Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells.

Intestinal Th17 cells are induced and accumulate in response to colonization with a subgroup of intestinal microbes such as segmented filamentous bacteria (SFB) and certain extracellular pathogens. Here, we show that adhesion of microbes to intestinal epithelial cells (ECs) is a critical cue for Th17 induction. Upon monocolonization of germ-free mice or rats with SFB indigenous to mice (M-SFB) or rats (R-SFB), M-SFB and R-SFB showed host-specific adhesion to small intestinal ECs, accompanied by host-specific induction of Th17 cells. Citrobacter rodentium and Escherichia coli O157 triggered similar Th17 responses, whereas adhesion-defective mutants of these microbes failed to do so. Moreover, a mixture of 20 bacterial strains, which were selected and isolated from fecal samples of a patient with ulcerative colitis on the basis of their ability to cause a robust induction of Th17 cells in the mouse colon, also exhibited EC-adhesive characteristics.

Current status of the surgical training system in Japan: results of a nationwide questionnaire survey of graduating surgical trainees.

PURPOSE: To identify the problems trainees face during surgical training in Japan. METHODS: A nationwide online questionnaire survey was conducted targeting newly certified surgical trainees. RESULTS: The response rate was 53.8% (758/1410). Among those respondents, 25.6% were women, 71.4% were either married or had a partner, 41.3% had children, 72.7% had performed over 200 surgeries under general anesthesia, and 54.1% had chosen, before graduating from medical school, to become a surgeon. While 88.8% were interested in learning surgical techniques, 63.8% were hesitant to become a surgeon for fear of a compromised quality of private life (QOL). Conversely, only 1.4% chose their surgical training programs based on QOL. Overall, 84.6% of the trainees were satisfied with their training and this correlated with the number of surgeries performed. Only 29.9% received non-technical skill training. The average number of night shifts per month was 5.6, and 10.6% worked over 80 h per week. Harassment was reported by 41.5% of the respondents. Moreover, 33.0% had considered dropping out at some time, primarily because of their QOL (51.1%) or the harassment they had encountered (50.4%). CONCLUSION: This survey revealed that while trainees were satisfied with the overall training system, issues such as long working hours and harassment are prevalent. Working to improve these issues could make surgery more attractive for young trainees.

Morphological changes in the biliary mucosa in pediatric patients with congenital biliary dilatation are more influenced by the duration of amylase exposure than by amylase levels in the gallbladder.

PURPOSE: We investigated the relationship between bile amylase (AMY) levels and biliary epithelial changes in pancreaticobiliary maljunction (PBM), a congenital anomaly characterized by pancreaticobiliary reflux due to duct fusion outside the duodenal wall. METHODS: We enrolled 43 children with congenital biliary dilatation (CBD) of Todani types Ia, Ic, and IVa who underwent surgery at the Hokkaido Medical Center for Child Health and Rehabilitation between November 2007 and June 2023. We defined total AMY exposure in bile as bile AMY levels multiplied by the patient's age (months), representing amount of estimated AMY exposure until surgery. We retrospectively investigated the relationships between bile AMY levels and clinicopathological findings. RESULTS: All patients exhibited hyperplasia in the gallbladder and bile duct epithelium, with dysplasia observed in 13 cases, but no carcinoma. Exposure to bile AMY ≥ 662,400 IU/L × months was an independent risk factor for dysplasia. CONCLUSION: The amount of estimated AMY exposure in bile rather than AMY levels in the bile is an independent risk factor for dysplasia in the biliary mucosa.

Comprehension of fundamental knowledge about pediatric endoscopic surgery: a cross-sectional study in Japan.

BACKGROUND: Pediatric endoscopic surgery has become an alternative to conventional techniques with the development of medical equipment. However, there is no formal, standardized curriculum for pediatric endoscopic surgery, and its requirement remains elusive. The purpose of this study is to determine the baseline knowledge of pediatric surgeons that is considered essential for pediatric laparoscopic and thoracoscopic surgery. METHODS: Sixteen web-based multiple-choice questions based on the fundamental cognitive knowledge of pediatric endoscopic surgery were administered. The questions were created based on the fields covered by the Fundamentals of Laparoscopic Surgery ™ (FLS) certification examination blueprints and eight specific diseases of pediatric surgery. Pediatric surgeons and pediatric surgical trainees participated in this study voluntarily. RESULTS: A total of 122 surgeons participated through the Japanese Society of Pediatric Surgeons. The response rate was 95% (122/128). The total mean examination score of all participants was 79.4% (77.3-81.4%). There were no significant differences in total scores between the board-certified pediatric surgeons without an endoscopic surgical skill qualification and the non-board-certified pediatric surgeons (80.4% vs. 77.1%, p = 0.12). The endoscopic surgical skill-qualified surgeons had significantly higher percentages of correct responses in specific subjects than board-certified pediatric surgeons and surgeons without pediatric board certification (94.3% vs. 82.9%, p = 0.02; 94.3% vs. 77.5%, p = 0.0002). The FLS original subjects' scores were not significantly different among them. The mean score of surgeons who had experienced more than 200 cases of endoscopic surgery, including adult cases, was 83.2% (80.4-85.9%). CONCLUSIONS: A knowledge gap exists between surgeons, board-certified pediatric surgeons, and endoscopic surgical skill-qualified surgeons in Japan. In the field of pediatric surgery, an effective formal curriculum, such as FLS, is required to help address this vast knowledge gap for the safe conduct of endoscopic surgeries.

How many cases do instructor class pediatric surgeons need to experience to be an independent operator in performing advanced endoscopic surgery? A nationwide survey to establish an ideal curriculum for pediatric endoscopic surgery in Japan.

PURPOSE: To ensure the safe spread of pediatric endoscopic surgery, it is essential to build a training curriculum, and a survey of the current situation in Japan is necessary. The present study assessed an efficient training curriculum by clarifying instructor class pediatric surgeons' experiences, including autonomy when performing advanced endoscopic surgeries. METHODS: An online nationwide questionnaire survey was conducted among pediatric surgeons who had Endoscopic Surgical Skill Qualification (ESSQ) and board-certified instructors who had skills comparable to ESSQ. We assessed participants' training experience, opinions concerning the ideal training curriculum, and the correlation between surgical experience and the level of autonomy. The Zwisch scale was used to assess autonomy. RESULTS: Fifty-two participants responded to the survey (response rate: 86.7%). Only 57.7% of the respondents felt that they had received sufficient endoscopic surgery training. Most respondents considered an educational curriculum for endoscopic surgery including off-the-job training essential during the training period. Autonomy had been acquired after experiencing two to three cases for most advanced endoscopic surgeries. CONCLUSION: This first nationwide survey in Japan showed that instructor class pediatric surgeons acquired autonomy after experiencing two to three for most advanced endoscopic surgeries. Our findings suggest that training, especially off-the-job training, has been insufficient.

In Vitro Production of Optically Active Octahydrocurcumin by Human Intestinal Bacterium.

Enterococcus avium, producing 5R-hexahydrocurcumin metabolized tetrahydrocurcumin to octahydrocurcumin in vitro. Based on a detailed analysis of the two secondary alcohols, the metabolite obtained from tetrahydrocurcumin via 5R-hexahydrocurcumin was identified as 3R,5R-octahydrocurcumin. The activities of 5R-hexahydrocurcumin and 3R,5R-octahydrocurcumin were compared to those of the synthetic compounds, using monocyte chemoattractant protein-1 produced via murine adipocytes in vitro. The optically active curcuminoids reduced the cytokine production similar to tetrahydrocurcumin without any difference in their stereochemistry.

Production of Optically Active Hexahydrocurcumin by Human Intestinal Bacterium in Vitro.

A hexahydrocurcumin-producing bacterium named 2a1-2b was isolated from human feces. It was observed that the bacterium had more than 99% similarity with Enterococcus avium ATCC14025T according to 16S ribosomal DNA (rDNA) sequence. The strain 2a1-2b produced optically active 5R-hexahydrocurcumin (enantiomeric excess (e.e.) > 95%) from tetrahydrocurcumin but not from curcumin. Our results showed that intestine is an important place for producing hexahydrocurcumin.

Perioperative outcomes of laparoscopic fundoplication for gastroesophageal reflux disease in children with or without scoliosis.

PURPOSE: This study aimed to evaluate the perioperative outcomes of laparoscopic fundoplication (LF) for gastroesophageal reflux disease (GERD) in children with scoliosis. METHODS: Data of consecutive patients with GERD who underwent LF from January 2015 to December 2020 at a single pediatric institution were retrospectively analyzed. RESULTS: Eighty-two patients underwent laparoscopic Nissen fundoplication. The median [interquartile range (IQR)] body weight was 9.3 [7; 14] kg. Seventy-five patients were neurologically impaired (91%), and other comorbidities included scoliosis (n = 33), lung disease (n = 39), and cardiac disease (n = 14). The median (IQR) operative time including the creation of the gastrostomy and volume of bleeding were 160 [143; 190] min and 2 [1; 5] mL, respectively. There were no significant differences between patients with and those without scoliosis (p = 0.17 and p = 0.90, respectively). Patients with cardiac disease had a longer operative time (167 [161; 193] vs. 157 [141; 190] min, p = 0.01). There were three post-operative complications in children with neurological impairment; however, there was no clear relationship between the severity of scoliosis and complications. CONCLUSION: Severity of scoliosis did not correlate with perioperative results and post-operative complications. This suggests that the same LF technique can be used regardless of the presence or absence of scoliosis in children.

Equol Inhibits Mushroom Tyrosinase in Vitro through Tight Binding.

Equol, an intestinal metabolite of daidzein, inhibited more potently mushroom tyrosinase in vitro than other inhibitors, genistein and kojic acid. We investigated the mechanism underlying tyrosinase inhibition by equol. Treating racemic equol with tyrosinase produced 3'-hydroxyequol. Because the optical activity of the product showed <25% enantiomeric excess, the reaction was not highly stereospecific. Using enzyme-linked immunosorbent assays with an anti-equol monoclonal antibody, we observed that equol bound to pre-coated tyrosinase in a dose-dependent manner. Our results suggested the formation of a stable equol-tyrosinase complex.

Identifying the needs for teaching fundamental knowledge of laparoscopic surgery: a cross-sectional study in Japan.

BACKGROUND: Recently, laparoscopic surgery (LS) has become a more common procedure than traditional open surgery. Although LS-related adverse events have been reported, there is no formal, standardized curriculum to teach the fundamentals of LS in Japan. Understanding surgeons' knowledge regarding LS is crucial for developing an educational curriculum. The purpose of this study was to determine the baseline knowledge on LS of surgeons and surgical trainees in Japan. METHODS: Participants completed 24 multiple-choice questions testing basic cognitive knowledge of LS and a questionnaire regarding the status of laparoscopic education. The examination was developed according to the 13 content domains of the Fundamentals of Laparoscopic Surgery (FLS) program. Scores were compared between post-graduate year (PGY) > 5 and PGY 1-5 participants. Data are expressed as median scores and interquartile ranges. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: A total of 195 surgeons and surgical trainees from 10 teaching hospitals (PGY1-5: 66, PGY > 5: 129) across Japan completed the examination. The median score in the entire cohort was 75 [67; 83] %, with significantly higher scores in the PGY > 5 group compared to the PGY1-5 group (79 [75; 83] % vs. 67 [58; 75] %, p < 0.001). The differences in performance were due to better scores for PGY > 5 group on the sections "equipment," "patient considerations," "abdominal access," "tissue handling," "hemorrhage and hemostasis," "tissue approximation," and "exiting the abdomen." Overall, the median scores in the "energy sources" and "establishment and physiology of the pneumoperitoneum" subsections were lower than in other domains. All participants agreed on the need for fundamental knowledge and a formal educational curriculum. CONCLUSIONS: Compared to experienced surgeons, surgical trainees had lesser knowledge about performing LS. Regardless of the years of experience, there are crucial knowledge gaps in specific areas regarding safe LS that should be addressed by implementing an educational curriculum.

Evaluation methods and impact of simulation-based training in pediatric surgery: a systematic review.

PURPOSE: The aim of this study was to identify (1) the type of skill evaluation methods and (2) how the effect of training was evaluated in simulation-based training (SBT) in pediatric surgery. METHODS: Databases of PubMed, Cochrane Library, and Web of Science were searched for articles published from January 2000 to January 2017. Search concepts of Medical Subject Heading terms were "surgery," "pediatrics," "simulation," and "training, evaluation." RESULTS: Of 5858 publications identified, 43 were included. Twenty papers described simulators as assessment tools used to evaluate technical skills. Reviewers differentiated between experts and trainees using a scoring system (45%) and/or a checklist (25%). Simulators as training tools were described in 23 papers. While the training's effectiveness was measured using performance assessment scales (52%) and/or surveys (43%), no study investigated the improvement of the clinical outcomes after SBT. CONCLUSION: Scoring, time, and motion analysis methods were used for the evaluation of basic techniques of laparoscopic skills. Only a few SBT in pediatric surgery have definite goals with clinical effect. Future research needs to demonstrate the educational effect of simulators as assessment or training tools on SBT in pediatric surgery.

Successful Antimicrobial Therapy of Esophageal Stenosis Because of Actinomycosis.

Esophageal stenosis can cause vomiting or dysphagia in children and is commonly treated with esophageal balloon dilation. However, surgery may be required if the stenosis does not respond to dilation. Although esophageal actinomycosis can cause severe esophageal strictures and be refractory to balloon dilation, it has been reported to respond effectively to antimicrobial therapy in adults. However, the course of the disease and appropriate treatment strategies in children are not well understood. We present a case of a previously healthy 2-year-old boy diagnosed with esophageal stenosis because of actinomycosis. The patient was treated with intravenous penicillin G, followed by oral amoxicillin for 8 weeks and 6 months, respectively. After completion of the antimicrobial treatment, the patient showed improvement in symptoms and endoscopic findings. At the 1-year follow-up, the patient showed consistent weight gain and normal growth without further intervention. This case highlights the importance of considering esophageal actinomycosis as a potential cause of esophageal stenosis in children and the potential effectiveness of antimicrobial therapy in avoiding surgical intervention.

Optimal Surgical Method and Timing for Low-birth-weight Esophageal Atresia Babies: Multi-institutional Observational Study.

AIM OF THE STUDY: Previous research has shown that low birth weight is one of the risk factors for esophageal atresia. However, there remains a paucity of evidence on the timing and the treatment method. METHOD: Data were collected using a multi-institutional observational study in 11 hospitals that performed surgeries on esophageal atresia babies whose birth weights were ≤1500 g from 2001 to 2020. RESULTS: Of the 46 patients analyzed, median birth weight was 1233 (IQR 1042-1412) g. Within 46 cases, 19 (41%) underwent definitive esophageal anastomosis at the median of age in 8 (IQR 2-101) days. Thirteen out of 19 experienced either closure of tracheoesophageal fistula, gastrostomy, or esophageal banding at the first operation, followed by esophageal anastomosis. Seven infants, including four cases of <1000 g, underwent anastomosis after one month of age to wait for weight gain (variously 2-3000 g). Twenty-one out of 27 infants (78%) who did not receive anastomosis died within one year of age, including 21 (78 %) with major cardiac anomalies and 24 (89%) with severe chromosomal anomalies (trisomy 18). Six survivors in this group, all with trisomy 18, lived with palliative surgical treatments. CONCLUSION: In our study, the definitive esophageal anastomosis was effective either at the first operation or as a later treatment after gaining weight. Although having severe anomalies, some infants receive palliative surgical treatments, and the next surgery was considered depending on their condition. EVIDENCE LEVEL: II.

Energy landscape analysis and time-series clustering analysis of patient state multistability related to rheumatoid arthritis drug treatment: The KURAMA cohort study.

Rheumatoid arthritis causes joint inflammation due to immune abnormalities, resulting in joint pain and swelling. In recent years, there have been considerable advancements in the treatment of this disease. However, only approximately 60% of patients achieve remission. Patients with multifactorial diseases shift between states from day to day. Patients may remain in a good or poor state with few or no transitions, or they may switch between states frequently. The visualization of time-dependent state transitions, based on the evaluation axis of stable/unstable states, may provide useful information for achieving rheumatoid arthritis treatment goals. Energy landscape analysis can be used to quantitatively determine the stability/instability of each state in terms of energy. Time-series clustering is another method used to classify transitions into different groups to identify potential patterns within a time-series dataset. The objective of this study was to utilize energy landscape analysis and time-series clustering to evaluate multidimensional time-series data in terms of multistability. We profiled each patient's state transitions during treatment using energy landscape analysis and time-series clustering. Energy landscape analysis divided state transitions into two patterns: "good stability leading to remission" and "poor stability leading to treatment dead-end." The number of patients whose disease status improved increased markedly until approximately 6 months after treatment initiation and then plateaued after 1 year. Time-series clustering grouped patients into three clusters: "toward good stability," "toward poor stability," and "unstable." Patients in the "unstable" cluster are considered to have clinical courses that are difficult to predict; therefore, these patients should be treated with more care. Early disease detection and treatment initiation are important. The evaluation of state multistability enables us to understand a patient's current state in the context of overall state transitions related to rheumatoid arthritis drug treatment and to predict future state transitions.

Persimmon fruit tannin-rich fiber reduces cholesterol levels in humans.

Bile acid-binding agents are known to lower blood cholesterol levels and have been clinically used for the treatment of hypercholesterolemia. We previously showed that tannin-rich fiber from young persimmon (Diospyros kaki) fruits had bile acid-binding properties. In this study, we performed a randomized, double-blind, placebo-controlled trial to investigate the hypocholesterolemic effects of tannin-rich fiber in humans. The subjects (n = 40, plasma total cholesterol levels 180-259 mg/dl) were divided into 3 groups and ingested cookie bars containing 0 g (placebo group, n = 14), 3 g (low-dose group, n = 13), or 5 g (high-dose group, n = 13) of tannin-rich fiber 3 times daily before meals for 12 weeks. Plasma total cholesterol levels decreased significantly in the low-dose (12 weeks, p < 0.005) and high-dose (6 weeks, p < 0.05; 12 weeks, p < 0.001) groups. In addition, plasma low-density lipoprotein cholesterol levels decreased significantly in the high-dose group (6 weeks, p < 0.05; 12 weeks, p < 0.001). These improvements were not accompanied by changes in plasma high-density lipoprotein cholesterol or plasma triglyceride levels. Our findings indicate that tannin-rich fiber from young persimmon fruits is a useful food material for treating hypercholesterolemia.

Dementia Scale Classification with Sequential Model from Sleep Activity Data.

Dementia, a disorder caused by brain diseases, has been found to influence the sleep patterns of patients. The finding indicates that monitoring sleep activity is helpful to detect the change in cognitive status. With this in mind, the aim of this study is to explore the possibility to develop a machine learning model for classifying the scores of dementia screening tests based on sleep activity data which could be recorded with less burden for participants. In this study, We collected sleep activity data from 124 elderly patients with varying cognitive states, including heart rate, respiratory rate and depth of sleep, using a single sensor. The score of Mini Mental State Estimation (MMSE) cognitive test is used to determine the level of cognitive states. First, we conducted a statistical analysis of the measured sleep activity data to find specific features observed in people with low-MMSE scores. Second, we utilized an efficient sequence model for capturing time-series changes in sleep activity for binary classification of the dementia scale to detect such low-MMSE people. Our findings revealed significant distinctions in sleep patterns between high and low cognitive status groups, and in the classification task, a maximum macro F1 score of 0.67 was achieved using LSTM models. Our results suggest the validity of using sleep activity data for the prediction of dementia classification.

Complete genomic sequence of the O-desmethylangolensin-producing bacterium Clostridium rRNA cluster XIVa strain SY8519, isolated from adult human intestine.

The O-desmethylangolensin-producing Clostridium rRNA cluster XIVa strain SY8519 was isolated from the intestinal flora of a healthy human as a key isoflavonoid-metabolizing bacterium. Here, we report the finished and annotated genomic sequence of this organism.

Complete genomic sequence of the equol-producing bacterium Eggerthella sp. strain YY7918, isolated from adult human intestine.

Eggerthella sp. strain YY7918 was isolated from the intestinal flora of a healthy human. It metabolizes daidzein (a soybean isoflavonoid) and produces S-equol, which has stronger estrogenic activities than daidzein. Here, we report the finished and annotated genomic sequence of this organism.

Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization.

Few reports have examined the effects of adult bone marrow multipotent stromal cells (MSCs) on large animals, and no useful method has been established for MSC implantation. In this study, we investigate the effects of MSC infusion from the coronary vein in a swine model of chronic myocardial infarction (MI). MI was induced in domestic swine by placing beads in the left coronary artery. Bone marrow cells were aspirated and then cultured to isolate the MSCs. At 4 weeks after MI, MSCs labeled with dye (n=8) or vehicle (n=5) were infused retrogradely from the anterior interventricular vein without any complications. Left ventriculography (LVG) was performed just before and at 4 weeks after cell infusion. The ejection fraction (EF) assessed by LVG significantly decreased from baseline up to a follow-up at 4 weeks in the control group (P<0.05), whereas the cardiac function was preserved in the MSC group. The difference in the EF between baseline and follow-up was significantly greater in the MSC group than in the control group (P<0.05). The MSC administration significantly promoted neovascularization in the border areas compared with the controls (P<0.0005), though it had no affect on cardiac fibrosis. A few MSCs expressed von Willebrand factor in a differentiation assay, but none of them expressed troponin T. In quantitative gene expression analysis, basic fibroblast growth factor and vascular endothelial growth factor (VEGF) levels were significantly higher in the MSC-treated hearts than in the controls (P<0.05, respectively). Immunohistochemical staining revealed VEGF production in the engrafted MSCs. In vitro experiment demonstrated that MSCs significantly stimulated endothelial capillary network formation compared with the VEGF protein (P<0.0001). MSC infusion via the coronary vein prevented the progression of cardiac dysfunction in chronic MI. This favorable effect appeared to derive not from cell differentiation, but from enhanced neovascularization by angiogenic factors secreted from the MSCs.

Removal of a ribosome small subunit-dependent GTPase confers salt resistance on Escherichia coli cells.

RsgA is a unique GTP hydrolytic protein in which GTPase activity is significantly enhanced by the small ribosomal subunit. Deletion of RsgA causes slow cell growth as well as defects in subunit assembly of the ribosome and 16S rRNA processing, suggesting its involvement in maturation of the small subunit. In this study, we found that removal of RsgA or inactivation of its ribosome small subunit-dependent GTPase activity provides Escherichia coli cells with resistance to high salt stress. Salt stress suppressed the defects in subunit assembly of the ribosome and processing of 16S rRNA as well as truncation of the 3' end of 16S rRNA in RsgA-deletion cells. In contrast, salt stress transiently impaired subunit assembly of the ribosome and processing of 16S rRNA and induced 3' truncation of 16S rRNA in wild-type cells. These results suggest that the action of RsgA on the ribosome, which usually facilitates maturation of the small subunit, disturbs it under a salt stress condition. Consistently, there was a drastic but transient decrease in the intracellular amount of RsgA after salt shock. Salt shock would make the pathway of maturation of the ribosome small subunit RsgA independent.