Search Results (898)

Background: Type 2 diabetes (T2D) is a global health epidemic with rising prevalence within Asian populations, particularly amongst individuals with high visceral adiposity and ectopic organ fat, the so-called Thin-Outside, Fat-Inside phenotype. Metabolomic and microbiome shifts may herald T2D onset, presenting potential biomarkers and mechanistic insight into metabolic dysregulation. However, multi-omics datasets across ethnicities remain limited. Methods: We performed cross-sectional multi-omics analyses on 171 adults (99 Asian Chinese, 72 European Caucasian) from the New Zealand-based TOFI_Asia cohort at 4-years follow-up. Paired plasma and faecal samples were analysed using untargeted metabolomic profiling (polar/lipid fractions) and shotgun metagenomic sequencing, respectively. Sparse multi-block partial least squares regression and discriminant analysis (DIABLO) unveiled signatures associated with ethnicity, glycaemic status, and sex. Results: Ethnicity-based DIABLO modelling achieved a balanced error rate of 0.22, correctly classifying 76.54% of test samples. Polar metabolites had the highest discriminatory power (AUC = 0.96), with trigonelline enriched in European Caucasians and carnitine in Asian Chinese. Lipid profiles highlighted ethnicity-specific signatures: Asian Chinese showed enrichment of polyunsaturated triglycerides (TG.16:0_18:2_22:6, TG.18:1_18:2_22:6) and ether-linked phospholipids, while European Caucasians exhibited higher levels of saturated species (TG.16:0_16:0_14:1, TG.15:0_15:0_17:1). The bacteria Bifidobacterium pseudocatenulatum, Erysipelatoclostridium ramosum, and Enterocloster bolteae characterised Asian Chinese participants, while Oscillibacter sp. and Clostridium innocuum characterised European Caucasians. Cross-omic correlations highlighted negative correlations of Phocaeicola vulgatus with amino acids (r = −0.84 to −0.76), while E. ramosum and C. innocuum positively correlated with long-chain triglycerides (r = 0.55–0.62). Conclusions: Ethnicity drove robust multi-omic differentiation, revealing distinctive metabolic and microbial profiles potentially underlying the differential T2D risk between Asian Chinese and European Caucasians. Full article

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by inattention, hyperactivity, and impulsivity, frequently observed in juvenile offenders. This systematic review explores the interplay between ADHD and juvenile delinquency, focusing on behavioural, psychological, and social dimensions. Following the PRISMA guidelines, a systematic literature review was conducted using EBSCO Discovery Service, Science Direct, PubMed, and snowballing techniques. Studies meeting specific inclusion criteria, including juvenile offenders diagnosed with ADHD and comparisons to non-offender or non-ADHD control groups, were analysed. The methodological quality of studies was assessed using the Joanna Briggs Institute appraisal tools. A total of 21 studies were included, highlighting significant associations between ADHD and juvenile delinquency. ADHD symptoms, especially impulsivity and emotional dysregulation, were linked to an earlier onset of offending and higher rates of property crimes. Comorbidities such as conduct disorder, substance use disorder, and depression exacerbated these behaviours. Sociodemographic factors like low education levels and adverse family environments were also critical modifiers. Early intervention and tailored treatment approaches were emphasised to address these challenges. The findings underscore the need for early diagnosis, individualised treatment, and integrative rehabilitation programmes within the juvenile justice system to mitigate long-term risks and promote social inclusion. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), and interleukin-6 (IL-6), have been associated with an increased risk of future cardiovascular events. While they provide valuable prognostic information, these associations do not necessarily imply a direct causal role. The combined prognostic utility of these markers, however, remains insufficiently studied. We analysed 3300 well-characterised participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, all of whom underwent coronary angiography. Participants were stratified based on their serum concentrations of hsCRP, SAA, and IL-6. Associations between biomarker combinations and mortality were assessed using multivariate Cox regression and ROC analysis. Individuals with elevated hsCRP and SAA or IL-6 showed higher prevalence rates of coronary artery disease, heart failure, and adverse metabolic traits. These “both high” groups had lower estimated glomerular filtration rate, higher NT-proBNP, and increased HbA1c. Combined elevations of hsCRP and SAA were significantly associated with higher all-cause and cardiovascular mortality in partially adjusted models. However, these associations weakened after adjusting for IL-6. IL-6 alone demonstrated the highest predictive power (AUC: 0.638) and improved risk discrimination when included in multi-marker models. The co-elevation of hsCRP, SAA, and IL-6 identifies a high-risk phenotype characterised by greater cardiometabolic burden and increased mortality. IL-6 may reflect upstream inflammatory activity and could serve as a therapeutic target. Multi-marker inflammatory profiling holds promise for refining cardiovascular risk prediction and advancing personalised prevention strategies. Full article

Background/Objectives: Romania remains a tuberculosis (TB) hotspot in the European Union, yet host-derived factors of poor outcomes are poorly characterised. We quantified circulating pro-inflammatory cytokines and examined their interplay with behavioural risk factors, the nutritional status, and the clinical course in adults hospitalised with pulmonary TB. We analysed 80 adults with microbiologically confirmed pulmonary TB and 40 respiratory symptom controls; four TB patients (5%) died during hospitalisation, all within 10 days of admission. Methods: A retrospective analytical case–control study was conducted at the Constanța regional TB referral centre (October 2020—October 2023). Patients with smear- or culture-confirmed TB were frequency-matched by sex, 10-year age band, and BMI class to culture-negative respiratory controls at a 2:1 ratio. The patients’ serum interferon-γ (IFN-γ), interleukin-1α (IL-1α), interleukin-1β (IL-1β), and tumour-necrosis-factor-α (TNF-α) were quantified within 24 h of admission; the neutrophil/lymphocyte ratio (NLR) was extracted from full blood counts. Independent predictors of in-hospital mortality were identified by multivariable logistic regression; factors associated with the length of stay (LOS) were modelled with quasi-Poisson regression. Results: The median TNF-α (24.1 pg mL⁻¹ vs. 16.2 pg mL⁻¹; p = 0.009) and IL-1β (5.34 pg mL⁻¹ vs. 3.67 pg mL⁻¹; p = 0.008) were significantly higher in the TB cases than in controls. TNF-α was strongly correlated with IL-1β (ρ = 0.80; p < 0.001), while NLR showed weak concordance with multiplex cytokine patterns. Among the patients with TB, four early deaths (5%) exhibited a tripling of TNF-α (71.4 pg mL⁻¹) and a doubling of NLR (7.8) compared with the survivors. Each 10 pg mL⁻¹ rise in TNF-α independently increased the odds of in-hospital death by 1.8-fold (95% CI 1.1–3.0; p = 0.02). The LOS (median 29 days) was unrelated to the smoking, alcohol, or comorbidity load, but varied across BMI strata: underweight, 27 days; normal weight, 30 days; overweight, 23 days (Kruskal–Wallis p = 0.03). In a multivariable analysis, under-nutrition (BMI < 18.5 kg m⁻²) prolonged the LOS by 19% (IRR 1.19; 95% CI 1.05–1.34; p = 0.004) independently of the disease severity. Conclusions: A hyper-TNF-α/IL-1β systemic signature correlates with early mortality in Romanian pulmonary TB, while under-nutrition is the dominant modifiable determinant of prolonged hospitalisation. Admission algorithms that pair rapid TNF-α testing with systematic nutritional assessment could enable targeted host-directed therapy trials and optimise bed utilisation in high-burden settings. Full article

Savanna systems are characterised by a community of large mammal herbivores with up to 30 species; coexistence is based on resource partitioning. In this paper we analyse the features of the landscape and plant structure which lead herbivores to use particular locations, a key to resource partitioning. The processes involved, top-down versus bottom-up, are well known for large species and small ones but not for medium-sized ones. We use two resident, medium-sized species, topi (Damaliscus lunatus jimela) and kongoni, (Alcelaphus buselaphus cokei) in the central woodlands of the Serengeti; selection of habitat by the residents is important for predator-prey interactions and for interactions among the grazers. Using Principal Component Analysis and Multiple Regression we develop highly predictive models which show that resource availability is the critical determinant of habitat selection in the dry season; and reduction in predation risk appears to be important in the wet season. These results show for the first time that habitat selection by the medium-sized herbivores is driven by different strategies in the two seasons. This contributes to understanding the processes involved in the dynamics of this globally important savanna system, a necessary foundation for management. Full article

Introduction: Dental caries and molar–incisor hypomineralisation (MIH) are prevalent conditions affecting children’s oral health, with functional, aesthetic, and psychosocial implications. In Spain, previous studies have highlighted geographic and sociodemographic disparities in their distribution, particularly among rural and migrant populations. Objective: To characterise oral health status, in terms of caries and MIH, among 6–7-year-old children from the towns of Palos de la Frontera, Mazagón, and San Bartolomé. Methods: A cross-sectional study was conducted involving 229 children recruited from public primary schools. Sociodemographic, anthropometric, and behavioural data were collected through clinical examination and interview. Statistical analysis included univariate and multivariate logistic regression. The study protocol was approved by the Ethics Committee of Huelva. Results: The prevalence of caries (DMFT ≥ 1) was 53.3%, with mean DMFT and dft indices of 1.78 and 0.31, respectively. MIH affected 32.8% of the cohort, with a predominance in the first permanent molars (teeth 36 and 26). Multivariate analysis identified independent predictors of caries: African (OR = 7.47; 95% CI: 2.84–23.8) and European (OR = 4.56; 95% CI: 1.26–22.3) parental origin, poor oral hygiene (OR = 3.07; 95% CI: 1.60–6.03), and the presence of MIH (OR = 3.20; 95% CI: 1.64–6.42). The municipality of San Bartolomé was associated with a higher risk of MIH (OR = 2.90; 95% CI: 1.21–7.45). Conclusions: The high prevalence of caries and MIH in the Condado-Campiña district, exceeding national averages, reflects oral health inequities linked to social determinants (migrant origin, locality) and clinical factors (MIH, oral hygiene). Targeted preventive interventions are urgently needed in high-risk populations, including culturally tailored education and policies ensuring equitable access to dental care services. Full article

The structural health monitoring of historic buildings represents one of the most significant challenges in contemporary structural analysis, particularly for large-scale structures with accumulated damage. Obtaining reliable diagnostics is crucial yet complex due to the inherent uncertainties in both geometric definition and material properties of historic constructions, especially when structural stability may be compromised. This study presents a comprehensive structural assessment of the Bullring of the Real Maestranza de Caballería de Ronda (Spain), an emblematic 18th-century structure, through an innovative multi-technique approach aimed at evaluating its structural stability. The methodology integrates various non-destructive techniques: 3D laser scanning for precise geometric documentation, operational modal analysis (OMA) for global dynamic characterisation, experimental modal analysis (EMA) for local assessment of critical structural elements, and sonic tests (ST) to determine the elastic moduli of the principal materials that define the historic construction. The research particularly focuses on the inner ring of sandstone columns, identified as the most vulnerable structural component through initial dynamic testing. A detailed finite-element (FE) model was developed based on high-precision laser-scanning data and calibrated using experimental dynamic properties. The model’s reliability was validated through the correlation between numerical predictions and experimental observations, enabling a thorough stability analysis of the structure. Results reveal concerning stability issues in specific columns of the inner ring, identifying elements at significant risk of collapse. This finding demonstrates the effectiveness of the proposed methodology in detecting critical structural vulnerabilities in historic buildings, providing crucial information for preservation strategies. Full article

Background/Objectives: Hot-melt extrusion (HME) has gained prominence for the manufacture of sustained-release oral dosage forms, yet the application of wax-based matrices and their resilience to alcohol-induced dose dumping (AIDD) remains underexplored. This study aimed to develop and characterise wax-based sustained-release felodipine formulations, with a particular focus on excipient functionality and robustness against AIDD. Methods: Felodipine sustained-release formulations were prepared via HME using Syncrowax HGLC as a thermally processable wax matrix. Microcrystalline cellulose (MCC) and lactose monohydrate were incorporated as functional fillers and processing aids. The influence of wax content and filler type on mechanical properties, wettability, and drug release behaviour was systematically evaluated. Ethanol susceptibility testing was conducted under simulated co-ingestion conditions (4%, 20%, and 40% v/v ethanol) to assess AIDD risk. Results: MCC-containing tablets demonstrated superior sustained-release characteristics over 24 h, showing better wettability and disintegration. In contrast, tablets formulated with lactose monohydrate remained structurally intact during dissolution, overly restricting drug release. This limitation was effectively addressed through granulation, where reduced particle size significantly improved surface accessibility, with 0.5–1 mm granules achieving a satisfactory release profile. Ethanol susceptibility testing revealed divergent behaviours between the two filler systems. Unexpectedly, MCC-containing tablets showed suppressed drug release in ethanolic media, likely resulting from inhibitory effect of ethanol on filler swelling and disintegration. Conversely, formulations containing lactose monohydrate retained their release performance in up to 20% v/v ethanol, with only high concentrations (40% v/v) compromising matrix drug-retaining functionality and leading to remarkably increased drug release. Conclusions: This study highlights the pivotal role of excipient type and constitutional ratios in engineering wax-based sustained-release formulations. It further contributes to the understanding of AIDD risk through in vitro assessment and offers a rational design strategy for robust, alcohol-resistant oral delivery systems for felodipine. Full article

Cadmium (CAD) is a prevalent environmental contaminant that poses serious cardiotoxic risks. The heart, kidney, liver, and brain are just a few of the essential organs that can sustain serious harm from CAD, a very poisonous heavy metal. The cardiotoxic mechanism of CAD is linked to oxidative damage and inflammation. A trace element with anti-inflammatory, anti-apoptotic, and antioxidant qualities, selenium (SEL) can be taken as a dietary supplement. The biotoxicity of heavy metal CAD is significantly inhibited by SEL, a mineral that is vital to human and animal nutrition. Through ROS-induced PARP-1/ADPR/TRPM2 pathways, this study seeks to assess the preventive benefits of selenium against cardiovascular damage caused by CAD. The SEL showed encouraging results in reducing inflammatory and oxidative reactions. Rats were given 0.5 mg/kg SEL and 3 mg/kg 2-Aminoethyl diphenylborinate (2-APB) intraperitoneally for five days, in addition to 25 mg/kg CAD given via gavage. Histopathological examination findings revealed that the morphologic changes in the hearts of the CAD group rats were characterised by marked necrosis and the degeneration of myocytes and congestion of vessels. Compared to the rats in the CAD group, the hearts of the SEL, 2-APB and SEL+2-APB groups showed fewer morphological alterations. Moreover, in rats given CAD, there was an increase in cardiac malondialdehyde (MDA), total oxidant (TOS), reactive oxygen species (ROS), caspase (Casp-3-9), and TNF-α, whereas glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and total antioxidant (TAS) decreased. SEL improved antioxidants, avoided tissue damage, and reduced cardiac MDA, TOS, and ROS. In rats given CAD, SEL decreased cardiac PARP-1, TRPM2, TNF-α, and caspase. In summary, by reducing oxidative stress and cardiac damage and modifying the ROS/PARP-1/TRPM2 pathway, SEL protected against CAD cardiotoxicity. Full article

Staphylococcus aureus frequently causes intramammary infections in dairy cows (bovine mastitis), which impair animal welfare, milk yield, and food safety. This study determined the prevalence and genetic diversity of S. aureus in bulk tank milk (BTM) samples from community-based Alpine dairy pastures in Tyrol, a major milk-producing region in Austria. Throughout the 2023 Alpine season (May–September), 60.3% (94/156) of BTM samples tested positive for S. aureus at least once over the course of up to four samplings. A total of 140 isolates collected from the 94 S. aureus-positive community-based Alpine dairy pastures revealed 33 distinct spa types, with t2953 (n = 33), t529 (n = 12), t267 (n = 11), and t024 (n = 10) being the most common. Selected isolates representing the different spa types were characterised by DNA microarray-based genotyping, multi-locus sequence typing (MLST), and antimicrobial susceptibility testing. Isolates with spa types associated with bovine-adapted CC8 (CC8bov/GTB) were identified as the most common subtype, being detected in BTM samples from 35.3% (55/156) of the pastures. This emphasises the high prevalence of this subtype in dairy herds across European Alpine countries. Other common bovine-associated subtypes were also detected, including CC97, CC151, and CC479. While antimicrobial resistance was rare, enterotoxin-producing genes were detected in all CC8bov-associated spa types. Overall, these findings underscore the importance of rigorous hygiene practices in dairy farming, particularly in community-based Alpine dairy pastures, where the risk of transmission is particularly high. It also emphasises the need for continued surveillance and subtyping to improve animal health, ensure food safety, and promote sustainable milk production. Full article

Geo-historical information deduced from geo-iconographical resources, derived from extensive research and the selection of cartographies and historical documents, enabled the investigation of the natural and anthropic transformations of the perifluvial area of the Po River in the Emilia-Romagna region (Italy). This territory, significant in terms of its historical, cultural, and environmental contexts, for centuries has been the scene of flood events. These have characterised the morphological and dynamic variability in the riverbed and relative floodplain. The close relationship between man and river is well documented: the interference induced by anthropic activity has alternated with the sometimes-damaging effects of river dynamics. The attention given to the fluvial region of the Po River and its main tributaries, in a peculiar lowland sector near Parma, is critical for understanding spatial–temporal changes contributing to current geo-hydrological risks. A GIS project outlined the geomorphological aspects that define the considerable variations in the course of the Po River (involving width reductions of up to 66% and length changes of up to 14%) and its confluences from the 16th to the 21st century. Knowledge of anthropic modifications is essential as a tool within land-use planning and enhancing community awareness in risk-mitigation activities and strategic management. This study highlights the importance of interdisciplinary geo-historical studies that are complementary in order to decode river dynamics in damaging flood events and latent hazards in an altered river environment. Full article

Assessing the risks associated with waste disposal is essential for environmental protection and sustainable development, especially given concerns about the impact of industrial activities on the environment. This study analyses soil contamination in the Defor Petrila tailings-dump area caused by the deposition of waste material resulting from coal exploitation. To characterise the heavy-metal contamination in detail, we applied a comprehensive methodology that includes the calculation of the geo-accumulation index (I_geo), contamination factor (Cf), and potential ecological risk index (PERI), along with an analysis of the heavy-metal concentration isolines and a statistical analysis using the Pearson correlation coefficient. The results reveal varying levels of heavy-metal concentrations, as indicated by the calculated indices. The findings underscore the need for remediation and ongoing monitoring to mitigate the environmental impacts. This study provides a scientific basis for decision making in environmental management and highlights the importance of assessing mining-waste disposal near human settlements using various contamination-assessment methods. Full article

Today, coastal storms represent one of the most formidable environmental challenges, causing significant impacts on coastal communities. This situation underscores both the importance and urgency of studying storms and their characterization. This study proposes an innovative approach combining Principal Component Analysis (PCA) and machine learning (Classification and Regression Trees, CART) to characterize and distinguish damaging storms from non-damaging ones along the coast of Dakar, Senegal. The analysis revealed that among several hydrometeorological variables studied (wave height, period, direction, runup, wave energy, sea level anomaly, tide, etc.), the variables SLA and tide play a central role in the occurrence of damage, although they are weakly correlated with the others. By cross-analyzing these variables, critical thresholds were established, such as Tide > 0.53 m combined with SLA ≥ 0.061 m, Tide > 0.53 m and ECWL ≥ 1.3 m, as well as Runup ≤ 0.64 m associated with a high wave period (Tp), allowing accurate differentiation of potentially damaging storms. The CART method validated these results and identified three key combinations: (1) Tide–SLA, where no damage is observed if Tide < 0.53 m, and damage occurs beyond this threshold when SLA ≥ 0.061 m; (2) Tide–ECWL, where storms are damaging if Tide > 0.53 m and ECWL ≥ 1.3 m; (3) Runup–Tp, where storms are damaging if Runup ≤ 0.64 m or if Runup > 0.82 m with Tp ≥ 16 s. These results constitute the first application of machine learning for storm classification on the Senegalese coast, providing a novel quantitative foundation for better understanding the hydrodynamic conditions associated with damaging storms. The findings of this study could be valuable for risk management and the development of early warning systems Full article

Background: Myocarditis and pericarditis are recognised risks following COVID-19 vaccination, including the mRNA-1273 vaccine. Most cases occur shortly following the second dose of this vaccine, and incidence is highest among young males. However, little is known about risk factors beyond age and sex and about the longer-term clinical course. This study aims to identify possible risk factors for myocarditis and pericarditis following mRNA-1273 vaccination, to characterise the clinical course of myocarditis and pericarditis, both associated with mRNA-1273 vaccination and not associated with vaccination, and to identify risk factors for severe outcomes (i.e., cardiac or thromboembolic complications, severe hospital outcomes, all-cause hospital readmission, and death). Methods: This study is being conducted within the Vaccine Monitoring Collaboration for Europe (VAC4EU) association using routinely collected healthcare data from five data sources from four European countries (Denmark, Norway, Spain, and the United Kingdom). The study is being performed using a common data model, and all analyses are performed separately in each data source in a federated manner following a common protocol. A case–cohort analysis set is identified within each data source for identifying potential risk factors for myocarditis and pericarditis following mRNA-1273 vaccination using logistic regression analysis. The clinical course of myocarditis and pericarditis is being assessed using a cohort study design and describes all cases (i.e., cases associated with mRNA-1273 and unexposed cases). Cox regression analysis is applied to assess the associations between risk factors and several follow-up outcomes. Conclusions: This protocol describes the study methodology of an international collaborative initiative with the aim of assessing the risk factors and clinical course of myocarditis and pericarditis following mRNA-1273 vaccination using a federated network of five European data sources. Full article