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[Purpose] To describe our newly developed Sedentary Behavior and Light-Intensity Physical Activity Questionnaire and examine its reliability and validity. [Participants and Methods] We identified and selected self-reported items through a literature review and interviews with 11 inactive individuals. Thirty-one individuals with lower limb prostheses and an expert panel assessed the content validity of the integrated items and identified 17 items. Patients who had undergone lower limb surgeries were regarded as inactive individuals, and 112 patients completed the questionnaire twice for test-retest reliability and wore an accelerometer for criterion validity. The ethics committee of Kyushu University approved this study (2019-126 and 2019-273). [Results] Item analysis was revised to the Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 (six light-intensity physical activity and four sedentary behavior items) because of the floor effect. The test-retest correlation coefficient showed high reliability. Moderate to weak correlation coefficient was observed between the questionnaire and accelerometer (light-intensity physical activity: 0.43 and sedentary behavior: 0.20), and the Bland-Altman plots indicated no bias. [Conclusion] The Sedentary Behavior and Light-Intensity Physical Activity Questionnaire-10 had acceptable validity and reliability among inactive individuals and it could be used for studying light-intensity physical activity.

Background Over 40% Japanese patients with lung cancer are above 75 years of age. A specific strategy to treat such older patients is necessary because most trials exclude older patients with poor physical health. Herein, we aimed to identify predictive factors associated with overall survival (OS) in older patients by evaluating patient backgrounds and laboratory data before the start of treatment. Methods This multicenter retrospective medical chart review study was conducted at three Japanese institutions and involved patients aged 75 years and above with epidermal growth factor receptor (EGFR) mutation-negative advanced non-small cell lung cancer (NSCLC). Of the patients, 75 had received best supportive care (BSC) and 49 mono-chemotherapy or platinum-doublet chemotherapy, including immune checkpoint inhibitors (ICIs). OS after diagnosis was analyzed using the Kaplan-Meier survival analysis. Cox proportional hazard models, which included age, Eastern Cooperative Oncology Group performance status (ECOG PS), staging, serum albumin levels, and receipt of chemotherapy were analyzed. Results Age at diagnosis was not shown to be related to OS in patients receiving BSC. In patients aged 81 years and above, the chemotherapy group tended to have longer survival than did the BSC group, but there was no statistically significant difference in the median OS between the two groups due to the very small number of subjects (n: 30 vs. 12, median: 52 vs. 30 weeks, hazard ratio: 0.512, 95% confidence interval: 0.232-1.130, P=0.088). The patients' performance status and albumin levels at lung cancer diagnosis had the highest impact on OS in the BSC group. Conclusions Careful consideration should be given to the indications of chemotherapy for patients aged 81 years and above with wild-type EGFR advanced non-small lung cancer.

The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) is used in many countries to determine patient expectations before surgery. This study aimed to assess the reliability and validity of the Japanese version of HSS-THRES.A total of 134 patients scheduled for total hip arthroplasty (THA) underwent a self-administered preoperative survey questionnaire. Patient's expectation and quality of life (QOL) were measured using the Japanese version of HSS-THRES, overall expectations for THA, Oxford hip score (OHS), and EuroQol-5D (EQ-5D). Some patients completed the Japanese version of HSS-THRES and the overall expectations for THA after a ten-day interval. Cross-cultural adaptation was validated by an expert committee comprising health professionals, a methodologist, language experts, and orthopedic specialists. The internal consistency was evaluated by the Cronbach α coefficient. The test-retest reliability was examined using the intraclass coefficient correlation (ICC) and the Bland and Altman analysis. To test the construct validity, nine priori hypotheses were tested by correlation analysis between the Japanese version of HSS-THRES and two QOL scales, and by examining the association with demographic variables.A total of 116 patients completed four scales. Patients were predominantly female (75.9%), with an average age of 62.2 ± 11.7. In the cross-cultural adaptation, all patients responded to the questionnaire without problems. The Japanese version of HSS-THRES showed good internal consistency (Cronbach α: 0.9). ICC was 0.94 and Bland-Altman analysis indicated no bias. The correlation between Japanese HSS-THRES and overall expectations for THA was high (r = 0.67). Similarly, the correlation with the OHS was higher than that with EQ-5D. A total of 77.8% of the hypotheses were confirmed.The Japanese version of HSS-THRES showed good cultural acceptability, high reliability, and validity to evaluate preoperative expectations for THA patients.

Purpose The primary objective of this study was to identify the potential predictors to assess impact of maintenance therapy after induction immunochemotherapy in the real-world setting of patients with advanced non-small cell lung cancer (NSCLC). Methods We retrospectively identified 152 patients with advanced NSCLC who received immunochemotherapy at eight hospitals in Japan between January 2019 to December 2019. Patients who received at least four cycles of induction immunochemotherapy and one cycle of maintenance therapy with immune-checkpoint inhibitors were included. We investigated the biomarkers for progression-free survival (PFS) for maintenance therapy after induction immunochemotherapy. Results Out of the 92 patients with advanced NSCLC included in the study, 42 received maintenance therapy with cytotoxic agents whereas 50 received maintenance therapy without cytotoxic agents. Among those who received maintenance therapy without cytotoxic agents, responders to prior immunochemotherapy had significantly longer PFS than non-responders (p = 0.004), except those with maintenance therapy with cytotoxic agents. In non-responders to prior immunochemotherapy, patients with maintenance therapy with cytotoxic agents had significantly longer PFS than those with maintenance therapy without cytotoxic agents (log-rank p = 0.007), whereas among responders to prior immunochemotherapy, there was no significant difference in PFS for different maintenance regimens (log-rank p = 0.31). Conclusions This retrospective study showed that response to prior immunochemotherapy was associated with clinical outcomes among patients with advanced NSCLC who received maintenance therapy.

Aim To evaluate the effects of an intensity display type accelerometer on diabetic patients' physical activity. Methods This was a two-arm, non-randomized controlled study. Both groups received information about the recommendation of 150 min/week moderate-to-vigorous physical activity (MVPA). The intervention group used an intensity display type accelerometer to monitor their physical activity intensity for 10 days at baseline and 3 months later. We compared intervention and control groups after 3 and 6 months. Primary outcomes were MVPA and number of steps over 7 days. Secondary outcomes were glycosylated hemoglobin (HbA1c), body mass index, and self-management. Results Of 62 participants, 30 and 32 were included in the intervention and control groups, respectively. Mean age in each group was 59.7 ± 10.8 and 58.8 ± 10.2 years, and mean HbA1c was 6.9 ± 0.9% and 6.9 ± 0.8%, respectively. There were no significant differences between the intervention and control groups at either time point, and no outcomes showed significant changes. In a subgroup analysis by physical activity intensity, MVPA of active individuals in the control group significantly decreased at 6 months from baseline. MVPA and number of steps among inactive individuals in the intervention group significantly increased at 6 months from baseline. Self-management of the intervention group showed a trend toward improvement, but HbA1c and body mass index showed no significant change. Conclusions Monitoring physical activity intensity led to increased MVPA of inactive patients and maintained MVPA of active patients with diabetes mellitus. This straightforward intervention could be applied in clinical practice.

Background: Demographic data of patients with sensorineural hearing loss (SNHL) in super-aged societies are still limited.Aims/objectives: To report audiometric statistics of SNHL and hearing aid (...

Aim: This study aimed to evaluate the effect of diet on serum lipids and to assess the effectiveness of long-term dietary therapy for hypertriglyceridemia. Methods: Seventy-nine patients (34 males and 45 females) with hypertriglyceridemia were enrolled and underwent dietary counseling for 12 months based on the following three recommendations: (1) reduce carbohydrate intake, (2) increase n-3 polyunsaturated fatty acid (PUFA) intake, and (3) limit alcohol drinking. We examined the effect of dietary therapy for 6 months on serum triglyceride (TG) levels and also compared the effectiveness of dietary and combined drug therapies on preventing arteriosclerotic disease from 7 to 12 months. Results: We observed that serum TG levels of the patients receiving dietary counseling were decreased compared with baseline at 6 months. Body weight and serum TG levels were decreased, and serum high-density lipoprotein levels were increased in the dietary therapy alone group, whereas BW, body mass index, and abdominal circumference were decreased in the combined drug treatment group compared with baselines at 6 and 12 months. Furthermore, the dietary therapy alone group demonstrated reductions in intake of total energy, carbohydrate, and saturated fatty acids, as well as n-6/n-3 PUFA ratio compared with baselines, but only n-6/n-3 PUFA ratio was decreased in the combined drug treatment group. Conclusion: This study demonstrated a decrease in serum TG level after 12 months of dietary therapy similar to drug therapy, which suggests that it is an effective treatment for hypertriglyceridemia, and heightened awareness should be made to encourage its use. The clinical trial registration number: UMIN000028860.

Currently, antimicrobial-resistant staphylococci, particularly methicillin-resistant Staphylococcus pseudintermedius (MRSP), are frequently isolated from canine superficial pyoderma in Japan. However, little is known regarding the nasal prevalence of MRSP in pet dogs. Here, we determined the prevalence of antimicrobial-resistant staphylococci in nares and affected sites of pet dogs with superficial pyoderma. Of the 125 nares and 108 affected sites of pet dogs with superficial pyoderma, 107 (13 species) and 110 (eight species) staphylococci strains, respectively, were isolated. The isolation rate of S. pseudintermedius from pyoderma sites (82/110 strains, 74.5%) was significantly higher than that from nares (57/107 strains, 53.3%) (P

Cancer immunotherapy, including atezolizumab monotherapy, is a promising alternative strategy for patients with advanced non-small-cell lung cancer (NSCLC). Several inflammatory indices have been reported as potential biomarkers regarding the effectiveness of various treatments. This study aimed to analyze the efficacy of atezolizumab monotherapy using baseline inflammatory markers in NSCLC patients. We retrospectively enrolled 81 NSCLC patients who received atezolizumab monotherapy at six different medical institutions in Japan. The Cox proportional hazards model was used to assess the impact of the clinical variables, including inflammatory indexes, on clinical outcomes. Median progression-free survival (PFS) and overall survival (OS) were 60 days and 252 days, respectively. The objective response rate was 7.4%, and the disease control rate was 54.3%. Patients with high neutrophil to lymphocyte ratio (NLR), low lymphocyte to monocyte ratio (LMR), and/or high platelet to lymphocyte ratio (PLR), at baseline, demonstrated substantially shorter PFS and OS compared to those with a low NLR, high LMR, and/or low PLR. The multivariate analysis demonstrated that a high baseline NLR was substantially associated with short PFS and short OS. Our retrospective observations suggest that inflammatory indices may be a potential negative prognostic factor of atezolizumab monotherapy outcomes in NSCLC patients.

Combined immunotherapy and chemotherapy is a promising standard treatment in patients with advanced non-small cell lung cancer (NSCLC). This study aimed to evaluate the relationship between the combined therapy and pretreatment serum antinuclear antibody (ANA) levels as a prognostic indicator in patients with NSCLC. We retrospectively analyzed patients with advanced NSCLC who were treated with combinatorial immunotherapy and chemotherapy between January and December 2019 at six institutions in Japan. Relationship between ANA status and patients’ characteristics were reviewed. A total of 77 patients with advanced NSCLC were enrolled in the study. Patients were divided into ANA-positive (ANA ≥ 1:160) and ANA-negative (ANA

AIM The aims of this study were to: (a) describe the physical activity (PA) and quality of life (QOL) in living donor liver transplant (LDLT) recipients pre-operatively and at 3 months and 6 months post-operatively; (b) compare PA and QOL at 6 months post-operatively with a healthy control group; and (c) explore pre-operative factors that predict PA changes. METHODS Patients over 20 years of age who were undergoing LDLT were recruited. PA was measured based on the number of steps/day and time spent performing moderate-to-vigorous PA (MVPA) during 1 week using an accelerometer. QOL was assessed based on a physical (PCS) and mental (MCS) component summary of the eight-item Short-Form Health Survey. The LDLT and healthy control groups were matched for age (±3 years) and gender. Pre-operative factors predicting a change in PA were calculated using a generalized linear mixed model. RESULTS Twenty-four patients completed the study. By 6 months post-LDLT, the MCS and PCS were comparable to those in the control group. The number of steps (3,887 steps/day) and MVPA (29.3 min/week) showed significant improvement by 6 months post-operatively, but remained much lower compared with those in the control group. The multivariate analysis showed that younger age (p

The contribution of physical activity (PA) to the prevention of metabolic abnormalities following liver transplantation (LT) has not been well documented. We aimed to assess PA in post-LT patients and to quantify its relationships with the development of postoperative metabolic abnormalities and health-related quality of life (HRQOL). We recruited 111 patients who had undergone LT ≥ 6 months previously. PA was measured by accelerometry, and HRQOL was evaluated using SF-8. PA was quantified as the number of steps per day, and the time spent performing moderate-to-vigorous PA and light PA per week. The prevalence of hypertension, diabetes, and dyslipidemia increased more than twofold following LT. The proportion of the participants with a sedentary lifestyle (

Mycobacterium shigaense has recently been recognized as an emerging human pathogen, and is well known as a skin pathogen in immunocompromised individuals. In this report we describe the first case of chronic pulmonary infectious disease caused by M. shigaense in an immunocompetent individual. Keywords: Chest computed tomography (CT) images, emerging infectious diseases, immunocompetent, Mycobacterium shigaense, Mycobacterium simiae complex, Pulmonary disease, skin disease

Background Although the beta-2 receptor agonist (B2RA) is occasionally prescribed in the prenatal period for women with preterm labor, few studies have referred to the long-term effects of intrauterine exposure to B2RA on fetus. We examined the association between intrauterine exposure to B2RA and asthma in the offspring. Methods We obtained data from a hospital-based birth cohort study conducted in Tokyo, Japan. The outcomes of interest were three indicators, consisting of current wheeze, current asthma and ever asthma at 5 years of age, based on the International Study of Asthma and Allergies in Childhood questionnaire. Logistic regression analysis was used to evaluate the association between intrauterine B2RA exposure and outcomes. To evaluate dose-dependent risk, we categorized children into three groups according to both the cumulative dose and duration (days) and conducted trend analysis. Results Of 1158 children, 94 (8.1%) were exposed to B2RA in utero, and 191 (16.5%), 111 (9.6%) and 168 (14.5%) children experienced current wheeze, current asthma and ever asthma, respectively. After adjusting for confounders, we found an increased risk of current asthma caused by B2RA exposure with an adjusted odds ratio of 2.04 (95% confidence interval: 1.02-4.05). Trend analysis showed that B2RA exposure in utero was associated with a dose-dependent increased risk of current asthma in terms of both cumulative dose and duration (p values for trend were 0.015 and 0.017, respectively). These results were similar to those for other outcome measures. Conclusion Exposure to B2RA in utero could be a risk for childhood asthma. This article is protected by copyright. All rights reserved.

To clarify how the pure-tone threshold (PTT) on the PTA predicts speech perception (SP) in elderly Japanese persons.Data on PTT and SP were cross-sectionally analyzed in Japanese persons (656 ears in 353 patients, aged ≥65 years). Correlations of SP and average PTT in all tested frequencies were evaluated by Pearson's correlation coefficient and simple linear regression. After adjusting for sex, laterality of ears, and age, the relationship of average and frequency-specific PTT with impaired SP ≤50% was estimated by logistic regression models.SP correlated well (r = -0.699) with the average PTT of all tested frequencies. On the other hand, the correlation between patient age and SP was weak, especially among ≤85-year-old persons (r = -0.092). Linear regression showed that the average PTT corresponding to SP of 50% was 76.4 dB nHL. Odds ratios for impaired SP were highest for PTT at 2000 Hz. Odds ratios were higher for middle (500, 1000, 2000 Hz) and high frequencies (4000, 8000 Hz) than low frequencies (125, 250 Hz).The PTT on the pure-tone audiogram (PTA) is a good predictor of SP by speech audiometry among older persons, which could provide clinically important information for hearing aid fitting and cochlear implantation.

Fusion images of diffusion-weighted whole-body imaging with background body signal suppression and T2-weighted image (DWIBS/T2) demonstrate a strong signal for malignancies, with a high contrast against the surrounding tissues, and enable anatomical analysis. In the present study, DWIBS/T2 was compared with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for diagnosing cancer in the abdomen. Patient records, including imaging results of examination conducted between November 2012 and May 2014, were analyzed retrospectively. In total, 10 men (age, 73.6±9.6 years) and 8 women (age, 68.9±7.1 years) were enrolled into the current study. Of the enrolled patients, 2 were diagnosed with hepatocellular carcinoma, 1 with cholangiocellular carcinoma, 1 with liver metastasis, 2 with pancreatic ductal adenocarcinoma, 1 with renal cell carcinoma and 1 with malignant lymphoma. Benign lesions were also analyzed, including adenomyomatosis of the gallbladder (5 patients), intraductal papillary mucinous neoplasm (4 patients) and right adrenal adenoma (1 case). All the patients with cancer showed positive results on DWIBS/T2 images. However, only 7 out of 8 patients were positive with PET/CT. One patient with right renal cellular carcinoma was positive with DWIBS/T2, but negative with PET/CT. All the patients with benign lesions were negative with DWIBS/T2 and PET/CT. In conclusion, DWIBS/T2 was more sensitive in diagnosing cancer of organs in the abdominal cavity compared with PET/CT. Furthermore, negative results with DWIBS/T2 and PET/CT were useful for the diagnosis of benign lesions, such as adenomyomatosis of the gallbladder and intraductal papillary mucinous neoplasm.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) images show significant contrast for cancer tissues against non-cancerous tissues. Fusion of a DWIBS and a T2-weighted image (DWIBS/T2) can be used to obtain functional, as well as anatomic, information. In the present study, the performance of DWIBS/T2 in the diagnosis of abdominal solid cancer was evaluated. The records of 14 patients were retrospectively analyzed [5 patients with hepatocellular carcinoma (HCC), 4 with metastatic liver cancer, 3 with pancreatic cancer, 1 with renal cellular carcinoma and 1 with malignant lymphoma of the para-aortic lymph node]. T1WI and T2WI scans did not detect pancreatic cancer in certain cases, whereas DWIs and DWIBS/T2 clearly demonstrated pancreatic cancer in all cases. In addition, metastatic liver cancer and HCC were successfully detected with abdominal US and CECT; however, US did not detect pancreatic cancer in 1 case, while CECT and DWIBS/T2 detected pancreatic cancer in all cases. In conclusion, the diagnostic performance of DWIBS/T2 was the same as that of abdominal US and CECT in detecting primary and metastatic liver cancer. DWIBS/T2 enabled the diagnosis of pancreatic cancer in cases where it was not detected with US, T1WI or T2WI.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) yields positive results for cancer against the surrounding tissues. The combination of DWIBS and T2-weighted images (DWIBS/T2) in the diagnosis of gastrointestinal tract cancers was retrospectively analyzed in the present study. Patients were subjected to magnetic resonance imaging after cancer was diagnosed through specimens obtained via biopsy or endoscopic mucosal resection. Sixteen patients were assessed between July, 2012 and June, 2013 and the correlation between detection with DWIBS/T2 and T staging was analyzed. Regarding patients who underwent surgery, the correlation between detection with DWIBS/T2 and the diameter or depth of invasion was analyzed. All cancers that had advanced to >T2 stage were detectable by DWIBS/T2, whereas all cancers staged as T2) or invading beyond the muscularis propria.

In fetal critical aortic stenosis (AS), a double reverse pattern in the pulmonary veins (PVs) is associated with a poor prognosis. We evaluated the hemodynamic changes using PV Doppler and the left atrium area/cardiac area (LA/CA) ratio in a fetus at 28 weeks of gestation with critical AS complicated with hydrops fetalis, polyhydramnios, and cardiac abnormality. A markedly enlarged LA and severe mitral regurgitation with critical AS were detected, with LA/CA ratio = 0.40 and double reverse pattern with forward/reverse velocity time integral ratio (FRVR) = 1.18 on PV Doppler. After amniotic reduction at 31 weeks, the LA/CA ratio decreased (0.24) and the FRVR in PV increased (7.11). Forward flow through the fetal aorta was seen spontaneously, and hydrops fetalis was relieved with LA volume reduction. A male neonate weighing 2171 g was delivered via cesarean section at 36 weeks with an Apgar score of 5 and 6 at 1 and 5 min, respectively. He required atrial septal opening and bilateral pulmonary artery banding after birth, followed by Norwood operation. The double reverse pattern in PVs might be reversible. The change in FRVR in PVs and LA/CA ratio would be helpful in understanding the hemodynamic change in fetal critical AS.

The objective of this study is to assess the outcomes and risk factors of fetal bradycardia after external cephalic version (ECV).We performed a retrospective study of women who underwent ECV after 35 weeks of gestation in 2010-2016. We assessed the birth outcomes, including umbilical cord artery pH, according to the duration of fetal bradycardia and the risk factors for bradycardia.Among 390 cases, 189 (48.5%) cases showed fetal bradycardia during or immediately after ECV. The duration of fetal bradycardia was1 min (n = 82, 43.4%),5 min (n = 168, 88.9%); and10 min (n = 186, 98.4%). All cases showed a good prognosis. Fetal bradycardia lasting10 min occurred in three cases; emergency cesarean section was performed in each case, with delivery after 12-4 min of bradycardia. Two of three cases showed low Apgar scores at 5 min, with an umbilical cord arterial pH of7.1. Lower maternal BMI and a prolonged ECV procedure were significantly associated with bradycardia (p for trend: .016 and .015, respectively).Fetal bradycardia lasting10 min after ECV was a risk factor for asphyxia. Thus, delivery should be completed within 10 min after bradycardia. A low maternal BMI and a prolonged ECV procedure were risk factors for bradycardia after ECV.

In a clinical setting, it is important to diagnose complications of acute cholecystitis accurately. Diffusion-weighted whole body imaging with background body signal suppression/T2-weighted image fusion (DWIBS/T2) provides high signal intensity with a strong contrast against surrounding tissues in anatomical settings. In the present study, patients who were being treated for acute cholecystitis and underwent DWIBS/T2 in the National Hospital Organization Shimoshizu Hospital between December 2012 and August 2015 were enrolled. A total of 10 men and 4 women underwent DWIBS/T2. Records, including DWIBS/T2 and computed tomography (CT) imaging, were retrospectively analyzed for patients with acute cholecystitis. CT images revealed thickened gallbladder walls in patients with acute cholecystitis, and high signal intensity was observed in DWIBS/T2 images for the thickened gallbladder wall. Inflammation of the pericholecystic space and the liver resulted in high intensity signals with DWIBS/T2 imaging, whereas CT imaging revealed a low-density area in the cholecystic space. Plain CT scanning identified a low-density area in the liver, which became more obvious with contrast-enhanced CT. DWIBS/T2 imaging showed the inflammation of the liver and pericholesyctic space as an area of high signal intensity. Detectability of inflammation of the pericholecystic space and the liver was the same for DWIBS/T2 and CT, which suggests that DWIBS/T2 has the same sensitivity as CT scanning for the diagnosis of complicated acute cholecystitis. However, the strong contrast shown by DWIBS/T2 allows for easier evaluation of acute cholecystitis than CT scanning.

Previous studies have suggested that professional musicians comprehend features of music-derived sound even if the sound sequence lacks the traditional temporal structure of music. We tested this hypothesis through behavioral and functional brain imaging experiments. Musicians were better than nonmusicians at identifying scrambled pieces of piano music in which the original temporal structure had been destroyed. Bilateral superior temporal gyri (STG) activity was observed while musicians listened to the scrambled stimuli, whereas this activity was present only in the right STG of nonmusicians under the same experimental conditions. We suggest that left STG activation is related to the processing of deviants, which appears to be enhanced in musicians. This may be because of the superior knowledge of musical temporal structure held by this population.

Previous studies have indicated that extended exposure to a high level of sound might increase the risk of hearing loss among professional symphony orchestra musicians. One of the major problems associated with musicians’ hearing loss is difficulty in estimating its risk simply on the basis of the physical amount of exposure, i.e. the exposure level and duration. The aim of this study was to examine whether the measurement of the medial olivocochlear reflex (MOCR), which is assumed to protect the cochlear from acoustic damage, could enable us to assess the risk of hearing loss among musicians. To test this, we compared the MOCR strength and the hearing deterioration caused by one-hour instrument practice. The participants in the study were music university students who are majoring in the violin, whose left ear is exposed to intense violin sounds (broadband sounds containing a significant number of high-frequency components) during their regular instrument practice. Audiogram and click-evoked otoacoustic emissions (CEOAEs) were measured before and after a one-hour violin practice. There was a larger exposure to the left ear than to the right ear, and we observed a left-ear specific temporary threshold shift (TTS) after the violin practice. Left-ear CEOAEs decreased proportionally to the TTS. The exposure level, however, could not entirely explain the inter-individual variation in the TTS and the decrease in CEOAE. On the other hand, the MOCR strength could predict the size of the TTS and CEOAE decrease. Our findings imply that, among other factors, the MOCR is a promising measure for assessing the risk of hearing loss among musicians.

Polycomb group gene Bmi1 functions as a tumor suppressor in myelofibrosis., Polycomb-group (PcG) proteins form the multiprotein polycomb repressive complexes (PRC) 1 and 2, and function as transcriptional repressors through histone modifications. They maintain the proliferative capacity of hematopoietic stem and progenitor cells by repressing the transcription of tumor suppressor genes, namely Ink4a and Arf, and thus have been characterized as oncogenes. However, the identification of inactivating mutations in the PcG gene, EZH2, unveiled a tumor suppressor function in myeloid malignancies, including primary myelofibrosis (PMF). Here, we show that loss of another PcG gene, Bmi1, causes pathological hematopoiesis similar to PMF. In a mouse model, loss of Bmi1 in Ink4a-Arf−/− hematopoietic cells induced abnormal megakaryocytopoiesis accompanied by marked extramedullary hematopoiesis, which eventually resulted in lethal myelofibrosis. Absence of Bmi1 caused derepression of a cohort of genes, including Hmga2, which is an oncogene overexpressed in PMF. Chromatin immunoprecipitation assays revealed that Bmi1 directly represses the transcription of Hmga2. Overexpression of Hmga2 in hematopoietic stem cells induced a myeloproliferative state with enhanced megakaryocytopoiesis in mice, implicating Hmga2 in the development of pathological hematopoiesis in the absence of Bmi1. Our findings provide the first genetic evidence of a tumor suppressor function of Bmi1 and uncover the role of PcG proteins in restricting growth by silencing oncogenes.

Posterior reversible encephalopathy syndrome (PRES) has been reported in childhood leukemia patients increasingly frequently. However, the development of PRES in adult leukemia patients during chemotherapy is very rare. We present a case of PRES in an adult patient with acute lymphoblastic leukemia (ALL) after remission induction chemotherapy. A 28-year-old woman with ALL was administered remission induction chemotherapy consisting of cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase. After initiation of chemotherapy, the patient developed paralytic ileus and hypertension, and on day 30, she suddenly developed generalized convulsions, loss of visual acuity, and muscle weakness in the legs. Magnetic resonance imaging findings and her signs and symptoms were typical of PRES. The symptoms gradually improved following treatment with an anticonvulsant and an antihypertensive agent, and the patient underwent allogeneic bone marrow transplantation. She has completely recovered from PRES and has been asymptomatic without leukemia relapse. During remission induction chemotherapy for ALL, PRES may be caused by multiple drugs, such as L-asparaginase, vincristine, and corticosteroids, with different mechanisms of action. PRES should be recognized as an important complication, which will occur more frequently with the increased intensity of chemotherapy for adult ALL patients.

Myeloproliferative neoplasms (MPN), a group of haematopoietic stem cell (HSC) disorders, are often accompanied by myelofibrosis. We previously identified the fusion of the ETV6 gene to the LYN gene (ETV6-LYN) in idiopathic myelofibrosis with ins(12;8)(p13;q11q21). The introduction of ETV6-LYN into HSCs resulted in fatal MPN with massive myelofibrosis in mice, implicating the rearranged LYN kinase in the pathogenesis of MPN with myelofibrosis. However, the signalling molecules directly downstream from and activated by ETV6-LYN remain unknown. In this study, we demonstrated that the direct activation of STAT5 by ETV6-LYN is crucial for the development of MPN. ETV6-LYN was constitutively active as a kinase through autophosphorylation. ETV6-LYN, but not its kinase-dead mutant, supported cytokine-free proliferation of haematopoietic cells. STAT5 was activated in a JAK2-independent manner in ETV6-LYN-expressing cells. ETV6-LYN interacted with STAT5 and directly activated STAT5 both in vitro and in vivo. Of note, ETV6-LYN did not support the formation of colonies by Stat5-deficient HSCs under cytokine-free conditions and the capacity of ETV6-LYN to induce MPN with myelofibrosis was profoundly attenuated in a Stat5-null background. These findings define STAT5 as a direct target of ETV6-LYN and unveil the LYN-STAT5 axis as a novel pathway to augment proliferative signals in MPN and leukaemia.

Various assessments of health are used to promote comprehensive, formulated worldwide policies for improvement of delivery of care. Perinatal mortality is one measure of global perinatal health. In this review, we clarify the definition of perinatal mortality and discuss the recent trends, backgrounds, contributing factors, and practical management strategies. The wide differences in perinatal mortality between developing and developed countries are well recognized. Of equal concern are the potentially avoidable perinatal deaths that occur in developed countries; the varying perinatal mortality rates between developed countries indicate that they are not yet at an irreducible minimum. To that effect, international health policies should include the unique circumstances of developed countries, and effective practices should be better shared amongst developed countries. The international goal for improving the perinatal mortality rate, in addition to improving public health and access to good care for all pregnant women, is to develop a unified and multifaceted approach as considerably more can be achieved.

The occurrence of a sound event in a sound stream can be perceived without difficulty even when it is difficult to define the acoustic boundary. This study was designed to investigate which acoustical feature functions as an effective cue to “mark” the occurrence of a new event. When two steady sounds are connected by a short frequency glide, at which point do we perceive the occurrence of the second sound: the starting point of the frequency glide or its ending point? To answer this question, experimental stimuli were designed to establish an isochronous structure that was conveyed exclusively by the starting or by the ending point of the glide. The frequency glide was made by modulating the carrier frequency of a sinusoid or the resonant frequency of a complex tone. In two experiments, the deviation from the isochronous structure was detected more easily under the starting-point condition than under the ending-point condition. The results suggest that the starting point functions as a more effective cue for marking a new event than does the ending point.

This study investigates whether the delay caused in the course of wave propagation along the basilar membrane (BM) of the cochlea (i.e., the cochlear delay) affects the perceptual judgment of the synchronization of two sounds. An experiment was conducted to examine the detection of asynchrony using two types of chirps (compensatory and enhanced chirps) and a pulse. A compensatory delay chirp was designed to align the peaks of the BM velocity. An enhanced delay chirp had a delay pattern that “enhances” the assumed cochlear delay. The pulse had a cosine phase relation and, as a result, an intrinsic cochlear delay at the auditory peripheral. The results suggest that it was difficult for the auditory system to distinguish sounds when the lower-frequency components arrived after the higher-frequency components, as happens with a pulse. An auditory model could closely simulate the BM velocity for all stimuli. From both experimental and simulation results, we concluded that the BM velocity corresponding to the higher-frequency components was one of the cues used in the perceptual judgment of synchronization.

Background: Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in patients with dementia and often cause serious problems. However, the cause of BPSD has not yet been elucidated. Moreover, the precise evaluation of BPSD in mild dementia has not been studied in any great detail. In the present study, we investigated the relationship between psychiatric symptoms and regional cerebral blood flow (rCBF) in patients with mild Alzheimer's disease (AD). Methods: The present study included 47 patients (20 men and 27 women) who were diagnosed with mild AD. Mean patient age was 72.8 ± 8.2 years. Single photon emission computed tomography (SPECT) with 99mTc-ethyl cysteinate dimer (99mTc-ECD) was performed in all patients. The SPECT data were analyzed using a three-dimensional stereotactic region of interest template, which evaluated CBF in 24 segments. Psychiatric symptoms were evaluated in patients using the Brief Psychiatric Rating Scale. Each psychiatric symptom was designated as ‘symptom present’ in cases in which the BPRS item score was more than 3. We compared 10 segments of rCBF in symptom-present patients with those in symptom-absent patients. Results: Motor retardation was the most common psychiatric symptom (36.2%), followed by depression (19.1%), anxiety (17.0%), emotional withdrawal (17.0%), and somatic concern (14.9%). Alzheimer's disease patients with motor retardation exhibited a tendency towards lower rCBF in seven segments (left callosomarginal, bilateral parietal, bilateral angular, and bilateral temporal). However, no specific tendency was observed in depression, anxiety, and somatic concern. Conclusions: In the present study, we observed a tendency for decreased brain perfusion in patients with motor retardation. Further studies are necessary to confirm that this trend contributes to the appearance of psychiatric symptoms in patients with mild AD.

The aim of this study was to determine whether there is a difference in pregnancy outcomes dependent on the kind of hormone replacement treatment in the luteal phase after transfer of frozen-thawed embryos in the natural ovulation cycle. Two hundred and twenty-three cycles were examined in this study. The cycles were divided into three groups. In group A (40 cycles), the luteal phase was supported by human chorionic gonadotropin (hCG). In group B (83 cycles), the luteal phase was supported by hCG and vaginal suppository of progesterone. In group C (100 cycles), the luteal phase was supported by hCG, vaginal progesterone and transdermal estradiol. The pregnancy rate and implantation rate in group C (63.0% and 44.3%) were significantly and 28.0%) and group B (45.8% and 30.3%). In conclusion, administration of vaginal progesterone and transdermal estradiol in addition to hCG in the luteal phase in the natural ovulation cycle is effective for improving pregnancy and implantation rates in patients und...

The purpose of this study was to evaluate the effectiveness of buserelin acetate (BA) for triggering endogenous LH surge before oocyte retrieval in clomiphene citrate (CC) or CC+hMG cycles. Patients were divided into two groups: a buserelin group, which consisted of patients treated with BA for 73 cycles 34–36 hours before oocyte retrieval, and an hCG group, which consisted of patients treated with hCG for 89 cycles 34–36 hours before oocyte retrieval. Rate of oocyte retrieval, ratio of metaphase II oocytes, fertilization rate in ICSI, fertilization rate in IVF, ratio of good cleaved embryos, rate of blastocyst development and pregnancy rate were 59.1%, 74.3%, 78.8%, 78.4%, 64.6%, 50.0% and 8.3%, respectively in the buserelin group and 63.2%, 71.3%, 80.6%, 67.6%, 58.6%, 66.7% and 12.5%, respectively, in the hCG group. There were no significant differences in those results between the groups. In conclusion, BA is present terse should be used for a conclusion effective for triggering LH surge befor...

Prompt and accurate diagnosis is critical in the treatment of acute cholecystitis. Diffusion-weighted whole-body magnetic resonance imaging with background body signal suppression/T2 image fusion (DWIBS/T2) identifies areas with high signal intensity, corresponding to inflammation. In the present study, the records and images of patients with acute cholecystitis who underwent DWIBS/T2 between January 2013 and March 2014 were retrospectively analyzed. A total of 11 patients with acute cholecystitis were enrolled. In one patient, DWIBS/T2 identified a thickened wall and high signal intensity, with high signal intensity in the pericholecystic space that suggested localized peritonitis. Positive DWIBS/T2 results indicating acute cholecystitis were obtained in 10/11 patients, with a sensitivity of 90.9%. In addition, wall thickening and high signal intensity were absent in DWIBS/T2 images when wall thickening was not detected by computed tomography. Wall thickening and high signal intensity was attenuated when patients with acute cholecystitis were clinically treated. These data suggest that a thickened gallbladder wall and high signal intensity are indicative of acute cholecystitis and that DWIBS/T2 may be a useful technique in evaluating the severity of acute cholecystitis.

Purpose: Canada’s perinatal, infant and maternal mortality rates were examined and compared with other Organization for Economic Cooperation and Development (OECD) countries. The type and the quality of the available data and best practices in several OECD countries were evaluated. Source: A literature search was performed in PubMed and the Cochrane Library. Vital statistics data were obtained from the OECD Health Database and Statistics Canada and subjected to secondary analysis. Principal findings: Overall, Canadian pregnancy mortality rates have fallen dramatically since the early 1960’s. Perinatal and infant mortality rates remain low and stable, but the maternal mortality rate has increased slightly and both mortality rates have declined in their relative OECD rankings over the last 20 years. Data quality and coverage across Canada and internationally, especially for Indigenous peoples, is inconsistent and registration practices differ greatly, making comparisons difficult. Available data do show that Indigenous people’s perinatal and infant mortality rates are nearly twice those of the general population. Best practices in other OECD countries include Australia’s National Maternity Services plan to improve Aboriginal perinatal health, the Netherlands’ midwifery services and National Perinatal Registry and Japan’s national pregnancy registration and Maternal Handbook. Conclusion: To diminish Canadian disparities in perinatal health rates and improve health outcomes we recommend a) uniform registration practices across Canada, b) better data quality and coverage especially among Indigenous communities, c) adoption of a national pregnancy registration and a maternal handbook along with d) improved midwifery and primary practice services to rural and remote communities. At a time when Canada is focusing upon improving pregnancy health in developing nations, it also needs to address its own challenges in improving pregnancy outcomes.

Leukemia differs substantially with respect to stromal milieu from tumors that progress locally as solid masses, and the physiological importance of immunosurveillance in leukemia remains unclear. However, currently available mouse leukemia models have critical limitations in the context of analyzing immunological regulation of leukemia development. In this study, we transferred mouse MLL/AF9 leukemia-initiating cells into immunocompetent recipient mice without any pre-conditioning such as irradiation, and then analyzed the spontaneous T cell response to an immunogenic antigen expressed in leukemia cells. When the minimum numbers of leukemia-initiating cells for engraftment were transferred, leukemia cells were eradicated by the adaptive immune response in most, if not all, wild-type mice, but not in Rag2 -/- recipient mice, which lack adaptive immunity. By contrast, mice transplanted with larger numbers of leukemia cells always developed leukemia. In mice with advanced leukemia, antigen-specific CTLs were also expanded, but were unresponsive to antigen stimulation and expressed high levels of PD-1 and LAG-3. These results provide the first clear demonstration that the spontaneous CTL response to a tumor-cell antigen has the potential to eradicate leukemia, whereas antigen-specific CTLs are exhausted in animals with advanced leukemia. This immunocompetent mouse leukemia model provides a useful platform for developing effective immunotherapies against leukemia.

Successful treatment with rituximab and donor lymphocyte infusions for fulminant EBV-associated lymphoproliferative disorder that developed 14 years after unrelated BMT

Problem Is increased leukocyte chemotactic activity (CA) from gestational tissues necessary for term or preterm labor in guinea pigs? Method of Study Tissue extracts were prepared from pregnant guinea pig decidua–myometrium, cervix, fetal membranes (amniochorion), and placenta during early third trimester (n = 8), term not in labor (TNL, n = 5), and term spontaneous labor (TL, n = 6), RU486-induced preterm labor (PTL, n = 6), or controls (cPTL, n = 5). Leukocyte CA was assessed using a modified Boyden chamber assay. Extract chemokine and maternal progesterone concentrations were quantified by enzyme immunoassay. Results Only the extracts from amniochorion demonstrated increased CA through late gestation and labor. In contrast, CA was decreased in extracts from amniochorion and cervix from animals after RU486-induced PTL. Maternal progesterone concentrations remained high in all groups. Conclusion Leukocyte CA of intrauterine tissues is increased in term spontaneous labor. However, RU486-induced preterm labor occurs in the absence of increased CA.

Loss-of-function mutations of EZH2, a catalytic component of polycomb repressive complex 2 (PRC2), are observed in ~\n10% of patients with myelodysplastic syndrome (MDS), but are rare in acute myeloid leukaemia (AML). Recent studies have shown that EZH2 mutations are often associated with RUNX1 mutations in MDS patients, although its pathological function remains to be addressed. Here we establish an MDS mouse model by transducing a RUNX1S291fs mutant into hematopoietic stem cells and subsequently deleting Ezh2. Ezh2 loss significantly promotes RUNX1S291fs-induced MDS. Despite their compromised proliferative capacity of RUNX1S291fs/Ezh2-null MDS cells, MDS bone marrow impairs normal hematopoietic cells via selectively activating inflammatory cytokine responses, thereby allowing propagation of MDS clones. In contrast, loss of Ezh2 prevents the transformation of AML via PRC1-mediated repression of Hoxa9. These findings provide a comprehensive picture of how Ezh2 loss collaborates with RUNX1 mutants in the pathogenesis of MDS in both cell autonomous and non-autonomous manners.

Background Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift. Methods Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD) 17, 20 and 22 (term gestation). We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays. Results We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif) ligand 2 (Ccl2) gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif) ligand 1/CXCL1, and CXCL10) were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22. Conclusion Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.