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Abstract Objectives Poor cardiorespiratory fitness (CRF) and high body mass index (BMI) increased the risk of developing metabolic Syndrome (MetS) mostly in Caucasians. However, the sex-specific combined association of CRF and BMI on MetS considering health-related behaviors has yet to be thoroughly examined in Japanese. This study aims to investigate the sex-specific independent and combined associations of CRF and BMI with MetS in middle-aged Japanese adults. Methods 421 participants were included in this cross-sectional study. CRF was estimated using a submaximal cycle ergometer. CRF and BMI were respectively divided into three categories according to tertile distribution. MetS was diagnosed based on five risk factors: waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression models were used to estimate independent and combined association of CRF and BMI with MetS. Results Results showed that 154 (57.5%) and 70 (45.8%) of men and women had MetS, respectively. Compared to men with lower CRF or higher BMI, men with middle and higher CRF or middle and lower BMI were less likely to have MetS. Compared with ‘unfit and higher BMI’ group, ‘unfit and lower BMI’, ‘fit and higher BMI’, and ‘fit and lower BMI’ groups in men showed statistically significant decreased prevalences of MetS. However, no significant associations were found in women. Conclusions This study found significant independent and combined associations of CRF and BMI with MetS only in men, but not in women. However, prospective studies are warranted to confirm sex-specific associations of CRF and BMI with MetS.

Abstract Cenesthopathy is a rare syndrome characterized by strange bodily and oral sensations and is classified as a delusional disorder, somatic type, according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders. Cenesthopathy has been considered difficult to treat. However, to improve cenesthopathy, many pharmacotherapeutic options are reported, including antidepressants and antipsychotics. In this case report, vortioxetine significantly alleviated the distress of oral cenesthopathy in a patient with cerebral ischemia and depression without any adverse effects. To the best of our knowledge, this is the first report on the efficacy of vortioxetine in treating cenesthopathy. Though it is unclear why vortioxetine was effective for cenesthopathy in our case, we stated two possibilities for improving his oral cenesthopathy. When treating oral cenesthopathy in elderly patients, clinicians consider to be one of the options to prescribe vortioxetine.

Introduction: Osteoarthritis (OA) is the most common form of arthritis. OA results from the breakdown of cartilage, which leads to deterioration of the entire joint and the connective tissue that holds the joint together, and gradually and irreversibly worsens over time. Adipose-derived stem/stromal cells (ADSCs) have been used in the treatment of knee OA. However, the safety and efficacy of ADSC treatment of OA remain unclear. In this study, we investigated the pathophysiology of severe knee arthritis that occurred after ADSC treatment by screening for autoantibodies in synovial fluid from patients who received ADSC treatment. Methods: Adult Japanese patients with OA who received ADSC treatment at Saitama Cooperative Hospital between June 2018 and October 2021 were enrolled. Antibodies (Abs) were screened using immunoprecipitation (IPP) with [35S]-methionine-labeled HeLa cell extracts. The detected protein was identified by liquid chromatography coupled with time-of-flight mass spectrometry (MS) and ion trap MS, and the corresponding proteins were confirmed as autoantigens using immunoblotting. Ab titers were measured using an enzyme-linked immunosorbent assay. Results: A total of 113 patients received ADSC treatment, and 75% (85/113) received ADSC injection at least twice with a 6-month interval between. No obvious abnormalities were observed in any patient after their first treatment; by contrast, 53% (45/85) of patients who received their second or third ADSC injection showed severe knee arthritis. IPP detected a common anti-15 kDa Ab in synovial fluid of 62% (8/13) of the samples analyzed from patients who showed severe arthritis. This Ab was not detected in synovial fluid obtained from the same joints before treatment. The corresponding autoantigen was identified as histone H2B. All available synovial samples from patients who tested positive for anti-histone H2B Ab were newly positive after the treatment; that is, none had been positive for anti-histone H2B Ab before treatment. Conclusions: Multiple ADSC injections for OA induced severe arthritis in a high percentage of patients, particularly after the second injection. Synovial fluid from some patients with knee arthritis contained Ab to histone H2B that appeared only after ADSC treatment. These findings provide new insights into the pathogenesis of ADSC treatment-induced severe arthritis.

Abstract Aims Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA‐seq data and a correlation analysis between levels of gene expression and lipids. Methods RNA‐Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). Results Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3‐kinase (PI3K)‐Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. Conclusions This study provided results of the integrated analysis of the schizophrenia‐associated transcriptome and lipidome within the PFC and revealed that lipid‐correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.

Background: Cerebral hyperperfusion syndrome (CHS) is a relatively rare but critical perioperative complication after CEA and CAS. We herein report a case with a preoperative increase in CBV, not OEF, in a patient who suffered from CHS both after CEA and after CAS for the same lesion. Case description: An 82-year-old female with a history of transient right hemiparesis was admitted to our hospital. 3DCTA demonstrated severe stenosis of the left neck ICA with severe calcification. 15O-PET indicated an increase of CBV was observed, but an increase of OEF was not observed in the left MCA territory. She underwent left CEA and suffered from CHS. After four months of left CEA, she suffered from right hemiparesis and was admitted to our hospital. MRI DWI revealed a spotty high signal lesion in the left frontal subcortex due to re-stenosis of the left neck ICA following CEA. She underwent CAS and suffered from CHS again. Finally, she was discharged home with mRS1. Conclusion: To our knowledge, no previous reports have described CHS after CEA and CAS for the same lesion, as occurred in our case. This case could suggest that regardless of CEA and CAS procedures, an increase of CBV was related to CHS rather than the longstanding chronic ischemia, which might increase OEF.

Abstract Background Financial incentives have been used to increase physical activity. However, the benefit of financial incentives is lost when an intervention ends. Thus, for this study, we combined social network incentives that leverage the power of peer pressure with financial incentives. Few reports have examined the impact of physical activity on social capital. Therefore, the main goal of this study was to ascertain whether a combination of two incentives could lead to more significant changes in physical activity and social capital during and after an intervention. Methods The participants were 39 older women over 65 years of age in Kumamoto, Japan. The participants were randomly divided into a financial incentive group (FI group) and a social network incentive plus financial incentive group (SNI + FI group). Both groups underwent a three-month intervention. Measurements of physical activity and social capital were performed before and after the intervention. Additionally, the effects of the incentives on physical activity and social capital maintenance were measured 6 months postintervention. The financial incentive group received a payment ranging from US$4.40 to US$6.20 per month, depending on the number of steps taken during the intervention. For the other group, we provided a social network incentive in addition to the financial incentive. The SNI + FI group walked in groups of three people to use the power of peer pressure. Results A two-way ANOVA revealed that in terms of physical activity, there was a statistically significant interaction between group and time (p = 0.017). The FI group showed no statistically significant improvement in physical activity during the observation period. In terms of the value of social capital, there was no significant interaction between group and time. Conclusion Our results suggest that social network incentives, in combination with financial incentives, are more effective for promoting physical activity than financial incentives alone among older women and that these effects can continue after an intervention. In the meantime, further studies should be conducted on the effect of physical activity on social capital. Trial registration UMIN000038080 , registered on 09/22/2019 (Retrospectively registered).

ObjectiveTo stratify patients with polymyositis/dermatomyositis-associated interstitial lung disease (ILD) who were initially treated with an intensive regimen consisting of high-dose corticosteroids, a calcineurin inhibitor, and intravenous cyclophosphamide (triple-combo therapy) into subgroups based on mortality outcomes by a cluster analysis using a large-scale multicenter retrospective cohort of Japanese patients with myositis-associated ILD (JAMI).MethodsTwo-step cluster analysis of preclustering and subsequent hierarchical clustering was conducted in 185 patients who received triple-combo therapy in an unbiased manner. Initial predictors for mortality previously reported in patients with myositis-associated ILD were used as variables and included age, sex, disease duration, classification of myositis, requirement of supplemental oxygen, anti-aminoacyl tRNA synthetase (ARS) antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, and serum levels of C-reactive protein (CRP) and Krebs von den Lungen-6 (KL-6). The cluster model was further applied to 283 patients who received conventional regimens consisting of corticosteroids with or without a single immunosuppressive agent (dual-combo therapy or monotherapy). Cumulative survival rates were compared using Kaplan-Meier analysis, and the log-rank test was used to test for significant differences between two groups.ResultsWe developed a cluster model consisting of 6 clusters, which were categorized by age at onset, clinically amyopathic dermatomyositis, CRP, KL-6, requirement of supplemental oxygen, anti-ARS antibody, and anti-MDA5 antibody. This model was judged to be of good quality based on the silhouette measure of cohesion and separation of 0.6. These clusters were regrouped into three subsets based on low (50%) mortality rates. The performance of the clustering was generally replicated in patients who received initial dual-combo therapy or monotherapy. Survival benefits of triple-combo therapy over dual-combo therapy or monotherapy were not observed in any of the clusters.ConclusionWe successfully developed a cluster model that stratified patients with myositis-associated ILD who were treated with initial triple-combo therapy into subgroups with different prognoses, although this model failed to identify a patient subgroup that showed survival benefits from triple-combo therapy over dual-combo therapy or monotherapy.

Abstracts: Echigoshirayukidake is an edible mushroom found in Uonuma, Japan in 1994. It was assigned to a new species of Basidiomycetes (BDM-X) but is uniquely defect of forming bashidium. The high antioxidant activity and β-glucan content of BDM-X suggest possible functions preventing type 2 diabetes. In the present study, anti-obesity and insulin resistance preventive functions of BDM-X were examined using genetically defined obese model rat, OLETF (Otsuka Long Evans Tokushima Fatty) by feeding regular diet with and without supplementation of 5% dried BDM-X powder (BDMP) for 15 weeks. BDMP supplementation to the diet significantly (p

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of systemic autoimmune diseases characterized mainly by inflammation of muscle tissue. Although IIM traditionally encompasses polymyositis, dermatomyositis (DM), and inclusion body myositis, the disease concept has been changing in association with progress in diagnostic techniques. Thus, the new disease entities of amyopathic DM (ADM) or clinically ADM and immune-mediated necrotizing myopathy have been recognized recently. Because of the variety of symptoms or low prevalence or difficulty in correct evaluation of muscle strength and function in IIM patients, no standard treatment strategies have been established yet. Currently, glucocorticoids remain the first line of treatment of IIMs, but in addition to these, several other immunosuppressive agents or intravenous immunoglobulin have been used in a variety of different combinations. However, due to clinical heterogeneity of these conditions as well as the number of therapeutic target organs, IIM therapy remains challenging, and refractory cases are especially difficult to treat. In recent years, new therapeutic approaches using biologics or Janus kinase inhibitors, plasma exchange therapy, and other agents have been evaluated for IIMs. However, validation of the efficacy of these new treatment options remains an issue to be resolved. In this article, the author reviews current treatment strategies and new emerging therapies for IIM patients.

The incidence of male reproductive system disorders, especially hypospadias, has been increasing in developed countries since the latter half of the 20th century. Endocrine-disrupting chemicals from the environment are considered to be involved in hypospadias onset through epigenetic alterations. This pilot study aimed to explore disease-specific methylated CpGs in human patient samples using the methylated-site display-amplified fragment length polymorphism (MSD-AFLP) technique developed by our research group [1]. We compared clinical samples from hypospadias and phimosis patients. Foreskin and blood samples were collected from one- to two-year-old patients with hypospadias (N = 3) and phimosis (N = 3) during surgical treatment. MSD-AFLP analysis showed significantly decreased CpG-methylation levels of genes such as MYH11 and increased CpG-methylation levels of genes such as PLA2G15 in hypospadias patients. Hierarchical clustering analysis showed that genes with significantly altered CpG levels were more markedly altered in DNA from blood than from foreskin. Because of the small number of samples, further investigation is necessary to elucidate the association between variations in CpG levels in foreskin and blood DNA and male genital abnormalities. However, our MSD-AFLP method appears to be a useful tool for exploring disease-specific methylated-CpGs in human epidemiological studies.

Abstract Background An Amyand’s hernia is defined by the presence of a vermiform appendix within an inguinal hernia sac. Most of these cases are not diagnosed preoperatively and the surgical approach is dependent on the type present and associated intraoperative findings. We present a case of a preoperatively diagnosed Amyand’s hernia in a man who underwent treatment by simultaneous laparoscopic totally extraperitoneal repair and laparoscopic appendectomy. Case presentation We encountered the case of a 76-year-old Japanese man with a right inguinal pain. Ultrasound and computed tomography confirmed his vermiform appendix herniated into the right inguinal canal. We managed a simultaneous laparoscopic total extraperitoneal inguinal hernia repair with mesh and laparoscopic appendectomy. He was discharged without any postoperative morbidity. Conclusions We recommend laparoscopic appendectomy and totally extraperitoneal hernia repair with mesh after laparoscopic reduction for Amyand’s hernia.

Background: Identifying the causes of low peak oxygen uptake (peak V̇O2) in heart disease patients with renal dysfunction is necessary for prognostic improvement strategies. The purpose of this study was to verify the determinants of peak V̇O2 for each stage of renal function in heart disease patients, focusing on end-tidal oxygen partial pressure (PETO2). Methods: Two hundred fifty heart disease patients who underwent cardiopulmonary exercise testing (CPET) in our institution were consecutively enrolled. Patients were divided into three groups by their estimated glomerular filtration rate (eGFR):

Basidiomycetes-X, of which Japanese vernacular name is Echigoshirayukidake, is a local speciality mushroom found and cultivated in Japan that has been distributed as a precious cuisine material or as a functional food with medicinal properties. Antioxidant activity-guided isolation of major ingredients in Basidiomycetes-X revealed the presence of ergosterol, trans-10,cis-12-octadecadienoic acid (a conjugated linolenic acid, 10(E),12(Z)-CLA) and 2,3-dihydro-3,5-dihydroxy-6-methyl‑4H‑pyran-4-one (DDMP). Approximately 21% of the 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazino radical (DPPH) scavenging activities in the methanolic extract were related to 10(E),12(Z)-CLA, while approximately 6.2% of the activity was related to ergosterol. DDMP was present in both methanolic and water extracts, and the activity related to DDMP was conspicuously detected in water extracts. Moreover, uridine and adenosine were identified as major components of Basidiomycetes-X. The ingredients identified in Basidiomycetes-X are expected to be involved in biological functions observed in this mushroom, which is an attractive functional food resource.

Objectives To investigate whether the onset of polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD) is influenced by season and residence in the context of myositis-specific autoantibodies.Methods For patients with PM/DM-associated ILD enrolled in a multicentre cohort, 365 and 481 patients were eligible for seasonal and geographical analysis, respectively, based on the availability of reliable clinical information. The patients were divided into three groups: (1) anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients, (2) anti-aminoacyl tRNA synthetase (anti-ARS) antibody-positive patients and (3) patients negative for those antibodies. Seasonality was assessed by the Rayleigh test. Distance from residence to the nearest waterfront was measured on Google Map and was compared between groups by the exact Wilcoxon rank-sum test.Results In anti-MDA5-positive patients, the disease developed more frequently in October–March (p=0.03), whereas a seasonal relationship was not found in the remaining two patient groups. Residence at disease onset in anti-MDA5-positive patients was significantly closer to the waterfront, especially to freshwater, compared with that in anti-ARS-positive or anti-MDA5-/ARS-negative patients (p=0.003 and 0.006, respectively).Conclusions Anti-MDA5-associated ILD occurred predominantly from October to March in individuals residing near freshwater, suggesting an environmental influence on the onset of this disease subset.

Herein, we present coastal-wave records under historically extreme conditions caused by a strong typhoon in Japan in 2017. The extreme typhoon generated large infragravity waves, reaching a height of 2 m in shallow water. We took advantage of the extraordinary conditions to analyze the effect of the energetic infragravity waves on the nearshore evolution of relatively short waves. Individual wave analyses clearly demonstrate that the instantaneous water-level rise and drawdown caused by the infragravity waves alternately decelerated and accelerated the breaking of short waves under extreme conditions. This mechanism transmitted the large short-wave energy on the infragravity wave crests to the shore, eventually increasing the height of the nearshore waves. This study provides in situ evidence that the infragravity waves significantly affect nearshore wave characteristics under extreme conditions.

ObjectiveSurfactant protein D (SP-D) is considered a serum biomarker of various forms of interstitial lung disease (ILD). In this study, we examined the utility of SP-D as a predictive biomarker for mortality in patients with ILD associated with polymyositis/dermatomyositis (PM/DM) using large-scale multicentre cohort data.MethodsWe enrolled 381 patients with incident PM/DM-associated ILD in a multicentre retrospective cohort based on the availability of serum SP-D at the baseline. Demographic and clinical characteristics as well as the presence of autoantibodies to melanoma differentiation-associated gene 5 (MDA5) and aminoacyl tRNA synthetase were measured at the time of diagnosis, and follow-up survival data were collected prospectively.ResultsSeventy-eight patients died during the median observation period of 18 months, and the majority of patients died of ILD. The SP-D levels at baseline were significantly lower (P = 0.02) in a non-survivor subset than in a survivor subset among the entire enrolled patients. However, the SP-D levels were higher in the non-survivor subset than in the survivor subset based on the stratification by anti-MDA5-positive, anti-ARS-positive and, double-negativity, although there was an only statistically significant difference (P = 0.01) in the double-negative group. Surprisingly, the SP-D levels were within the upper limit of normal, 110 ng/mL, in 54 (87%) of 62 anti-MDA5-positive patients who died. In the double-negative group, the mortality rates were significantly higher (P = 0.002) in a subset with SP-D ≥127.6 ng/mL, the cut-off value for mortality calculated by the receiver operating characteristic curve, than the other subset. All of patients with SP-D ConclusionSerum SP-D levels behave differently among patients with stratified by anti-MDA5 antibody, anti-ARS antibody and both negativity in PM/DM-associated ILD. Its use in clinical practice should be applied with caution on the basis of the presence or absence of anti-MDA5 antibody or anti-ARS antibody.

This study aimed to investigate the direct influence of a decrease in the cellular thiamin level, before the onset of anorexia (one of the symptoms of thiamin deficiency) on glycogen metabolism and the AMP-activated protein kinase (AMPK) activation levels in skeletal muscle at rest and in response to exercise. Male Wistar rats were classified as the control diet (CON) group or the thiamin-deficient diet (TD) group and consumed the assigned diets for 1 week. Skeletal muscles were taken from the rats at rest, those that underwent low-intensity swimming (LIS), or high-intensity intermittent swimming (HIS) conducted immediately before dissection. There were no significant differences in food intake, locomotive activity, or body weight between groups, but thiamin pyrophosphate in the skeletal muscles of the TD group was significantly lower than that of the CON group. Muscle glycogen and lactate levels in the blood and muscle were equivalent between groups at rest and in response to exercise. The mitochondrial content was equal between groups, and AMPK in the skeletal muscles of TD rats was normally activated by LIS and HIS. In conclusion, with a lowered cellular thiamin level, the exercise-associated glycogen metabolism and AMPK activation level in skeletal muscle were normally regulated.

Abstract Background There is still considerable debate about the effects of exposure to bisphenol A (BPA) an endocrine disrupter at low doses. Recently, many studies using animal models have shown that prenatal BPA exposure induces behavioral and neuronal disorders due to epigenetic changes in the brain. However, striking evidence of epigenomic changes has to be shown. Methods To investigate whether low-dose BPA exposure in the fetal stage can alter CpG methylation levels in the central nervous system, the hippocampus of the inbred C57BL/6 J mouse as the target tissue was collected to detect alterations in CpG methylation levels using a highly sensitive method of genome-wide DNA methylation analysis, methylated site display–amplified fragment length polymorphism (MSD-AFLP). Results BPA showed the sex-hormone like effects on male reproductive organs. Although we examined the methylation levels of 43,840 CpG sites in the control and BPA (200 μg/kg/day)-treated group (6 mice per group), we found no statistically significant changes in methylation levels in any CpG sites. Conclusions At least under the experimental condition in this study, it is considered that the effect of low-dose BPA exposure during the fetal stage on hippocampal DNA methylation levels is extremely small.

In this article, we seek to reconceptualize content-based instruction (CBI) curricula and practices from a critical perspective. Further, we propose developing criticality as an essential component of CBI, advocating for an approach we call critical content-based instruction (CCBI). While the importance of CBI has long been recognized, previous discussions predominantly focused on its effectiveness for language learning (and content learning to a lesser degree), and overlooked its fundamental linkage and relevance to broader educational missions. In order to fully maximize the potential of CBI and envision language education as integral to the advancement of society, we argue that a critical approach to CBI should be considered. First, we lay out how CBI came to be and how it has been treated in language pedagogy. We believe CBI is indeed a suitable forum for introducing and implementing a critical perspective because of its original contribution of broadening language education to meet societal needs. Second, we provide an overview of recent discourse surrounding world language education. Based on these reviews, we lastly and most importantly delineate directions for CCBI by presenting examples and possible challenges.

Abstract Recent guidelines regarding pharmacological interventions for major depressive disorder (MDD) recommend first using serotonin (5HT) selective reuptake inhibitors (SSRIs) or 5HT and norepinephrine (NE) reuptake inhibitors (SNRIs). Although SSRIs and SNRIs are effective and well‐tolerated, apathy occurs as an adverse effect in some SSRIs‐treated patients. Because apathy would be associated with the 5HT pathway, if a patient exhibits apathy symptoms under SSRIs treatment, a clinical strategy has been to change the SSRIs to treatment with an SNRIs. Here, I report two cases in which low‐dose venlafaxine, an SNRIs, induced apathy symptoms.

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 μg g−1 compound I and 484 μg g−1 compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.

Clinical guidelines for pulmonary hypertension recommend evaluating treatment response through various methods; however, electrocardiography (ECG) is not included as one of the methods of choice. We aimed to identify ECG parameters that correlated with prognosis in patients with pulmonary arterial hypertension (PAH). A total of 112 consecutive patients with PAH were enrolled in this study. Among them, 83 with treatment escalation were studied for further analysis. Survival analyses were conducted using the Kaplan–Meier method with the log-rank test. Cox proportional hazards regression modeling was used to identify predictors of survival. Receiver operating characteristic analysis was used to determine cut-off values for selected variables. ECG parameters were changed from baseline to three months after treatment. Patients in whom the R wave amplitude in lead V1 decreased by ≥1 mm (0.1 mV) within three months demonstrated significantly better survival ( P = 0.017). Our results suggest that evaluation of ECG parameters can contribute to assessments of survival in patients with PAH.

In this study, we investigated the retention of technetium-99m sestamibi (MIBI), a radiopharmaceutical that accumulates in mitochondria, in patients with type 2 diabetes. We hypothesized that patients with type 2 diabetes had lower MIBI counts in their legs than non-diabetic volunteers, and that these abnormalities reflected a low anaerobic threshold (AT) during cardiopulmonary exercise testing (CPX). Eight non-diabetic volunteers (Group N) and 11 patients with type 2 diabetes (Group D) underwent CPX. Mitochondrial function was assessed using MIBI imaging of both legs. The MIBI counts in the legs were significantly lower in Group D than in Group N (D vs. N: 74.1 vs. 94.1 counts/pixel, p < 0.05). Similarly, peak oxygen uptake (peakVO2) and AT were lower in Group D than in Group N (peakVO2: 19.8 vs. 26.5 ml/kg/min, p < 0.05; AT: 13.1 vs. 17.2 ml/kg/min, p < 0.05). A strong correlation was observed between MIBI counts and the peakVO2 and AT (peakVO2: r = 0.62, p < 0.01; AT: r = 0.76, p < 0.01). After the exclusion of an outlying subject, the correlation between peakVO2 and MIBI count in the legs was lost (r = 0.28, p = 0.26); however, the AT correlation was maintained (r = 0.59, p = 0.01). Patients with type 2 diabetes had reduced skeletal muscle MIBI counts, indicating reduced mitochondrial function. This abnormality may be linked to a low AT.

A 34-year-old woman with primary antiphospholipid syndrome was admitted to the Gastroenterology Department of our hospital with fever, acute abdomen, watery diarrhea, and extremely high levels of inflammatory parameters. She had a history of left lower limb deep vein thrombosis and pulmonary embolism and was taking warfarin potassium. Acute gastroenteritis was suspected and an antibiotic was administered, but symptoms progressed. Abdominal ultrasonography showed occlusion of the left hepatic vein and the middle hepatic vein and her D-dimer level was high. Accordingly, Budd-Chiari syndrome was diagnosed and high-dose intravenous infusion of heparin was initiated. Her abdominal symptoms improved and the levels of inflammatory parameters and D-dimer decreased rapidly. It is known that antiphospholipid syndrome can be complicated by Budd-Chiari syndrome that usually occurs as subacute or chronic onset, but acute onset is rare. It is difficult to diagnose acute Budd-Chiari syndrome complicating antiphospholipid syndrome and this complication generally has a poor outcome. However, the present case can get early diagnosis and successful treatment with tight anticoagulant therapy.

Chronic intestinal pseudoobstruction (CIPO) is a serious complication in patients with connective tissue disease (CTD) and is sometimes life-threatening or fatal despite intensive medical treatment. Here, we report a patient with dermatomyositis (DM) and anti-EJ autoantibody who developed CIPO that was improved by octreotide. Because her abdominal pain and bloatedness were so severe and persistent, we introduced octreotide to relieve symptoms. In this case, continuous intravenous administration as well as long-acting subcutaneous injection of octreotide was effective for treating CIPO.

Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies.Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients' serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated.In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006).Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM.

Neurodegenerative brain disorders such as Alzheimer’s disease (AD) have been well investigated. However, significant methods for the treatment of the promotion and progression of AD are unavailable to date. Recent studies suggested that the redox imbalance and the accumulation of amyloid-β (Aβ) peptide occurring in the brain of AD patients lead to oxidatively-induced apoptotic cell death. Here, we show the effects of Shengmai-san (SMS) on Aβ-induced cytotoxicity in PC-12 cells. SMS dose-dependently attenuated the cytotoxicity by Aβ incubation and also prevented the morphological damage in neurites of the PC-12 cells. Heme-oxygenase-1 and glutathione peroxidase-1 expressions were increased by SMS pretreatment. SMS decreased the phosphorylation level of c-jun amino-terminal kinase (JNK) and the activity of caspase-3, which were enhanced by Aβ incubation. Of importance, SMS treatment promoted neurite outgrowth. These data demonstrated dual roles of SMS in PC-12 cells. SMS prevents the apoptosis through the enhancement of anti-oxidant enzymes and inhibition of the JNK signaling pathway with the promotion of nerve cell maturation, thus suggesting benefits of SMS for the treating of neurodegenerative diseases. It may also be beneficial not only for the treatment of brain disorders but also for other diseases caused by oxidative stress. Keywords:: Alzheimer’s disease, apoptosis, mitogen-activated protein kinase (MAPK), neurite outgrowth, Shengmai-san

A 57-year-old woman with rheumatoid arthritis (RA) and limited systemic sclerosis (lSSc) was suspected to have lymphadenopathy and primary biliary cirrhosis (PBC). Lymph node biopsy showed reactive follicular lymphadenopathy with intrafollicular plasmacyte infiltration that was interleukin-6 positive by immunohistostaining. Because of gradually worsening arthritis, tocilizumab was administered and arthritis improved markedly. Interestingly, lymphadenopathy and PBC improved simultaneously. This suggested that interleukin-6 might play an important role in reactive lymphadenopathy and PBC associated with RA/lSSc.

Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis.

A 77-year-old man suffering from prolonged fever of unknown origin and bilateral leg edema was referred to our hospital. On physical examination, he had fever, general fatigue, bilateral lower leg edema, and muscle weakness of the right upper extremity and left lower extremity. Neurological examination indicated motor and sensory disturbance. Electromyography revealed mononeuritis multiplex and myopathy. A biopsy of the left biceps muscle indicated necrotizing vasculitis with fibrinoid necrosis. Considering all the data together, he was diagnosed as having polyarteritis nodosa (PAN) and concurrent active cytomegalovirus (CMV) infection. His symptoms improved promptly on treatment with 50 mg of prednisolone. This case emphasizes the importance of CMV infection as one of possible etiologies of PAN and reports a therapeutic strategy for this syndrome.

Formation of neurofibrillary tangles (NFTs) is the most common feature in several neurodegenerative diseases, including Alzheimer's disease (AD). Here we report the formation of filamentous tau aggregations having a β-sheet structure in transgenic mice expressing mutant human tau. These mice contain a tau gene with a mutation of the frontotemporal dementia parkinsonism (FTDP-17) type, in which valine is substituted with methionine residue 337. The aggregation of tau in these transgenic mice satisfies all histological criteria used to identify NFTs common to human neurodegenerative diseases. These mice, therefore, provide a preclinical model for the testing of therapeutic drugs for the treatment of neurodegenerative disorders that exhibit NFTs.

Genome-wide association studies (GWAS) have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA). Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC) for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR) algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate biological pathways.

In the repair works of Japan's infrastructure maintenance and management, there is a need to develop a technology that can easily remove coating and rust without a thermal effect on the base material, and the laser blasting technology, which can achieve this by only emitting laser beams, is a candidate for this goal. In various fields of infrastructure maintenance and management, we have been progressing on an agile system product development based on customer's feedbacks in accordance with our in-house systematized new business development process. In this report, we will describe the development of the "InfraLaser" system and the laser blasting technology, where we apply a high-power laser and the processing technology that we have cultivated. The laser blasting technology can remove coating and rust faster than existing methods without affecting the base material, and is expected to be friendly to both workers and environment. [ABSTRACT FROM AUTHOR]