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Interstitial lung disease (ILD), as an adverse effect of certain drugs, leads to inflammation and damage in the walls of the alveoli, making it difficult for the alveoli to take up oxygen. Interstitial pneumonia with no identifiable cause is called idiopathic interstitial pneumonia (IIP), and, among the major IIPs, idiopathic pulmonary fibrosis (IPF) is diagnosed in about half of patients. Current treatment options are limited, among which the antifibrotic drugs nintedanib (Ofev) and pirfenidone (Pirespa) are the first-line drugs. In this study, we investigated the incidence of ILD possibly caused by antifibrotic agents using data from the Japanese Adverse Drug Event Report (JADER) database, a database of spontaneous adverse event reports published by the Pharmaceuticals and Medical Devices Agency (PMDA), and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), published by the FDA. We used the FAERS and JADER to detect the signals of adverse events on the basis of reporting odds ratios. The relationship between indications and adverse events was clarified by separating indications and adverse events using the spontaneous adverse event reporting database with novel drug involvement. Regarding the involvement of nintedanib and pirfenidone in the development of ILD, JADER and FAERS showed signals for both nintedanib and pirfenidone as suspect drugs, and no signals for nintedanib or pirfenidone as concomitant drug interactions were detected. We highlight this because there are only a few effective drugs for IPF, and effective and safe drug therapies should be implemented by taking into consideration drug-induced ILD.

Shared decision making (SDM) is a collaborative process in which patients and healthcare providers jointly make a medical decision. This cross-sectional study aimed to identify the facilitators and barriers to self-reported implementation of SDM in Japan, and to explore if there is effect modification by hospital types.A total of 129 physicians in Japan completed a questionnaire that asked about their perception of SDM based on SDM-Q-Doc and its facilitators and barriers, which corresponded to each construct of the integrated behavioral model (IBM). The association between facilitators and barriers and SDM-Q-doc score was assessed using linear regression analysis. Stratified analysis by hospital types was also performed.Significant facilitators included physicians' attitude, injunctive norm, intention and habit. Significant barriers included physicians' unfavorable attitude, lack of self-efficacy, knowledge, salience and experience. Moreover, experiential attitude (concerning patient characteristics), injunctive norm (concerning patient preferences), and physician's habit were significant facilitators for physicians working in university hospitals when compared to those working in municipal hospitals.The facilitators and barriers to implementing SDM in Japan were identified.More opportunities for training on SDM are needed to provide knowledge and skills, which will enhance salience and contribute their habitual practice.

An 89-year-old woman underwent examinations for leg edema. Blood tests indicated low nutrition and low pancreatic enzymes, and a stool examination indicated fatty stool. Computed tomography showed pleural effusion, ascites, and cystic lesions in the pancreatic head and mural nodules within the cysts. Pancreatic juice cytology revealed adenocarcinoma. The diagnosis was pancreatic exocrine insufficiency caused by intraductal papillary mucinous carcinoma. The patient did not wish to undergo surgery. Therefore, diuretics, component nutrients, and pancreatic exocrine replacement therapy using pancrelipase were initiated. After starting treatment, her leg edema, pleural effusion, and ascites disappeared, and her activities of daily living improved markedly.

We compared the outcomes of autologous stem cell transplantation (auto-SCT) with those of allogeneic stem cell transplantation (allo-SCT) from a human leukocyte antigen-matched related donor in patients with Philadelphia chromosome-negative B-lineage acute lymphoblastic leukemia (ALL). Newly diagnosed patients who underwent allo-SCT (n = 486) or auto-SCT (n = 99) after achieving first complete remission (CR) were included. Propensity score matching (PS) and an inverse probability of the treatment weighting (IPTW) analysis were applied to compensate for imbalances in baseline characteristics. The 5 years rates of overall survival (OS) among those in the PS-matched cohorts were 57% [95% confidence interval (CI) 46-67%] for those who received allo-SCT and 44% (95% CI 33-54%) for those who received auto-SCT. Multivariable, propensity score-matched, and IPTW analyses all revealed no statistically significant differences in OS between the two groups [hazard ratios (HR) 0.81, 95% CI 0.53-1.27, p = 0.36; HR 0.84, 95% CI 0.40-1.78, p = 0.65; HR 0.71, 95% CI 0.25-2.02, p = 0.53, respectively]. Prospective trials that include autologous transplantation as a treatment option are needed to examine the potential of autologous transplantation.

An 80-year-old man underwent follow-up examinations after endoscopic submucosal dissection (ESD) for esophageal cancer. Computed tomography (CT) showed enlarged lymph nodes of the right recurrent nerve. The patient had esophageal stenosis due to repeated ESD for multiple esophageal tumors. The stenosis made the passage of an endoscopic ultrasound (EUS) scope through the esophagus difficult. Thus, an endobronchial ultrasound bronchoscope, which had a thinner diameter than that of the EUS scope, was used for transesophageal endoscopic ultrasound with bronchoscope-guided fine-needle aspiration. This technique led to the diagnosis of mediastinal lymph node metastasis of esophageal cancer.

Radial artery is the preferred site for cannulation. Recently, the ulnar artery was chosen as an alternative in adults.We aimed to measure the diameter and depth of the ulnar and radial arteries using ultrasound, and our secondary purpose was to evaluate their anatomical position using a near-infrared transcutaneous illumination device.Forty-eight children (age range: 0-144 months) were assigned to the following groups: group Infant (aged12 months), group Preschool (aged ≤12 to72 months), and group School (aged ≥72 months). The diameter, depth, and position of the ulnar and radial arteries were compared between groups.There was no significant difference between the diameters of the ulnar and radial arteries. In group Infant, group Preschool, and group School, mean diameters of the ulnar artery were 1.27 ± 0.15 mm, 1.62 ± 0.27 mm, and 2.03 ± 0.28 mm, respectively, and the radial artery were 1.29 ± 0.15 mm, 1.69 ± 0.27 mm, and 2.06 ± 0.29 mm, respectively. The corresponding differences between the diameters of ulnar and radial arteries were -0.02 mm, -0.07 mm, and -0.02 mm [95% CI -0.16 mm to 0.12 mm, -0.25 mm to 0.11 mm, and -0.25 mm to 0.21 mm; p = .776, p = .411, and p = .852]. In groups Preschool and School, the ulnar artery was at the recommended depth of 2-4 mm for arterial cannulation compared with the radial artery. In the Infant, Preschool, and School age groups, the ulnar and radial arteries were at the recommended depth of 2-4 mm for arterial cannulation in 70.0%, 100.0%, 93.8%, and 80.0%, 65.0%, and 50.0% of the cases, respectively. (difference: -10.0%, 35.0%, and 43.8%, 95%; CI -43.4% to 23.4%, 14.1% to 55.9%, and 19.4% to 68.1%, respectively).The ulnar artery can be considered a promising alternative to the radial artery for facilitating arterial cannulation in children.

The effectiveness of public-use of automated external defibrillators in reducing the number of sudden cardiac death (SCD) cases at the national level is largely unknown. Our study aimed to evaluate whether the nationwide introduction of public-access-defibrillation (PAD) in 2004 affected the trend of annual sudden cardiac death (SCD) rates in Japan.The number of nationwide SCDs occurring in people aged five years and older was extracted from Japanese demographic statistics (1995-2015). Segmented regression analysis was performed on the interrupted time series data stratified by age and sex to evaluate changes in trends of rates of annual SCDs after the PAD introduction in Japan.After the PAD introduction in 2004, we observed a significant decrease in trends of annual SCD rates for those aged 5-19 years (the ratio of trends between pre and post PAD introduction (RT) = 0.886, 95%CI: 0.801 to 0.980), 20-34 years (RT = 0.932; 95%CI: 0.906, 0.958), 35-49 years (RT = 0.953; 95%CI: 0.929, 0.977) and 50-64 years (RT = 0.971; 95%CI: 0.971, 0.991). However, the decrease was not observed for those aged 65 years and older. In the age and sex stratified analysis, there was a significant decrease in RT among males aged 5-64 years, and among females 35-49 years.The nationwide trend of annual rate of SCDs between 5 and 64 years old significantly decreased after the introduction of PAD in 2004 in Japan. Further, the reduction was more evident in males.

Background Arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is a rare autosomal recessive disorder caused by mutations in VPS33B (ARCS1) and VIPAS39 (ARCS2). As per literature, most patients with ARCS died of persistent infections and bleeding by the age of 1 year. We report the first Japanese cases with ARCS1 and ARCS2 who presented with mild phenotypes and were diagnosed via genetic testing. Case presentation Case 1: A 6-year-old boy born to nonconsanguineous Japanese parents presented with jaundice and normal serum gamma-glutamyl transferase (GGT) levels, proteinuria, bilateral nerve deafness, motor delay, failure to thrive, and persistent pruritus. After cochlear implantation for deafness at the age of 2 years, despite a normal platelet count and prothrombin time-international normalized ratio, the patient presented with persistent bleeding that required hematoma removal. Although he did not show any obvious signs of arthrogryposis, he was suspected to have ARCS based on other symptoms. Compound heterozygous mutations in VPS33B were identified using targeted next-generation sequencing (NGS), which resulted in no protein expression. Case 2: A 7-month-old boy, the younger brother of case 1, presented with bilateral deafness, renal tubular dysfunction, failure to thrive, and mild cholestasis. He had the same mutations that were identified in his brother’s VPS33B. Case 3: A 24-year-old man born to nonconsanguineous Japanese parents was suspected to have progressive familial intrahepatic cholestasis 1 (PFIC1) in his childhood on the basis of low GGT cholestasis, renal tubular dysfunction, sensory deafness, mental retardation, and persistent itching. A liver biopsy performed at the age of 16 years showed findings that were consistent with PFIC1. He developed anemia owing to intraperitoneal hemorrhage from a peripheral intrahepatic artery the day after the biopsy, and transcatheter arterial embolization was required. ARCS2 was diagnosed using targeted NGS, which identified novel compound heterozygous mutations in VIPAS39. Conclusions The first Japanese cases of ARCS1 and ARCS2 diagnosed using genetic tests were reported in this study. These cases are milder than those previously reported. For patients with ARCS, invasive procedures should be performed with meticulous care to prevent bleeding.

A significant number of reported COVID-19 cases can be traced back to superspreader events (SSEs), where a disproportionally large number of secondary cases relative to the standard reproductive rate, R0, are initiated. Although a superspreader is an individual who undergoes more viral shedding and transmission than others, it appears likely that environmental factors have a substantial role in SSEs. We categorise SSEs into two distinct groups: 'societal' and 'isolated' SSEs.We summarise SSEs that have occurred using multiple databases that have been cross referenced to ensure numbers are as reliable as we can ascertain. This enables more focussed and productive control of the current pandemic and future pandemics, especially as countries and regions ease lockdown restrictions.'Societal' SSEs pose a significant threat as members of the event are free to mingle and can infect individuals in the outside community. On the other hand, 'isolated' SSEs can be effectively quarantined as only a few individuals can transmit the virus from the isolated community to the outside community, therefore lowering further societal infection.

This study was conducted to characterize lymphoma occurring during pregnancy and to investigate the outcomes of the patients and the fetuses.Clinical data were gathered retrospectively from 29 patients at 13 participating institutions, and data from 28 eligible patients were analyzed.Six (21%) patients had Hodgkin lymphoma (HL) and 22 (79%) patients had non-Hodgkin lymphoma (NHL). All patients with HL presented with lymphadenopathy, but 15 (68%) of the 22 patients with NHL presented with extranodal sites only. At the median follow-up period of 1325 (range 6-4461) days, the 5-year overall survival rate was 63% for patients with NHL and 100% for patients with HL. Three of the 13 patients who received chemotherapy during pregnancy (23%) developed Pneumocystis jiroveci pneumonia (PCP). There was 1 intrauterine fetal death, 1 spontaneous abortion in the first trimester, and 15 (54%) preterm births.This study showed a higher proportion of NHL than HL during pregnancy in Japan, which was inconsistent with the proportions observed in Western countries. The high incidence of maternal PCP and preterm birth suggested the need for improvements in our management of lymphoma during pregnancy.

Objectives Despite relatively poor health outcomes of migrants in Japan, little is known about their access to reproductive healthcare. We conducted qualitative research to explore perceived barriers to access, with a specific focus on contraceptive services, and their consequences among Myanmar migrants in Japan. Study design From January to April 2020, we conducted 17 in-depth interviews with Myanmar migrant women and 4 key informant interviews with Myanmar interpreters working in health services in Tokyo, Saitama, and Chiba prefectures. We transcribed interviews and coded them in ATLAS.ti primarily using a deductive approach based on the 5 components of Levesque et al.'s conceptual framework of healthcare access. We also used inductive coding to allow for other themes outside of the framework to emerge. Results Among the 17 women, almost half stated that they were using periodic abstinence based on the presumed fertility window or the withdrawal method. Furthermore, slightly over half of the women had a history of unintended pregnancy. Language barriers, limited health information sources, cultural and health beliefs and financial factors played important roles in access to contraceptives among Myanmar migrant women. Women described how these barriers resulted in feeling lack of control over family planning and unintended pregnancies. Conclusions Findings suggested that Myanmar migrants in Japan are faced with limited contraceptive access. Language barriers, limited information sources, health beliefs, and cultural and financial factors affected access. Implications Results suggest that to increase public awareness and contraceptive access of Myanmar women in Japan nonprofit support programs would benefit from the help of existing social networks of Myanmar migrants, interpreters, and Japanese doctors and researchers in reproductive health.

The coronavirus disease 2019 (COVID-19) pandemic necessitated down-scaling of in-hospital care to prohibit the spread of severe acute respiratory syndrome-coronavirus-2. We (1) assessed patient perceptions on quality of care by telesurvey (cohort 1) and written questionnaire (cohort 2), and (2) analyzed trends in elective and nonelective admissions before (December 2019 to February 2020) and during (March to May 2020) the COVID-19 pandemic in Austria. A total of 279 outpatients were recruited into cohort 1 and 138 patients into cohort 2. All admissions from December 2019 to May 2020 to the Division of Gastroenterology/Hepatology at the Vienna General Hospital were analyzed. A total of 32.6% (n = 91 of 279) of cohort 1 and 72.5% (n = 95 of 131) of cohort 2 had telemedical contact, whereas 59.5% (n = 166 of 279) and 68.2% (n = 90 of 132) had face-to-face visits. A total of 24.1% (n = 32 of 133) needed acute medical help during health care restrictions; however, 57.3% (n = 51 of 89) reported that contacting their physician during COVID-19 was difficult or impossible. Patient-reported satisfaction with treatment decreased significantly during restrictions in cohort 1 (visual analog scale [VAS] 0-10: 9.0 ± 1.6 to 8.6 ± 2.2; P

ObjectiveSince introduction of the programme in April 2021, COVID-19 vaccine uptake has been low at less than 20%. This study explored community members’ and health workers’ perspectives on the COVID-19 vaccine uptake and its influencing factors in Zambia.Study designA qualitative study employing focus group discussions (FGDs) and in-depth interviews (IDIs).Study settingSixteen primary healthcare facilities selected from Lusaka, Copperbelt, Central and Southern provinces.ParticipantsA total of 32 FGDs comprising local community members and 30 IDIs including health workers, traditional, religious and civic leaders (n=272). FGDs were separated based on age (youth and adults), sex (male and female) and place of residence (urban and rural).ResultsBoth FGD and IDI participants agreed that vaccine uptake was low. Limited knowledge, access to information, myths and misconceptions, negative attitude, low-risk perception and supply in remote areas affected vaccine uptake. Overall, FGD participants expressed limited knowledge about the COVID-19 vaccine compared with health workers. Further, FGD participants from urban sites were more aware about the vaccine than those from rural areas. Health workers perceived the vaccine to be beneficial; the benefits included prevention of infection and limiting the severity of the disease. Moreover, FGD participants from urban sites expressed a negative attitude towards the vaccine. They believed the vaccine conferred no benefits. By contrast, participants from rural communities had mixed views; they needed more information about the vaccine benefits. Participants’ attitude seems to have been influenced by personal or family experience with the COVID-19 disease or vaccination; those who had experienced the disease had a more positive attitude. In contrast, most young people believed they were not at risk of the COVID-19 disease. Misinformation from social media influenced their attitude.ConclusionThese results provide starting points for future policies and interventions for increasing COVID-19 vaccine uptake.

A multimethod archaeometry study (zooarchaeological, isotopic, ancient DNA, paleobotanical, and radiocarbon dating) of a spider monkey sacrificed in the ceremonial center of Teotihuacan, Mexico (1 to 550 CE) is interpreted as a diplomatic gift exchange with neighboring Maya. Not only does this spider monkey provide the earliest known instance of primate translocation and captivity in Mesoamerica, it helps date incipient modes of interregional diplomacy between two major powers during Early Classic Mesoamerica: Teotihuacan and the Maya. Details of human–primate interaction include age at capture and transport (before ∼3 y of age), captive duration (over 2 y), anthropogenic diet (staple was maize, though secondary resources unique to anthropogenic diet including arrowroot and chili pepper were also found), context of sacrifice (tethered and associated with complete golden eagle and an array of other statecrafts), and general site context (including presence of Maya vessels and Maya-style murals). The timing of the spider monkey’s sacrifice (250 to 300 CE) and its life history suggest a reconsideration of epigraphically attested militaristic involvement of Teotihuacan at certain Maya sites. We propose that a period of more multilateral and fluid ritual exchange with Maya dignitaries preceded the Teotihuacan state’s eventual ascent to prominence.

Adipocyte-rich omentum offers "good soil" for disseminating ovarian cancer (OvCa), contributing to therapeutic difficulty. However, little is understood about the association between adipocytes and tumor growth at peritoneal dissemination site. Herein, we report the induction of adipocyte dedifferentiation by OvCa cells and pro-tumorigenic effects of resulted adipocyte-derived fibroblasts. We confirmed that malignant ascites promoted the dedifferentiation of the primary human adipocytes obtained from surgical omental specimen into omental adipocyte-derived fibroblast (O-ADF) that possess both mesenchymal stem cell and myofibroblast-like features. This promotion of dedifferentiation by malignant ascites was blocked by addition of Wnt signaling inhibitor. The effects of dedifferentiated adipocytes in proliferation and migration of OvCa cells were analyzed with in vitro co-culturing experimental models and in vivo mice model, and we demonstrated that OvCa cell lines showed enhanced proliferative characteristics, as well as increased migratory abilities upon co-culturing with O-ADF. Additionally, exogenous transforming growth factor-β1 augmented desmoplastic morphological change of O-ADF, leading to higher proliferative ability. Our results suggest that OvCa cells promote dedifferentiation of peritoneal adipocytes by activating Wnt/β-catenin signaling, and generated O-ADFs exhibit pro-tumoral hallmarks. This article is protected by copyright. All rights reserved.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Their diagnostic marker value was explored in 41 AAA patients and 38 healthy controls. The NET parameter citrullinated histone H3 (citH3) was then validated in 63 AAA patients and 63 controls matched for cardiovascular disease. The prognostic marker potential was investigated in 54 observation periods of AAA growth over 6 months. NETs were further assessed in conditioned medium and sections of aortic tissue. CitH3 was found to be increased in blood (median 362 vs 304 ng/mL, P = 0.004) and aortic tissue (50 vs 1.5 ng/mg, P0.001) of AAA patients compared to healthy controls and accumulated in the intraluminal thrombus (629 ng/mg). The diagnostic potential of citH3 ranged at 0.705 area under the ROC curve (AUROC) and was validated with the independent sample set. Furthermore, plasma citH3 predicted AAA growth over the next 6 months (AUROC: 0.707, P = 0.015) and dropped significantly after surgical aneurysm repair. In an angiotensin II - based mouse model of experimental AAA, an inhibitor of histone citrullination was applied to block NET formation and AAA progression. Of note, further growth of an established aneurysm was prevented in mice treated with the NET inhibitor (P = 0.040). In conclusion, histone citrullination represents a promising AAA biomarker and potential therapeutic target to control disease progression.

IntroductionLittle is known about the clinical course of COVID-19 following mild symptoms, and how the disease affects the survivors over time. Moreover, information on the severity of the long-term health effects as well as the associated risk factors is scant. This study aims to determine the short, intermediate and long-term health effects of COVID-19 on the survivors and the associated risk factors.Methods and analysisWe propose conducting a 24-month prospective quantitative study in 10 health facilities (2 specialist, 3 regional, 2 mission and 3 subdistrict hospitals) from Lusaka and Southern Province of Zambia. Health facilities will be those which served as COVID-19 treatment centres during the third wave (June–August 2021). Study participants will comprise a randomly selected cohort of 450 COVID-19 survivors who had mild or no symptoms (80%) and severe cases (20%). Using a questionnaire, respondent demographic, clinical and laboratory data will be collected at baseline and at a 3-month interval for 18 months using a questionnaire. Respondents’ medical records will be reviewed and data collected using a checklist. Descriptive statistics will be computed to summarise respondents’ characteristics and clinical outcomes. Bivariate analysis (Χ2 and t-test) will be conducted to test the association between respondent characteristics and clinical outcomes. Multivariate logistic regression analysis will be run to determine the risk factors for short, intermediate and long-term health effects; adjusted ORs will be computed to test the strength of the association (pEthics and disseminationEthical approval was obtained from the University of Zambia Biomedical Research and the National Health Research Authority. Results will be disseminated to key stakeholders in Zambia, international open-access peer-reviewed journals, websites and international conferences, and likely lead to design of evidence-informed strategies to mitigate health effects of COVID-19 on survivors.

In the face of unknown risks, including the coronavirus disease 2019 (COVID-19) pandemic, we tend to have stigmatized perceptions. The current study aimed to examine the association of social engagements with the level of stigmatization of COVID-19 infection among the general population. The data of 429 participants of the Utsunomiya COVID-19 seroprevalence neighborhood association (U-CORONA) study, a population-based cohort study conducted in Utsunomiya City, Japan, were analyzed. Their stigmatized perception of people with COVID-19 infection was evaluated via a questionnaire for the situation if they or others in their community were to get infected. The association between social engagements (community social capital, social network diversity, and social network size) and stigmatization were analyzed by a multiple linear regression model with generalized estimating equations. Overall, females reported a higher stigmatized perception of people with COVID-19 than males. Lower education and depressive symptoms were also positively associated with higher stigmatization, while age, household income, and comorbidities were not. People with higher community social capital reported lower stigmatization (B = −0.69, 95% CI = −1.23 to −0.16), while social network diversity and social network size did not show an association with stigmatization. We found an association between community social capital and stigmatization, suggesting that enhancing their community social capital, but not social network diversity and size, has the potential to mitigate the levels of stigmatization.

Context Passive smoking in childhood has been reported to be associated with dyslipidemia in Western countries. However, this association in Asian countries remains unclear. Further, no study has investigated the sex difference of the association. Objective This study aimed to elucidate the association between passive smoking and dyslipidemia in adolescent boys and girls in Japan. Methods We used a cross-sectional data of junior high school students in the Adachi Child Health Impact of Living Difficulty (A-CHILD) study in Adachi City, Tokyo, Japan in 2016 and 2018. Of the 1431 available students, 1166 students and their parents responded to the survey, including frequency of passive smoking (response rate 81.5%). We assessed dyslipidemia using total cholesterol (TC) levels, low-density lipoprotein cholesterol (LDL-C) levels and high-density lipoprotein cholesterol (HDL-C) levels. The association between passive smoking and dyslipidemia was evaluated by using multivariate regression analyses adjusted for socioeconomic status and lifestyle factors stratified by boys (N = 564) and girls (N = 602). Results Among boys, HDL-C levels were significantly lower if exposed to passive smoking frequently, compared with those not exposed (β = −3.19; 95% CI, −5.84 to −0.55). However, this trend does not hold true among girls. Passive smoking was not associated with TC levels and LDL-C levels in either boys or girls. Conclusion We found that exposure to passive smoking was associated with HDL-C level among boys in Japan, but not in girls. Further longitudinal study is needed to confirm the association between passive smoking and dyslipidemia among boys in Japan.

Background: This study aimed to determine the relationship between exercise performance and spinal function based on clenching strength. Hypothesis: Low-intensity clenching contributes to joint movement, whereas high-intensity clenching contributes to joint fixation. Study Design: Randomized crossover trial. Level of Evidence: Level 3. Methods: Two experiments were conducted using 2 groups of 20 healthy adults. The 4 clenching conditions in experiment 1 were 0%, 12.5%, 25%, and 50% of the maximum voluntary contraction (MVC) of the masseter muscle. Experiment 2 consisted of 3 conditions: no-bite condition, moderate effort, and maximum effort (max condition). In experiment 1, spinal function and ankle dorsiflexion tasks were measured for each clenching condition, and the ankle dorsiflexion task was measured in experiment 2. Regarding spinal function, we measured spinal reciprocal inhibition (RI) and excitability of spinal anterior horn cells. For the ankle dorsiflexion task, ankle dorsiflexion MVC was performed for 3 seconds under each clenching condition. The items analyzed were reaction time, peak ankle dorsiflexion torque, and soleus (Sol)/tibialis anterior (TA) electromyography (EMG) ratio. Results: The results of experiment 1 illustrated that RI was significantly attenuated or eliminated with increasing clenching strength (>25% MVC). Spinal anterior horn cell excitability increased significantly with increasing clenching strength. The peak torque was significantly higher at 50% MVC than that at 0% MVC. In experiment 2, the peak torque was significantly higher under moderate and max conditions than no-bite condition, and the Sol/TA EMG ratio was significantly higher under max condition than that under moderate condition. Conclusion/Clinical Relevance: The results illustrated that during high-strength clenching (≥50% MVC), antagonist muscles are activated simultaneously to increase muscle strength. High-strength clenching improved kinetic performance (joint fixation), whereas low-strength clenching (

Purpose Total skin electron beam therapy (TSEBT) is useful for primary cutaneous lymphoma. However, helical skin radiation therapy (HSRT) using tomotherapy may avoid the complexity and uncertainty of TSEBT. Methods and Materials All patients with primary cutaneous lymphoma who underwent HSRT at our hospital between June 2015 and July 2019 were investigated, including 7 patients registered in a clinical trial approved by an institutional review board (ID UMIN000022142). HSRT was performed in 3 partitioned skin areas: head and neck, trunk and arms, and legs. Results A total of 24 patients with 53 skin areas (including 8 patients with 24 skin areas who had undergone sequential total skin irradiation), with a median follow-up time of 13 months (range, 2-50), were investigated. Twenty patients (83.3%) had mycosis fungoides (MF). For 41 of 53 (77.4%) cases, a dose of 20 Gy in 10 fractions was used. The overall response rate in the treated fields of each HSRT in patients with MF was 100%, including 38 (80.9%) complete response, 4 (8.5%) good partial response, and 5 (10.6%) partial response. Eight patients with MF who underwent sequential total skin irradiation showed a 100% complete response. For patients with MF, the median survival time after a first round of HSRT was 22 months (95% confidence interval [CI], 13.6-30.4 months), the median response duration of each HSRT was 5 months (95% CI, 3.67-6.32 months), and the median time to in-field reirradiation for each HSRT was 15 months (95% CI, 9.76-20.24 months). Bone marrow suppression (grade ≥3) often occurred (94.1%) with HSRT on trunk and arm skin. An early patient died of HSRT-caused grade 5 leukopenia. Conclusions HSRT targeting trunk and arm skin induced severe bone marrow suppression that led to a temporary palliative effect. TSEBT should still be considered standard treatment for primary cutaneous lymphoma covering the total body surface area.

BACKGROUND Epidural tunneling could help with prolonged catheterization and be effective in preventing infection and dislodgement. However, epidural tunneling techniques carry a risk of catheter shear or needlestick injuries. AIMS This study aimed to examine the safety of our epidural tunneling technique in terms of catheter shear. METHODS This study was designed as a double-blinded, single-crossover, in vitro study. Each of the operators performed two techniques to create a subcutaneous tunnel. We compared outcomes between the control tunneling technique (group C) and our improved technique (group I). Microscopic findings of catheter shear were assessed as the primary outcome. Secondary outcomes included the tension and displacement required to break the epidural catheter and the frequency of catheter breakage due to catheter shear. Data were analyzed using the Fisher's exact test and Mann-Whitney U test. A p-value of

Collagenofibrotic glomerulopathy or LMX1B-associated nephropathy is a rare disease in which type III collagen accumulates in the glomeruli. We herein report a 64-year-old Japanese woman with an elevated serum creatinine level and persistent proteinuria for 7 years. An electron microscopic study using tannic acid showed curved and frayed collagen fibers within mesangial and subendothelial regions compatible with type III collagen depositions. The distribution of type IV collagen α1-6 chains was normal. Since no pathogenic mutations were identified in the LMX1B gene, she was diagnosed with collagenofibrotic glomerulopathy and treated with angiotensin II receptor blocker and calcium antagonist to control her blood pressure.

Globally, unintentional injuries are one of the leading causes of infant death. Established risk factors for injuries during infancy include single parent households, socioeconomic disadvantage and maternal postpartum depression. We sought to examine whether maternal working status is associated with unintentional injury among infants in Japan. We used data from an original questionnaire targeting mothers who participated in a 3 or 4-month health check-up program in Aichi prefecture, Japan. Experience of any type of unintentional injury was used as the primary outcome, and we also examined the experience of “falls” and “near-drowning” as secondary outcomes. We conducted multivariable logistic regression analysis, adjusting for covariates. We also performed propensity score matching in order to balance covariates between paid employment and unpaid employment groups. Among 6,465 valid responses (response rate, 67%), 9.8% of infants experienced unintentional injuries. After matching on propensity for maternal employment (based on 26 covariates), we found that infants of mothers in paid employment were 1.35 times (95% CI: 1.04–1.74) more likely to experience injures, including 1.60 times higher likelihood of falls (95% CI: 1.14–2.24). Near-drowning was not significantly associated with maternal employment. We also found that father’s employment status was positively associated with risk of falls. Both multivariable logistic analysis and propensity score matching analysis revealed that maternal paid employment status was associated with unintentional injuries among Japanese infants. To prevent infant injuries, comprehensive support for working families should be considered.

Chromatin remodelling is an important process in neural development and is related to autism spectrum disorder (ASD) and schizophrenia (SCZ) aetiology. To further elucidate the involvement of chromatin remodelling genes in the genetic aetiology of ASD and SCZ in the Japanese population, we performed a case-control study. Targeted sequencing was conducted on coding regions of four BAF chromatin remodelling complex genes

Using a plane‐parallel advanced Markus ionization chamber and a stack of water‐equivalent solid phantom blocks, percentage surface and build‐up doses of Elekta 6 MV flattening filter (FF) and flattening‐filter‐free (FFF) beams were measured as a function of the phantom depth for field sizes ranging from 2 × 2 to 10 × 10 cm2. It was found that the dose difference between the FF and the FFF beams was relatively small. The maximum dose difference between the FF and the FFF beams was 4.4% at a depth of 1 mm for a field size of 2 × 2 cm2. The dose difference was gradually decreased while the field size was increased up to 10 × 10 cm2. The measured data were also compared to published Varian FF and FFF data, suggesting that the percentage surface and build‐up doses as well as the percentage dose difference between FF and FFF beams by our Elekta linac were smaller than those by the Varian linac.

This study aimed to reconstruct the dose distribution of single fraction of stereotactic body radiotherapy for patients with prostate cancer using cone-beam computed tomography (CBCT) and a log file during volumetric-modulated arc therapy (VMAT) delivery with flattening-filter-free (FFF) mode. Twenty patients with clinically localized prostate cancer were treated with FFF-VMAT, and projection images for in-treatment CBCT (iCBCT) imaging were concomitantly acquired with a log file. A D95 dose of 36.25 Gy in five fractions was prescribed to each planning target volume (PTV) on each treatment planning CT (pCT). Deformed pCT (dCT) was obtained from the iCBCT using a hybrid deformable image registration algorithm. Dose distributions on the dCT were calculated using Pinnacle3 v9.10 by converting the log file data to Pinnacle3 data format using an in-house software. Dose warping was performed by referring to deformation vector fields calculated from pCT and dCT. Reconstructed dose distribution was compared with that of the original plan. Dose differences between the original and reconstructed dose distributions were within 3% at the isocenter and observed in PTV and organ-at-risk (OAR) regions. Differences in OAR regions were relatively larger than those in the PTV, presumably because OARs were more deformed than the PTV. Therefore, our method can be used successfully to reconstruct the dose distributions of one fraction using iCBCT and a log file during FFF-VMAT delivery.

With increasing focus on the importance of long-term survivorship care after allogeneic hematopoietic cell transplantation (allo-HCT), more institutions have been establishing long-term follow-up (LTFU) clinics. Currently, however, with varying volumes of HCT procedures and resources, there is no standardized operation of these clinics in HCT centers. We conducted a nationwide questionnaire survey to characterize the current operation of LTFU clinics in Japan. We targeted 271 HCT centers (189 adult and 82 pediatric) that registered allo-HCT cases to the national transplant registry database. The response rate was 69%, and 117 of the 188 participating centers (62%) had an established LTFU clinic. The most frequent reason cited for not operating an LTFU clinic was a "lack of human resources," especially nurses. Most centers with an LTFU clinic targeted allo-HCT recipients, although autologous HCT survivors were followed up at 18% of adult centers and 48% of pediatric centers. Ninety-two percent of centers did not terminate LTFU at a specific time point, and 56% recommended that patients visit the LTFU clinic beyond 5 years after HCT. Fifteen of 20 pediatric centers indicated that they did not routinely refer survivors who underwent HCT at a young age to an adult HCT center for their adulthood LTFU. We found that staffing and standard practices varied widely among centers, and that most centers continued to see long-term HCT survivors at their own outpatient clinics. The development of common LTFU tools may help standardize LTFU practices and facilitate efficient transitions.

Objective The opioid epidemic in the United States increasingly affects women of reproductive age and has resulted in a rise in concurrent polydrug use. The objective of this study was to investigate the effect of this polydrug use on preterm birth in a multiethnic birth cohort. Methods We analyzed data from 8261 mothers enrolled in the Boston Birth Cohort from 1998 to 2018 in Boston, Massachusetts. We grouped substances used during pregnancy based on their primary effects (stimulant or depressant) and assessed independent and combined associations with smoking on preterm birth. Results Of 8261 mothers, 131 used stimulant drugs and 193 used depressant drugs during pregnancy. The preterm birth rate was 27.5% (2271 of 8261) in the sample. Mothers who smoked had 35% increased odds of preterm birth across adjusted models. Mothers who used stimulant drugs without smoking were not at increased risk of preterm delivery compared with mothers who used neither (odds ratio [OR] = 0.69; 95% confidence interval [CI], 0.19-1.98), whereas mothers who used depressant drugs without smoking had more than twice the odds of having preterm delivery (OR = 2.31; 95% CI, 1.19-4.44), and infants were at risk of a 1-week reduction in gestational age (OR = −1.05; 95% CI, −2.07 to −0.03). Concurrently smoking and using depressant drugs was associated with increased odds of preterm birth (OR = 1.83; 95% CI, 1.28-2.61), as was concurrently smoking and using stimulant drugs (OR = 1.73; 95% CI, 1.14-2.59). Conclusions Using stimulant drugs and depressant drugs during pregnancy is a risk factor for preterm birth. The individual and combined effects of using these drugs with smoking must be considered together to reduce the risk of preterm birth in the United States.

Purpose The purpose of this study was to estimate the prevalence of subjects with chronic cough and phlegm and describe their characteristics including the presence or absence of airflow limitation among the general population in Japan. Subjects and methods This was an observational cross-sectional survey targeting multiple regions of Japan. Subjects aged 40 years or above who were undergoing comprehensive health examination were recruited. The existence of chronic cough and phlegm, airflow limitation, and treatment for respiratory diseases were examined. Chronic cough and phlegm were defined as having both symptoms for at least 3 months of the year and for at least 2 consecutive years, or as receiving any treatment for chronic bronchitis at the time of recruitment. Airflow limitation was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) less than 0.7. Results In a total of 22,293 subjects, 380 subjects (1.7%) had chronic cough and phlegm. Among these 380 subjects, 21.8% received treatment for a respiratory disease, and 11.6% had airflow limitation. Compared to subjects without both chronic cough and phlegm but with airflow limitation, subjects with chronic cough and phlegm without airflow limitation were younger, more likely to be current smokers (39.6%), and had higher total scores on a chronic obstructive pulmonary disease (COPD) assessment test (CAT). Scores of CAT questions 1-4 (cough, phlegm, chest tightness, breathlessness, respectively) were higher in subjects with chronic cough and phlegm regardless of airflow limitation. Conclusion This study demonstrated that subjects identified to have chronic cough and phlegm in comprehensive health examination settings were symptomatic, while most of them did not receive any treatment for respiratory diseases and did not have airflow limitation. Screening subjects for chronic cough and phlegm in a comprehensive health examination followed by a detailed examination of screened subjects could be an effective approach for better management of chronic cough and phlegm. Smoking cessation should be included in the management, in consideration that around 40% of subjects with chronic cough and phlegm were current smokers.

Folate receptor alpha (FRα) is overexpressed in >80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as a first‐line chemotherapeutic agent in combination with platinum‐based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor‐EL, a traditional formulation vehicle that causes significant side effects, including neutropenia. Several years ago, folate‐appended β‐CyD (Fol‐c1‐β‐CyD) was developed as an FRα‐targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol‐c1‐β‐CyD (PTX/Fol‐c1‐β‐CyD) in EOC‐derived cell lines. We found that PTX/Fol‐c1‐β‐CyD killed not only FRα‐expressing cells but also FRα‐negative cells. In the FRα‐negative A2780 cells, knockdown of proton‐coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol‐c1‐β‐CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or proton‐coupled folate transporter (PCFT) decreased the cytotoxicity of PTX/Fol‐c1‐β‐CyD in FRα‐expressing SK‐OV‐3 cells. Furthermore, the cytotoxicity of PTX/Fol‐c1‐β‐CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα‐expressing or PCFT‐expressing EOC cells, intraperitoneal administration of PTX/Fol‐c1‐β‐CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol‐c1‐β‐CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity., To date, folate‐appended drug carriers or antifolates have been considered to target folate receptor alpha (FRa). In this report, we show that a cyclodextrin‐based folate‐appended drug carrier targets proton‐coupled folate transporter (PCFT) as well as FRa. For the FRa‐independent mechanism, PCFT is necessary but not enough for uptake of the folate‐appended drug carrier. The folate‐appended drug carrier suppressed the growth of ovarian cancer cells expressing FRa or PCFT in the mouse peritoneal cavity.

Aims Although distinct DNA methylation patterns have been reported, its localization and roles remain to be defined in heart failure. We investigated the cellular and subcellular localization of DNA methylation and its pathophysiological significance in human failing hearts. Methods and results Using left ventricular (LV) endomyocardial biopsy specimens from 75 patients with dilated cardiomyopathy (DCM; age: 58 ± 14 years old, %female: 32%) and 20 patients without heart failure (controls; age: 56 ± 17 years old, %female: 45%), we performed immunohistochemistry and immunoelectron microscopy for methylated DNA, 5‐methylcytosine (5‐mC). We next investigated possible relations of the incidence of 5‐mC‐positive (%5‐mC+) cardiomyocytes with clinicopathological parameters. Immunopositivity for 5‐mC was detected in the cardiomyocytes and other cell types. The %5‐mC+ cardiomyocytes was significantly greater in DCM hearts than in controls (57 ± 13% in DCM vs. 25 ± 12% in controls, P < 0.0001). The localization of 5‐mC immunopositivity in cardiomyocyte nuclei coincided well with that of heterochromatin, as confirmed by immunoelectron microscopy. Substantial DNA methylation was also observed in interstitial non‐cardiomyocytes, but the incidences did not differ between control and DCM hearts (39 ± 7.9% in DCM vs. 41 ± 10% in controls, P = 0.4099). In DCM patients, the %5‐mC+ cardiomyocytes showed a significant inverse correlation with LV functional parameters such as heart rate (r = 0.2391, P = 0.0388), end‐diastolic pressure (r = 0.2397, P = 0.0397), and ejection fraction (r = −0.2917, P = 0.0111) and a positive correlation with LV dilatation (volume index at diastole; r = 0.2442, P = 0.0347; and volume index at systole; r = 0.3136, P = 0.0062) and LV hypertrophy (mass index; r = 0.2287, P = 0.0484)—that is, LV remodelling parameters. No significant correlations between DNA methylation and the histological parameters of the biopsies, including cardiomyocyte hypertrophy, fibrosis, and inflammatory cell infiltration, were noted. Conclusions The present study revealed increased nuclear DNA methylation in cardiomyocytes, but not other cell types, from DCM hearts, with predominant localization in the heterochromatin. Its significant relations with LV functional and remodelling parameters imply a pathophysiological significance of DNA methylation in heart failure.

Objective Dental students follow different academic performance trajectories in response to increasing study load, based on individual and school factors. Group-based trajectory modeling is useful for clarifying the underlying trajectory patterns of students' academic performance and its determinants. To our knowledge, no studies have used group-based trajectory modeling to examine the effects of individual and school factors on academic performance trajectories in dental students. The objective of this study was to examine the effects of individual and school factors on academic performance trajectories in Japanese dental students using group-based trajectory modeling. Methods The analytical sample consists of 103 dental students admitted to Tokyo Medical and Dental University, Tokyo, Japan, in 2013 and 2014. Students' academic performance was assessed by biannual grade point average (GPA) score and GPA in the preclinical phase (second to fourth grade) was used for this study. We used group-based trajectory modeling to categorize students' GPA trajectories into different groups. A multinomial logistic regression model was fit to examine associations between students' individual and school factors, and odds of being assigned to certain GPA groups. Results GPA trajectories of dental students were classified into 4 different groups. Students' past academic performance in high school was associated with lower GPA trajectories and withdrawal or repeating years. Males were significantly associated with lower GPA trajectories and withdrawal or repeating years, even after adjusting for past academic performance. Conclusions Past lower academic performance and being male were positively associated with lower academic performance trajectories in Japanese dental students.

During the mobile clinic activities in Tak Province, Thailand, Paragonimus sp. eggs were found in a fecal sample of a 72-year-old Karen resident. Paragonimus DNA was amplified from the stool sample and identified to P. heterotremus. The patient did not have any symptoms. Apparent pulmonary lesion was not found on the chest X-ray. The patient admitted habitual consumption of semi-cooked or roasted waterfall crabs for several years. The waterfall crabs collected from stream near the village were found negative for Paragonimus metacercariae. In northern Thailand, paragonimiasis remains as one of the public health concerns and should be ruled out for asymptomatic pulmonary patients.

Peritoneal dissemination of ovarian cancer (OvCa) arises from the surface of the peritoneum, covered by monolayer of mesothelial cells (MCs). Given that both OvCa cells and MCs are present in the same peritoneal metastatic microenvironment, they may establish cell‐to‐cell crosstalk or phenotypic alterations including the acquisition of platinum‐resistance in OvCa cells. Herein, we report how OvCa‐associated mesothelial cells (OCAMs) induce platinum‐resistance in OvCa cells through direct cell‐to‐cell crosstalk. We evaluated mutual associations between OvCa cells and human primary MCs with in vitro coculturing experimental models and in silico omics data analysis. The role of OCAMs was also investigated using clinical samples and in vivo mice models. Results of in vitro experiments show that mesenchymal transition is induced in OCAMs primarily by TGF‐β1 stimulation. Furthermore, OCAMs influence the behavior of OvCa cells as a component of the tumor microenvironment of peritoneal metastasis. Mechanistically, OCAMs can induce decreased platinum‐sensitivity in OvCa cells via induction of the FN1/Akt signaling pathway via cell‐to‐cell interactions. Histological analysis of OvCa peritoneal metastasis also illustrated FN1 expression in stromal cells that are supposed to originate from MCs. Further, we also confirmed the activation of Akt signaling in OvCa cells in contact with TGF‐β1 stimulated peritoneum, using an in vivo mice model. Our results suggest that the tumor microenvironment, enhanced by direct cell‐to‐cell crosstalk between OvCa cells and OCAMs, induces acquisition of platinum‐resistance in OvCa cells, which may serve as a novel therapeutic target for prevention of OvCa peritoneal dissemination., What's new? The clinical characteristics of refractory advanced ovarian cancer suggest that the peritoneum acts as an anchoring point for metastatic tumors, enabling persistent ovarian cancer (OvCa) cell survival. This study shows that ovarian cancer‐associated mesothelial cells (OCAMs) and OvCa cells invade the extracellular matrix of the peritoneum. OCAMs were further found to directly influence persistent OvCa cell survival via FN1 signaling. FN1 on the surface of OCAMs induced activation of the Akt signaling pathway, thereby fueling platinum resistance in OvCa cells. The findings highlight the potential for targeting OCAMs as a novel therapeutic strategy for preventing peritoneal dissemination of ovarian cancer.

Statistical iterative reconstruction is expected to improve the image quality of computed tomography (CT). However, one of the challenges of iterative reconstruction is its large computational cost. The purpose of this review is to summarize a fast iterative reconstruction algorithm by optimizing reconstruction parameters. Megavolt projection data was acquired from a TomoTherapy system and reconstructed using in-house statistical iterative reconstruction algorithm. Total variation was used as the regularization term and the weight of the regularization term was determined by evaluating signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and visual assessment of spatial resolution using Gammex and Cheese phantoms. Gradient decent with an adaptive convergence parameter, ordered subset expectation maximization (OSEM), and CPU/GPU parallelization were applied in order to accelerate the present reconstruction algorithm. The SNR and CNR of the iterative reconstruction were several times better than that of filtered back projection (FBP). The GPU parallelization code combined with the OSEM algorithm reconstructed an image several hundred times faster than a CPU calculation. With 500 iterations, which provided good convergence, our method produced a 512 × 512 pixel image within a few seconds. The image quality of the present algorithm was much better than that of FBP for patient data. J. Med. Invest. 67 : 30-39, February, 2020.

Little is known about stem cell transplantation in solid organ transplantation (SOT) recipients. We conducted a nationwide retrospective survey of Japan Society for Hematopoietic Stem Cell Transplantation centers. A total of 19 patients who underwent 22 hematopoietic stem cell transplantations (HSCTs) after SOT were identified: 5 autologous HSCTs and 17 allogeneic HSCTs were performed. Patients who underwent autologous HSCT received a liver (n = 4) or kidney (n = 1) transplant. All 5 patients achieved neutrophil engraftment, and 2 of 3 patients with hepatoblastoma were alive at 1 year after HSCT. Allogeneic HSCT was performed in 16 patients (7 liver transplant recipients and 9 kidney transplant recipients). Among these, 2 donors were identical for both transplantations. All but 1 patient achieved neutrophil engraftment. The 5-year overall survival rate was 41.7%, but that in patients with malignant disease (n = 13) was much lower than the overall rate (23.1%). Only 1 patient with malignant disease underwent allogeneic HSCT in nonremission. In allogeneic HSCT after kidney transplantation, post-transplantation (1 year) kidney function in 5 evaluable patients was significantly lower than that before allogeneic HSCT, and 3 patients experienced renal rejection. However, no severe hepatic rejection was noted. In SOT recipients, HSCT is a potentially curable treatment for hematologic disorders, but it must be performed with caution, especially in patients with malignancy.

Purpose Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN). Method Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness. Result We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT. Conclusion We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.

TAR DNA-binding protein 43 (TDP-43) is a causative factor of amyotrophic lateral sclerosis (ALS). Cytoplasmic TDP-43 aggregates in neurons are a hallmark pathology of ALS. Under various stress conditions, TDP-43 localizes sequentially to two cytoplasmic protein aggregates, namely, stress granules (SGs) first and then aggresomes. Accumulating evidence suggests that delayed clearance of TDP-43-positive SGs is associated with pathological TDP-43 aggregates in ALS. We found that ubiquitin-specific protease 10 (USP10) promotes the clearance of TDP-43-positive SGs in cells treated with proteasome inhibitor, thereby promoting the formation of TDP-43-positive aggresomes, and the depletion of USP10 increases the amount of insoluble TDP-35, a cleaved product of TDP-43, in the cytoplasm. TDP-35 interacted with USP10 in an RNA-binding-dependent manner; however, impaired RNA binding of TDP-35 reduced the localization in SGs and aggresomes and induced USP10-negative TDP-35 aggregates. Immunohistochemistry showed that most of the cytoplasmic TDP-43/TDP-35 aggregates in the neurons of ALS patients were USP10 negative. Our findings suggest that USP10 inhibits aberrant aggregation of TDP-43/TDP-35 in the cytoplasm of neuronal cells by promoting the clearance of TDP-43/TDP-35-positive SGs and facilitating the formation of TDP-43/TDP-35-positive aggresomes.

Short-term study-abroad (STSA) programs provide a more accessible alternative for students who would otherwise not consider engaging in academic activities overseas. Though improvements in the levels of intercultural sensitivity and general academic aspects attained by STSA programs have been previously examined, much less is known regarding the impact such programs have in the mood of students. Here, we examined changes in mood state associated with participation in an STSA program in a group of Japanese university students. Mood states were assessed using the Profile of Mood States (POMS), the Satisfaction With Life Scale (SWLS), and the Gratitude Questionnaire (GQ-6). Results indicated that the POMS mean scores of Vigor-Activity and SWLS peaked at the time immediately following participation in the STSA program; moreover, the same scores were found to be at comparable levels even one month after the end of the program. These results indicate that participation in STSA programs can positively influence the mood state of university students, suggesting that the benefits associated with participation in such programs extend beyond typically reported improvements in the academic domain.

An increase in extreme heat events has been reported along with global warming. Heat exposure in ambient temperature is associated with all-cause diabetes mortality and all-cause hospitalization in diabetic patients. However, the association between heat exposure and hospitalization for hyperglycemic emergencies, such as diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hypoglycemia is unclear. The objective of our study is to clarify the impact of heat exposure on the hospitalization for DKA, HHS, and hypoglycemia.Data of daily hospitalizations for hyperglycemic emergencies (i.e., DKA or HHS) and hypoglycemia was extracted from a nationwide administrative database in Japan and linked with temperature in each prefecture in Japan during 2012-2019. We applied distributed lag non-linear model to evaluate the non-linear and lagged effects of heat exposure on hospitalization for hyperglycemic emergencies.The pooled relative risk for hyperglycemic emergencies of heat effect (the 90th percentile of temperature with reference to the 75th percentile of temperature) and extreme heat effect (the 99th percentile of temperature with reference to the 75th percentile of temperature) over 0-3 lag days was 1.27 (95 %CI: 1.16-1.39) and 1.64 (95 %CI: 1.38-1.93), respectively. The pooled relative risk for heat effect on hospitalization for hypoglycemia and extreme heat effect over 0-3 lag days was 1.33 (95 %CI: 1.17-1.52) and 1.65 (95 %CI: 1.29-2.10), respectively. These associations were consistent by type of hyperglycemic emergencies and type of diabetes and were generally consistent by regions.Heat exposure was associated with hospitalizations for DKA, HHS and hypoglycemia. These results may be useful to guide preventive actions for the risk of fatal hyperglycemic emergencies and hypoglycemia.

Progression-free survival in patients with untreated follicular lymphoma (FL) has significantly improved with obinutuzumab plus chemotherapy followed by obinutuzumab maintenance, compared with rituximab plus chemotherapy. However, the survival outcome and adverse event profile in Japanese FL patients treated with obinutuzumab plus bendamustine (GB) therapy are not well investigated. Recently, we encountered some cases of grade 3-4 thrombocytopenia during GB therapy in patients with FL. This retrospective multicenter survey aimed to identify the characteristics of patients who received GB therapy and developed thrombocytopenia. A total of 54 patients with FL treated by GB therapy between August 2018 and December 2020 were investigated. After a median follow-up of 12.6 months, thrombocytopenia of any grade was observed in 48 (88.9%) patients, including 9 (16.7%) patients with grade 3-4 thrombocytopenia. Notably, although eight of nine patients with grade 3-4 thrombocytopenia were female, no patient characteristics (including gender) were significantly associated with grade 3-4 thrombocytopenia. Importantly, grade 3-4 thrombocytopenia frequently occurred in the first GB therapy cycle, which suggests that platelet count should be monitored carefully in patients who have just started GB therapy.

How effective and safe is telerehabilitation for people with COVID-19 and post-COVID-19 conditions?Systematic review of randomised trials.People with COVID-19 and post-COVID-19 conditions.Any type of telerehabilitation.Satisfaction, quality of life, adverse events, adherence to telerehabilitation, dyspnoea, functional performance, readmissions, mortality, pulmonary function and level of independence.Database searches retrieved 2,962 records, of which six trials with 323 participants were included in the review. Breathing exercises delivered via telerehabilitation improved 6-minute walk distance (MD 101 m, 95% CI 61 to 141; two studies), 30-second sit-to-stand test performance (MD 2.2 repetitions, 95% CI 1.5 to 2.8; two studies), Multidimensional Dyspnoea-12 questionnaire scores (MD -6, 95% CI -7 to -5; two studies) and perceived effort on the 0-to-10 Borg scale (MD -2.8, 95% CI -3.3 to -2.3; two studies), with low certainty of evidence. Exercise delivered via telerehabilitation improved 6-minute walk distance (MD 62 m, 95% CI 42 to 82, four studies), 30-second sit-to-stand test performance (MD 2.0 repetitions, 95% CI 1.3 to 2.7; two studies) and Multidimensional Dyspnoea-12 scores (MD -1.8, 95% CI -2.5 to -1.1; one study), with low certainty of evidence. Adverse events were almost all mild or moderate and occurred with similar frequency in the telerehabilitation group (median 0 per participant, IQR 0 to 2.75) as in the control group (median 0 per participant, IQR 0 to 2); Hodges-Lehmann median difference 0 (95% CI 0 to 0), with low certainty of evidence.Telerehabilitation may improve functional capacity, dyspnoea, performance and physical components of quality of life and does not substantially increase adverse events.PROSPERO CRD42021271049.

Bifidobacterium breve is widely used as a probiotic in preterm infants and children with congenital surgical conditions, however, some cases of probiotics-induced bacteremia have been reported recently.To examine the clinical and bacteriologic features of Bifidobacterium breve bacteremia caused by a probiotic (BBG-01) in term and preterm infants.We included 298 patients who were admitted to the neonatal intensive care unit of Miyagi Children's Hospital and were given BBG-01 as a probiotic within the period June 2014 to February 2019. We experienced six cases of B. breve bacteremia and assessed their features retrospectively.The incidence rate of B. breve bacteremia in our hospital was 2% (6/298), higher than reported previously. The median age at onset, corrected age, and weight of the patients was 8 days (range: 5-27 days), 35 weeks (range: 26-39 weeks), and 1,940 g (range: 369-2734 g), respectively. The bacteremia triggers were gastrointestinal perforations in two cases, food protein-induced enterocolitis syndrome in two cases, adhesive ileus in one case, ileal volvulus in one case, and aspiration pneumonia following esophageal atresia repair in one case. B. breve was detected on blood cultures after a median of 5 days 13 hours (range: 4 days 18 hours-9 days 13 hours). No patient demonstrated serious symptoms, such as septic shock. All patients received antibiotics and recovered without any sequelae.Ileus and intestinal mucosal damage, such as enteritis, can cause B. breve bacteremia. The incidence of B. breve bacteremia may be higher than reported previously and detection via culture may require a longer time than typically needed for more common bacteria. It is associated with a good prognosis.