Characteristics and clinical outcomes of patients with combined burns and trauma in Japan: Analysis of a nationwide trauma registry database.

INTRODUCTION: Patients with combined burns and trauma are often seen in the United States. The combination of trauma with burns increases mortality. In contrast, the characteristics and outcomes of these cases remain unknown in Japan. This study investigated the characteristics and outcomes of trauma associated with burns in Japan. METHODS: This multicenter retrospective cohort study was conducted by utilizing data from the Japan Trauma Data Bank for the period between 2004 and 2017. We evaluated the characteristics of burn patients (n = 5783) divided into two groups: burns only (n = 5537) and combined burns and trauma (n = 246). Clinical characteristics, including patient background, severity of trauma, injury mechanism, total body surface area affected, injury location, treatments, and clinical outcomes, were examined. RESULTS: Most patients in both the groups were injured by flames. The number proportion of patients with 40-89% of the total body surface area affected was 1069/5537 (19.3%) in the burn-only group and 23/246 (9.3%) in the combined burn and trauma group. The in-hospital mortality was 1006/5537 (18.2%) in the burn-only group and 17/246 (6.9%) in the combined burn and trauma group. CONCLUSIONS: We demonstrated the characteristics of Japanese patients with burns only compared with those with combined burns and trauma. Flames were the main cause of burns, and in-hospital mortality was lower in the combined burn and trauma group associated with a smaller burn area.

Source contribution of black carbon aerosol during 2020-2022 at an urban site in Indo-Gangetic Plain.

The extensive emissions of black carbon (BC) from the Indo-Gangetic Plain (IGP) region of India have been recognized to contribute significantly to global climatic warming and negatively affect human health. Particularly, biomass emissions from month-specific crop-residue burning (April, May, October, November) and heating activities (December-February) are considered substantial contributors to BC emissions in the IGP. However, their precise contribution to ambient BC aerosols has not been quantified yet and remains an issue of debate. Therefore, this study aims to fill this gap by quantifying the contribution of these month-specific biomass emissions to ambient BC at an urban site in IGP. This study presents the analysis of BC mass concentrations (MBC) measured for 3 years (2020-2022) in Delhi using an optical photometer i.e., continuous soot monitoring system (COSMOS)). A statistical analysis of monthly mean MBC and factors affecting the MBC (ventilation coefficients, air mass back trajectories, fire counts) is performed to derive month-wise contribution due to background concentration, conventional emission, regional transport, crop-residue burning, and heating activities. The yearly mean MBC (5.3 ±â€¯4.7, 5.6 ±â€¯5.0, and 5.3 ±â€¯3.5 µg m-3 during 2020, 2021, and 2022, respectively) remained relatively consistent with repetitive monthly patterns in each year, where peak concentrations were observed from November to January and low concentrations from June to September. Anthropogenic activities contributed significantly to MBC over Delhi with background concentration contributing only 30 % of observed MBC. The percentage contribution of emissions from crop-residue burning varied from 15 % (May) to 37 % (November), while the contribution from heating activities ranged from 25 % (December) to 39 % (January). This source quantification study highlights the significant impact of month-specific biomass emissions in the IGP and can play a vital role in better management and control of these emissions in the region.

Exclusive expression of KANK4 promotes myofibroblast mobility in keloid tissues.

Keloids are characterized by abnormal wound healing with excessive accumulation of extracellular matrix. Myofibroblasts are the primary contributor to extracellular matrix secretion, playing an essential role in the wound healing process. However, the differences between myofibroblasts involved in keloid formation and normal wound healing remain unclear. To identify the specific characteristics of keloid myofibroblasts, we initially assessed the expression levels of well-established myofibroblast markers, α-smooth muscle actin (α-SMA) and transgelin (TAGLN), in scar and keloid tissues (n = 63 and 51, respectively). Although myofibroblasts were present in significant quantities in keloids and immature scars, they were absent in mature scars. Next, we conducted RNA sequencing using myofibroblast-rich areas from keloids and immature scars to investigate the difference in RNA expression profiles among myofibroblasts. Among significantly upregulated 112 genes, KN motif and ankyrin repeat domains 4 (KANK4) was identified as a specifically upregulated gene in keloids. Immunohistochemical analysis showed that KANK4 protein was expressed in myofibroblasts in keloid tissues; however, it was not expressed in any myofibroblasts in immature scar tissues. Overexpression of KANK4 enhanced cell mobility in keloid myofibroblasts. Our results suggest that the KANK4-mediated increase in myofibroblast mobility contributes to keloid pathogenesis.

Intensive care unit follow-up clinic activities: a scoping review.

The importance of ongoing post-discharge follow-up to prevent functional impairment in patients discharged from intensive care units (ICUs) is being increasingly recognized. Therefore, we conducted a scoping review, which included existing ICU follow-up clinic methodologies using the CENTRAL, MEDLINE, and CINAHL databases from their inception to December 2022. Data were examined for country or region, outpatient name, location, opening days, lead profession, eligible patients, timing of the follow-up, and assessment tools. Twelve studies were included in our review. The results obtained revealed that the methods employed by ICU follow-up clinics varied among countries and regions. The names of outpatient follow-up clinics also varied; however, all were located within the facility. These clinics were mainly physician or nurse led; however, pharmacists, physical therapists, neuropsychologists, and social workers were also involved. Some clinics were limited to critically ill patients with sepsis or those requiring ventilation. Ten studies reported the first outpatient visit 1-3 months after discharge. All studies assessed physical function, cognitive function, mental health, and the health-related quality of life. This scoping review revealed that an optimal operating format for ICU follow-up clinics needs to be established according to the categories of critically ill patients.

Risk stratification of synchronous gastric cancers including alcohol-related genetic polymorphisms.

BACKGROUND AND AIM: We previously identified that ever-smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol-related genetic polymorphism with SGCs and also stratify their risk. METHODS: This multi-center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study. RESULTS: Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0-3 risk factors in the combined evaluation of three risk factors (ever-smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001). CONCLUSIONS: Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy. Depletion of TUG1 increased sensitivity to cisplatin in the OVCA cell lines, SKOV3 and KURAMOCHI. Combination therapy of cisplatin with antisense oligonucleotides targeting TUG1 coupled with a drug delivery system effectively relieved the tumor burden in xenograft mouse models. Mechanistically, TUG1 acts as a competing endogenous RNA by downregulating miR-4687-3p and miR-6088, both of which target DNA polymerase eta (POLH), an enzyme required for translesion DNA synthesis. Overexpression of POLH reversed the effect of TUG1 depletion on cisplatin-induced cytotoxicity. Our data suggest that TUG1 upregulation allows OVCA to tolerate DNA damage via upregulation of POLH; this provides a strong rationale for targeting TUG1 to overcome cisplatin resistance in OVCA.

Mutation of the SWI/SNF complex component Smarce1 decreases nucleosome stability in embryonic stem cells and impairs differentiation.

The SWI/SNF chromatin remodeling complex consists of more than ten component proteins that form a large protein complex of >1 MDa. The catalytic proteins Smarca4 or Smarca2 work in concert with the component proteins to form a chromatin platform suitable for transcriptional regulation. However, the mechanism by which each component protein works synergistically with the catalytic proteins remains largely unknown. Here, we report on the function of Smarce1, a component of the SWI/SNF complex, through the phenotypic analysis of homozygous mutant embryonic stem cells (ESCs). Disruption of Smarce1 induced the dissociation of other complex components from the SWI/SNF complex. Histone binding to DNA was loosened in homozygous mutant ESCs, indicating that disruption of Smarce1 decreased nucleosome stability. Sucrose gradient sedimentation analysis suggested that there was an ectopic genomic distribution of the SWI/SNF complex upon disruption of Smarce1, accounting for the misregulation of chromatin conformations. Unstable nucleosomes remained during ESC differentiation, impairing the heterochromatin formation that is characteristic of the differentiation process. These results suggest that Smarce1 guides the SWI/SNF complex to the appropriate genomic regions to generate chromatin structures adequate for transcriptional regulation.

Post-intensive care syndrome: Recent advances and future directions.

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome.

Astrocyte-induced mGluR1 activates human lung cancer brain metastasis via glutamate-dependent stabilization of EGFR.

There are limited methods to stably analyze the interactions between cancer cells and glial cells in vitro, which hinders our molecular understanding. Here, we develop a simple and stable culture method of mouse glial cells, termed mixed-glial culture on/in soft substrate (MGS), which serves well as a platform to study cancer-glia interactions. Using this method, we find that human lung cancer cells become overly dependent on metabotropic glutamate receptor 1 (mGluR1) signaling in the brain microenvironment. Mechanistically, interactions with astrocytes induce mGluR1 in cancer cells through the Wnt-5a/prickle planar cell polarity protein 1 (PRICKLE1)/RE1 silencing transcription factor (REST) axis. Induced mGluR1 directly interacts with and stabilizes the epidermal growth factor receptor (EGFR) in a glutamate-dependent manner, and these cells then become responsive to mGluR1 inhibition. Our results highlight increased dependence on mGluR1 signaling as an adaptive strategy and vulnerability of human lung cancer brain metastasis.

Association of Contrast Extravasation Grade With Massive Transfusion in Pediatric Blunt Liver and Spleen Injuries: A Multicenter Retrospective Cohort Study.

BACKGROUND: This study aimed to assess whether the grade of contrast extravasation (CE) on CT scans was associated with massive transfusion (MT) requirements in pediatric blunt liver and/or spleen injuries (BLSI). METHODS: This multicenter retrospective cohort study included pediatric patients (≤16 years old) who sustained BLSI between 2008 and 2019. MT was defined as transfusion of all blood products ≥40 mL/kg within the first 24 h of admission. Associations between CE and MT requirements were assessed using multivariate logistic regression analysis with cluster-adjusted robust standard errors to calculate the adjusted odds ratio (AOR). RESULTS: A total of 1407 children (median age: 9 years) from 83 institutions were included in the analysis. Overall, 199 patients (14 %) received MT. CT on admission revealed that 54 patients (3.8 %) had CE within the subcapsular hematoma, 100 patients (7.1 %) had intraparenchymal CE, and 86 patients (6.1 %) had CE into the peritoneal cavity among the overall cohort. Multivariate analysis, adjusted for age, sex, age-adjusted shock index, injury severity, and laboratory and imaging factors, showed that intraparenchymal CE and CE into the peritoneal cavity were significantly associated with the need for MT (AOR: 2.50; 95 % CI, 1.50-4.16 and AOR: 4.98; 95 % CI, 2.75-9.02, respectively both p < 0.001). The latter significant association persisted in the subgroup of patients with spleen and liver injuries. CONCLUSION: Active CE into the free peritoneal cavity on admission CT was independently associated with a greater probability of receiving MT in pediatric BLSI. The CE grade may help clinicians plan blood transfusion strategies. LEVEL OF EVIDENCE: Level 4; Therapeutic/Care management.

Challenges hindering emergency physicians; involvement in multicenter collaborative studies in Japan: A nationwide survey analysis.

Aim: Multicenter collaborative research accelerates patient recruitment and strengthens evidence. Nevertheless, the factors influencing emergency and critical care physicians' involvement in such research in Japan remain unclear. Methods: A nationwide web-based survey conducted in early 2023 targeted emergency physicians working a minimum of 3 days per week in Japan. The survey descriptively assessed their backgrounds, work and research environments, experiences, and perceived impediments and motivators for multicenter research. Results: Of the 387 respondents, 348 were included in the study, yielding a 5.1% response rate. Women comprised 11% of the participants; 33% worked in university hospitals, 65% served in both emergency departments and intensive care units, and 54% did shift work. Only 12% had designated research time during working hours, with a median of 1 hour per week (interquartile range 0-5 h), including time outside of work. While 73% had participated in multicenter research, 58% noted barriers to participation. The key obstacles were excessive data entry (72%), meeting time constraints (59%), ethical review at each facility (50%), and unique sample collection, such as bronchoalveolar lavage specimens or pathological tissues (51%). The major incentives were networking (70%), data sets reuse (65%), feedback on research results (63%), and recognition from academic societies (63%). Financial rewards were not highly prioritized (38%). Conclusions: While valuing clinical research, emergency physicians face barriers, especially data entry burden and limited research time. Networking and sharing research findings motivate them. These insights can guide strategies to enhance collaborative research in emergency and critical care in Japan.

Japanese Clinical Practice Guidelines for Rehabilitation in Critically Ill Patients 2023 (J-ReCIP 2023).

Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the "Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit" to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions.

Efficacy of therapeutic drug monitoring-based antibiotic regimen in critically ill patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of therapeutic drug monitoring (TDM)-based antimicrobial dosing optimization strategies on pharmacokinetics/pharmacodynamics and specific drug properties for critically ill patients is unclear. Here, we conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of TDM-based regimen in these patients. METHODS: Articles from three databases were systematically retrieved to identify relevant randomized control studies. Version two of the Cochrane tool for assessing risk of bias in randomized trials was used to assess the risk of bias in studies included in the analysis, and quality assessment of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation approach. Primary outcome was the 28-day mortality and secondary outcome were in-hospital mortality, clinical cure, length of stay in the intensive care unit (ICU) and target attainment at day 1 and 3. RESULTS: In total, 5 studies involving 1011 patients were included for meta-analysis of the primary outcome, of which no significant difference was observed between TDM-based regimen and control groups (risk ratio [RR] 0.94, 95% confidence interval [CI]: 0.77-1.14; I2 = 0%). In-hospital mortality (RR 0.96, 95% CI: 0.76-1.20), clinical cure (RR 1.23, 95% CI: 0.91-1.67), length of stay in the ICU (mean difference 0, 95% CI: - 2.18-2.19), and target attainment at day 1 (RR 1.14, 95% CI: 0.88-1.48) and day 3 (RR 1.35, 95% CI: 0.90-2.03) were not significantly different between the two groups, and all evidence for the secondary outcomes had a low or very low level of certainty because the included studies had serious risk of bias, variation of definition for outcomes, and small sample sizes. CONCLUSION: TDM-based regimens had no significant efficacy for clinical or pharmacological outcomes. Further studies with other achievable targets and well-defined outcomes are required. TRIAL REGISTRATION: Clinical trial registration; PROSPERO ( https://www.crd.york.ac.uk/prospero/ ), registry number: CRD 42022371959. Registered 24 November 2022.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Defining super-enhancers by highly ranked histone H4 multi-acetylation levels identifies transcription factors associated with glioblastoma stem-like properties.

BACKGROUND: Super-enhancers (SEs), which activate genes involved in cell-type specificity, have mainly been defined as genomic regions with top-ranked enrichment(s) of histone H3 with acetylated K27 (H3K27ac) and/or transcription coactivator(s) including a bromodomain and extra-terminal domain (BET) family protein, BRD4. However, BRD4 preferentially binds to multi-acetylated histone H4, typically with acetylated K5 and K8 (H4K5acK8ac), leading us to hypothesize that SEs should be defined by high H4K5acK8ac enrichment at least as well as by that of H3K27ac. RESULTS: Here, we conducted genome-wide profiling of H4K5acK8ac and H3K27ac, BRD4 binding, and the transcriptome by using a BET inhibitor, JQ1, in three human glial cell lines. When SEs were defined as having the top ranks for H4K5acK8ac or H3K27ac signal, 43% of H4K5acK8ac-ranked SEs were distinct from H3K27ac-ranked SEs in a glioblastoma stem-like cell (GSC) line. CRISPR-Cas9-mediated deletion of the H4K5acK8ac-preferred SEs associated with MYCN and NFIC decreased the stem-like properties in GSCs. CONCLUSIONS: Collectively, our data highlights H4K5acK8ac's utility for identifying genes regulating cell-type specificity.

TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.

Oncogene-induced DNA replication stress (RS) and consequent pathogenic R-loop formation are known to impede S phase progression. Nonetheless, cancer cells continuously proliferate under such high-stressed conditions through incompletely understood mechanisms. Here, we report taurine upregulated gene 1 (TUG1) long noncoding RNA (lncRNA), which is highly expressed in many types of cancers, as an important regulator of intrinsic R-loop in cancer cells. Under RS conditions, TUG1 is rapidly upregulated via activation of the ATR-CHK1 signaling pathway, interacts with RPA and DHX9, and engages in resolving R-loops at certain loci, particularly at the CA repeat microsatellite loci. Depletion of TUG1 leads to overabundant R-loops and enhanced RS, leading to substantial inhibition of tumor growth. Our data reveal a role of TUG1 as molecule important for resolving R-loop accumulation in cancer cells and suggest targeting TUG1 as a potent therapeutic approach for cancer treatment.

The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma.

BACKGROUND: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. METHODS: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7-9 or 10-12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. RESULTS: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49-2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. CONCLUSIONS: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. TRIAL REGISTRATION NUMBER: umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018.

Burnout among Japanese emergency medicine physicians: A multicentric questionnaire study.

Objective: Burnout negatively affects the wellness and performance of emergency physicians (EPs). This study aimed to clarify the actual prevalence of burnout and its associated factors among Japanese EPs. Methods: We conducted a cross-sectional questionnaire study of selected 27 Japanese emergency departments (EDs). We examined the Maslach Burnout Inventory-Human Services Survey score and its associations with ED-level- and EP-level factors in a multivariable analysis. Results: A total of 267 EPs (81.9%) completed survey. Of these, 43 EPs (16.1%) scored severe emotional exhaustion (EE), 53 (19.8%) scored severe depersonalization (DP), and 179 (67.0%) scored severe personal accomplishment (PA), and 24 (8.9%) scored severely in all three domains. In our multivariable analysis, emergency medical service centers were associated with severe PA scores (odds ratio [OR], 10.56; 95% confidence interval [CI], 1.78-62.66; p = 0.009). A 3 to 6 hour-sleep period was associated with severe EE scores (OR, 2.04; 95% CI, 1.04-3.98; p = 0.036), and EPs in their 20s were associated with severe DP scores (OR, 7.37; 95% CI, 1.41-38.38; p = 0.018). Conclusion: Our results suggest that 8.9% of Japanese EPs are in higher degrees of burnout. In particular, Japanese EPs scored more severely on PA. To avoid burnout in Japanese EPs, it is important to improve the working environment by ensuring more than 6 h of sleep, providing more support for young EPs, and taking effective action to combat low EP self-esteem.

Fusobacterium infection facilitates the development of endometriosis through the phenotypic transition of endometrial fibroblasts.

Retrograde menstruation is a widely accepted cause of endometriosis. However, not all women who experience retrograde menstruation develop endometriosis, and the mechanisms underlying these observations are not yet understood. Here, we demonstrated a pathogenic role of Fusobacterium in the formation of ovarian endometriosis. In a cohort of women, 64% of patients with endometriosis but <10% of controls were found to have Fusobacterium infiltration in the endometrium. Immunohistochemical and biochemical analyses revealed that activated transforming growth factor-ß (TGF-ß) signaling resulting from Fusobacterium infection of endometrial cells led to the transition from quiescent fibroblasts to transgelin (TAGLN)-positive myofibroblasts, which gained the ability to proliferate, adhere, and migrate in vitro. Fusobacterium inoculation in a syngeneic mouse model of endometriosis resulted in a marked increase in TAGLN-positive myofibroblasts and increased number and weight of endometriotic lesions. Furthermore, antibiotic treatment largely prevented establishment of endometriosis and reduced the number and weight of established endometriotic lesions in the mouse model. Our data support a mechanism for the pathogenesis of endometriosis via Fusobacterium infection and suggest that eradication of this bacterium could be an approach to treat endometriosis.