Estimation of genetic parameters for bull conception rate and its genetic correlations with semen production traits in Japanese Black bulls.

The P of achieving pregnancy is an important trait of bull fertility in beef cattle and is defined as the bull conception rate (BCR). This study aimed to clarify and better understand the genetic architecture of the BCR calculated using artificial insemination and pregnancy diagnosis records from a progeny testing program in Japanese Black bulls. In this study, we estimated the genetic parameters of the BCR and their correlation with semen production traits. In addition, we assessed the correlated responses in BCR by considering the selection of semen production traits. Nine hundred and sixteen Japanese Black bulls were selected based on fertility, with 28 869 pregnancy diagnostic records from the progeny testing program. Our results showed that the heritability estimate was 0.04 in the BCR at the first service and 0.14 in BCR for the three services, and an increase in the inbreeding coefficient led to a significant decrease in BCR. The phenotypic trend of BCR remained almost constant over the years, whereas the genetic trend increased. In addition, the changes in the progeny testing year effect showed a similar tendency to the phenotypic trends, suggesting that the phenotypic trends could be mainly due to non-genetic effects, including progeny testing year effects. The estimated genetic correlation of BCR with sperm motility traits was favorably moderate to high (ranging from 0.49 to 0.97), and those with sperm quantity traits such as semen volume were favorably low to moderate (ranging from 0.23 to 0.51). In addition, the correlated responses in BCR at the first service by selection for sperm motility traits resulted in a higher genetic gain than direct selection. This study provides new insights into the genetic factors affecting BCR and the possibility of implementing genetic selection to improve BCR by selecting sperm motility traits in Japanese Black bulls.

Analysis of COVID-19 mRNA Vaccine-induced Mouth Ulcers Using the Japanese Adverse Drug Event Report Database.

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

Genome-wide detection of non-additive quantitative trait loci for semen production traits in beef and dairy bulls.

Semen production traits are important aspects of bull fertility, because semen quantity leads to direct profits for artificial insemination centres, and semen quality is associated with the probability of achieving a pregnancy. Most genome-wide association studies (GWASs) for semen production traits have assumed that each quantitative trait locus (QTL) has an additive effect. However, GWASs that account for non-additive effects are also important in fitness traits, such as bull fertility. Here, we performed a GWAS using models that accounted for additive and non-additive effects to evaluate the importance of non-additive effects on five semen production traits in beef and dairy bulls. A total of 65 463 records for 615 Japanese Black bulls (JB) and 50 734 records for 873 Holstein bulls (HOL), which were previously genotyped using the Illumina BovineSNP50 BeadChip, were used to estimate genetic parameters and perform GWAS. The heritability estimates were low (ranged from 0.11 to 0.23), and the repeatability estimates were low to moderate (ranged from 0.28 to 0.45) in both breeds. The estimated repeatability was approximately twice as high as the estimated heritability for all traits. In this study, only one significant region with an additive effect was detected in each breed, but multiple significant regions with non-additive effects were detected for each breed. In particular, the region at approximately 64 Mbp on Bos taurus autosome 17 had the highest significant non-additive effect on four semen production traits in HOL. The rs41843851 single nucleotide polymorphism (SNP) in the region had a much lower P-value for the non-additive effect (P-value = 1.1 × 10-31) than for the additive effect (P-value = 1.1 × 10-8) in sperm motility. The AA and AB genotypes on the SNP had a higher phenotype than the BB genotype in HOL, and there was no bull with the BB genotype in JB. Our results showed that non-additive QTLs affect semen production traits, and a novel QTL accounting for non-additive effects could be detected by GWAS. This study provides new insights into non-additive QTLs that affect fitness traits, such as semen production traits in beef and dairy bulls.

A case of recurrent acute febrile neutrophilic dermatosis in a patient with idiopathic cytopenia of undetermined significance.

This is the first report of recurrent acute febrile neutrophilic dermatosis in a patient with idiopathic cytopenia of undetermined significance. The patient progressed to acute myeloid leukaemia 4 months after onset.

Estimation of genetic parameter for feed efficiency and resilience traits in three pig breeds.

Recently, automatic feeders have become popular for collecting daily feed intake data in the pig industry, making it possible to evaluate genetic effects on feed efficiency and resilience traits, expressed as day-to-day fluctuations in feeding records. This study aimed to understand the influence of genetic factors on feed efficiency traits, including residual intake and BW gain (RIG), and resilience traits, as well as to compare the differences in genetic parameter estimates among three purebred pig breeds. A total of 6 103 pigs from three breeds (Large White: 1 193 pigs, Landrace: 3 010 pigs, and Duroc: 1 900 pigs) were raised in a specific pathogen-free environment. The growth and feed intake records during the testing period were obtained using automatic feeders, and the average daily gain (ADG) and average feed intake (AFI) were calculated. Feed conversion ratio (FCR), residual feed intake (RFI), residual gain, and RIG were calculated as feed efficiency traits, and the log-transformed variance of deviation for the daily feed intake (LnVar_FI), daily occupation time (LnVar_OC), and the daily number of visits to the feeder (LnVar_VT) was calculated as resilience traits. After estimating the genetic parameters for each breed, a meta-analysis was performed to obtain the weighted mean of heritability estimates (hm2) and genetic correlation estimates (GCm) for the three breeds. The hm2 were moderate and ranged from 0.31 to 0.39 for feed efficiency traits and 0.31 to 0.40 for resilience traits, and there were no significant differences in heritability estimates among the three breeds except for AFI, RFI, and RIG. For feed efficiency traits, the FCR and RIG showed favourably moderate GCm with AFI (0.29 and -0.33, respectively) and ADG (-0.39 and 0.31, respectively). For resilience traits, the LnVar_FI and LnVar_VT showed favourably low to moderate GCm with FCR (0.33 and 0.28, respectively) and RIG (-0.37 and 0.28, respectively), and there were no genetic relationships of LnVar_OC with FCR and RIG (the absolute value of GCm was 0.01). There was no significant difference in the genetic correlation estimates among the three breeds for feed efficiency and resilience traits. Our results suggest that feed efficiency and resilience traits were heritable, and resilience traits showed favourable or no genetic correlation with feed efficiency traits. In addition, the influence of genetic factors on feed efficiency and resilience traits could be the same among breeds.

Fibronectin plays a major role in hypoxia-induced lenvatinib resistance in hepatocellular carcinoma PLC/PRF/5 cells.

Resistance to lenvatinib mesylate (LEN), a systemic chemotherapy that can be administered orally, has been a major issue for treatment of hepatocellular carcinoma (HCC). Although HCC is the tumor that most exhibits intratumoral hypoxia, which has been shown to be involved in the development of treatment resistance, there are no reports of LEN resistance in HCC treatment under hypoxia. The purpose of our study was to elucidate the mechanism of treatment resistance to LEN under hypoxia using HCC cell lines. We confirmed LEN resistance under hypoxic conditions in HCC cell lines. There was a significant increase in the IC50 value of PLC/PRF/5 cells from 13.0±0.8 µM in normoxia to 21.3±1.1 µM in hypoxia, but in HepG2 cells, the increase was not significant. To elucidate the LEN resistance mechanism of PLC/PRF/5 cells under hypoxia, we performed microarray analysis and extracted genes that are thought to be related to this mechanism. Furthermore, in-silico analysis confirmed significant changes in the extracellular matrix, and among them, FN1 encoding fibronectin was determined as the hub of the gene cluster. The expression of fibronectin in PLC/PRF/5 cells examined with immunofluorescence staining was significantly elevated in and outside of cells under hypoxia, and tended to decrease when cells were exposed to LEN under normoxia. Furthermore, the fibronectin concentration in the culture solution of PLC/PRF/5 cells examined by ELISA was 2.3 times higher under hypoxia than under normoxia under LEN(-) conditions, and 1.6 times higher under hypoxia than under normoxia under LEN(+) conditions. It is assumed that in PLC/PRF/5 cells, fibronectin is probably suppressed as an indirect effect of LEN under normoxia, but transcription factors such as HIF-1α are induced under hypoxia, thus enhancing the production of fibronectin and attenuating the effect of LEN, resulting in drug resistance. This behavior of fibronectin with LEN exposure under hypoxia is probably specific to PLC/PRF/5 cells. Further studies should verify the combined effective inhibition of fibronectin and the MAPK pathway as a promising therapeutic strategy to enhance the value of LEN in HCC treatment.

Evaluation of a novel particle-based assay for detection of autoantibodies in idiopathic inflammatory myopathies.

BACKGROUND: Myositis specific antibodies (MSA) represent not only important diagnostic tools for idiopathic inflammatory myopathies (IIM), but also help to stratify patients into subsets with particular clinical features, treatment responses, and disease outcome. Consequently, standardization of MSA is of high importance. Although many laboratories rely on protein immunoprecipitation (IP) for the detection of MSA, IP standardization is challenging and therefore reliable alternatives are mandatory. Recently, we identified significant variation between IP and line immunoassay (LIA) for the detection of MSA and myositis associated antibodies. In this study we aimed to compare the results from our previous study to the results obtained with a novel fully automated particle-based technology for the detection of MSA and MAA. METHODS: A total of 54 sera from patients with idiopathic inflammatory myopathy (IIM) were tested using three methods: IP, LIA (Euroimmun, Germany) and a novel particle-based multi-analyte technology (PMAT, Inova Diagnostics, US, research use only). The analysis focused on antibodies to EJ, SRP, Jo-1, NXP-2, MDA5, TIF1-γ, and Mi-2. RESULTS: Significant variations were observed among all methods. Overall, the novel PMAT assays showed slightly better correlation with IP, but the kappa agreement was strongly dependent on the antibody tested. When the results obtained from IP were used as reference for receiver operating characteristic (ROC) curve analysis, good discrimination and a high area under the curve (AUC) value were found for PMAT (AUC = 0.83, 95% confidence interval, CI 0.70-0.95) which was significantly higher (p = .0332) than the LIA method (AUC = 0.70, 95% CI 0.56-0.84). CONCLUSION: The novel PMAT used to detect a spectrum of MSA in IIM represents a potential alternative to IP and other diagnostic assays. Additional studies based on larger cohorts are needed to fully assess the performance of the novel PMAT system for the detection of autoantibodies in myositis.

Fenómeno de Koebner en el síndrome de Sweet / Koebner Phenomenon In Sweet's Syndrome

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Evaluation of economic burden of colonic surgical site infection at a Japanese hospital.

BACKGROUND: Several reports have been published regarding cost increases attributable to surgical site infections (SSIs) in Europe and the USA. However, such studies have been limited in Japan. AIM: To evaluate the economic burden of colorectal SSIs on hospitals in Japan. METHODS: This study was undertaken at a Japanese university hospital. Amongst 265 patients who had undergone colorectal surgery in the Department of Coloproctological Surgery between November 2014 and March 2016, 16 patients who developed SSIs and could be allocated a diagnosis procedure combination code were selected as SSI cases. Individual SSI cases were matched to non-SSI cases based on a combination of surgical category, age band, sex, wound class, presence of stoma and risk index. Median length of stay (LOS) and piecework reference cost were compared between SSI episodes and non-SSI episodes. FINDINGS: The median LOS for patients with SSI and without SSI was 25.5 [interquartile range (IQR) 21.5-39.3] and 16.5 (IQR 12.5-18.5) days, respectively (P<0.01). The median piecework reference cost for patients with SSI and without SSI was ¥842,155 (IQR ¥716,423-1,388,968) and ¥575,795 (IQR ¥529,638-680,105), respectively (P<0.01). CONCLUSION: SSIs led to a significant increase in LOS and economic burden. Although the SSI episodes appear to be more profitable than the non-SSI episodes, the economic profit for SSI episodes was less than that for non-SSI episodes in the observation period, when opportunity costs were taken into account.

Nerve growth factor regulation and production by macrophages in osteoarthritic synovium.

Nerve growth factor (NGF) functions to modulate osteoarthritis (OA)-associated pain. Although recent studies suggest that tumour necrosis factor (TNF)-α and interleukin (IL)-1ß mediate NGF activity in human synovial fibroblasts, the regulation of NGF expression in human synovial macrophages remains unclear. Here, we examined the role of macrophages in the production and regulation of synovial (SYN) NGF in osteoarthritic knee joints by examining the mRNA expression of TNF-α and IL-1ß in freshly isolated CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction) in synovial tissue from OA patients by quantitative polymerase chain reaction. We also examined the effects of IL-1ß and TNF-α on NGF mRNA expression in cultured CD14-positive (macrophage-rich fraction) and CD14-negative cells (fibroblast-rich fraction). In addition, to examine the contribution of macrophages to NGF, TNF-α and IL-1ß expression, we injected clodronate liposomes systemically into STR/Ort mice, an osteoarthritis animal model, to deplete macrophages. TNF-α and IL-1ß mRNA levels in CD14-positive cells from the SYN of OA patients was significantly higher than that in CD14-negative cells, while NGF expression did not differ markedly between the two cell fractions. In addition, treatment of human cultured CD14-positive and -negative cells with IL-1ß and TNF-α enhanced NGF mRNA and protein levels. Expression of NGF, IL-1ß and TNF-α was also reduced significantly in STR/Ort mice upon macrophage depletion. These findings suggest that IL-1ß and TNF-α regulate NGF expression and production in synovial macrophages and fibroblasts in osteoarthritic joints.

Concomitant pyoderma gangrenosum and erythema nodosum in a patient with ulcerative colitis / Pioderma gangrenoso concomitante y eritema nudoso en paciente con colitis ulcerosa

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Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015.

The second meeting for the International Consensus on Antinuclear antibody (ANA) Pattern (ICAP) was held on 22 September 2015, one day prior to the opening of the 12th Dresden Symposium on Autoantibodies in Dresden, Germany. The ultimate goal of ICAP is to promote harmonization and understanding of autoantibody nomenclature, and thereby optimizing ANA usage in patient care. The newly developed ICAP website www.ANApatterns.org was introduced to the more than 50 participants. This was followed by several presentations and discussions focusing on key issues including the two-tier classification of ANA patterns into competent-level versus expert-level, the consideration of how to report composite versus mixed ANA patterns, and the necessity for developing a consensus on how ANA results should be reported. The need to establish on-line training modules to help users gain competency in identifying ANA patterns was discussed as a future addition to the website. To advance the ICAP goal of promoting wider international participation, it was agreed that there should be a consolidated plan to translate consensus documents into other languages by recruiting help from members of the respective communities.

Genetic analysis of the cumulative pseudo-survival rate during lactation of Holstein cattle in Japan by using random regression models.

Longevity is a crucial economic trait in the dairy farming industry. In this study, our objective was to develop a random regression model for genetic evaluation of survival. For the analysis, we used test-day records obtained for the first 5 lactations of 380,252 cows from 1,296 herds in Japan between 2001 and 2010; this data set was randomly divided into 7 subsets. The cumulative pseudo-survival rate (PSR) was determined according to whether a cow was alive (1) or absent (0) in her herd on the test day within each lactation group. Each lactation number was treated as an independent trait in a random regression multiple-trait model (MTM) or as a repeated measure in a random regression single-trait repeatability model (STRM). A proportional hazard model (PHM) was also developed as a piecewise-hazards model. The average (± standard deviation) heritability estimates of the PSR at 365 d in milk (DIM) among the 7 data sets in the first (LG1), second (LG2), and third to fifth lactations (LG3) of the MTM were 0.042±0.007, 0.070±0.012, and 0.084±0.007, respectively. The heritability estimate of the STRM was 0.038±0.004. The genetic correlations of PSR between distinct DIM within or between lactation groups were high when the interval between DIM was short. These results indicated that whereas the genetic factors contributing to the PSR between closely associated DIM would be similar even for different lactation numbers, the genetic factors contributing to PSR would differ between distinct lactation periods. The average (± standard deviation) effective heritability estimate based on the relative risk of the PHM among the 7 data sets was 0.068±0.009. The estimated breeding values (EBV) in LG1, LG2, LG3, the STRM, and the PHM were unbiased estimates of the genetic trend. The absolute values of the Spearman's rank correlation coefficients between the EBV of the relative risk of the PHM and the EBV of PSR at 365 DIM for LG1, LG2, LG3, and the STRM were 0.75, 0.87, 0.91, and 0.93, respectively. These results indicated that the EBV of PSR could predict the genetic contribution to survival. The EBV based on the PSR of the STRM was highly correlated with that of the MTM (0.83-0.96). Furthermore, the calculation load of the STRM was lighter than that of the MTM because the rank of the matrix of the STRM was smaller than that of the MTM. These results indicated that the STRM is an appropriate model for estimating survivability by using random regression models.

Genomic best linear unbiased prediction method reflecting the degree of linkage disequilibrium.

The degree of linkage disequilibrium (LD) between markers differs depending on the location of the genome; this difference biases genetic evaluation by genomic best linear unbiased prediction (GBLUP). To correct this bias, we used three GBLUP methods reflecting the degree of LD (GBLUP-LD). In the three GBLUP-LD methods, genomic relationship matrices were conducted from single nucleotide polymorphism markers weighted according to local LD levels. The predictive abilities of GBLUP-LD were investigated by estimating variance components and assessing the accuracies of estimated breeding values using simulation data. When quantitative trait loci (QTL) were located at weak LD regions, the predictive abilities of the three GBLUP-LD methods were superior to those of GBLUP and Bayesian lasso except when the number of QTL was small. In particular, the superiority of GBLUP-LD increased with decreasing trait heritability. The rates of QTL at weak LD regions would increase when selection by GBLUP continues; this consequently decreases the predictive ability of GBLUP. Thus, the GBLUP-LD could be applicable for populations selected by GBLUP for a long time. However, if QTL were located at strong LD regions, the accuracies of three GBLUP-LD methods were lower than GBLUP and Bayesian lasso.

Living situations associated with poor dietary intake among healthy Japanese elderly: the Ohasama Study.

BACKGROUND: Rapid increases in life expectancy have led to concurrent increases in the number of elderly people living alone or those forced to change living situations. Previous studies have found that poor dietary intake was common in elderly people living alone. However, there have been few studies about the dietary intake in elderly people living in other situations, particularly those living with family other than a spouse (nonspouse family), which is common in Japan. OBJECTIVE: To examine the differences in dietary intake by different living situations in elderly Japanese people. We analyzed the data of 1542 healthy residents in the town of Ohasama aged 60 years and over who had completed self-administered questionnaires. METHODS: The dietary intake was measured using a validated 141-item food frequency questionnaire. Multiple regression models with robust (White-corrected) standard errors were individually fitted for nutrients and foods by living situation. RESULTS: In men, although the presence of other family was correlated with significantly lower intake of protein-related foods, e.g., legumes, fish and shellfish, and dairy products, these declines were more serious in men living with nonspouse family. Conversely, in men living alone the intake of fruits and vegetables was significantly lower. In women, lower intakes of fruit and protein-related foods were significantly more common in participants living with nonspouse family than those living with only a spouse. CONCLUSION: These findings revealed that elderly people living alone as well as those living with family other than a spouse had poor dietary intake, suggesting that strategies to improve food choices and skills for food preparation could promote of healthy eating in elderly Japanese people.