therefore necessary for developing effective control measures against disease spread. In Japan, a cattle tracing system was established in 2003, following a bovine spongiform encephalopathy epidemic, and the information on all cattle movements has been stored in a national database maintained by the National Livestock Breeding Center. Using these data, we previously analyzed the movement of dairy cows, concluding that heterogeneities in cattle movement are associated with regional and seasonal factors. In the present study, we aimed to identify specific factors affecting the regional and seasonal movement patterns of beef cows in Japan. From April 2012 to March 2017, 797,553 farm-to-farm movement events were recorded. We analyzed movements by month and by cattle age and looked at the frequency of movement within and between seven regions spanning the national territory. Our results show that calf movement peaked at 9-10 months old; these movements were considered to be via the market and were frequent within and between regions. For inter-regional movements, Kyushu region was the top producer of calves for calf trading markets throughout Japan. With regard to intra-regional movements, round-trip movements for summer grazing were observed in May and October for cattle of various ages in the northern regions, especially Hokkaido and Tohoku. Moreover, the movements of Japanese Shorthorn breeds in Tohoku region exhibited consistent annual peaks in May and October/November, in accordance with their seasonal breeding practice. In the areas with high relative densities of dairy cows, such as Hokkaido, the shipping of newborn beef calves produced via embryo transfer to dairy cows was also observed. Overall, understanding the patterns of beef cow movement will help develop effective disease surveillance measures, such as pre-movement inspections focused on specific regions and types of movement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Murato, Hayama, Kondo, Sawai, Yamaguchi and Yamamoto.)

When an infectious disease occurs in an area, early detection of infected farms is important to respond quickly and contain the outbreak on a small scale. Estimating the time window for the introduction of the infection is important for its prevention and control. The aim of this study was to estimate the farm-specific time window from the introduction of the highly pathogenic avian influenza (HPAI) virus into poultry farms using field data from the HPAI H5N8 outbreak in the 2020-2021 winter season in Japan. Daily mortality data from 12 broiler chicken farms during the outbreak were used for the analysis. A mathematical model (Susceptible-Exposed-Infectious-Removed, SEIR model) was applied to generate the within-flock transmission of HPAI. The model-predicted mortality was fitted to the observed excess mortality data induced by HPAI to estimate the farm-specific transmission rate and the time of virus introduction. The estimated value of the transmission rate in each farm was 1.449 day -1 in median (min: 0.661 day -1 , max: 3.387 day -1 ). The time window from the introduction of the virus to notification in each farm was estimated at 14.0 days in median (min: 8.6 days, max: 24.1 days) in the deterministic model. In addition, in the stochastic model considering the randomness of transmission in the early phase of the outbreak, the upper value of 95 % credible interval of the time window ranged from 12 to 34 days, with a median of 21 days. The results suggest that although one to three weeks had elapsed on most farms until notification after the virus introduction, the time window could exceed three weeks considering the stochasticity of disease transmission. As for the potential farm characteristics affecting within-flock transmission, the transmission rate was smaller (p-value=0.02) and the estimated time window from introduction to notification was longer (p-value=0.02) when birds were older. This study provides reliable information for setting up a tracing period for a potential source farm and enhancing the efforts for early detection., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Understanding the impact of vaccination in a host population is essential to control infectious diseases. However, the impact of bait vaccination against wildlife diseases is difficult to evaluate. The vaccination history of host animals is generally not observable in wildlife, and it is difficult to distinguish immunity by vaccination from that caused by disease infection. For these reasons, the impact of bait vaccination against classical swine fever (CSF) in wild boar inhabiting Japan has not been evaluated accurately. In this study, we aimed to estimate the impact of the bait vaccination campaign by modelling the dynamics of CSF and the vaccination process among a Japanese wild boar population. The model was designed to estimate the impact of bait vaccination despite lack of data regarding the demography and movement of wild boar. Using our model, we solved the theoretical relationship between the impact of vaccination, the time-series change in the proportion of infected wild boar, and that of immunised wild boar. Using this derived relationship, the increase in antibody prevalence against CSF because of vaccine campaigns in 2019 was estimated to be 12.1 percentage points (95% confidence interval: 7.8-16.5). Referring to previous reports on the basic reproduction number (R0) of CSF in wild boar living outside Japan, the amount of vaccine distribution required for CSF elimination by reducing the effective reproduction number under unity was also estimated. An approximate 1.6 (when R0 = 1.5, target vaccination coverage is 33.3% of total population) to 2.9 (when R0 = 2.5, target vaccination coverage is 60.0% of total population) times larger amount of vaccine distribution would be required than the total amount of vaccine distribution in four vaccination campaigns in 2019., Competing Interests: The authors have declared that no competing interests exist.

Beta-blockers are well known to reduce myocardial oxygen consumption (MVO 2 ) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (P LA ), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and P LA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean P LA were controlled within the acceptable ranges (AP within 5 mmHg below target; P LA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2-3.8)] and P LA [3.6% (2.2-5.7)]. The system decreased MVO 2 and P LA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and P LA to avoid circulatory collapse, and reduced MVO 2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted., (© 2021. The Author(s).)