• Concurrent Ferroptosis and Apoptosis in Resveratrol-Treated Glioblastoma Cells: Relevance With NRF2 Downregulation and Oxidative Stress.
    2 weeks ago
    Glioblastomas (GBMs) are lethal brain tumors characterized by rapid growth and resistance to standard treatment. Resveratrol (RES) increases the levels of reactive oxygen species (ROS) and induces cell death in sensitive GBM cells. However, the death patterns induced by RES and their relevance to NFE2-related factor 2 (NRF2) remain unclear. The current study aimed to address these issues using RES-sensitive U251 and less-sensitive LN428 GBM cell lines, as well as an orthotopic GBM xenograft rat model. In silico analysis revealed high NRF2 expression in GBM tissues and a strong correlation with tumor progression in the TCGA dataset. After 48 h of 100 µM RES treatment, NRF2 levels remained stable in LN428 cells but significantly decreased by 2.3-fold in U251 cells, accompanied by suppressed growth and NRF2-regulated and ferroptosis-related xCT and GPX4 downregulation. Elevated Fe2+, ROS levels, lipid peroxidation, and ferroptotic frequency were evidenced in RES-treated U251 cells; meanwhile, apoptosis and reduced NRF2-HO-1 expression were also evident in U251 cells. Combined treatment with Ferrostatin-1 and Z-VAD FMK rescued 60% of U251 cells compared to RES-treated counterparts. In vivo, lumbar puncture (LP) administration of RES induced both ferroptosis and apoptosis in rat orthotopic GBM xenografts. These findings highlight the dual cell death induced by RES in sensitive GBM cells and identify NRF2 signaling status as a novel determinant of cellular response to RES treatment.
    Cancer
    Policy
  • Therapeutic Targets for Lung Squamous Cell Carcinoma: Proteome-Wide Mendelian Randomization and Potential Drug Prediction.
    2 weeks ago
    Lung squamous cell carcinoma (LUSC) is one of the most prevalent subtypes of lung cancer, accounting for approximately 25%. Mendelian randomization (MR) analysis of plasma proteins can identify potential drug targets for LUSC.

    We obtained genetic instruments for plasma proteins from a GWAS by Sun BB et al. conducted on 3301 healthy adults. GWAS summary statistics of LUSC were from ILCCO. We conducted a two-sample MR analysis to investigate the causal relationships between plasma proteins and the risk to LUSC. Colocalization analysis was used to test whether two traits share the same causal variables. Survival analysis based on potential proteins was conducted using transcriptomic data from TCGA database to determine whether gene expression levels are associated with the prognosis of LUSC patients. Moreover, predictions of potential drug ligands and molecular dockings were performed to evaluate the pharmaceutical properties of the target genes.

    Proteome-wide MR analysis identified three proteins (MICB, SPINK2, TXNDC11) that showed a strong association with decreased risk of LUSC after FDR correction. Increased levels of MICB [OR(95% CI) = 0.72(0.63, 0.83); p = 3.90E-06], SPINK2 [OR (95% CI) = 0.74 (0.66, 0.84); p = 1.25E-06], TXNDC11 [OR (95% CI) = 0.63(0.51, 0.78); p = 2.69E-05] per SD decreased the risk of LUSC specifically. Sensitivity analysis revealed that there was no significant heterogeneity, pleiotropy, or reverse causality between these proteins and LUSC. Colocalization analysis indicated that three proteins shared the same variants with LUSC. Survival analysis showed that upregulation of SPINK2 was associated with a favorable prognosis in LUSC patients, while MICB and TXNDC11 were not. The expression of MICB, SPINK2, TXNDC11 was found to be potentially affected by specific substances, and our molecular docking showed a stable binding between SPINK2 and danazol, suggesting its potential as a drug target.

    This study identified SPINK2 causally associated with the risk and prognosis of LUSC, which is a promising target for LUSC. The drug prediction we performed illustrated the medicinal potential of SPINK2, and the high binding activity of molecular docking indicated its strong potential as a drug target.
    Cancer
    Chronic respiratory disease
    Advocacy
  • Advanced breast cancer detection: leveraging MIM structure containing triangular cavity and elliptical island for refractive index and temperature sensing.
    2 weeks ago
    In this study, a highly sensitive surface plasmon polariton (SPP)-based sensor with a metal-insulator-metal (MIM) configuration is proposed and numerically investigated for multifunctional detection, including refractive index sensing, breast cancerous cell discrimination, and temperature sensing. The sensor consists of an air-filled MIM waveguide integrated with a triangular cavity, further optimized by embedding an internal elliptical silver island to enhance light-matter interaction. Finite element method simulations reveal that the elliptical cavity design significantly improves transmission characteristics, extinction ratio, and RI sensitivity (RIS) due to the increased effective optical path length. The optimized structure achieves a RIS of 1207.14±4.12nm/RIU and a detection resolution as low as 8.28×10-7RIU. Furthermore, the sensor demonstrates the capability to distinguish between normal and malignant breast cells, making it an advantageous platform for biomedical diagnostics. Additionally, the sensor exhibits a significant temperature sensitivity of 0.945±0.003nm/K. The proposed design also shows strong potential for nanofabrication via techniques such as electron beam lithography, enabling its integration into compact optoelectronic and biosensing devices.
    Cancer
    Education
  • High-sensitivity nanometamaterial near-infrared biosensor for label-free early cancer detection via exosomal biomarkers.
    2 weeks ago
    This study presents a novel, to the best of our knowledge, ultra-wideband nanobiosensor based on a double-negative (DNG) metamaterial perfect absorber for early cancer detection through exosomal biomarker analysis. Our biosensor operates across a broad frequency range from 70 THz to 3 PHz, exhibiting near-unity absorption, i.e., exceeding 99%, and angular and polarization insensitivity, i.e., providing polarization-independent absorption across the full spectrum of polarization angles (0° to 90°), ensuring stable performance under both transverse electric (TE) and transverse magnetic (TM) polarized waves. Of particular interest is its performance in the near-infrared (NIR) region (70-400 THz), where the sensor's DNG characteristics manifest through simultaneously negative permittivity and permeability, enhancing field confinement and sensitivity. This spectral window is especially conducive to label-free, non-invasive detection of circulating exosomes, critical indicators of early stage oncogenesis. The sensor is constructed using a tri-layer metal-insulator-metal (MIM) architecture comprising nickel (Ni) layers and a silicon dioxide (SiO2) dielectric spacer. The design leverages the plasmonic and thermal stability properties of Ni and the low optical attenuation of SiO2 to achieve optimal absorption and structural robustness. Electromagnetic simulations demonstrate strong electric and magnetic resonances, producing significant near-field enhancements. These improve the detection of subtle dielectric changes associated with exosomal binding events. The sensor maintains high absorption efficiency across oblique incidence angles and various polarization states, making it suitable for real-world biomedical diagnostic applications. By focusing on the NIR regime where tissue transparency and molecular vibrational modes intersect, the proposed biosensor enables the discrimination between cancer-derived exosomes and their normal counterparts, as confirmed through spectral and field distribution analyses. The demonstrated performance highlights the sensor's promise for next-generation photonic platforms targeting early cancer diagnostics, with potential extension to environmental monitoring and energy harvesting technologies.
    Cancer
    Education
  • Stress, Burnout, Contributions, and Coping Mechanisms of Community Pharmacists in Puerto Rico during the COVID-19 Pandemic.
    2 weeks ago
    To evaluate perceived stress and burnout among community pharmacists and to explore their coping mechanisms and perceived contributions.

    A cross-sectional study among pharmacists in Puerto Rico was conducted during the COVID-19 Pandemic using Cohen's 10-item Perceived Stress Scale and the Oldenburg Burnout Inventory. Open-ended questions explored pharmacists' contributions and coping mechanisms. The survey was distributed via the Puerto Rico Pharmacist Association listserv, social media, and professional chats.

    A total of 193 pharmacists were included in the analysis. Eighty-five responded to the open-ended questions, and 150 responded to the 2 scales. Most of the participants were women (82%) with a mean age of 45 years. The mean perceived stress score was 22.0 ± 6.6, indicating moderate stress levels. While 46.7% exhibited moderate burnout, 25.3% showed high burnout. Female pharmacists had higher stress than male pharmacists (22.61 vs. 18.56, P < .05). Pharmacists working in chain pharmacies had higher stress and burnout levels compared to those working in independent pharmacies (24.40 vs. 20.48 and 46.87 vs. 40.24, respectively; P < .05). Pharmacists' greatest contributions during the pandemic were ensuring continuity of care and providing pharmaceutical services and education. Although they experienced a sense of underappreciation, coping mechanisms and institutional adaptation strategies helped them overcome the broader challenges of the pandemic.

    Community pharmacists, particularly those in chain pharmacies and those who were female, reported moderate stress and moderate-high burnout. It is necessary to explore the reasons for these disparities. This study highlights the importance of allocating resources to improve and protect the wellbeing of pharmacists.
    Chronic respiratory disease
    Access
    Advocacy
  • The Role of Mutual Aid Organizations in Promoting Food Sovereignty in Puerto Rican Rural Communities: A Qualitative Analysis.
    2 weeks ago
    Previous research has shown that, during both climate and non-climate disasters-such as hurricanes, the COVID-19 pandemic, and other climate-related crises-and despite political control from the mainland United States, mutual aid organizations in Puerto Rico have played a central role in supporting community health and advancing food sovereignty. However, this research has largely focused on urban contexts and post-disaster recovery. The present study examined how mutual aid organizations in rural Puerto Rico contribute to food sovereignty through their everyday practices and beyond periods of disaster. Semistructured interviews were conducted with representatives from 5 mutual aid organizations serving rural municipalities across the island. The study findings identified 3 core themes that reflect how mutual aid organizations in rural Puerto Rico advance food sovereignty. The results suggest that mutual aid serves as a critical mechanism for decolonizing Puerto Rico's food system, emphasizing local leadership and community-based strategies for sustainable self-determination.
    Chronic respiratory disease
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    Care/Management
    Advocacy
  • [Low levels of vitamin D at one month of age and its association with bronchopulmonary dysplasia in premature newborns under 32 weeks and/or under 1500 g].
    2 weeks ago
    Premature newborns (PTNBs) are at increased risk of vitamin D (VD) deficiency. VD is currently recognized for its multiple functions, including its role in lung maturation, and a reported association between VD deficiency and the development of bronchopulmonary dysplasia (BPD).

    To determine whether there is an association between low 25(OH)D levels measured at 1 month of age in PTNBs and BPD.

    A retrospective study was conducted with data collected from clinical records of VLBW infants (< 1,500 grams) and/or < 32 weeks of gestational age. 25(OH) D levels at 1 month of age, perinatal characteristics, and postnatal outcomes were analyzed. Low 25(OH)D levels were defined as < 30 ng/ml, and a statistical association with BPD and other comorbidities was evaluated.

    A total of 147 PTNBs were included in the analysis. The mean VD level was 22.0 ± 10.3 ng/ml. 85.0% (125/147) had low levels and 45.0% (66/147) developed BPD. No association was observed between low 25(OH)D levels and comorbidities, including BPD. The BPD group had a lower gestational age (p < 0.0001), birth weight (p < 0.0001), and greater need for any respiratory support (p < 0.001), along with a significant association with all comorbidities evaluated (p < 0.001).

    Most PTNBs had VD deficiency. No association was found between low VD levels and BPD.
    Chronic respiratory disease
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    Care/Management
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  • Subglottic stenosis: characteristics and results in patients underwent to a laryngotracheal reconstruction.
    2 weeks ago
    Subglottic stenosis (SGS) can be either congenital or acquired. Acquired SGS is more frequent and is mainly caused by prolonged intubation. Treatment includes laryngotracheal reconstruction (LTR) with anterior and/or posterior rib graft, partial cricotracheal resection (PCTR), and endoscopic dilatation.

    To describe and analyze the characteristics, surgical outcomes, and postoperative complications of the pediatric population with SGS surgically treated.

    Retrospective study of surgical outcomes and postoperative complications of 44 pediatric patients with SGS treated with LTR or PCTR between 2015 and 2024 in a tertiary pediatric hospital.

    88.6% of patients presented acquired SGS. LTR was performed in 33 patients with grade II and III SGS with a success rate of 93%. PCTR was performed in 11 patients with SGS grade III- IV, with a success rate of 91%.

    LTR as well as PCTR are safe and effective options for the treatment of SGS in children. Surgical success depends on specialized, individualized, and multidisciplinary care.
    Chronic respiratory disease
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    Advocacy
  • [Evaluation of ventilatory muscles in infants with severe botulism].
    2 weeks ago
    Infant botulism is a toxic infection that causes flaccid muscle paralysis, requiring invasive mechanical ventilation (IMV) in severe cases. Weaning from ventilatory support in this group of patients is challenging due to the difficulties in evaluating the recovery of muscle strength.

    To evaluate the recovery of ventilatory muscle strength in infants with severe botulism.

    Demographic variables and daily measurements of maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and diaphragmatic excursion (DE) were retrospectively evaluated in infants with severe botulism who required IMV, from the beginning of ventilatory support (baseline) until extubation (final).

    10 patients were included with a median age of 4 months (IQR 3.2-4.7); all received equine botulinum antitoxin with a median delay of 89.5 hours (IQR 61.4114.2). The infants remained in PICU for a median of 15 days (IQR 12.5-16), with requirement of IMV for 15.2 ± 6.4 days. The baseline values recorded of IMV increased progressively, with significant differences compared to the final values (right DE 0.62 ± 0.1 vs 1.09 ± 0.29 cm, MEP 16 ± 6.7 vs 43±17.1 cmH20, and MIP 24 ± 12.4 vs 46 ± 6.9 cmH20, respectively). No patient failed extubation.

    The parameters evaluated significantly improved during botulinum diaphragmatic paralysis. They could be useful tools for mechanical ventilation weaning in children with this neuromuscular weakness.
    Chronic respiratory disease
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    Care/Management
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  • [Sociodemographic and environmental factors in infants under one year of age hospitalized for acute bronchiolitis: case-control study].
    2 weeks ago
    Inequity in access to healthcare and environmental conditions are factors that affect health.

    To analyze sociodemographic and environmental factors in infants under 1 year of age admitted due to acute bronchiolitis.

    Retrospective case-control study conducted in a public pediatric hospital. Cases were infants under 1 year of age hospitalized due to bronchiolitis and controls were infants of the same age hospitalized due to non-respiratory pathologies, matched by origin and date of consultation. Incomplete medical records were excluded, as well as cases in which parents could not be contacted by telephone. The variables analyzed were age, gender, comorbidities, nutritional status, exclusive breastfeeding, socioeconomic level, exposure to environmental and tobacco smoke, living less than 100 meters from a high-traffic area, and living with siblings under 10 years. Data were analyzed with SPSS, using descriptive and inferential statistics.

    A total of 200 cases and 200 controls were included. In the multivariate analysis, factors associated with hospitalization were the lack of exclusive breastfeeding at 3 months of age (OR = 2 [1.1-3.8]), exposure to tobacco (OR = 1.8 [1.2-3]), age less than 6 months(OR = 2 [1.3-3.2]), and living with siblings under 10 years of age (OR = 1.7 [95% CI 1.2-2.6]).

    The absence of exclusive breastfeeding in the first 3 months of life, living with smokers, age less than 6 months and living with siblings under 10 years of age were the sociodemographic and environmental risk factors independently associated with hospitalization due to bronchiolitis.
    Chronic respiratory disease
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    Care/Management
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