Conectar
by Teruo Nakamura, Tomohiro Shibata, Ken-ichi Ito
Anaplastic thyroid cancer (ATC) is a rare but highly aggressive malignancy with a dismal prognosis. Although recent advances in targeted therapies have modestly improved survival, the molecular mechanisms driving ATC progression remain incompletely elucidated. Epithelial cell adhesion molecule (EpCAM), a multifunctional cell-surface protein, is implicated in proliferation, migration, and stemness in various cancers. However, its role in thyroid cancer progression remains unclear. In this study, we investigated the function of EpCAM in thyroid cancer cell lines of varying differentiation status. EpCAM expression was significantly elevated in ATC cell lines compared with differentiated thyroid cancer (DTC) lines. EpCAM knockdown by siRNA suppressed proliferation, adhesion, motility, and invasion in ATC cells, but had minimal effects on DTC cells. Morphological analyses revealed that EpCAM silencing induced differentiation features, including follicle-like structure formation and increased expression of thyroid differentiation markers such as thyroglobulin and PAX8 in ATC cells. Furthermore, EpCAM inhibition decreased mesenchymal marker expression, reduced filopodia formation, and suppressed extravasation of cancer cells into the lung in an in vivo mouse model. Mechanistically, EpCAM knockdown attenuated epithelial–mesenchymal transition (EMT)-related pathways but did not affect major proliferation signaling cascades in ATC cells. These findings suggest that EpCAM promotes dedifferentiation and metastatic potential in ATC through EMT modulation. Our results provide new insights into the role of EpCAM in thyroid cancer biology and highlight its potential as a therapeutic target in ATC. Further studies are warranted to elucidate the mechanisms linking EpCAM to anaplastic transformation and to explore the therapeutic efficacy of EpCAM-targeting strategies in aggressive thyroid cancers.by Caio R. Monteiro, Victor Augusto de Oliveira, Rabeche Schmith, João Pedro A. Rezende, Tales L. Resende, João A. Negrão, Marina A. C. Danés
This study aimed to evaluate the effects of rumen-protected methionine (RPM) supplementation on productive and physiological responses of primiparous Holstein cows during summer. We hypothesized that RPM supplementation would maintain or improve milk yield and composition due to beneficial physiological, redox, and inflammatory responses in cows exposed to summer heat. The trial was conducted in a randomized block design during nine weeks in Brazil using 80 primiparous cows (182 ± 64 DIM; 42.9 ± 4.7 kg/d milk). Cows were blocked by milk yield and DIM and assigned to a control diet (CON; no added RPM) or the same diet supplemented with RPM (Mepron®, Evonik) at 0.75 g/kg diet dry matter, targeting 20 g/cow/day (product contains 62% metabolizable methionine) to the average cow. Milk yield and composition, vaginal temperature, respiratory rate, and plasma samples were collected in weeks 3, 6, and 9. Data were analyzed using mixed models including treatment, week, and their interaction as fixed effects, and block and cow as random effects. Cows were maintained under naturally occurring summer conditions. Environmental monitoring during weeks 3, 6, and 9 indicated elevated temperature–humidity index (THI) values, with values remaining above the heat-stress threshold (THI > 68) for 68.3% of the monitored hours (mean THI = 70.6; range 61.0–84.4). Overall (least squares mean across weeks 3, 6, and 9), RPM increased milk yield by 2.0 kg/d (44.9 vs. 42.9 kg/d), protein yield by 50 g/d (1,464 vs. 1,414 g/d), lactose yield by 108 g/d (2,109 vs. 2,001 g/d), and total solids yield by 176 g/d (5,331 vs. 5,155 g/d). Lactose concentration was lower in RPM (4.71 vs. 4.76%). Fat yield was unaffected, but a treatment × week interaction was observed for fat content. Milk fatty acid (FA) profile was unchanged, although treatment × week interactions were observed for individual fatty acids (C16:0, C18:0, C18:1, and preformed FA). Plasma glucose was lower, and insulin was higher in RPM than in CON cows (39.3 vs. 43.2 mg/dL and 0.52 vs. 0.35 ng/mL, respectively). Antioxidant capacity improved, with RPM cows having greater ferric reducing antioxidant power (32.9 vs. 28.5 µM) and lower malondialdehyde (2.48 vs. 2.78 nmol/mL). Other biochemical, inflammatory, and immune markers were unaffected. Respiratory rate was slightly higher in RPM than in CON cows (55 vs. 50 breaths/min). Mean vaginal temperature did not differ between treatments; however, a treatment × time × hour interaction was observed. Supplementation with RPM improved milk and solids yield, and enhanced antioxidant capacity and insulin levels, supporting its use to improve metabolic resilience under warm conditions.To identify obstacles faced by nurses when using health technologies in Intensive Care Units (ICUs).
Systematic review following PRISMA and registered in PROSPERO.
Six databases were searched. Two reviewers independently screened studies and appraised methodological quality using the Joanna Briggs Institute tool. Data were synthesized narratively.
Eight studies met eligibility criteria. Barriers clustered around limited training and technical competence, shorter professional experience, increased workload with multiple devices, organizational culture, and reduced direct patient contact, which may undermine patient-centered care. Heterogeneity of study designs precluded meta-analysis.
Obstacles to technology use in ICUs arise from individual and organizational factors. Addressing these barriers requires structured education, mentoring for novice nurses, workload management, and supportive policies that integrate technology without displacing bedside care.
Nursing leaders and educators should implement ongoing, ICU-specific technology training and mentoring. Managers and policymakers must ensure adequate staffing and promote Health Technology Assessment to align device implementation with clinical needs, safeguarding patient safety and the human dimensions of care.
Integrated digital diagnostics can support complex surgeries in many anatomic sites, and brain tumour surgery represents one of the most complex cases. Neurosurgeons face several challenges during brain tumour surgeries, such as differentiating critical tissue from brain tumour margins. To overcome these challenges, the STRATUM project will develop a 3D decision support tool for brain surgery guidance and diagnostics based on multimodal data processing, including hyperspectral imaging, integrated as a point-of-care computing tool in neurosurgical workflows. This paper reports the protocol for the development and technical validation of the STRATUM tool.
This international multicentre, prospective, open, observational cohort study, STRATUM-OS (study: 28 months, pre-recruitment: 2 months, recruitment: 20 months, follow-up: 6 months), with no control group, will collect data from 320 patients undergoing standard neurosurgical procedures to: (1) develop and technically validate the STRATUM tool and (2) collect the outcome measures for comparing the standard procedure versus the standard procedure plus the use of the STRATUM tool during surgery in a subsequent historically controlled non-randomised clinical trial.
The protocol was approved by the participant ethics committees. Results will be disseminated in scientific conferences and peer-reviewed journals.
To clarify the role performance of gerontological nurse specialists (GNSs) and identify associated factors.
A cross-sectional survey.
A self-designed questionnaire based on the Donabedian model was developed to assess structure, process, and outcome variables using a 5-point Likert scale. The questionnaire was administered to 230 GNSs. Descriptive statistics (e.g., means, standard deviations, frequencies) were calculated in SPSS to summarise GNSs' role performance, and multiple regression analysis identified factors influencing GNSs' role performance.
Ninety-six GNSs (response rate of 44.3%) scored 3.15 to 3.81 out of 5 in GNSs' role performance, including clinical practice, education and guidance, consultation, research, leadership and coordination. High self-ratings were observed in clinical practice and consultation, whereas research and leadership scored lower. Education and guidance, as well as consultation, were primarily performed among hospital nurses, with GNSs' role performance largely confined to the hospital. Multiple regression revealed that GNSs' role performance was significantly associated with factors such as GNS competency, identification of stakeholder needs and perceived social recognition of GNS.
To enhance the role performance of GNSs, it is necessary to expand their activities outside the hospital, improve gerontological nursing competency, and promote the social recognition of their role. The results also suggest that it is important for GNSs to understand the needs of patients, nurses, and other related healthcare workers, and enhance collaboration with multiple professionals.
Clarifying the role performance of GNSs in China enables future outcome evaluations. Identifying influencing factors provides insights for effective support, which will further contribute to the success and development of GNSs.
No public or patient involvement.
Dyspnoea is an existentially burdensome symptom in patients with advanced and progressive diseases such as cancer, chronic obstructive pulmonary disease (COPD) and advanced heart failure. Recent studies have highlighted that symptomatic treatment of dyspnoea is often ineffective and may depend on the underlying disease. Immersive virtual reality (IVR) has emerged as a ‘digital therapeutic’ for conditions such as pain, anxiety, and dyspnoea. Brain functional MRI (fMRI) offers the opportunity to identify distinct patterns of dyspnoea. Current findings are mainly limited to healthy volunteers, but clinical data from patients with life-limiting conditions are needed. The aim of this study is to assess the feasibility of identifying dyspnoea patterns in different life-limiting conditions using fMRI and IVR.
This is an observational monocentric feasibility study, conducted in a tertiary university centre. Healthy volunteers and patients diagnosed with advanced cancer, COPD, or heart failure and suffering from persistent dyspnoea will undergo an fMRI of the brain using IVR. The primary outcome of feasibility will be evaluated using descriptive statistics. Secondary outcomes include analysis of fMRI patterns of dyspnoea across populations, patient-reported burden of participation, and correlation between dyspnoea and psychological symptoms. These preliminary data will help determine the sample size required for a future study evaluating differences in dyspnoea patterns. Exploratory comparison between the characteristics of all four groups will be assessed with Fisher’s test (for proportions) and either independent Student’s t-test or Mann-Whitney test, depending on distribution. Correlations between variables will be tested using the Pearson’s correlation coefficient. Statistical analysis will be performed using STATA.
This study protocol received ethical approval on 23 April 2025 from the Commission cantonale d’éthique de la recherche in the Canton of Geneva, Switzerland. The identification number is 2024-02289. Submission to peer-reviewed journals and presentation in international congresses for the dissemination of the study findings are planned.
Clinical Trials number is NCT07319039; Pre-results.
To assess health service use between days 43 and 365 postdelivery, comparing individuals with and without severe maternal morbidity (SMM).
Population-based cohort study.
Linked datasets from Population Data BC in British Columbia, Canada, April 2013–March 2021.
Postpartum individuals aged >18 years with a hospital or home delivery, with/without SMM occurring from 20 weeks’ gestation through 42 days post partum. Ectopic pregnancies, missing identifiers and maternal deaths at delivery or within 42 days post partum were excluded.
The primary outcome was high health service use, defined as being in the 95th percentile for use of one or more of the following non-obstetric visits: emergency department, hospitalisations and outpatient visits to a primary care physician or specialist—each occurring between 43 and 365 days after delivery hospitalisation discharge. Secondary outcomes included being in the 95th percentile for each visit type. Log binomial regression assessed the rate and risk of high health service use in SMM compared with non-SMM pregnancies, adjusting for confounders.
The cohort included 261 287 deliveries (5575 (2.1%) with SMM). Those with >15 visits within 43–365 days postdelivery were classified as having high health service use. SMM-affected individuals were twice as likely to have high health service use (9.2% vs 4.3%; adjusted relative risk (aRR)=1.96, 95% CI 1.78 to 2.17). Individuals with non-hypertensive cardiovascular SMM had markedly higher health service use (21.4% vs 4.3%; aRR=5.18, 95% CI 3.28 to 8.16). There was heterogeneity in the association between SMM and high health service use among those without versus with previous comorbidities, without versus with high service use in the 2 years prior to delivery, and without vs with preterm birth.
Our study revealed high health service use after SMM. These findings can help guide the development of standardised postpartum care pathways.
Childhood and adolescence are critical developmental periods marked by increasing physical inactivity, stress and mental health problems. TABATA training, a supramaximal form of high-intensity interval training, has been increasingly promoted as a time-efficient approach to improving health. However, evidence on its specific effects in children and adolescents remains limited, fragmented and not systematically synthesised. The objective of this review is to determine whether TABATA training improves physical fitness and mental health outcomes in children and adolescents aged 6–18 years.
We will perform a systematic review of experimental studies in the following databases: PubMed, Scopus, Cochrane Library and Web of Science. The initial literature search was conducted in May 2025, and the systematic review is expected to be completed by March 2026. Eligible studies will include multisession Tabata interventions defined as repeated 20 s high-intensity bouts with 10 s rest intervals, typically performed for 7–8 cycles per set, with or without multiple sets. Outcomes will include physical fitness indicators and mental health indicators. Study selection and data extraction will follow the Population, Intervention, Comparison, Outcomes, Study design framework and Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The risk of bias will be assessed using the Cochrane Risk of Bias 2 tool for randomised trials and Risk Of Bias In Non-randomised Studies - of Interventions for non-randomised studies. When sufficient data are available, quantitative synthesis will be conducted using a three-level random-effects meta-analytic model to account for dependency among effect sizes and anticipated clinical and methodological heterogeneity across studies. Effect sizes for continuous outcomes will be calculated as standardised mean differences. Sensitivity analyses will be performed, and publication bias will be assessed using funnel plots when an adequate number of studies is available. Statistical analyses will be performed using R and Review Manager (RevMan) V.5.4, where appropriate.
The results of the systematic review will be disseminated via publication in a peer-reviewed journal and presented at a relevant conference. As we will not use individual patient data, ethical approval is not required.
CRD42025632986.
This study assessed the feasibility of implementing a phase 3 field-based clinical trial protocol to evaluate paediatric praziquantel (PED-PZQ) for the treatment of Schistosoma mansoni infection in children aged 3 months to 6 years in endemic areas of Brazil, focusing on operational aspects such as recruitment logistics, documentation management, investigational product handling and protocol adherence.
Pilot and feasibility study for a phase 3 clinical trial, comprising two components: a randomised, open-label, parallel-group, two-arm trial and a single-arm trial.
Conde, Bahia, Brazil, from December 2024 to January 2025.
Two trials aim to screen 5774 participants from three rural areas in Bahia and three in Sergipe, states in northeastern Brazil, and enrol 403 children eligible for either randomisation or allocation. Trial 1 will randomise (1:1 ratio) 240 children aged 4–6 years into the PED-PZQ treatment arm or the standard praziquantel (PZQ) 1. Trial 2 will enrol 163 children aged 3 months to 3 years, all receiving PED-PZQ. Both trials are open label. Eligible participants shall meet age criteria, test positive for S. mansoni and fulfil other inclusion criteria. In the first recruiting centre, Conde (Bahia), it was estimated that 650 participants would need to be screened for trial 1 and 552 for trial 2, assuming schistosomiasis prevalence of 5% and 4%, respectively. This pilot study reports on the first 60 participants enrolled.
The primary outcome of this pilot study is the feasibility of implementing the research protocol in a real-world field setting, focusing on key aspects such as study documentation challenges, participant safety, investigational medicinal product custody chain and protocol adherence. In addition to providing preliminary data on the parasitological cure rate, secondary outcomes include the prevalence of S. mansoni infection and the reduction in S. mansoni egg count (Kato-Katz method). Furthermore, the occurrence and severity of drug-related adverse events are monitored from drug administration to day 21 post-treatment, alongside changes in renal, hepatic and cardiac functions assessed through biochemical markers.
A total of 60 participants were recruited, and 55 provided stool samples for screening. The pilot phase demonstrated the feasibility of implementing the clinical protocol under field conditions, with successful completion of all planned procedures and minimal protocol deviations. Operational challenges were identified mainly in documentation processes, participant recruitment and investigational product management and were addressed through preventive and corrective quality assurance actions. The experience also highlighted logistical and infrastructural barriers typical of field-based trials in remote endemic areas, which informed adjustments for the subsequent phase 3 study. Preliminary parasitological results indicated an overall S. mansoni prevalence of 9.1% (5/55), with 21% in trial 1 and 2.8% in trial 2. All infected participants met the eligibility criteria, received treatment and completed follow-up. Four achieved a parasitological cure, and one case of treatment failure was observed (trial 1, PZQ group). Two mild adverse events (diarrhoea) were reported, with no serious complications or clinically significant changes in biochemical parameters.
This pilot study demonstrated the feasibility of implementing a field-based phase 3 clinical trial protocol for PED-PZQ in endemic areas of Brazil. The findings confirm that the protocol can be successfully applied in primary care settings, despite operational challenges related to recruitment, logistics and documentation. The study also provided preliminary evidence supporting the safety and effectiveness of the paediatric formulation and highlighted the need to revise prevalence assumptions to improve future screening strategies. Overall, the experience offers valuable insights to guide the large-scale phase 3 trial and supports the incorporation of PED-PZQ into national schistosomiasis control policies.
Brazilian Clinical Trials Registry; RBR-86kcy37.
Nursing students experience heightened stress and emotional burden during clinical training, but opportunities for structured resilience skill development remain limited.
To explore undergraduate nursing students' lived experiences of participation in a resilience-enhancement program.
Qualitative descriptive phenomenology.
Undergraduate students participated in a resilience-enhancement pilot program adapted from Japan for American nursing students. Upon program completion, four semi-structured focus groups were conducted. Sessions were audio-recorded, transcribed and analysed inductively.
Three themes were identified: (1) Intrapersonal Resilience Strategies; (2) Interpersonal & Accountability Supports; and (3) Intervention Design & Delivery Factors. Students described increased emotional insight, stronger coping tools and the value of social accountability.
This study demonstrates that an undergraduate resilience-enhancement program grounded in mindfulness, journaling and peer support is both feasible and meaningful for nursing students. Integrating brief, scalable resilience interventions into nursing curricula may help prepare the next generation of nurses to care effectively for patients and navigate the emotional, ethical and interpersonal demands of a rapidly evolving global healthcare landscape.
This study addresses the global challenge of preparing nursing students for the emotional and relational demands of contemporary healthcare. The program's scalability and alignment with global workforce priorities highlight its potential relevance for nursing education internationally.
This study adhered to the SRQR guidelines.
None.
This study aims to explore the trajectories and co-occurrence of perceived control and caregiver self-efficacy among patients with heart failure (HF) and their caregivers within 3 months post-discharge and identify associated risk factors.
A prospective cohort design.
A prospective cohort study was conducted from March to June 2024 in Tianjin, China. Information on perceived control and caregiver self-efficacy was collected 24 h before discharge, 2 weeks, 1 month, and 3 months after discharge. Group-Based Dual Trajectory Modelling (GBDTM) and logistic regression were used for analysis.
The study included 203 dyads of patients with HF and their caregivers (HF dyads). Perceived control identified three trajectories: low curve (15.3%), middle curve (57.1%) and high curve (27.6%). Caregiver self-efficacy demonstrated three trajectories: low curve (17.2%), middle curve (56.7%) and high stable (26.1%). GBDTM revealed nine co-occurrence patterns, with the highest proportion (36.7%) being ‘middle-curve group for perceived control and middle-curve group for caregiver self-efficacy’, and 16.7% being ‘high-curve group for perceived control and high-stable group for caregiver self-efficacy’. Age, gender, household income, NYHA class, symptom burden and psychological resilience were identified as risk factors for perceived control trajectories; marital status, regular exercise and psychological resilience were identified as risk factors for caregiver self-efficacy trajectories.
We identified distinct trajectories, co-occurrence patterns and risk factors of perceived control and caregiver self-efficacy among HF dyads. These findings help clinical nurses to better design and implement interventions, strengthening the comprehensive management and care outcomes for HF dyads.
These findings highlighted the interactive relationship between perceived control and caregiver self-efficacy trajectories, suggesting that interventions should boost both to improve personalised treatment plans and outcomes for HF dyads.
This study adhered to the STROBE checklist.
Patients and their caregivers contributed by participating in the study and completing the questionnaire.
To examine the relationship between weight loss and problems with oral intake in institutionalised older adults.
A 1-year longitudinal observational study.
Data were obtained from a prospective study conducted in three nursing homes and two long-term care facilities in Japan. Participants' problems with oral intake were assessed using items published in 2021 by the Japanese Ministry of Health, Labour and Welfare. Baseline and follow-up factors were compared between individuals who experienced a weight loss of 5% or more and those who did not. Separate multivariable logistic regression models were constructed for each oral intake assessment item to examine its independent association with weight loss of 5% or more, accounting for transitions in each item between baseline and the 1-year follow-up.
In total, 172 institutionalised older adults were included in the analysis. Among them, 57 (33.1%) participants experienced a weight decrease of 5% or more. The emergence of somnolence or clouding of consciousness during meals at the 1-year follow-up in participants without these signs at baseline was independently associated with a weight loss of 5% or more, after adjustment for baseline characteristics.
Recognising signs of somnolence or clouding of consciousness during meals may be useful for the early detection and prevention of weight loss in institutionalised older adults.
Early detection of individuals at risk is essential to prevent significant weight loss and its associated adverse outcomes. Recognising somnolence or clouding of consciousness during meals may enable earlier detection and intervention to prevent weight loss and improve the quality of care for older adults.
Strengthening the Reporting of Observational Studies in Epidemiology.
No patient or public contribution.
Thirst is the most common self-reported symptom in intensive care unit (ICU) patients. There is evidence that oral cooling interventions may alleviate thirst symptoms in ICU patients. However, the evidence needs to be critically evaluated.
To investigate the effect of oral cooling interventions on alleviating thirst symptoms of ICU patients and explore the effectiveness of different types of oral cooling by subgroup analysis.
The PubMed, Ovid Embase, the Cochrane Library, Wanfang Data and China National Knowledge Infrastructure databases were searched from inception to 29 October 2023. Randomised controlled trials (RCTs) that reported thirst intensity or thirst distress as outcomes were included. The certainty of the evidence was evaluated by the GRADE approach.
The meta-analysis comprised eight RCTs that included 813 ICU patients. The pooled analysis from eight RCTs showed that oral cooling interventions had significant beneficial effects on thirst intensity (weighted mean difference [WMD] = −2.73, 95% confidence interval [CI] = −3.62 to −1.85, p < 0.01; moderate certainty). The pooled analysis from four RCTs showed that oral cooling interventions could significantly lower the thirst distress scores (standardised mean difference = −0.80, 95% CI = −1.13 to −0.47, p < 0.01; low certainty). Subgroup analysis indicated that cold stimulation (WMD = −3.12) and cold combined with menthol stimulation (WMD = −1.72) could significantly lower the thirst intensity scores.
Oral cooling interventions including cold and menthol had beneficial effects on thirst intensity and thirst distress in ICU patients. The high heterogeneity in methods should be considered when interpreting the results.
This study provides references for the application of oral care strategy in the ICU care field, and encourages nurses to apply the oral cooling plan to improve patients' comfort.
This was a meta-analysis based on data from previous studies.
PROSPERO: CRD42023416059
Statins are a cornerstone of cardiovascular disease prevention yet remain underused among eligible patients. Clinical decision support systems embedded in electronic health records (EHRs) are commonly used to encourage guideline-concordant prescribing. Interruptive reminders (eg, pop-ups) may be effective but interfere with clinical workflows and contribute to alert fatigue. Non-interruptive alerts are less intrusive, but their effectiveness remains unclear. The Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC) trial is designed to evaluate the comparative effectiveness of interruptive and non-interruptive reminders on statin-prescribing rates.
INIRSHA-PC is a single-centre, pragmatic, three-arm, parallel-group randomised controlled trial embedded in the EHR at Vanderbilt University Medical Center. The trial will enrol adults aged 18–74 seen in primary care who are eligible for, but not currently prescribed, statin therapy. The planned sample size is 3000 patients (1000 per arm). Enrolled patients will be randomised 1:1:1 to (1) interruptive reminder, (2) non-interruptive reminder or (3) no reminder (usual care). The primary outcome is statin prescription within 24 hours of enrolment. Secondary outcomes are statin prescribing within 12 months and low-density lipoprotein cholesterol levels measured between 30 days and 12 months after enrolment. Enrolment began on 14 August 2024. The study is expected to be completed on 19 November 2025.
The trial has been approved by the Vanderbilt University Medical Center Institutional Review Board with waiver of patient informed consent (IRB number: 240419). Results will be disseminated through peer-reviewed publication and presentation at scientific conferences.
by Masanori Nishi, Yasushi Yoshikawa, Yuki Usui, Hajime Nishida, Shota Nakamura, Koichiro Tashiro, Yoshifumi Kudo
The purpose of this study was to investigate the correlation between femoral morphological indices from anteroposterior hip radiographs and dual-energy X-ray absorptiometry-assessed bone mineral density in postmenopausal female patients undergoing primary total hip arthroplasty for hip osteoarthritis. We also evaluated the impact of hip deformity on these correlations and the diagnostic cut-off values for osteoporosis. This retrospective study, conducted at a single institute (February 2018 to July 2024), reviewed the data of postmenopausal patients (>50 years old) with hip osteoarthritis who underwent total hip arthroplasty. Patients with a history of hip surgical procedures, infection, metabolic bone disease, or inadequate imaging findings were excluded. Dual-energy X-ray absorptiometry was used to assess bone mineral density at the femoral neck, total hip, lumbar spine, and distal radius. Five femoral indices were measured: the canal-to-calcar ratio, canal flare index, cortical thickness index, canal diaphysis ratio, and canal bone area ratio. Analyses included Pearson’s correlation and receiver operating characteristic curve analysis. Moderate correlations were observed between total hip bone mineral density and indices in 95 hip osteoarthritic joints (all Tönnis grade 3) and 86 normal joints. The canal bone area ratio had the strongest correlation (hip osteoarthritis: r = −0.61; normal: r = −0.62; pby 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 Ryosuke Segawa, Makiko Yagisawa, Chihiro Miyata, Noriyasu Hirasawa
Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that induces type 2 immune responses through dendritic cell activation, and its aberrant regulation is implicated in TSLP-associated inflammatory disorders including atopic dermatitis. We previously demonstrated that hypoxia-inducible factor (HIF) suppresses TSLP expression in human keratinocyte cells; however, the underlying mechanism remained unclear. In this study, we aimed to explore the suppressive mechanism of enarodustat, an HIF-prolyl hydroxylase inhibitor. Enarodustat selectively suppressed TSLP expression induced by the fibroblast-stimulating lipopeptide (FSL-1), a toll like receptor 2/6 agonist in HaCaT, a human keratinocyte cell line. Although both the nuclear factor-κB (NF-κB) and activator protein (AP)-1 contributed to FSL-1-induced TSLP induction, enarodustat preferentially attenuated AP-1 signaling by reducing c-Jun N-terminal kinase (JNK) phosphorylation. This JNK dephosphorylation required both HIF1α and HIF2α and was accompanied by increased expression of dual-specificity phosphatases (DUSPs), which target JNK for dephosphorylation. Collectively, our findings identify a previously uncharacterized HIF–DUSP–JNK axis that negatively regulates TSLP expression. This study provides mechanistic insight into how HIF activation shapes epithelial cytokine responses, offering a basis for understanding the pathogenesis of TSLP-associated diseases such as atopic dermatitis.RESUMEN:
Introducción: las representaciones culturales y sociales de las madres de las comunidades indígenas andinas determinan el tipo de padecimiento y la ruta terapéutica a seguir.
Objetivo: Identificar los síndromes culturalmente delimitados que describen las mujeres Kichwas — en Chugchilán-Ecuador— en el contexto de los cuidados materno-infantiles, así como sus causas, sintomatología y tratamientos. Metodología: Estudio etnográfico, llevado a cabo entre 16 de septiembre 2020 y 30 de abril 2021. Participaron 14 mujeres indígenas. Las técnicas aplicadas fueron: observación participante y entrevistas en profundidad. Los escenarios observados fueron tanto comunitarios como en el hogar, acompañando a las madres en sus actividades de la vida diaria. Resultados: En las narrativas de las madres se muestra cómo identifican los síndromes culturalmente delimitados desde su sistema de representaciones. Estos padecimientos responden al sistema de conocimientos locales —de la propia comunidad— y no tienen traducción por la biomedicina. De los síndromes culturalmente delimitados presentes en esta comunidad, se destacan dos “el espanto” y “el aire”. A partir de los saberes maternos se describe cómo los delimitan y clasifican: pronóstico o gravedad y el itinerario terapéutico o proceso de atención que inician. Conclusiones: En “el espanto” y “el aire”, las representaciones sociales de las comunidades indígenas andinas influyen en la decisión del tratamiento, reconociendo que en la biomedicina no encontraran respuesta para este tipo de afecciones, pero en cambio sí en la Medicina Tradicional indígena. El conocimiento de los síndromes culturalmente delimitados, pone en valor la aplicación de cuidados interculturales a las personas indígenas, ya sea en sus propias comunidades de origen, como en los contextos migratorios donde éstas se asienten.
FreshRSS 