Conectar
by Tomoo Hidaka, Takeyasu Kakamu, Hideaki Kasuga, Yuko Suzuki, Toshihiro Terui, Shizuka Kawamoto, Tatsuya Sato
Municipal government officials (MGOs) have played key roles in managing decontamination project of radioactive materials in the aftermath of the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. However, the subjective distress experienced by MGOs during the decontamination project, mainly stemming from challenges in coordination with the national government, is not yet fully documented. The purpose of this study is to descriptively understand the nature and causes of subjective distress among MGOs and to make an exploratory conceptual model of the process through which such subjective distress becomes manifest. Narratives from three MGOs were collected through interviews and subjected to qualitative analysis using the Steps for Coding and Theorisation method. For the first purpose, the results indicate that inconsistencies in national reconstruction and decontamination designs impose substantial burdens at the operational level; these burdens are further amplified by inadequate management by national authorities, and subjective distress emerges through a breakdown of trust among national government officials, municipalities, and residents. For the second purpose, an exploratory conceptual model explaining the progression toward subjective distress through the following four stages was created: the emergence of distrust and adversarial orientations toward the national government, the dilemma of occupying an intermediate position, the erosion of ties with residents, and the threat to professional pride. Overall, through experiences such as questioning the national government’s reconstruction policies, enduring the psychological burden of occupying an intermediate position, and witnessing a breakdown in trust with residents, MGOs may find their professional pride undermined; consequently, subjective distress, manifesting as a profound sense of emptiness, may arise. As MGOs are likely to stand at the frontline of managing post-radiation-disaster reconstruction and decontamination efforts, it is essential to develop protective measures for their mental health from both macro-level, organisational perspectives and micro-level, occupational and psychological perspectives.Evidence-Based Practice (EBP) is essential to healthcare quality and safety, integrating scientific evidence with clinical expertise and patient preferences. Despite its importance, EBP implementation still faces major challenges. Educational interventions have proven effective in strengthening EBP competencies among healthcare.
To evaluate the impact of a personalized educational intervention on EBP competencies among healthcare professionals. Working at a private tertiary general hospital, comparing performance before and after the intervention.
A randomized controlled trial involving healthcare professionals was conducted. Eligible and consented participants were randomly assigned to either an Intervention Group (IG) receiving an Evidence-Based Practice (EBP) course or a Control Group (CG) not receiving the course, stratified by job level, role, and work shift. From the completers, 18 participants were randomly selected for the IG, and all 7 available CG participants were included in the final sample for analysis. All study participants completed two validated instruments: the Assessing Competencies in Evidence-Based Medicine (ACE) and the Fresno Test. The educational intervention consisted of a seven-week course with weekly three-hour sessions, for a total of 21 h. Comparative analyses were conducted using a Linear Mixed Model, adjusted for educational level, job level, time working at the hospital, and weekly workload.
A statistically significant increase in general EBP knowledge was observed in the IG following the intervention, with a mean gain of 19.1%. Separate analysis showed improvements of 10.8% in ACE and 24.2% in Fresno Test scores. No statistically significant changes were observed in the CG. Furthermore, after the intervention, the IG outperformed the CG for both general EBP knowledge and Fresno Test scores on both pre- and post-intervention comparisons.
The educational intervention had a positive statistically significant impact on EBP knowledge and skills among healthcare professionals in the IG compared to the CG. These findings underscore the potential of structured educational initiatives to enhance the quality of clinical practice through improved EBP competencies.
UTN U1111-1322-8443
by Cecilia Aguilar-Vega, Jaime Bosch, Satoshi Ito, Benjamin Ivorra, Hyunkyu Jeong, José Manuel Sánchez-Vizcaíno
African swine fever (ASF) is a lethal disease of swine that has spread across Asia since its introduction in 2018. South Korea first reported the disease in September 2019 in domestic pigs, and since then, more than 4,000 cases have been reported in wild boars during its expansion up to August 2024. Due to the high number of ASF notifications in wild boars in South Korea, contrasted with their scarcity in most Asian countries, analyzing the spatiotemporal spread of the disease in a setting with active surveillance provides valuable insights. In this study, we performed a trend-surface analysis on temporally gridded case data to characterize the overall geographic spread and direction of ASF in wild boars across South Korea, from its emergence to August 2022. Additionally, we propose a novel approach distinct from previous studies, to estimate spread velocity by incorporating an upper threshold to avoid unrealistic values. The model described the spread of ASF in the study area. The disease showed greater expansion in the east of the country. Initially, a south and eastward direction was estimated. The estimated median velocity was 19.53 km/month, with cell-level velocities ranging from 2.45 to 69.99 km/month. Velocity increased notably from autumn 2021 onward and varied substantially across years. Our results show the dynamics of ASF in wild boars of South Korea, providing new evidence of their role in the epidemiology of the disease.Negative-pressure wound therapy (NPWT) is widely used in clinical practise to enhance wound healing; however, its biological effects on intact skin remain poorly understood. Given the expanding applications of NPWT, understanding its impact beyond open wounds is increasingly important. This study aimed to evaluate the biological responses of intact skin to negative-pressure, specifically focusing on epithelial-mesenchymal transition (EMT). The effects of negative-pressure loading were assessed using an in vitro model of non-diabetic human keratinocytes and an in vivo model of intact diabetic mouse skin. Human keratinocytes exposed to negative-pressure exhibited increased expression of thrombospondin-1 (THBS1), transforming growth factor-beta 1 (TGF-β1), plasminogen activator inhibitor-1 (PAI-1), and hypoxia-inducible factor 1-alpha (HIF-1α), alongside decreased epithelial markers and increased mesenchymal markers. These EMT-related changes were mitigated by inhibiting the THBS1-TGF-β1 interaction. Similarly, in diabetic mice, intermittent negative-pressure loading applied to intact dorsal skin significantly increased THBS1 and TGF-β1 levels, resulting in epidermal and dermal thickening, and promoted hypoxic, prothrombotic and angiogenic responses, as evidenced by increased HIF-1α, PAI-1, fibrinogen and vascular endothelial growth factor expression. These findings suggest that negative-pressure loading can induce EMT-like responses and tissue remodelling in intact skin primarily via mechanisms involving the THBS1-TGF-β1 signalling axis. This study expands the understanding of the biological influence of NPWT beyond traditional wound treatment applications, potentially informing future therapeutic considerations and safety guidelines.
Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown.
The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population.
The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries.
Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025
by Naoya Nakagawa, Ami Igarashi, Hideaki Yokogawa, Akira Kobayashi, Tomomi Higashide, Satoru Yamagami, Takahiko Hayashi
The aim of this study was to identify the clinical factors associated with postoperative visual acuity following Descemet’s membrane endothelial keratoplasty (DMEK), with emphasis on the impact of macular diseases. This retrospective multicenter study included consecutive eyes that underwent DMEK between March 1, 2011, and June 30, 2022, and had available optical coherence tomography findings. Eyes with other ocular diseases causing visual loss were excluded. Overall, 77 eyes of 66 patients were included in the study. Univariable and multivariable regression analyses were performed to identify the predictors of best-corrected visual acuity (BCVA) at the final follow-up. Worse preoperative visual acuity and macular comorbidity were identified as independent predictors of poorer postoperative BCVA. Among macular pathologies, cystoid macular edema was most strongly correlated with reduced vision in the univariable analysis (β = 0.195; p = 0.016). In the subgroup analysis, worse preoperative visual acuity and macular comorbidity remained significant predictors (pby Jingwen Gao, Yasushige Shingu, Ryota Azuma, Satoru Wakasa
BackgroundInflammatory response plays a pivotal role in myocardial injury and post-infarction remodeling after acute myocardial infarction (AMI). Mechanical unloading (UL) of the left ventricle (LV) has been proposed as a potential therapeutic strategy to preserve cardiac function; however, its effects on myocardial inflammation remain incompletely understood.
MethodsWe employed a rat model of partial UL using heterotopic heart-lung transplantation following AMI. RNA sequencing (RNA-seq) was performed to evaluate transcriptomic changes, with a specific focus on inflammatory pathways in the non-infarcted remote area. Immune cell abundance was estimated using deconvolution analysis (QUANTISEQ). Quantitative PCR was performed to analyze some inflammatory cytokines, and macrophage polarization was evaluated by immunohistochemistry.
ResultsAMI significantly impaired cardiac function, which was mitigated by UL. RNA-seq analysis revealed marked activation of inflammatory pathways and identified several hub genes involved in cytokine signaling following AMI, while these transcriptional changes were not significantly altered in UL groups after AMI. Immune cell profiling demonstrated an increase in M2 macrophages after AMI, while UL preserved M2 macrophage levels. Histological analysis further supported UL’s modulatory effect on macrophage polarization. Pro-inflammatory cytokines TNFα and IL1β were upregulated after AMI but showed attenuation with UL.
ConclusionPartial UL potentially attenuates cardiac functional deterioration after AMI while exerting substantial effects on inflammatory gene expression and macrophage polarization. These findings suggest that the cardioprotective effects of UL may be correlated with the modulation of inflammatory pathways in the remote area after AMI.
Rising patient numbers and limited resources are creating a challenging environment for healthcare providers recently. Anaesthesiologists are also increasingly faced with complex situations, requiring high adaptability in the operating room. To enhance team adaptability during emergencies, effective communication methods are essential. This study aimed to compare the impact of mobile phones and intercoms on the response time and effectiveness of anaesthesiologist teams in emergency situations.
Prospective, observational and simulation study.
Anaesthesiology and Critical Care, Yokohama City University Medical Center, Yokohama, Japan.
This study, conducted at Yokohama City University Medical Center (Yokohama, Japan), evaluated how communication methods (intercoms vs mobile phones) impact the efficiency of anaesthesiologists in the simulation setting. Two scenarios were tested: (1) retrieving a video laryngoscope during a difficult intubation and (2) gathering support during cardiac arrest.
Outcomes measured included time to secure equipment, time for assistance to arrive and staff numbers gathered. The Wilcoxon signed-rank test was used to compare the outcomes between the intercom and mobile phone groups.
In scenario 1, the time to secure the video laryngoscope was significantly shorter with intercom use compared with mobile phones (intercom vs mobile phone, median (IQR): 29 (25–33) s vs 50 (39–62) s; p=0.013, effect size 20 (95% CI 7 to 31)). In scenario 2, the time from the request for assistance until the first supporting staff member reached the operating room was significantly shorter in using the intercoms (intercom vs mobile phone, median (IQR): 16 (14–18) s vs 35 (31–38) s; p=0.04, effect size 17 (95% CI 6 to 24)), and more personnel were available in the intercom group (intercom vs mobile phone, median (IQR): 3 (3–3.5) persons vs 2 (1–2) persons; p=0.04, effect size 1.5 (95% CI 1 to 3)).
Real-time information sharing through intercoms improved the ability of the anaesthesiologist team to respond more rapidly and effectively in emergency situations, enhancing overall team adaptability. This approach may improve patients’ outcomes by shortening response times and increasing team coordination.
The Novara Cohort Study (NCS) was established to investigate the biological, psychological and social factors that influence ageing in the general population. The study aims to identify early risk factors for frailty, allostatic load and cognitive decline, and to uncover molecular and functional markers of accelerated biological ageing. NCS addresses the need for detailed life-course data from Southern Europe to support personalised prevention and early diagnosis, and to promote healthy longevity.
NCS is a population-based, longitudinal cohort in the Novara province (Northern Italy), originally enrolling adults aged 35 and older. The inclusion criteria were later expanded to encompass all residents aged 18 and over, facilitating the study of ageing trajectories from early adulthood onward. As of mid-2025, about 1000 participants have been enrolled, and recruitment is ongoing. The cohort’s diversity in age, employment status and health conditions enhances its value for life-course analysis.
Following a pilot phase in 2022–2023, the whole study protocol now includes detailed demographic, clinical, behavioural, cognitive and psychosocial data, along with biological samples stored in the UPO Biobank. The protocol incorporates validated tools, comprehensive physical and cognitive assessments, and over 90 laboratory biomarkers covering inflammation, metabolism, hormonal function and coagulation. Additionally, a subset of participants underwent advanced inflammatory profiling by simultaneous measurement of 92 immune-related proteins and comprehensive genomic profiling using Illumina Single Nucleotide Polymorphism (SNP) arrays, capturing common genetic variation across multiple biological domains. Preliminary results demonstrate the feasibility of integrating deep phenotyping, reveal the roles of frailty in ageing and show initial evidence of age-related changes in inflammatory proteins.
NCS plans to enrol at least 10 000 participants and will conduct long-term follow-up using both passive methods, such as linking with clinical records and administrative health databases, and active in-person reassessments. Future phases will integrate clinical, behavioural and cognitive data with large-scale omics analyses, including genomics, proteomics, metabolomics and transcriptomics. Machine learning techniques will be employed to model biological age, identify early signs of age-related decline and develop personalised prevention strategies. By combining high-resolution phenotyping with multidimensional data, NCS aims to find modifiable risk factors and molecular signatures of ageing, supporting national and European research efforts and encouraging collaborative studies through open data-sharing frameworks.
by Aditya Sri Listyoko, Ryota Okazaki, Tomoya Harada, Genki Inui, Hiroki Kohno, Miyu Nishigami, Miki Takata, Masato Morita, Akira Yamasaki
BackgroundThe interaction between viral components and type 1 or type 2 cytokines during asthma exacerbations in the airway epithelium may contribute to worsening inflammation. However, these interactions in the small airway epithelium—particularly those involving alarmins (TSLP, IL-25, and IL-33) and IL-8—remain unclear. Dupilumab, a biologic agent used in severe asthma, blocks IL-4 receptor alpha (IL-4Rα) and may offer therapeutic benefits in virus-induced asthma exacerbations. In this study, we evaluate the effects of double-stranded RNA (dsRNA), in combination with various cytokines and dupilumab, on the Human Small Airway Epithelial Cells (HSAECs) line.
MethodsPrimary HSAECs were preincubated with dsRNA to induce the gene and protein expression of alarmins and IL-8. To evaluate the effects of cytokines on dsRNA-induced alarmin and IL-8 expression, various type 1 and type 2 cytokines were co-stimulated with dsRNA. Dupilumab was used as a pretreatment prior to co-stimulation with dsRNA and IL-4 or IL-13. Gene expression of TSLP, IL-25, IL-33, and IL-8 was assessed by quantitative PCR, and protein expression was evaluated by Western Blotting.
ResultsdsRNA significantly increased the expression of TSLP and IL-8. IL-4 and IL-13 further enhanced dsRNA-induced TSLP and IL-8 gene and protein expression. In contrast, TNF-α reduced dsRNA-induced TSLP expression but enhanced IL-8 gene and protein expression. Dupilumab attenuated the expression of TSLP and IL-8 induced by co-stimulation with dsRNA and IL-4 or IL-13 in HSAECs.
ConclusionIn the microenvironment of small airway epithelial cells, particularly during viral infections, the presence of IL-4 or IL-13 may enhance the expression of TSLP and IL-8. Dupilumab attenuates this expression, potentially offering additional benefits in the treatment of asthma, especially during virus-induced asthma exacerbations.
by Suksan Kanoksin, Suphakarn Techapongsatorn
BackgroundSurgical smoke generated during energy-based operations is a known hazard containing particulate matter (PM), volatile organic compounds (VOCs), and biological debris, with insufficient adoption of commercial smoke evacuators due to cost and complexity.
ObjectiveThis study aimed to develop a cost-effective, modular and passive smoke evacuator and evaluate its efficacy in reducing PM and VOC levels during simulated laparoscopic procedures.
MethodsA prototype smoke evacuator incorporating a distilled water bubbling trap, activated carbon filter, and ULPA filter was tested in a sealed chamber simulating laparoscopic surgery using porcine liver tissue. The system was connected to a laparoscopic port through a three-way valve, allowing manual, on-demand smoke evacuation without continuous suction. Air quality metrics, including PM1.0, PM2.5, PM10, VOC, and CO₂, were measured continuously. Results were compared to baseline and performance benchmarks from commercial smoke evacuation systems. Statistical analysis was performed using paired t-tests.
ResultsThe prototype evacuator reduced PM2.5 levels by >99.5% and VOC concentrations by >95% compared to no-evacuation control trials (p 2.5 and VOC levels were restored to near-baseline values.
ConclusionThe developed modular passive smoke evacuator offers a promising and cost-effective solution to improve air quality and enhance occupational safety in operating rooms. The model represents an idealized simulation of laparoscopic smoke evacuation; further clinical validation in live surgical environments is warranted.
Treatment failure remains a major challenge in tuberculosis (TB) management. Rapid and objective assessment of treatment response is essential, as existing tools have limited accuracy and slow turnaround times. The PATHFAST TB LAM Ag assay (PATHFAST-LAM), an automated chemiluminescent enzyme immunoassay, was developed to quantify lipoarabinomannan (LAM) in sputum within 1 hour. Previous studies have shown a strong correlation between sputum LAM concentration and culture-based bacterial load. However, its clinical utility for predicting poor outcomes during treatment has not been prospectively evaluated.
We will conduct a prospective longitudinal study enrolling newly diagnosed, bacteriologically confirmed patients with pulmonary TB at Rhodes Chest Clinic and Mbagathi County Referral Hospital in Nairobi, Kenya. We will follow participants throughout the 6-month treatment course, attempting to collect sputum weekly during weeks 1–4, biweekly during weeks 5–12 and monthly during months 3–6. We will measure LAM concentrations at these time points using the PATHFAST-LAM assay. The primary outcome is to assess whether changes in sputum LAM concentration during the intensive phase (baseline to week 4 and/or week 8) predict a composite poor outcome, defined as positive sputum culture at month 6, treatment failure, death during treatment or relapse within 3 months after treatment completion. The primary endpoint is the area under the curve from the receiver operating characteristic analysis, representing the predictive performance of changes in sputum LAM concentration for the composite poor outcome. We will identify the optimal cut-off value for LAM change and estimate sensitivity and specificity with 95% CIs using 2x2 tables. We will apply an adaptive design that allows sample-size re-estimation after interim analysis.
The study was approved by the Kenya Medical Research Institute (KEMRI/SERU/CRDR/124/5241) and Nagasaki University (250619327). Findings will be disseminated through peer-reviewed publications and scientific meetings.
Siblings of children with disabilities or chronic illnesses often face significant challenges during their upbringing. Despite these difficulties, many develop a positive outlook and adapt successfully. To help individuals navigate developmental challenges in a healthy and manageable way, this study focuses on the concept of resilience. Although previous studies have primarily focused on the challenges and difficulties faced by siblings of children with disabilities and chronic illnesses, the factors influencing resilience in these siblings remain unclear. This review aims to inform the development of effective support systems for siblings of children with disabilities and chronic illnesses.
We will search PubMed (MEDLINE), CINAHL (EBSCOhost), Web of Science and Ichushi-Web (a Japanese Medical Literature Database). Two independent reviewers will apply the inclusion and exclusion criteria to screen the titles and abstracts of the retrieved articles. Full texts of relevant studies will be reviewed. This scoping review focuses on studies addressing resilience in siblings of children with disabilities and chronic illnesses during childhood, with particular focus on the perspectives of siblings. The review will exclude conference proceedings, abstracts, posters, editorials, commentaries, opinion papers and review papers. However, important documents found during the search will be added if relevant. Using a custom data extraction method developed for this review, the researchers will extract relevant data, inductively and comprehensively organise similar codes, and identify key components of resilience.
This study does not involve human subjects and therefore does not require approval from an ethics committee for human subjects research. The results of this exploratory review will be disclosed through conference presentations and publication in peer-reviewed academic journals.
To explore patients' experiences of participation in surgical wound care and provide an in-depth understanding of their experiences with post-operative wound care during and post-hospitalisation.
A descriptive qualitative study.
Adult participants who had undergone surgery within 30 days were purposively selected from two surgical wards at Gold Coast University Hospital. Seventeen semi-structured phone interviews were conducted using a specifically developed and piloted interview guide. Textual data were analysed using inductive content analysis.
Three main categories were identified. The first category, ‘I didn't expect how distressing post-operative wound care would be; it's tougher than I thought,’ highlights the significant and unexpected physical and emotional challenges participants faced, which initially hindered their engagement. The second category highlights the impact of healthcare professional interactions on patient participation, ‘I want to be involved, but conflicting advice and dismissive behaviour discourage me.’ The third category, ‘With my family's help, wound care got easier as I tried, learned, and recovered,’ illustrates how family support facilitated participants' independence and engagement over time.
The spectrum of patient participation in surgical wound care is dynamic and impacted by environmental, physical and psychological factors. This research deepens understanding of patient participation by highlighting the importance of family support and a temporal perspective in patients' wound care journeys.
Findings showed participants were unprepared for surgical wound care, greatly influenced by healthcare provider communication and family support, and evolved in participation as time passed and their wounds healed. Additionally, participants valued intent just as significantly as their behaviours and regarded even minor involvement as totally participative. These insights can inform strategies to improve patient participation in surgical settings.
SRQR (Standards for Reporting Qualitative Research).
No patient was involved in this study.
Chronic subdural haematoma (CSDH) is a common neurosurgical condition in older adults, with a recurrence rate of approximately 7.1–13% after burr-hole drainage. Although surgical adjuncts such as subdural drains and middle meningeal artery embolisation may reduce recurrence, these are not suitable for all patients. Pharmacological strategies, including tranexamic acid, Goreisan and carbazochrome sodium sulfonate hydrate, have shown potential, but high-level evidence remains lacking. A prior retrospective study suggested that a triple oral regimen combining these agents may reduce recurrence. This randomised controlled trial aims to evaluate its efficacy and safety.
This is a prospective, multicentre, open-label, randomised controlled trial conducted across six hospitals in Ibaraki, Japan. A total of 180 patients undergoing first-time burr-hole surgery for CSDH will be randomised 1:1 to receive either triple therapy (Goreisan 7.5 g/day, carbazochrome sodium sulfonate hydrate 90 mg/day and tranexamic acid 750 mg/day for up to 90 days) or standard postoperative care. The primary outcome is recurrence requiring reoperation within 90 days. Secondary outcomes include time to recurrence and haematoma volume reduction on serial CT imaging. All analyses will follow the intention-to-treat principle, using logistic regression, Cox proportional hazards models and mixed-effects models.
Written, informed consent will be obtained from all participants at each participating hospital by trained staff from that hospital. The trial protocol has been approved by the ethics committee of the University of Tsukuba Hospital (approval no. TCRB23-025) and the Institutional Review Boards of all participating centres. Study findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals. A summary of the results will also be provided to participating institutions and made publicly available in accordance with the BMJ Open data sharing policy.
jRCTs031240007.
by Azusa Kubota, Kentaro Kojima, Shinnosuke Koketsu, Takayuki Kannon, Takehiro Sato, Kazuyoshi Hosomichi, Yoshiaki Shinohara, Atsushi Tajima
Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.Over 777 million COVID-19 infections have occurred globally, with data suggesting that 10%–20% of those infected develop Long COVID. Fatigue is one of the most common and disabling symptoms of Long COVID. We aim to assess the feasibility and safety of a new, remotely delivered, multimodal rehabilitation intervention, paced to prevent post-exertional malaise (PEM), to support the conduct of a future, definitive randomised trial.
We will conduct a randomised, two-arm feasibility trial (COVIDEx intervention vs usual care). Sixty participants with Long COVID will be recruited and randomised prior to giving informed consent under a modified Zelen design using 1:1 allocation with random permuted blocks via central randomisation to receive either the COVIDEx intervention or usual care. The 50-minute, remotely delivered, COVIDEx intervention will occur twice weekly for 8 weeks. All participants will wear a non-invasive device throughout their entire study participation, to track heart rate, blood oxygen saturation, steps, sleep and monitor PEM. The primary feasibility objectives will be recruitment rates, intervention fidelity, adherence, acceptability (intervention and design), retention, blinding success and outcome completeness. Secondary objectives will include refined estimates for the standard deviation and correlation between baseline and follow-up measurements of fatigue. Feasibility and clinical outcomes will be collected at baseline, 4, 8, 12 and 24 weeks. Qualitative interviews with participants and physiotherapists will explore intervention acceptability and barriers/facilitators.
Ethical approval for this study was obtained by the Western University Health Sciences Research Ethics Board (REB# 123902). Dissemination plans include sharing of trial findings at conferences and through open access publications and patient/community channels.
This study aims to estimate the prevalence and dual use of cigarettes, heated tobacco products (HTPs) and electronic cigarettes (e-cigarettes) among individuals aged 18–24 in Japan.
This cross-sectional study involved a door-to-door survey administered by trained interviewers using a structured questionnaire.
Individuals aged 18–24 residing in 220 areas within 10 ordinance-designated cities (Sapporo, Sendai, Saitama, Chiba, Yokohama, Kawasaki, Sagamihara, Nagoya, Osaka and Fukuoka) as well as Tokyo’s 23 wards in Japan in 2019 were included.
A total of 1738/5500 individuals were included in the analysis, with participants evenly distributed by sex, age and residential area.
Cigarette, HTP and e-cigarette use was assessed.
The weighted prevalence of the current use of cigarettes, HTPs and e-cigarettes accounted for 10.1% (95% CI 8.7, 11.5), 5.1% (95% CI 4.1, 6.1) and 1.8% (95% CI 1.2, 2.4), respectively. Approximately 68.2% of the people who used HTPs at the time were dual users of both HTPs and cigarettes. There was a significant gap in tobacco product use between individuals aged 20–24 and those aged 18–19, with this difference remaining after adjusting for covariates.
In 2019, cigarettes were the most used tobacco-related product among young adults in Japan. Smoking initiation appears to notably increase at age 20 when smoking becomes legal in Japan. The prevalence of HTP use among young adults in Japan is notably higher than in other countries.
This research paper presents a study protocol for an exploratory clinical trial evaluating the safety and potential efficacy of autologous peripheral blood mononuclear cell (PBMNC)-loaded injectable cell scaffold (ICS-001) for angiogenic therapy in chronic limb-threatening ischaemia (CLTI). CLTI, the advanced stage of peripheral artery disease, presents significant therapeutic challenges.
Angiogenic therapy using ICS-001 with PBMNCs—a novel approach designed to enhance local cell retention and promote neovascularisation—will be explored. The study will address the pathophysiology of CLTI, the limitations of current treatments and the rationale for cell-based therapies, alongside the clinical trial design for evaluating the safety and efficacy of ICS-001. We hypothesise that ICS-001 will improve ulcer healing and reduce ischaemic rest pain in patients with CLTI. This paper outlines the methodology, including patient selection, CD34+ cell mobilisation, scaffold preparation, injection protocols, clinical assessments, data collection and safety monitoring. The anticipated results, discussion and conclusion will offer insight into the clinical significance and potential impact of ICS-001 as a pioneering angiogenic therapy for CLTI.
The institutional review boards of all participating hospitals approved this study protocol (latest version V.6.0, 5 June 2025). Final data will be made publicly available. A report detailing the study results will be submitted for publication in an appropriate peer-reviewed journal.
Data are available on reasonable request. Technical appendix, statistical code is available by contacting the corresponding author. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and licence their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
jRCT2052230115, Japan Registry of Clinical Trials.
FreshRSS 