Effect of atopic conditions on development and recurrences of infectious keratitis.

BACKGROUND: Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV). METHODS: This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR. RESULTS: Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025). CONCLUSIONS: Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.

Additive Bayesian network analysis of the relationship between bovine respiratory disease and management practices in dairy heifer calves at pre-weaning stage.

BACKGROUND: Nursery farms that accept nursing and growing pre-weaned heifer calves from private dairy farms must work to prevent bovine respiratory disease (BRD). Knowledge of the BRD-associated risk factors related to calf management and calves' condition will help to develop appropriate neonatal management practices at original farms and to identify calves at higher risk for BRD at nursery farms. In this study, the relationship between BRD and calf management practices (colostrum feeding, dam parity, serum total protein concentration at introduction (TP), body weight at introduction, introduction season, and daily average growth) was investigated using observational data from pre-weaned dairy calves introduced into a nursery farm in Hokkaido, Japan between 2014 and 2018 (n = 3185). Using additive Bayesian network (ABN) analysis, which is a multivariate statistical modelling approach, the direct and indirect associations between these factors were assessed. RESULTS: Colostrum feeding contributed to an increase in TP (correlation 1.02 [95 % CI, 0.94;1.10]), which was negatively associated with BRD directly (log odds ratio - 0.38 [- 0.46;-0.31]) and indirectly through increasing daily growth (correlation 0.12 [0.09;0.16]). Calves of multiparous dams had higher body weight at introduction (correlation 0.82 [0.74;0.89]), which indirectly reduced BRD risk through the increasing daily growth (correlation 0.17 [0.14;0.21]). Calves introduced during winter had the highest risk for BRD (log odds ratio 0.29 [0.15;0.44]), while those introduced in summer had the lowest risk (log odds ratio - 0.91 [- 1.06;-0.75]). The introduction season was also associated with BRD indirectly through dam parity, body weight at introduction, and daily growth. CONCLUSIONS: The following calf management practices are recommended for preventing BRD in pre-weaned calves at nursery farms: (1) encouraging colostrum feeding to neonatal calves at their original farms; and (2) identifying calves with higher BRD risk, i.e., those without feeding colostrum, born to primiparous cattle, with low body weight at introduction, and/or introduced in winter, and paying intensive attention to the calves for rapid detection of BRD. ABN analysis applied enabled us to understand the complex inter-relationships between BRD incidence and the risk factors, which will help to reduce BRD incidence and to rear healthy calves at nursery farms.

Region-wise analysis of dairy cow movements in Japan.

BACKGROUND: Animal movement is considered the most significant factor in the transmission of infectious diseases in livestock. A better understanding of its effects would help provide a more reliable estimation of the disease spread and help develop effective control measures. If the movement pattern is heterogeneous, its characteristics should be considered in epidemiological analyses, such as when using simulation models to obtain reliable outputs. In Japan, following the bovine spongiform encephalopathy epidemic, a traceability system for cattle was established in 2003, and the registration of all cattle movements in the national database began. This study is the first to analyze cattle movements in Japan. We examined regional and seasonal heterogeneity in dairy cow movements, which accounted for most Japanese breeding cattle. RESULTS: In the 14 years from April 2005 to March 2018, 4,577,709 between-farm movements of dairy cows were recorded, and the number of movements was counted by month and age for both inter- and intra-regional movements. As a result, two characteristic round-trip movements were observed: one was non-seasonal and inter-regional movements related to cattle-breeding ranches in Hokkaido (the northern region of Japan), which consists of the movement of cows around ages 6 to 8 and 21 to 23 months old. In addition, the seasonal movement of heifers for summer grazing within Hokkaido occurred in May and October at the peak ages of 13 to 14 and 19 to 20 months old, respectively. The observed heterogeneity seemed to reflect the suitability of raising the Holstein breed in Hokkaido and the shortage of supply of replacement heifers and available farming areas outside Hokkaido. CONCLUSIONS: Understanding the patterns of dairy cow movements will help develop reliable infectious disease models and be beneficial for developing effective control measures against these diseases.

Epidemiological analysis of classical swine fever in wild boars in Japan.

BACKGROUND: Classical swine fever (CSF) is a contagious disease of pigs and wild boars that is transmitted through direct/indirect contact between animals or CSF virus-contaminated fomites. When the disease re-emerged in 2018 in Japan, a CSF-infected wild boar was reported shortly after the initial pig farm outbreak; subsequently, the disease spread widely. To control the disease spread among wild boars, intensive capturing, fencing, and oral bait vaccination were implemented with concomitant virological and serological surveillance. This study aimed to describe the disease spread in the wild boar population in Japan from September 2018, when the first case was reported, to March 2020, based on the surveillance data. We conducted statistical analyses using a generalized linear mixed model to identify factors associated with CSF infection among wild boars. Moreover, we descriptively assessed the effect of oral bait vaccination, which started in March 2019 in some municipalities in the affected areas. RESULTS: We observed a faster CSF infection spread in the wild boar population in Japan compared with the CSF epidemics in European countries. The infection probability was significantly higher in dead and adult animals. The influence of the multiple rounds of oral bait vaccination was not elucidated by the statistical modeling analyses. There was a decrease and increase in the proportion of infected and immune animals, respectively; however, the immunization in piglets remained insufficient after vaccination for 1 year. CONCLUSIONS: Conditions regarding the wild boar habitat, including forest continuity, higher wild boar population density, and a larger proportion of susceptible piglets, were addressed to increase the infection risk in the wild boar population. These findings could improve the national control strategy against the CSF epidemic among wild boars.

First nationwide survey of the seroprevalence of Toxoplasma gondii in wild boars in Japan.

The increase in some wildlife species is of global concern. The utilization of wildlife meat as food and feed represents a potential source of food-borne pathogens; this is particularly a potential concern for the use of wild board as a food source in Japan. Regarding food safety and an animal infectious disease control, however, little is known about the infection level of zoonotic pathogens including Toxoplasma gondii (T. gondii) in wild boar populations in their natural habitats in Japan. A total of 1279 blood samples from 41 prefectures were collected from apparently healthy wild boars during the three hunting periods (September to February) of 2014-2015, 2015-2016, and 2017-2018. Out of these sera, 461 samples tested positive by a commercial indirect ELISA for T. gondii, and the total apparent and adjusted true seroprevalence were estimated to 36.0% (95% confidence interval [CI], 33.4-38.7) and 31.3% (95% CI, 33.1-38.9), respectively. The seroprevalence was significantly higher in yearlings and adults than in piglets (P < 0.05); however, no significant difference according to gender was noted. These results indicate the importance of adequate heating of wild boar meat before consumption to prevent transmission of T. gondii to humans. Furthermore, freezing meat for several days before cooking is recommended to reduce the risk of infection. In addition, although the incidence of toxoplasmosis in pig farms is relatively low in Japan, biosecurity measures against the felids and the varied intermediate hosts should be strengthened, especially, at the farms located in the wild boar habitats to prevent livestock infection.

Role Played by Receptors for Advanced Glycosylation End Products in Corneal Endothelial Cells after HSV-1 Infection.

Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-ß secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-ß secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response.

Knowledge-based planning using pseudo-structures for volumetric modulated arc therapy (VMAT) of postoperative uterine cervical cancer: a multi-institutional study.

BACKGROUND: The aim of this study was to investigate the performance of the RapidPlan (RP ) using models registered pseudostructures, and to determine how many structures are required for automatic optimization of volumetric modulated arc therapy (VMAT) for postoperative uterine cervical cancer. MATERIALS AND METHODS: Pseudo-structures around the PTV were retrospectively contoured for patients who had completed treatment at five institutions. For 22 common patients, plans were generated with a single optimization for models with two (RP_2), four (RP_4), and five (RP_5) registered structures, and the dosimetric parameters of these models were compared with a clinical plan with several optimizations. RESULTS: Most dosimetric parameters showed no major differences between each RP model. In particular, the rectum Dmax, V50Gy, and V40Gy with RP_2, RP_4, and RP_5 were not significantly different, and were lower than those of the clinical plan. The average proportions of plans achieving acceptable criteria for dosimetric parameters were close to 100% for all models. Using RP_2, the average time for the VMAT planning was reduced by 88 minutes compared with the clinical plan. CONCLUSION: The RapidPlan model with two registered pseudo-structures could generate clinically acceptable plans while saving time.

Effectiveness of 16S ribosomal DNA real-time PCR and sequencing for diagnosing bacterial keratitis.

PURPOSE: To evaluate the efficacy of real-time PCR for 16S ribosomal DNA (16S r-DNA) and sequencing for diagnosing microbial keratitis. METHODS: We studied 272 eyes of 272 patients with keratitis. Eyes with keratitis were classified as "definite" (N = 118), "likely" (N = 71), or "non-bacterial" (N = 83) to have bacterial keratitis. The diagnostic efficacy of real-time PCR and conventional testing was determined by receiver operating characteristic analysis. The copy numbers of bacterial DNA and clinical characteristics were retrospectively analyzed for association with concordant culture results in the "definite" cases. RESULTS: The level of bacterial DNA was significantly associated with the diagnostic probability of the three diagnostic categories. The level of bacterial DNA had comparable diagnostic efficacy with the area under the curve (AUC) at 0.67, by culture at 0.65, and by smear testing at 0.73. The efficacy was significantly improved by combining the DNA level with the conventional culture testing with an AUC of 0.81. Analysis of the "definite" cases showed culture positivity in 51.8% (58 eyes), and of these, 41 eyes (70.7%) were higher than the cutoff PCR values and 40 eyes were identified by 16S r-DNA sequencing. In the culture-negative eyes, the level of bacterial DNA was significantly lower (P = 0.0008). Eyes with higher bacterial DNA levels had significantly concordant outcomes with sequencing and culture results (P = 0.006). Previous antibiotic treatments decreased the bacterial DNA amount by 0.09-fold, and it was a significant factor for discordance (P = 0.006). CONCLUSION: Quantification of the bacterial DNA level and conventional testing improves the diagnostic efficacy of infectious bacterial keratitis.

Controlling Bi-Provoked Nanostructure Formation in GaAs/GaAsBi Core-Shell Nanowires.

We control the formation of Bi-induced nanostructures on the growth of GaAs/GaAsBi core-shell nanowires (NWs). Bi serves as not only a constituent but also a surfactant and nanowire growth catalyst. Thus, we paved a way to achieve unexplored III-V nanostructures employing the characteristic supersaturation of catalyst droplets, structural modifications induced by strain, and incorporation into the host GaAs matrix correlated with crystalline defects and orientations. When Ga is deficient during growth, Bi accumulates on the vertex of core GaAs NWs and serves as a nanowire growth catalyst for the branched structures to azimuthal <112>. We find a strong correlation between Bi accumulation and stacking faults. Furthermore, Bi is preferentially incorporated on the GaAs (112)B surface, leading to spatially selective Bi incorporation into a confined area that has a Bi concentration of over 7%. The obtained GaAs/GaAsBi/GaAs heterostructure with an interface defined by the crystalline twin defects in a zinc-blende structure can be potentially applied to a quantum confined structure. Our finding provides a rational design concept for the creation of GaAsBi based nanostructures and the control of Bi incorporation beyond the fundamental limit.

Epidemiological aspects of allergic conjunctivitis.

The prevalence of ocular allergies has been increasing worldwide for the past several decades. The geographical distribution and hot spots of rhinoconjunctivitis have been documented in a global survey by the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC indicated that Africa, Latin America, and Japan were notable for their high prevalence of rhinoconjunctivitis. The outcomes of follow-up studies of regional differences and the characteristics of allergic conjunctivitis are summarized in this review. Currently, comorbid diseases and socioeconomic and environmental factors, including climate and air pollution, are proposed to contribute to the regional differences in the prevalence of allergic conjunctivitis. Of them, rhinitis has been shown repeatedly to be significantly associated with allergic conjunctivitis. Their mechanistic aspects on association with the prevalence of systemic allergic diseases have been reviewed by examining the birth cohort or in vitro analyses. A vision threatening form of ocular allergy, vernal keratoconjunctivitis, is prevalent in the African countries and Japan. Of the proposed associated factors, air pollution was shown to contribute not only to aggravating the symptoms but also to the increase in the incidence of its severe forms. Its mechanistic aspects are discussed in this review in the context of comorbid diseases.

Diagnostic efficacy of real-time PCR for ocular cytomegalovirus infections.

PURPOSE: The aim of this study is to determine the efficacy of quantitative real-time PCR (qPCR) and clinical characteristics to diagnose ocular cytomegalovirus (CMV) infections. METHODS: The technical factors were assessed by the outcomes of the qPCR assay at five institutions in Japan using the WHO International Standard of cytomegalovirus. The clinical factors were assessed by examining the aqueous humor samples of 197 eyes of 197 consecutive patients suspected of CMV using the receiver operating characteristics (ROCs). RESULTS: All of the institutions had excellent detection efficacy, although the copy number ranged from 0.82 to 4.66 copies/IU. In the clinical samples, CMV was detected in 51 eyes, and the amount of CMV DNA was significantly higher for CMV retinitis. In corneal diseases, the amount of CMV DNA was significantly associated with frequency of recurrences and IOP elevations. The sensitivity and specificity of qPCR for the diagnosis was 90.0 and 98.7%, respectively. For the corneal and anterior uveitis types of CMV diseases, the area under the curve (AUC) of qPCR was 0.95 and 0.96, followed by frequency of recurrences with AUC of 0.89 and 0.82, and IOP elevations with AUC of 0.78 and 0.76. Unclassified cytomegalovirus detection, which did not meet diagnostic criteria of CMV corneal endotheliitis, anterior uveitis, or retinitis, was 4.6%, and it was significantly associated with corneal diseases and history of corneal transplantation. CONCLUSIONS: qPCR with standardization is specific and accurate; however, the inclusion and knowledge of the clinical characteristics improve the diagnostic efficacy.

Corneal endothelial cells activate innate and acquired arm of anti-viral responses after cytomegalovirus infection.

Infection of the corneal endothelial cells by human cytomegalovirus (CMV) is an important cause of corneal endotheliitis. CMV endotheliitis is difficult to completely cure and relapses are frequent. This can cause blinding corneal bullous keratopathy. However, the pathogenesis of CMV endotheliitis remains undetermined. To understand the immunopathology of endotheliitis, we examined how corneal endothelial cells prime the anti-viral immunity after CMV infection based on global transcriptional responses. To accomplish this, human corneal endothelial (HCEn) cells were infected with CMV, and the global transcriptional responses were determined by microarray analyses for primary anti-viral responses using network analysis. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and protein array analyses were used to examine whether anti-viral cytokines were induced, i.e., to determine whether innate immune responses were activated. To examine whether priming of acquired immune response was activated, CMV-infected HCEn cells were co-cultured with allogeneic CD8+ T cells from CMV seropositive donors and tested for priming activity for the CD8+ effector T cells by measuring interferon-γ secretion. The CMV-induced responses of HCEn cells were characterized by type I interferon and pattern recognition receptor pathways which represent innate immune priming. The global transcriptional activation was specifically associated with antigen presentation with the antimicrobial response functions. Protein array analyses indicated a significant increase in the secretion of anti-viral inflammatory cytokines including CXCL10 as innate immune responses. When HCEn cells were examined to determine whether CMV infection activated anti-viral acquired immunity, CMV-infected HCEn cells directly stimulated the proliferation of CD8+ T cells from CMV-seropositive donors, and pp65 viral epitope induced interferon-γ secretion from the CD8+ T cells. We conclude that CMV-infected HCEn cells induce innate immune priming along with provisions of acquired immune priming of CD8+ effector T cells. This information should help in the development of useful diagnostic procedures and efficacious therapeutic strategy to treat refractory corneal endotheliitis.

[Effects of an intervention program for community-dwelling elderly to improve frailty and dietary habits].

OBJECTIVES: The effects of a comprehensive intervention program for community-dwelling elderly on frailty and dietary habits were examined. METHODS: We conducted randomized control trials to examine the efficacy of the intervention. To examine lasting changes, we made paired comparisons between pre- and post- intervention and at a three-month follow-up. The subjects were recruited in Hatoyama town, Saitama prefecture. The program was composed of exercise, nutritional education, and social participation and was held from October to December 2011. The exercise program aimed at fall prevention and took place twice per week for 60 min. The nutritional education aimed at prevention of malnutrition, and the social participation program aimed at prevention of "homeboundness"; both were held once per week for 30 min. Questionnaires inquired about frailty and dietary variety. A blood test was conducted to ascertain nutritional state, and a brief self-administered diet history questionnaire was used to estimate food and nutrient intake. To examine the efficacy of the intervention, 22 control subjects (CR) and 21 subjects in the intervention group (IV) were analyzed with intention to treat. To examine lasting changes, 16 subjects in IV who correctly completed surveys at each of the three time points were analyzed, using repeated ANOVA and a multiple comparison procedure. RESULTS: 1. Men comprised 70-80% of subjects, and the average age was 75.7±5.4 and 74.7±5.4 years in IV and CR, respectively. 2. There was no significant difference in pre- and post-intervention changes between IV and CR in frailty, which was the main outcome of the study. 3. A significant difference in pre- and post-intervention values was noted in ① "homeboundness", one of the components of frailty (median [25-75%tile]): IV 0 [0-0] and CR 0 [0-1] (P=0.023); ② nutrient intake (mean±standard deviation [SD], energy ratio [%E]): protein, IV 2.3±0.7 and CR -0.3±2.0 (P=0.002); animal protein, IV 2.4±1.5 and CR -0.5±1.5 (P=0.002); and ③ food intake (mean±SD, g/1000 kcal): fish, IV 18.1±25.1 and CR -4.1±21.9 (P=0.004); egg, IV 5.0±11.2 and CR -2.1±11.3 (P=0.046). All variables improved in IV. 4. Lasting improvement was observed in "homeboundness" and protein intake [%E]. CONCLUSION: Although the intervention did not improve frailty, it may improve frailty and dietary habits by improving homeboundness and increasing protein intake.

Employment rates for working-age patients receiving hemodialysis increasing: Changing economic environment.

INTRODUCTION: This study explored employment trends among working-age patients undergoing hemodialysis using 5-year surveys from 1996 to 2021. Policy changes affecting individuals with disabilities, the economic environment, and employment status among the general population in Japan were considered. Differences in trends by gender and health status were examined. METHODS: Employment status was categorized into employment and nonemployment; and regular, nonregular, and self. Analytical data with similar characteristics were generated over the six surveys using the propensity score method. RESULTS: The employment rate, especially among women, increased from 1996 to 2021. However, the employment rate ratio to the general population was approximately 80% for men and 50% for women, even in 2021. The employment rate increased with an expansion in nonregular employment. Women's employment trends could be explained by changes in real gross domestic product and employment quotas for individuals with disabilities. CONCLUSION: Employment trends differ by gender and by regular versus nonregular employment.

Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases.

PURPOSE: To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease. STUDY DESIGN: Cross-sectional study. METHODS: Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation. RESULTS: The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%. CONCLUSIONS: The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.

A Community-Based Intervention to Enhance Subjective Well-Being in Older Adults: Study Design and Baseline Participant Profiles.

Promoting subjective well-being is a crucial challenge in aging societies. In 2022, we launched a community-based intervention trial (the Chofu-Digital-Choju Movement). This initiative centered on fostering in-person and online social connections to enhance the subjective well-being of older adults. This paper describes the study design and baseline survey. This quasi-experimental study involved community-dwelling older adults aged 65-84 years in Chofu City, Tokyo, Japan. A self-administered questionnaire was distributed to 3742 residents (1681 men and 2061 women), and a baseline survey was conducted in January 2022. We assessed subjective well-being (primary outcome); psychosocial, physical, and dietary factors; and the use of information and communication technology variables (secondary outcomes) among the participants. After the intervention involving online classes, community hubs, and community events, a 2-year follow-up survey will be conducted to evaluate the effects of the intervention, comparing the intervention group (participants) with the control group (non-participants). We received 2503 questionnaires (66.9% response rate); of these, the analysis included 2343 questionnaires (62.6% valid response rate; mean age, 74.4 (standard deviation, 5.4) years; 43.7% male). The mean subjective well-being score was 7.2 (standard deviation, 1.9). This study will contribute to the development of a prototype subjective well-being strategy for older adults.

The SNP in the promoter region of the bovine ELOVL5 gene influences economic traits including subcutaneous fat thickness.

Genetic analyses have contributed to improvements of economically important traits derived from adipose tissue such as fatty acid composition in beef. Elongation of very long chain fatty acids (ELOVL) genes encode for the enzymes that play an important role in elongation of long-chain fatty acids. In this study, we aimed to discover genetic polymorphisms of ELOVL gene family in cattle populations to develop genetic markers. As a result, five synonymous mutations were detected in the coding regions of the ELOVL1, ELOVL2, ELOVL3 and ELOVL5 genes. In addition, six mutations were identified in promoter region of the ELOVL5. Two of five mutations in the promoter region of ELOVL5 were expected to alter the ELOVL5 expression and influence the economic traits, because of the high synteny of the region which was essential for activation of Elovl5 in mouse. Therefore, we performed association analysis between the genotypes and traits and our result revealed that T allele of g.-110T>C in ELOVL5 gene promoter indicated significantly thinner subcutaneous fat thickness (TT, 2.39 cm; CT, 2.35 cm) than that of C allele (CC, 2.68 cm) in a Japanese Black population. Our results suggest that the g.-110T>C is a useful genetic marker for the breeding in beef cattle.

[Validity of the "Kaigo-Yobo Check-List" as a frailty index].

OBJECTIVES: A frailty index for Japanese older people is not yet available. This study examined the validity of "Kaigo-Yobo Check-List" (CL) as a frailty index. METHODS: The study site was Kusatsu town, Gunma prefecture. Out of 612 older persons aged 65 years and over who undertook a comprehensive geriatric assessment in 2007, results from 526 who had no missing data were used to examine the cross-sectional relationship between frailty as defined by Fried's criteria (= external criteria) and CL scores in order to evaluate concurrent and construct validity. Further, 916 older individuals aged 70 years and over who responded to the baseline survey in 2001 were followed for the subsequent 4 years and 4 months regarding the onset of ADL disability, service use under the Long Term Care Insurance program, and mortality. We examined the predictive validity of the CL for such adverse outcomes after adjustment for gender, age, and comorbidity. RESULTS: The CL (cut-off point = 3/4) discriminated frailty from non-frailty at the sensitivity of 70.0% and specificity of 89.3%. The higher the CL score, the higher the prevalence of frailty; the trend was highly significant (P < 0.001). The Multitrail Multimethod Model showed that there were significant associations among three components of CL (homeboundness, falling, and lower nutrition) and four out of five components of Fried's frailty criteria (shrinking, exhaustion, low activity, and slowness), whereas those components of the CL did not have an association with the weakness component of Fried's frailty criteria. As compared with older persons who had CL scores of 3 points or below, those who had CL scores of 4 or more points had a significantly higher risk for developing adverse outcomes. Multivariate-adjusted odds ratios for ADL disability at 2 and 4 years after baseline were 5.25 (95% confidence interval, 2.79-9.89) and 3.42 (1.79-6.54), respectively. Likewise, multivariate-adjusted hazard ratios for the onset of service use under the Long Term Care Insurance program and mortality during the follow-up period of 4 years and 4 months were 3.50 (2.41-5.07) and 2.43 (1.70-3.47), respectively. Although the construct validity remained inconclusive, the "Kaigo-Yobo Check-List" showed CONCLUSION: good concurrent and predictive validity as a frailty index. Since it comprises 15 easy-to-answer questions, it could be widely used for research on frailty and its preventive intervention.

Influence of dialysis-related stigma on health-related indicators in Japanese patients undergoing hemodialysis.

INTRODUCTION: Focusing on impacts to health-related indicators in older Japanese patients, this study analyzed both the direct influence of dialysis-related stigma and influences of its intersectionality with other stigmatized characteristics. METHODS: Data were collected through a cross-sectional survey of 7461 outpatients in dialysis facilities. Other stigmatized characteristics include lower income, lower education, disabled activities of daily living, and diabetic end-stage renal disease (ESRD) as a cause for starting dialysis treatment. RESULTS: The average rate of an "agree" response on dialysis-related stigma items was 18.2%. Dialysis-related stigma significantly influenced all three health-related indicators, including suspected depression, informal networks, and compliance with dietary therapy. In addition, each interaction between dialysis-related stigma and educational attainment, gender, and diabetic ESRD significantly influence one health-related indicator. CONCLUSION: These results suggest that dialysis-related stigma has both a significant direct and synergic influence with other stigmatized characteristics on health-related indicators.

Standardization of knowledge-based volumetric modulated arc therapy planning with a multi-institution model (broad model) to improve prostate cancer treatment quality.

PURPOSE: To evaluate whether knowledge-based volumetric modulated arc therapy plans for prostate cancer with a multi-institution model (broad model) are clinically useful and effective as a standardization method. METHODS: A knowledge-based planning (KBP) model was trained with 561 prostate VMAT plans from five institutions with different contouring and planning policies. Five clinical plans at each institution were reoptimized with the broad and single institution model, and the dosimetric parameters and relationship between Dmean and the overlapping volume (rectum or bladder and target) were compared. RESULTS: The differences between the broad and single institution models in the dosimetric parameters for V50, V80, V90, and Dmean were: rectum; 9.5% ± 10.3%, 3.3% ± 1.5%, 1.7% ± 1.6%, and 3.6% ± 3.6%, (p < 0.001), bladder; 8.7% ± 12.8%, 1.5% ± 2.6%, 0.7% ± 2.4%, and 2.7% ± 4.6% (p < 0.02), respectively. The differences between the broad model and clinical plans were: rectum; 2.4% ± 4.6%, 1.7% ± 1.7%, 0.7% ± 2.4%, and 1.5% ± 2.0%, (p = 0.004, 0.015, 0.112, and 0.009) bladder; 2.9% ± 5.8%, 1.6% ± 1.9%, 0.9% ± 1.7%, and 1.1% ± 4.8%, (p < 0.018), respectively. Positive values indicate that the broad model has a lower value. Strong correlations were observed (p < 0.001) in the relationship between Dmean and the rectal and bladder volume overlapping with the target in the broad model (R = 0.815 and 0.891, respectively). The broad model had the smallest R2 of the three plans. CONCLUSIONS: KBP with the broad model is clinically effective and applicable as a standardization method at multiple institutions.