Search Results (3,123)

Background: This study described real-world patterns of intravenous magnesium sulfate (MgSO₄) use among children hospitalized with asthma exacerbations, including how MgSO₄ use related to markers of exacerbation severity and to hospital length of stay (LOS). Because treatment was not randomized, this design cannot isolate a causal effect of MgSO₄ on LOS; groups defined by MgSO₄ receipt differ systematically in baseline severity, and any LOS comparison must be interpreted as descriptive rather than causal. Methods: A retrospective cohort study was conducted on 423 pediatric patients admitted to King Abdullah Specialist Children’s Hospital, Riyadh, Saudi Arabia, between January 2021 and December 2025. Patients were categorized according to whether they received intravenous MgSO₄ during hospitalization. Demographic characteristics, clinical features, treatment variables, and outcomes were analyzed. Results: The median age was 4 years, with 63.8% of patients aged ≤ 5 years, and 60.8% were male. Common clinical findings included suprasternal indrawing (57%), scalene retractions (43.7%), and wheezing (91.5%). Decreased air entry was observed in 48.2% of patients, and 64.3% required oxygen support. Of the study population, 175 patients (41.4%) received intravenous MgSO₄. Administration of MgSO₄ was significantly more frequent among younger patients, males, patients with respiratory distress, decreased air entry, oxygen requirement, and lower oxygen saturation levels (all p < 0.05). Patients receiving MgSO₄ had a significantly longer median LOS compared with those who did not receive MgSO₄ (50.57 vs. 32.30 h, p < 0.001). Conclusions: Intravenous MgSO₄ administration was more commonly used among children with more severe asthma exacerbations and was accompanied by longer hospital LOS in this unmatched, non-randomized cohort. Because MgSO₄ receipt and LOS are both driven by underlying severity that was only partly captured by the available covariates, this design cannot distinguish a causal effect of MgSO₄ on LOS from confounding by indication, and the findings should be read as a descriptive account of real-world MgSO₄ use in severe pediatric asthma rather than as evidence for or against an effect of MgSO₄ on LOS. Full article

Peatlands, critical global carbon sinks, are facing increasing threats from climate change-driven heatwaves and droughts. These threats can cause a midday depression in carbon uptake through photosynthetic inhibition. Using high-temporal-resolution solar-induced chlorophyll fluorescence (SIF; ~30 s) and chamber-based CO₂ flux measurements, we investigated the coupling between SIF and gross primary production (GPP) during extreme events (air temperature > 25 °C and vapour pressure deficit > 15 hPa) in a northern peatland. Our results show that SIF tracks GPP closely under non-stress conditions (daily R² = 0.86–0.96). However, during combined heat and drought stress, midday correlations collapsed (Case A: R² = 0.04 on 27 June; Case B: R² = 0.15 and 0.01 on 29 and 30 June, respectively), indicating severe decoupling. Importantly, we discovered legacy effects from multi-day heat exposure: on 26 June, vegetation with prior cumulative stress (Case A) showed weak morning coupling (R² = 0.07), while vegetation without prior stress history (Case B) maintained strong coupling (R² = 0.93). This suggests that cumulative stress alters baseline physiology and can exacerbate midday mismatches; therefore, not just current condition controls photosynthetic regulation. These findings highlight limitations of SIF-based GPP estimation at sub-daily timescales during stress, particularly in heterogeneous peatland systems where canopy composition and physiological responses could vary among plant functional types. Full article

Infections caused by flaviviruses, including dengue virus (DENV), Zika virus (ZIKV), and West Nile virus (WNV), can lead to severe hemorrhagic or neurological disease. Antibody-dependent enhancement (ADE) remains a major obstacle to the development of safe flavivirus vaccines and antibody-based therapeutics. ADE includes ADE of infection, in which antibodies increase in viral entry, replication, or infection load, and ADE of disease, in which antibody-dependent inflammatory and immunopathological responses exacerbate disease severity. Previous reviews have largely addressed the general virological and immunological mechanisms of ADE, but few have integrated antibody isotypes and subclasses, Fc-region modifications, Fc receptor diversity, host FcγR polymorphisms, and complement activation within a translational framework. Consequently, how these factors jointly shape ADE of infection, progression to ADE of disease, and individual risk remains incompletely understood. Here, we synthesize evidence linking antibody properties, Fc receptor expression and signaling, FcγR genetic variation, and complement regulation to both forms of ADE. We then discuss how these findings can inform antigen selection, Fc engineering, complement-informed intervention, and systems serology-based risk stratification. By connecting mechanistic evidence with vaccine and therapeutic development, this review offers a framework for designing safer flavivirus interventions and advancing individualized assessment of ADE risk. Full article

Deoxynivalenol (DON) and patulin (PAT) are common mycotoxins in cereals and fruits, posing health risks for animals and human beings. In order to study their liver toxicity, 24 mice were randomly assigned to four groups, with six replicates in each group (one mouse per cage). The mice were intragastrically administered with DON, PAT, DON + PAT (DP), or without DON and PAT (the control group) for 28 days, respectively. The results showed that body weight gain was significantly reduced by all toxin treatments, compared with the control group, and the lowest body weight gain was observed in the DP group. Histopathology revealed that hepatocyte damage and inflammatory infiltration were more serious in the DP group, exhibiting the highest mRNA abundances of MyD88, IFN-γ, and JAK2. The severity of hepatocyte apoptosis induced in each group followed the order: DON > DP > PAT; the severity of oxidative stress was ranked as DP > DON > PAT. Transcriptomic analysis revealed that numerous differentially expressed genes were regulated by DP treatment, which were mainly enriched in the MAPK, JAK-STAT, and transforming growth factor (TGF)-β signaling pathways. In conclusion, individual exposure to DON or PAT triggered hepatic injury, and their co-exposure further exacerbated liver damage. Full article

Background/Objectives: Real-world evidence on dupilumab-induced clinical remission on treatment and on the predictors of complete response in severe uncontrolled asthma (SUA) is still limited. Methods: We conducted a single-centre ambispective uncontrolled observational study including 152 adults with SUA who started dupilumab. Lung function, type-2 (T2) biomarkers, patient-reported outcomes, exacerbations, oral corticosteroid (OCS) use, emergency-department (ED) visits and hospitalisations were compared between baseline and last follow-up. Response was graded with FEOS and EXACTO. Independent predictors of complete response (EXACTO = 1) were explored by multivariable logistic regression. Results: Mean age was 50 ± 12 years, 67.1% were women, baseline FEV1 was 82 ± 22% predicted, blood eosinophils were 612 ± 577 cells/µL and FeNO was 55 ± 46 ppb. After 21 ± 8 months, ACT improved from 15.7 to 23.3, ACQ-5 from 4.0 to 0.35, mini-AQLQ from 2.18 to 4.53, SNOT-22 from 52 to 16, and FEV1 by 275 ± 180 mL (all p < 0.001). Annual exacerbations decreased from 7.9 to 0.7, ED visits from 3.17 to 0.28, hospitalisations from 0.71 to 0.08, and maintenance OCS use from 11.8% to 3.9%. According to EXACTO, 95 patients (62.5%) achieved complete response/super-response. Independent predictors were higher baseline FEV1, higher eosinophil count, allergic rhinitis, rhinosinusitis with nasal polyps and atopic dermatitis, whereas prior OCS bursts and higher FeNO were inversely associated. Model discrimination was adequate (AUC = 0.91). Conclusions: Dupilumab achieved clinical remission on treatment in almost two-thirds of patients with SUA and markedly reduced healthcare utilisation. A T2-comorbidity-rich profile identified patients with the highest probability of complete response. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder influenced by environmental factors including cold stress. While cold exposure exacerbates intestinal inflammation, the specific microbial metabolites linking environmental stress to colitis remain unclear. 3-Hydroxypropionate (3-HPA) is a gut microbial metabolite elevated following cold exposure, but its pathogenic role in intestinal inflammation has not been investigated. This study aimed to determine whether 3-HPA contributes to colitis progression and to characterize its effects on gut microbiota and intestinal epithelial function. Methods: We employed a dextran sulfate sodium (DSS)-induced colitis mouse model to assess the impact of cold exposure and exogenous 3-HPA administration. Paired shotgun metagenomic and metabolomic analyses were performed to evaluate gut microbial composition and metabolic outputs. Mechanistic studies using NCM460 intestinal epithelial cells were conducted to examine mitochondrial respiration and tight junction integrity under nutrient-limited conditions. Results: Cold exposure increased fecal 3-HPA levels and aggravated DSS-induced colitis, characterized by enhanced weight loss, histological damage, and immune cell infiltration. Direct 3-HPA supplementation alone was sufficient to worsen colitis severity. Multi-omics profiling revealed that 3-HPA reshaped gut microbiota composition, depleted short-chain fatty acids (SCFAs), and disrupted microbial tryptophan and bile acid metabolism. In vitro, 3-HPA impaired mitochondrial oxidative phosphorylation, reduced ATP production, and compromised tight junction organization in intestinal epithelial cells. Conclusions: These findings identify 3-HPA as a gut microbial metabolite elevated by cold exposure that contributes to colitis progression by disrupting beneficial microbial metabolism while also impairing epithelial mitochondrial function and barrier integrity. Modulating 3-HPA production or its downstream epithelial effects may represent a potential therapeutic approach for IBD exacerbated by environmental stress. Full article

Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of seasonal influenza vaccination against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Methods: We conducted a nationwide retrospective test-negative design study using administrative healthcare data from the National Health Security Office linked with laboratory-confirmed influenza surveillance data between 1 June 2013 and 31 May 2025, covering twelve influenza seasons (2013–2024). COPD-related clinical episodes among patients aged ≥40 years who presented with pneumonia or acute exacerbation of COPD and underwent RT-PCR testing for influenza were included. Modified Poisson regression with cluster-robust standard errors was used to estimate adjusted risk ratios (RRs), and VE was calculated as (1 − adjusted RR) × 100. Results: A total of 606,072 COPD-related clinical episodes were included, of which 192,224 (31.7%) were influenza-positive. The overall adjusted VE against influenza-associated pneumonia was 55.9% (95% CI: 47.3–63.1), while VE against influenza-associated COPD exacerbations was 67.0% (95% CI: 48.8–78.8). VE estimates were broadly similar across age groups and consistent across COPD severity strata. Conclusions: Seasonal influenza vaccination was associated with substantial protection against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Full article

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with substantial morbidity and mortality, highlighting the need for simple and reliable biomarkers for early risk stratification. The C-reactive protein to albumin ratio (CAR) and the modified Glasgow Prognostic Score (mGPS) reflect systemic inflammation and nutritional status, but their prognostic value in hospitalized patients with AECOPD remains incompletely defined. This study aimed to evaluate the associations of CAR and mGPS with one-year mortality and indicators of disease severity in hospitalized patients with AECOPD. Methods: In this retrospective single-center cohort study, 1556 adult patients hospitalized with a primary diagnosis of AECOPD between January 2020 and January 2026 were included. Patients with concomitant pneumonia and other major inflammatory conditions were excluded. Demographic, clinical, laboratory, arterial blood gas, and pulmonary function data were retrospectively analyzed. CAR was calculated from admission C-reactive protein and serum albumin levels, whereas mGPS was determined according to established criteria. Independent predictors of one-year mortality were identified using multivariable logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminatory performance of CAR. Results: During the one-year follow up, 140 patients (9.0%) died. Compared with survivors, non-survivors had significantly higher CRP levels, higher CAR values, lower serum albumin levels, more severe hypercapnia and acidosis, and higher rates of intensive care unit admission and invasive mechanical ventilation (all p < 0.001). The distribution of mGPS differed significantly according to mortality status, with patients in the mGPS 2 category exhibiting the highest mortality rates (p < 0.001). After adjustment for clinically relevant covariates, age, acidosis, invasive mechanical ventilation, and CAR remained independently associated with one-year mortality. CAR demonstrated excellent discriminatory performance for predicting one-year mortality (AUC 0.907, 95% CI 0.893–0.922; p < 0.001), with an optimal cut-off value of >3.96, yielding 98.6% sensitivity and 84.3% specificity. Increasing mGPS scores were associated with progressively worse clinical outcomes, including higher rates of intensive care unit admission, invasive mechanical ventilation, in-hospital mortality, and one-year mortality. Conclusions: Inflammation and nutrition-based biomarkers are closely associated with disease severity and one-year mortality in hospitalized patients with AECOPD. CAR remained an independent predictor of one-year mortality and demonstrated excellent discriminatory performance, supporting its role as a simple and readily available complementary biomarker for prognostic assessment. Increasing mGPS scores were associated with progressively worse clinical outcomes, suggesting that mGPS may also contribute to risk stratification in hospitalized patients with AECOPD. Prospective multicenter studies with external validation are warranted to confirm these findings and to further define the prognostic value of these biomarkers. Full article

Acne vulgaris is a chronic inflammatory skin disease associated with a substantial psychological burden that may extend beyond visible lesions and objective disease severity. Psychological factors such as stress, coping strategies, quality-of-life impairment, self-esteem, psychiatric symptoms, and treatment adherence are associated with disease perception, self-reported exacerbation, and treatment-related outcomes. This narrative review examines psychological stress and proposed biological mechanisms, coping strategies, treatment adherence, quality of life, self-esteem, sleep disturbance, and psychiatric comorbidity in people with acne. Relevant literature was identified through MEDLINE/PubMed, Scopus, Web of Science, and PsycINFO; the final literature search was conducted on 29 May 2026. Acne-specific studies were prioritized, with broader psychodermatology evidence used where acne-specific data were limited. The psychosocial burden of acne is individualized and only partly aligned with clinician-rated severity, supporting person-centered assessment. For each domain, the review outlines brief, commonly used screening instruments that may be feasible in routine dermatology. Incorporating psychological assessment and targeted supportive strategies into acne care may contribute to quality of life, adherence to therapy, and patient-centered care. The evidence is predominantly cross-sectional and derives from heterogeneous populations, instruments, and study designs, limiting causal inference. Full article

This paper investigates nanoparticle emissions from older diesel passenger cars in four European countries outside of PTI (periodic technical inspection) testing facilities, using a methodology similar to that of the PTI. Per opportunistic sampling and voluntary testing, 618 diesel cars with an average mileage of 163,348 km were measured between 2020 and 2022 on the streets around university campuses and in public areas in Brussels (Belgium), Aveiro (Portugal), Belgrade (Serbia) and Birkenfeld (Germany). Through subsequent research, 109 vehicles were found not to be equipped with a diesel particulate filter (DPF) and were separated. Portable nanoparticle detectors were used to measure PN emissions in a PTI-like approach at low idle. From the 509 analysed diesel cars equipped with DPF, a high share of 31% revealed PN tailpipe concentrations of over 250 kP/cm³ and would therefore have failed the PTI established in Germany. That rate is 2–9 times higher than that found in Belgian and German PTI PN measurements, possibly caused by the fact that vehicles are serviced immediately before the PTI. Moreover, 45% of all tested diesel cars with DPF emitted concentrations higher than 20 kP/cm³. This level was found, both in the literature and in our measurements, to be indicative of a DPF operating outside its normal performance range, taking into account the measurement uncertainty. Even among relatively new vehicles with DPF (up to mileages of 180,000 km), 13% emitted as much PN as diesel cars without DPF (1000 kP/cm³ or more). In Portugal and Serbia, a higher share of cars showed elevated emissions compared to Germany and Belgium. DPF technology can in principle greatly reduce particle emissions of diesel cars. However, its efficiency degrades with time and vehicle mileage. Several factors leading to higher PN emissions have been reported; however, they cannot be discriminated in the results. This is primarily because active filter regeneration generates particle emission peaks every several 100 km, which were found to be up to four orders of magnitude higher than normal. Within the fleet on the streets, up to 4% of all diesel cars equipped with a modern DPF can be found in active regeneration mode. While at present politics and carmakers focus on electrifying the new vehicle generation, the emission problem of around 69 million diesel cars with elevated PN emissions on European streets remains unresolved so far. In European countries with a particularly high share of diesel cars, an old vehicle fleet, and a low income level, emission problems may be exacerbated. Full article

Background: Chronic obstructive pulmonary disease (COPD) disproportionately affects older adults. While targeted biologic therapies have shown efficacy in type 2 eosinophilic endotypes, elderly patients remain underrepresented in pivotal clinical trials. This narrative review examines the pathophysiological rationale, efficacy data, and unique geriatric challenges of biologic therapies in older adults. Methods: A literature search was conducted in PubMed and Scopus for phase II and III randomized controlled trials (RCTs) and observational studies evaluating biologic agents (anti-IL-5, anti-IL-4/IL-13, and anti-alarmins) in COPD, focusing on populations aged ≥ 65 years, comorbidities, and frailty. Discussion: Phase III data for dupilumab and mepolizumab indicate significant reductions in annualized exacerbations in patients with blood eosinophils ≥ 300 cells/μL. However, the mean age in the landmark trials (65 years) is a decade lower than the real-world average. Age-related immune remodeling—specifically immunosenescence and inflammaging—coexists with disease-specific pathways, potentially altering therapeutic responses. Furthermore, clinical trials systematically exclude older individuals with severe multimorbidity, physical frailty, cognitive impairment, and malnutrition. Conclusions: Biologics provide a precise, mechanism-based approach, yet evidence in the oldest-old remains limited. Future management should utilize the treatable traits framework, shifting selection criteria from chronological age to biological age metrics, including frailty status and functional reserve. Full article

Background/Objectives: Gingival recession frequently affects the anterior mandibular region. Anatomical features, such as thin buccal bone, narrow keratinized gingiva, and root proximity, increase susceptibility to periodontal disease. Recession can progress over time and may be exacerbated by orthodontic treatment. However, it remains uncertain whether the severity of crowding before treatment contributes to recession after orthodontic therapy The present study aimed to determine whether a relationship exists between the degree of mandibular anterior crowding before orthodontic treatment and the development or progression of gingival recession after treatment completion. Methods: This retrospective study was conducted on 269 participants with pre- and post-treatment records. The Little’s irregularity index was used to assess the degree of crowding. Clinical photographs of the six mandibular anterior teeth (1614 sites) were digitally calibrated permit millimeter-based assessment of gingival recession and keratinized tissue (KT) width. Oral hygiene (OH) was also evaluated at both time points. Results: Post-treatment recession was detected in 76 teeth. (4.7% of sites) among 48 participants (17.8%). Pretreatment crowding severity was not significantly associated with the occurrence of recession after treatment. Pretreatment mucogingival deformities were independently associated with post-treatment gingival recession. Mandibular central incisors demonstrated the highest prevalence of post-treatment gingival recession. Conclusions: Pretreatment mandibular anterior did not appear to predict gingival recession at treatment completion. Periodontal characteristics may play a more important role in recession development, supporting careful periodontal evaluation before and throughout orthodontic care. Full article

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by progressive motor neuron (MN) degeneration and severe skeletal muscle atrophy. Despite extensive research, the mechanisms driving disease onset and progression remain incompletely understood. While MN loss is a defining feature of ALS, increasing evidence indicates that mitochondrial dysfunction contributes to disease pathogenesis. Here, we investigated the hypothesis that Mdivi-1, a pharmacological inhibitor of mitochondrial fission protein Drp-1, may exert neuroprotective properties in the SOD1^G93A mouse model of ALS. Treatment was initiated prior to symptomatic onset to assess its potential disease-modifying effects. Mdivi-1 administration resulted in partial preservation of spinal MNs, however, this benefit did not translate into functional improvement. Moreover, treated animals exhibited exacerbated muscle atrophy, increased cytoplasmic localization of TDP-43 in MNs and compromised synaptic plasticity. Drp-1 expression was reduced in SOD1 mice and further decreased following Mdivi-1 treatment, suggesting that mitochondrial dynamics may already be compromised in this model. Overall, our results also highlight possible off-target effects of Mdivi-1 and point to a context-dependent role of mitochondrial dynamics in ALS. Full article

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which type 2 inflammation, epithelial dysfunction, and tissue remodeling determine severity, recurrence, and treatment response. Although molecular biomarkers have clarified disease endotypes, their routine use remains limited by cost, availability, and invasiveness. Nasal cytology offers a simple, repeatable, and minimally invasive method to assess—at the mucosal surface—both epithelial morphology and the dominant inflammatory infiltrate, whether neutrophilic, eosinophilic, mast cell, or mixed. Clinical-Cytological Grading (CCG) integrates the dominant cytological pattern with selected comorbidities, including asthma, allergy, and NSAID-exacerbated respiratory disease (N-ERD), into a weighted clinical-cytological framework. In the founding cohort, the highest relapse association was observed when mixed eosinophil–mast cell inflammation coexisted with asthma and N-ERD. This review discusses the rationale, clinical relevance, and translational applications of CCG in CRSwNP, addressing eosinophilic and mixed mast cell–eosinophilic inflammation, epithelial morphology, disease recurrence, difficult-to-treat phenotypes, biologic monitoring, and the operative dialogue between nasal cytology and histopathology. By linking cytological findings with selected clinical comorbidities, CCG may support biologically informed patient characterization and may prompt targeted mast cell assessment in tissue. However, its prognostic accuracy, incremental clinical value, and role in therapeutic decision-making require independent external validation. Full article

Background/Objectives: Exacerbations of chronic obstructive pulmonary disease (COPD) are a common reason for emergency department (ED) attendance and hospital admission. Acute respiratory worsening is non-specific, and previous spirometric confirmation may be unavailable at presentation. We aimed to translate current recommendations into an ED-specific clinical pathway that standardizes safety-critical steps without replacing individualized clinical judgment. Methods: We performed a targeted synthesis of international and Spanish guidance and key studies relevant to ED diagnosis, severity assessment, pharmacological treatment, respiratory support, antimicrobial stewardship, and disposition. The evidence base was updated in June 2026, and the pathway was reviewed by a multidisciplinary clinical group. Results: The revised pathway comprises four stages: (1) verify previous COPD confirmation, identify an acute exacerbation-like syndrome, and assess alternative or concomitant diagnoses; (2) grade acute severity using point-of-care variables and separately assess patient vulnerability; (3) provide severity-adjusted treatment with early reassessment; and (4) determine disposition and follow-up. It incorporates controlled oxygen, individualized bronchodilator delivery, explicit criteria for systemic corticosteroids and antibiotics, assessment of risk for Pseudomonas aeruginosa, non-invasive ventilation (NIV), and a defined adjunctive role for high-flow nasal cannula (HFNC). Patients without previous post-bronchodilator spirometry are classified as having suspected COPD and require confirmation after recovery. Conclusions: This evidence-informed pathway is a preliminary clinical framework, not a diagnostic rule or validated decision instrument. It is intended to support, rather than replace, professional judgment. Feasibility, acceptability, diagnostic safety, and clinical impact require prospective evaluation, beginning with a pilot implementation study. Full article