Objectives:Chronic hepatitis C is commonly associated with metabolic abnormalities that can influence adherence to direct-acting antiviral (DAA) therapy. This paper discussed the relationship between metabolic syndrome risk and compliance with DAA for 6 months. Materials and Methods:A longitudinal observational study was conducted among 402 patients with chronic hepatitis C taking DAA. Metabolic risk was measured using the Metabolic Screening Questionnaire (MSQ), and treatment adherence was measured at baseline, 3 months and 6 months using the Morisky Medication Adherence Scale (MMAS-8). Descriptive statistics, Spearman correlations, Mann-Whitney U test, Kruskal-Wallis tests and repeated-measures ANOVA were used as statistical tests. Results:Adherence at baseline (ρ = 0.28, p < 0.001), after 3 months (ρ = 0.22, p < 0.001), and after 6 months (ρ = 0.26, p < 0.001) was significantly associated with metabolic risk in a negative direction. Women adhered more than men (U = 16,950, p = 0.002), and men were more at risk of metabolism (U = 17,250, p = 0.008). MSQ (χ2 = 12.84, p = 0.012) and MMAS-8 (χ2 = 10.92, p = 0.028) differed in terms of age. Compliance at baseline (12.74) was compared with that at 6 months (13.62; F = 21.67, p < 0.001), and with metabolic risk being a significant mediator (F = 7.18, p < 0.001). Conclusion:Reduced treatment adherence to DAA therapy is closely associated with increased metabolic risk. Implementing metabolic risk management into standard care can enhance adherence and treatment outcomes among patients with hepatitis C.
Purpose:Medical students experience significant academic and psychosocial stressors. Resilience may help mitigate negative psychological outcomes. This study assessed the level of resilience among MBBS undergraduate students and examined its associations with selected socio-demographic and academic variables. Methods:A cross-sectional online survey was conducted among MBBS students at AIIMS Rishikesh using the validated 16-item Child and Youth Resilience Measure (CYRM-16). Responses were scored on a five-point Likert scale ranging from 1 ("Not at all") to 5 ("A lot"). Data were analyzed using descriptive statistics and appropriate inferential tests. Results:Of 500 invited students, 324 valid responses were analyzed. The mean age was 20.31 ± 1.9 years and 59% were male. Based on CYRM-16 scores, 16% demonstrated low resilience, 68.8% moderate resilience, and 15.1% high resilience. Higher resilience was significantly associated with academic year, number of siblings, and participation in extracurricular activities (p < 0.05). Conclusions:Most MBBS students reported moderate resilience. Students further along in training, those with more siblings, and those participating in extracurricular activities demonstrated higher resilience. Institutions should consider structured resilience-building interventions.
Objectives:Epilepsies due to variation of the HCN1 gene can be associated with long-term neurological and psychiatric comorbidities, which may impact daily living. The degree of patient empowerment in managing their disease substantially impacts how they assess QoL. This study aimed to investigate the relationship between patient activation and health-related quality of life (HRQOL) in adults with HCN1-related epilepsies. Materials and Methods:A cross-sectional study was conducted among 403 adult patients with controlled epilepsy attending neurology clinics. Informed consent was taken verbally. Participants completed the Patient Activation Measure (PAM) and Quality of Life in Epilepsy Inventory (QOLIE-31). Descriptive, correlation, and regression analyses were performed using IBM SPSS Statistics version 26. Results:There was a moderate, positive correlation between patient activation and HRQOL (r = 0.412, p < 0.001). PAM scores were higher in females (p < 0.001), and HRQOL is reported to be better by males (p = 0.010). PAM and QOLIE scores differed significantly with age (p < 0.001), with the highest proportions in the 35-44 and ≥55 years age groups, respectively. Regression analysis showed that greater patient activation (B value 1.85, p < 0.001) and older age (B value 0.48, p = 0.017) were positive predictors of HRQOL. At the same time, female gender, later onset of epilepsy and frequency of seizures were negative predictors. Conclusion:Increased patient activation is strongly associated with better HRQOL in HCN1-associated epilepsy. Interventions that enhance patient involvement, self-management, and disease awareness may improve psychosocial and clinical outcomes in these patients.
Objectives:This study aimed to clarify the characteristics of medical education and clinical practice at early Juntendo under its first three generations of directors. Materials:We collected and analyzed historical documents related to early Juntendo, as well as bibliographic materials on medical and surgical textbooks published in the early modern and modern periods. Methods:The textbooks in early Juntendo were specified and contents of their originals were analyzed and evaluated. Results:The first three directors of Juntendo-Sato Taizen, Sato Takanaka, and Sato Susumu-studied Western medicine and surgery in Nagasaki or abroad and subsequently introduced and developed these practices at Juntendo in three successive stages. In the first stage (1838-1862), following Taizen's return from Nagasaki, Taizen and Takanaka translated pre-modern surgical textbooks, particularly those by Chelius, and applied their contents in clinical practice. In the second stage (1862-1875), after Takanaka's training under Pompe van Meerdervoort, he translated semi-modern textbooks by Stromeyer and Wunderlich and established systematic medical education. In the third stage (1875-1921), after Susumu's return from Germany, modern surgery incorporating anesthesia and antiseptic techniques was introduced, and Takanaka translated Niemeyer's modern textbook of internal medicine. These developments reflected the rapid modernization of Western medicine in the nineteenth century, particularly in surgery and internal medicine. Conclusions:The first three directors of Juntendo continuously adopted the most advanced phases of Western medicine and surgery of their time, thereby establishing Juntendo as a leading medical school and hospital in modern Japan.
Cannabinoid hyperemesis syndrome (CHS) is characterized by recurrent nausea, vomiting, and abdominal pain in chronic cannabis users. We report a case of suspected CHS in a 37-year-old Canadian male who presented to a Japanese emergency department (ED) with severe abdominal pain and persistent vomiting. He reported chronic cannabis use two to four times per week for several years, with the last use the day before departure from Canada. Urine drug screening was positive for tetrahydrocannabinol. Although the clinical presentation was consistent with the hyperemetic phase of CHS, a definitive diagnosis could not be established due to the single-visit nature of the encounter and incomplete acquisition of key diagnostic information. This case highlights the diagnostic challenges of CHS in foreign travelers presenting to EDs in cannabis-prohibited countries, where linguistic, cultural, and legal barriers may impede timely recognition. Early consideration of CHS and systematic history-taking are essential to avoid diagnostic delays in this population.
Background:Sepsis is characterized by dysregulated inflammation and thromboinflammation in which regulated cell death and damage-associated molecular patterns (DAMPs) contribute to organ injury. Ferroptosis has recently emerged as a potential mechanism of inflammatory cell injury in sepsis. Objective:To investigate ferroptosis-associated leukocyte injury and inflammatory lytic cell death in an in vitro endotoxin model. Methods:Rat peritoneal leukocytes were stimulated with lipopolysaccharide (LPS; 0.4 mg/mL). Intracellular, mitochondrial, and lysosomal Fe2+ accumulation was evaluated using FerroOrange®, Mito-FerroGreen®, and Lyso-Ferro Red® fluorescence probes. Cellular morphology was assessed using May-Grünwald-Giemsa staining, DAPI staining, and immunofluorescence for histone H3 and citrullinated histone H3. Results:LPS stimulation induced marked leukocyte injury characterized by membrane rupture, cytoplasmic collapse, and extracellular dispersion of cellular contents. Fluorescence imaging demonstrated increased intracellular, mitochondrial, and lysosomal Fe2+ accumulation, suggesting ferroptosis-associated iron dysregulation. DAPI staining showed chromatin injury and extracellular DNA release. Histone H3-positive and citrullinated histone H3-positive cells coexisted within the same inflammatory population, indicating overlap between inflammatory lytic cell death and NETosis-like responses. Conclusions:Ferroptosis-associated iron accumulation, DAMP release, and overlapping inflammatory cell death phenotypes may collectively contribute to thromboinflammation and organ injury in sepsis.
Juntendo University has three faculties and three graduate schools on its Hongo and Ochanomizu campuses, which collectively serve over 3,000 students. In 2019, the university established a Student Counseling Center to provide psychological support for students from diverse backgrounds. Following the expansion of services, including the addition of psychologists and psychiatrists, both the number of operating days and the volume of consultations increased markedly, particularly from 2023 onward. This trend mirrors patterns reported at other universities in Japan and reflects the growing global recognition of the importance of student mental health support. In collaboration with student affairs departments across faculties, we conduct regular awareness activities to promote mental health and encourage service utilization. Despite these efforts, several challenges remain, including limited awareness of the center among students, space and accessibility constraints affecting the counseling environment, and the need to enhance support for the mental well-being of university students.
Objective:To examine the 12-month relationship between physical function-focused training and lower-limb function among community-dwelling elderly. Design:In this single-center retrospective cohort study, 93 adults aged ≥ 65 years (median age 85.0 years; 74.2% women) who attended a function-focused day service at least once per week and completed the Short Physical Performance Battery (SPPB) at baseline and 12 months were included. Methods:Each 105-minute session consisted of 80 minutes of group training for flexibility, strength, and balance, and 25 minutes of individualized machine-based aerobic, resistance, and flexibility training. The primary outcome was the 12-month change in SPPB total score; secondary outcomes included SPPB subscores and grip strength. Participants were categorized according to change in SPPB as Improved (≥ +1 point), Maintained (0), or Deteriorated (≤ -1 point). Results:Median SPPB total score remained stable (10.0 [7.0-12.0] to 10.0 [7.5-12.0]; Hodges-Lehmann change, 0.0 [0.0-0.5]; p = 0.76); 34 participants (36.6%) improved, 32 (34.4%) maintained, and 27 (29.0%) deteriorated. The Improved group showed increases in balance and chair-stand scores, while all subscores declined in the Deteriorated group. Grip strength decreased significantly in the total group but remained stable within the Improved group. Conclusions:These findings suggest that low-frequency, low-intensity function-focused training performed at least once per week may help maintain lower-limb function, even among community-dwelling oldest-old individuals.
Objectives:A combination of tissue clearing technology and light-sheet fluorescence microscopy enables volumetric analysis of intact biological specimens. To analyze complex spatial organizations of molecules and cells, the number of imaging channels available for simultaneous visualization from a single sample is a key parameter. This study aimed to expand the previously reported DIY compact light-sheet microscope, descSPIM, for four-color volumetric imaging of whole biological samples. Materials:A four-color-labeled optical phantom and an entire E12.5 mouse embryo labeled with a nuclear stain and three distinct antibodies were used. Methods:We modified the previously reported DIY compact light-sheet microscope, descSPIM, for four-color volumetric imaging. Chromatic aberration was evaluated across the visible wavelength range (400-700 nm) using the four-color-labeled optical phantom. Four-color three-dimensional imaging was then performed on the entire E12.5 mouse embryo. Results:The chromatic aberration of the extended descSPIM was mostly negligible across the visible wavelength range (400-700 nm). The extended system also enabled four-color three-dimensional imaging covering the entire E12.5 mouse embryo. Conclusions:Together, these results validate the reliability and expandability of the extended system, supporting its broader use for multicolor imaging of cleared tissue samples.
Granulomonocytapheresis (GMA) is an extracorporeal leukocyte adsorption therapy that selectively removes activated granulocytes and monocytes through interactions involving Fcγ receptors (FcγR) and complement receptor 3 (CR3). Initially developed for chronic inflammatory diseases such as ulcerative colitis, GMA has recently attracted attention as a potential adjunctive therapy for sepsis. Contemporary understanding of sepsis emphasizes thromboinflammation, immunothrombosis, endothelial injury, and inflammatory cell death as central mechanisms underlying organ dysfunction. Activated FcγR-positive and CR3-positive myeloid cells contribute to cytokine storm, neutrophil extracellular trap (NET) formation, oxidative injury, coagulation activation, and release of damage-associated molecular patterns (DAMPs). These processes amplify endothelial dysfunction, microvascular thrombosis, and disseminated intravascular coagulation. GMA may interrupt these self-amplifying inflammatory and thromboinflammatory loops by selectively depleting activated inflammatory leukocytes while relatively preserving adaptive immunity. Mechanistically, removal of FcγR-positive cells may suppress inflammasome activation, pyroptosis, and DAMP-mediated cytokine amplification, whereas removal of CR3-positive cells may attenuate NETosis, oxidative burst, endothelial adhesion, and microvascular injury. Although preliminary clinical and experimental studies suggest potential benefits in sepsis, important concerns remain regarding patient selection, optimal timing, infection risk, thrombocytopenia, and cost-effectiveness. Further phenotype-oriented clinical trials are required to define the therapeutic role of GMA in sepsis and thromboinflammatory critical illness.
Objectives:Sarcopenia, characterized by age-associated loss of skeletal muscle mass, function, and physical performance, is a major challenge in aging societies because of its association with a decreased lifespan. Existing gene expression-based diagnostic methods often rely on large gene sets, requiring high costs and analytical complexity. In this study, we developed a machine learning-driven framework to identify senescence-associated cell states in skeletal muscle tissue. Methods:Publicly available single-cell RNA sequencing data from 2- and 24-month-old C57BL/6J male mice from single-cell and single-nucleus RNA sequencing datasets comprising over 365,000 cells from skeletal muscle were obtained from the DRYAD Repository and consolidated into 15 cell populations. Candidate genes for machine learning were selected from differential expression analysis. Multiple machine learning algorithms, including logistic regression, support vector machines, and random forest, were trained with recursive feature elimination. Model performance was evaluated using the area under the receiver operating characteristic curve. Results:Differential expression analysis across 15 distinct cell populations yielded 30 candidate genes, to which five machine learning models were applied to select biomarkers. Using our approach, we identified a four-gene panel (Malat1, Wdr89, Zfp36, and Jund) exhibiting high predictive accuracy. This panel was validated using additional aging datasets and compared with existing models, which highlighted its potential as a reliable tool for detecting senescence-associated cells. Conclusions:In this study, we established a four-gene biomarker panel for detecting senescence-associated cells in skeletal muscle, providing a practical tool for investigating sarcopenia pathophysiology and identifying therapeutic targets.
Septic shock remains a leading cause of mortality despite advances in critical care. Polymyxin B hemoperfusion (PMX-HP) has long been proposed to improve outcomes by removing circulating endotoxin, yet randomized trials have yielded inconsistent results. Early enthusiasm from EUPHAS was followed by neutral findings in ABDO-MIX and EUPHRATES, highlighting the limitations of non-enriched trial designs. The latest evidence from the TIGRIS trial, a randomized controlled trial, provides important new insight. In patients with endotoxic septic shock, defined by an endotoxin activity assay (EAA) of 0.60-0.89 and high organ dysfunction, polymyxin B hemoadsorption was associated with a high posterior probability of mortality reduction, particularly at 90 days. This article critically appraises the rationale and limitations of EAA-guided PMX-HP in light of these updated data. While the findings support a biologically enriched strategy, important uncertainties remain regarding assay performance, feasibility, and generalizability. The integration of EAA with complementary biomarkers and clinical phenotypes is likely necessary to advance precision medicine in sepsis.
Objectives:Schizophrenia (SCZ) is a common psychiatric disorder with relatively high morbidity and heritability. Affecting approximately 1% of the global population, SCZ is estimated to have an individual heritability of 60-85%. In recent years, several promising genetic loci have been identified using novel approaches such as genome-wide association studies (GWAS). Multiple GWAS have consistently reported that inter-alpha-trypsin inhibitor heavy chain (ITIH) family genes located on chromosome 3p21 are associated with SCZ in European populations, as demonstrated by the Schizophrenia Working Group of the Psychiatric Genomics Consortium and subsequent studies, as well as with bipolar disorder, another major psychotic disorder. Methods:In the present study, we conducted a case-control association analysis and haplotype analysis of single-nucleotide polymorphisms (SNPs) within the ITIH gene cluster at the 3p21 region to examine whether these variants confer genetic risk for schizophrenia in a Japanese population. In addition, we resequenced the ITIH1 gene to identify single-nucleotide variants (SNVs) and performed protein structural analyses to predict the effects of these variants on protein stability, aiming to clarify the potential contribution of ITIH1 to the pathophysiology of schizophrenia. Results:A significant difference in haplotype frequencies for the two-SNP window comprising rs2710322 and rs1042779 was observed. Resequencing identified 4 potentially deleterious variants. Conclusions:This study suggests a possible role of ITIH1 in the pathophysiology of schizophrenia.
Objective:This study aimed to evaluate the relationship between transcranial motor-evoked potentials (Tc-MEPs) and compound muscle action potentials (CMAPs) during spinal deformity correction surgery and to assess the clinical utility of their simultaneous evaluation. Methods:We retrospectively analyzed 42 patients who underwent spinal deformity correction surgery and had reliable Tc-MEP and CMAP recordings available for correlation analysis. CMAPs were recorded from the median nerve after supramaximal stimulation, whereas Tc-MEPs were recorded from six target muscles. Correlation analyses of percentage changes in Tc-MEP and CMAP amplitudes were performed across three phase comparisons using four intraoperative measurement time points. Results:Significant positive correlations between CMAP and Tc-MEP amplitudes were observed mainly in the abductor pollicis brevis and abductor hallucis muscles at multiple surgical phases, whereas no consistent correlation was observed in the tibialis anterior muscle. Overall, these correlations were small to moderate. In three patients, Tc-MEP amplitude decreased by ≥ 70% during scoliosis correction. In one case, CMAP amplitude remained preserved despite marked Tc-MEP reduction, whereas in the other two cases, both Tc-MEP and CMAP amplitudes decreased simultaneously. All patients recovered after intraoperative intervention, and no postoperative neurological deficits were observed. These findings suggest that simultaneous evaluation of Tc-MEP and CMAP may provide complementary information for interpreting intraoperative waveform changes. Conclusions:Small-to-moderate correlations were observed between Tc-MEP and CMAP amplitudes during spinal deformity correction surgery. Although the strength of these correlations was limited, simultaneous evaluation of Tc-MEP and CMAP may aid interpretation of intraoperative Tc-MEP amplitude reductions and may represent a practical strategy for improving intraoperative decision-making.
Objectives:Chronic pain usually results in prolonged use of NSAIDs, thus raising the chance of experiencing self-reported kidney risk indicators. The present study examined the relationships between pain intensity, NSAID-related compliance patterns, and patients' self-reported kidney risk indicators over 12 months. Methods:A one-year prospective cohort study was conducted involving 300 adults with chronic pain. The parameters of pain severity (Brief Pain Inventory), NSAID adherence behaviour (Medication Adherence Rating Scale), and self-reported kidney risk indicators were evaluated at the start of the study and at 3, 6 and 12 months. Mann-Whitney U, Kruskal-Wallis tests, Spearman correlations, and repeated-measures analysis were utilised. Results:During the whole period, the patients who reported the highest pain severity had a strong correlation with a greater risk of NSAID adherence and self-reported kidney risk indicators (p < 0.001). Women exhibited much higher pain severity, adherence risk, and kidney risk compared to men (p < 0.05). The oldest age group (≥ 50 years) received the highest scores for all outcomes. Long-term analysis revealed small but significant increments in pain, adherence risk, and kidney risk over the year (p < 0.001). Conclusions:The association between chronic pain intensity, poor adherence to non-steroidal anti-inflammatory drugs (NSAIDs) and an increase in self-reported kidney risk indicators was observed over time. It is suggested that older people and women might need to receive more frequent checks and also be given the proper instructional material to prevent renal side effects during long-term pain management.
Objectives:The objectives were to identify subclinical AF in young individuals and to examine its association with cardiovascular risk profile and quality of life (QoL) in a young adult cohort. Design:A cross-sectional survey was conducted with 403 adults aged 18-40 years in public and private hospitals. Methods:The INTERHEART Modifiable Risk Score (IHMRS), Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire, and the Modified European Heart Rhythm Association (mEHRA) were used to collect data. The statistics were performed using descriptive statistics, Spearman's correlation, the Mann-Whitney U test, the Kruskal-Wallis test, and multiple linear regression in IBM SPSS 26. Results:Of the 403 respondents, the majority were male (85%) and aged 36-40 (30%). A stronger negative correlation with QoL (0.42, p < 0.001) and a weaker positive correlation with cardiovascular risk (0.13, p = 0.009) were observed between higher EHRA symptom severity and cardiovascular risk. There was also a negative correlation between QoL and IHMRS (r = -0.29, p = < 0.001). Women presented with greater symptoms and low QoL (p < 0.001). The regression analysis showed that predictors of better IHMRS were age, male gender, higher EHRA scores, physical inactivity, and a family history of CVD. In contrast, better QoL was a protective factor (p < 0.01). Conclusions:Subclinical AF symptoms were highly correlated with increased cardiovascular risks and decreased QoL in young adults. Early detection of high-risk individuals, especially in settings with limited resources, could be achieved through simple questionnaire-based screening.
