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Aims: This study was conducted to clarify the taxonomic status of Bacteroides type A strains with high vitamin B12-producing ability that is widely distributed in the intestinal tracts of freshwater fish. Methods and Results: Seventeen strains of Bacteroides type A isolated from five fish species were all rod-shaped and gram-negative. The strains were positive for esculin hydrolysis, nitrate reduction, resistance to bile, acid phosphatase, and negative for the production of catalase and urease and the susceptibility to vancomycin. The G+C content of DNA from the 17 strains was 29·1–31·9 mol%, and 16S rDNA sequence analysis revealed a close phylogenetic relationship between Bacteroides type A strains and Cetobacterium somerae sharing 99·7–100% sequence similarity. In addition, strains were capable of producing vitamin B12 at a rate of 1·82–13·98 ng ml−1 in 48 h. Conclusion: Phenotypic and phylogenetic characteristics indicated that all isolates previously classified as Bacteroides type A strains belong to C. someare. Significance and Impact of the Study: This study provided the important finding of novel niche of vancomycin-resistant bacteria such as C. somerae in the intestinal tract of freshwater fish. [ABSTRACT FROM AUTHOR]

Aims: This study was undertaken to examine the properties of chitinases purified from Clostridium sp. E-16, an intestinal bacterium of the South American sea lion ( Otaria flavescens). We also elucidated the taxonomic status of this bacterium to better understand the role of intestinal anaerobic bacteria in marine animals. Methods and Results: Two chitinases were purified with ammonium sulfate precipitation, affinity chromatography and preparative electrophoresis from culture supernatant fluid from Clostridium sp. E-16. Molecular mass was estimated to be 77 kDa for chitinase 1 and 98 kDa for chitinase 2 by SDS-PAGE. Optimum pH of both purified chitinases was between 5·0 and 7·0. Chitinase 1 was inhibited with Cu2+, Fe2+, Hg2+ and Zn2+, while chitinase 2 was inhibited with Fe2+. Phylogenetic analysis using 16S ribosomal DNA (rDNA) sequences and phenotypic characterization revealed that Clostridium sp. E-16 was closely related to Clostridium baratii. Conclusions: It is likely that chitinases from C. baratii or a C. baratii-like bacterium play an important role in degradation of chitin in the intestinal tract of the South American sea lion and in marine environments. Significance and Impact of the Study: This is the first report of chitinase purification and characterization from a marine Clostridium strain. [ABSTRACT FROM AUTHOR]

Background: While previous studies have reported on the prognostic value of total plasma cell-free deoxyribonucleic acid (cfDNA) in lung cancers, few have prospectively evaluated its predictive value for systemic therapy response. Patients and methods: We conducted a prospective study to evaluate the association between changes in total cfDNA and radiologic response to systemic therapy in patients with stage IIIB/IV non-small-cell lung cancers (NSCLCs). Paired blood collections for cfDNA and computed tomography (CT) assessments by RECIST v1.0 were performed at baseline and 6-12 weeks after therapy initiation. Total cfDNA levels were measured in plasma using quantitative real-time polymerase chain reaction. Associations between changes in cfDNA and radiologic response, progression-free survival (PFS), and overall survival (OS) were measured using Kruskal-Wallis and Kaplan-Meier estimates. Results: A total of 103 patients completed paired cfDNA and CT response assessments. Systemic therapy administered included cytotoxic chemotherapy in 57% (59/103), molecularly targeted therapy in 17% (17/103), and combination therapy in 26% (27/103). Median change in cfDNA from baseline to response assessment did not significantly differ by radiologic response categories of progression of disease, stable disease and partial response (P = 0.10). However, using radiologic response as continuous variable, there was a weak positive correlation between change in radiologic response and change in cfDNA (Spearman's correlation coefficient 0.21, P = 0.03). Baseline cfDNA levels were not associated with PFS [hazard ratio (HR) = 1.06, 95% confidence interval (CI) 0.93-1.20, P = 0.41] or OS (HR=1.04, 95% CI 0.93-1.17, P = 0.51), neither were changes in cfDNA. Conclusions: In this large prospective study, changes in total cfDNA over time did not significantly predict radiologic response from systemic therapy in patients with advanced NSCLC. Pretreatment levels of total cfDNA were not prognostic of survival. Total cfDNA level is not a highly specific predictive biomarker and future investigations in cfDNA should focus on tumor-specific genomic alterations using expanded capabilities of next-generation sequencing. [ABSTRACT FROM AUTHOR]

Aims: To reveal the cause of the difference in activity of chitinase A from Vibrio proteolyticus and chitinase A from a strain of Vibrio carchariae (a junior synonym of Vibrio harveyi), we investigated the pH-dependent activity of full-length V. proteolyticus chitinase A and a truncated recombinant corresponding to the V. harveyi form of chitinase A. Methods and Results: After overexpression in Escherichia coli strain DH5α, the full-length and truncated recombinant chitinases were purified by ammonium sulphate precipitation and anion exchange column chromatography. Chitinase activity was measured at various pH values using α-crystal and colloidal chitins as the substrate. The pH-dependent patterns of the relative specific activities for α-crystal chitin differed between the full-length and truncated recombinant chitinases, whereas those for colloidal chitin were similar to each other. Conclusion: The difference in the activity of V. proteolyticus chitinase A and V. harveyi chitinase A might be partly due to a change in the pH dependence of the chitinase activities against α-crystal chitin, resulting from C-terminal processing. Significance and Impact of Study: The present results are important findings for not only ecological studies on the genus Vibrio in association with survival strategies, but also phylogenetic studies. [ABSTRACT FROM AUTHOR]

Two scombropid fishes, Scombrops boops and Scombrops gilberti, are closely related and commercially important species in Japan. These species are often confused in commercial markets because of their morphological similarity. In this study, scombropid specimens collected from various Japanese coastal waters were subjected to polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) analysis and phylogenetic analysis of the 16S rRNA gene in mitochondrial DNA. These analyses showed that all the scombropid specimens collected from localities in the Sea of Japan were identified as S. boops, whereas those from the Pacific Ocean included two species, S. boops and S. gilberti. Almost all juvenile (<200 mm standard body length, SL) S. gilberti originated from the Pacific coastal waters of the northern Japan, whereas adults (>400 mm SL) were found only in deep water off the Izu Peninsula to the Izu Islands. This suggests that S. gilberti might migrate extensively during its life cycle. In addition, differences in the number of specimens and the distribution between the two species suggest that S. gilberti is less abundant than S. boops in Japanese waters. [ABSTRACT FROM AUTHOR]

Aims: We compared phenotypic characteristics of Lactococcus lactis subsp. lactis derived from different sources including the intestinal tract of marine fish and freshwater fish, and cheese starter culture. Methods and Results: In the phylogenetic analysis based on partial 16S rRNA gene nucleotide sequences (1371 bp), freshwater fish-, marine fish- and cheese starter culture-derived strains were identical to that of L. lactis subsp. lactis previously reported. Fermentation profiles determined using the API 50 CH system were similar except for fermentation of several sugars includingl-arabinose, mannitol, amygdalin, saccharose, trehalose, inulin and gluconate. The strains did have distinct levels of halotolerance: marine fish-derived strains > cheese starter-derived strain > freshwater fish-derived isolate. Conclusions: Lactococcus lactis subsp. lactis showed extensive diversity in phenotypic adaptation to various environments. The phenotypic properties of these strains suggested that L. lactis subsp. lactis strains from fish intestine have additional functions compared with the cheese starter-derived strain that has previously described. Significance and Impact of the Study: The unique phenotypic traits of the fish intestinal tract-derived L. lactis subsp. lactis might make them useful as a probiotics in aquaculture, and contribute to the development of functional foods and novel food additives, since the strains derived from fish intestines might have additional functions such as antibacterial activity. [ABSTRACT FROM AUTHOR]

Aims: To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking-related interstitial lung disease. Methods and results: Patients who had undergone lobectomy for lung cancer were reviewed. Subjects included 230 non-smokers and 587 smokers, of whom 572 had a known smoking index (SI). They were classified into mild, moderate and heavy smokers. Centrilobular emphysema (CLE), respiratory bronchiolitis, airspace enlargement with fibrosis (AEF), the presence of foci resembling usual interstitial pneumonia pattern (UIP/P) and the rate of postoperative respiratory failure were assessed. The incidence of AEF was 6.5% in mild smokers, and 17.7% in moderate smokers ( P < 0.01) with lower lobe predominance. There were significant correlations ( P < 0.01) between AEF and CLE and AEF and UIP/P. The rate of respiratory failure after lobectomy was 6%, and 10% in patients having UIP/P with or without AEF, but was not seen in patients with AEF alone ( P < 0.01). Conclusions: AEF is an important smoking-related change in the lung that appears to correlate with the smoking history, and its distinction from UIP/P may be important. [ABSTRACT FROM AUTHOR]

A chitin-degrading bacterial strain, KN1699, isolated from Yatsu dry beach (Narashino, Chiba Prefecture, Japan), was identified as Vibrio parahaemolyticus. Treatment of powdered chitin with crude enzyme solution prepared from the supernatant of KN1699 cultures yielded a disaccharide, β- d- N-acetylglucosaminyl-(1,4)- d-glucosamine (GlcNAc-GlcN), as the primary chitin degradation product. The extracellular enzymes involved in the production of this heterodisaccharide, chitinase ( Pa-Chi; molecular mass, 92 kDa) and chitin oligosaccharide deacetylase ( Pa-COD; molecular mass, 46 kDa), were isolated from the crude enzyme solution, and their hydrolysis specificities were elucidated. These studies confirmed that (1) Pa-Chi hydrolyzes chitin to produce (GlcNAc)2 and (2) Pa-COD hydrolyzes the acetamide group of reducing end GlcNAc residue of (GlcNAc)2. These findings indicate that GlcNAc-GlcN is produced from chitin by the cooperative hydrolytic reactions of both Pa-Chi and Pa-COD. [ABSTRACT FROM AUTHOR]

Abstract: This study elucidates the immune modulation including the expression of cytokine genes following dietary administration of three selected probiotic bacteria—Lactobacillus rhamnosus, Enterococcus faecium and Bacillus subtilis to fish, rainbow trout Oncorhynchus mykiss. They were fed for 45 days on either a basal control diet or one of the three probiotic diets containing the specific bacteria in freeze-dried form at a density of 109 CFUgfeed−1. The non-specific immune parameters examined—superoxide anion production by the head kidney leukocytes and the alternate complement activity of serum was improved by probiotic feeding. Besides this, the relative gene expressions of interleukin-1β1, tumor necrosis factor 1 and 2 and transforming growth factor-β were up regulated in the spleen and the head kidney. The comparatively better performance of E. faecium could possibly be linked to their suitable ambient temperature conditions. Thus, probiotic bacteria delivered in feed exerts its influence on the immune system of fish, both at cellular and molecular levels. [Copyright &y& Elsevier]

Abstract: The objective of the present study was to understand the immune response induced by different forms of the probiont Lactobacillus rhamnosus JCM 1136 in rainbow trout Oncorhynchus mykiss and to clarify the carry over effect after withdrawal of the probiotic diet. A prebiotic-based diet was formulated, which served as the control diet, and to it the selected lactic acid bacteria (LAB) was incorporated in one of the three forms: (1) heat-killed, (2) live-sprayed or (3) freeze-dried. A rearing trial was conducted in triplicate with juvenile rainbow trout (average 126 g), which were fed on the control and three other diets containing the respective forms of the probionts, two times daily until the satiation level for a period of 30 days, following which the test diets were withdrawn and control diet was fed up to 45 days. Sampling was done at 10, 20, 30 and 45 days for gut microflora composition and the non-specific humoral and cellular immune responses of the fish. The viable forms (live spray or freeze-dried) were found to induce better phagocytic activity and complement activity compared to that of the non-viable heat-killed form. The plasma immunoglobulin level showed an increasing trend in the fish groups that received the viable probiont, but the trend did not exist towards the end of the study. Upon withdrawal of the probiotic diets, the LAB disappeared from the intestine and the elevated immune parameters returned to the prefed level. This study elucidates that probiont viability could probably influence the immune responses they induce. [Copyright &y& Elsevier]

Abstract: This study was undertaken to examine the effect of supplementing a suggested probiotic bacteria Lactobacillus rhamnosus JCM 1136 in feed on immune response and gut flora composition of rainbow trout Oncorhynchus mykiss. The probiotic bacteria were incorporated into a commercial feed to constitute two experimental diets containing either 109 or 1011 colony forming unit of live bacteria/g of feed while a third diet without the bacterial supplement served as the control diet. The diets were offered to rainbow trout (75g average weight) in triplicate tanks for 30 days. Fish were sampled at 10, 20 and 30 days after commencement of the feeding trial to determine the proportion of the given probiont in the gut microflora composition and the nonspecific humoral and cellular immune responses on the 30th day. The relative proportion of the probiont increased with the feeding duration in the intestine, but not in the stomach. The proportion of L. rhamnosus in the stomach corresponded to the intake levels while no such relation existed in the intestine. The serum lysozyme and complement activities were significantly greater in fish fed the higher level of probiont compared with the control fish. The phagocytic activity of head kidney leucocytes also showed similar tendencies. These observations indicate the potential immuno-regulatory role of probiotic organisms in rainbow trout. [Copyright &y& Elsevier]

Irradiation experiments were performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility, National Institute of Radiological Sciences. The radioactive spallation products in a thick Cu target were obtained for Ar(230, 400 MeV/nucleon), Si(800 MeV/nucleon), Ne(100, 230, 400 MeV/nucleon), C(100, 230, 400 MeV/nucleon), He(100, 230 MeV/nucleon), p(100, 230 MeV) ions. The gamma-ray spectra from irradiated Cu, C, Al, Cr, Fe, Ni, Pb samples inserted into the composite Cu target were measured with a HPGe detector. From the gamma-ray spectra, we obtained the reaction cross section data on the Cu, C, Al, Cr, Fe, Ni and Pb samples. The measured cross sections were fitted to a modified form of Rudstam’s semi-empirical formula in order to evaluate the cross sections of unmeasured nuclides. These estimated cross sections were added to the experimental yields for each mass number and the total mass-yield and isobaric charge distributions. We also calculated the cross sections for the production of residual nuclides by high-energy heavy ions by the particle and heavy-ion transport code system (PHITS) code and compared with measured results. The PHITS code provides good results on cross section calculations. [Copyright &y& Elsevier]

Purpose: In the current situation of an increasing older adult population with perihilar cholangiocarcinoma (PHCC), the benefits and risks of surgical treatment of PHCC in older people remain controversial. Portal vein embolization (PVE) is a useful preoperative procedure to improve hepatic reserve in the future remnant liver (FRL) and avoid postoperative liver failure after extended hepatectomy for PHCC. This study aimed to evaluate the influence of aging on PVE., Methods: We enrolled 25 patients who underwent right hepatectomy with percutaneous transhepatic PVE. Participants aged <70 years (n = 13) and ≥70 years (n = 12) were compared; correlation coefficients were evaluated using all cases. The FRL volume/total liver volume (FRLV/TLV) ratio and the indocyanine green (ICG) clearance rate (ICG-K) fraction of FRL to total liver (ICG-Krem) were analyzed as FRL hepatic reserves., Results: FRLV/TLV ratio increased after PVE in <70 years and ≥70 years groups (p = 0.002 and p = 0.013, respectively). The change in ICG-K values from before to after PVE varied between both groups (p = 0.040). The ICG-Krem value after PVE increased only in the <70 years group (p = 0.009). A review of all cases showed a negative correlation between the change (after - before PVE) in the ICG-K and ICG-Krem values and age (r = -0.4827, p = 0.0145 and r = -0.4328, p = 0.0306, respectively)., Conclusions: This study showed aging suppresses hepatic reserve improvement in the FRL, particularly in ICG clearance after PVE in PHCC cases., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Although postoperative portal vein thrombosis (PVT) is a frequent complication of splenectomy, few studies have examined PVT after simultaneous hepatectomy and splenectomy (HS). The aim of this study was to clarify the risk factors for and characteristics of PVT after HS., Methods: This retrospective observational study included 102 patients, including 76 with liver cirrhosis (LC) and 26 without, who underwent HS between April 2004 and April 2021. The incidence and location of postoperative PVT detected on contrast-enhanced CT 1 week after surgery were analyzed. In addition, pre- and intraoperative parameters were compared between patients with postoperative PVT and those without in order to determine risk factors for PVT after HS., Results: Among the 102 patients, 29 (28.4 %), including 32.9 % with LC and 15.4 % without LC, developed PVT after surgery. Among the 29 patients with PVT, 21 (72.4 %), 4 (13.8 %), and 4 (13.8 %) developed thrombus in the intrahepatic portal vein only, extrahepatic portal vein only, and both the extra- and intrahepatic portal veins, respectively. Multivariable analysis showed that preoperative splenic vein dilatation was an independent risk factor for PVT after HS (odds ratio: 1.53, 95 % confidence interval: 1.156-2.026, P = 0.003)., Conclusion: Our results suggest that splenic vein dilatation is an independent risk factor for PVT after simultaneous HS, and that PVT after HS occurs more frequently in the intrahepatic portal vein. After HS for cases with dilated splenic veins, we should pay particular attention to the PVT development in the intrahepatic portal vein regardless of the type of liver resection., Competing Interests: Declaration of competing interest The authors have no conflicts of interest or disclosures to report., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Zinc is an essential trace element for various physiological functions, including reproduction. The influx/efflux of zinc ions is regulated by zinc transporters (Zip1-14 and ZnT1-8, 10). However, the precise roles of zinc transporters and zinc dynamics in reproductive functions are unknown. In this study, ZnT3/Slc30a3 gene knockout (KO) mice were used to analyze the role of ZnT3. In ZnT3 KO mice, intracellular zinc ions in oocytes/zygotes were significantly reduced compared to those in controls, and free zinc ions did not accumulate in the oocyte cytoplasm. However, fertilization of these oocytes and the average litter size were comparable to those of control mice. Our results suggest that ZnT3 plays an important role in the accumulation of zinc ions in oocytes but not in the developmental ability of mice. ZnT3 KO mice will be useful for examining zinc dynamics in oocytes and other tissues.

Introduction: This study compared the short-term outcomes of older adult patients with locally advanced gastric cancer who underwent open distal gastrectomy (ODG) with those who underwent laparoscopic distal gastrectomy (LDG) using propensity score matching analysis., Methods: Overall, 341 consecutive older adult patients aged 75 years with gastric cancer who underwent ODG or LDG between January 2013 and December 2020 were retrospectively assessed. Among them, 121 patients with locally advanced gastric cancer were included. To compare short-term outcomes, a 1:1 propensity score matching analysis was performed., Results: After matching, 29 patients were included in both groups. Compared with the ODG group, the LDG group had a longer operative time (mean, 290 vs. 190 min; p < .0001) and lower estimated blood loss (mean, 39 vs. 223 mL; p < .0001). Overall postoperative complications of grade 2 and higher were observed in 2 (6.9%) and 12 (41%) patients in the LDG and ODG groups, respectively (p = .0046). Of these, the LDG group had a significantly lower incidence rate of infectious complications than the ODG group (3.4% vs. 27.6%; p = .025). Furthermore, in multivariate analysis, the laparoscopic approach was an independent protective factor against postoperative complications (p = .029)., Conclusions: LDG is safe and feasible for locally advanced gastric cancer in patients aged ≥75 years. Moreover, it may be a promising alternative to ODG with better short-term outcomes, including significantly lower incidence rates of postoperative complications., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Objectives: Anastomotic leakage in esophageal cancer surgery may be reduced by evaluating the blood flow to the reconstructed organ, but quantitative evaluation of arterial and venous blood flow is difficult. This study aimed to quantitatively assess blood flow using a new technique, as well as determine the relationship between the blood flow in the gastric tube and anastomotic leakage using near-infrared spectroscopy., Methods: This single-center, observational study included 50 patients aged 51-82 years who underwent radical esophagectomy with gastric tube reconstruction for esophageal cancer between June 2022 and January 2023. Regional tissue oxygen saturation was measured at the antrum (point X), the anastomotic point (point Z), and the midpoint between points X and Z (point Y) before and after gastric tube formation. These three points of oxygen saturation were investigated in relation to anastomotic leakage., Results: When comparing the presence of leakage to its absence, regional tissue oxygen saturation at points X and Z after gastric tube formation was significantly lower (X: p = 0.03, Z: p = 0.02), with the decreasing rate significantly higher at point Z (p = 0.01). There was no significant difference in the decreasing rate of regional tissue oxygen saturation between points X and Y (X: p = 0.052, Y: p = 0.83)., Conclusion: Regional tissue oxygen saturation levels may be useful for measuring blood flow and could be a predictor of anastomotic leakage., (© 2024. The Author(s).)

Background/aim: Genomic examination of tumor tissue has been clinically accepted, and the identification of actionable mutations for molecular-targeted therapy may provide substantial survival benefit for patients with advanced malignancies., Case Report: A female patient in her 60s showed a stenosis of the afferent loop of the small intestine because of circumferential metastatic tumor 14 months after curative surgery for hilar cholangiocarcinoma. Chemotherapy with gemcitabine plus cisplatin was administered for 18 months. An oncopanel examination was performed during chemotherapy, and a high tumor mutation burden was revealed. At 38 months after surgery, a new recurrent tumor, 2.7 cm in size, was observed in the abdominal wall, which was histologically proven to be metastatic adenocarcinoma. Atezolizumab was administered. After three cycles of treatment, treatment was switched to pembrolizumab because of its acceptance by healthcare insurance. The recurrent tumors in the abdominal wall and small intestine disappeared 6 months after the administration of immune checkpoint inhibitor, and the patient has continued pembrolizumab, surviving for 76 months after surgery without any clinical evidence of tumor., Conclusion: Immune checkpoint blockade successfully prolonged the survival of a patient with advanced hilar cholangiocarcinoma with high tumor mutation burden, although the optimal number of mutations for such a successful response needs to be clarified., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Endoscopic surgery is widely accepted for both elective and emergent abdominal surgery. This study was performed to assess the accuracy of preoperative adhesion mapping by abdominal ultrasonography (US)., Methods: Intra-abdominal intestinal adhesions on the abdominal wall in 50 patients with a history of abdominal surgery were prospectively assessed by the visceral slide test with US before laparoscopic surgery from 2019 to 2022. Adhesion was assessed in six separate abdominal zones during US. Actual adhesion on the abdominal wall was confirmed during laparoscopic surgery., Results: The sliding distances in upper right, upper central, upper left, lower right, lower central, and lower left zones in patients with versus without intestinal adhesion were 4.4 versus 1.4 cm (P = .004), 3.4 versus 2.5 cm, 4.3 versus 1.3 cm (P = .011), 3.1 versus 1.5 cm (P = .0014), 3.3 versus 1.1 cm (P = .013), and 3.4 versus 0.8 cm (P = .0061), respectively. Receiver operating characteristic analysis revealed the optimal value of sliding distance as 2.5 cm and the area under the curve as 0.86. The specificity of US assessment of adhesion was lower in the central zone than in lateral zones. Loose adhesion mostly seen around the scar was attributed to either filmy tissue or omental adhesion, leading to visceral sliding during US., Conclusion: This study revealed the reason for insufficient accuracy of preoperative US assessment of intestinal adhesion around the scar area because of loose adhesion. The upper lateral area might be optimal for first port insertion., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background and Aim: Safe radical hepatectomy is important for patients with colorectal liver metastases complicated by sinusoidal obstruction syndrome (SOS) after oxaliplatin-based chemotherapy. This study aimed to investigate the impact of preoperative administration of cilostazol (CZ), an oral selective phosphodiesterase III inhibitor, on hepatectomy in rat SOS model., Material and Methods: Rats were divided into NL (normal liver), SOS (monocrotaline [MCT]-treated), and SOS + CZ (MCT + CZ-treated) groups. MCT or CZ was administered orally, and a 30% partial hepatectomy was performed 48 h after MCT administration. Postoperative survival rates were evaluated (n = 9, for each). Other rats were sacrificed on postoperative days (POD) 1 and 3 and evaluated histologically, immunohistochemically, biochemically, and using transmission electron microscopy (TEM), focusing particularly on SOS findings, liver damage, and liver sinusoidal endothelial cell (LSEC) injury., Results: The cumulative 10-day postoperative survival rate was significantly higher in the SOS + CZ group than in the SOS group (88.9% vs 33.3%, P = 0.001). Total SOS scores were significantly lower in the SOS + CZ group than in the SOS group on both POD 1 and 3. Serum biochemistry and immunohistochemistry showed that CZ reduced liver damage after hepatectomy. TEM revealed that LSECs were significantly preserved morphologically in the SOS + CZ group than in the SOS group on POD 1 (86.1 ± 8.2% vs 63.8 ± 9.3%, P = 0.003)., Conclusion: Preoperative CZ administration reduced liver injury by protecting LSECs and improved the prognosis after hepatectomy in rats with SOS., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background/objectives: The outcomes of patients with intraepithelial neoplasia at the pancreatic transection margin after pancreatic cancer surgery remain unclear. We evaluated the clinical impact of pancreatic transection margin status., Methods: This retrospective observational study included 171 patients who underwent surgery for pancreatic ductal adenocarcinoma between January 2008 and December 2019. Patients were classified into three groups: negative pancreatic transection margin (group N), positive low-grade (group L), and positive high-grade (group H) intraepithelial neoplasia. The clinicopathological findings and prognoses were analyzed for each group., Results: There were 140, 14, and 9 patients in groups N, L, and H, respectively. The median age was significantly higher in group H (p = 0.035). There were no significant differences in male ratio, preoperative chemotherapy administration rate, pretreatment tumor markers, operative procedure, operative time, or blood loss. Overall survival and recurrence-free survival were not significantly different; however, the cumulative risk of recurrence in the remnant pancreas was significantly higher in group H (p = 0.018)., Conclusions: Intraepithelial neoplasia at the pancreatic transection margin did not affect overall/recurrence-free survival. As patients with high-grade intraepithelial neoplasia at the pancreatic transection margin have an increased risk of recurrence in the remnant pancreas, careful postoperative follow-up is required., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/aim: Neutrophil-to-lymphocyte ratio (NLR) is a prognostic indicator for several malignancies, including pancreatic cancer. We developed a novel combined NLR score (cNLRS) based on baseline NLR and change in NLR after chemotherapy (ΔNLR), and examined its prognostic value and role in chemotherapeutic response in patients with advanced pancreatic cancer., Patients and Methods: This study retrospectively assessed 210 advanced pancreatic cancer patients receiving chemotherapy between 2010 and 2021. The cNLRS was developed and its association with chemotherapeutic response and prognosis was investigated., Results: The cNLRS consisted of baseline NLR ≥2.5 and ΔNLR ≥0, both of which were remained as independent poor predictors of prognosis adjusting for other traditional clinicopathological features. A high cNLRS served as an independent prognostic factor of reduced overall survival. Of note, the cNLRS was significantly associated with disease control rate and treatment duration not only in 1st line treatment but also in 2nd line treatment., Conclusion: The cNLRS established as a useful prognostic biomarker might be associated with chemotherapeutic response and could predict survival in advanced patients with pancreatic ductal adenocarcinoma treated with chemotherapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

During mammalian fertilization, repetitive intracellular Ca 2+ increases known as Ca 2+ oscillations occur. These oscillations are considered crucial for successful fertilization and subsequent embryonic development. Numerous researchers have endeavored to elucidate the factors responsible for inducing Ca 2+ oscillations across various mammalian species. Notably, sperm-specific phospholipase C zeta (PLCζ) emerged as a prominent candidate capable of initiating Ca 2+ oscillations, particularly in mammals. Genetic mutation of PLCζ in humans results in the absence of Ca 2+ oscillations in mouse oocytes. Recent studies further underscored PLCζ's significance, revealing that sperm from PLCζ-deficient ( Plcz1 -/- ) mice fail to induce Ca 2+ oscillations upon intracytoplasmic sperm injection (ICSI). Despite these findings, observations from in vitro fertilization (IVF) experiments using Plcz1 -/- sperm revealed some residual intracellular Ca 2+ increases and successful oocyte activation, hinting at potential alternative mechanisms. In this review, we introduced the current hypothesis surrounding oocyte activation in mammals, informed by contemporary literature, and probed into the enigmatic mechanisms underlying mammalian fertilization-induced oocyte activation.

Cholangiolocarcinoma (CLC) is an extremely rare tumor classified as a subtype of small duct-type intrahepatic cholangiocarcinoma (iCCA). There are few detailed reports on CLC and the prognostic impact of tumor heterogeneity is not clear. Between April 2006 and June 2022, of the 774 primary liver cancer resection cases who presented at Kanazawa University Hospital, 14 patients were pathologically diagnosed with CLC through immunohistochemical analysis of their molecular and biological features. Clinicopathological features and prognoses were evaluated retrospectively. Additionally, tumor heterogeneity was assessed and tumors were classified into pure and partial types according to the CLC component proportion in a single tumor. Chronic liver disease was observed in nine patients (64.3%). All tumors were mass-forming, and pathological R0 resection was achieved in 11 patients (78.6%). Tumor heterogeneity was classified as pure in 11 (78.6%) and partial in three (21.4%) patients. The median follow-up was 59.5 months (12-114 months). There was no difference in the 5-year disease-specific survival rates between the pure and partial (90.0% vs. 100.0%; P=0.200) types, but rates were significantly higher in the R0 resection group compared with those in the R1 resection group (100.0% vs. 50.0%; P=0.025). In conclusion, these results suggest that it is important for CLC patients to achieve curative resection, and CLC may have a good prognosis regardless of the proportion of CLC components in a single tumor., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Sugita et al.)

Purpose: In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss., Methods: We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis., Results: A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection., Conclusions: Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Herein, we report the case of a 7-year-old girl with a history of atopic dermatitis because of infancy. Her grandfather grew Egoma (Perilla frutescens), and her family frequently consumed food items prepared using Egoma; however, she never consumed them because she did not enjoy these food items; she experienced vomiting, facial swelling, and oral discomfort upon ingesting Egoma during school lunch for the first time. Her food oral challenge test was positive, as well as a skin-prick test with sesame powder. Egoma antigen protein was extracted and reacted with patient serum by immunoblotting, which detected a positive band of approximately 26kDa. She was brought up in an environment with high exposure to Egoma; hence, she most likely developed an allergy to Egoma because of percutaneous sensitization. This is the first time an Egoma allergen analysis has been conducted in Japan, and we consider it to be a valuable case.

Comprehensive genomic profiling (CGP) of a metastatic liver tumor biopsy specimen suggested that the patient, who was initially diagnosed with cholangiocarcinoma, had colorectal cancer. The identification of both FBXW7 and APC mutations is deemed characteristic of colorectal cancer. Indeed, subsequent colonoscopy revealed sigmoid colon carcinoma that led to tumor resection followed by systemic chemotherapy. CGP is principally used to identify agents that might potentially benefit the patient. However, results must be interpreted carefully to ensure consistency with the initial diagnosis.

Competing Interests: The authors have no conflicts of interest to declare.

Vitrification is a valuable technology that enables semipermanent preservation and long-distance or international transportation of genetically modified and native animals. In laboratory mice, vitrification maintains and transports embryos, and many institutions and companies sell vitrified embryos. In contrast, despite numerous papers reporting on vitrification in livestock over the past decade, practical implementation has yet to be achieved. However, with advances in genome editing technology, it is anticipated that the number of genetically modified domestic animals will increase, leading to a rise in demand for vitrification of oocytes and embryos. Here, we provide an objective overview of recent advancements in vitrification technology for livestock, drawing a comparison with the current developments in laboratory animals. Additionally, we explore the future prospects for vitrification in livestock, focusing on its potential benefits and drawbacks., (© 2024 Japanese Society of Animal Science.)

Introduction: Recent trials have shown that glucagon-like peptide-1 receptor agonists considerably reduce atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Oxidative stress, a surrogate marker of cardiovascular risk, is associated with glucose variability. However, to the best of our knowledge, no studies have compared the effects of injectable semaglutide and dulaglutide therapies on oxidative stress and glucose variability assessed via continuous glucose monitoring (CGM). This study aimed to analyze and compare the effects of semaglutide and dulaglutide therapies on oxidative stress and glucose variability as assessed through CGM., Methods: This is an open-label, multicenter, randomized, prospective, parallel-group comparison study. Overall, 37 patients with T2DM treated with dulaglutide for at least 12 weeks were randomized into two groups: one receiving continuous dulaglutide therapy (n = 19) and one receiving injectable semaglutide therapy (n = 18) groups. The coprimary endpoints were changes in the results of the diacron-reactive oxygen metabolites test, an oxidative stress marker, and CGM-evaluated glucose variability after 24 weeks. The secondary endpoint was changes in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores., Results: Switching to semaglutide therapy was better than continuous dulaglutide therapy in reducing oxidative stress, glucose variability, and glycated hemoglobin levels. Conversely, continuous dulaglutide therapy was better than semaglutide therapy in terms of DTSQ scores for "Convenience" and "Recommend.", Conclusion: Injectable semaglutide therapy may be more effective than dulaglutide therapy in ameliorating oxidative stress and regulating glucose metabolism, including glucose variability, in patients with T2DM, while dulaglutide therapy may be more effective in terms of treatment satisfaction., Clinical Trial Registration: UMIN-CRT ID: UMIN000042670 (registered 7 December 2020)., (© 2023. The Author(s).)

Aims/introduction: Small dense low-density lipoprotein (sdLDL) is a more potent atherogenic lipoprotein than LDL. As sdLDL-cholesterol (C) levels are determined by triglyceride and LDL-C levels, pemafibrate and statins can reduce sdLDL-C levels. However, it remains unclear whether adding pemafibrate or increasing statin doses would more effectively reduce sdLDL-C levels in patients receiving statin therapy., Materials and Methods: A total of 97 patients with type 2 diabetes and hypertriglyceridemia who were treated with statins were randomly assigned to the pemafibrate 0.2 mg/day addition or statin dose doubled, and followed for 12 weeks. sdLDL-C was measured by our established homogenous assay., Results: The percentage and absolute reductions of sdLDL-C levels were significantly greater in the pemafibrate add-on group than the statin doubling group (-32.8 vs -8.1%; -16 vs -3 mg/dL, respectively). Triglyceride levels were reduced only in the pemafibrate add-on group (-44%), and LDL-C levels were reduced only in the statin doubling group (-8%), whereas levels of non-high-density lipoprotein-C and apolipoprotein B were similarly decreased (7-9%) in both groups. The absolute reductions of sdLDL-C levels were closely associated with decreased triglyceride, LDL-C, non-high-density lipoprotein-C and apolipoprotein B. In the subgroup analysis, the effect of pemafibrate add-on on sdLDL-C reductions was observed irrespective of baseline lipid parameters or statin type. No serious adverse effects were observed in both groups., Conclusions: In patients with type 2 diabetes and hypertriglyceridemia, the addition of pemafibrate to a statin is superior to doubling a statin in reducing sdLDL-C without increasing adverse effects., (© 2023 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Laparoscopic gastrectomy is a common procedure for early gastric cancer treatment. Improving postoperative pain control enhances patient recovery after surgery. The use of multimodal analgesia can potentially enhance the analgesic effect, minimize side effects, and change the postoperative management. The purpose of this study was to evaluate and compare the efficacies of the use of patient-controlled intravenous analgesia with regular acetaminophen (PCIA + Ace) and patient-controlled thoracic epidural analgesia (PCEA) for postoperative pain control., Methods: We retrospectively collected the data of 226 patients who underwent laparoscopic distal gastrectomy (LDG) with delta-shaped anastomosis between 2016 and 2019. After 1:1 propensity-score matching, we compared 83 patients who used PCEA alone (PCEA group) with 83 patients who used PCIA + Ace (PCIA + Ace group). Postoperative pain was assessed using a numeric rating scale (NRS) with scores ranging from 0 to 10. An NRS score ≥ 4 was considered the threshold for additional intravenous rescue medication administration., Results: Although NRS scores at rest were comparable between the PCEA and PCIA + Ace groups, NRS scores of patients in the PCIA + Ace group during coughing or movement were significantly better than those of patients in the PCEA group on postoperative days 2 and 3. The frequency of additional rescue analgesic use was significantly lower in the PCIA + Ace group than in the PCEA group (1.1 vs. 2.7, respectively, p < 0.001). The rate of reduction or interruption of the patient-controlled analgesic dose was higher in the PCEA group than in the PCIA + Ace group (74.6% vs. 95.1%, respectively, p = 0.0002), mainly due to hypotension occurrence in the PCEA group. Physical recovery time, postoperative complication occurrence, and liver enzyme elevation incidence were not significantly different between groups., Conclusions: PCIA + Ace can be safely applied without an increase in complications or deterioration in gastrointestinal function; moreover, PCIA + Ace use may provide better pain control than PCEA use in patients following LDG., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Tetrodotoxin (TTX), or pufferfish toxin, has been frequently detected in edible bivalves around the world during the last decade and is problematic in food hygiene and safety. It was reported recently that highly concentrated TTX was detected in the midgut gland of the akazara scallop Chlamys (Azumapecten) farreri subsp. akazara collected in coastal areas of the northern Japanese archipelago. The toxification of the bivalve was likely to involve the larvae of the flatworm, Planocera multitentaculata. However, the overall status of bivalve TTX toxification has not been elucidated. In this study, 14 species/subspecies of bivalves from various Japanese waters were subjected to LC-MS/MS analysis to reveal TTX toxification state, demonstrating that the Pectinidae, including C. farreri akazara, Chlamys farreri nipponensis, Chlamys (Mimachlamys) nobilis, and Mizuhopecten yessoensis, accumulated TTX in their midgut gland. Many individuals of C. farreri akazara and C. farreri nipponensis were found with high concentrations of TTX, while C. nobilis and M. yessoensis exhibited low concentrations. The extent of TTX accumulation in C. farreri akazara and C. farreri nipponensis varied widely by region and season. Curiously, no other bivalve species investigated in this study showed evidence of TTX. These results suggest that monitoring for TTX, like other shellfish toxins, is necessary to ensure that pectinid bivalves are a safe food resource., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hemophagocytic lymphohistiocytosis (HLH) is a rare but lethal complication of liver transplantation (LT). HLH is characterized by pathologic macrophage activation with hypercytokinemia, excessive inflammation, and tissue destruction, resulting in progressive organ dysfunction. HLH is also known as macrophage activation syndrome (MAS) when complicated by rheumatic or autoinflammatory diseases. Measuring several serum cytokines could be helpful in diagnosing HLH and MAS. Cytokines related to macrophage activation: neopterin, interleukin-18 (IL-18), and soluble tumor necrosis factor receptors (sTNF-R) I and II have not been assessed in patients with HLH complicated by LT. In this case, these cytokines were evaluated in the perioperative period of LT. The patient was a 24-year-old woman who underwent living-donor LT for acute worsening of autoimmune hepatitis. On postoperative day 12, the patient was diagnosed with HLH on the basis of the criteria. Plasma exchange, steroid pulse therapy, intravenous immunoglobulin and granulocyte-colony stimulating factor effectively inhibited progression to lethal HLH. When HLH occurred after LT, cytokine analysis showed that neopterin, IL-18, sTNFR-I, and II were elevated: cytokine storm. Of note, cytokine analysis on hospital admission also revealed elevated cytokine levels. Particularly, IL-18 levels were markedly elevated, suggesting that activation of the innate immune system was involved. These results revealed that a cytokine storm and macrophage activation developed before LT. Based on these findings, cytokine analysis related to macrophage activation may be useful for diagnosing and predicting HLH and MAS in patients with LT., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN., Methods and Analysis: We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B 12 , goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ 2 , Cochran's Q test and I² statistic., Ethics and Dissemination: This review does not require ethical approval. The research will be published in a peer-reviewed journal., Prospero Registration Number: CRD42022371829., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Tetrodotoxin (TTX)-bearing fish are thought to accumulate TTXs in their bodies through a food chain that begins with marine bacteria. However, the mechanism of TTXs transfer between prey and predators in the food chain remains unclear and the reasons for regional differences in pufferfish toxicity are also unknown. To investigate these matters, we collected juveniles of four species of pufferfish, Takifugu alboplumbeus, Takifugu flavipterus, Takifugu stictonotus, and Chelonodon patoca, from various locations in the Japanese Islands, and subjected them to liquid chromatography-tandem mass spectrometry analysis for TTX and its analog 5,6,11-trideoxyTTX (TDT). Concentrations of these substances tended to be higher in pufferfish juveniles collected from the Sanriku coastal area (Pacific coast of northern Japan) than in those from other locations. Juveniles had higher concentrations of TTX at all locations than of TDT. Mitochondrial cytochrome c oxidase subunit I (COI) sequences specific to the TTX-bearing flatworm, Planocera multitentaculata, were detected in the intestinal contents of up to 100% of pufferfish juveniles from various sampling sites, suggesting that P. multitentaculata was widely involved in the toxification of the juveniles in the coastal waters of Japan. A toxification experiment was conducted on three species of pufferfish juveniles (T. alboplumbeus, Takifugu rubripes and C. patoca) using TTX-bearing flatworm eggs harboring equal amounts of TTX and TDT. The TTX content of juveniles fed on flatworm eggs was found to be more than twice that of TDT, suggesting that pufferfish preferentially incorporate TTX compared to TDT., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Early monitoring and feedback on the treatment of infectious diseases are some of the methods for optimising antimicrobial treatment throughout the treatment period. Prospective audits and feedback interventions have also been shown to improve antimicrobial use and reduce antimicrobial resistance. We examined the appropriate use of antimicrobials by focusing on the initial timing for audits and feedback intervention of antimicrobial prescription by Infection Control Team pharmacists., Methods: We conducted a retrospective observational study in a university hospital in Tokyo, Japan from 1 January 2019 to 31 May 2021. We retrospectively enrolled patients with infections and those patients suspected of having an infection, who were administered vancomycin and assessed at our hospital. The definition of primary outcome was the maintenance of target vancomycin trough blood concentrations of 10-20 μg/ml during treatment. Multivariable logistic regression and multivariate linear regression analyses were performed to test the effectiveness of the initial timing of the intervention by Infection Control Team pharmacists as the explanatory variable., Results: A total of 638 patients were included in this study, with a median age of 69 years (interquartile range: 54-78 years). Multivariable logistic regression revealed that the maintenance of target vancomycin trough concentrations was not associated with the timing of the audit and the initiation of monitoring by Infection Control Team pharmacists (adjusted odds ratio: 0.99, 95% confidence interval: 0.99-1.00, p = 0.990). Multivariate linear regression revealed that the duration of vancomycin administration was significantly correlated with the timing of initiation of monitoring by Infection Control Team pharmacists (adjusted estimate: 0.0227, standard error: 0.0051, p = 0.012)., Conclusions: Our study showed that early initiation of a comprehensive audit and monitoring by Infection Control Team pharmacists did not affect the maintenance of the target vancomycin trough blood concentration. However, it reduced the duration of vancomycin administration., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: EI received lecture fees from Pfizer Japan Inc., Bristol-Myers Squibb Co., and Eisai Co., Ltd., and consulting fees from Nippontect Systems Co., Ltd., and Cyberdine, Inc. The other authors declare no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sugita 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.)

Intramolecular catalyst transfer on benzoheterodiazoles was investigated in Suzuki-Miyaura coupling reactions and polymerization reactions with t Bu 3 PPd precatalyst. In the coupling reactions of dibromobenzotriazole, dibromobenzoxazole, and dibromobenzothiadiazole with pinacol phenylboronate, the product ratios of monosubstituted product to disubstituted product were 0/100, 27/73, and 89/11, respectively, indicating that the Pd catalyst undergoes intramolecular catalyst transfer on dibromobenzotriazole, whereas intermolecular transfer occurs in part in the case of dibromobenzoxazole and is predominant for dibromobenzothiadiazole. The polycondensation of 1.3 equivalents of dibromobenzotriazole with 1.0 equivalent of para- and meta-phenylenediboronates afforded high-molecular-weight polymer and cyclic polymer, respectively. In the case of dibromobenzoxazole, however, para- and meta-phenylenediboronates afforded moderate-molecular-weight polymer with bromine at both ends and cyclic polymer, respectively. In the case of dibromobenzothiadiazole, they afforded low-molecular-weight polymers with bromine at both ends. Addition of benzothiadiazole derivatives interfered with catalyst transfer in the coupling reactions., (© 2023 Wiley-VCH GmbH.)

Radical-type mechanophores (RMs) are attractive molecules that undergo homolytic scission of their central C-C bond to afford radical species upon exposure to heat or mechanical stimuli. However, the lack of a rational design concept limits the development of RMs with pre-determined properties. Herein, we report a rational design strategy of RMs with high thermal tolerance while maintaining mechanoresponsiveness. A combined experimental and theoretical analysis revealed that the high thermal tolerance of these RMs is related to the radical-stabilization energy (RSE) as well as the Hammett and modified Swain-Lupton constants at the para -position ( σ p ). The trend of the RSE values is in good agreement with the experimentally evaluated thermal tolerance of a series of mechanoresponsive RMs based on the bisarylcyanoacetate motif. Furthermore, the singly occupied molecular orbital (SOMO) levels clearly exhibit a negative correlation with σ p within a series of RMs that are based on the same skeleton, paving the way toward the development of RMs that can be handled under ambient conditions without peroxidation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: This study aims to clarify the appropriate follow-up period after aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy for internal hemorrhoids by transanal ultrasonography., Methods: Forty-four patients (98 lesions) who underwent ALTA sclerotherapy were analyzed. Transanal ultrasonography was performed pre and post-ALTA sclerotherapy to observe the thickness and the internal echo image of hemorrhoid tissue. Patients who developed complications were excluded., Results: No recurrence in 12 months was observed in 44 patients. After 1-3 months of ALTA sclerotherapy, hemorrhoids were observed in the low-echo imaging region. During this period, hemorrhoidal tissue was observed thickest by granulation. Moreover, hemorrhoid tissue contracted by fibrosis formed 5-7 months post-ALTA sclerotherapy, with a thinner hemorrhoid. Furthermore, hemorrhoids hardened and regressed with intense fibrosis 12-months after the therapy and eventually became thinner than pre-ALTA sclerotherapy., Conclusions: After ALTA sclerotherapy, the suggested follow-up period with and without the development of complications is ～6 and ～3 months, respectively., Competing Interests: Conflicts of Interest There are no conflicts of interest., (Copyright © 2023 The Japan Society of Coloproctology.)

During mammalian fertilization, repetitive rises of intracellular calcium called calcium oscillations are required for full activation of oocytes. Therefore, oocytes such as round spermatid injected or somatic cell nuclear transferred require additional artificial activation which mimics the calcium oscillations. It is well recognized that sperm specific phospholipase C (PLCζ) is a strong candidate as the sperm factor which can induce calcium oscillations and, at least in mammals, the genetic mutation of PLCζ in human causes male infertility due to the lack of calcium oscillations in the oocytes. Recent studies showed that the sperm lacking PLCζ ( Plcz1 -/- ) still could induce rise(s) of intracellular calcium in the oocytes after IVF but not intracytoplasmic sperm injection (ICSI). In the ICSI oocytes, no pronuclear formation or development to the two-cell stage was observed. However, it is still unclear whether additional activation treatment can rescue the low developmental ability of Plcz1 -/- -sperm-derived oocytes after ICSI. In this study, we examined whether oocytes injected with a Plcz1 -/- sperm can develop to term by additional artificial activation. In oocytes injected a Plcz1 -/- sperm and Plcz1 -/- and eCS (another candidate of the sperm factor) double knockout sperm ( Plcz1 -/- eCS -/- ), the rates of pronuclear formation were very low (2.0 ± 2.3% and 6.1 ± 3.7%, respectively) compared to control (92.1 ± 2.6%). However, these rates were dramatically improved by additional procedures of PLCζ-mRNA injection or SrCl 2 treatment ( Plcz1 -/- sperm + PLCζ mRNA, Plcz1 -/- sperm + SrCl 2 and Plcz1 -/- eCS -/- sperm + PLCζ mRNA; 64.2 ± 10.8%, 89.2 ± 2.4% and 72.6 ± 5.4%, respectively). Most of the oocytes were developed to the two-cell stage. After embryo transfer, healthy pups were obtained in all these groups ( Plcz1 -/- sperm + PLCζ mRNA:10.0 ± 2.8%, Plcz1 -/- sperm + SrCl 2 :4.0 ± 4.3% and Plcz1 -/- eCS -/- sperm + PLCζ mRNA: 10.0 ± 5.7%). The rate in Plcz1 -/- sperm + SrCl 2 group was significantly lower than that in control (26.0 ± 2.4%). Taken together, our present results show that additional activation treatment such as SrCl 2 and PLCζ mRNA can fully support to develop to term even in oocyte injected Plcz1 -/- sperm. In addition, PLCζ-induced oocyte activation is more suitable for successful development to term compared to that such as phenomenon induced by SrCl 2 . These findings will contribute to improvement for male-dependent human infertility and reproductive technologies in other mammalian species.

Tetrodotoxin (TTX), also known as pufferfish toxin, is an extremely potent neurotoxin thought to be used as a biological defense compound in organisms bearing it. Although TTX was thought to function as a chemical agent for defense and anti-predation and an attractant for TTX-bearing animals including pufferfish, it has recently been demonstrated that pufferfish were also attracted to 5,6,11-trideoxyTTX, a related compound, rather than TTX alone. In this study, we attempted to estimate the roles of TTXs (TTX and 5,6,11-trideoxyTTX) in the pufferfish, Takifugu alboplumbeus , through examining the location of TTXs in various tissues of spawning pufferfish from Enoshima and Kamogawa, Japan. TTXs levels in the Kamogawa population were higher than those in the Enoshima population, and there was no significant difference in the amount of TTXs between the sexes in either population. Individual differences were greater in females than in males. However, the location of both substances in tissues differed significantly between sexes: male pufferfish accumulated most of their TTX in the skin and liver and most of their 5,6,11-trideoxyTTX in the skin, whereas females accumulated most of their TTX and 5,6,11-trideoxyTTX in the ovaries and skin.

Purpose: The present study investigated the relationship between sleep bruxism (SB) and obstructive sleep apnea (OSA) in relation to the sleep architecture., Methods: We conducted a cross-sectional study. Polysomnographic recordings were performed on 36 patients. Sleep, respiratory, and oromotor variables, such as rhythmic masticatory muscle activity (RMMA) and non-specific masticatory muscle activity (NSMA), were compared between OSA patients with or without SB. A correlation analysis of the frequency of respiratory and oromotor events in NREM and REM sleep was performed. The frequency of oromotor events following respiratory events was also assessed., Results: The proportion of REM sleep was higher in OSA patients with SB than in those without SB ( p  = 0.02). The apnea-hypopnea index (AHI) did not significantly differ between the two groups; however, AHI was approximately 8-fold lower during REM sleep in OSA patients with SB ( p  = 0.01) and the arousal threshold was also lower ( p  = 0.04). Although the RMMA index was higher in OSA patients with than in those without SB ( p  < 0.01), the NSMA index did not significantly differ. The percentage of RMMA following respiratory events was significantly higher in OSA patients with than in those without SB, whereas that of NSMA did not significantly differ. The frequency of oromotor events throughout the whole night positively correlated with AHI. However, regardless of the sleep state, AHI did not correlate with the RMMA index, but positively correlated with the NSMA index., Conclusion: In consideration of the limitations of the present study, the results obtained indicate that OSA patients with SB have a unique phenotype of OSA and also emphasize the distinct relationship of respiratory events with RMMA and NSMA., 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 © 2023 Okura, Kato, Mashita, Muraki, Sugita, Ohi and Taniguchi.)

Background: Synovial sarcoma is a malignant tumor that constitutes up to 10% of all soft-tissue sarcomas. The most frequent metastatic sites of synovial sarcoma are the lungs, lymph nodes, and bone, whereas pancreatic metastasis is extremely rare. Here, we report a case of pancreatic metastasis of synovial sarcoma., Case Presentation: Nine years before presentation, a 31-year-old woman underwent extensive resection of the primary tumor after chemotherapy for left upper extremity synovial sarcoma. Six months before presentation, interscapulothoracic amputation was performed for an enlarged mass in the left upper extremity; the patient was treated with pazopanib. Three months before presentation, chest computed tomography showed multiple lung metastases; during subsequent follow-up, abdominal computed tomography revealed a pancreatic metastasis of synovial sarcoma. The doubling time of the pancreatic tumor was 14 days, and it grew rapidly. Furthermore, treatment-resistant pancreatitis symptoms were detected; thus, we performed distal pancreatectomy and administered one course of a 70% dose of trabectedin. However, the patient died of rapid progression of lung metastasis and respiratory failure within 2 months after surgery., Conclusions: Pancreatectomy may be carefully performed in cases of isolated pancreatic metastasis. However, the presence of other distant extrapancreatic metastases (e.g., uncontrolled lung metastases) may rule out pancreatectomy treatment., (© 2023. The Author(s).)