• Acupuncture Treatment Alleviating Pyroptosis on Asthma Inflammation in Mice via Micro-RNA-223/NLRP3 Pathway.
    3 weeks ago
    Evidence has shown that acupuncture treatment could significantly reduce the activation inflammation in asthmatic mice. However, the underlying mechanism through which acupuncture influences asthma has not yet been elucidated.

    OVA-induced asthma in NLRP3‒/‒ and wild-type C57BL mice, and lipopolysaccharides (LPS) induced inflammation in 16HBE cell were established in vivo and in vitro. H&E, Masson, and Sirius staining, along with ELISA kits, Western Blot, PCR, lactate dehydrogenase (LDH), immunohistochemistry, and immunofluorescence techniques were employed to assess the miR-223/NLRP3-mediated pyroptosis pathway in mitigating asthma-induced inflammation.

    In vitro, acupuncture treatment alleviated airway inflammation in asthmatic mice, upregulated miR-223 expression, inhibited the genes and proteins expression level in NLRP3 pathway, such as NLRP3, GSDMD, ASC, and Caspase-1, it also lowered the presence of cytokines tied to T cells. Activation of the NLRP3 pathway seemed to make asthma symptoms worse, whereas acupuncture treatment effectively alleviated the inflammation by modulating the miR-223/NLRP3 pathway. In vivo, after upregulating or downregulating miR-223 expression in an LPS-induced cell inflammation model, the expression levels of the NLRP3 pathway changed significantly. The dual-luciferase assay revealed the specific interaction of miR-223 to the NLRP3 gene, thereby suppressing its transcription.

    miR-223-3p can bind to NLRP3 and suppresses the expression of NLRP3 gene. Acupuncture treatment can activate miR-223/NLRP3-related pyroptosis pathway to regulate T-lymphocyte immunity and effectively reduce airway inflammation in asthmatic mice.
    Chronic respiratory disease
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  • Investigating languishing in North American genetic counselors.
    3 weeks ago
    Often, mental health is considered as a binary of being mentally well or mentally ill. Realistically, mental health exists on a broad spectrum with "flourishing" on one end and "depression" on the other. "Languishing" is the state that lies between the two; it is characterized by a lack of motivation, numbness, decreased productivity, and feeling sluggish or apathetic without veering into clinical depression. Furthermore, languishing is a state that is distinct from burnout and compassion fatigue, despite some overlap in presentation. The term gained popularity during the COVID-19 pandemic and has persisted since. However, to our knowledge, there has been no research on languishing in genetic counselors. Therefore, English-speaking, full-time, North American genetic counselors were solicited through the Minority Genetics Professionals Network (MGPN) and the National Society of Genetic Counselors (NSGC) to participate in a study designed to explore factors associated with languishing among genetic counselors. Purposive sampling was used to select interviewees to most effectively represent diverse backgrounds and identities. The guide for the semi-structured interviews included questions that assessed participants' social, emotional, and psychological well-being at their current place of work. Interviews were deductively and inductively coded and then analyzed for themes using a phenomenological framework. Nineteen genetic counselors consented to have their interviews included in the publication of this study. The cohort reported feeling replaceable in their professional role, an appreciation for diversity in the workplace but a concern of being made to feel like an "other," and varying levels of comfort with their life once they achieved their academic goals. Some participants also cited intersectionality as well as personal and professional experiences that contributed to their self-perception and impression of their work community. Results suggest that institutions, leaders, and supervisors would benefit from considering these factors when their genetic counselors present with symptoms indicative of languishing.
    Chronic respiratory disease
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  • Children's Birthday Gatherings and SARS-CoV-2 Infection in Grandparents.
    3 weeks ago
    During the COVID-19 pandemic, the major burden of morbidity and mortality was in older age groups. While within-household transmission is well documented, the wider role of social networks for transmission to the older population is less well understood.

    To estimate whether children's birthdays were associated with grandparents' SARS-CoV-2 infection risk.

    This nationwide, register-based cohort study included grandparents residing in Denmark with 1 to 5 grandchildren aged 0 to 15 years during the period between February 19, 2020, and February 28, 2022. The timing of birthdays of grandchildren was used as a natural experiment to examine whether birthday-related opportunity for family gatherings was associated with the risk of SARS-CoV-2 infection in grandparents. Family structures were mapped at the individual level. Data were analyzed from June 2024 to December 2026.

    Birthdays of grandchildren turning 1 to 16 years. A birthday risk window, the period when positive test results could be ascribed to a celebration, was defined as the 7-day time window from 2 to 8 days after the grandchild's birthday.

    The primary outcome was a positive result on a SARS-CoV-2 test (by polymerase chain reaction or antigen testing) recorded in the national surveillance system. Hazard ratios comparing the hazard of having positive test result for SARS-CoV-2 (outcome) in grandparents in birthday-windows vs grandparents who at the same moment were in nonbirthday periods, were estimated using Cox proportional hazards regression with birthdays as time-varying covariates.

    Among 1 106 493 grandparents (median [IQR] age, 67 [60-73] years; 54% female), grandparents had 9.9% (95% CI, 7.9%-12.0%) higher hazard of SARS-CoV-2 infection during birthday risk windows. The hazard varied over time and by variant and was not seen during the period when Alpha dominated. The risk was greater for birthdays of preschool-aged grandchildren (adjusted hazard ratio, 1.15; 95% CI, 1.12-1.18) than during birthdays of school-aged grandchildren (adjusted hazard ratio, 1.07; 95% CI, 1.04-1.09).

    This cohort study of grandparents found that grandchild birthdays, despite official advice not to gather during part of the pandemic, were associated with increased SARS-CoV-2 infection risk among grandparents during much of the pandemic, with magnitude of risk varying over time and by viral variant. These results emphasize the role of culturally important events in intergenerational transmission dynamics, supporting future targeted risk mitigation around small family events.
    Chronic respiratory disease
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  • Feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for giant emphysematous bulla.
    3 weeks ago
    Giant emphysematous bulla (GEB) is a form of emphysematous lung destruction and patients experience progressive dyspnea and decline in quality of life. Conventional surgical reduction is not available for all patients, especially those in poor condition, and a less invasive approach is needed.

    This study aimed to evaluate the feasibility and preliminary clinical outcomes of medical thoracoscopic bulla volume reduction for GEB.

    Single-center retrospective observational study.

    A total of 35 GEB patients who underwent medical thoracoscopic bulla volume reduction were retrospectively analyzed. Preoperative and postoperative clinical data and chest computed tomography were collected. The feasibility of the technique was evaluated by radiological changes (bullae volume and diameter) and postoperative complications. Improvement in dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Accessible six-minute walk distance (6MWD) and spirometry test follow-up data were analyzed to assess preliminary clinical functional improvement.

    The targeted bulla volume was 1183.8 ± 636.7 mL preoperatively and decreased to 169.2 ± 237.2 mL postoperatively, representing an 87.7 ± 17.1% decrease compared to the baseline. A total of 91.4% (32/35) of the patients achieved more than 50% volume reduction relative to baseline, and the diameter of the targeted bulla also showed a significant decrease (p < 0.0001). Nine subcutaneous emphysema cases and one thoracic infection case were reported as postoperative complications. In the overall population, the mMRC score decreased by 1.2 ± 0.6 points at the 6-month follow-up. Available follow-up data on 6MWD and spirometry tests also showed improvement.

    Medical thoracoscopic bulla volume reduction may represent a feasible and less invasive therapeutic option for patients with GEB and demonstrated preliminary clinical outcomes.
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  • Development and validation of a multimodal risk prediction model for early COPD progression: a retrospective study integrating clinical, functional, and CT radiomic features.
    3 weeks ago
    Early identification of rapid progression in patients with preserved ratio but chronic cough remains challenging.

    To develop and validate an integrated multimodal prediction model that combines clinical phenotypes, small airway function indices, and chest CT quantitative features for stratifying progression risk in individuals with preserved ratio, chronic cough, and early COPD features.

    Retrospective cohort study with external validation.

    In this retrospective cohort study of 408 participants with chronic cough (⩾3 months) and preserved spirometry (FEV1/FVC ⩾ 0.7), we integrated clinical profiles, pulmonary function (including small airway indices), and AI-quantified chest CT quantitative features. A three-stage modeling approach was used: variable screening with generalized estimating equations, predictor selection via LASSO regression, and construction of a Random Survival Forest-Cox hybrid model to predict a composite outcome of accelerated lung function decline (annual FEV1 decline >40 mL) or acute exacerbation. External validation was performed using an independent cohort (COPDGene, n = 312, 82 outcome events), with 3-year follow-up for prediction. The model underwent internal validation (10-fold cross-validation), with interpretability assessed via SHapley Additive exPlanations (SHAP).

    Multivariable analysis confirmed small airway dysfunction and mucus plug burden as independent predictors of accelerated FEV1 decline (all p < 0.001), with a significant synergistic interaction (β = 2.34, p = 0.003). The final nine-feature model showed excellent discrimination, with a time-dependent AUC of 0.872 (95% CI: 0.843-0.901) on internal validation and 0.843 (95% CI: 0.812-0.874) on external validation. SHAP analysis identified small airway parameters and mucus plug burden as the top contributors, jointly accounting for 68.4% of predictive output. A nomogram and online calculator were developed for clinical use.

    We developed and validated a robust multimodal prediction model that accurately stratifies progression risk in individuals with preserved ratio, chronic cough, and early COPD features. This tool facilitates personalized risk assessment and holds promise for guiding precision management strategies to improve outcomes in this high-risk population.
    Chronic respiratory disease
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  • [Vaccination for pregnant women].
    3 weeks ago
    A vaccine is a preparation capable of inducing a specific and lasting immune response in the vaccinated patient to protect him in the event of exposure to the pathogen, against infection or to mitigate its consequences. Vaccination during pregnancy has a dual objective: to protect the vaccinated pregnant woman from potentially more severe infections due to pregnancy (flu, Covid-19) and to protect the newborn from birth from potentially serious infections during his first months (whooping cough, respiratory syncytial virus [RSV]). Currently four vaccines are recommended for all pregnant women (anti-flu vaccine, anti-whooping cough vaccine, anti-Sars-Cov-2 vaccine and anti-RSV vaccination). Only live vaccines are contraindicated.On a global and individual scale, vaccination is one of the most effective tools to defend against the infectious world, but the emergence of mistrust of vaccines and variable acceptability of vaccination during pregnancy could threaten its effectiveness.
    Chronic respiratory disease
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  • Thyroid function and outcomes in heart failure with mildly reduced ejection fraction: insights from a large, retrospective registry.
    3 weeks ago
    This study aimed to investigate the prognostic impact of thyroid function on the outcomes of patients with heart failure with mildly reduced ejection fraction (HFmrEF).

    Thyroid function is crucial for the optimal performance of the cardiovascular system. However, the prognostic impact of subclinical thyroid dysfunction in patients with heart failure (HF), specifically HFmrEF, remains unclear.

    For the present study, patients hospitalized with HFmrEF and known thyroid function were included from 2016 to 2022. Patients were divided into four groups: euthyroid (reference group, n = 1186 [TSH 0.45-4.5 mU/L]), subclinical hypothyroidism (n = 95 [TSH > 4.5 mU/L, fT4 7.5-23 pmol/L]), subclinical hyperthyroidism (n = 139 [TSH < 0.45 mU/L, fT4 7.5-23 pmol/L]), and low T3 syndrome (n = 148 [fT3 ≤ 3.3 pmol/L]). Patients with manifest hyper- and hypothyroidism were excluded related to the low sample size. The primary endpoint was all-cause mortality at 30 months (median follow-up). Key secondary endpoint was HF-related rehospitalization at 30 months.

    From 1568 patients with HFmrEF, most patients presented with euthyroidism (75.6%), followed by low T3 syndrome (9.4%), subclinical hyperthyroidism (8.9%), and subclinical hypothyroidism (6.1%). The risk of all-cause mortality at 30 months was highest in patients with low T3 syndrome (51.4%), followed by subclinical hypothyroidism (38.9%) and subclinical hyperthyroidism (36.7%), whereas euthyroid patients (26.6%) had the lowest risk of long-term all-cause mortality (p = 0.001). In multivariable Cox regression analyses, subclinical hypothyroidism (hazard ratio [HR] 1.454, 95% confidence interval [CI] 1.001-2.113, p = 0.049), subclinical hyperthyroidism (HR 1.458, 95% CI 1.046-2.033, p = 0.026), and low T3 syndrome (HR 1.594, 95% CI 1.185-2.145, p = 0.002) were identified as independent predictors of all-cause mortality at 30 months compared to euthyroid patients. Patients with low T3 syndrome were even associated with impaired prognosis as compared to patients with subclinical hyperthyroidism (HR 1.553, 95% CI 1.088-2.212; p = 0.015). However, thyroid status was not associated with the risk of HF-related rehospitalization at 30 months.

    In patients with HFmrEF, the presence of subclinical hypothyroidism, subclinical hyperthyroidism, and low T3 syndrome were identified as predictors of all-cause mortality, but not of HF-related rehospitalization at 30 months.
    Cardiovascular diseases
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  • Fracture of the cannula tip during removal of a long-term indwelling Impella 5.5: a case report.
    3 weeks ago
    We report a rare device fracture during Impella 5.5 explantation for cardiogenic shock in a 77-year-old man with prolonged device support. Following stabilization, device removal was attempted on day 50. During withdrawal, marked resistance was encountered and the cannula tip fractured, remaining within the prosthetic graft. The tip was surgically retrieved following extension of the dissection. Post-explantation, the patient developed acute right upper extremity ischemia, likely due to vasospasm, which resolved spontaneously. This case underscores the importance of recognizing marked resistance during Impella explantation, as excessive stress concentration and mechanical shearing forces may contribute to device fracture.
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  • Flow diversion in proximal superior cerebellar artery aneurysms: Systematic review of clinical outcomes and exploratory hemodynamic analysis.
    3 weeks ago
    Flow diverters (FDs) are emerging as a treatment strategy for superior cerebellar artery aneurysms (SCAs) despite the limited data on their efficacy and safety. This study evaluated flow diversion (FD) treatment for proximal SCA aneurysms through a single center analysis, systematic review of the literature, and exploratory computational fluid dynamics (CFDs) simulations. Retrospective review of patients with proximal SCA aneurysms treated with FDs at our neurovascular service between 2013 and 2024. We then conducted a systematic review of the literature using the EMBASE, PubMed, and Web of Science to identify patients with SCA aneurysms treated with FD. Data extracted from these studies included demographics, aneurysm characteristics, treatment, and outcomes. Thereafter, a steady-state CFD simulations using a porous-media representation of the implanted device were performed to qualitatively explore hemodynamic differences when the device distally landed in the ipsilateral versus contralateral posterior cerebral artery relative to the aneurysm. Our literature search identified 13 proximal aneurysms from 6 eligible studies; combined with 5 institutional cases, a total of 18 aneurysms were analyzed. Among these, 16 (88.9%) of the aneurysms were saccular, with a mean size of 6.5 mm (range: 2.2-22) and treated with PED (84.6%) and SILK (15.4%) devices. At a mean of 16.1 months (range: 4-53) angiographic evaluation indicated that 72.2% (13/18) achieved complete or near-complete occlusion, with no long-term neurological deficits. Exploratory CFD analysis suggested greater modeled reductions in aneurysm WSS, kinetic energy, and inflow when stent deployment was simulated ipsilateral to the aneurysm. FD is a reported treatment for proximal SCA aneurysms, and can be technically performed in selected cases. However, further studies with larger cohorts and extended follow-up are needed to evaluate long-term efficacy, functional outcomes, and potential delayed complications.
    Cardiovascular diseases
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  • Identifying Platelet Lipidomic Networks and Evaluating Machine-Learning Models to Identify Distinctive Features Between Chronic and Acute Coronary Syndrome.
    3 weeks ago
    Platelet lipidomics offers a window into the thromboinflammatory responses to acute coronary syndromes (ACS) and chronic coronary syndromes (CCS), yet differences between the platelet lipidomes of these two coronary artery disease subtypes remain poorly characterized. In this pilot study, untargeted platelet lipidomics and miRNA transcriptomics were performed on platelets isolated from 19 ACS and 57 CCS patients undergoing coronary angiography, integrated with routine clinical and hematological traits in statistical network analyses and cross-validated machine learning models. Platelet lipidomics identified 81 lipid features significantly altered between ACS and CCS (FDR q < 0.05), predominantly involving phosphatidylcholines, lysophosphatidylcholines, and ceramides. Cer 18:2;O2/24:0 showed the strongest inverse association with ACS of any identifiable lipid (q = 0.0394, OR = 0.297, 95% CI [0.171, 0.515]), while increased Cer 18:0;O2/22:1 (q = 0.088, OR = 3.072, 95% CI [1.607, 5.878]) and Cer 18:0;O2/18:0 (q = 0.088, OR = 2.791, 95% CI [1.515, 5.145]) demonstrate nominally significant promotive effects on ACS. Differential correlation analysis further identified oxidized phospholipid species as connectivity hubs in ACS-specific lipid networks, a pattern not detectable by differential abundance approaches alone. Although untargeted lipidomics did not meaningfully outperform a routine clinical trait benchmark in ACS classification, phosphatidylcholine-trained models achieved modest gains in AUROC, and the prominent ceramide signal-platelet-specific and mechanistically distinct from plasma ceramide risk scores-supports a targeted validation strategy centered on a ceramide-enriched platelet lipid panel in prospective, adequately powered cohorts.
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