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Mature cystic teratomas (MCTs) of the ovary comprise tissues from all three germ layers. The coexistence of the complete intestinal tract, prostatic tissue, and bladder component within the same ovarian MCT is unprecedented. Here, we report the diagnosis and management of such a rare case. A 26-year-old woman presented with a right ovarian mass, which was later confirmed as an MCT by histopathological examination. The patient underwent a successful laparoscopic cystectomy with no evidence of malignancy or postoperative complications. Histological examination revealed that this MCT contained the complete organ structures including a lower intestinal tract and male genital tract with prostate, urethra, and bladder components, which is unusual. This case underscores the importance of understanding the pathogenesis of extensive organogenesis in MCTs and raises questions about the differentiation processes leading to such unique presentations., Competing Interests: Declarations Conflict of Interest None. Informed consent The patient provided written consent for the publication of this case report. All personal identifiers have been removed to ensure privacy.Coexistence of Complete Intestinal Tract, Prostatic Tissue, Prostatic Urethra and Bladder., (© 2024. The Author(s).)

Background: Tigecycline is an antimicrobial agent with a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. However, mobile tigecycline resistance gene clusters, such as tnfxB-tmexCD-toprJ, have spread globally. The prevalence of tigecycline-resistant Enterobacterales in clinical settings in Japan is unknown., Objectives: To investigate the tnfxB-tmexCD-toprJ gene cluster in the genome sequences of Enterobacterales clinical isolates in Japan., Methods: We investigated the tnfxB-tmexCD-toprJ cluster from the genome sequences of 5143 Enterobacterales isolates collected from 175 hospitals around Japan between 2019 and 2020 as part of a national genomic surveillance program for antimicrobial-resistant bacteria., Results: The tnfxB1-tmexCD1-toprJ1 cluster was detected in two Klebsiella pneumoniae isolates in 2019. One isolate possessed a 299.4 kb IncFIB(K) plasmid, pJBBGAAF19431, and the other possessed a 224.9 kb IncHI1B/IncFIB(K) hybrid plasmid, pJBEAACG19501, co-carrying multiple antimicrobial resistance genes, including extended-spectrum β-lactamase genes, blaOXA-1 and blaCTX-M-27, respectively, along with tnfxB1-tmexCD1-toprJ1. The genetic context of the tnfxB1-tmexCD1-toprJ1-surrounding structure on pJBBGAAF19431 was similar to that of a K. pneumoniae plasmid pHNAH8I-1 from a chicken in China in 2017, and the cluster was embedded in an apparently intact mobile DNA element: strand-biased circularizing integrative element. The tnfxB1-tmexCD1-toprJ1 on pJBEAACG19501 was embedded in a Tn3 family transposon related to TnAs1. The plasmid pJBEAACG19501 was highly similar to that of K. pneumoniae, isolated from humans in China in 2021., Conclusions: tmexCD-toprJ was present in Japan as of 2019. Even in Japan, where the clinical use of tigecycline is significantly rare, tmexCD-toprJ-harbouring multidrug-resistant Enterobacterales is a public health threat and requires continuous monitoring., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Struma ovarii is a mature ovarian teratoma characterized by the predominant presence of thyroid-tissue components. Typically, struma ovarii presents as relatively small masses (<10 cm) that often appear as multilocular cystic tumors with solid components. Herein, we report the unique case of a 44-year-old female with a large tumor including a solid mass. The solid components of the tumor comprised typical thyroid tissues with multiple small cystic structures containing colloid-like material. Given the rarity of struma ovarii, atypical imaging features can sometimes be misleading. This article highlights the unusual magnetic resonance imaging characteristics of a large struma ovarii, with a specific focus on the presence of solid components., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Decidualization denotes the morphological and biological differentiating process of human endometrial stromal cells (HESCs). Fatty acid pathways are critical for endometrial decidualization. However, the participation of fatty acids as an energy source and their role in endometrial decidualization have received little attention. To identify fatty acids and clarify their role in decidualization, we comprehensively evaluated free fatty acid profiles using liquid chromatography/Fourier transform mass spectrometry (LC/FT-MS). LC/FT-MS analysis detected 26 kinds of fatty acids in the culture medium of decidualized or un-decidualized HESCs. Only the production of octanoic acid, which is an essential energy source for embryonic development, was increased upon decidualization. The expressions of genes related to octanoic acid metabolism including ACADL, ACADM, and ACADS; genes encoding proteins catalyzing the first step of mitochondrial fatty acid beta-oxidation; and ACSL5 and ACSM5; genes encoding fatty acid synthesis proteins were significantly altered upon decidualization. These results suggest that decidualization promotes lipid metabolism, implying that decidualized HESCs require energy metabolism of the mitochondria in embryo implantation.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has necessitated significant changes in medical systems, social behaviours, and non-pharmaceutical interventions (NPIs). We aimed to determine the effect of the COVID-19 pandemic on changes in the epidemiology of respiratory-transmitted bacteria that have been unexplored., Methods: We utilised a comprehensive national surveillance database from 2018 to 2021 to compare monthly number of patients with four respiratory-transmitted human-to-human bacteria (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes) before and after the COVID-19 pandemic, stratified by specimen sources and age groups., Results: The incidence of detected patients with S. pneumoniae, H. influenzae, and S. pyogenes from both respiratory and blood cultures significantly decreased from 2019 to 2020. In 2021, the incidence of detected patients with the respiratory-transmitted bacterial species, except for S. pyogenes, from respiratory cultures, increased again from April to July, primarily affecting the 0-4-year age group., Conclusions: Our comprehensive national surveillance data analysis demonstrates the dynamic changes and effects of NPIs on respiratory-transmitted bacteria during the COVID-19 pandemic, with variations observed among species, specimen sources, and age groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We report on single case of intraplacental choriocarcinoma (IC) coexisting with feto-maternal hemorrhage from our hospital, a rare malignant tumor that occurs in the chorionic villous trophoblast. To investigate genetic and epigenetic changes to the carcinogenesis of IC, we employed cancer gene panel analysis and whole methylation analysis from a recent case of IC. By Short Tandem Repeats analysis, we confirmed that the tumor of present IC was derived from concurrent normal chorionic villous trophoblast cells. No mutation was found in 145 cancer-related genes. Meanwhile, amplification in MDM2 gene was observed. Furthermore, we observed deferentially methylated CpG sites between tumor and surrounding normal placenta in present IC case. These observations suggest that IC might be arisen as a result of aberrations of methylation rather than of DNA mutations. Further studies are needed to clarify association between aberrant methylation and choriocarcinogenesis., (© 2024. The Author(s).)

Japan is a country with an approximate 10% prevalence rate of carbapenem-resistant Pseudomonas aeruginosa (CRPA). Currently, a comprehensive overview of the genotype and phenotype patterns of CRPA in Japan is lacking. Herein, we conducted genome sequencing and quantitative antimicrobial susceptibility testing for 382 meropenem-resistant CRPA isolates that were collected from 78 hospitals across Japan from 2019 to 2020. CRPA exhibited susceptibility rates of 52.9%, 26.4%, and 88.0% against piperacillin-tazobactam, ciprofloxacin, and amikacin, respectively, whereas 27.7% of CRPA isolates was classified as difficult-to-treat resistance P. aeruginosa . Of the 148 sequence types detected, ST274 (9.7%) was predominant, followed by ST235 (7.6%). The proportion of urine isolates in ST235 was higher than that in other STs ( P = 0.0056, χ 2 test). Only 4.1% of CRPA isolates carried the carbapenemase genes: bla GES (2) and bla IMP (13). One ST235 isolate carried the novel bla IMP variant bla IMP-98 in the chromosome. Regarding chromosomal mutations, 87.1% of CRPA isolates possessed inactivating or other resistance mutations in oprD , and 28.8% showed mutations in the regulatory genes ( mexR , nalC , and nalD ) for the MexAB-OprM efflux pump. Additionally, 4.7% of CRPA isolates carried a resistance mutation in the PBP3-encoding gene ftsI . The findings from this study and other surveillance studies collectively demonstrate that CRPA exhibits marked genetic diversity and that its multidrug resistance in Japan is less prevailed than in other regions. This study contributes a valuable data set that addresses a gap in genotype/phenotype information regarding CRPA in the Asia-Pacific region, where the epidemiological background markedly differs between regions., Competing Interests: The authors declare no conflict of interest.

This study aimed to investigate assisted reproductive technology (ART) factors associated with placenta accreta spectrum (PAS) after vaginal delivery. This was a registry-based retrospective cohort study using the Japanese national ART registry. Cases of live singleton infants born via vaginal delivery after single embryo transfer (ET) between 2007 and 2020 were included (n = 224,043). PAS was diagnosed in 1412 cases (0.63% of deliveries), including 1360 cases (96.3%) derived from frozen-thawed ET cycles and 52 (3.7%) following fresh ET. Among fresh ET cycles, assisted hatching (AH) (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI] 1.4-4.7) and blastocyst embryo transfer (aOR, 2.2; 95% CI 1.3-3.9) were associated with a significantly increased risk of PAS. For frozen-thawed ET cycles, hormone replacement cycles (HRCs) constituted the greatest risk factor (aOR, 11.4; 95% CI 8.7-15.0), with PAS occurring in 1.4% of all vaginal deliveries following HRC (1258/91,418 deliveries) compared with only 0.11% following natural cycles (55/47,936). AH was also associated with a significantly increased risk of PAS in frozen-thawed cycles (aOR, 1.2; 95% CI 1.02-1.3). Our findings indicate the need for additional care in the management of patients undergoing vaginal delivery following ART with HRC and AH., (© 2024. The Author(s).)

Objective: To evaluate assisted reproductive technology-associated risk factors for retained products of conception among live births., Design: Registry-based retrospective cohort study., Setting: Not applicable., Patient(s): Cycle-specific data for a total of 369,608 singleton live births after fresh and frozen-thawed embryo transfers (FETs) between 2007 and 2017 were obtained from the Japanese assisted reproductive technology registry., Intervention(s): None., Main Outcome Measure(s): Retained products of conception after delivery. Odds ratios and 95% confidence intervals for risk factors associated with retained products of conception during fresh and frozen cycles., Result(s): In total, 132 deliveries (0.04% of eligible assisted reproductive technology registry deliveries) had retained products of conception; 122 (92.4%) of these deliveries occurred after FET transfer cycles. Cases with retained products of conception were significantly more likely to have undergone vaginal delivery than cases without retained products of conception (78.0% vs. 61.1%); they were also more likely to have been complicated with the placenta accreta spectrum (24.2% vs. 0.45%). Among patients undergoing FETs, factors associated with a significantly increased risk of retained products of conception were embryo stage at transfer, use of hormone replacement cycles, and assisted hatching. Use of hormone replacement cycles represented the largest risk factor (adjusted odds ratio, 4.9; 95% confidence interval, 2.0-12.4), such that retained products of conception occurred in 0.05% (51 of 97,958) of deliveries after hormone replacement cycles but only 0.01% (5 of 47,079) of deliveries after natural cycles. Subgroup analysis showed that hormone replacement cycles and assisted hatching remained significant risk factors for retained products of conception in cases without polycystic ovary syndrome and anovulation and cases with vaginal delivery, but not cases with cesarean section. Among fresh embryo transfers, an increased number of retrieved oocytes was the only significant risk factor for retained products of conception., Conclusion(s): Our analyses demonstrated that most of the cases involving retained products of conception were derived from FETs, and we identified the use of hormone replacement cycles as the largest risk factor for retained products of conception within this group., Competing Interests: Declaration of interests S.C.J. is a board member of the International Committee for Monitoring Assisted Reproductive Technologies (ICMART). H.T. has nothing to disclose. S.T. has nothing to disclose. M.T. has nothing to disclose. A.N. has nothing to disclose. T.K. has nothing to disclose. O.I. has received consultation fees from Organon, an honorarium from Ferring Pharmaceuticals and Nippon Shinyaku Pharma and advisory board members for Ferring Pharmaceuticals and Merck biopharma and a board member of ICMART. Y.K. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Staphylococcus aureus is a commensal bacterium in humans, but it sometimes causes opportunistic infectious diseases such as suppurative skin disease, pneumonia, and enteritis. Therefore, it is important to determine the prevalence of S. aureus and methicillin-resistant S. aureus (MRSA) in individuals, especially older adults. In this study, we investigated the prevalence of S. aureus and MRSA in the oral cavity and feces of residents in long-term care facilities (LTCFs). S. aureus was isolated from the oral cavity of 61/178 (34.3%) participants, including 28 MRSA-positive participants (15.7%), and from the feces of 35/127 (27.6%) participants, including 16 MRSA-positive participants (12.6%). S. aureus and MRSA were isolated from both sites in 19/127 individuals (15.0%) and 10/127 individuals (7.9%), respectively. Among 19 participants with S. aureus isolation from both sites, 17 participants showed the same sequence type (ST) type. Then, we analyzed the correlation of S. aureus and MRSA in the oral cavity and rectum with the participant's condition. S. aureus and MRSA positivity in the oral cavity was significantly related to tube feeding, while there was no correlation of rectal S. aureus/MRSA with any factors. Our findings regarding the oral inhabitation of MRSA and its risk factors indicate the importance of considering countermeasures against MRSA infection in LTCFs., (© 2023 The Societies and John Wiley & Sons Australia, Ltd.)

Background: Although there is a growing concern and policy regarding infections or colonization caused by resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), the prognosis of MRSA infections compared to that of methicillin-susceptible Staphylococcus aureus (MSSA) infections remains controversial. Moreover, there have not been any studies comparing both the burden of disease and its impact on the healthcare economy between MRSA infection and colonization while adjusting for confounding factors. These comparisons are crucial for developing effective infection control measures and healthcare policies. We aimed to compare the disease and economic burden between MRSA and MSSA infections and between MRSA infection and colonization., Methods: We retrospectively investigated data of 496 in-patients with MRSA or MSSA infections and of 1178 in-patients with MRSA infections or MRSA colonization from a university hospital in Japan from 2016 to 2021. We compared in-hospital mortality, length of stay, and hospital charges between in-patients with MRSA and MSSA infections and those with MRSA infections and MRSA colonization using multiple regressions. We combined surveillance data, including all microbiological test results, data on patients with infections, treatment histories, and clinical outcomes, to create the datasets., Results: There was no statistically significant difference in in-hospital mortality rates between matched MRSA vs. MSSA infections and MRSA infection vs. colonization. On the contrary, the adjusted effects of the MRSA infection compared to those of MSSA infection on length of stay and hospital charges were 1.21-fold (95% confidence interval [CI] 1.03-1.42, P = 0.019) and 1.70-fold (95% CI 1.39-2.07, P < 0.00001), respectively. The adjusted effects of the MRSA infection compared to those of MRSA colonization on length of stay and hospital charges were 1.41-fold (95% CI 1.25-1.58, P < 0.00001) and 1.53-fold (95% CI 1.33-1.75, P < 0.00001), respectively. Regarding confounding factors, hemodialysis or hemofiltration was consistently identified and adjusted for in the multiple regression analyses comparing MRSA and MSSA infections, as well as MRSA infection and MRSA colonization., Conclusions: MRSA infection was associated with longer length of stay and higher hospital charges than both MSSA infection and MRSA colonization. Furthermore, hemodialysis or hemofiltration was identified as a common underlying factor contributing to increased length of stay and hospital charges., (© 2024. The Author(s).)

Monitoring antibiotic-resistant bacteria (ARB) and understanding the effects of antimicrobial drugs on the human microbiome and resistome are crucial for public health. However, no study has investigated the association between antimicrobial treatment and the microbiome-resistome relationship in long-term care facilities, where residents act as reservoirs of ARB but are not included in the national surveillance for ARB. We conducted shotgun metagenome sequencing of oral and stool samples from long-term care facility residents and explored the effects of antimicrobial treatment on the human microbiome and resistome using two types of comparisons: cross-sectional comparisons based on antimicrobial treatment history in the past 6 months and within-subject comparisons between stool samples before, during and 2-4 weeks after treatment using a single antimicrobial drug. Cross-sectional analysis revealed two characteristics in the group with a history of antimicrobial treatment: the archaeon Methanobrevibacter was the only taxon that significantly increased in abundance, and the total abundance of antimicrobial resistance genes (ARGs) was also significantly higher. Within-subject comparisons showed that taxonomic diversity did not decrease during treatment, suggesting that the effect of the prescription of a single antimicrobial drug in usual clinical treatment on the gut microbiota is likely to be smaller than previously thought, even among very elderly people. Additional analysis of the detection limit of ARGs revealed that they could not be detected when contig coverage was <2.0. This study is the first to report the effects of usual antimicrobial treatments on the microbiome and resistome of long-term care facility residents.

Background: Antimicrobial use (AMU) in primary care is a contributing factor to the emergence of antimicrobial-resistant bacteria. We assessed the potential effects of AMU on the prevalence of a combination of resistance phenotypes in bacteraemic Escherichia coli in outpatient care settings between primary care facilities ('clinics') and hospitals., Methods: Population-weighted total AMU calculated from the national database was expressed as DDDs per 1000 inhabitants per day (DID). National data for all routine microbiological test results were exported from the databases of a major commercial clinical laboratory, including 16 484 clinics, and the Japan Nosocomial Infections Surveillance, including 1947 hospitals. AMU and the prevalence of combinations of resistance phenotypes in bacteraemic E. coli isolates were compared between clinics and hospitals., Results: The five most common bacteria isolated from patients with bacteraemia were the same in clinics, outpatient settings and inpatient settings in hospitals, with E. coli as the most frequent. Oral third-generation cephalosporins and fluoroquinolones were the top two AMU outpatient drugs, except for macrolides, and resulted in at least three times higher AMU in clinics than in hospitals. The percentage of E. coli isolates resistant to both drugs in clinics (18.7%) was 5.6% higher than that in hospitals (13.1%) (P < 10-8)., Conclusions: Significant AMU, specifically of oral third-generation cephalosporins and fluoroquinolones, in clinics is associated with a higher prevalence of E. coli isolates resistant to both drugs. This study provides a basis for national interventions to reduce inappropriate AMU in primary care settings., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

So far, power input has been used as the main parameter for bioreactor scale-up/-down in upstream process development and manufacturing. The rationale is that maintaining a consistent power input per unit volume should result in comparable mixing times at different scales. However, shear generated from turbulent flow may compromise the integrity of non-robust cells such as those used during the production of cell and gene therapies, which may lead to low product quality and yield. Of particular interest is the Kolmogorov length parameter that characterizes the smallest turbulent eddies in a mixture. To understand its impact on scale-up/-down decisions, the distribution of Kolmogorov length along the trajectory flow of individual particles in bioreactors was estimated in silico with the help of computational fluid dynamics simulations. Specifically, in this study the scalability of iPSC-derived lymphocyte production and the impact of shear stress across various differentiation stages were investigated. The study used bioreactors of volumes from 0.1 to 10 L, which correspond to the scales most used for parameter optimization. Our findings, which align with in vitro runs, help determine optimal agitation speed and shear stress adjustments for process transfer between scales and bioreactor types, using vertically-oriented wheel and pitched-blade impellers. In addition, empirical models specific to the bioreactors used in this study were developed. The provided computational analysis in combination with experimental data supports selection of appropriate bioreactors and operating conditions for various cell and gene therapy process steps., (© 2023 The Authors. Biotechnology Journal published by Wiley-VCH GmbH.)

Antimicrobial resistance is a global health concern; Enterobacterales resistant to third-generation cephalosporins (3GCs) and carbapenems are of the highest priority. Here, we conducted genome sequencing and standardized quantitative antimicrobial susceptibility testing of 4,195 isolates of Escherichia coli and Klebsiella pneumoniae resistant to 3GCs and Enterobacterales with reduced meropenem susceptibility collected across Japan. Our analyses provided a complete classification of 3GC resistance mechanisms. Analyses with complete reference plasmids revealed that among the bla CTX-M extended-spectrum β-lactamase genes, bla CTX-M-8 was typically encoded in highly similar plasmids. The two major AmpC β-lactamase genes were bla CMY-2 and bla DHA-1 . Long-read sequencing of representative plasmids revealed that approximately 60% and 40% of bla CMY-2 and bla DHA-1 were encoded by such plasmids, respectively. Our analyses identified strains positive for carbapenemase genes but phenotypically susceptible to carbapenems and undetectable by standard antimicrobial susceptibility testing. Systematic long-read sequencing enabled reconstruction of 183 complete plasmid sequences encoding three major carbapenemase genes and elucidation of their geographical distribution stratified by replicon types and species carrying the plasmids and potential plasmid transfer events. Overall, we provide a blueprint for a national genomic surveillance study that integrates standardized quantitative antimicrobial susceptibility testing and characterizes resistance determinants., (© 2023. The Author(s).)

Background: The increasing prevalence of anaerobic bacteremia is a major concern worldwide and requires longitudinal monitoring., Methods: We present one of the largest and longest longitudinal studies on the prevalence and antimicrobial resistance of Bacteroides , Clostridium , Fusobacterium , and Prevotella spp. isolated from blood culture samples using national comprehensive surveillance data in Japan during 2011-2020 as part of the Japan Nosocomial Infections Surveillance., Results: Data for 41 949 Bacteroides spp., 40 603 Clostridium spp., 7013 Fusobacterium spp., and 5428 Prevotella spp. isolates were obtained. The incidences of bacteremia caused by Bacteroides fragilis , Clostridium perfringens , and Fusobacterium nucleatum significantly increased during the period ( P < .0001). Among the 20 species analyzed, 18 showed no significant changes in susceptibility over time, including B. fragilis , C perfringens , and F. nucleatum . However, resistance to clindamycin increased in B. thetaiotaomicron ( P = .0312), and resistance to ampicillin increased in B. ovatus ( P = .0008)., Conclusions: Our comprehensive national surveillance data analysis demonstrated a continuous increase in the incidence of anaerobic bacteremia, particularly in B. fragilis , C. perfringens , and F. nucleatum . This may be linked to the increasing number of colorectal cancer cases or advancing methods for species identification and susceptibility testing, requiring cautious interpretation. The discovery of an upsurge in anaerobic bacteremia and potential alterations in susceptibility highlights the necessity for more extensive studies in this field., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: From April 2022, the Japanese government funding system for assisted reproductive technology (ART) has shifted from government subsidies to universal health insurance. To date, studies estimating the health care expenditure for ART are scarce. We estimated health care expenditures for ART cycles and compared the proportion of patients' out-of-pocket payment by ovarian stimulation protocols under the Japanese government subsidy system., Methods: We linked payment information for government subsidies in Saitama Prefecture during 2016 and 2017 with the Japanese ART registry. Health care expenditures for all treatment cycles in Japan during 2017 among women aged <43 years (n = 369 757) were estimated using a generalized linear model., Results: We linked 6269 subsidy applications to the Japanese ART registry. The average treatment fee for a fresh cycle was 376 434 JPY (standard deviation = 159 581). However, significant variation was observed across ovarian stimulation protocols. The estimated health care expenditure for ART during 2017 was 101 278 629 888 JPY (920 714 817 USD), leading to a 0.24% increase in the national health care expenditure for fiscal year 2017. Fresh cycles accounted for 70% of the expenditure. The proportion of the average patient out-of-pocket payment for one treatment cycle was smaller for natural (0%) and mild ovarian stimulation using clomiphene citrate (4.5%-20.7%) than those of conventional stimulation (30.3%-32.4%)., Conclusions: Health insurance coverage for ART would increase national health care expenditure by 0.24%. Under the subsidy system, the proportion of the average patient out-of-pocket payment was smaller for natural and mild ovarian stimulation than conventional stimulations., (© 2023 Japan Society of Obstetrics and Gynecology.)

Background: Surgical site infections (SSIs) are among the most common healthcare-associated infections. Laparoscopy is increasingly being used in various surgical procedures. However, no study has examined the association between the proportion of laparoscopic procedures and the incidence of SSIs in digestive surgery using nationwide surveillance data., Methods: We retrospectively investigated national SSI surveillance data from the Japan Nosocomial Infections Surveillance between 2009 and 2019. The annual trend of the SSI rate and the proportion of laparoscopic procedures were assessed, focusing on five major digestive surgeries. This was based on data from 109,544 (appendix surgery), 206,459 (gallbladder surgery), 60,225 (small bowel surgery), 363,677 (colon surgery), and 134,695 (rectal surgery) procedures. The effect of a 10% increase in the proportion of laparoscopic procedures on the reduction of the SSI rate was estimated using mixed-effect logistic regression., Findings: The average SSI rate of the five digestive surgeries decreased from 11.8% in 2009 to 8.1% in 2019. The proportion of laparoscopic procedures in each of the five digestive surgeries increased continuously (p<0.001). The SSI rate for laparoscopic procedures was always lower than that for open procedures. The results were consistent between all and core hospitals participating in the surveillance. The odds ratios of the 10% increase in the proportion of laparoscopic procedures for five digestive surgeries were always <0.950 (p<0.001)., Conclusion: An increase in the proportion of laparoscopic procedures was associated with a reduction in the SSI rate in digestive surgeries., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kajihara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We have recently reported the isolation of third-generation-cephalosporin-resistant Gram-negative bacteria from the oral cavity of residents of a long-term-care facility (LTCF). Since disinfectants are often used in the oral cavity, it is important to investigate the disinfectant susceptibility of oral bacteria. Here, we evaluated the susceptibilities of Gram-negative antimicrobial-resistant bacteria (GN-ARB), including Pseudomonas, Acinetobacter, and Enterobacteriaceae , obtained from the oral cavity of residents of LTCFs to povidone-iodine (PVPI), cetylpyridinium chloride (CPC), benzalkonium chloride (BZK), and chlorhexidine chloride (CHX). We also evaluated the susceptibilities of isolates from the rectum to the same agents to compare the susceptibility profiles of oral and rectal isolates. Next, we investigated the relationship between their susceptibility and disinfectant resistance genes delineated by whole-genome sequencing of the isolates. Additionally, we evaluated the correlation between disinfectant-resistant GN-ARB and clinical information. In oral GN-ARB, the MIC of PVPI showed almost identical values across isolates, while the MICs of CPC, BZK, and CHX showed a wide range of variation among species/strains. In particular, Pseudomonas aeruginosa exhibited high-level resistance to CPC and BZK. The disinfectant susceptibility of rectal GN-ARB showed a tendency similar to that of oral GN-ARB. The presence of qacE Δ 1 was correlated with CPC/BZK resistance in P. aeruginosa, while other species exhibited no correlation between qacE Δ 1 and resistance. Multiple analyses showed the correlation between the presence of CPC-resistant bacteria in the oral cavity and tube feeding. In conclusion, we found that some oral GN-ARB isolates showed resistance to not only antibiotics but also disinfectants. IMPORTANCE Antibiotic-resistant bacteria (ARB) are becoming a serious concern worldwide. We previously reported the isolation of third-generation-cephalosporin-resistant Gram-negative bacteria from the oral cavity of residents of a long-term-care facility (LTCF). To prevent infection with ARB in hospitals and eldercare facilities, we must pay more attention to the use of not only antibiotics but also disinfectants. However, the effect of disinfectants on ARB is unclear. In this study, we evaluated the susceptibility of Gram-negative ARB (GN-ARB) from the oral cavity of residents of LTCFs to some disinfectants that are often used for the oral cavity; we found that some isolates showed resistance to several disinfectants. This is the first comprehensive analysis of the disinfectant susceptibility of oral GN-ARB. These results provide some important information for infection control and suggest that disinfectants should be applied carefully.

Both Achilles and masticatory muscle tendons are large load-bearing structures, and excessive mechanical loading leads to hypertrophic changes in these tendons. In the maxillofacial region, hyperplasia of the masticatory muscle tendons and aponeurosis affect muscle extensibility resulting in limited mouth opening. Although gene expression profiles of Achilles and patellar tendons under mechanical strain are well investigated in rodents, the gene expression profile of the masticatory muscle tendons remains unexplored. Herein, we examined the gene expression pattern of masticatory muscle tendons and compared it with that of Achilles tendons under tensile strain conditions in the Japanese macaque Macaca fuscata. Primary tenocytes isolated from the masticatory muscle tendons (temporal tendon and masseter aponeurosis) and Achilles tendons were mechanically loaded using the tensile force and gene expression was analyzed using the next-generation sequencing. In tendons exposed to tensile strain, we identified 1076 differentially expressed genes with a false discovery rate (FDR) < 10-10. To identify genes that are differentially expressed in temporal tendon and masseter aponeurosis, an FDR of < 10-10 was used, whereas the FDR for Achilles tendons was set at > 0.05. Results showed that 147 genes are differentially expressed between temporal tendons and masseter aponeurosis, out of which, 125 human orthologs were identified using the Ensemble database. Eight of these orthologs were related to tendons and among them the expression of the glycoprotein nmb and sphingosine kinase 1 was increased in temporal tendons and masseter aponeurosis following exposure to tensile strain. Moreover, the expression of tubulin beta 3 class III, which promotes cell cycle progression, and septin 9, which promotes cytoskeletal rearrangements, were decreased in stretched Achilles tendon cells and their expression was increased in stretched masseter aponeurosis and temporal tendon cells. In conclusion, cyclic strain differentially affects gene expression in Achilles tendons and tendons of the masticatory muscles., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: The prevalence of antimicrobial-resistant bacteria (ARB) in long-term care facilities (LTCFs) remains unclear. Furthermore, the effect of ARB colonization on the clinical outcomes of LTCF residents has not been explored., Methods: We conducted a prospective multicenter cohort study and investigated the residents (N = 178) of six Japanese LTCFs (three Welfare Facilities for the Elderly Requiring Long-term Care and three Geriatric Health Service Facilities) for oral and rectal carriage of ARB. The clinical outcomes of the residents were evaluated based on isolating bacterial strains and subjecting them to whole-genome sequencing., Results: Of the 178 participants, 32 belonging to Geriatric Health Service Facilities with no information on their clinical outcome were excluded, and the remaining 146 were followed up for at most 21 months. Extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and Pseudomonas aeruginosa were detected in 42.7% (n = 76) and 2.8% (n = 5) of the rectal swabs and 5.6% (n = 10) and 3.4% (n = 6) of the oral swabs, respectively. Detection of ARB in the oral and rectal cavities showed remarkable association with enteral nutrition. Further, P. aeruginosa was significantly associated with an increase in mortality of the residents, but there were not significant association between ESBL-producing Enterobacterales and mortality. Core-genome phylogeny of P. aeruginosa revealed a wide-spread distribution of the isolated strains across the phylogeny, which included a cluster of ST235 strains with substantially higher biofilm formation ability than the other isolated P. aeruginosa strains., Discussion/conclusion: This study is the first to investigate the carriage of both oral and rectal ARB, genomic relatedness and determinants of antimicrobial resistance in isolated strains, and clinical outcomes of LTCF residents. Our study provides the first direct evidence for the burden of antimicrobial resistance in LTCFs., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: Hematopoietic tissues of vertebrates are highly radiation sensitive and the effects of ionizing radiation on the hematopoiesis have been studied in mammals and teleosts for decades. In this study, radiation responses in the kidney, the main hematopoietic organ in teleosts, were investigated in Japanese medaka ( Oryzias latipes ), which has been a model animal and a large body of knowledge has been accumulated in radiation biology., Methods: Kidney, the main hematopoietic tissue of adult medaka fish, was locally irradiated using proton and carbon ion beams irradiation system of Takasaki Ion Accelerator for Advanced Radiation Application (TIARA), QST, and the effects on peripheral blood cells and histology of the kidney were investigated., Results: When only kidneys were locally irradiated with proton or carbon ion beam (15 Gy), the hematopoietic cells in the irradiated kidney and cell density in the peripheral blood decreased 7 days after the irradiation in the same manner as after the whole-body irradiation with γ-rays (15 Gy). These results demonstrate that direct irradiation of the hematopoietic cells in the kidney induced cell death and/or cell cycle arrest and stopped the supply of erythroid cells. Then, the cell density in the peripheral blood recovered to the control level within 4 days and 7 days after the γ-ray and proton beam irradiation (15 Gy), respectively, while the cell density in the peripheral blood did not recover after the carbon ion beam irradiation (15 Gy). The hematopoietic cells in the irradiated kidneys temporarily decreased and recovered to the control level within 21 days after the γ-ray or proton beam irradiation (15 Gy), while it did not recover after the carbon ion beam irradiation (15 Gy). In contrast, the recovery of the cell density in the peripheral blood delayed when anemic medaka were irradiated 1 day after the administration of phenylhydrazine. With and without γ-ray irradiation, a large number of hematopoietic cells was still proliferating in the kidney 7 days after the anemia induction., Conclusions: The results obtained strongly suggest that the hematopoietic stem cells in medaka kidney prioritize to proliferate and increase peripheral blood cells to eliminate anemia, even when they are damaged by high-dose irradiation.

The increasing incidence of candidemia and the emergence of drug-resistant Candida species are major concerns worldwide. Therefore, long-term surveillance studies are required. Here, we provide one of the largest longitudinal overviews of the trends in the prevalence of Candida species using national data of 57 001 candidemia isolates obtained from > 2000 hospitals for the 2010-2019 period in the Japan Nosocomial Infections Surveillance database. The proportion of Candida species, except Candida krusei and Candida guilliermondii, was almost the same during the study period. The proportion of C. guilliermondii surpassed that of C. krusei in 2014. The incidence of candidemia due to C. albicans (P < 0.0001), C. parapsilosis (P = 0.0002), and C. tropicalis (P < 0.0001) have decreased significantly over this period. Azole susceptibility of C. tropicalis was low, with 17.8% of isolates resistant to fluconazole and 13.5% resistant to voriconazole. The micafungin susceptibility of C. glabrata was low, with 8.0% of isolates showing resistance. The resistance rate of C. krusei toward amphotericin B fluctuated considerably (between 3.2% and 35.7%) over this period. The incidence rate of candidemia caused by C. parapsilosis and C. guilliermondii in hospitals responsible for bone marrow transplantation was significantly higher than that in other hospitals. Overall, our study suggests that in Japan, the species distribution of Candida was almost the same in this period and similar to that reported in North America and Europe. A relatively high resistance to azoles and micafungin was observed in C. glabrata, C. tropicalis, and C. krusei isolates, which require continued surveillance., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Endometriosis is characterized by the presence of inflamed and fibrotic endometrial tissue outside the uterine cavity. Previously, we found decreased SERPINA1 (alpha-1 antitrypsin) expression in endometriosis-like lesions in a mouse model of endometriosis, suggesting that it exacerbated inflammation in these lesions. However, the molecular mechanism(s) by which SERPINA1 affects expression of inflammatory factors and development of endometriotic lesions have not been fully characterized. To investigate the role of intracellular SERPINA1 in endometrial stromal cells (ESCs), we performed RNA sequence analysis using RNA extracted from ESCs in which SERPINA1 was knocked down. The analysis identified several toll-like receptor (TLR)-related factors as being upregulated. Silencing of SERPINA1 increased expression of TLR3 and TLR4 in ESCs, as well as several TLR signaling pathway components, including MYD88, IRAK1/4, interleukin (IL)-1β, and interferon (IFN)-β. TLR3 or TLR4 agonists increased expression of inflammatory factors in SERPINA1-knockdown ESCs, whereas TLR3 or TLR4 inhibitors decreased expression. In addition, treatment with recombinant IL-1β or IFN-β increased expression of MYD88 and inflammatory factors in ESCs. Immunohistochemical analysis of endometriotic tissues showed that TLR3, TLR4, and MYD88 were localized in endometriosis lesions. Taken together, the data suggest that reduced expression of SERPINA1 induces expression of inflammatory factors by ESCs, which in turn are associated with TLR3/4, IL-1β, and IFN-β signaling. Regulation of intracellular SERPINA1 levels in ESCs may be a strategy to inhibit inflammatory responses in endometriotic lesions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kusama, Satoyoshi, Azumi, Yoshie, Kojima, Mizuno, Ono, Nishi, Kajihara and Tamura.)

Background: This study aimed to determine the factors associated with an unfavorable clinical course (emergency surgery and/or prolonged hospitalization) in patients requiring hospitalization owing to pelvic inflammatory disease (PID)., Methods: A retrospective study was performed on 117 patients diagnosed with PID who were admitted to our hospital between January 2014 and December 2018. Multivariate regression analysis was conducted to determine the factors associated with emergency surgical intervention, and prolonged hospitalization in a subgroup of successful expectant management (n = 93)., Results: The average age (mean ± standard deviation) of the patients was 41.2 ± 12.5 years; 16 (13.7%) were postmenopausal; 81 patients (69.2%) complicated with a tubo-ovarian abscess (TOA) of which 59 (72.9%) had an ovarian endometrioma; and 19 patients (16.2%) had a history of various intrauterine manipulations. Emergency surgery was performed in 24 patients (20.5%), and patients with TOA underwent emergency surgery more often than did patients without TOA (25.9% vs. 8.3%, p = 0.03), and TOA was associated with longer length of hospital stay (17.1 days vs. 8.0 days, p = 0.01). Smoking, postmenopausal status, past medical history of PID, and high C-reactive protein (CRP) level at admission were significantly associated with emergency surgery. In patients with successful expectant management, obesity (body mass index ≥ 30) and high WBC and CRP level at admission were significantly associated with prolonged hospitalization., Conclusions: Of the patients requiring hospitalization owing to PID, TOA was associated with both emergency surgery and prolonged hospital stay. Patients with increased inflammatory markers and obesity should be considered to be at a high risk for unfavorable clinical course in the management of PID., (© 2022. The Author(s).)

Determining the concentrations of different Sn ions in glass containing iron oxide by wet chemical analysis is a challenge because a redox reaction occurs between Sn 2+ and Fe 3+ . A chemical analysis method for determining the concentrations of Sn 2+ and Sn 4+ in soda lime glass containing iron oxide was proposed. A mixture of ascorbic acid, hydrochloric acid, and hydrofluoric acid was used to decompose the sample in a vessel with nitrogen flow. Ascorbic acid functioned as a reductant for Fe 3+ . Subsequently, the Sn 2+ were separated as a diethyldithiocarbamate complex. Furthermore, inductively coupled plasma atomic emission spectroscopy was used to determine the concentrations of Sn 4+ and total Sn, from which the concentration of Sn 2+ can be calculated. The results were validated by comparing ratios of Sn 2+ to total Sn to results obtained using Mössbauer spectroscopy. The results were in agreement, thereby validating the use of the proposed approach., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Brain radiation necrosis (RN) or neurocognitive disorder is a severe adverse effect that may occur after radiation therapy for malignant brain tumors or head and neck cancers. RN accompanies inflammation which causes edema or micro-bleeding, and no fundamental treatment has been developed. In inflammation, lysophospholipids (LPLs) are produced by phospholipase A 2 and function as bioactive lipids involved in sterile inflammation in atherosclerosis or brain disorders. To elucidate its underlying mechanisms, we investigated the possible associations between lysophospholipids (LPLs) and RN development in terms of microglial activation with the purinergic receptor P2X purinoceptor 4 (P2RX4). We previously developed a mouse model of RN and in this study, measured phospholipids and LPLs in the brains of RN model by liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. We immune-stained microglia and the P2RX4 in the brains of RN model with time-course. We treated RN model mice with ivermectin, an allosteric modulator of P2RX4 and investigate the effect on microglial activation with P2RX4 and LPLs' production, and resulting effects on overall survival and working memory. We revealed that LPLs (lysophosphatidylcholine (LPC), lysophosphatidyl acid, lysophosphatidylserine, lysophosphatidylethanolamine, lysophosphatidylinositol, and lysophosphatidylglycerol) remained at high levels during the progression of RN with microglial accumulation, though phospholipids elevations were limited. Both microglial accumulation and activation of the P2RX4 were attenuated by ivermectin. Moreover, the elevation of all LPLs except LPC was also attenuated by ivermectin. However, there was limited prolongation of survival time and improvement of working memory disorders. Our findings suggest that uncontrollable increased LPC, even with ivermectin treatment, promoted the development of RN and working memory disorders. Therefore, LPC suppression will be essential for controlling RN and neurocognitive disorder after radiation therapy., (© 2022. The Author(s).)

The national action plan on antimicrobial resistance (AMR) in Japan emphasizes the importance of understanding antimicrobial use (AMU). Some studies have been conducted on oral and parenteral AMU in Japan. However, there are few studies on the use of topical antimicrobials, such as in dermatology and ophthalmology. Therefore, the purpose of this study was to investigate the use of topical AMU in Japan. Data on AMU in dermatology and ophthalmology were obtained from the 2017 National Database of Health Insurance Claims and Specific Health Checkups of Japan Open Data. The number of dermatological products used was 58,396,530 in 2017. The proportions of betamethasone/gentamicin and gentamicin used were 50.5% and 16.7%, respectively, whereas that of the ingredient quantity in gentamicin was 7.8%. It has been suggested that topical AMU should be evaluated based on the number of products being used. The number of ophthalmological products used was 24,655,653 in 2017, and the proportion of quinolones used was 95.9%. The high prescription rate of quinolones may cause an increase in quinolone resistance in the ophthalmologic field. Topical AMU, which is a potential "blind spot" in the measures against AMR, needs to be continuously monitored, together with systemic AMU.

Endometriosis is characterized by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal hemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, menstruation-related factors, PGE2 and thrombin (P/T), a PAR1 agonist induced epithelial-mesenchymal transition (EMT) of endometrial cells under hypoxia. However, the molecular mechanisms by which P/T induce development of endometriosis have not been fully characterized. To investigate the effects of P/T, RNA extracted from endometrial stromal cells (ESCs) treated with P/T were subjected to RNA sequence analysis, and identified activin A, FOS, and GATA2 as upregulated genes. Activin A increased the expression of connective tissue growth factor (CTGF) and mesenchymal marker genes in ESCs. CTGF induced the expression of fibrosis marker type I collagen, fibronectin, and α-smooth muscle actin (αSMA), indicating fibroblast to myofibroblast transdifferentiation (FMT) of ESCs. In addition, activin A, FOS, GATA2, CTGF, and αSMA were localized in endometriosis lesions. Taken together, our data show that P/T induces changes resembling EMT and FMT in ectopic ESCs derived from retrograde menstruation, and that these are associated with fibrotic changes in the lesions. Pharmacological means that block P/T-induced activin A and CTGF signaling may be strategies to inhibit fibrosis in endometriotic lesions., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The impact of the coronavirus disease (COVID-19) pandemic on antimicrobial resistance (AMR) is a major concern., Aim: To compare the number of patients and isolation rate of antimicrobial-resistant bacteria before and after the beginning of the COVID-19 pandemic using the comprehensive national surveillance data., Methods: We utilized comprehensive surveillance data, collected in the Japan Nosocomial Infections Surveillance programme, which included a total of 16.7 million samples of 5.9 million tested patients from >1300 hospitals. We compared the number of patients and isolation rate of five bacteria between 2019 and 2020, including antimicrobial-susceptible and -resistant bacteria of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa., Findings: The number of patients and isolation rate of S. aureus and meticillin-resistant S. aureus decreased slightly; those of S. pneumoniae and penicillin-resistant S. pneumoniae decreased by 60%; and those of third-generation cephalosporin-resistant K. pneumoniae increased. The isolation rate of the remaining bacteria apparently increased, although the number of patients decreased. This was due to a substantial decrease in the total number of tested patients (the denominator of the isolation rate), which was larger than that of the number of patients (the numerator of the isolation rate). Consistent results were obtained when the same data were re-aggregated using the procedure of the World Health Organization Global Antimicrobial Resistance Surveillance System, demonstrating the general importance of this problem., Conclusion: Surveillance data during the COVID-19 pandemic must be carefully interpreted based on examination of the numerator, denominator and background factors that affect the denominator., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Studies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles., (© 2021. The Author(s).)

Background: The association between the frequency of surgeries and the incidence of surgical site infections (SSIs) has been reported for various surgeries. However, no previous study has explored this association among video-assisted thoracic surgeries (VATS). Hence, we aimed to investigate the association between the frequency of surgeries and SSI in video-assisted thoracic surgeries., Methods: We analyzed the data of 26,878 thoracic surgeries, including 21,154 VATS, which were collected during a national surveillance in Japan between 2014 and 2018. The frequency of surgeries per hospital department was categorized into low (< 50/year), moderate (50-100/ year), and high (> 100/year). Chi-squared test or Fisher's exact test was used for discrete explanatory variables, whereas Wilcoxon's rank-sum test or Kruskal-Wallis test was used for continuous explanatory variables. Univariate analysis of the department groups was conducted to explore confounding factors associated with both SSIs and the department groups. We used a multiple logistic regression model focusing on VATS and stratified by the National Nosocomial Infections Surveillance System (NNIS) risk index., Results: The rates of SSIs in the hospital groups with low, moderate, and high frequency of surgeries were 1.39, 1.05, and 1.28%, respectively. In the NNIS risk index 1 stratum, the incidence of SSIs was significantly lower in the moderate-frequency of surgeries group than that in the other groups (odds ratio [OR]: vs. low-frequency of surgeries: 2.48 [95% confidence interval [CI]: 1.20-5.13], P = 0.0143; vs. high-frequency of surgeries: 2.43 [95% CI: 1.44-4.11], P = 0.0009). In the stratum of NNIS risk indices 2 and 3, the incidence of SSI was significantly higher in the low-frequency of surgeries group (OR: 4.83, 95% CI: 1.47-15.93; P = 0.0095)., Conclusion: The result suggests that for departments with low-frequency of surgeries, an increase in the frequency of surgeries to > 50 per department annually potentially leads to a decrease in the incidence of SSIs. This occurs through an increase in the experience of the departmental surgeons and contributes to the improvement of VATS outcomes in thoracic surgeries.

Japan Nosocomial Infections Surveillance (JANIS) is one of the largest national antimicrobial resistance (AMR) surveillance systems in the world. The JANIS Clinical Laboratory division collects comprehensive specimen-based data from diagnostic microbiology laboratories of participating hospitals to monitor the isolation rate of 11 major bacteria and specific AMR bacteria, and creates antibiograms of approximately 20 bacterial species. Data on the JANIS web database system are also annually tabulated and shared with the WHO Global Antimicrobial Resistance Surveillance System. To create a network of international AMR surveillance systems among Asian countries, Japan is developing an international web database system named ASIan Antimicrobial Resistance Surveillance Network (ASIARS-Net) based on the JANIS system; ASIARS-Net is an open-source database and confidentially available at almost no cost. JANIS continues to evolve in multiple directions; some are discussed at the end of this review.

Enterobacterales resistant to carbapenems, a class of last-resort antimicrobials, are ranked as an "urgent" and "critical" public health hazard by CDC and WHO. IMP-type carbapenemase-containing Enterobacterales are endemic in Japan, and blaIMP-6 is one of the notable carbapenemase genes responsible for the resistance. The gene is plasmid-encoded and confers resistance to meropenem, but not to imipenem. Therefore, IMP-6-producing Enterobacterales isolates are occasionally overlooked in clinical laboratories and are referred to as 'stealth-type'. Since previous reports in Japan were confined only to some geographical regions, their distribution across prefectures and the factors affecting the distribution remain unclear. Here, we revealed the dynamics of the geographical distribution of Enterobacterales with IMP-6 phenotype associated with antimicrobial use in Japan. We utilized comprehensive national surveillance data of all routine bacteriological test results from more than 1,400 hospitals in 2015 and 2016 to enumerate Escherichia coli and Klebsiella pneumoniae isolates with the antimicrobial susceptibility pattern (phenotype) characteristic of IMP-6 (imipenem susceptible, meropenem resistant), and to tabulate the frequency of isolates with the phenotype for each prefecture. Isolates were detected in approximately half of all prefectures, and combined analysis with the national data of antimicrobial usage revealed a statistically significant association between the frequency and usage of not carbapenems but third-generation cephalosporins (p = 0.006, logistic mixed-effect regression) and a weaker association between the frequency and usage of fluoroquinolones (p = 0.043). The usage of third-generation cephalosporins and fluoroquinolones may select the strains with the IMP-6 phenotype, and contribute to their occasional spread. We expect the findings will promote antimicrobial stewardship to reduce the spread of the notable carbapenemase gene., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the risk of ectopic pregnancies (EPs) for fresh cycles according to different ovarian stimulation protocols., Design: Registry-based retrospective cohort study., Setting: Not applicable., Patient(s): A total of 68,851 clinical pregnancies after fresh single embryo transfer between 2007 and 2015., Intervention (s): None MAIN OUTCOME MEASURE(S): Ectopic pregnancies. Odds ratios and 95% confidence intervals for EPs were calculated by using generalized estimating equations adjusted for potential maternal and treatment characteristics., Result(s): Among 68,851 clinical pregnancies, 1,049 (1.46%) cases of EP were reported. Compared with natural cycles, all ovarian stimulation protocols were associated with a significantly increased risk of EP. Ovarian stimulation with clomiphene (CC) demonstrated the highest odds ratios for EPs. Significant associations between ovarian stimulation protocols and EP compared with natural cycles were prominent when the number of retrieved oocytes was low (1-3) to moderate (4-7), but there were no significant associations when the number of retrieved oocytes was high (≥8)., Conclusion(s): Ovarian stimulation protocols were significantly associated with an increased risk of EP. In particular, ovarian stimulation with CC had the highest risk of EP compared with other stimulation protocols. Further studies are essential to investigate possible confounding factors for different ovarian stimulation protocols, especially CC, and the risk of EP., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression. They play fundamental roles in several biological processes, including cell differentiation and proliferation, embryo development, organ development, and organ metabolism. Besides regulating the physiological processes, miRNAs regulate various pathological conditions such as tumors, metastases, metabolic diseases, and osteoporosis. Although several studies have been performed on miRNAs, only few studies have described the miRNA expression and functions in human reproductive tract tissues. During menstruation, the human endometrium undergoes extensive cyclic morphological and biochemical modifications before embryo implantation. In addition to the ovarian steroid hormones (estrogen and progesterone), endometrial autocrine or paracrine factors and embryo-derived signals play a significant role in endometrial functions. miRNAs are considered key regulators of gene expression in the human endometrium and implantation process, and their aberrant expression levels are associated with the development of various disorders, including tumorigenesis. In this review, we summarize the studies that show the role of miRNAs in regulating the physiological conditions of the endometrium and the implantation process and discuss the aberrant expression of miRNAs in ectopic pregnancy, endometriosis, and endometrial cancer.

Purpose: Subendometrial myometrium exerts wave-like activity throughout the menstrual cycle, and uterine peristalsis is markedly reduced during the implantation phase. We hypothesized that abnormal uterine peristalsis has an adverse effect on the endometrial decidualization process. We conducted an in vitro culture experiment to investigate the effect of cyclic stretch on the morphological and biological endometrial decidual process., Methods: Primary human endometrial stromal cells (HESCs) were isolated from hysterectomy specimens and incubated with or without 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and medroxyprogesterone acetate (MPA) for 3 days. After decidualization, cultures were continued for 24 hours with or without cyclic stretch using a computer-operated cell tension system., Results: Cyclic stretch significantly repressed expression of decidual markers including insulin-like growth factor-binding protein 1 ( IGFBP1 ), prolactin ( PRL ), forkhead box O1 ( FOXO1 ), and WNT4 on decidualized HESCs. In addition, cyclic stretch of decidualized HESCs affected the decidual morphological phenotype to an elongated shape. The alternation of F-actin localization in decidualized HESCs was not observed in response to cyclic stretch., Conclusions: These data suggest that cyclic stretch inhibits the morphological and biological decidual process of HESCs. Our findings imply that uterine abnormal contractions during the implantation period impair endometrial decidualization and contribute to infertility., Competing Interests: Conflict of interest: The authors declare no conflict of interest. Human rights statement and informed consent: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institution and national) and with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from all patients included in the study. The Institutional Review Board of the Saitama Medical University Hospital approved this study., (© 2020 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

A major issue in the surveillance of antimicrobial resistance (AMR) is "de-duplication" or removal of repeated isolates, for which there exist multiple methods. The World Health Organization (WHO) Global Antimicrobial Resistance Surveillance System (GLASS) requires de-duplication by selecting only the first isolate of a given bacterial species per patient per surveillance period per specimen type per age group, gender, and infection origin stratification. However, no study on the comparative application of this method has been reported. The objective of this study was to evaluate differences in data tabulation between the WHO GLASS and the Japan Nosocomial Infections Surveillance (JANIS) system, which counts both patients and isolates after removing repeated isolates of the same bacterial species isolated from a patient within 30 days, regardless of specimen type, but distinguishing isolates with change of antimicrobial resistance phenotype. All bacterial data, consisting of approximately 8 million samples from 1795 Japanese hospitals in 2017 were exported from the JANIS database, and were tabulated using either the de-duplication algorithm of GLASS, or JANIS. We compared the tabulated results of the total number of patients whose blood and urine cultures were taken and of the percentage of resistant isolates of Escherichia coli for each priority antibiotic. The number of patients per specimen type tabulated by the JANIS method was always smaller than that of GLASS. There was a small (< 3%) difference in the percentage of resistance of E. coli for any antibiotic between the two methods in both out- and inpatient settings and blood and urine isolates. The two tabulation methods did not show considerable differences in terms of the tabulated percentages of resistance for E. coli. We further discuss how the use of GLASS tabulations to create a public software and website that could help to facilitate the understanding of and treatment against AMR., Competing Interests: The authors have declared that no competing interests exist.

There has been scarce evidence about deaths due to blood stream infection (BSI) in Japan so far. The main objective of this study is to understand the epidemiological trend of deaths caused by BSIs due to Staphylococcus aureus and Escherichia coli including Methicillin-resistant S. aureus (MRSA) and fluoroquinolone-resistant E. coli (FQREC) at national level. We annually estimated the number of BSI caused by S. aureus and E. coli between 2011 and 2017 across Japan using comprehensive data of bacterial culturing and drug susceptibilities collected in Japan Nosocomial Infection Surveillance (JANIS). The number of death was estimated by using BSI mortality obtained from previous studies in Japan. The number of BSI death attributable to S. aureus was estimated to 17,412 in 2011 and 17,157 in 2017, respectively, out of the whole population (126.8 million) in Japan. Among them, cases attributed to MRSA accounted for 5924 (34.0%) in 2011, and decreased to 4224 (24.6%) cases in 2017. On the other hand, the number of BSI death attributable to E. coli was estimated to 9044 in 2011 and increased to 14,016 in 2017. Among them, cases attributed to FQREC accounted for 2045 (22.6%) in 2011 and increased to 3915 (27.9%) cases in 2017. The number of BSI death attributable to MRSA has been decreasing and that attributable to FQREC has been increasing. This study provides the first annual estimate of disease burden of BSI caused by antimicrobial resistant (AMR) bacteria in Japan, and basis for formulating health policy to deal with AMR., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aeromonas dhakensis, a newly recognized species, is often misidentified as A. hydrophila, A. veronii, or A. caviae by commercial phenotypic tests. Limited data about A. dhakensis are available in Japan. We retrospectively analyzed the patients with monomicrobial Aeromonas bacteremia at Hiroshima University Hospital from January 2011 to December 2017, and species re-identification was conducted using rpoD and gyrB gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Of the 19 strains from blood isolates, A. caviae (n = 9, 47.4%), A. dhakensis (n = 4, 21.1%), A. hydrophila (n = 3, 15.8%), and A. veronii (n = 3, 15.8%) were re-identified. A. dhakensis was phenotypically misidentified as A. hydrophila (n = 3, 75%) or A. sobria (n = 1, 25%). A. dhakensis was also misidentified as A. caviae (n = 2, 50%), A. hydrophila (n = 1, 25%), and A. jandaei (n = 1, 25%) in MALDI-TOF MS system. Malignancies (n = 12, 63.2%) and liver cirrhosis (n = 7, 36.8%) were common comorbidities. Biliary tract infection was the most frequent source of Aeromonas bacteremia (n = 11, 57.9%). The major source of A. dhakensis bacteremia was also biliary tract infection (n = 3, 75%), and the 14-day infection-related mortality of A. dhakensis was 25%. A. dhakensis isolates showed similar clinical characteristics, antimicrobial susceptibility, and mortality with those of other Aeromonas species isolates. This study demonstrated that A. dhakensis is not a rare cause of Aeromonas bacteremia, but is often misidentified as A. hydrophila in Hiroshima, Japan. Further studies should be conducted to identify the geographical distribution and clinical impact of A. dhakensis in Japan., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Clinical trials have shown that administering heparin during the luteal phase has beneficial effects on implantation and live birth rates. Heparin exerts direct effects on decidual human endometrial stromal cells (HESCs), which are independent of its anticoagulant effect. However, the accurate effects of heparin on the decidualization process remain unidentified. Here, we demonstrate that HESCs become dramatically resistant to oxidative stress upon decidualization, and we hypothesize a possible direct action of heparin on the decidualization of HESCs, which would lead to improved implantation. To test this hypothesis, we established primary HESC cultures and propagated them, and then we decidualized confluent cultures with 8-bromo-cAMP, with medroxyprogesterone acetate, and with or without heparin. We treated the cells with hydrogen peroxide (H 2 O 2 ) as a source of reactive oxygen species (ROS). Adding heparin to decidualized HESCs induced prolactin secretion. Decidualized HESCs treated with heparin were prevented from undergoing apoptosis induced by oxidative stress. Heparin induced nuclear accumulation of the forkhead transcription factor FOXO1 and expression of its downstream target, the ROS scavenger superoxide dismutase 2. These results demonstrate that heparin-treated decidualized HESCs acquired further resistance to oxidative stress, suggesting that heparin may improve the implantation environment.

The emergence of a Japan-intrinsic community associated methicillin-resistant Staphylococcus aureus strain (CA-MRSA/J) has been reported. A 70-year-old man with recurrent colon cancer and a history of mitral valve replacement was admitted to the hospital in a state of shock. He was diagnosed with prosthetic valve endocarditis (PVE) caused by MRSA and underwent cardiac surgery. The MRSA isolates belonged to multilocus sequence type 8 and carried staphylococcal cassette chromosome mec IVl and the genes of toxic shock syndrome toxin-1, enterotoxin C, and enterotoxin L. These characteristics indicated a CA-MRSA/J clone. This is the first reported case of PVE caused by CA-MRSA/J.

Saccharomyces cerevisiae sake yeast strain Kyokai no. 7 (K7) and its relatives carry a homozygous loss-of-function mutation in the RIM15 gene, which encodes a Greatwall family protein kinase. Disruption of RIM15 in nonsake yeast strains leads to improved alcoholic fermentation, indicating that the defect in Rim15p is associated with the enhanced fermentation performance of sake yeast cells. In order to understand how Rim15p mediates fermentation control, we here focused on target-of-rapamycin protein kinase complex 1 (TORC1) and protein phosphatase 2A with the B55δ regulatory subunit (PP2A B55δ ), complexes that are known to act upstream and downstream of Rim15p, respectively. Several lines of evidence, including our previous transcriptomic analysis data, suggested enhanced TORC1 signaling in sake yeast cells during sake fermentation. Fermentation tests of the TORC1-related mutants using a laboratory strain revealed that TORC1 signaling positively regulates the initial fermentation rate in a Rim15p-dependent manner. Deletion of the CDC55 gene, encoding B55δ, abolished the high fermentation performance of Rim15p-deficient laboratory yeast and sake yeast cells, indicating that PP2A B55δ mediates the fermentation control by TORC1 and Rim15p. The TORC1-Greatwall-PP2A B55δ pathway similarly affected the fermentation rate in the fission yeast Schizosaccharomyces pombe , strongly suggesting that the evolutionarily conserved pathway governs alcoholic fermentation in yeasts. It is likely that elevated PP2A B55δ activity accounts for the high fermentation performance of sake yeast cells. Heterozygous loss-of-function mutations in CDC55 found in K7-related sake strains may indicate that the Rim15p-deficient phenotypes are disadvantageous to cell survival. IMPORTANCE The biochemical processes and enzymes responsible for glycolysis and alcoholic fermentation by the yeast S. cerevisiae have long been the subject of scientific research. Nevertheless, the factors determining fermentation performance in vivo are not fully understood. As a result, the industrial breeding of yeast strains has required empirical characterization of fermentation by screening numerous mutants through laborious fermentation tests. To establish a rational and efficient breeding strategy, key regulators of alcoholic fermentation need to be identified. In the present study, we focused on how sake yeast strains of S. cerevisiae have acquired high alcoholic fermentation performance. Our findings provide a rational molecular basis to design yeast strains with optimal fermentation performance for production of alcoholic beverages and bioethanol. In addition, as the evolutionarily conserved TORC1-Greatwall-PP2A B55δ pathway plays a major role in the glycolytic control, our work may contribute to research on carbohydrate metabolism in higher eukaryotes., (Copyright © 2018 American Society for Microbiology.)

Purpose: High-mobility group N (HMGN) proteins are the only non-histone proteins that specifically bind within the nucleosome between core histones and DNA. Among them, HMGN5 is one of the candidates that could participate in mouse endometrial decidualization; however, the specific role of HMGN5 remains to be clarified in human endometrial stromal cells (HESCs)., Methods: Primary HESCs were isolated from hysterectomy specimens and incubated with or without 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and medroxyprogesterone acetate (MPA)., Results: We demonstrated that HMGN5 expression in decidualized HESCs stimulated by 8-br-cAMP and MPA decreased significantly. The inhibition of HMGN5 expression by small interfering RNA (siRNA) induced the major decidual marker genes expression, including IGFBP1 (insulin-like growth factor binding protein 1) and PRL (prolactin). In addition, microRNA-542-3p (miR-542-3p), which was identified as a regulatory miRNA of IGFBP1 during decidualization, was significantly suppressed by HMGN5 siRNA. However, the expression of HMGN5 was not alternated by miR-542-3p overexpression., Conclusions: These findings suggest that the down-regulation of HMGN5 plays a role in the promotion of human endometrial stromal decidualization and acts upstream of miR-542-3p.

Background: The Japanese government adopted a national action plan on antimicrobial resistance, which aims to reduce drug-resistant pathogens and antimicrobial use. A point-prevalence survey (PPS) is a useful surveillance method to gain information about hospital epidemiology; however, no multi-centre PPS has previously been performed in Japan., Aim: To investigate general information about hospital epidemiology, healthcare-associated infections (HCAIs), and antimicrobial use in multiple Japanese university hospitals., Methods: In July 2016, a multi-centre PPS was conducted using a standardized protocol at four university hospitals in Japan., Findings: A total of 3199 patients were included. Median age and duration of hospital stay were 64 years and 10 days, respectively. A total of 246 (7.7%; 95% confidence interval (CI): 6.8-8.7) patients had 256 active HCAIs, and 933 (29.2%; 95% CI: 27.6-30.8) patients received 1318 antimicrobials. Pneumonia and gastrointestinal system infection were the most common HCAIs (N = 42, 16.4%), and Enterobacteriaceae (N = 49, 30.8%) were the predominant causative organisms. Carbapenems (N = 52, 17.8%), anti-MRSA medications, and cephems with antipseudomonal activity were the most frequently prescribed antimicrobials for HCAIs. As surgical prophylaxis, 46 of 278 antimicrobials (16.5%) were administered orally. Proportions of HCAI and antimicrobial use in each hospital ranged from 4.8% to 9.5% and 19.3%-35.0%, respectively., Conclusion: This multi-centre PPS recorded detailed HCAI data and distinct antimicrobial use in Japanese university hospitals. Further surveillance is necessary to reduce HCAIs and formulate feasible plans to achieve the national action plan on antimicrobial resistance., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal infections; however, its penetration into abdominal sites is unclear. A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously administered to 10 patients before abdominal surgery for inflammatory bowel disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end of infusion (0.5 h) and up to 4 h thereafter. PIP and TAZ concentrations were measured, both noncompartmental and compartmental pharmacokinetic parameters were estimated, and a simulation was conducted to evaluate site-specific pharmacodynamic target attainment. The mean peritoneal fluid:plasma ratios in the area under the drug concentration-time curve (AUC) were 0.75 for PIP and 0.79 for TAZ, and the mean peritoneal fluid:plasma ratios in the AUC were 0.49 for PIP and 0.53 for TAZ. The mean PIP:TAZ ratio was 8.1 at both peritoneal sites. The regimens that achieved a bactericidal effect with PIP (time above minimum inhibitory concentration [MIC] >50%) at both peritoneal sites were PIP-TAZ 4.5 g twice daily for an MIC of 8 mg/L, as well as 4.5 g three times daily, and 3.375 g four times daily for an MIC of 16 mg/L. These findings clarify the peritoneal pharmacokinetics of PIP-TAZ, and help consider the dosing regimens for intraabdominal infections based on site-specific pharmacodynamic target attainment., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)