Search

Background: Mapping of atypical atrial arrythmias arising in the left atrium is often challenging. The Local Activation Time (LAT) Histogram, a new function of the 3D color mapping system CARTO version 7, may help improve identification of atrial tachycardia circuits. We aimed to assess the effectiveness of the LAT Histogram for identification of left atrial tachycardia circuits., Methods: This retrospective study compared 25 consecutive cases of left atrial tachycardia that were treated before use of LAT Histogram (unused group) and 25 consecutive cases that were treated after introduction of LAT Histogram (used group) at Nagano Chuo Hospital. We evaluated whether we could identify the circuit of left atrial tachycardia from the electrophysiology lab data during ablation and the CARTO system data and whether we could perform effective ablation., Results: Door-to-door time, skin-to-skin time, and fluoroscopy time (p ≤ .011) were all shorter in the LAT Histogram used group versus unused group, while mapping analysis times were longer in the used group (p ≤ .019). A significantly greater number of cases in the LAT Histogram used compared with the unused group had ablation for entrance or exit points (19 vs. 10 cases; p = .001 for first map). Ablation resulted in a return to sinus rhythm and changed cycle length at the first mapping in 20 cases (80%) in the LAT Histogram unused group and in 24 cases (96%) in the used group., Conclusions: LAT Histogram may provide a simple and effective method to identify entrance and exit locations in left atrial tachycardia., (© 2024 The Author(s). Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background and Aim: Endoscopic retrograde cholangiopancreatography (ERCP) may help detect cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC), but it may be associated with complications. This study was aimed at determining the prognostic impact of ERCP on patients with PSC without cholangitis., Methods: Patients with PSC without cholangitis were divided into two groups: those who underwent ERCP within three years after diagnosis (ERCP-performed group) and those who did not (non-ERCP group). These groups were compared in terms of clinical outcomes (liver-related death or liver transplantation, endoscopic treatment requirement and repeated cholangitis) and the composite outcome., Results: Of 99 patients with PSC with detailed medical history, 49 were included in the ERCP-performed group and 21 in the non-ERCP group. In Kaplan-Meier analysis, the non-ERCP group was less likely to achieve the three outcomes and the composite outcome, showing statistical significance (endoscopic treatment requirement; p = 0.017 and composite outcome; p = 0.014). A Cox proportional hazards model indicated that ERCP in the asymptomatic state was a significant predictor of endoscopic treatment requirement (hazard ratio [HR]: 4.37, 95% confidence interval [CI]: 1.03-18.59) and the composite outcome (HR: 4.54, 95% CI: 1.07-19.28)., Conclusion: ERCP in patients with PSC without cholangitis is likely to require further endoscopic treatment and may be associated with poor prognosis., (© 2024. The Author(s).)

Background: Janus kinase (JAK) inhibitors (JAKis) are effective therapeutic agents against rheumatoid arthritis (RA). However, patients having RA with particular risk factors may have a higher incidence of adverse effects (AEs), including major cardiovascular events (MACE) and infections. In this multicenter cohort study, we aimed to clarify the risk factors affecting the drug retention of JAKis in patients with RA., Methods: We retrospectively evaluated patients with RA who received their first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) at our institute. The clinical outcomes, including AEs, were recorded, particularly MACE and serious infections. The drug retention rates were analyzed using the Kaplan-Meier method, and risk factors affecting drug retention rates were determined using a multivariable Cox regression hazards model., Results: Overall 184 patients with RA receiving their first use of baricitinib (57.6%), tofacitinib (23.9%), upadacitinib (12.0%), or filgotinib (6.5%) were included in this study. Fifty-six (30.4%) patients discontinued JAKi treatment owing to ineffectiveness (9.2%) or AEs, including infections (21.2%). The overall drug retention rates were significantly lower in patients treated with pan-JAKi than in those treated with JAK1 inhibitors (p = 0.03). In the Cox regression model, the presence of baseline high RA disease activity, use of glucocorticoid and treatments with pan-JAKis were associated with reduced drug retention rates of JAKis (p < 0.001, p = 0.01 and 0.04, respectively). Pan-JAKi treated patients with high disease activity had significantly lower drug retention rates (p < 0.001)., Conclusions: In a real-world setting, the drug retention rates of JAKis were reduced mainly by treatment discontinuation owing to AEs. Treatment with pan-JAKis and high baseline RA disease activity were identified as predictive factors for the discontinuation of JAKis. Lower drug retention rates were found in patients receiving pan-JAKis with high disease activity than in those without high disease activity., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: K.M. has received research grants from Chugai Pharmaceutical Co., Ltd. and Novartis Pharma K.K. The above-mentioned pharmaceutical companies were not involved in the study design, data collection and analysis, manuscript writing, and manuscript submission. Rest of the authors declare that they have no conflict of interests., (Copyright: © 2024 Saito 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.)

Purpose: The current study investigated whether sustained mild dehydration affects thermoregulatory function and cognitive performance during prolonged exercise., Methods: Twelve young adults performed a test consisting of three sets of 20-min exercise with 2-min intervals under euhydrated (control, CON) and mildly dehydrated conditions (MDEH) at an ambient temperature of 30 °C and 60% relative humidity. MDEH was established by restricting water intake for 24 h, resulting in urine specific gravity of ≥ 1.020. Heart rate (HR), mean arterial blood pressure (MAP), skin blood flow (SkBF), sweat rate (SR) on the chest and forearm, and ear canal and mean skin surface temperatures (T ear and mean T skin , respectively) were continuously recorded. For each exercise set, thermal and humid sensations and thermal discomfort were assessed using visual analog scales (VAS), and the rating of perceived exertion (RPE) was estimated. Cognitive performance on the Go/No-Go (easy) and incongruent Stroop (difficult) tasks was assessed before and after the test., Results: No differences were observed in HR, MAP, SkBF, SR, T ear , and mean T skin between the CON and MDEH. Thermal and humidity sensations, thermal discomfort, and RPE were higher in MDEH than in CON. Moreover, response time to the Stroop task was prolonged in MDEH., Conclusion: These findings suggest that sustained mild dehydration does not affect autonomic thermoregulation during exercise. Augmented thermal perception and perceived exertion, which are necessary for behavioral thermoregulation, were noted; however, cognitive function may be attenuated under MDEH., (© 2024. The Author(s).)

Aims: In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional-inflammatory markers and lymphocyte-to-C-reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF., Methods and Results: This study was a secondary analysis of the FRAGILE-HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2 ± 7.8 years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n = 498), 1 (n = 533), and 2 (n = 181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all-cause death within 2 years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6-min walk distance. At 2 years, all-cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P = 0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2-year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14-2.35; P = 0.007; log-transformed LCR: hazard ratio, 0.88; 95% CI, 0.81-0.95; P = 0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007-0.299; P = 0.041)., Conclusions: LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Proton conductors have potential applications such as fuel cells, electrolysis cells, and sensors. These applications require new materials with high proton conductivity and high chemical stability at intermediate temperatures. Herein we report a series of new hexagonal perovskite-related oxides, Ba 5 R 2 Al 2 SnO 13 ( R = Gd, Dy, Ho, Y, Er, Tm, and Yb). Ba 5 Er 2 Al 2 SnO 13 exhibited a high proton conductivity without chemical doping (e.g., 0.01 S cm -1 at 303 °C), which is attributed to its high proton concentration and diffusion coefficient. The high diffusion coefficient of Ba 5 Er 2 Al 2 SnO 13 can be attributed to the fast proton migration in the octahedral layers. The high proton concentration is attributed to full hydration in hydrated Ba 5 Er 2 Al 2 SnO 13 and the large amount of intrinsic oxygen vacancies in the dry sample, as evidenced by both neutron diffraction and thermogravimetric analysis. Ba 5 Er 2 Al 2 SnO 13 was found to exhibit high chemical stability under wet atmospheres of O 2 , air, H 2 , and CO 2 . High proton conductivity and high chemical stability indicate that Ba 5 Er 2 Al 2 SnO 13 is a superior proton conductor. Ba 5 R 2 Al 2 SnO 13 ( R = Gd, Dy, Ho, Y, Tm, and Yb) exhibited high electrical conductivity in wet N 2 , suggesting that these materials also exhibit high proton conductivity. These findings will open new avenues for proton conductors. The high proton conductivity via full hydration and fast proton migration in octahedral layers in highly oxygen-deficient hexagonal perovskite-related materials would be an effective strategy for developing next-generation proton conductors.

Background: Secondary carnitine deficiency in patients with anorexia nervosa has been rarely reported. This study aimed to investigate the occurrence of carnitine deficiency in severely malnourished patients with eating disorders during refeeding and assess its potential adverse effects on treatment outcomes., Method: In a cohort study of 56 female inpatients with eating disorders at a single hospital from March 2010 to December 2020, we measured plasma free carnitine (FC) levels and compared to those of a healthy control group (n = 35). The patients were categorized into three groups based on FC levels: FC deficiency (FC< 20 µmol/L), FC pre-deficiency (20 µmol/L ≤ FC< 36 µmol/L), and FC normal (36 µmol/L ≤ FC)., Results: Upon admission, the patients had a median age of 26 years (interquartile range [IQR]: 21-35) and a median body mass index (BMI) of 13.8 kg/m 2 (IQR: 12.8-14.8). Carnitine deficiency or pre-deficiency was identified in 57% of the patients. Hypocarnitinemia was associated with a decline in hemoglobin levels during refeeding (odds ratio [OR]: 0.445; 95% confidence interval [CI]: 0.214-0.926, p = 0.03), BMI at admission (OR: 0.478; 95% CI: 0.217-0.874, p = 0.014), and moderate or greater hepatic impairment at admission (OR: 6.385; 95% CI: 1.170-40.833, p = 0.032)., Conclusions: Hypocarnitinemia, particularly in cases of severe undernutrition (BMI< 13 kg/m 2 at admission) was observed in severely malnourished patients with eating disorders during refeeding, a critical metabolic transition phase. Moderate or severe hepatic impairment at admission was considered a potential indicator of hypocarnitinemia. Although hypocarnitinemia was not associated with any apparent adverse events other than anemia during refeeding, the possibility that carnitine deficiency may be a risk factor for more serious complications during sudden increases in energy requirements associated with changes in physical status cannot be denied. Further research on the clinical significance of hypocarnitinemia in severely malnourished patients with eating disorders is warranted., (© 2024. The Author(s).)

Objective: Hybrid of reversed image of positive endolymph signal and negative image of perilymph signal (HYDROPS) in delayed gadolinium-enhanced magnetic resonance imaging (MRI) typically depicts normal inner ear as "white-tone" and endolymphatic hydrops as "black-transparent" appearances, whereas ears with auditory and vestibular disorders are occasionally depicted as "gray-tone." This study aimed to investigate the pathological basis of sudden sensorineural hearing loss (SSNHL) patients with "gray-tone" appearances on HYDROPS., Methods: Delayed gadolinium-enhanced MRI examinations were conducted on 29 subjects with unilateral SSNHL. We mainly analyzed positive perilymph image (PPI) and positive endolymph image (PEI), which were components HYDROPS., Results: On PPI, signal intensity (SI) values extracted from the cochlear and vestibular region of interest (ROI) were higher in the SSNHL ears with dizziness/vertigo symptom at the first visit compared to the healthy ear. Additionally, the PPI/PEI enhancement pattern in the vestibule was associated with a high prevalence of hearing and vestibular deteriorations at the first visit and poor hearing improvement after treatment., Conclusion: Enhancement on PPI/PEI may result from leakage of gadolinium into the inner ear following breakdown of the blood-labyrinth barrier, with high SI being correlated with the amount of leakage. Particularly, a significant leakage into the endolymphatic space, defined as PPI+/PEI+, indicates severe inner ear pathology. Ultimately, we emphasize that the "gray-tone" appearance in the inner ear on HYDROPS comprises enhancements on both PPI and PEI and propose a new classification for evaluating SSNHL Peri- and Endolymphatic image Enhancement pattern in Delayed gadolinium-enhanced MRI (SPEED)., Level of Evidence: 4., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

We examined the correlation between three different methods of Mycobacterium tuberculosis quantification: time to positivity (TTP), log 10 CFU, and an assay to detect differentially detectable M. tuberculosis (DD Mtb) from three different prospective studies. Participants with DD Mtb have significantly more variation in the CFU/TTP correlation than participants with no DD Mtb ( P < 0.001). This may impact the design of early bactericidal activity studies that use TTP as the primary outcome., Competing Interests: The authors declare no conflict of interest.

Objectives: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis., Methods: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis., Results: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity., Conclusions: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation., Competing Interests: Declaration of competing interest All authors have no conflicts of interests relevant to this article to disclose., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Probiotics refer to living microorganisms that exert a variety of beneficial effects on human health. On the contrary, they also can cause infection, produce toxins within the body, and transfer antibiotic-resistant genes to the other microorganisms in the digestive tract necessitating a comprehensive safety assessment. This study aimed to conduct functional genomic analysis and some relevant biochemical tests to uncover the probiotic potentials of Lactobacillus delbrueckii subsp. indicus TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. The strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus, whose genome (1,916,674 bp) contained 1911 CDS, and no gene was identified for either antibiotic resistance or toxic metabolites. It carried genes for the degradation of toxic metabolites, treatment of lactose intolerance, toll-like receptor 2-dependent innate immune response, heat and cold shock, bile salts tolerance, and acidic pH tolerance. Genes were annotated for inhibiting pathogenic bacteria by inhibitory substances [bacteriocin: Helveticin-J (331 bp) and Enterolysin-A (275 bp), hydrogen peroxide, and acid]; blockage of adhesion sites; and competition for nutrients. The genes involved in its metabolic pathway were detected as suitable for digesting indigestible nutrients in the human gut. The TY-11 genome possessed an additional 37 core genes of subspecies indicus which were deficient in the core genome of the most popular subsp. bulgaricus . During the phenotypic testing, the isolate TY-11 demonstrated high antagonistic activity (inhibition zone of 21.33 ± 1.53 mm) against Escherichia coli ATCC 8739 and was not sensitive to any of the 10 tested antibiotics. This study was the first study to explore the molecular insights into probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of Lactobacillus delbrueckii subsp. indicus ., Importance: This study aimed to conduct functional genomic analysis to uncover the probiotic potential of Lactobacillus delbrueckii subsp. indicus TY-11 isolated from native yogurt in Bangladesh. We also performed transmission electron microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. In our current investigation, we revealed a number of common and unique excellences of the probiotic Lactobacillus delbrueckii subsp. indicus TY-11 that are likely to be important to illustrate its intestinal residence and probiotic roles. This is the first study to explore the molecular insights into intestinal residence and probiotic roles, including antimicrobial activities and antibiotic sensitivity, of a representative strain (TY-11) of Lactobacillus delbrueckii subsp. indicus ., Competing Interests: The authors declare no conflict of interest.

Background: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders, a subset of which develop progressive pulmonary fibrosis (PPF). There is little information on the epidemiology and treatment of PPFs in Japan. This retrospective cohort study estimated the incidence probability of progression to PPFs in patients with fibrosing ILDs other than idiopathic pulmonary fibrosis in a real-world Japanese setting. Management procedures and treatment patterns were also quantified., Methods: Data were extracted from the Medical Data Vision database from 01-Jan-2012 to 28-May-2020, comprising a 6.91-year patient identification period, 1-year pre-index period, and post-index period. The primary outcome was the cumulative incidence probability of progression to PPF up to 24 months. Subgroup analyses were performed by the presence/absence of connective tissue disease-ILD and by pre-specified ILD clinical diagnosis., Results: Of the 34,960 eligible patients (mean age: 71.1 years, males: 52.5%), 14,580 (41.7%) progressed to PPF. The 24-month incidence probability of progression to PPF was 39.5%. A relatively comparable percentage of patients progressed across all ILD subtypes. Oral corticosteroids and tacrolimus were the most common therapies during the pre- and post-index periods. Treatment rates were very low in the post-index period., Conclusions: This is the first claims database study to estimate the incidence probability of progression to PPF in Japan. Progression appeared common in patients with chronic fibrosing ILDs, with comparable percentages of patients across all subtypes developing PPF at 2 years. Future studies should assess the impact of regular monitoring and early intervention on treating fibrotic ILDs and preventing progression., Competing Interests: Declaration of competing interest Yasuhiro Kondoh reports consulting fees from Boehringer Ingelheim, Chugai Pharmaceutical Co., Ltd., Healios K.K., Janssen Pharmaceutical K.K., Shionogi and Co., Ltd., and Taiho Pharmaceutical Co.; payments or honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, Eisai Inc., Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma, Novartis Pharma K.K., Shionogi and Co., Ltd., and Teijin Pharma. Tomohiro Ito, Kumiko Saito, Haikun Bao, and Wataru Sakamoto are employees of Boehringer Ingelheim., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Background: Nerve injury is one of the most serious complications of total hip arthroplasty (THA). It is suspected to be a result from nerve compression or direct injury caused by an acetabular retractor. The anatomical relationship between the acetabular rim and the femoral and sciatic nerves, including hip motion, has not been investigated. This study aimed to identify the optimal position for retractor insertion during THA to prevent nerve damage., Methods: A total of 28 hip joints from 14 freshly frozen cadavers were used. Using an anterolateral approach, each cadaver was immobilised in the lateral decubitus position and deployed to measure the distance between the nerves and the acetabular rim, while the hip joint was changed to the extension, neutral, and flexion positions., Results: Three femoral nerves were closest to the anterior margin of the acetabulum at 90° and 120° of extension and farthest away at 30° of flexion. The sciatic nerve was closest to the posterior margin of the acetabulum at 90° and 120° of flexion and farthest away at 30° and 150° of extension compared with the other points., Conclusions: To prevent nerve damage during THA, we suggest that the retractor be inserted at the points where the nerves are the farthest away, such as at 30° and 150°. The femoral and sciatic nerves vary in their movements depending on the hip position. Therefore, the safe insertion of a retractor is recommended for hip flexion of the femoral nerve and extension of the sciatic nerve. Additionally, it is important to carefully insert the retractor along the acetabular margin without penetrating the joint capsule. Overall, this study provides valuable insights into the anatomical location and movement of the femoral and sciatic nerves in relation to hip motion and can help inform surgical techniques for safer THA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Brain-specific angiogenesis inhibitor 1 (BAI1) belongs to the adhesion G-protein-coupled receptors, which exhibit large multi-domain extracellular N termini that mediate cell-cell and cell-matrix interactions. To explore the existence of BAI1 isoforms, we queried genomic datasets for markers of active chromatin and new transcript variants in the ADGRB1 (adhesion G-protein-coupled receptor B1) gene. Two major types of mRNAs were identified in human/mouse brain, those with a start codon in exon 2 encoding a full-length protein of a predicted size of 173.5/173.3 kDa and shorter transcripts starting from alternative exons at the intron 17/exon 18 boundary with new or exon 19 start codons, predicting two shorter isoforms of 76.9/76.4 and 70.8/70.5 kDa, respectively. Immunoblots on wild-type and Adgrb1 exon 2-deleted mice, reverse transcription PCR, and promoter-luciferase reporter assay confirmed that the shorter isoforms originate from an alternative promoter in intron 17. The shorter BAI1 isoforms lack most of the N terminus and are very close in structure to the truncated BAI1 isoform generated through GPS processing from the full-length receptor. The cleaved BAI1 isoform has a 19 amino acid extracellular stalk that may serve as a receptor agonist, while the alternative transcripts generate BAI1 isoforms with extracellular N termini of 5 or 60 amino acids. Further studies are warranted to compare the functions of these isoforms and examine the distinct roles they play in different tissues and cell types., (© 2024. The Author(s).)

The hydrophobic cuticle is the first line of defense between aerial portions of plants and the external environment. On maize (Zea mays L.) silks, the cuticular cutin matrix is infused with cuticular waxes, consisting of a homologous series of very long-chain fatty acids (VLCFAs), aldehydes, and hydrocarbons. Together with VLC fatty-acyl-CoAs (VLCFA-CoAs), these metabolites serve as precursors, intermediates, and end-products of the cuticular wax biosynthetic pathway. To deconvolute the potentially confounding impacts of the change in silk microenvironment and silk development on this pathway, we profiled cuticular waxes on the silks of the inbreds B73 and Mo17, and their reciprocal hybrids. Multivariate interrogation of these metabolite abundance data demonstrates that VLCFA-CoAs and total free VLCFAs are positively correlated with the cuticular wax metabolome, and this metabolome is primarily affected by changes in the silk microenvironment and plant genotype. Moreover, the genotype effect on the pathway explains the increased accumulation of cuticular hydrocarbons with a concomitant reduction in cuticular VLCFA accumulation on B73 silks, suggesting that the conversion of VLCFA-CoAs to hydrocarbons is more effective in B73 than Mo17. Statistical modeling of the ratios between cuticular hydrocarbons and cuticular VLCFAs reveals a significant role of precursor chain length in determining this ratio. This study establishes the complexity of the product-precursor relationships within the silk cuticular wax-producing network by dissecting both the impact of genotype and the allocation of VLCFA-CoA precursors to different biological processes and demonstrates that longer chain VLCFA-CoAs are preferentially utilized for hydrocarbon biosynthesis., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Competing Interests: Declaration of Competing Interest Yousuke Nakai has received research grants by Taiho Pharmaceutical. No funding agency had input into the design and conduct of this study.

Background: It is unclear whether inactivated influenza vaccination (IIV) or pneumococcal vaccination are associated with the risk of dementia; however, both types of vaccination are recommended for older adults. Studies have shown that the IIV is negatively associated with incident dementia; however, the uptake of pneumococcal vaccinations has not been considered. We investigated the independent associations of IIV and 23-valent pneumococcal polysaccharide vaccine (PPSV23) with incident dementia in older adults., Methods: Health-related information on older Japanese adults was obtained through a baseline survey conducted in 2013 (baseline survey). The uptake of IIV and PPSV23 was determined in a second survey conducted in 2016 (second wave). Both surveys were conducted among independent Japanese older adults aged ≥ 65 years at the two surveys and who had not been certified as needing long-term care (LTC). In the second wave, 9,865 participants were followed up for 3.5 years (short-term follow-up), and 6,995 participants were followed up for six years and five months (long-term follow-up) until they required LTC due to dementia onset (incident dementia). A competing risk model with stabilized inverse probability weighting (SIPW) was constructed to calculate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of incident dementia., Results: PPSV23 uptake was negatively associated with incident dementia among participants in both the short- and long-term follow-up periods after SIPW (short-term follow-up: HR: 0.77, 95 % CI: 0.63 - 0.95; long-term follow-up: HR: 0.83, 95 % CI: 0.70 - 0.97). Conversely, IIV uptake was not associated with incident dementia among participants in either follow-up group (short-term follow-up: HR: 0.86, 95 % CI: 0.63-1.16; long-term follow-up: HR: 0.99, 95 % CI: 0.76-1.29). The PPSV23 uptake was negatively associated with incident dementia in participants without the IIV uptake (short-term follow-up: HR: 0.44, 95 % CI: 0.24 - 0.81; long-term follow-up: HR: 0.47, 95 % CI: 0.29 - 0.76). Conversely, the IIV uptake was not associated with incident dementia regardless of the PPSV23 status (short-term follow-up: HR: 0.87, 95 % CI: 0.62 - 1.23; long-term follow-up: HR: 1.00, 95 % CI: 0.74 - 1.35)., Conclusion: Our results suggest that the PPSV23 uptake was independently associated with the incidence of dementia. However, the IIV uptake was not associated with the incidence of dementia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This case report describes rare concomitant allergic fungal rhinosinusitis (AFRS) and chronic granulomatous invasive fungal sinusitis (CGIFS) in a 34-year-old woman with acute lymphoblastic leukemia and graft-versus-host disease (GVHD) post bone marrow transplantation. Initially presenting with rhinorrhea and nasal obstruction, the patient was diagnosed with AFRS in the right maxillary sinus, followed by a postoperative course of CGIFS in the left nasal cavity, showcasing the unique occurrence. She was not immunocompromised during diagnosis. CGIFS may have occurred because of surgery; however, voriconazole led to significant improvement. This case highlights noninvasive and invasive fungal infections in patients with chronic rhinosinusitis and a history of GVHD and underscores the complexity of diagnosing and managing such cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cell biologists have long sought the ability to observe intracellular structures in living cells without labels. This study presents procedures to adjust a commercially available apodized phase-contrast (APC) microscopy system for better visualizing the dynamic behaviors of various subcellular organelles in living cells. By harnessing the versatility of this technique to capture sequential images, we could observe morphological changes in cellular geometry after virus infection in real time without probes or invasive staining. The tune-up APC microscopy system is a highly efficient platform for simultaneously observing the dynamic behaviors of diverse subcellular structures with exceptional resolution.

Storytelling is one of the most important learning activities for children since reading aloud from a picture book stimulates children's curiosity, emotional development, and imagination. For effective education, the procedures for storytelling activities need to be improved according to the children's level of curiosity. However, young children are not able to complete questionnaires, making it difficult to analyze their level of interest. This paper proposes a method to estimate children's curiosity in picture book reading activities at five levels by recognizing children's behavior using acceleration and angular velocity sensors placed on their heads. We investigated the relationship between children's behaviors and their levels of curiosity, listed all observed behaviors, and clarified the behavior for estimating curiosity. Furthermore, we conducted experiments using motion sensors to estimate these behaviors and confirmed that the accuracy of estimating curiosity from sensor data is approximately 72%.

Purpose: Although there have been many reports on learning curves for robotic surgery, it is unclear how surgeons' conventional laparoscopic surgical skills influence their ability in performing robotic surgery for colorectal cancer (CRC). The aim of this study was to determine the surgical outcomes of robotic surgery for CRC during the induction phase by skilled laparoscopic surgeons., Methods: Surgical outcomes of consecutive CRC cases between January 2021 and March 2023 following the skilled phase of laparoscopic surgery and introductory phase of robotic surgery performed by three skilled laparoscopic surgeons were compared., Results: Overall, 77 consecutive patients diagnosed with sigmoid colon or rectosigmoid cancer were analysed, including 50 in the laparoscopy group (LAP) and 27 in the robotic group (Ro). Patient characteristics, including age, sex, body mass index, and tumour progression, did not differ between the groups. The median operation time was 204 min in the robotic group and 170 min in the laparoscopic group (p < 0.001). Blood loss was significantly lower in the robotic group (p = 0.0059). The incidence of grade 2 or higher complications did not differ between the two groups (LAP, 10.0% vs. Ro, 7.4%, p = 1). In the robotic group, the time required for lymph node dissection had a greater impact on operative duration., Conclusion: Skills acquired from performing conventional laparoscopic surgery may contribute to the safe and reliable performance of robotic surgery for CRC., Trial Registration: UMIN000050923., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Light plays an essential role in a variety of physiological processes, including vision, mood, and glucose homeostasis. However, the intricate relationship between light and an animal's feeding behavior has remained elusive. Here, we found that light exposure suppresses food intake, whereas darkness amplifies it in male mice. Interestingly, this phenomenon extends its reach to diurnal male Nile grass rats and healthy humans. We further show that lateral habenula (LHb) neurons in mice respond to light exposure, which in turn activates 5-HT neurons in the dorsal Raphe nucleus (DRN). Activation of the LHb → 5-HT DRN circuit in mice blunts darkness-induced hyperphagia, while inhibition of the circuit prevents light-induced anorexia. Together, we discovered a light responsive neural circuit that relays the environmental light signals to regulate feeding behavior in mice. Significance statement Feeding behavior is influenced by a myriad of sensory inputs, but the impact of light exposure on feeding regulation has remained enigmatic. Here, we showed that light exposure diminishes food intake across both nocturnal and diurnal species. Delving deeper, our findings revealed that the LHb → 5-HT DRN neural circuit plays a pivotal role in mediating light-induced anorexia in mice. These discoveries not only enhance our comprehension of the intricate neuronal mechanisms governing feeding in response to light but also offer insights for developing innovative strategies to address obesity and eating disorders., (Copyright © 2024 the authors.)

Tizoxanide (TZX) is an active metabolite of nitazoxanide (NTZ) originally developed as an antiparasitic agent, and is predominantly metabolized into TZX glucuronide. In the present study, TZX glucuronidation by the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice, and recombinant human UDP-glucuronosyltransferase (UGT) were examined. The kinetics of TZX glucuronidation by the liver and intestinal microsomes followed the Michaelis-Menten or biphasic model, with species-specific variations in the intrinsic clearance (CL int ). Rats and mice exhibited the highest CL int values for liver microsomes, while mice and rats were the highest for intestinal microsomes. Among human UGTs, UGT1A1 and UGT1A8 demonstrated significant glucuronidation activity. Estradiol and emodin inhibited TZX glucuronidation activities in the human liver and intestinal microsomes in a dose-dependent manner, with emodin showing stronger inhibition in the intestinal microsomes. These results suggest that the roles of UGT enzymes in TZX glucuronidation in the liver and small intestine differ extensively across species and that UGT1A1 and/or UGT1A8 mainly contribute to the metabolism and elimination of TZX in humans. This study presents the relevant and novel-appreciative report on TZX metabolism catalyzed by UGT enzymes, which may aid in the assessment of the antiparasitic, antibacterial, and antiviral activities of NTZ for the treatment of various infections., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that may have influenced the work reported in this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: With increasing labor shortage and production costs, water scarcity and climate change, there is increased interest in ratooning as a green, resource-efficient technology to boost sustainable rice production, especially in China. Since the performance of ratoon rice (regenerating a second crop from the stubble left in the fields after the main harvest) and the impact of agronomic practices on its yield have shown mixed results across the world, a better understanding is needed to determine under which conditions ratoon rice performs well., Objective: The objectives are (i) to quantify variation in rice yield of main and ratoon crops, (ii) to assess genetic variation in and impact of agronomic practices on rice yield, focusing on the yield of ratoon crop and total yield (main and ratoon crops), and (iii) review of economic and environmental benefits of ratoon rice in comparison with single and double rice cropping., Methods: In researching ratoon rice, we compiled a database from 68 studies published from 2000 to 2023. Descriptive data analysis was performed., Results: Studies from non-tropical regions account for about 70%. Large variation exists in the yield of ratoon crop across the studies, with lower yield from the tropics than non-tropics. The ratio of yield of ratoon crop to that of main crop also varied widely from 0.13 to 0.67 with 0.36 and 0.5 in tropics and non-tropics, respectively. The yield of ratoon crop was positively related to the yield of main crop, crop duration and nitrogen fertilizer application rate, which were generally higher in non-tropics. Hybrid varieties out-yielded inbred varieties in both main and ratoon crops in non-tropical regions. Direct seeding and AWD had a positive impact on the yield of ratoon crop. The impact of stubble cutting height was mixed. While agronomic nitrogen use efficiency (AEN) during entire ratoon rice cropping was similar to that reported for single rice cropping in previous studies, AEN for ratoon crop in tropical regions tended to be lower than those from previous studies on single rice cropping. Ratoon rice cropping reduced labor input and production cost and increased net economic return compared with double rice cropping., Conclusions: We propose a research agenda, with the focus on improvement of genetic and agronomic practices to explore the potential of ratoon rice cropping, especially in the tropics., Implications: This study provides insight into the progress in ratoon rice research over the past two decades globally, and specifically in the tropics., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Necrotizing fasciitis is a fatal, soft tissue infection of the skin that requires prompt treatment. Historically, most cases have been attributed to group A beta-hemolytic Streptococcus infection. However, in recent years, other bacteria have been identified as causing necrotizing fasciitis. In the current study, we analyzed cases of necrotizing fasciitis and examined the significant differences in symptoms caused by pathogenic bacteria. We included 79 patients (43 males and 36 females, mean age 65.4 years) diagnosed with necrotizing fasciitis who visited our hospital between April 2004 and July 2023. The patients were classified into five groups based on the identified pathogen: group A beta-hemolytic Streptococcus; group B beta-hemolytic streptococcus; group G beta-hemolytic Streptococcus; mixed infection, including anaerobic bacteria; and Staphylococcus (S) aureus. The clinical characteristics of patients, including treatment duration and laboratory values, were analyzed. Group G beta-hemolytic Streptococcus was more common in older patients (Bonferroni method, p < 0.05). Patients with S. aureus tended to be hyperglycemic (Bonferroni method, p < 0.05), had a higher rate of bacteremia (Fisher's direct probability test, p < 0.05), and had a longer treatment duration than the other examined groups (Bonferroni method, p = 0.0132). Although the five groups did not differ in the mortality rate, overall survival was shorter in the mixed infection group than in the other groups (log-rank test, p < 0.05). The legs were the most common site of infection in the non-mixed infection group; in the mixed infection group, the pubic area was identified as the most common site of infection, accompanied by a poor prognosis. Collectively, these findings suggest that necrotizing fasciitis can be characterized by pathogenic bacteria and that these characteristics may inversely predict the pathogen of origin., (© 2024 Japanese Dermatological Association.)

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We additionally investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Pg- or Ec-LPS and TAK-242 were administered intraperitoneally. Ec-LPS (840 μg/kg), but not Pg-LPS (100, 500 and 840 μg/kg), inhibited novelty-induced locomotion, which was antagonized by TAK-242 (3.0 mg/kg). Ec-LPS (840 μg/kg) increased blood levels of IL-6 and IL-10, which were antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 μg/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 μg/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood levels of IL-10, a cytokine thought to prevent the development of periodontal disease., Competing Interests: The authors report no conflict of interest., (Copyright: © 2024 Aono 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.)

To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; P = .0014) and (12.8 vs 9.9; P = .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, P = .0003), AST (IU/L) (54 vs 26, P < .0001), ALT (IU/L) (80 vs 34, P = .0004), and γ-GTP (IU/L) levels (64 vs 34, P = .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to investigate the utility of intensive triamcinolone acetonide (TA) injections after extensive esophageal endoscopic submucosal dissection (ESD)., Methods: This retrospective study included 27 lesions in 27 consecutive patients who underwent ESD (ulcers encompassing ≥3/4 of the esophageal circumference) and received TA injections without oral steroid administration. Groups A and B included patients undergoing ESD with and without complete circumferential resection, respectively. All patients received TA injections (100 mg/session) immediately after ESD. In Group A, weekly based TA injections were performed until near-complete ulcer epithelialization. In Group B, patients did not receive additional injections or received weekly or biweekly TA injections. The primary outcome was stricture rate, and the secondary outcomes were the proportion of patients requiring endoscopic balloon dilation (EBD) and the number of TA injections., Results: Group A included 7 lesions, and Group B included 20 lesions. The median (range) tumor lengths were 40 (30-90) and 45 (30-110) mm in Groups A and B, respectively. In Group A, the median circumferential resection diameter was 40 (20-80) mm. The stricture rate and the proportion of patients requiring EBD were 0 (0%) in Group A and 1 (5.0%) in Group B. The number of TA injection sessions was significantly higher in Group A than in Group B (8 [5-25] vs 1.5 [1-3]; p  < 0.001)., Conclusions: Intensive weekly or biweekly based TA injections might aid in preventing post-ESD stricture and the need for EBD in patients undergoing extensive resection involving the entire esophageal circumference.

Objective: To assess the association among preoperative total testosterone levels, postoperative sexual function, and prognosis after robot-assisted radical prostatectomy., Methods: Patients who underwent robot-assisted radical prostatectomy in our institution were included in the study. Based on preoperative total testosterone levels, they were divided into low (<3.0 ng/mL) and high (≥3.0 ng/mL) total testosterone groups. Sexual function was evaluated using the International Index of Erectile Function scores, Expanded Prostate Cancer Index Composite scores, and the potency rate from preoperatively to 12 months after surgery. Oncological outcomes were evaluated based on biochemical recurrence., Results: Out of 233 patients included, no significant difference in sexual function was found between the high (n = 183) and the low (n = 50) total testosterone groups at any point before or after surgery. However, in nerve-sparing cases, preservation in postoperative sexual function was observed only in the high total testosterone group (International Index of Erectile Function scores and Expanded Prostate Cancer Index Composite sexual function scores, at any point after surgery, p < 0.05; potency rate, at 3, 6, and 12 months after surgery; p < 0.05). Additionally, the high total testosterone group showed better biochemical recurrence-free survival than the low total testosterone group (p = 0.008)., Conclusions: In the high total testosterone group, preservation in sexual function was observed after the nerve-sparing procedure, while the biochemical recurrence rate was low. Therefore, patients with high levels of total testosterone may be advised to consider nerve-sparing interventions., (© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Cervical cancer affects women worldwide and is the most common human papillomavirus (HPV)-associated cancer. Carcinogenesis caused by HPV results in specific cancer behavior because of the underlying viral infection. The mechanism and timing of the transformation from viral infection to cancer cells have been elucidated in detail. Treatments for this cancer are based on its characteristics and are being implemented. Moreover, HPV infection is widespread worldwide and is transmitted through sexual activity. Although the HPV vaccination is the most effective strategy of preventing cervical cancer, it is not feasible to vaccinate the entire human population especially in low- and middle-income countries. In order to consider the next step for HPV vaccination, we need to understand the characteristics of HPV carcinogenesis and cervical cancer. Additionally, treatment aimed at preservation of reproductive function in patients with cervical cancer is often required, as the cervix is a reproductive organ and because the disease is more prevalent in the adolescent and young adult generation. Thus, there are still many challenges in the diagnosis, treatment, and prevention of cervical cancer., (© 2024 Japan Society of Obstetrics and Gynecology.)

Nanostructures of pores and protrusions in the insect cuticle modify molecular permeability and surface wetting and help insects sense various environmental cues. However, the cellular mechanisms that modify cuticle nanostructures are poorly understood. Here, we elucidate how insect-specific Osiris family genes are expressed in various cuticle-secreting cells in the Drosophila head during the early stages of cuticle secretion and cover nearly the entire surface of the head epidermis. Furthermore, we demonstrate how each sense organ cell with various cuticular nanostructures expressed a unique combination of Osiris genes. Osiris gene mutations cause various cuticle defects in the corneal nipples and pores of the chemosensory sensilla. Thus, our study emphasizes on the importance of Osiris genes for elucidating cuticle nanopatterning in insects., Competing Interests: Conflicts of interest. The author(s) declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Exiguobacterium sibiricum rhodopsin (ESR) functions as a light-driven proton pump utilizing Lys96 for proton uptake and maintaining its activity over a wide pH range. Using a combination of methodologies including the linear Poisson-Boltzmann equation and a quantum mechanical/molecular mechanical approach with a polarizable continuum model, we explore the microscopic mechanisms underlying its pumping activity. Lys96, the primary proton uptake site, remains deprotonated owing to the loss of solvation in the ESR protein environment. Asp85, serving as a proton acceptor group for Lys96, does not form a low-barrier H-bond with His57. Instead, deprotonated Asp85 forms a salt-bridge with protonated His57, and the proton is predominantly located at the His57 moiety. Glu214, the only acidic residue at the end of the H-bond network exhibits a p K a value of ∼6, slightly elevated due to solvation loss. It seems likely that the H-bond network [Asp85···His57···H 2 O···Glu214] serves as a proton-conducting pathway toward the protein bulk surface.

Aim: To establish cut-off values for anti-Müllerian hormone (AMH) and antral follicle count (AFC) in the diagnostic criteria for polycystic ovary syndrome (PCOS) applicable to the Japan Society of Obstetrics and Gynecology (JSOG) 2024 criteria and the Rotterdam/International Evidence-Based Guideline for the assessment and management of PCOS (IEBG) 2023 criteria based on a nationwide survey, respectively, taking into account age, assays, and structure of the diagnostic criteria., Methods: Data were collected for 986 PCOS cases and 965 control cases using a national survey in Japan and used to establish cut-off values for AMH and AFC., Results: Serum AMH levels were significantly higher in the PCOS group compared to the control group. Serum AMH showed a significant negative correlation with age and significant positive correlation with AFC in both groups. In multiple regression analysis, serum AMH level was independently affected by AFC and total testosterone. AMH cut-off values suitable for the JSOG 2024 criteria and the Rotterdam/IEBG 2023 criteria were separately established for the 20-29 and 30-39 years of age groups, respectively, and for Access, Lumipulse and Elecsys/ECLusys, respectively. AFC cut-off values suitable for the JSOG 2024 criteria and Rotterdam/IEBG 2023 criteria were also established separately. AFC exhibited statistically greater variability than AMH., Conclusion: The serum AMH level is the biochemical representation of ovarian findings in PCOS and considered objective and highly reliable. Therefore, it could serve as a surrogate for AFC as a marker of polycystic ovarian morphology in diagnostic criteria., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Demyelinating diseases including multiple sclerosis (MS) are chronic inflammatory diseases of the central nervous system. Indoleamine 2,3-dioxygenase 2 (Ido2) is a recently identified as catalytic enzyme involved in the rate-limiting step of the tryptophan-kynurenine pathway that influences susceptibility to inflammatory diseases. However, the pathological role of Ido2 in demyelination remains unclear. In this study, we investigated whether Ido2 deficiency influences the pathogenesis of proteolipid protein transgenic (Plp tg) mice, an animal model of chronic demyelination. Ido2 deficiency exacerbates impairments of motor function in the locomotor activity test, wire hanging test, and rotarod test. Ido2 deficiency caused severe demyelination associated with CD68-positive microglial activation in Plp tg mice. In the cerebellum of Plp tg mice, Ido2 deficiency significantly increased the expression of Tnfα. Ido2 deficiency reduced tryptophan metabolite kynurenine (KYN) levels and subsequent aryl hydrocarbon receptor (AhR) activity, which play an important role in anti-inflammatory response. These results suggest that Ido2 has an important role in preventing demyelination through AhR. Taken together, Ido2 could be a potential therapeutic target for demyelinating diseases., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to elucidate the clinical features, outcomes and risk factors of flares in patients with systemic lupus erythematosus (SLE). Data were collected from patients with newly diagnosed SLE at the Fukushima Medical University Hospital between 2011 and 2022. Patients who experienced a flare during the study period constituted the flare group, and their clinical features were compared with those of the no-flare group. The cumulative flare-free survival regarding several clinical items was compared between the two groups using Kaplan-Meier's curves. Among 387 patients with SLE, 83 patients with newly diagnosed SLE were included. Their mean age was 37.9 years, and 29 patients experienced flares during the study period. The general characteristics were similar between the two groups, with the exception of the observation period and anti-SS-A antibody positivity. Regarding therapy, a significantly increased frequency of hydroxychloroquine intake and combination with immunosuppressive agents were observed in the no-flare group. The Kaplan-Meier analysis revealed a significantly higher cumulative flare-free survival in the anti-SS-A negative group and combination immunosuppressive therapy group. In conclusion, anti-SS-A positivity may be a risk factor for SLE flare. In turn, combination immunosuppressive therapy may be beneficial for SLE treatment in daily clinical practice.

The bicellular tight junction molecule cingulin (CGN) binds to microtubules in centrosomes. Furthermore, CGN contributes to the tricellular tight junction (tTJ) proteins lipolysis-stimulated lipoprotein receptor (LSR) and tricellulin (TRIC). CGN as well as LSR decreased during the malignancy of endometrioid endometrial cancer (EEC). Although tTJ protein LSR is involved in the malignancy of some cancers, including EEC, the role of CGN is unknown. In this study, we investigated the roles of CGN with tTJ proteins in human EEC cells by using the CGN-overexpressing EEC cell line Sawano. In 2D cultures, CGN was colocalized with LSR and TRIC at tTJ or at γ-tubulin-positive centrosomes. In immunoprecipitation with CGN antibodies, CGN directly bound to LSR, TRIC, and β-tubulin. Knockdown of CGN by the siRNA decreased the epithelial barrier and enhanced cell proliferation, migration and invasion, as well as knockdown of LSR. In the Sawano cells cocultured with normal human endometrial stromal cells, knockdown of CGN decreased expression of LSR and TRIC via MAPK and AMPK pathways. In 2.5D cultures, knockdown of CGN induced the formation of abnormal cysts and increased the permeability of FD-4 to the lumen. In 2D and 2.5D cultures, treatment with β-estradiol with or without EGF or TGF-β decreased CGN expression and the epithelial permeability barrier and enhanced cell migration, and pretreatment with EW7197+AG1478, U0126 or an anti-IL-6 antibody prevented this. In conclusion, CGN, with tTJ proteins might suppress the malignancy of human EEC and its complex proteins are sensitive to estrogen and growth factors derived from stromal cells.

High pathogenicity avian influenza is an acute zoonotic disease with high mortality in birds caused by a high pathogenicity avian influenza virus (HPAIV). Recently, HPAIV has rapidly spread worldwide and has killed many wild birds, including endangered species. Baloxavir marboxil (BXM), an anti-influenza agent used for humans, was reported to reduce mortality and virus secretion from HPAIV-infected chickens ( Gallus domesticus , order Galliformes) at a dosage of ≥2.5 mg/kg when administered simultaneously with viral challenge. Application of this treatment to endangered birds requires further information on potential avian-specific toxicity caused by repeated exposure to BXM over the long term. To obtain information of potential avian-specific toxicity, a 4-wk oral repeated-dose study of BXM was conducted in chickens ( n = 6 or 7 per group), which are commonly used as laboratory avian species. The study was conducted in reference to the human pharmaceutical guidelines for nonclinical repeated-dose drug toxicity studies to evaluate systemic toxicity and exposure. No adverse changes were observed in any organs examined, and dose proportional increases in systemic exposure to active pharmaceutical ingredients were noted from 12.5 to 62.5 mg/kg per day. BXM showed no toxicity to chickens at doses of up to 62.5 mg/kg per day, at which systemic exposure was approximately 71 times higher than systemic exposure at 2.5 mg/kg, the reported efficacious dosage amount, in HPAIV-infected chickens. These results also suggest that BXM could be considered safe for treating HPAIV-infected endangered birds due to its high safety margin compared with the efficacy dose. The data in this study could contribute to the preservation of endangered birds by using BXM as a means of protecting biodiversity.