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Allergic diseases and ulcerative colitis (UC) share pathophysiological similarities. This study aimed to investigate the unclear association between allergic diseases and mucosal healing (MH), an important factor in the prognosis of UC. We studied 289 Japanese patients with UC. Information on allergic diseases (bronchial asthma, atopic dermatitis, pollen allergy, food allergy, and drug allergy), as diagnosed by physicians, was collected through self-reported questionnaires. The definition of MH was Mayo Endoscopic Score 0. The association between each allergic disease and its multimorbidity with MH was evaluated using multivariate logistic regression analyses. Pollen allergy was the most common allergic condition (36.3%). Pollen allergy and food allergy were independently associated with MH (pollen allergy adjusted OR: 1.82 [95% CI: 1.01-3.26]; food allergy adjusted OR: 3.47 [95% CI: 1.26-9.68]). The rates of MH for 0 and 3 or more allergic diseases were 24.6% and 4.2%, respectively. After adjustment for confounders, 3 or more allergic diseases were independently associated with MH (adjusted OR: 8.13 [95% CI: 2.17-34.04], p for trend = 0.020). This study demonstrates a significant positive association between specific allergic diseases (pollen and food allergies) and MH in UC patients, with a stronger association in cases of allergic multimorbidity., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that there is no conflict of interest regarding the publication of this article., (© 2025. The Author(s).)

Duchenne muscular dystrophy (DMD) is a severe muscle disorder caused by mutations in the DMD gene, leading to dystrophin deficiency. Antisense oligonucleotide (ASO)-mediated exon skipping offers potential by partially restoring dystrophin, though current therapies remain mutation specific with limited efficacy. To overcome those limitations, we developed brogidirsen, a dual-targeting ASO composed of two directly connected 12-mer sequences targeting exon 44 using phosphorodiamidate morpholino oligomers. An open-label, dose-escalation, phase 1/2 trial assessed the safety, pharmacokinetics, and efficacy of brogidirsen in six ambulant patients with DMD amenable to exon 44 skipping. Following dose escalation, extended 24-week treatment with 40 mg/kg and 80 mg/kg yielded dose-dependent increases in dystrophin (16.63% and 24.47% of normal). Functional assessments indicated motor stabilization, and plasma proteomics revealed reductions in peptidyl arginine deiminase 2 (PADI2), titin (TTN), and myomesin 2 (MYOM2), highlighting potential biomarkers. Brogidirsen's efficacy was supported in vitro using urine-derived cells from patients with DMD. These promising results warrant a subsequent trial for DMD. This study was registered at ClinicalTrials.gov (NCT04129294)., Competing Interests: Declaration of interests H.K. received consulting fees from Nippon Shinyaku for work related to this study and from Biogen, Novartis, Sanofi, Sarepta, Chugai, Daiichi Sankyo, Kaneka, and Astellas for work unrelated to this study. H.K. received grant funding from Nippon Shinyaku for work related to this study and from Sanofi, Chugai, PTC Therapeutics, Taiho, and Pfizer for work unrelated to this study. E.T. received grant funding from Nippon Shinyaku for work related to this study and from Daiichi Sankyo, Taiho, and Takeda for work unrelated to this study. Y.A. received grant funding from Nippon Shinyaku for work associated with this study and from Shionogi, Takeda, and Kaneka for work unrelated to this study., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Becker muscular dystrophy (BMD) is an allelic disorder of Duchenne muscular dystrophy (DMD) in which pathogenic variants in DMD cause progressive worsening of motor dysfunction, muscle weakness and atrophy, and death due to respiratory and cardiac failure. BMD often has in-frame deletions that preserve the amino acid reading frame, but there are some cases with microvariants or duplications. In recent years, the importance of therapeutic development and care for BMD has been emphasized. Therefore, the purpose of this study was to understand the clinical characteristics of BMD patients with microvariants or duplications and to determine the genotype-phenotype relationship., Methods: The study focused on patients with pathogenic microvariants or duplications in DMD who were ambulatory after 16 years of age or had specific muscle biopsy results between June 13, 2017, and March 31, 2023. Informed consent was obtained from the patients or their surrogates. Data concerning DMD variants, muscle biopsy findings, skeletal muscle, respiratory and cardiac function, and CNS involvement were collected and analyzed statistically., Results: Thirty-three patients with BMD had pathogenic microvariants (missense variants, nonsense variants, splice site variants, and other microvariants), and 16 patients had in-frame duplications in DMD . Many patients with microvariants had abnormal ECG findings. The effect of variant type on patient outcomes varied. Regardless of the type of microvariant, skeletal muscle and respiratory dysfunction was more severe in mutants of the cysteine-rich/C-terminal domain than in rod domain mutants. On the other hand, there was no significant difference in the complication rate of CNS disorders among the 3 domains of dystrophin., Discussion: Microvariant forms, in particular, tend to vary in clinical severity according to the site of the dystrophin protein mutation rather than the type of pathogenic variant. The results of this study may be useful for genetic counseling, care, and treatment of patients with BMD., Competing Interests: The authors report no conflicts of interest regarding this study. Dr. Madoka Mori-Yoshimura is deceased; to the best of our knowledge, the relevant disclosures are none. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Lissencephaly is a rare brain malformation characterized by abnormal neuronal migration during cortical development. In this study, we performed a comprehensive genetic analysis using next-generation sequencing in 12 unsolved Japanese lissencephaly patients, in whom PAFAH1B1, DCX, TUBA1A, and ARX variants were excluded using the Sanger method. Exome sequencing (ES) was conducted on these 12 patients, identifying pathogenic variants in CEP85L, DYNC1H1, LAMC3, and DCX in four patients. Next, we performed genome sequencing (GS) on eight unsolved patients, and structural variants in PAFAH1B1, including an inversion and microdeletions involving several exons, were detected in three patients. Notably, these microdeletions in PAFAH1B1 could not to be detected by copy number variation (CNV) detection tools based on the depth of coverage methods using ES data. The density of repeat sequences, including Alu sequences or segmental duplications, which increase the susceptibility to structural variations, is very high in some lissencephaly spectrum genes (PAFAH1B1, TUBA1A, DYNC1H1). These missing CNVs were due to the limitations of detecting repeat sequences in ES-based CNV detection tools. Our study suggests that a combined approach integrating ES with GS can contribute to a higher diagnostic yield and a better understanding of the genetic landscape of the lissencephaly spectrum., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)

Background: Constipation is a very common medical issue among the general population worldwide. However, the association between exercise habits and constipation is still not fully understood. Additionally, no evidence regarding the association between exercise partners and constipation exists. This study aimed to evaluate this issue in a young Japanese population, taking the presence or absence of an exercise partner as an additional variable., Methods: The study subjects consisted of 12,497 Japanese university students. Information on constipation, exercise frequency, exercise intensity, and exercise partners was obtained through a self-administered questionnaire. Constipation was defined as present if a student answered "Yes" to the question, "Have you been constipated often recently?", Results: The prevalence of self-reported constipation was 6.5%. Frequency and intensity of exercise were independently inversely associated with constipation. After adjustment for age, body mass index, drinking, smoking, anemia, and sports injury, exercise with groups and friends was independently inversely associated with constipation (groups: adjusted odds ratio (OR) - 0.70 (95% confidence interval (CI): 0.53-0.90), friends: adjusted OR - 0.56 (95% CI: 0.42-0.74)). After further adjustment by adding intensity and frequency of exercise to confounding factors, only the association between exercise with friends and constipation was still significant (adjusted OR: 0.61 (95% CI: 0.39-0.96))., Conclusions: In this young Japanese population, the frequency and the intensity of exercise and the presence of exercise partners might be independently inversely associated with self-reported constipation. Exercising, especially exercising with others, may have a preventive effect on constipation, and opportunities to exercise with others should be provided., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Ethics Committee of the Ehime University Graduate School of Medicine issued approval 1610012. All subjects were provided an opt-out, and the study protocol was developed in accordance with the ethical guidelines of the Declaration of Helsinki. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Watanabe et al.)

Pathogenic variants of WD repeat domain 45 ( WDR45 ) cause neurodegeneration with brain iron accumulation 5 (NBIA5), which is characterised by progressive neurological regression and brain iron accumulation in adulthood. Early diagnosis of NBIA5 patients is difficult because they often show only a non-specific developmental delay in childhood, but it is essential for lifelong medical management. We investigated 32 females with developmental delays for coding variants of WDR45 using Sanger sequencing. Whole-genome sequencing (WGS) and X chromosome inactivation (XCI) analysis were also performed. We identified two disease-causing variants, one of which was a novel stop-loss variant, c.1051delG p.(Val351CysfsTer60), in a female with severe developmental delay from early infancy with epileptic spasms. The XCI analysis (which we originally developed) suggested a random pattern in white blood cells. WGS did not reveal any other pathogenic variants, including those in two iron transporter genes. Together with our previous findings in the WGS study, WDR45 variants accounted for 12% (6/51) of the females with developmental delay, suggesting that WDR45 is a major gene in females with developmental delay. Pathogenic variants of WDR45 result in various phenotypes that do not necessarily correlate with variant types or XCI skewing patterns., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Interleukin (IL)-23 is involved in the pathogenesis of ulcerative colitis (UC). A genome-wide significant association between IL23R p.G149R (rs76418789) and UC was previously identified in Japan and Korea. This case-control study aims to examine this association within the Japanese population., Methods: The study included 384 cases diagnosed with UC within the past 4 years and 661 control subjects. Adjustment was made for sex, age, and smoking., Results: The frequency of the AA genotype of rs76418789 was 0.0 % in cases and 0.5 % in control subjects. In comparison to study subjects with the GG genotype of rs76418789, those with the GA or AA genotype had a significantly reduced risk of UC, with an adjusted odds ratio of 0.67 (95 % confidence interval: 0.44-0.999). A significant multiplicative interaction was observed between rs76418789 and having ever smoked influencing UC (p for interaction = 0.03). A significant positive association was found between having ever smoked and UC in individuals with at least one A allele, while no such positive relationship was observed in those with the GG genotype., Conclusion: IL23R SNP rs76418789 showed a significant association with UC. This study provides new evidence regarding the interaction between rs76418789 and smoking in relation to UC., 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 Elsevier Ltd. All rights reserved.)

Introduction: Nocturia is a common symptom of lower urinary tract syndrome (LUTS). In previous studies, a close association between LUTS and colorectal inflammation has been reported. However, evidence regarding the association between nighttime urinary frequency and ulcerative colitis (UC) is limited. Herein, we investigated the association between nighttime urinary frequency and clinical outcomes of UC., Methods: We surveyed 287 Japanese patients with UC. A self-administered questionnaire was used to collect the information on the variables studied. Patients were divided into three groups based on nighttime urinary frequency: (1) no voids, (2) one void, and (3) two or more voids. The assessment of clinical outcomes was based on mucosal healing (MH) and clinical remission (CR). The association between nighttime urinary frequency and prevalence of MH and CR was evaluated using multivariate logistic regression analyses., Results: The prevalence of one nighttime frequency and two or more nighttime frequency in this cohort was 35.5% and 26.8%, respectively. The percentage of MH and CR was 24.7% and 59.2%, respectively. Two or more nighttime frequency (adjusted odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.13-0.73) was independently and inversely associated with MH. In nonelderly patients (<70 years) and patients in CR, an association between two or more nighttime frequency and MH remained significant (non-elderly: adjusted OR: 0.27, 95% CI: 0.09-0.72 and only CR: adjusted OR: 0.34, 95% CI: 0.12-0.90)., Conclusion: Nighttime urinary frequency was independently and inversely associated with MH in Japanese patients with UC. Nighttime urinary frequency may serve as a complementary physical sign of MH in patients with UC., (© 2024 Wiley Periodicals LLC.)

Objective and Rationale: To investigate the longitudinal incidence of kidney/urinary stones in patients with severe motor and intellectual disabilities and explore health burden events in patients with stone formation., Methods: This was a retrospective, observational study. We identified patients with severe motor and intellectual disabilities who had the following: 1) admission to our hospital wards for >10 years; 2) two or more assessments for stone formation by ultrasonography or computed tomography; and 3) absence of kidney/urinary stones in the first imaging study. The Kaplan-Meier method was used to analyze the cumulative incidence of kidney/urinary stones. Recurrent urinary tract infections, hydronephrosis, renal dysfunction, and death were identified as health burdens., Results: Among the 41 patients (19 men, 22 women; median age, 28 years; range, 8-50 years), stone formation was detected in 11 (27%) patients during the observation period. The cumulative incidence rate of stone formation was 9.8% (95% confidence interval, 3.8-23.9) and 18.7% (95% confidence interval, 9.2-35.7) at five and 10 years, respectively. Death was frequently observed in patients with stone formation; six (55%) of the 11 patients with stone formation died during the follow-up period; two (15%) died among the other 30 patients without stone formation. However, only one patient with stone formation died in a renal event; the causal relationship between the stone formation and the deaths was not clarified., Conclusion: The longitudinal incidence of kidney/urinary stones was higher in patients with severe motor and intellectual disabilities than in the general population. Considering the difficulty of patients with severe motor and intellectual disabilities in conveying their symptoms, regular assessment of the kidney using abdominal imaging may be recommended., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. The National Center of Neurology and Psychiatry Ethics Committee issued approval 2021-422. This study was approved by the National Center of Neurology and Psychiatry ethics committee on July 7, 2021 and conformed to the provisions of the Declaration of Helsinki. Written informed consent was waived due to the retrospective nature of this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was partly supported by an Intramural Research Grant (3-6) for Neurological and Psychiatric Disorders from the National Center for Neurology and Psychiatry. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hashimoto et al.)

Objective: This study aimed to investigate the clinical characteristics of pediatric-onset dystonia in Japan, addressing the diagnostic challenges arising from symptom variations and etiological diversity., Methods: From 2020 to 2022, questionnaires were distributed to 1218 board certified child neurologists (BCCNs) by Japanese Society of Child Neurology. In the primary survey, participants were asked to report the number of patients with pediatric-onset dystonia under their care. Subsequently, the follow-up secondary survey sought additional information on the clinical characteristics of these patients., Results: The primary survey obtained 550 responses (response rate: 45 %) from BCCNs for their 736 patients with dystonia. The predominant etiologies included inherited cases (with DYT10   being the most prevalent, followed by DYT5 and ATP1A3-related neurologic disorders), acquired cases (with perinatal abnormalities being the most common), and idiopathic cases. The secondary survey provided clinical insights into 308 cases from 82 BCCNs. Infancy-onset dystonia presented as persistent and generalized with diverse symptoms, primarily linked to ATP1A3-related neurologic disorders and other genetic disorders resembling acquired dystonia. Conversely, childhood/adolescent-onset dystonia showed paroxysmal, fluctuating courses, predominantly affecting limbs. The most common etiologies were DYT5 and DYT10 , leading to therapeutic diagnoses., Conclusion: Pediatric-onset dystonia in Japan was treated by 28 % of BCCNs. The majority of cases were inherited, with high prevalence rates of DYT5 and DYT10 . Infancy-onset dystonia exhibits diverse etiologies and symptoms, emphasizing the utility of various examinations, including genetic testing. These findings significantly contribute to our understanding of pediatric-onset dystonia in Japan, although this study has the limitation of questionnaire survey., 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 Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Pneumatosis cystoides intestinalis (PCI) is a rare disease wherein air accumulates in the intestinal subserosa and submucosa, causing multiple gaseous cysts within the gastrointestinal wall. While PCI has various known risk factors, reports identifying muscular diseases as a factor are scarce. The aim of this study is to elucidate the clinical characteristics of PCI in muscle disease. We present a case series of five cases, including two cases of Duchenne muscular dystrophy (DMD) and three cases of rare congenital myopathies. All cases are of male patients, with poor intestinal peristalsis and constipation, who underwent tube feeding and mechanical ventilation via tracheostomy. They had no signs of severe complications, such as intestinal necrosis, and all of them improved with conservative treatment. Case 1 is a 23-year-old man with DMD who developed cardiopulmonary arrest at the age of 20 years. Pulmonary hemorrhage occurred three months before the incidental detection of PCI in the ascending colon, which resolved with conservative oxygen treatment. Case 2 is a 25-year-old man with DMD who progressed to immobility necessitating tracheostomy at the age of 20 years. He experienced persistent abdominal pain and nausea, and PCI was detected in the cecum and ascending colon. He showed near-complete resolution of PCI after three months of conservative treatment. Case 3 is a six-year-old boy with reducing body myopathy. Constipation was diagnosed at four years of age. He experienced intermittent bloody stools, leading to the incidental detection of PCI at six years of age. After two months of conservative treatment, the PCI resolved with no subsequent recurrence. Case 4 is a 33-year-old man with infantile severe myotubular myopathy. He required mechanical ventilation immediately after birth and later underwent tracheostomy and tube feeding due to complications. At the age of 27 years, PCI was incidentally detected on abdominal CT. He had episodes of remission and worsening for a few years; however, PCI completely resolved after three years. Case 5 is a 27-year-old man with nemaline myopathy. At the age of 14 years, he had persistent bloody stools. After lower gastrointestinal endoscopy, he was diagnosed with PCI with numerous rectal cysts. PCI required no specific therapeutic intervention. There was spontaneous resolution of PCI and bloody stools. Given that PCI lacks specific symptoms and cases with muscular diseases often experience abdominal issues, many cases are liable to be overlooked or misdiagnosed. Cases with muscular diseases complaining of persistent abdominal symptoms should undergo radiographic imaging to rule out PCI., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Ethical Review Board of the National Center of Neurology and Psychiatry issued approval A2022-094. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Eri Takeshita declare(s) a grant from National Center of Neurology and Psychiatry. This research is supported by the Intramural Research Grants in the writing of the report (5-5 to E.T. for Neurological and Psychiatric Disorders of National Center of Neurology and Psychiatry (NCNP)). Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aihara et al.)

Background The ABO blood type has been associated with several digestive diseases. Some evidence has shown an association between ABO blood type and clinical outcomes among Asian patients with Crohn's disease. However, there are no reports about the association between ABO blood type and clinical outcomes in ulcerative colitis (UC). In this study, we aimed to evaluate the association between ABO blood type and clinical characteristics among patients with UC. Methodology The study subjects consisted of 277 Japanese patients with UC. Information on clinical characteristics and ABO blood type data was collected using medical records and a self-reported questionnaire. The information on clinical remission was collected using medical records. The definition of mucosal healing (MH) and partial MH was Mayo endoscopic subscore of 0 or 0-1, respectively. Results Of the enrolled patients, 39.4% (109/277), 18.4% (51/277), 29.2% (81/277), and 13.0% (36/277) had blood types A, B, O, and AB, respectively. The mean current age, age at onset of UC, and body mass index were 51.3 years, 42.1 years, and 22.7 kg/m 2 , and the proportion of male patients was 59.2% (164/277). The proportion of patients with clinical remission, MH, partial MH, and prednisolone use were 58.1% (161/277), 25.6% (71/277), 63.2% (175/277), and 21.3% (59/277), respectively. Conclusions None of the blood types were associated with any of the variables in this study. Among Japanese patients with UC, ABO blood type might not be associated with clinical characteristics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yagi et al.)

Socioeconomic status is a risk factor for poor disease prognosis. No studies of patients with ulcerative colitis (UC) have investigated the association between socioeconomic status and erectile dysfunction (ED), although UC is independently positively associated with ED. Therefore, the purpose of this survey to evaluate this issue in Japanese patients with UC. The study enrolled 165 patients with UC. Education status (low, middle, high) and household income (low, middle, high) were classified in three groups using self-administered surveys. The information regarding the Sexual Health Inventory for Men (SHIM) was obtained using self-administered questionnaires. The definition of mild to moderate or severe ED and severe ED was SHIM score <17 and SHIM score <8, respectively. The prevalence of mild to moderate or severe ED and severe ED was 64.9% and 47.9%, respectively. In crude analysis, household income was inversely associated with mild to moderate or severe ED and severe ED. After adjustment for age, current drinking, current smoking, exercise habit, body mass index, mucosal healing, and duration of UC, high household income was independently and inversely associated with mild to moderate or severe ED (adjusted odds ratio [OR] 0.23, 95% confidence interval [CI] [0.05, 0.93], p for trend = .038) and severe ED (adjusted OR 0.26, 95% CI [0.07, 0.85], p for trend = .024). In contrast, no association between education status and ED was found. In conclusion, household income was independently and inversely associated with ED in Japanese UC patients., 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.

Background/aims: Although certain allergic diseases have been reported to be associated with the prevalence of functional dyspepsia (FD) and irritable bowel syndrome (IBS), it is unclear whether the presence of multiple allergic diseases further increases the prevalence of FD and IBS. The aim of this study is to determine this issue in young people., Methods: A cohort of 8923 Japanese university students was enrolled and diagnoses of FD and IBS were confirmed using Rome III criteria. Allergic disorders diagnosed at medical institutions were obtained by means of a self-administered questionnaire., Results: The prevalence of FD, IBS, and their overlap was found to be 1.9%, 6.5%, and 1.1%, respectively. Pollen allergy was independently positively correlated with FD, IBS, and overlap of FD and IBS. Allergic rhinitis was positively linked to IBS. Drug allergy was positively associated with FD. The presence of multiple allergic diseases was positively correlated with FD and IBS (FD: adjusted OR for 2 allergic diseases: 1.95 [95% CI, 1.24-2.98], P for trend = 0.003; and IBS: adjusted OR for 1 allergic disease: 1.40 [95% CI, 1.15-1.69], 2 allergic diseases 1.47 [95% CI, 1.12-1.91], and 3 or more allergic diseases: 2.22 [95% CI, 1.45-3.28], P for trend = 0.001). Additionally, the concomitant existence of multiple allergic diseases was also demonstrated to have a trend that correlated with the overlap of FD and IBS ( P for trend = 0.018)., Conclusion: Allergic disease multimorbidity is positively correlated with the prevalence of FD and IBS in a young population.

Objectives: Some upper-limb function assessments can evaluate treatments in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The Functional Classification of the Upper Extremities (FCUE) was developed for DMD in Japan. The FCUE is easier to use than the Performance of Upper Limb (PUL) and is more detailed than the Brooke Upper Extremity Scale. This study aimed to determine the concurrent validity of FCUE with other methods of assessment for DMD., Methods: This retrospective study reviewed the medical records of 39 boys with DMD from the National Center of Neurology and Psychiatry to evaluate the concurrent validity of the FCUE and PUL using non-parametric Spearman rank correlation (ρ). We also determined the concurrent validity of the Brooke Upper Extremity Scale and PUL for comparison., Results: The ρ value between the FCUE and PUL was -0.914 (P<0.001). The FCUE showed robust concurrent validity with the PUL. That correlation between the FCUE and Brooke Upper Extremity Scale gave a ρ value of -0.854 (P<0.001)., Conclusions: The FCUE had a higher concurrent validity with the PUL than with the Brooke Upper Extremity Scale. The FCUE is considered a valid assessment tool of upper-limb function in boys with DMD. Selecting the best assessment method depends on the severity of the patient's condition and a balance between assessment accuracy and evaluation time., Competing Interests: CONFLICTS OF INTEREST: KM has received annual payments from the General Insurance Association of Japan. HK has received research grants from Chugai Pharmaceutical and Taiho Pharmaceutical. ET has received research grants from Daiichi Sankyo, Nippon Shinyaku, Taiho Pharmaceutical, and Takeda Pharmaceutical. HK has received lecture fees from Chugai Pharmaceutical, Nippon Shinyaku, Biogen Japan, Novartis, and Pfizer. The remaining authors declare no conflict of interest., (2024 The Japanese Association of Rehabilitation Medicine.)

Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC., (© 2024. The Author(s).)

The association between ulcerative colitis (UC) and erectile dysfunction (ED) has been previously reported. Numerous previous studies have also reported an association between gastrointestinal symptoms and ED. Constipation and diarrhea are common in patients with UC. However, the specific association between bowel movement frequency and ED remains unclear. The aim of this study is to investigate the association between bowel movement frequency and ED in 164 patients with UC. The definition of ED, moderate to severe ED, and severe ED was the Sexual Health Inventory for Men score <22, <12, and <8, respectively. Bowel movement frequency was divided into three categories: (1) high (More than once a day), (2) normal (once a day, reference), and low (less than one time/day). The definition of constipation was based on the Rome I criteria and/or medication for constipation. The prevalence of constipation and ED was 10.4% and 86.0%, respectively. The rate of high, normal, and low bowel movement frequency was 56.1%, 25.0%, and 18.9%, respectively. High bowel movement frequency was independently and positively associated with ED and moderate to severe ED (ED: adjusted odds ratio [OR] 4.42, 95% confidence interval [CI] 1.35-15.98; moderate to severe: adjusted OR 2.98, 95% CI 1.22-7.61). Low bowel movement frequency was independently and positively associated with moderate to severe ED and severe ED (moderate to severe: adjusted OR 3.96, 95% CI 1.27-13.08; severe: adjusted OR 3.20, 95% CI 1.08-9.86). No association between constipation and ED was found. In conclusion, in Japanese patients with UC, both high and low bowel movement frequency were independently and positively associated with ED., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Constipation is a common gastrointestinal symptom in patients with ulcerative colitis (UC). Several studies on the general population have demonstrated a link between allergic diseases and constipation. However, evidence regarding the association between allergic diseases and constipation in UC is limited. This study aims to evaluate this issue in Japanese patients with UC., Methods: This cross-sectional study recruited consecutive 387 patients with UC. We used a self-administered questionnaire to estimate the prevalence of physician-diagnosed allergic diseases. The definition of constipation was based on Rome I criteria and/or medication for constipation., Results: The prevalence of constipation was 12.5%. The prevalence rates of asthma, atopic dermatitis, pollen allergy, food allergy, and drug allergy were 11.8%, 9.0%, 36.3%, 6.2%, and 8.3%, respectively. Allergic diseases were not associated with constipation (adjusted odds ratio [OR] with asthma (adjusted OR 0.98 [95% confidence interval [CI] 0.27-2.80]), atopic dermatitis (adjusted OR 0.67 [95% CI 0.10-2.56]), pollen allergy (adjusted OR 0.92 [95% CI 0.41-1.97]), food allergy (adjusted OR 0.76 [95% CI 0.11-2.95]), and drug allergy (adjusted OR 1.06 [95% CI 0.28-3.24]). Additionally, the number of allergic diseases was not associated with the prevalence of constipation., Conclusions: In Japanese UC patients, no association between allergic diseases and constipation was found., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yagi et al.)

Background and Aim: Although diet is one of the potential environmental factors affecting ulcerative colitis (UC), evidence is not sufficient to draw definitive conclusions. This Japanese case-control study examined the association between the consumption of coffee, other caffeine-containing beverages and food, and total caffeine and the risk of UC., Methods: The study involved 384 UC cases and 665 control subjects. Intake of coffee, decaffeinated coffee, black tea, green tea, oolong tea, carbonated soft drinks, and chocolate snacks was measured with a semiquantitative food-frequency questionnaire. Adjustments were made for sex, age, pack-years of smoking, alcohol consumption, history of appendicitis, family history of UC, education level, body mass index, and intake of vitamin C, retinol, and total energy., Results: Higher consumption of coffee and carbonated soft drinks was associated with a reduced risk of UC with a significant dose-response relationship (P for trend for coffee and carbonated soft drinks were <0.0001 and 0.01, respectively), whereas higher consumption of chocolate snacks was significantly associated with an increased risk of UC. No association was observed between consumption of decaffeinated coffee, black tea, green tea, or oolong tea and the risk of UC. Total caffeine intake was inversely associated with the risk of UC; the adjusted odds ratio between extreme quartiles was 0.44 (95% confidence interval: 0.29-0.67; P for trend <0.0001)., Conclusions: We confirmed that intake of coffee and caffeine is also associated with a reduced risk of UC in Japan where people consume relatively low quantities of coffee compared with Western countries., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: Recently, a close association between ulcerative colitis (UC) and erectile dysfunction (ED) was reported. An inverse relationship between serum albumin and ED is found in patients with chronic disease. However, the association between serum albumin levels and ED in patients with UC is unclear. This study aims to investigate this issue in Japanese patients with UC., Methods: One hundred and thirty-six Japanese male UC patients were enrolled in this study. Information on serum albumin levels and medications for UC from medical records, Sexual Health Inventory for Men (SHIM) score information from self-administered questionnaires and information on the severity of UC from physician reports were obtained from medical records, self-administered questionnaires, and reports from physicians. The participants were divided into tertiles based on the total protein, serum globulin, serum albumin, aspartate aminotransferase, and C-reactive protein levels. The definition of ED and severe ED was SHIM score < 22 and SHIM score < 8, respectively. The association between these serum markers and ED was assessed by multivariate logistic regression., Results: The prevalence of severe ED in the low, moderate, and high albumin groups was 66.0%, 51.0%, and 28.3%, respectively. After adjusting for confounding factors, the low albumin group was independently and positively associated with severe ED (adjusted odds ratio: 2.74, 95% confidence interval: 1.03-7.48, p for trend =0.044). No association between other marker and ED was found., Conclusion: Serum albumin was independently inversely associated with severe ED in Japanese patients with UC. Hypoalbuminemia might be a useful complementary marker for assessing the prevalence and severity of ED in UC patients., (© 2023 The Japanese Urological Association.)

Objective: Becker muscular dystrophy (BMD) is a milder variant of Duchenne muscular dystrophy (DMD), a lethal X-linked muscular disorder. Here, we aim to investigat the clinical involvement of skeletal, respiratory, cardiac, and central nervous systems in patients with BMD, as well as genotype-phenotype relationships., Methods: This nationwide cohort study investigated the clinical manifestations and genotype-phenotype relationships in 225 patients with BMD having in-frame deletion from 22 medical centers. The primary outcome was to elucidate the association of genotype with skeletal muscle, respiratory, cardiac, and central nervous system disorders. Descriptive statistics were used to analyze the data., Results: The average age of the subjects was 31.5 (range, 1-81) years. Initial symptoms of BMD were muscular (60%), followed by asymptomatic hypercreatine kinasemia (32.4%) and central nervous system disorders (5.3%). Gait disturbance was observed in 53.8% of patients and the average age at wheelchair introduction was 36.5 years. The ventilator introduction rate was 6.7% at an average age of 36.6 years. More than 30% of patients had an abnormal electrocardiogram and approximately 15% had heart failure symptoms. Cardiac function on echocardiography varied significantly among the patients. The frequencies of seizures and intellectual/developmental disability were 8.0% and 16.9%, respectively. Exon 45-47deletion (del) was the most common (22.6%), followed by exon 45-48del (13.1%). Patients with exon 45-49del patients demonstrated severe skeletal muscle damage. Patients with exon 45-47del and exon 45-55del patients did not require ventilator use., Interpretation: The study provides important prognostic information for patients and clinicians to establish therapy plans and to implement preventative medicine., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Aim: Age is a risk factor for constipation. Constipation is common in patients with ulcerative colitis (UC) and has been positively associated with disease activity, but evidence is limited. This study aimed to assess the association between disease activity and constipation in patients with UC. Methods : The study subjects consisted of 290 Japanese UC patients. The definition of constipation was based on Rome I criteria and/or medication for constipation. Information on and lifestyle habits was obtained from a self-administered questionnaire. Mucosal healing (MH) was defined as Mayo endoscopic subscore 0. Clinical remission (CR) was defined as both the absence of rectal bleeding and no abnormally high stool frequency (<3 times per day). Results: The prevalence of constipation is not associated with MH, CR, duration of UC and disease extent of UC. The prevalence of constipation among age groups, <40, 40-49 years, 50-59 years, 60-69 years, and >70 years was 10.0%, 5.8%, 15.7%, 11.8%, and 25.6%, respectively. >70 years was independently and positively associated with the prevalence of constipation (adjusted odds ratio 3.64 [95% confidence interval 1.26, 10.95], p for trend: .001). Conclusions: Aging was independently and positively associated with the prevalence of constipation in UC., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Objective: To investigate the association between nocturia and constipation in patients with ulcerative colitis (UC). Constipation has recently been recognized as an important symptom in patients with UC. Although nocturia has been associated with constipation in the general population, the association between nocturia and constipation in UC patients is uncertain., Methods: Consecutive series of 290 Japanese patients with UC, Information on constipation, nocturia, and lifestyle habits was obtained using self-administered questionnaires. The definition of constipation was based on Rome I criteria and/or current medication for constipation. Patients were divided into three groups based on nighttime urination: (1) no nocturia, (2) mild nocturia (nocturnal urination - one), and (3) serious nocturia (nocturnal urination - two or more). Multivariate logistic regression was used to evaluate the association between nocturia and constipation., Results: Among all of the UC patients, the prevalence of mild nocturia, serious nocturia, and constipation was 35.2%, 26.9%, and 12.4%, respectively. The prevalence of constipation in the none, mild, and serious nocturia groups was 8.2%, 10.8%, and 20.5%, respectively. After adjustment for confounders such as age, sex, current drinking, current smoking, body mass index, and steroid use, nocturia severity was independently and positively associated with constipation (adjusted odds ratio for mild nocturia: 1.55 [95% confidence interval: 0.57-4.28], serious nocturia: 3.19 [95% confidence interval: 1.09-9.81], P for trend=.035)., Conclusion: The severity of nocturia is positively associated with constipation, and physicians should consider the interrelationships between nocturia and constipation in managing UC patients., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disease caused by ATP1A3 mutations. Using voxel-based morphometry (VBM) analysis, we compared an AHC patient cohort with controls. Additionally, with single-case VBM analysis, we assessed the associations between clinical severity and brain volume in patients with AHC., Materials and Methods: To investigate structural brain changes in gray matter (GM) and white matter (WM) volumes between 9 patients with AHC and 20 age-matched controls, VBM analysis was performed using three-dimensional T1-weighted magnetic resonance imaging. Single-case VBM analysis was also performed on nine patients with AHC to investigate the associations between the respective volumes of GM/WM differences and the motor level, cognitive level, and status epilepticus severity in patients with AHC., Results: Compared with controls, patients with AHC showed significant GM volume reductions in both hippocampi and diffuse cerebellum, and there were WM reductions in both cerebral hemispheres. In patients with AHC, cases with more motor dysfunction, the less GM/WM volume of cerebellum was shown. Three of the six cases with cognitive dysfunction showed a clear GM volume reduction in the insulae. Five of the six cases with status epilepticus showed the GM volume reduction in hippocampi. One case had severe status epilepticus without motor dysfunction and showed no cerebellar atrophy., Conclusion: With single-case VBM analysis, we could show the association between region-specific changes in brain volume and the severity of various clinical symptoms even in a small sample of subjects., (© 2023 International Society for Developmental Neuroscience.)

Purpose: Intra-abdominal infection is a common postoperative complication of laparoscopic pylorus-preserving gastrectomies (PPGs). Many studies have reported that intra-abdominal infectious complications after gastrectomy adversely affect patient survival outcomes. To prevent gastric fluid leakage into the abdominal cavity, we developed a novel anastomosis method in which the stomach lumen is not opened (termed the non-opened clean end-to-end anastomosis method [NoCEAM]) and evaluated its feasibility., Materials and Methods: Subsequent to lymphadenectomy, the oral and anal resection lines were sutured using an intraoperative endoscope. After closing the stomach circumferentially with clips, the specimen was rolled outward like a "donut." We resected the specimen circumferentially using a linear stapler, and anastomosis was completed simultaneously. We examined the feasibility of this procedure ex vivo, using three porcine stomachs, and in vivo, using one pig. Subsequently, we applied the procedure to 13 consecutive patients with middle-third early gastric cancer utilizing laparotomic, laparoscopic, and robotic PPG., Results: NoCEAM was completed in all porcine models and human cases. In the human cases, the mean operation time (±standard deviation) was 279±51 minutes, and mean blood loss volume was 22±45 mL. The mean number of linear staples used was 5.06±0.76. None of the patients had complications, and all were discharged on the eighth postoperative. The serum total protein, serum albumin, and hemoglobin levels did not change significantly after surgery., Conclusions: NoCEAM is feasible and safe for performing totally laparoscopic or robotic PPG. It may reduce postoperative complications, such as intra-abdominal infections., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2023. Korean Gastric Cancer Association.)

Aim: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance., Methods: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results., Results: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome., Conclusions: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status., (© 2023 Japan Society of Hepatology.)

Aim: The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS-089/NCNP-02 which can induce exon 44 skipping, in patients with DMD. Additionally, we aimed to identify markers predictive of therapeutic efficacy and determine the optimal dosing for future studies., Methods: This is an open-label, dose-escalation, two-center phase I/II trial in ambulant patients with DMD, presence of an out-of-frame deletion, and a mutation amenable to exon 44 skipping. Part 1 is a stepwise dose-finding stage (4 weeks) during which NS-089/NCNP-02 will be administered intravenously at four dose levels once weekly (1.62, 10, 40, and 80 mg/kg); Part 2 is a 24-week evaluation period based on the dosages determined during Part 1. The primary (safety) endpoints are the results of physical examinations, vital signs, 12-lead electrocardiogram and echocardiography tests, and adverse event reporting. Secondary endpoints include expression of dystrophin protein, motor function assessment, exon 44 skipping efficiency, plasma and urinary NS-089/NCNP-02 concentrations, and changes in blood creatine kinase levels., Discussion: Exon-skipping therapy using ASOs shows promise in selected patients, and this first-in-human study is expected to provide critical information for subsequent clinical development of NS-089/NCNP-02., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Objective: Evidence regarding the association between exercise habits and irritable bowel syndrome (IBS) remains scarce in a young population. It is also unknown whether the existence of an exercise partner affects this issue. The purpose of this study was to explore the association between exercise habits that include an exercise partner and IBS in a young Japanese population., Methods: This study enrolled 8923 Japanese university students and examined exercise frequency and intensity, and exercise partners using self-administered questionnaires. IBS and functional dyspepsia were defined according to the Rome III criteria., Results: The prevalence of IBS in this survey was 6.5%. Moderate frequency exercise was inversely related with IBS [adjusted odds ratio (aOR): 0.65 (95% confidence interval, CI: 0.51-0.83), P for trend = 0.005]. Moderate and high exercise intensities were independently and inversely related with IBS, respectively [aORs were moderate: 0.76 (95% CI: 0.61-0.95) and high: 0.62 (95% CI: 0.48-0.78), P for trend = 0.001]. Exercising with a group or with friends instead of alone was independently inversely related with IBS [aOR with groups: 0.53 (95% CI: 0.40-0.70) and with friends: aOR 0.71 (95% CI: 0.54-0.93)]. After excluding subjects with overlapping IBS and functional dyspepsia, an inverse association between high intensity of exercise or exercise in a group and IBS remained significant., Conclusion: The frequency and intensity of exercise may be independently inversely related with IBS in a young Japanese population. Also, exercise with others may be important for preventing IBS., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The association between disease activity and erectile dysfunction (ED) in patients with inflammatory bowel disease (IBD) is inconsistent, although IBD, including ulcerative colitis (UC), is reported as a risk factor for ED., Aim: The purpose of this study was to explore this association in Japanese patients with UC., Methods: In this study, we enrolled 165 Japanese male patients with UC. Information regarding the Sexual Health Inventory for Men (SHIM) score, medication, and severity of UC was obtained from medical records, self-administered questionnaires, and reports from physicians. The definition of ED and severe ED is a SHIM score <17 and <8, respectively., Outcomes: No association between severity of UC and ED was found in Japanese patients. Aging is independently positively associated with ED in patients with UC., Results: The prevalence of severe ED and ED was 47.9% and 64.9%, respectively. In this study, mucosal healing, clinical remission, duration of UC, disease extent, and medication were not associated with the prevalence of ED. Older age (≥63 years of age) was independently positively associated with ED (adjusted odds ratio, 12.93; 95% CI: 4.51-43.00) and severe ED (adjusted odds ratio, 9.02; 95% CI: 3.66-23.91)., Clinical Implications: Disease severity of UC might not be associated with the prevalence of ED in patients with UC., Strengths and Limitations: This is the first study to investigate the association between several factors regarding UC activity and ED. The limitation of this study is the definition of ED based on SHIM scores., Conclusion: No association between severity of UC and ED was found in Japanese patients. As expected, aging may be independently positively associated with ED in patients with UC., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: ST3GAL5 encodes GM3 synthase (ST3 beta-galactoside alpha-2,3-sialyltransferase 5; ST3GAL5), which synthesizes GM3 by transferring sialic acid to lactosylceramide. GM3, a sialic acid-containing glycosphingolipid known as ganglioside, is a precursor to the biosynthesis of various more complex gangliosides that are active in the brain. Biallelic variants in ST3GAL5 cause GM3 synthase deficiency (GM3SD), a rare congenital disorder of glycosylation. GM3SD was first identified in the Amish population in 2004., Case: We report two siblings diagnosed with GM3SD due to novel compound heterozygous ST3GAL5 variants. The novel ST3GAL5 variants, detected by whole-exome sequencing in the patients, were confirmed to be pathogenic by GM3 synthase assay. The clinical courses of these patients, which began in infancy with irritability and growth failure, followed by developmental delay and hearing loss, were consistent with previous case reports of GM3SD. The older sibling underwent deep brain stimulation for severe involuntary movements at the age of 9 years. The younger sibling suffered from acute encephalopathy at the age of 9 months and subsequently developed refractory epilepsy., Discussion: Reports of GM3SD outside the Amish population are rare, and whole-exome sequencing may be required to diagnose GM3SD in non-Amish patients. Since an effective treatment for GM3SD has not yet been established, we might select deep brain stimulation as a symptomatic treatment for involuntary movements in GM3SD., 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 © 2023 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Purpose: The albumin to globulin ratio (AGR) is a recognized chronic inflammation marker. No evidence regarding the relationship between AGR level and ulcerative colitis (UC) exists. The aim of this study was to evaluate the association between AGR and clinical outcomes among Japanese subjects with UC., Methods: The study subjects consisted of 273 Japanese individuals with UC. AGR was divided into 4 categories (low, moderate, high, and very high). The definition of complete mucosal healing (MH) was based on the Mayo endoscopic subscore of 0. Clinical remission (CR) was defined as no rectal bleeding and no abnormally high stool frequency (<3 times per day)., Results: The percentage of MH was 26.4%. High AGR and very high AGR were significantly positively correlated with CR (adjusted odds ratio [OR], 5.85; 95% confidence interval [CI], 2.52-14.18 and adjusted OR, 4.97; 95% CI, 2.14-12.04) and complete MH (adjusted OR, 4.03; 95% CI, 1.56-11.51 and adjusted OR, 5.22; 95% CI, 1.97-14.89), respectively after adjustment for confounding factors (P for trend=0.001). Only in the low C-reactive protein (CRP) group (≤0.1 mg/dL), very high AGR was significantly positively correlated with complete MH but not CR (adjusted OR, 4.38; 95% CI, 1.06-21.77; P for trend=0.017). In the high CRP group, no correlation between AGR and complete MH was found., Conclusion: Among Japanese patients with UC, AGR may be independently positively correlated with complete MH. In particular, among UC patients with low CRP, AGR might be a useful complementary marker for complete MH.

Background: Real-world data have shown variability in treatment responses to nusinersen in spinal muscular atrophy (SMA). We investigated whether the magnitude of muscle impairment assessed by magnetic resonance imaging (MRI) at baseline can predict the treatment response., Methods: We retrospectively assessed the clinical data in relevance to the thigh and pelvic MRI taken before the nusinersen treatment. A total of 16 patients with SMA types 2 and 3 (age = mean [SD]; 9.2 [4.6] year) receiving nusinersen treatment were enrolled. The T1-weighted MRI images of the pelvis and thigh were scored for muscle fatty infiltration and atrophy. The minimally clinically important difference (MCID) was considered as gaining at least 3 points of Hammersmith Functional Motor Scale-Expanded (HFMSE) from baseline., Results: Of these 16 individuals, 14 had been treated for at least 15 months with baseline data. At 15 months, seven individuals obtained MCID in HFMSE. Baseline muscle MRI score could not differentiate the two groups; however, individuals who obtained MCID had significantly less severe scoliosis. In addition, there was a significant and negative relationship between baseline MRI score and the change of score in HFMSE after 15 months of treatment. Further, baseline Cobb angle along with MRI score also indicated the correlation to the degree of change in motor function., Conclusion: The degree of muscle damage may confer the variability in response to nusinersen in SMA types 2 and 3. Muscle MRI score along with the severity of scoliosis assessed at baseline may help to predict the motor function change., 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 © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Introduction: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC., Methods: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0-1, respectively., Results: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04-6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22-11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia., Conclusions: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C., (© 2022 S. Karger AG, Basel.)

Introduction: There is evidence regarding the association between dysmenorrhea and irritable bowel syndrome (IBS), although it is lacking in the Asian population. Therefore, the purpose of this study was to investigate the association between menstrual status and IBS in a young Japanese., Methods: Overall, 4,693 female college students were included in the analysis of this study. Information regarding lifestyle habits, menstrual status (irregularity, pain severity, and medication), and IBS (Rome III criteria) was obtained using a self-reported questionnaire. Age, body mass index, exercise habits, smoking, drinking habits, and anemia were analyzed as potential confounders., Results: The prevalence of IBS was 6.1%. Moderate {adjusted odds ratio (OR): 1.89 (95% confidence interval [CI]: 1.27-2.91)} and heavy (adjusted OR: 2.14 [95% CI: 1.42-3.45]) menstrual pain were independently positively associated with IBS (p for trend = 0.001). Using medication sometimes (adjusted OR: 1.41 [95% CI: 1.09-1.84]) and often (adjusted OR: 1.60 [95% CI: 1.13-2.24]) was independently positively associated with IBS. There was no association between menstrual cycle and IBS. In subjects without functional dyspepsia, irregular menstrual cycle was independently positively associated with IBS., Conclusion: In the young Japanese population, menstrual pain and medications for menstrual pain may have a significant positive association with IBS., (© 2023 S. Karger AG, Basel.)

Restless legs syndrome (RLS) is a common sleep disorder in the Western population. The prevalence of restless legs syndrome in the Japanese population is 4.6%. Inflammatory and/or immune alteration might be associated with the development of restless legs syndrome. Ulcerative colitis is a chronic inflammatory bowel disease. Evidence regarding the association between ulcerative colitis and the prevalence of restless legs syndrome is limited. Herein, we investigated the association between clinical outcomes and the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis. This was a cross-sectional study using baseline data from a prospective cohort study. Subjects in this study were 273 patients with ulcerative colitis. The definition of restless legs syndrome was achieved using a self-administered questionnaire based on the diagnostic criteria for restless legs syndrome in an epidemiological study approved by the Executive Committee of the International Restless Leg Syndrome Study Group in 2002. Clinical outcomes were clinical remission and mucosal healing. The association between clinical remission and mucosal healing and the prevalence of restless legs syndrome was assessed by multivariate logistic regression analyses. The percentage of clinical remission and mucosal healing was 58.4% and 63.1%, respectively. The prevalence of restless legs syndrome in this cohort was 4.7%. Clinical remission (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.93) and mucosal healing (adjusted odds ratio 0.23, 95% confidence interval 0.05-0.90) were independently inversely associated with restless legs syndrome. No association between serum haemoglobin and restless legs syndrome was found. In conclusion, clinical remission and mucosal healing were independently and inversely associated with the prevalence of restless legs syndrome in Japanese patients with ulcerative colitis., (© 2022 European Sleep Research Society.)

Competing Interests: The authors declare that they have no conflict of interest.

Purpose: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects., Methods: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated., Results: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments., Conclusion: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Purpose: The association between body mass index (BMI) and irritable bowel syndrome (IBS) has been inconsistent in the Asian population. Also, no evidence regarding this issue in the young population exists. The aim of the present study is to investigate the association between BMI and IBS based on the Rome III criteria in young Japanese people., Methods: This study was a cross-sectional study consisted of 8923 Japanese university students. The definition of IBS was based on the Rome III criteria. BMI was divided into four categories (quartiles) on the basis of the study subjects' distribution (lowest, low, moderate, and high [reference]). The definition of lean, normal, and overweight was BMI < 18.5 kg/m 2 , 18.5 ≤ BMI < 25 kg/m 2 (reference), and 25 ≤ BMI kg/m 2 , respectively. Age, sex, drinking, smoking, exercise habit, anemia, and sports injury were selected a priori as potential confounding factors., Results: The prevalence of IBS was 6.5%, with females having a significantly higher prevalence than males (6.0% vs. 7.2%, p = 0.029). In females, being overweight was independently positively associated with IBS after adjustment (adjusted odds ratio [OR]: 1.81 [95% confidence interval (CI): 1.13-2.79]). In contrast, in males, no association between being lean or overweight and IBS was found., Conclusions: Among the young Japanese population, being overweight might be independently positively associated with prevalence of IBS in females but not in males., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (RORγt) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-γ) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD., (© 2022. The Author(s).)

Objective: Socioeconomic status is a risk factor for worse outcomes in many diseases. However, evidence on the association between socioeconomic status and clinical outcome in patients with ulcerative colitis (UC) is limited. In the clinical setting, the therapeutic goal for UC is to achieve mucosal healing (MH). Thus, the aim of this study is to examine the association between socioeconomic status and MH in patients with UC., Methods: The study population consisted of 298 patients with UC. Education status and household income were divided into three groups based on a self-administered questionnaire. MH and complete MH were defined as a Mayo endoscopic subscore of 0-1 and 0, respectively. The association of socioeconomic status with MH and complete MH was assessed by multivariate logistic regression analysis. Patients with UC were divided into a younger group (<51 years old) and an older group (≥51 years old) based on median age., Results: The percentage of MH and complete MH was 62.4% and 25.2%, respectively. In all patients, socioeconomic status was not associated with MH and complete MH, respectively. In the older group, education but not household income was independently positively associated with MH and complete MH. In contrast, in the younger group, no association between socioeconomic status and MH and complete MH was found., Conclusion: In older Japanese patients with UC, education status but not household income was independently positively associated with MH and complete MH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We report neurodevelopmental manifestations in boys with Duchenne muscular dystrophy (DMD) and evaluate the correlations between mutation location and three neurodevelopmental abnormalities: intellectual disability, autism spectrum disorder, and attentional problems., Methods: This cross-sectional study included 55 Japanese boys with genetically confirmed DMD who visited the outpatient department of the National Center for Psychiatry and Neurology of Japan from October 2017 to April 2018. Neurodevelopmental manifestations were evaluated using the Raven's Colored Progressive Matrices (RCPM), the Parent-Interview Autism Spectrum Disorder Rating Scale-Text Revision (PARS-TR), and the Attention-Deficit Hyperactivity Disorder-Rating Scale., Results: Among the 55 boys (mean [standard deviation, SD] age, 9.5 [1.6] years), 24 (43.6%) scored below -2.0 SD in RCPM, indicating intellectual disability. Further, 83% had DMD variants in exon 45 or downstream to it (P = 0.005). On the PARS-TR, 30 (55%) and 21 boys (38%) scored higher than the clinical cutoff score in childhood and present scores, respectively. Stereotyped behavior and restricted interests scores were found to decrease with age (P = 0.003 and P = 0.01, respectively)., Discussion: The results show that boys with DMD who have intellectual disability commonly have DMD variants in exon 45 or downstream to it. Stereotyped behavior and restricted interests improved with age, while intellectual disability did not., Conclusion: Understanding these characteristics of neurodevelopmental disability may reduce risky behaviors and improve the overall quality of life of patients with DMD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims/introduction: To investigate whether the Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease., Materials and Methods: Based on fatty liver disease and Fibrosis-4 index (cut-off value 1.3), we retrospectively divided 9,449 individuals, who underwent at least two annual health checkups, into four groups stratified by sex: normal; high Fibrosis-4 index without fatty liver disease; low Fibrosis-4 index with fatty liver disease; and high Fibrosis-4 index with fatty liver disease., Results: Onset rates for diabetes mellitus in the normal, high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8% and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3% and 7.0%, respectively, in women. Compared with the normal group, the high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female participants. Furthermore, in both sexes, high Fibrosis-4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis-4 index with fatty liver disease group: adjusted hazard ratio 4.03, 95% confidence interval 2.19-7.42 [men] and adjusted hazard ratio 6.40, 95% confidence interval 1.77-23.14 [women])., Conclusions: Individuals with fatty liver disease and high Fibrosis-4 index had a higher risk of diabetes mellitus onset. Therefore, Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Evidence regarding the association between sleep disturbance and functional dyspepsia (FD) remains limited in the young population., Aims: This study aimed to investigate the association between sleep disturbance and FD including subgroups among Japanese young people., Methods: Study subjects were 8923 university students. FD was defined according to the Rome III criteria. Subjects with FD were further categorized as having postprandial distress syndrome (PDS) or epigastric pain syndrome (EPS). Subjects completed a self-reported questionnaire assessing self-reported sleep duration, sleep disturbance, difficulty falling asleep, deep sleep disorder, nocturnal awakening, early awakening, and daytime sleepiness., Results: The prevalence of FD was 1.9%. After adjustment, all types of sleep disturbances were independently positively associated with FD (total sleep disturbance: OR 4.11 [95% CI: 2.89-5.78], difficulty falling asleep: OR 3.97 [95% CI: 2.53-6.01], deep sleep disorder: OR 4.85 [95% CI: 3.06-7.40], nocturnal awakening: OR 4.35 [95% CI: 1.90-8.67], early awakening: OR 4.50 [95% CI: 1.97-8.97], and daytime sleepiness: OR 2.83 [95% CI: 1.25-5.56]). While nocturnal awakening and daytime sleepiness were not associated with EPS, the other types of sleep disturbance were independently positively associated with EPS and PDS. No association between self-reported sleep duration and FD was found., Conclusions: Sleep disturbance may be independently positively associated with the prevalence of FD among Japanese young people. Nocturnal awakening and daytime sleepiness were not associated with EPS; the other types of sleep disturbance were independently positively associated with EPS and PDS., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Functional dyspepsia (FD) is a very common disease worldwide. Dysmenorrhea impairs quality of life among females of reproductive age. Although dysmenorrhea is associated with irritable bowel syndrome (IBS), no study has yet evaluated the association between dysmenorrhea and FD., Methods: This study's subjects consisted of 4693 female Japanese university students. We defined FD according to the Rome III criteria. Subjects completed a self-reported questionnaire regarding menstrual irregularity, menstrual pain, and medication for menstrual pain. Age, body mass index, drinking, smoking, exercise habit, anemia, and first-year student status were selected as potential confounding factors., Results: The prevalence of FD, epigastric pain syndrome (EPS), and postprandial distress syndrome (PDS) was 2.5%, 0.6%, and 2.1%, respectively. Heavy menstrual pain was independently positively associated with FD and PDS but not EPS (adjusted ORs: FD, 3.18 [95% CI: 1.60-6.89] and PDS, 2.93 [95% CI: 1.56-7.93] for heavy menstrual pain, p for trend = 0.001 and 0.004, respectively). Using medication for menstrual pain often was independently positively associated with FD, EPS, and PDS, respectively, (adjusted ORs: FD, 2.41 [95% CI: 1.50-3.83], EPS, 2.93 [95% CI: 1.04-7.93], PDS, 2.44 [95% CI: 1.46-4.01]). Irregular menstrual cycle was not associated with FD or with subtype of FD., Conclusion: Among the young female Japanese population, menstrual pain might be independently positively associated with FD and PDS but not EPS. The use of medication for menstrual pain might be independently positively associated with FD including subtype of FD., (© 2022 John Wiley & Sons Ltd.)

Background/aims: Functional dyspepsia (FD) may be a common digestive disease worldwide and reduces the quality of life of patients. However, only a few studies have investigated the association between eating behavior and FD. The purpose of this cross-sectional study is to examine the association between eating behavior and prevalence of FD in a young Japanese cohort., Methods: In this study, we enrolled 8923 Japanese university students. FD is diagnosed based on the Rome III criteria. Eating habits and frequency of meals were investigated using a self-administered questionnaire., Results: The FD subjects had a younger mean age, a lower body mass index, and a lower proportion of men compared to the non-FD subjects. An independent positive association between skipping breakfast and/or lunch and FD was found (adjusted ORs were 1.60 [95% CI, 1.10-2.32] for breakfast and 2.52 [95% CI, 1.04-5.18] for lunch). Skipping dinner, extra meals (snacks) or midnight snacks was not associated with FD. The prevalence of FD in subjects eating 1, 2, and 3 meals per day was 4.8%, 2.2%, and 1.7%, respectively. The frequency of meals was independently inversely associated with prevalence of FD (adjusted ORs were 1 per day: 2.72 [95% CI, 1.19-5.42], and 2 per day: 1.69 [95% CI, 1.16-2.43], P for trend = 0.001)., Conclusions: In the young Japanese people, the frequency of meals may be independently inversely associated with prevalence of FD. In particular, skipping breakfast and/or lunch was associated with the prevalence of FD.