Search Results (415)

Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations. Full article

Urban air pollution remains a significant environmental and public health issue, especially in European coastal cities such as Klaipėda. However, there is still a lack of local-scale knowledge on how land use structure influences pollutant distribution, highlighting the need to address this gap. This study addresses this by examining the spatial distribution of nitrogen dioxide (NO₂) concentrations in Klaipėda’s seaport city and several inland and coastal resort towns in Lithuania. The research specifically asks how different land cover types and demographic factors affect NO₂ variability and population exposure risk. Data were collected using passive sampling methods and analyzed within a GIS environment. The results revealed clear air quality differences between industrial/port zones and greener resort areas, confirmed by statistically significant associations between land cover types and pollutant levels. Based on these findings, a Land Use Pollution Pressure index (LUPP) and its population-weighted variant (PLUPP) were developed to capture demographic sensitivity. These indices provide a practical decision-support tool for sustainable urban planning, enabling the assessment of pollution risks and the forecasting of air quality changes under different land use scenarios, while contributing to local climate adaptation and urban environmental governance. Full article

Food safety concerns related to pesticide residues in fruits and vegetables have increased globally, particularly in regions where monitoring programs are scarce or inconsistent. This study provides the first multi-year evaluation of pesticide contamination and associated dietary risks in Cape Verde, an African island nation increasingly reliant on imported produce. A total of 570 samples of fruits and vegetables—both locally produced and imported—were collected from major markets across the country between 2017 and 2020 and analyzed using validated multiresidue methods based on gas chromatography coupled to Ion Trap mass spectrometry (GC-IT-MS/MS), and both gas and liquid chromatography coupled to triple quadrupole tandem mass spectrometry (GC-QqQ-MS/MS and LC-QqQ-MS/MS). Residues were detected in 63.9% of fruits and 13.2% of vegetables, with imported fruits showing the highest contamination levels and diversity of compounds. Although only one sample exceeded the maximum residue limits (MRLs) set by the European Union, 80 different active substances were quantified—many of them not authorized under the current EU pesticide residue legislation. Dietary exposure was estimated using median residue levels and real consumption data from the national nutrition survey (ENCAVE 2019), enabling a refined risk assessment based on actual consumption patterns. The cumulative hazard index for the adult population was 0.416, below the toxicological threshold of concern. However, when adjusted for children aged 6–11 years—taking into account body weight and relative consumption—the cumulative index approached 1.0, suggesting a potential health risk for this vulnerable group. A limited number of compounds, including omethoate, oxamyl, imazalil, and dithiocarbamates, accounted for most of the risk. Many are banned or heavily restricted in the EU, highlighting regulatory asymmetries in global food trade. These findings underscore the urgent need for strengthened residue monitoring in Cape Verde, particularly for imported products, and support the adoption of risk-based food safety policies that consider population-specific vulnerabilities and mixture effects. The methodological framework used here can serve as a model for other low-resource countries seeking to integrate analytical data with dietary exposure in a One Health context. Full article

Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article

Background/Objectives: Current dosing recommendations for piperacillin/tazobactam suggest adjustments only for patients with creatinine clearance (CrCl) below 40 mL/min, potentially neglecting the variability in drug exposure among patients with a CrCl greater than 40 mL/min. This study aimed to develop a population pharmacokinetic (PK) model for piperacillin/tazobactam and explore optimal dosage regimens tailored by renal function and pathogen susceptibility. Methods: Twelve healthy adults received a single intravenous dose of piperacillin/tazobactam (4 g/0.5 g). Population PK models were developed using nonlinear mixed-effects modeling. Monte Carlo simulations were conducted to identify optimal dosing regimens across various renal functions and MIC levels, guided by pharmacodynamic targets defined as the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (fT_>MIC). Results: PK profiles of both drugs were best described by two-compartment models. Estimated glomerular filtration rate (eGFR) adjusted by body surface area and body weight were identified as significant covariates influencing drug clearance and peripheral volume of distribution. Simulations showed that the standard dosing regimen (4/0.5 g q6h with 30 min infusion) achieved a 90% probability of target attainment (PTA) for 50%fT_>MIC at MIC values up to 4 mg/L in patients with normal renal function. However, this regimen often did not achieve a 90% PTA for stringent targets (100%fT_>MIC, 100%fT_>4MIC) or higher MICs, particularly in patients with eGFR ≥ 130 mL/min. Conclusions: These findings suggest current dosing regimens may be inadequate and highlight the potential of alternative strategies, such as extended or continuous infusion, which warrant further investigation in clinical populations to optimize therapeutic outcomes. Full article

Honey bees (Apis mellifera ligustica) are essential pollinators in both ecosystems and agricultural production. However, their populations are declining due to various factors, including pesticide exposure. Despite their importance, the reproductive castes, particularly drones, remain understudied in terms of pesticide effects. To investigate the effects of azoxystrobin and picoxystrobin on honey bee drones, the drones were exposed to different concentrations of azoxystrobin and picoxystrobin for 14 days; the drone survival, body weight, nutrient content, reproductive organs, and sperm concentration were assessed. Results showed that exposure to both fungicides caused a significant reduction in drone survival rates, with survival rates decreasing progressively as the duration of exposure increased. Compared to the control group, the body weights of drones in all treatment groups were significantly lower on days 7 and 14. Nutrient analysis revealed that low concentrations of azoxystrobin and picoxystrobin increased protein levels, while free fatty acid content decreased significantly in all treatment groups. No significant changes were observed in the total carbohydrate content. Morphological examination of reproductive organs showed that the lengths of the mucus glands and seminal vesicles in drones were significantly shorter in the treatment groups compared to the control group. Furthermore, exposure to azoxystrobin and picoxystrobin resulted in a significant decline in sperm concentration in the drones. These findings indicate that azoxystrobin and picoxystrobin have adverse effects on the health and reproductive capacity of honey bee drones. The present study highlights the need to reassess the risks posed by these fungicides to pollinators, particularly given the critical role of drones in maintaining the genetic diversity and resilience of honey bee colonies. Further research is warranted to elucidate the underlying mechanisms of these effects and explore potential mitigation strategies. Full article

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease (IBD) that has been associated with overconsumption of calories and lipids, compared to the healthy population, and summer temperatures have been reported to be closely related to the prevalence of UC. To evaluate the effects of dietary and lifestyle factors on UC, a combination of 2.0% dextran sulfate sodium (DSS), a high-fat/high-sugar diet, and exposure to high temperature and humidity was used to construct mouse models of UC. Changes in body weight, disease activity index (DAI) scores, histopathological analysis, serum lipid levels, serum diamine oxidase (DAO), and D-Lactate (D-LA) levels, as well as the expression of inflammatory cytokines and tight junction proteins in colonic tissue, were all assessed to study the impacts of the high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. The symptoms observed in the UC mouse model induced by 2.0% DSS alone were similar to those seen in patients with UC, while the high-fat and high-sugar diet, along with humid and hot exposure, exacerbated DSS-induced UC in the mice. This included more severe histopathological damage to the colon tissue, increased expression of pro-inflammatory cytokines (IL-6, IL-17A, and IL-1β), and a more significantly compromised intestinal barrier, characterized by the destruction of ZO-1 and elevated levels of DAO and D-LA. Additionally, the high-fat/high-sugar diet and high-temperature/high-humidity exposure led to further disturbances in glucose and lipid metabolism in the mice, which were not observed in those treated with DSS alone. This study is the first to investigate the effects of a high-fat/high-sugar diet and high-temperature/high-humidity exposure on the progression of UC. Full article

This study investigates rural settlement patterns and land suitability in Rwanda’s Western Highlands, a mountainous region highly vulnerable to geohazards like landslides and flooding. Its primary aim is to inform sustainable, climate-resilient development planning in this fragile landscape. We employed high-resolution satellite imagery, a Digital Elevation Model (DEM), and comprehensive geospatial datasets to analyze settlement distribution, using Thiessen polygons for influence zones and Kernel Density Estimation (KDE) for spatial clustering. The Analytic Hierarchy Process (AHP) was integrated with the GeoDetector model to objectively weight criteria and analyze settlement pattern drivers, using population density as a proxy for human pressure. The analysis revealed significant spatial heterogeneity in settlement distribution, with both clustered and dispersed forms exhibiting distinct exposure levels to environmental hazards. Natural factors, particularly slope gradient and proximity to rivers, emerged as dominant determinants. Furthermore, significant synergistic interactions were observed between environmental attributes and infrastructure accessibility (roads and urban centers), collectively shaping settlement resilience. This integrative geospatial approach enhances understanding of complex rural settlement dynamics in ecologically sensitive mountainous regions. The empirically grounded insights offer a robust decision-support framework for climate adaptation and disaster risk reduction, contributing to more resilient rural planning strategies in Rwanda and similar Central African highland regions. Full article

Background: Accurately determining pediatric dosing is essential prior to initiating clinical trials or administering medications in routine clinical settings. In children, ethical considerations demand careful evaluation of both safety and effectiveness. Typically, dosing recommendations for therapeutic proteins, such as monoclonal antibodies (mAbs), are derived from adult dosages using body weight as a scaling factor. However, this method overlooks key physiological and biochemical distinctions between pediatric and adult patients. Therefore, this could lead to the underexposure of mAbs, limiting their efficacy in this population. Additional methods are necessary to predict pediatric doses mechanistically. For small molecules, physiologically based pharmacokinetic (PBPK) models have been extensively used to predict pediatric doses based on physiological age-related changes and enzymes/transporters ontogeny. This study aims to evaluate the ability of PBPK models to predict mAbs’ pediatric exposure. Methods: Three mAbs were used for model development and validation: bevacizumab, infliximab, and atezolizumab. The PBPK models were built using GastroPlus^© Biologics module. For each mAb, the PBPK model was developed based on observed data in healthy and/or patient adults. Then, the physiological parameters were scaled to describe the pediatric physiology to predict exposure to the pediatric populations. Predicted plasma concentration–time courses were overlaid with reported observed data to assess the ability of the PBPK model to predict pediatric exposure. Results: Results showed that PBPK models accurately predicted pediatric pharmacokinetics for mAbs. Conclusions: This research marks a significant step in validating mechanistic extrapolation methods for biologics exposure prediction in children using PBPK models. Full article

Agricultural organic pollutants have been identified as a key factor contributing to amphibian population decline, particularly during early developmental stages when tadpoles are frequently exposed to neonicotinoids (NEOs) and microplastics (MPs). In this study, Hoplobatrachus rugulosus tadpoles were exposed to imidacloprid (IMI: 0.045, 0.45, and 4.5 mg L⁻¹) and polyethylene-derived MPs (10 mg L⁻¹) from agricultural mulch films, both individually and in combination. We systematically evaluated acute toxicity, bioaccumulation, developmental and oxidative stress responses, and changes in the skin and gut microbiota. The results showed that the 96 h median lethal concentration (LC₅₀) of IMI was 44.8 mg L⁻¹ in the IMI-only group and was 40.5 mg L⁻¹ in the IMI + MPs group, indicating the negligible impact of MPs on acute toxicity. However, in the highest co-exposure group (IMI4.5 + MPs), tadpole body length and weight decreased by 14.7% and 22.6%, respectively, alongside marked changes in oxidative stress, whereby catalase (CAT) and superoxide dismutase (SOD) activities were suppressed, while malondialdehyde (MDA) levels increased by 35%, indicating elevated lipid peroxidation. Furthermore, the micronucleus frequency in erythrocytes was significantly elevated, suggesting genotoxic effects. Microbial community analysis revealed significant shifts in the relative abundance of gut and skin microbiota under IMI + MPs exposure, with a notable enrichment of Proteobacteria, Fusarium, Actinomycetota, and Bacteroidota, indicating the disruption of host–microbiome interactions. This study proposes a comprehensive multi-tiered assessment framework encompassing environmental exposure, bioaccumulation, toxicological endpoints, oxidative stress biomarkers, and microbiome shifts. Our findings provide new mechanistic insights and quantitative evidence on the compound threats posed by IMI and MPs to amphibians in aquatic environments. Full article

This study evaluated the prevalence of aflatoxin M1 (AFM1) in milk marketed in Tirana, Albania, along with dietary exposure and associated potential health risks. The World Health Organization has categorized Albania in cluster G02 of GEMS/FOOD, highlighting that milk is a staple in the Albanian diet, which points to a possible health risk. A total of 141 milk samples, comprising both Ultra-High Temperature (UHT) and pasteurized types, were collected from local markets in Tirana and analyzed from March 2023 to February 2024. The determination of AFM1 levels was carried out using High-Pressure Liquid Chromatography with a Fluorescence Detector (HPLC-FLD), a precise and dependable technique for identifying and measuring aflatoxins in food products. Aflatoxin M1 was found in 62.4% of the milk samples, with 26.2% surpassing the European Union’s maximum residue levels (MRL). The mean AFM1 concentrations were 58.8 ± 95.8 ng/kg, reaching a maximum level of 399.0 ng/kg. The Estimated Daily Intake (EDI) for various groups—toddlers, children, adolescents, and adults—was determined to be 2.161, 1.297, 0.519, and 0.370 ng/kg of body weight per day, respectively. The Hazard Index (HI), derived from the AFM1 exposure for four population groups, was 10.81 (toddlers), 6.48 (children), 2.59 (adolescents), and 1.85 (adults). The Margin of Exposure (MoE) was 1.85, 3.08, 7.71, and 10.81, respectively. The incidence of hepatocellular carcinoma (HCC) per 100,000 people in the four groups was 0.034, 0.021, 0.008, and 0.006, respectively. The study is the first comprehensive evaluation of AFM1 prevalence, highlighting the potential risks associated with milk consumption, as milk is a dietary staple in Albanian households. It addresses a critical public health concern regarding aflatoxin M1 (AFM1) contamination in milk consumed in Tirana, Albania, by highlighting the need for ongoing monitoring, regulatory measures, and educational outreach to enhance food safety and safeguard public health in Albania, as well as in other regions facing similar concerns. Full article

Background: Histoplasma capsulatum is an environmentally acquired dimorphic fungus. Infection results in histoplasmosis, a clinical syndrome often underdiagnosed and that may progress to life-threatening disseminated infection not only in immunocompromised individuals but also, following high-level exposure, in immunocompetent hosts. Epidemiological data from Caribbean regions, and particularly from Guadeloupe, remain limited. Methods: We performed a retrospective cohort study of all microbiologically confirmed histoplasmosis cases managed at the University Hospital of Guadeloupe between January 2014 and October 2024. Demographic, clinical, diagnostic, therapeutic, and outcome data were retrieved from medical records and analyzed using descriptive statistics. Results: Forty-two patients met the inclusion criteria, corresponding to an estimated annual incidence rate of 1 per 100,000 inhabitants. The median age was 52 years, and the male-to-female ratio was 4:1. An underlying immunocompromising condition was present in 85% of cases, most commonly HIV infection (48%). Common clinical features included weight loss (97%), fever (89%), and pulmonary manifestations (81%). The mean time to diagnosis from hospital admission was 3.5 ± 10.3 days. Direct microscopy was positive in 67% of cases, and culture was positive in 88% of cases. Intravenous liposomal amphotericin B constituted the initial therapy in 71% of patients. Overall, the in-hospital mortality was 29%, rising to 40% among HIV-positive individuals. The 30-day survival rate was 71%. Conclusions: Histoplasmosis in Guadeloupe is under-recognized and associated with appreciable morbidity and mortality in both immunocompromised and immunocompetent patients. The wider availability of rapid diagnostics and heightened clinical vigilance are essential to shorten diagnostic delays and improve outcomes in this Caribbean population. Full article

Background: Statins are commonly used cholesterol-lowering drugs with evidence of additional chemoprotective and immunomodulatory effects resulting from the inhibition of DNA replication, cell proliferation, and TH1-cell inhibition. There are conflicting reports regarding the potential benefit of concurrent statin treatment on non-muscle invasive bladder cancer (NMIBC) and specifically on intravesical Bacillus Calmette–Guerin (BCG) outcomes. We therefore aimed to analyze the effects of concurrent BCG and statin use in patients with NMIBC. Methods: National Veterans Affairs databases were used to retrospectively identify men with NMIBC between 2000 and 2010 who were treated with BCG. Pharmacy data was interrogated, and patients were divided according to statin therapy status. Statins had to be given at the beginning of BCG treatments and continued for at least 6 months. Cox proportional hazard ratios after inverse propensity score-weighted and competing risks adjustments were calculated for recurrence, secondary events (e.g., progression), cancer-specific survival, and overall survival. Results: Among 8814 patients, with a median follow-up of 11.3 years, statins were used by 38% of the patients. Patients taking statins were older (71 vs. 68, p < 0.0001), had more comorbidities (Charlson Comorbidity Index (CCI > 2; 38.6% vs. 31.4%, p < 0.0001), and had a higher-grade disease (40.2% vs. 34.3%, p < 0.0001) compared to those not on statins. After adjusting for stage, grade, age, race, CCI, agent orange exposure, and year of diagnosis, Cox proportional hazard analysis revealed no association with recurrence (HR 1.05, 95% CI 0.97–1.15, p = 0.23), secondary events (HR 0.91, 95% CI 0.80–1.05, p = 0.189), or bladder cancer specific survival (HR 0.88, 95% CI 0.76–1.02, p = 0.09) of statin use. However, statins were associated with improved overall survival (HR 0.89, 95% CI 0.83–0.96, p = 0.002). Conclusions: Concurrent statin and BCG use in patients with NMIBC was associated with improved overall survival, but not recurrence, secondary events, or bladder cancer-specific survival. These results confirm the real-world well-established cardiovascular benefit of statin treatment and primary preventive care. However, this large population study did not find any association between statins and the outcomes of patients with NMIBC treated with BCG immunotherapy. Full article

Landslides threaten railway safety and operational sustainability. This study developed a game theory-based weighting method that integrates the Entropy Weight Method (EWM) and CRITIC with Analytic Hierarchy Process (AHP) techniques to determine indicator weights, reducing single-method biases. A risk assessment was conducted that coupled hazard likelihood with exposure. These components formed a comprehensive risk index visualized as a landslide risk map. A GIS-integrated assessment of Shandong Province railways incorporated multi-source data to support resilient infrastructure planning. The results show that high-risk zones consistently coincide with mountainous terrain, high-precipitation areas, and concentration of the population/economic activity, identifying critical intervention areas. The integrated weighting method proves effective for multi-criteria risk analysis. Decision-makers can prioritize mitigation measures using these insights, enhancing railway resilience and reducing regional disaster risk. Full article

In this study, the migratory agricultural pest Spodoptera frugiperda was exposed to three periodic short-term heat stress regimes at 37 °C, 40 °C, and 43 °C (2 h daily), with a constant 26 °C control. We systematically evaluated the effects of periodic thermal stress on developmental traits across all life stages. Combined with 16S rRNA high-throughput sequencing, we analyzed the structural and functional characteristics of the gut bacterial community in adults under heat stress. The results demonstrated that 37 °C exposure accelerated egg-to-adult development, whereas 43 °C markedly extended it. Additionally, 43 °C heat stress suppressed pupation and eclosion rates. Increasing stress temperatures were negatively correlated with pupal weight and body size in both sexes. Notably, 43 °C heat stress caused complete loss of hatching ability in offspring eggs, thereby rendering population reproduction unattainable. 16S rRNA sequencing revealed that Proteobacteria (>90%) dominated the gut bacterial community at the phylum level across all treatments. Under 43 °C heat stress, although female and male adults exhibited an increase in specific bacterial species within their gut bacteria, Alpha diversity analysis revealed no significant differences in the diversity (Shannon index) and richness (Chao index) of gut bacterial communities between sexes under temperature treatments. PICRUSt2 functional prediction indicated that metabolic pathways, biosynthesis of secondary metabolites, and microbial metabolism in diverse environments constituted the dominant functions of gut bacteria in both sexes, while heat stress exerted minimal effects on the functional profiles of gut bacteria in S. frugiperda. These findings not only provide a theoretical basis for predicting summer population dynamics and formulating ecological control strategies for S. frugiperda but also offer critical insights into the adaptive interactions between this pest and its gut bacterial community under heat stress. The results lay a foundation for further exploring the interactions between insect environmental adaptability and bacterial symbiosis. Full article