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ABSTRACT Aim/Introduction Xanthine oxidoreductase (XOR) inhibitor treatment, which reduces reactive oxygen species (ROS) production and increases adenosine triphosphate (ATP) synthesis, has been reported to improve glycemic control. The possible protective effects of XOR inhibitor treatment on insulin secretory capacity were investigated in patients with type 2 diabetes. Materials and Methods This retrospective cross‐sectional study included 428 patients with type 2 diabetes. Insulin secretory capacity was assessed based on fasting serum C‐peptide concentration (CPR) and C‐peptide index (CPI) in all subjects, while insulin resistance in non‐insulin users (n = 312) was determined using the homeostasis model assessment of insulin resistance (HOMA‐IR) index. Results Median values for CPR and CPI in all subjects were 2.4 ng/mL and 1.5, respectively, while that for HOMA‐IR in non‐insulin users was 3.2. The XOR inhibitor users (n = 72) had significantly (P 6.0 mg/dL) uric acid levels (P for interaction

A pheochromocytoma is a malignant tumor with metastatic potential. Moreover, the cardiovascular effects of abnormal amounts of catecholamines resulting from pheochromocytoma impact prognosis. Resection of the primary tumor is useful for reducing catecholamine production; however, the significance of resection of metastases remains unclear. Herein, we report a case in which multiple lung resections for metastases from pheochromocytoma were performed 5 years after primary tumor resection. Complete resection of 6 pulmonary lesions was achieved, maintaining reduced catecholamine levels and blood pressure without any sign of recurrence for a year.

The safety of railways is ensured by the regular maintenance of tracks, signals and rolling stocks. This mainly involves manual inspection by skilled maintainers and automated inspection systems are not commonly used. The development of an automated inspection system is crucial for maintaining good rail conditions. In this study on automatic surface defect detection systems, we focused on wheels as the target because they are critical components of rolling stocks, and any wheel defects can cause severe safety problems. Wheel-tread-profile dimensions have been measured using laser instruments in previous studies. In this research, to validate the accuracy of the measurement equipment, special test pieces with surface defects are prepared. We propose a combined inspection system using laser sensors, and a machine vision technique to confirm the effectiveness of the proposed system. An artificial intelligence (AI)-based surface defect detection system is employed to improve the proposed system. Combining edge detection through image transformation with an AI-based surface defect detection system offers remarkable benefits. The effectiveness of the system is experimentally confirmed using test pieces that simulate different materials and passing speeds of wheels.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Abstract There is no treatment for acute aortic dissection (AAD) targeting inflammatory cells. We aimed to identify the new therapeutic targets associated with inflammatory cells. We characterized the specific distribution of myeloid cells of both human type A AAD samples and a murine AAD model generated using angiotensin II (ANGII) and β-aminopropionitrile (BAPN) by single-cell RNA sequencing (scRNA-seq). We also examined the effect of an anti-interleukin-1β (IL-1β) antibody in the murine AAD model. IL1B+ inflammatory macrophages and classical monocytes were increased in human AAD samples. Trajectory analysis demonstrated that IL1B+ inflammatory macrophages differentiated from S100A8/9/12+ classical monocytes uniquely observed in the aorta of AAD. We found increased infiltration of neutrophils and monocytes with the expression of inflammatory cytokines in the aorta and accumulation of inflammatory macrophages before the onset of macroscopic AAD in the murine AAD model. In blocking experiments using an anti-IL-1β antibody, it improved survival of murine AAD model by preventing elastin degradation. We observed the accumulation of inflammatory macrophages expressing IL-1β in both human AAD samples and in a murine AAD model. Anti-IL-1β antibody could improve the mortality rate in mice, suggesting that it may be a treatment option for AAD.

BackgroundRecent clinical studies suggest protective effects of SGLT2 inhibitors on kidney disease outcome. Chronic hypoxia has a critical role in kidney disease development, thus we speculated that canagliflozin, an SGLT2 inhibitor, can improve kidney oxygenation.MethodsA single-arm study was conducted to investigate the effects of canagliflozin on T2* value, which reflects oxygenation level, in patients with type 2 diabetes (T2D) using repeated blood oxygenation level-dependent MRI (BOLD MRI) examinations. Changes in cortical T2* from before (Day 0) to after single-dose treatment (Day 1) and after five consecutive treatments (Day 5) were evaluated using 12-layer concentric objects (TLCO) and region of interest (ROI) methods.ResultsIn the full analysis set (n=14 patients), the TLCO method showed no change of T2* with canagliflozin treatment, whereas the ROI method found that cortical T2* was significantly increased on Day 1 but not on Day 5. Sensitivity analysis using TLCO in 13 well-measured patients showed that canagliflozin significantly increased T2* on Day 1 with no change on Day 5, whereas a significant improvement in cortical T2* following canagliflozin treatment was found on both Day 1 and 5 using ROI.ConclusionsShort-term canagliflozin treatment may improve cortical oxygenation and lead to better kidney outcomes in patients with T2D.

Abstract Background Infusion-related reactions (IRRs) are major side effects of rituximab administration. Male sex, high body weight, body surface area (BSA), and body mass index are predictive markers of rituximab-induced IRRs. However, as rituximab was not administered at a fixed dosage in a previous study, whether a higher dosage or factors associated with a larger physique are more strongly associated with rituximab-induced IRRs is unknown. Main body Thirteen adults with frequently relapsing minimal change nephrotic syndrome (MCNS) who received an initial rituximab dose of 500 mg between September 2015 and November 2022 were retrospectively evaluated. Data on IRRs were collected from medical records. The incidence of rituximab-induced IRRs was 38.5% (5/13). The IRR group had a significantly higher BSA than the non-IRR group (median, 1.86 vs. 1.48 m2; p = 0.045). Additionally, rituximab dosage normalized by BSA in the IRR group was significantly lower than that in the non-IRR group (median, 268.8 vs. 337.9 mg/m2; p = 0.045). Conclusions Our study revealed that adults with frequently relapsing MCNS who experienced IRRs tend to have a higher BSA, even with fixed-dose rituximab treatment. Therefore, when patients with higher BSA receive rituximab treatment, clinicians should be careful about monitoring patient condition whether the dosage is fixed or not.

AbstractAccess to sexual health services and information is critical to achieving the highest attainable standard of sexual health, and enabling legal environments are key to advancing progress in this area. In determining overall alignment with human rights standards to respect, protect, and fulfil sexual health-related rights without discrimination, there are many aspects of laws, including their specificity and content, which impact which sexual health services and information are availed, which are restricted, and for whom. To understand the nature of existing legal provisions surrounding access to sexual health services and information, we analysed the content of 40 laws in English, French, and Spanish from 18 countries for the specific sexual health services and information to which access is ensured or prohibited, and the non-discrimination provisions within these laws. Overall, there was wide variation across countries in the types of laws covering these services and the types and number of services and information ensured. Some countries covered different services through multiple laws, and most of the laws dedicated specifically to sexual health addressed only a narrow aspect of sexual health and covered a small range of services. The protected characteristics in non-discrimination provisions and the specificity of these provisions with regard to sexual health services also varied. Findings may inform national legal and policy dialogues around sexual health to identify opportunities for positive change, as well as to guide further investigation to understand the relationship between such legal provisions, the implementation of these laws within countries, and relevant sexual health outcomes.

Children's attitudes are shaped by the information to which they are exposed. To foster improved peer relationships in inclusive settings, there is a need for typically developing children to exhibit positive attitudes toward peers with disabilities. The aim of this study was to examine the relationship between children's attitudes toward their peers with disabilities and the available information about disabilities. Furthermore, through this study, we sought to report the process of developing a Japanese version of the Chedoke-McMaster Attitudes Towards Children with Handicaps Scale (CATCH-J). The participants were 215 children in fourth through sixth grades who attended an elementary school that does not provide special education services. A questionnaire containing the CATCH-J and other pertinent information was administered to the participants. Three sources of information about disabilities were investigated: conversations; school lessons; and media including books, television, or the internet. After removing some items, the CATCH-J demonstrated good validity and reliability. Participants who obtained information about disabilities through conversations showed more positive attitudes than those who did not. Meanwhile, there were no significant differences between those who obtained information from school lessons or media and those who did not. The findings imply that typically developing children's participation in academic lessons or exposure to television programs or internet content is not sufficient to foster positive attitudes toward peers with disabilities. Talking about disabilities with family could be the first step in this direction.

Adenocarcinoma is a common histological type of ulcerative colitis-associated cancer (UCAC), whereas neuroendocrine carcinoma (NEC) is extremely rare. UCAC is generally diagnosed at an advanced stage, even with regular surveillance colonoscopy. A 41-year-old man with a 17-year history of UC began receiving surveillance colonoscopy at the age of 37 years; 2 years later, dysplasia was detected in the sigmoid colon, and he underwent colonoscopy every 3 to 6 months. Approximately 1.5 years thereafter, a flat adenocarcinoma lesion occurred in the rectum. Flat lesions with high-grade dysplasia were found in the sigmoid colon and surrounding area. The patient underwent laparoscopic total proctocolectomy and ileal pouch-anal anastomosis with ileostomy. Adenocarcinoma was diagnosed in the sigmoid colon and NEC in the rectum. One year postoperation, recurrence or metastasis was not evident. Regular surveillance colonoscopy is important in patients with long-term UC. A histological examination of UCAC might demonstrate NEC.

Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.

In Western countries, the gold-standard therapeutic strategy for rectal cancer is preoperative chemoradiotherapy (CRT) following total mesorectal excision (TME), without lateral lymph node dissection (LLND). However, preoperative CRT has recently been reported to be insufficient to control lateral lymph node recurrence in cases of enlarged lateral lymph nodes before CRT, and LLND is considered necessary in such cases. We performed a literature review on aspects of pelvic anatomy associated with rectal surgery and LLND, and then combined this information with our experience and knowledge of pelvic anatomy. In this review, drawing upon research using a 3-dimensional anatomical model and actual operative views, we aimed to clarify the essential anatomy for LLND. The LLND procedure was developed in Asian countries and can now be safely performed in terms of functional preservation. Nonetheless, the longer operative time, hemorrhage, and higher complication rates with TME accompanied by LLND than with TME alone indicate that LLND is still a challenging procedure. Laparoscopic or robotic LLND has been shown to be useful and is widely performed; however, without a sufficient understanding of anatomical landmarks, misrecognition of vessels and nerves often occurs. To perform safe and accurate LLND, understanding the landmarks of LLND is essential.