Modern football is characterized by playing both in defense and attack, which requires greater energy demands from players, and the amount and intensity of movement increases from year to year. The aim of the study was to determine differences in the distance covered and movement intensities of players in relation to their position in the team. The sample was players who played all 90 minutes of the knockout phase of the 2022 World Cup (N=224), according to positions: goalkeepers (n=31), defense (n=101), midfielders (n=61), and attackers (n=31). Data were taken from the official FIFA website (www.fifa.com): distance covered (m), distance covered in zone 1 (speed 0-7 km/h), in zone 2 (7-15 km/h), in zone 3 (15-20 km/h), in zone 4 (20-25 km/h) and in zone 5 (>25 km/h), number of runs in zone 4, number of sprints in zone 5, maximum achieved speed (km/h). Differences between positions were determined by discriminant analysis. Three discriminant functions were isolated that are statistically significant at the 99% level (sig.=0.000) (Can. Cor.=0.934; Can. Cor =0.492 and Can. Cor.=0.356). The highest correlations with the first function, which maximally differentiates positions (Wilks Lambda =0.085; sig.=0.000), have the variables: intensity of movement in zone 2, number of runs in zone 4 and total distance covered. The second function (Wilks Lambda =0.662; sig.=0.000) is determined by the maximum achieved speed and distance covered in zone 3. The third function (Wilks Lambda =0.873; sig.0.000) is determined by intensity of movement in zone 4, number of sprints, distance covered in zone 5 and in zone 1. Excluding the goalkeeper position, it is evident that positions in the team are approaching each other in relation to distance covered, intensity of movement and maximum speed of movement, which supports the thesis that in modern football, polyvalent football players who can be used in multiple positions in the team are increasingly profiled

Unergative verbs assign the agent theta role to subjects whereas unaccusative verbs occur with theme subjects. Theory suggests that, unlike subjects of unergative verbs, theme subjects of unaccusative verbs are merged in the post-verbal internal argument position and moved to the pre-verbal external argument position. In a cross-modal lexical priming experiment, we tracked (re‑)activation patterns of the subject in sentences with imperfective and perfective unergative and unaccusative verbs in Bosnian/Croatian/Serbian (BCS). We investigated the interplay between unaccusativity and verbal aspect. Our findings are that the subject of perfective unaccusative verbs is (re‑)activated post-verbally, at the gap position, whilst this is not the case for unergative verbs and imperfective unaccusative verbs.

Background/Objectives: Antimicrobial resistance (AMR) is a major public health problem driven partly by inappropriate antibiotic use. Students of health studies represent future healthcare professionals with an important role in patient education, infection prevention, and antimicrobial stewardship. This study assessed knowledge, attitudes, and behaviours regarding antibiotic use and AMR among students of the Faculty of Health Studies, University of Mostar. Methods: An anonymous cross-sectional online survey was conducted in March 2025 using a self-selected convenience sample. The questionnaire was adapted from a previously published survey among Cypriot university students and distributed through student WhatsApp groups and by e-mail. Of 1113 invited students, 220 completed the survey, yielding a response rate of 19.8%. Results: During the previous 12 months, 39.5% of respondents reported antibiotic use. Most respondents reported adherence to medical instructions regarding dosage and duration of therapy, while 20.5% reported self-medication with antibiotics and 29.5% reported keeping unused antibiotics at home. Approximately 42% perceived antibiotics as easy or very easy to obtain without a prescription. Only 36.4% of respondents correctly distinguished antibiotics from other medications. Although most respondents recognised that bacteria can develop resistance, misconceptions persisted regarding humans and viruses. Differences between study programmes were observed for some attitudes and perceptions, whereas gender and year of study were not significantly associated with most responses. Conclusions: Health studies students demonstrated partial knowledge of antibiotics and AMR, together with behaviours that may contribute to inappropriate antibiotic use. Strengthened curricular content on rational antibiotic use, infection management, infection prevention, and antimicrobial stewardship appears justified. The findings are also consistent with the need to consider broader stewardship measures, including better enforcement of existing prescription-only dispensing requirements in Bosnia and Herzegovina.

Background and Objectives: Vitamin D signaling plays critical roles in immune regulation, bone metabolism, and cellular differentiation across multiple tissues. However, the spatial and temporal expression patterns of key vitamin D signaling components—the vitamin D receptor (VDR) and the enzyme 1α-hydroxylase (encoded by CYP27B1)—during human nephrogenesis have not been mapped at the protein level. The primary objective of this study was to characterize VDR and 1α-hydroxylase expression across critical stages of human kidney development, complementing prior transcriptomic and single-cell descriptions, and to contextualize these developmental observations against the dysregulation of vitamin D pathway genes in adult renal and urothelial malignancies. Materials and Methods: Immunofluorescence analysis was performed on FFPE kidney tissue from 12 specimens (3 per stage) at 10, 22 and 38 gestational weeks and postnatally at 1.5 years. For each specimen, at least three non-adjacent sections were stained and 6 non-overlapping cortical fields were imaged at ×40 (18 fields per stage). Fluorescence-area percentages were quantified in ImageJ 1.54g, and group differences were assessed by one-way ANOVA with Tukey’s post hoc test at both field- and specimen-level. An accompanying bioinformatic analysis evaluated the differential expression of VDR, CYP27B1, and CYP24A1 in adult renal and urothelial malignancies (TCGA cohorts: KICH, KIRC, KIRP, BLCA) using unpaired Welch’s t-test, with Benjamini–Hochberg FDR correction applied across all 16 tumor-versus-normal comparisons (12 gene-wise + 4 post hoc log2(CYP24A1/CYP27B1) ratios). Results: VDR showed its highest mean fluorescence area at 10 weeks (3.40% (95% CI 3.24–3.56); field-level Tukey p < 0.0001 versus other stages) and its lowest at 22 weeks (0.69% (0.64–0.74)). 1α-hydroxylase was also highest at 10 weeks (5.44% (5.29–5.60); p < 0.0001) and stabilized at lower levels thereafter (3.04–4.26%). Co-expression of both proteins was observed throughout development except in 22-week glomeruli. In TCGA, all 12 significant gene-wise comparisons retained significance after BH FDR correction (q < 0.05). VDR showed cohort-specific dysregulation: reduced in KICH (q = 2 × 10−4) but increased in KIRC and KIRP (q = 2 × 10−4 for both). CYP24A1 was reduced in all three renal cohorts (q ≤ 0.029) and unchanged in BLCA. CYP27B1 showed cohort-specific direction (reduced in KIRC; increased in KICH, KIRP, and BLCA). Conclusions: This study provides an initial immunofluorescence-based spatial description of VDR and 1α-hydroxylase across human kidney development, revealing a coordinated redistribution from immature glomeruli at 10 weeks to mature tubular segments at later stages. The TCGA analysis demonstrates that vitamin D pathway dysregulation in renal carcinoma is cohort-specific and is not abolished by multiple-testing correction. Together, these results indicate that the developmentally engaged vitamin D pathway retains kidney-specific functional relevance in adult renal pathology and provide a baseline reference for future mechanistic studies.

Pomegranate peel, an abundant agro-industrial by-product, represents a sustainable source of bioactive polyphenols, particularly punicalagin, which has been associated with antioxidant and photoprotective potential. This study aimed to develop microemulsions (MEs) containing pomegranate peel extract for dermal delivery of punicalagin using biocompatible surfactant systems. Three MEs differing in surfactant–cosurfactant composition (ME-A, ME-P, and ME-E) were prepared. Each formulation solubilized 1% (w/w) of pomegranate peel extract and was evaluated regarding in vitro release behavior, skin permeation/retention, antioxidant activity, and in vitro sun protection factor (SPF). All investigated MEs provided sustained release of punicalagin (≈10–17% of the applied dose in 8 h). ME-A, based on an alkyl polyglucoside surfactant, showed a significantly higher cumulative release of punicalagin (60.4 µg/cm2) compared with ME-E and ME-P. In skin penetration/permeation studies, ME-A also exhibited the highest numerical total delivery of punicalagin (≈48.2 µg/cm2 after 24 h), although differences among formulations were not statistically significant. All formulations demonstrated high antioxidant activity in the DPPH assay and measurable in vitro photoprotective potential, with SPF values ranging from approximately 11 to 14. Overall, pomegranate peel extract-loaded MEs showed potential as dermal delivery systems capable of improving solubilization and modulating skin delivery of punicalagin. The combination of agro-waste-derived bioactives with biocompatible surfactants highlights the potential of these systems as sustainable approaches for skincare formulations.

Acute coronary syndrome (ACS) is increasingly prevalent among young patients. The prevalence of ACS among young women has also increased. It is well known that coronary artery disease (CAD) follows a different pattern in women and men. In order to provide timely and appropriate treatment, it is necessary to understand the gender differences in the risk factors, clinical profile, and early outcome in the young ACS patient population. Understanding and addressing the risk factors linked to the early onset of the disease is therefore essential to lowering the burden of premature CAD (PCAD). This study aimed to analyse the gender differences in the presence of major coronary risk factors, clinical presentation, diagnosis and immediate outcomes in patients with PCAD. We evaluated 218 consecutive patients who were hospitalised in the ICCU of cardiology department with diagnosis of PCAD between November 2023 and May 2025, after satisfying the inclusion criteria. All included patients were 45 years of age or younger, were admitted for their first acute coronary syndrome and underwent primary PCI with optimal revascularization results. The study included 72 female and 146 male patients. The mean age of females was 42.5 ± 2.22 years and males was 39.6 ± 3.85 years (p<0.001). Young women had significantly more risk burden of hypertension (70.2% vs 36.5% p<0.001) diabetes (38.9% vs 28.7%, p<0.001) and dyslipidaemia (61.4% vs. 38.4%, p<0.001) compared to young men. Among young males, smoking was significantly higher (76.5% vs. 25.2%, p<0.001). NSTEMI was more common presentation among females (22.5% vs 8.4%, p<0.001) with more prevalent non obstructive CAD (13.1% vs. 8.2%, p=0.15). Young male patients showed angiographically more severe CAD and greater frequency of multivessel CAD (22.8% vs 17.9%, p=0.58). Young female patients had significantly better mean ejection fraction (EF) (48.1±7.9% vs 39.2±9.8%, p=0.13). Young women had more often acute heart failure (Kilip class ≥ 2) and longer length of stay in the intensive care unit (12.4% vs.6.29%, P=0.04; 5.5 vs 2.7 days, p <0.001 respectively). Mortality rate in the first 48 hours of admission was higher in man than in woman (1.65% vs.1.13%, p=0.65). A distinct gender difference in the risk factor profile for PCAD supports an early, comprehensive, but gender-specific approach to prevention. Young patients with premature CAD may benefit from these findings in terms of risk factor modification and gender-based management approach.

This study aimed to examine the influence of effective playing time (EPT) on match running performance (MRP) in elite soccer players competing in the UEFA Champions League (UCL), while controlling for contextual factors. In total, 1371 individual observations, involving 437 outfield players, participating in 32 teams, were collected from 122 matches using an optical tracking system. The MRP variables included total distance (TD), low- (LIR), moderate- (MIR), and high-intensity running (HIR). Linear mixed models were applied, with match outcome, match location, and opponent quality included as fixed effects, and player and team identity as random effects. The results showed that EPT significantly influenced TD (f=5.01–14.20, all p<0.01) and LIR (f=3.23–21.93, all p<0.05) across most playing positions, with players covering 9–10% greater distances in matches with very long EPT compared to very short EPT. In contrast, no significant effects of EPT were observed for MIR and HIR across any playing position. These findings indicated that longer EPT primarily increased overall activity, mainly through low-intensity activities, while moderate- and high-intensity activities remained relatively stable. Importantly, this pattern was consistent across players from multiple national contexts. From a practical perspective, EPT should be considered when planning and monitoring overall load, whereas moderate- and high-intensity activities should be systematically developed and maintained through training independent of EPT.

Compounds from olive (Olea europaea L.) and pomegranate (Punica granatum L.) have many beneficial effects on human health. This review paper considers the inhibitory potential, under in vitro conditions, of bioactive components of olive and pomegranate on different enzyme systems. Research shows that olive polyphenols (oleuropein, hydroxytyrosol, luteolin, and oleocanthal), as well as pomegranate polyphenols (punicalagin, urolithin A, ellagic acid), inhibit cyclooxygenase and lipoxygenase enzymes, which are associated with inflammatory processes. They also show an inhibitory effect on acetylcholinesterase, butyrylcholinesterase, and β-secretase, which opens up the possibility of a strong neuroprotective effect. Olive and pomegranate polyphenols also have an inhibitory effect on enzymes involved in carbohydrate metabolism, such as amylase and glucosidase, and can help fight diabetes and regulate human metabolism. In addition, polyphenols and extracts of both plants showed an inhibitory effect on cytochrome P450 enzymes, which metabolize most drugs. These data open up the possibility of interactions with certain groups of drugs. The current evidence supports the view that olive and pomegranate polyphenols act as biologically versatile compounds with considerable pharmaceutical and nutraceutical potential. Future investigations integrating enzymology, metabolomics, molecular docking, and clinical validation will be essential for translating these promising in vitro findings into evidence-based therapeutic applications.

BACKGROUND Enteric infectious diseases claim more than 1 million lives annually and are among the top ten causes of death in children younger than 5 years. Remarkable global investment has been dedicated to enteric infectious disease prevention and control; however, the shifting global health landscape is testing the continuance of progress. To evaluate the current status and guide future interventions, we present the latest epidemiological estimates of enteric infectious diseases from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 and assess progress towards the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target of fewer than 20 deaths per 100 000 children younger than 5 years by 2025. METHODS We quantified the incidence, mortality, and disability-adjusted life-years (DALYs) of enteric infectious diseases by age, sex, and year across 204 countries and territories from 1990 to 2023. In GBD 2023, the following were considered under the category of enteric infectious diseases: diarrhoeal diseases, enteric fever (typhoid and paratyphoid), invasive non-typhoidal Salmonella spp (iNTS) infections, and other intestinal infectious diseases. We also examined 15 aetiologies contributing to diarrhoeal diseases. Incidence and prevalence were estimated with DisMod-MR (version 2.1), a Bayesian meta-regression tool, drawing on data from systematic reviews, population-based surveys, claims data, and hospital sources. Cause-specific mortality was modelled with Cause of Death Ensemble Modelling based on data from sources including vital registration, mortality surveillance, verbal autopsy, and minimally invasive tissue sampling. Years of life lost and years lived with disability were computed and combined to derive DALYs. For aetiology-specific estimation, population-attributable fractions (PAFs) for 15 pathogens were derived with a counterfactual framework. Point estimates and 95% uncertainty intervals (UIs) were generated from 250 draws from the posterior distribution. FINDINGS In 2023, enteric infectious diseases resulted in an estimated 1·27 million (95% UI 0·963-1·68) deaths globally, declining from 3·69 million (3·04-4·56) in 1990. The global age-standardised mortality rate (ASMR) decreased from 74·1 (62·0-92·9) per 100 000 population to 16·4 (12·6-21·3) per 100 000 population during the same period. Diarrhoeal diseases accounted for most deaths in 2023 (1·11 million [0·811-1·54]), followed by enteric fever and iNTS. South Asia and sub-Saharan Africa remained the most affected regions in 2023, with 599 000 (441 000-882 000) and 501 000 (373 000-648 000) deaths due to enteric infectious diseases, respectively, predominantly from diarrhoeal disease. Rotavirus was the leading cause of all-age diarrhoeal disease deaths (PAF 16·3% [12·0-21·5]), followed by norovirus (10·2% [2·4-17·0]) and Shigella spp (9·3% [5·4-15·2]). Among children younger than 5 years, PAFs of deaths due to diarrhoeal diseases were 40·2% (32·5-48·5) for rotavirus, 24·0% (15·1-36·7) for Shigella spp, and 23·4% (13·7-34·3) for adenovirus. Across 204 countries and territories, 141 met the GAPPD mortality target in 2023. The driving aetiologies among countries that did not meet the target in 2023 varied slightly by GBD super-region, but the highest or second-highest number of deaths in children younger than 5 years were consistently attributed to rotavirus. Astrovirus and sapovirus, newly included in GBD 2023, were responsible for 24 600 (6290-49 000) and 18 800 (4650-44 400) deaths, respectively, in 2023, mainly in children younger than 5 years. INTERPRETATION Our findings show that mortality and ASMRs of enteric infectious diseases declined substantially between 1990 and 2023. This decline is consistent with the expansion of public health measures and broader socioeconomic development. However, the burden in 2023 remains considerably high, with the highest mortality concentrated in sub-Saharan Africa and south Asia. Considering that more than a quarter of all countries had yet to meet the GAPPD mortality target in 2023, sustained efforts are needed to address the persistent burden in affected countries and to adapt to the changing global health landscape. FUNDING Gates Foundation.

Background: Hofbauer cells (HBCs) are the only immunocompetent cells within the stroma of chorionic villi and play a key role in immune regulation and placental development throughout gestation. Their phenotype, abundance, and proliferative activity change in accordance with the needs of the fetoplacental unit. Methods: Thirty healthy human placentas across all three trimesters were analyzed. Samples were processed using standard histological protocols and immunohistochemically stained with CD45, CD68, CD86, and Ki-67 markers. Morphometric analysis was performed to determine the following parameters: percentage of HBCs, numerical areal density, and proliferative index. Results: HBCs were immunoreactive for CD45 and CD68, while CD86 immunoreactivity was not observed in any trimester. The proportion of HBCs was highest in the second trimester and lowest in the third. Numerical areal density was highest in the second trimester (22.21 ± 3.86) and lowest in the first (8.27 ± 4.18). The proliferative index was highest in the first trimester (82.45 ± 10.19%), decreased significantly in the second, and was completely absent in the third trimester. Conclusions: During physiological placental development, Hofbauer cells maintain a predominantly non-M1 macrophage phenotype, accompanied by a gradual reduction in proliferative activity.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and the leading cause of end‐stage renal disease. Oxidative stress and inflammation are central drivers of DN progression, yet no effective therapies exist to prevent or delay renal injury. This study investigated the renoprotective effects of glycine (GLY), N‐acetylcysteine (NAC), and their combination administered at early versus late stages of streptozotocin induced diabetes. Forty‐eight male Wistar rats (n = 48) were allocated into five groups: healthy controls (Group 1, n = 6), untreated diabetic rats (Group 2, n = 6), and three treatment groups (Groups 3–5, each n = 12). Diabetes was induced by a single intraperitoneal streptozotocin injection (55 mg/kg). Group 3 received NAC (100 mg/kg), Group 4 received GLY (250 mg/kg), and Group 5 received NAC + GLY. Each treatment group was subdivided into early (6 week, n = 6) and late (12 week, n = 6) intervention subgroups. Treatments were administered orally. Renal tissue was evaluated using classic histology, geometric morphometric analysis, and biochemical assays of superoxide dismutase (SOD) and myeloperoxidase (MPO). Statistical analyzes were performed using ANOVA with appropriate post hoc tests (p < 0.05). Untreated diabetic rats (Group 2) showed significantly decreased SOD activity, increased MPO levels, marked mesangial matrix expansion, glomerular hypercellularity, tubular epithelial degeneration, and interstitial inflammation with fibrosis. NAC (Group 3) and GLY (Group 4) each improved oxidative stress markers and partially restored glomerular and tubular morphology, with early treatment subgroups exhibiting more substantial benefit than late subgroups. The combined NAC + GLY therapy (Group 5) demonstrated the strongest renoprotective effect, preserving renal structure and biochemical parameters closest to healthy controls. To conclude, early combined administration of glycine and N‐acetylcysteine yields superior protection against diabetes‐induced renal injury compared with individual treatments. These findings support the therapeutic potential of antioxidant‐amino acid combinations in preventing or delaying diabetic nephropathy.