Medicine

Background Postoperative sleep disorder, a frequently observed complication, is associated with heightened pain sensitivity, exacerbated inflammatory reactions, and compromised tissue repair. Sufentanil, a highly selective -opioid receptor agonist, is widely used in patient-controlled intravenous analgesia (PCIA) and has been associated with reduced sleep efficiency. Oxycodone, as a /{kappa} dual receptor agonist, has shown a lower incidence of adverse effects in clinical practice. Despite these pharmacological differences, the comparative effects of oxycodone- versus sufentanil-based PCIA on postoperative sleep remain poorly characterized. Recent advances in wearable devices demonstrate strong agreement with polysomnography (PSG) in intergroup comparisons of sleep efficiency and total sleep time, enabling continuous, non-invasive, multi-night sleep monitoring and offering a viable alternative for clinical postoperative sleep research. Hence, we design this clinical trial to compare postoperative sleep efficiency between patients receiving oxycodone-based versus sufentanil-based PCIA under wearable sleep monitoring. Methods This study is a randomized, double-blind, placebo-controlled trial that was conducted at a single center. A sample size of 68 patients was determined through calculation, and these patients will be randomly assigned to either the oxycodone group or the sufentanil group. Sleep monitoring was initiated using a wristband device one day before surgery after recruitment. The sleep quality data at different setting time will be monitored. All patients will be followed up by blinded evaluators at baseline and 1, 2, and 30 days after the intervention. The follow-up included pain scores, postoperative complications and adverse events, etc. Discussion By integrating a modern photoelectric device with first-line analgesics, we hope the result of the study will inform perioperative sleep management, guide clinical analgesic selection, and improve patient recovery quality.

Abstract Background: Pediatric respiratory infections are a leading cause of morbidity and mortality globally, representing a major health challenge in children. Research Gap: Despite extensive studies on epidemiology, clinical management, and specific pathogens, no bibliometric analysis has systematically evaluated the most influential research in this field. Objectives: This study aimed to evaluate the characteristics of the top 50 most-cited articles on pediatric respiratory infections and to identify emerging research trends. Methods: The Web of Science database was searched without publication year restrictions. Independent reviewers screened studies based on predefined inclusion and exclusion criteria. Data were extracted using a standardized form, including study details. Results: The 50 most-cited articles ranged from 34 to 384 citations and showed a right-skewed distribution with a sharp drop after the top ten. Publication years ranged from 1978 to 2021, with over half published in the 2010s. Articles appeared in 31 journals, with Pediatrics contributing five. Leading countries were the United States (18%), China (12%), and Canada (10%), with research largely concentrated in high-income regions and limited multicenter collaboration. Cohort studies dominated (66%), while randomized trials (12%) and reviews/meta-analyses (16%) were less common. Research clustered around three themes: clinical outcomes (e.g., pneumonia, bronchiolitis); viral etiology/diagnostics (e.g., RSV, SARS-CoV-2); and antimicrobial stewardship. Conclusion: Over the past decades, pediatric respiratory infection research has developed but remains unbalanced, relying heavily on observational evidence from high-income countries, with limited randomized trials, systematic reviews, multicenter collaborations, and LMIC-led studies. These findings provide insights that may direct researchers to identify potential focal points and guide future research in the field.

Introduction Recent respiratory illness, especially influenza, may trigger acute cardiac events via elevated inflammatory mediators. During the 2018 influenza season in Bangladesh, this study examined whether recent acute clinical respiratory illness (CRI) or laboratory-confirmed influenza was associated with elevated hs-CRP and IL-6, linked to acute cardiac events. Methods A total of 139 participants aged [&ge;]40 were recruited from a Dhaka cardiac hospital: 70 with acute myocardial infarction (AMI), 30 with other acute cardiac events, and 39 healthy individuals. CRI was defined as fever with cough and/or respiratory symptoms within seven days. Respiratory swabs were tested for influenza, and blood was analyzed for hs-CRP and IL-6. Results Median hs-CRP and IL-6 were higher in participants with CRI or influenza but not significantly. Cardiac patients had elevated hs-CRP (9.98 mg/L in other cardiac; 4.86 mg/L in AMI vs. 1.73 mg/L in healthy) and IL-6 (0.1 pg/mL in other cardiac; 0.145 pg/mL in AMI vs. 0.08 pg/mL in healthy) (p<0.001). CRI was not significantly associated with elevated hs-CRP or IL-6, though influenza in healthy participants was linked to higher IL-6. Cardiac patients had a higher risk of hs-CRP [&ge;]3 mg/L and elevated IL-6. Conclusion Cardiac patients showed significantly increased inflammatory markers, but CRI was not clearly linked to inflammation. Further research should assess biomarker utility for early cardiac risk.

Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

Abstract Objective. To determine the incidence and identify independent clinical predictors of emergence delirium (ED) in children aged 2-12 years. Material and methods. A prospective observational study included 56 children aged 2-12 years undergoing elective surgery under general anaesthesia. Preoperative anxiety (m-YPAS), induction behaviour (4 point scale), anaesthesia duration, opioid use, and postoperative pain (FLACC) were assessed. ED was diagnosed when the maximum PAED score was [&ge;]12. Results. The incidence of ED was 55.4% (31/56). Univariate analysis with false discovery rate (FDR) correction identified significant associations with ED for anaesthesia duration (q=0.002), induction behaviour (q=0.007), and surgery type (q=0.027). Multivariable logistic regression revealed three independent predictors: induction behaviour (category 3 vs 1) - odds ratio (OR) 14.2 (95% CI 2.6-78.1); anaesthesia duration (per minute) - OR 1.07 (95% CI 1.02-1.13); opioid use - OR 12.1 (95% CI 1.3-113.0). The model showed good discriminatory ability: area under the ROC curve (AUC) = 0.83 (95% CI 0.72-0.94). Conclusion. Emergence delirium in children aged 2-12 years without pharmacological premedication occurs in 55.4% of cases. The strongest independent predictors are adverse induction behaviour, longer anaesthesia duration, and intraoperative opioid use. The derived model can be used for personalised risk stratification of ED. Keywords: emergence delirium; children; risk factors; PAED; prediction model.

Background: Post-dural puncture headache (PDPH) affects up to 11.2% of patients after neuraxial anesthesia. The sphenopalatine ganglion block (SPGB) is a promising minimally invasive intervention, but high-quality randomized trial data are limited. We conducted a pilot randomized controlled trial to assess feasibility and inform a future definitive trial. Methods: Twenty-six patients with PDPH following accidental dural puncture with 17G Tuohy needles were randomized to conservative management (bed rest, hydration) or SPGB (bilateral intranasal 2% lidocaine). Primary outcomes were feasibility (recruitment, retention, protocol adherence). Secondary outcomes included pain intensity (Numeric Rating Scale, NRS 0-10) at 30 minutes, 12 hours, and 24 hours; rescue analgesia requirements; mobilization time; and adverse events. Results: Feasibility was confirmed: 100% recruitment of target sample, 100% retention, 100% protocol adherence. At 30 minutes, all SPGB patients reported complete pain resolution (NRS=0) versus median NRS 3 (IQR 2) in controls (p<0.001), though this finding is limited by lack of blinding and baseline assessment. No SPGB patients required rescue analgesia or experienced adverse events. Conservative group patients had prolonged hospitalization (46%). Sample size calculation for a definitive trial (90% power, =0.05) yields 120 participants (60/group). Conclusions: A definitive RCT comparing SPGB to conservative management for PDPH is feasible. Preliminary efficacy data suggest rapid analgesia with SPGB, but rigorous confirmation in a sham-controlled trial is required. Trial registration: ClinicalTrials.gov -NCT07494383 (retrospectively registered). Keywords: Post-dural puncture headache, sphenopalatine ganglion block, pilot study, feasibility, regional anesthesia, randomized controlled trial

Background: Platinum-based chemotherapy is known to cause severe and debilitating hearing loss, but unlike cisplatin, the true incidence of carboplatin-induced hearing loss remains unclear. We evaluated functional hearing outcomes in children receiving carboplatin to determine the incidence and severity of ototoxicity. Procedure: We identified a large cohort of children with cancer treated with carboplatin and graded their audiograms using the SIOP ototoxicity scale. Patients with inadequate audiological follow-up, prior hearing loss, or exposure to cisplatin were excluded. Fishers exact test, logistic regression, and ROC analyses were performed to investigate associations of demographic, treatment, and exposure-related risk factors with incidence of hearing loss. Results: 200 patients were included, all of whom had been treated with carboplatin. Only nine (4.5%) patients developed clinically significant hearing loss (SIOP grade [&ge;]2). Younger age at first exposure to carboplatin was the only significant predictor of hearing loss (OR = 0.7888, p=0.0241). Age [&le;]28 months was significantly associated with hearing loss (OR 12.37, p=0.0042). No other risk factors or exposures were statistically significant. Conclusions: Clinically significant carboplatin-associated hearing loss was uncommon (incidence 4.5%). We show that young age is the single-most important risk factor for hearing loss; of nine children who developed hearing loss, eight were aged [&le;]28 months. Children below this age have twelve-fold higher odds of developing hearing loss compared to those above this age (OR 12.37). These findings will allow physicians to provide more appropriate counselling to families regarding ototoxic risk and support intensified hearing surveillance in young children.

Background: Orthopedic surgeries are associated with significant intraoperative and postoperative pain, necessitating effective anesthesia strategies. Spinal anesthesia is commonly used for lower limb procedures due to its rapid onset and reliability; however, its limited duration may compromise prolonged surgical procedures and early postoperative pain control. Adjuvants such as dexamethasone have been explored to enhance and prolong the effects of local anesthetics. While evidence supports its efficacy, data from low-resource settings remain limited. Objective: To assess the effect of intrathecal dexamethasone as an adjuvant to bupivacaine on sensory block duration, time to first postoperative analgesia, and postoperative pain in patients undergoing lower limb orthopedic surgery at KCMC. Methodology: A randomized, double-blind controlled trial was conducted among 96 adult patients undergoing elective lower limb orthopedic surgery under spinal anesthesia. Participants were allocated using a computer-generated randomization sequence to receive either bupivacaine 15 mg with dexamethasone 4 mg (intervention group) or bupivacaine 15 mg with 1 ml normal saline (control group). Outcomes included sensory and motor block duration, time to first postoperative analgesia, and postoperative pain scores. Results: The dexamethasone group demonstrated a significantly prolonged sensory block duration (231 +/- 6 vs. 156 +/- 9 minutes; mean difference 75.11 minutes, 95% CI: 71.92-78.29; p < 0.001) and delayed time to first postoperative analgesia (252 +/- 7 vs. 181 +/- 7 minutes; mean difference 71.89 minutes, 95% CI: 68.91-74.86; p < 0.001). Motor block duration was also significantly longer (184 +/- 7 vs. 130 +/- 5 minutes; mean difference 53.42 minutes, 95% CI: 50.99-55.85; p < 0.001). Postoperative pain scores were significantly lower at 1 hour (mean difference -1.29 points, 95% CI: -1.52 to -1.05; p < 0.001) and at 2 hours (mean difference -1.97 points, 95% CI: -2.21 to -1.73; p < 0.001). Intraoperative opioid and benzodiazepine use were significantly reduced in the intervention group. Conclusion: The addition of intrathecal dexamethasone to bupivacaine significantly enhances sensory block duration, delays postoperative analgesia need, and improves early pain control. These findings support its use as a potentially practical adjuvant in resource-limited settings.

ObjectiveTo assess the prevalence, determinants, and health associations of vitamin D deficiency among workers in Cikarang, Indonesia. MethodsCross-sectional study of 107 workers. Serum 25(OH)D was measured by ECLIA; deficiency was <20 ng/mL. Data included demographics, occupation, sun exposure, diet, anthropometry, laboratory parameters, and self-reported health. Analyses used t-test/Mann-Whitney U, chi-square, and multivariable regression. ResultsDeficiency was prevalent (57.9%; median 18.6 ng/mL). Males had higher levels (+7.60 ng/mL) and lower risk (OR 8.56), while younger age (<38.5 years) showed lower levels (-5.60 ng/mL) and higher risk (OR 4.73; all p<0.0001). Greater sun exposure increased levels, whereas sunscreen use and greater clothing coverage reduced them. Only sex and age remained significant. ConclusionVitamin D deficiency is common, especially among female and younger workers, with modifiable sun-avoidance behaviors contributing. LEARNING OUTCOMESO_LISummarize the prevalence and key determinants of vitamin D deficiency among industrial workers in equatorial Indonesia, contributing to limited occupational health data in this setting. C_LIO_LIHighlight the role of modifiable behaviors--particularly sun exposure and sun-avoidance practices--in influencing vitamin D status among workers. C_LIO_LIEmphasize the need for targeted workplace interventions, including safe sun exposure strategies and nutritional support, especially for high-risk groups such as female and younger workers. C_LI

Background. Lung metastases in osteosarcoma (OS) are the main cause of the death. The accuracy of the diagnosis of nodules by computed tomography (CT) of the lungs is critically important for determining the disseminated stage of the disease and planning surgical treatment. The use of artificial intelligence (AI) in the search for lung nodules increases the accuracy of diagnosis and reduces the chance of missing metastases. Objective: to evaluate the accuracy of lung nodules diagnosis in adolescents with OS using AI. Methods. A retrospective assessment of CT scans of adolescents with OS was performed. A pathological nodule with an average size of [&ge;]4 mm was considered a target finding. The diagnostic accuracy of an AI algorithm previously trained on an adult dataset was evaluated, and the number of false positives (FP) and false negatives (FN) was determined. Sensitivity, specificity, accuracy, area under the ROC curve (AUC), positive predictive value, negative predictive value, and F1-measure were calculated. Based on the obtained results, the effectiveness of the algorithm was assessed. Results. 248 CT scans of adolescents with OS were evaluated. The following results were obtained: in 5 cases, the AI algorithm showed a FP result (2.02%), in 34 cases, it showed a FN result (13.71%), and in 209 cases, a correct result (both true positive and true negative) (84.27%). The diagnostic accuracy of the algorithm was 0.843 (95% CI 0.794-0.887). The application of the AI algorithm in the practice of an X-ray doctor in a specific clinical task would allow to increase the sensitivity from 0.805 to 0.891, while ensuring an absolute decrease in the number of FN results by 8.59% and a relative decrease by 44%. Conclusion. The obtained results confirm the practical value of the application of the AI algorithm and justify the implementation of AI-assisted systems in the diagnostic protocols for lung metastases in adolescents with OS.

Background Bystander automated external defibrillator (BAED) use improves out-of-hospital cardiac arrest (OHCA) outcomes but remains uncommon globally. This study evaluated the outcomes of Singapore's 11-year public-access AED expansion and volunteer-responder implementation in terms of trends in BAED use, associated factors, and clinical outcomes. Methods This population-based, retrospective cohort study used Singapore Pan-Asian Resuscitation Outcomes Study (SG-PAROS) data (2010-2020) for adult, non-traumatic OHCAs. The primary outcome was bystander AED application. Multivariable logistic regression identified factors associated with use. Secondary outcomes included favorable neurological status (CPC 1-2), survival to discharge, and prehospital return of spontaneous circulation (ROSC). Results Of 21,439 included OHCA cases (median age 70.0 years; 63.8% male), BAED use increased from 1.7% to 9.6% over 11 years, with a corresponding increase in overall survival from 2.4 to 4.0%. Malay ethnicity (aOR 1.25, 1.06-1.49), calendar year (aOR 1.26, 1.22-1.29), and delayed emergency medical services (aOR 1.24, 1.06-1.45) were positive predictors of BAED use. Conversely, BAED use was lower among females (aOR 0.80, 95% CI 0.69-0.94), at night (aOR 0.69, 0.56-0.86), and in residential settings (aOR 0.06, 0.05-0.07). Volunteer arrival strongly increased application (aOR 4.16, 3.41-5.09), with a significant interaction (p<0.001); the effect was greater in residential (aOR 7.38, 5.81-9.38) than non-residential settings (aOR 1.71, 1.22-2.40). AED use predicted favorable neurological outcome (aOR 2.80, 2.24-3.50; NNT 8.7), survival (aOR 2.30, 1.89-2.80), and ROSC (aOR 2.11, 1.81-2.46). Conclusion Over 11 years, we saw a significant increase in BAED application and favorable neurological survival. This success was associated with the implementation of an integrated strategy combining widespread AED deployment, national training, and smartphone-activated volunteer responders. Singapore's experience provides a scalable model for urban centers seeking to expand their AED strategy.

Spinal fractures are an important contributor to disability worldwide, particularly in aging populations. However, comprehensive long-term comparisons between China and other major economies remain limited. Using data from the Global Burden of Disease (GBD) 2021 study, we analyzed temporal trends in the incidence, prevalence, and years lived with disability (YLDs) of spinal fractures in China and the overall G20 from 1990 to 2021. Age-standardized rates were assessed using Joinpoint regression and age-period-cohort analysis. Future burden through 2050 was projected using autoregressive integrated moving average modeling, and decomposition analysis was performed to quantify the contributions of demographic and epidemiological factors. Between 1990 and 2021, China experienced substantial increases in absolute burden. Incident cases increased by 52.27%, prevalent cases by 113.66%, and YLDs by 107.21%. The age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) increased significantly, whereas the age-standardized incidence rate (ASIR) showed a non-significant upward trend. In contrast, the overall G20 aggregate showed increasing absolute case numbers but significantly declining age-standardized rates. Age-period-cohort and age-specific analyses indicated that older adults represented the main burden-bearing population. Projections suggested that Chinas ASIR may decline by 2050, whereas prevalence and YLD burden, particularly among males, may remain relatively high compared with the overall G20 level. Decomposition analysis identified population aging as the major driver of burden growth. China experienced a rising burden of spinal fractures over the past three decades, in contrast to declining age-standardized trends in the overall G20 aggregate. These findings highlight the substantial role of population aging in shaping spinal fracture burden and provide epidemiological evidence for prevention planning and aging-related health policy.

Background: The quality of palliative care in non-designated cancer hospitals, where approximately 70% of deaths of patients with cancer occur, remains unevaluated. This study aimed to clarify the quality of palliative care in these hospitals by comparing patient characteristics and evaluating the quality of palliative care provided by bereaved families. Methods: A questionnaire survey was conducted among bereaved family members of patients with cancer who died in 2018 at designated and non-designated cancer hospitals (excluding palliative care units). We compared the two groups regarding patient and bereaved family characteristics, quality assessment of palliative care (including Memorial Symptom Assessment Scale [MSAS]), care satisfaction, and the presence of end-of-life discussions. Results: In total, 27,944 bereaved family members agreed to participate. The mean age at death was 73.2 ({+/-}11.9) and 79.7 ({+/-}10.9) years for designated and non-designated cancer hospitals, respectively (p < 0.001, Effect Size [ES] = 0.55). The mean MSAS total score (symptom intensity) was significantly higher for designated cancer hospitals than for non-designated cancer hospitals, even after adjusting for patient characteristics (p < 0.001, ES = 0.39). Conversely, the mean adjusted overall satisfaction was significantly higher in non-designated cancer hospitals (p < 0.001, ES = 0.21) than in designated cancer hospitals. Conclusions: Non-designated cancer hospitals had older and less symptomatic patients than designated cancer hospitals. However, there was no significant clinical difference in the quality of palliative care, as assessed by the bereaved families.

Background Sierra Leones neonatal mortality rate is among the highest in the world. Koidu Government Hospital opened a Special Care Baby Unit (SCBU) in 2020. To increase knowledge of the SCBU health care providers (HCPs), a neonatal curriculum was implemented to facilitate HCP education on management of neonatal conditions. The aim of this study was to understand the effect of the curriculum on knowledge acquisition and the perception of the teaching methodologies among participating HCPs. Methods US-based mentors facilitated a two-phase, flipped classroom, virtual neonatal medicine curriculum between October 2024 and April 2025, followed by one-week in-person education sessions with SCBU HCPs. With each phase, participants completed pre- and post-test educational assessments. At the end of the curriculum, they completed a subjective assessment to capture perceptions related to the quality of teaching methodologies integrated within the curriculum. Wilcoxon signed rank test was used to assess pre- versus post-test change. Descriptive statistics were used to analyse the subjective assessment. Results Thirty-eight participants completed the educational assessments, 30 (79%) took all four pre- and post-tests; 25/38 (65.8%) were female, 27 (71.1%) were nurses. Median correct answers for both phases increased from the pre- to post-test for individual learners [Phase 1, pre-test 14/27 (51.9%), post-test 23/27 (85.2%), p<0.001], [Phase 2, pre-test 14/25 (56.0%), post-test 23/25 (92.0%), p <0.001]. Thirty-one participants completed the subjective assessment, of whom 96.8% (30/31) rated the curriculum to be "very effective." All 31 participants indicated that the in-person instruction was "very helpful." Through open text responses, they offered valuable insight into challenges, strengths, and next steps. Conclusion This neonatal curriculum resulted in significantly increased knowledge and was well regarded. Adapting this curriculum or similar curricula show promise to improve the quality of care for small and/or sick neonates in low resource settings.

BackgroundDichapetalin M (Dic M), an active compound extracted from medicinal plants in the Dichapetalum genus, has been previously shown to possess anti-proliferative activity against cancer cell lines. However, the specific mechanism through which it exerts its anticancer effects remains unknown. PurposeThis study focused on elucidating the mechanism of action of dichapetalin M to further explore its potential as a therapeutic agent for resistant and metastatic breast cancer. MethodWe confirmed the Estrogen Receptor (ER) as a target of Dic M, using an in vitro approach. Furthermore, we examined both the apoptotic and migrastatic effects of dichapetalin M by assessing its impact on the expression of key apoptosis-related and cancer cell migration genes. Finally, we evaluated the compounds effect on Multi-drug Resistance Gene MDR1 expression, a gene linked to cancer drug resistance. ResultsOur target validation experiments demonstrated that Dic M exhibited considerably higher cytotoxicity in ER-positive breast cell lines compared to ER-negative cell lines. Furthermore, treatment of MCF-7 cells (which are ER-positive) with Dic M led to a dose-dependent increase in AREG (amphiregulin), a downstream effector of the Estrogen Receptor. Additionally, Dic M inhibited actin polymerization and significantly downregulated genes involved in the turnover of actin monomers. Scratch-wound assay results further demonstrate that Dic M reduces the rate of cell migration, although its impact on EMT-related gene expression was only observed at high doses. Additionally, Dic M treatment in MCF-7 cells resulted in a significant decrease in the expression of pro-apoptotic genes and MDR1 expression. ConclusionsThese findings indicate that Dic M likely interacts with the Estrogen Receptor and employs the apoptotic pathway to exert its cytotoxic and anti-proliferative effects. Dic M exhibits promising potential, such as anti-migrastatic properties and downregulation of a key breast cancer resistance gene, warranting further investigation.

Background: The determinants of immunoglobulin E (IgE) remain poorly understood in older adults, a population with an increasing burden of chronic diseases. Identifying IgE's determinants may improve its clinical interpretation in the evaluation of allergic and IgE-related conditions. Objective: To investigate age, sex, smoking, alcohol, body mass index (BMI), corticosteroid use, and season as potential determinants of total IgE (tIgE) and inhaled allergen-specific IgE (sIgE). Methods: Using Rotterdam Study data, we investigated the determinants of tIgE and sIgE using multivariable linear regression. Longitudinal changes and the effects of corticosteroids were assessed with linear mixed models. Results: We included 8769 participants, of which 478 had repeated IgE measurements. Age showed a U-shaped relationship with tIgE and L-shaped relationship with sIgE (both p<0.001). Women had lower tIgE (OR [95%CI]: 0.69 [0.65-0.74]), whereas current smokers (1.34 [1.23-1.46]), higher BMI (1.01 [1.01-1.02]), topical corticosteroid users (1.27 [1.07-1.50]) and inhaled corticosteroid users (1.93 [1.64-2.26]) showed higher tIgE. Women (0.96 [0.92-1.00]), former smokers (0.87 [0.83-0.91]) and current smokers (0.72 [0.68-0.76]) had lower sIgE, whereas topical corticosteroid users (1.20 [1.07-1.35]) and inhaled corticosteroid users (1.20 [1.07-1.35]) showed higher sIgE. Over time, tIgE and sIgE decreased (p<0.001) but did not significantly change after corticosteroid use. Conclusion: We identified age, sex, smoking, BMI, season and topical and inhaled corticosteroids as determinants of tIgE and sIgE. Incorporating these determinants may improve IgE's clinical interpretation for the diagnosis and management of allergic and IgE-related conditions. Future research should investigate how these determinants shape IgE's relationship with chronic diseases in aging populations.

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype lacking well-defined molecular targets, leaving chemotherapy as the primary treatment despite drug resistance, systemic toxicity, and high recurrence rates. Therefore, the development of effective and less toxic therapeutic agents is essential. This study investigated the anti-cancer potential of gloriosine, a bioactive alkaloid with antiproliferative activity and low toxicity toward normal breast cells. MethodsPotential targets of gloriosine were predicted using SwissTargetPrediction, TargetNet, and PharmMapper, and overlapping genes related to TNBC and glutamine metabolism were selected. Protein-protein interaction networks, Gene Ontology, and KEGG pathway enrichment analyses were performed. Molecular docking evaluated binding affinity, followed by in vitro validation using cell viability, colony formation, and wound healing assays. ROS levels were measured by DCFDA and GSH assays, and ferroptosis was assessed by Western blot and FerroOrange staining in MDA{square}MB{square}231 cells. ResultsA total of 100 potential targets were identified, with 60 overlapping with TNBC and glutamine metabolism-related genes. Key targets included SRC, EGFR, mTOR, and HSP90AA1. Enrichment analyses indicated involvement in cancer progression, metabolic regulation, and resistance pathways, including central carbon metabolism, EGFR inhibitor resistance, and ErbB signaling. Gloriosine showed strong binding affinity toward hub targets. Experimental studies confirmed concentration-dependent inhibition of cell proliferation and migration. Mechanistically, gloriosine suppressed glutamine metabolism via GLS1 downregulation and induced ferroptosis, evidenced by increased ROS, glutathione depletion, GPX4 downregulation, and elevated intracellular iron levels. ConclusionsGloriosine exerts significant anti-cancer effects in TNBC through multi-target modulation and induction of ferroptosis, highlighting its potential as a promising therapeutic candidate. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/725321v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@ce0ebcorg.highwire.dtl.DTLVardef@29603borg.highwire.dtl.DTLVardef@6d0025org.highwire.dtl.DTLVardef@249700_HPS_FORMAT_FIGEXP M_FIG C_FIG Flow chart of the network pharmacological and in vitro study of gloriosine

Introduction: Stroke care is time-sensitive, yet patients in low-resource settings may reach tertiary services only after passing through multiple formal and informal care options. This study examined documented care-seeking pathways and time to presentation among stroke cases recorded at the University of Medical Sciences Teaching Hospital (UNIMEDTH), Ondo State, Nigeria. Methods: A retrospective hospital record review was conducted using secondary data from the Stroke Registry, radiology department records, referral notes, and ambulance records at UNIMEDTH. The analysis included 371 stroke cases with documented time from symptom onset to UNIMEDTH presentation and reconstructable care pathways. First-contact routes were classified as hospital/biomedical, self/informal or traditional/faith-based care, and the number of documented steps defined pathway complexity before and including tertiary presentation. Frequencies and percentages described pathway patterns; median presentation times were compared using Mann-Whitney U and Kruskal-Wallis tests. Results: The median time to tertiary presentation was 24 hours (interquartile range [IQR] 9-72), and 317 patients (85.4%) presented after four hours. Only 30 patients (8.1%) presented directly to UNIMEDTH; 44 distinct care-pathway sequences were recorded. Hospital-facility first contact was documented for 81 patients (21.8%). It was associated with a median presentation time of 3 hours (IQR 2-6), compared with 48 hours (IQR 24-72) among patients whose initial contact was outside a hospital facility (U = 699.50, p < 0.001). The median time also differed across grouped first-contact categories and pathway complexity levels (both p < 0.001). Conclusion: Non-hospital or multi-step care-seeking pathways commonly preceded tertiary stroke presentations in this setting. The findings indicate that delayed tertiary arrival is partly embedded in the pathway followed after symptom onset. Interventions should combine public recognition of stroke warning signs with urgent referral linkages involving hospitals, patent medicine vendors, traditional and faith-based providers, and emergency transport systems.

Background: The Colour Blind Quality of Life Scale (CBQoL) is a questionnaire developed to assess the quality of life of individuals with congenital colour vision deficiency (CVD). This study aimed to translate the English version of the CBQoL into Vietnamese and evaluate the validity and reliability of the Vietnamese version (CBQoL-VN). Methods: A forward-backward translation method was performed to produce the Vietnamese text. Content validity was assessed by six experts in vision care. Reliability testing involved 30 participants with congenital CVD, while discriminant validity was evaluated by comparing this group against 30 participants with normal colour vision. Results: Following expert consensus, two items were removed and one transportation-related item was added. The content validation index (CVI) values of 1.0 for relevance, clarity, and understandability indicated excellent content validity. Internal consistency was high, with a Cronbach's alpha of 0.95 for the full scale. Discriminant validity analysis showed that participants with congenital CVD scored significantly lower across all CBQoL-VN domains compared to those with normal colour vision. Conclusions: The modified CBQoL-VN is a valid and reliable instrument for assessing the quality of life of individuals with congenital CVD in the Vietnamese population.

PurposeGlasdegib is a Sonic Hedgehog (SHH) pathway inhibitor used for treating newly diagnosed acute myeloid leukemia in elders or patients unfit for intensive chemotherapy. This study sought to demonstrate growth inhibition and increased apoptosis of B-cell acute lymphoblastic leukemia (B-ALL) in vitro under glasdegib, alone and combined with inotuzumab, using a novel co-culture system and validated chemosensitivity testing model to determine whether glasdegib with and without inotuzumab may represent a promising treatment strategy in B-ALL. MethodsSeven blood and marrow samples from B-ALL patients were co-cultured with HS-5 stromal cells in a co-culturing system designed to mimic the tumor microenvironment to maintain B-ALL cell viability for chemosensitivity testing under glasdegib and inotuzumab. ResultsCo-culturing improved B-ALL viability from four to nine days. Dosage-dependent responses to glasdegib were consistent among B-ALL samples on day four based on culture viability, and varied based on expressions of SSH genes GLI1, GLI3, SMO, and PTCH1. Combination with inotuzumab had varied effects on treatment response. ConclusionCo-culturing B-ALL cells with HS-5 stromal cells improves B-ALL growth and viability. Glasdegib with and without inotuzumab treatments impact the viability of co-cultured B-ALL cells by day four. SHH gene expressions suggest different B-ALL patients may be sensitive or resistant to glasdegib and inotuzumab.