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关键词： Benign prostatic hyperplasia   alpha-1 blockers   5 alpha-reductase inhibitors   PDE5 inhibitors   FDA adverse event reporting system  

摘要： ObjectiveTo compare the real-world safety profiles of alpha 1-adrenoceptor antagonists (alpha 1-blockers 5 alpha-reductase inhibitors (5ARIs and phosphodiesterase type 5 inhibitor (PDE5I) used in the treatment of benign prostatic hyperplasia (BPH).MethodsThis retrospective pharmacovigilance study analyzed FDA Adverse Event Reporting System (FAERS) from Q1 of 2004 to Q2 of 2025. Reports of adverse events (AEs) in male BPH patients receiving AUA guideline-recommended drugs including alpha-1 blockers (tamsulosin, silodosin, doxazosin, and alfuzosin 5ARIs (finasteride and dutasteride and tadalafil were extracted. Disproportionality analysis was performed to detect significant safety signals. AEs were classified using MedDRA terms.ResultsAmong 9,540 unique reports and 25,796 AEs entries, patients aged 65-80 years accounted for the majority of the reports. Most AEs occurred within 30 days of treatment initiation. Hospitalization was the most common serious outcome. Sixteen significant AEs were detected, including pollakiuria, gynecomastia, breast pain and so on, with distinct reporting patterns across drug classes.ConclusionsThis large-scale pharmacovigilance analysis identified distinct post-marketing safety signals among guideline-recommended pharmacotherapies for BPH, confirming known risks and suggesting potential novel adverse-event signals warranting further investigation.

关键词： MALAT1   coronary artery disease   complex CAD   predictor   risk assessment  

摘要： BackgroundCoronary artery disease (CAD) remains a major global health burden with limited precision for early risk assessment and stratification. This study aims to investigate circulating Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) potentially associated with the presence and severity of CAD as a non-invasive biomarker.MethodsThis cross-sectional study included 179 participants undergoing coronary angiography comprising 84 with angiographically confirmed CAD and 95 without CAD. Coronary lesion severity was assessed using the Gensini score and categorized as non-CAD, non-complex CAD, or complex CAD. Circulating MALAT1 expression was quantified by qPCR. Correlation analyses, hierarchical logistic regression, ordinal logistic regression, and ROC analyses were applied to evaluate the diagnostic performance between MALAT1, CAD risk, and CAD severity.ResultsMALAT1 expression was significantly higher in CAD participants than those without CAD, and greatest among participants with complex CAD. MALAT1 positively correlated with BMI, LDL, non-HDL, and triglycerides, while negatively correlated with LVEF, CI, CO, RV diameter, and HDL. In multivariable models, MALAT1 independently associated with CAD alongside age, sex, BMI, CI, hypertension, concomitant cardiovascular disease, and medication therapy. MALAT1 showed high specificity but moderate sensitivity for identifying CAD and improved diagnostic performance when combining with agePredictive accuracy was strongest in participant aged >= 60spaceyears. After multivariable adjustment, MALAT1 remained independently associated with CAD severity, particularly for complex CAD.ConclusionCirculating MALAT1 is independently associated with both CAD risk and coronary lesion severity. Its enhanced predictive performance in older individuals suggests promising value as a non-invasive biomarker for refined cardiovascular risk stratification.

关键词： Hexavalent vaccine   preterm infants   extremely preterm infants   immunogenicity   reactogenicity   safety   phase IV trial   2+1 immunization schedule  

摘要： Preterm infants are at higher risk of mortality, disabilities, and infections. Hexavalent DTaP-IPV-HB-Hib vaccines against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b are standards of care in pediatric immunization. Evidence on the use of these vaccines in preterm infants remains limited, particularly in extreme preterms. This open-label, multicenter, non-randomized phase IV trial conducted in Spain evaluated the immunogenicity and safety of a 2 + 1 schedule of the DTaP-IPV-HB-Hib vaccine in preterm infants (stratified by gestational age: 24-27, 28-30, 31-33, 34-36 weeks). Immunogenicity was described using seroprotection/vaccine response (VR) rates. Safety was described using solicited and unsolicited adverse events (AEs). A total of 143 infants received at least one vaccination (22 born at 24-27 weeks of gestation, 29 at 28-30 weeks, 38 at 31-33 weeks, and 54 at 34-36 weeks 135 received three doses, and 132 completed the study. Post-dose 3 seroprotection rates were 100% against diphtheria (>= 0.1 UI/mL tetanus (>= 0.1 UI/mL and polio type 1/2/3 (>= 8/dil 94.5% against hepatitis B (>= 10 mIU/mL and 92.3% against polyribosylribitol phosphate (>= 1 & micro;g/mL). VR rates against pertussis toxoid and filamentous hemagglutinin were 94.1% and 76.5%, respectively. Within 7 days post-vaccination, 51.0% of participants experienced solicited AE related to vaccination, 0.7% reporting Grade 3 AEs. Within 30 days post-vaccination, 9.8% of infants had unsolicited related AEs (none of Grade 3). No serious AEs considered related were reported. This study demonstrated that a 2 + 1 schedule of the hexavalent DTaP-IPV-HB-Hib vaccine is immunogenic and well tolerated in preterm infants.Trial registration: EudraCT Number: 2018-004581-34.

关键词： Hypertension   circadian blood pressure   dipper hypertension   non-dipper hypertension   endothelin-1   endothelin-2   endothelial dysfunction  

摘要： Objective: The aim of this study was to evaluate serum endothelin-1 (ET-1) and endothelin-2 (ET-2) levels in patients with dipper and non-dipper hypertension compared to normotensive controls and to investigate the potential diagnostic value of these biomarkers in distinguishing circadian blood pressure phenotypes. Methods: This prospective case-control study included 163 participants classified into three groups based on 24-hour ambulatory blood pressure monitoring (ABPM normotensive controls (n = 60 dipper hypertensive (n = 61 and non-dipper hypertensive (n = 42) patients. Dipper status was defined as a 10% nocturnal reduction in both systolic and diastolic blood pressure. Individuals with diabetes, established cardiovascular disease, or secondary hypertension were excluded. Serum endothelin-1 (ET-1) ET-1 and endothelin-2 (ET-2) ET-2 levels were analyzed using double-antibody sandwich ELISA kits. Results: ET-1 levels were significantly lower in dipper hypertensive patients (p < 0.001) compared to other groups. Conversely, ET-2 levels did not significantly differ between hypertensive phenotypes. ET-1 proved to be a strong diagnostic marker for distinguishing non-dipper hypertension (AUC = 0.830, sensitivity 83.3%, specificity 75.4%). While advanced age independently predicted the non-dipper pattern (OR = 1.101, p = 0.002 BMI and D-dimer were associated with the dipper phenotype. Conclusion: This study identifies serum endothelin-1 is a strong, independent marker of the non-dipper hypertensive phenotype, which is associated with increased cardiovascular risk. The preservation of low endothelin-1 levels in dipper hypertension patients reflects intact endothelial and circadian regulation, whereas the absence of this response in non-dipper patients indicates impaired vascular adaptation. The inverse association of endothelin-2 with non-dipper status further suggests a protective buffering role that may be attenuated by increasing metabolic burden.

关键词： Malus domestica Borkh   allergen   Mal d 1   pathogen-related proteins   ypr10 gene  

摘要： Mal d 1, the major apple allergen, is well characterized at the genomic and proteomic levels;however, limited information is available regarding the natural variability of its gene expression. This study characterizes the expression variability of 16 MdPR10 gene isoforms in the fruit flesh of 61 Malus domestica Borkh. cultivars classified into four color groups - red-skinned, yellow-skinned, green-red skinned and yellow-red skinned apples. The Mal d 1.03 isoform exhibited the most consistent expression levels (predominantly isotypes 1.03D/E/F/G whereas Mal d 1.02 and Mal d 1.08 showed the lowest variability. Regarding intra-cultivar variability of expression levels, the highest variabilities were recorded for Mal d 1.11B, ranging from 0.11 (Delore) to 31.26 (Melrose) relative to the reference variety Santana. When comparing expression levels according to fruit color, higher expression of Mal d 1 is apple varieties from a red base skin color when compared to yellow base skin color.

关键词： Self-management   diabetes education   youth health   health services accessibility   scoping review methodology  

摘要： This scoping review aims to systematically explore the extent, nature, and gaps in the existing literature on self-care practices among adolescents and young adults aged 10-24 years living with type 1 diabetes mellitus (T1D) in Sub-Saharan Africa. The review will examine self-care knowledge, attitudes, practices, perceived barriers and facilitators, and interventions developed to support self-care. Type 1 diabetes mellitus accounts for approximately 5-10% of all diabetes cases globally and disproportionately affects children and young people in low- and middle-income countries. Adolescence and young adulthood are critical developmental periods during which self-care behaviours are established and may influence long-term health outcomes. In Sub-Saharan Africa, adolescents and young adults with T1D face challenges including limited healthcare infrastructure, inadequate disease awareness, restricted access to insulin and diabetes supplies, and high out-of-pocket costs. This scoping review will include quantitative and qualitative studies, systematic reviews, and grey literature published in English from January 2004 onwards. The review will follow the Joanna Briggs Institute methodology for scoping reviews. A three-step search strategy will be applied across PubMed, MEDLINE, Web of Science, CINAHL, and Embase. Two independent reviewers will screen titles, abstracts, and full texts. Data will be extracted using a structured tool and synthesised using narrative, tabular, graphical, and thematic approaches.

关键词： mRNA vaccine   influenza   adverse events   hemagglutination inhibition titers   cell-mediated immunity  

摘要： This first-in-human, randomized, controlled, phase 1 proof-of-principle study evaluated the safety, reactogenicity, and immunogenicity of an investigational mRNA-based monovalent influenza vaccine encoding influenza A/H1N1 hemagglutinin (FLUmHA). Younger adults (YA) aged 18-45 y received one dose of FLUmHA at one of 10 dose levels (0.5-100 & micro;g, n = 24/25 per group) or licensed Flu Dresden-quadrivalent seasonal influenza vaccine (Flu D-QIV, n = 35) on day (D)1. Older adults (OA) aged 60-80 y received FLUmHA (18 & micro;g, n = 32) or Flu D-QIV (n = 16). Reporting rates for solicited adverse events (AEs) occurring within 7 d post-vaccination generally increased with increasing FLUmHA dose levels, and were 62.5%-100% (severe: 0.0%-20.8%) in YA across FLUmHA dose levels versus 88.6% (severe: 2.9%) in Flu D-QIV-vaccinated YA, and 62.5% (severe: 0.0% FLUmHA) versus 56.3% (severe: 0.0% Flu D-QIV) in OA. Unsolicited AEs within 28 d post-vaccination were reported by 50.0%-70.8% of YA across FLUmHA dose levels versus 68.6% of Flu D-QIV-vaccinated YA, and by 43.8% (FLUmHA) versus 50.0% (Flu D-QIV) of OA. No safety concerns were identified. A/H1N1 hemagglutination inhibition titers increased from pre-vaccination to D22, with adjusted geometric mean increases (GMIs) of 6.2-36.7 across YA and OA groups;the observed response was dose-dependent and higher in FLUmHA (for doses > 1 & micro;g) versus Flu D-QIV recipients. Titers decreased but remained above pre-vaccination levels at D183 (GMI: 2.9-14.0). Additionally, FLUmHA elicited a numerically higher hemagglutinin-specific CD4+ T-cell response (predominantly Th1 profile) than Flu D-QIV, both in YA and OA. These results support the progression to clinical development of a multivalent mRNA Flu vaccine candidate.

关键词： Gout   macrophage polarization   CA72-4   Siglec-15   TIGIT/SHP-1 signaling  

摘要： Excessive M1 polarization of macrophages is a key driver of inflammatory processes in gout, while the regulatory mechanisms involved remain unclear. Herein, the role of carbohydrate antigen 72-4 (CA72-4 derived from human synovial cells (HFLS in regulating macrophage M1 polarization during gout progression was investigated. PMA was used to induce differentiation of THP-1 cells into macrophages, and the macrophages were then treated with a conventional medium (CM the CM was from Non-treated HFLS (NCM or the CM from MSU-treated HFLS (MCM and then incubated with MSU treatment for 24 h. Cell viability was assessed by CCK-8 assay. IL-1 beta, TGF-beta 1, and CA72-4 levels in the supernatant of macrophages were detected by ELISA. The interaction between CA72-4 and sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) was analyzed by Co-IP assay. MSU-induced HFLS to secrete CA72-4, and CA72-4 derived from HFLS inhibited MSU-induced macrophage M1 polarization. Mechanistically, CA72-4 activated the TIGIT/SHP-1 signaling in macrophages by binding to Siglec-15 on macrophages. As expected, Siglec-15 knockdown weakened the activation effect of MCM on TIGIT/SHP-1 signaling and the inhibitory effect on macrophage M1 polarization. MSU stimulated HFLS to secrete CA72-4, and CA72-4 derived from HFLS suppressed MSU-induced macrophage M1 polarization by activating TIGIT/SHP-1 signaling through targeting Siglec-15.

关键词： Water resources   hydrogeology   GIS mapping   national-scale map   participatory process   sustainable water management  

摘要： This paper presents the Hydrogeological Map of Italy at a scale of 1:500,000 (CII500K). The map is organized into four sheets, accompanied by supplementary notes and tables, and complemented by an online version providing an updated and harmonized national overview of groundwater systems in Italy. The CII500K synthesizes the country's hydrogeological framework, describing groundwater distribution, recharge conditions, and use. It builds on recent regional cartographic studies and integrated datasets, adopting a unified methodology for defining hydrogeological complexes, relative permeability classes, and aquifer productivity. Developed through extensive GIS processing, including a WebGIS platform to promote a participatory work with technicians and researchers of different institutions, the map includes key thematic layers such as perennial freshwater tapped springs, thermal and coastal springs, piezometric contours, and major groundwater flowpaths. This cartographic product provides key information for sustainable water management and climate adaptation strategies consistent with European water policies.