Search Results (25,464)

This study investigated the effects of probiotic supplementation on performance, egg quality, antioxidant capacity, gut morphology, fecal microbiota, and bone morphology in Lohmann Brown laying hens aged 44 weeks over a 16-week period. Ninety-six hens were randomly divided into control and probiotic groups (n = 48 each). The probiotic group received probiotic supplement containing Lactobacillus acidophilus KUEN 1607 and Pediococcus acidilactici KUEN 1608 via drinking water at 0.5%. Probiotic supplementation significantly improved feed conversion ratio (FCR), eggshell strength and thickness, and albumen quality (p < 0.001) and reduced the incidence of cracked and shell-less eggs (p < 0.05). Yolk and serum cholesterol levels decreased (p < 0.001), and antioxidant parameters improved, along with elevated serum IgG (p < 0.001). Histological analysis showed an increased ratio of villus height to crypt depth (p < 0.001) in the jejunum, indicating enhanced intestinal health. Fecal samples revealed increased Lactobacillus spp. and reduced coliform counts (p < 0.001), suggesting improved gut microbiota balance. While bone volume and surface area showed no significant difference, 3D geometric morphometric analysis identified subtle shape changes in long bones, especially the femur and tibiotarsus. These findings demonstrate that the selected probiotic combination supports nutrient utilization, egg quality, gut integrity, immune status, and skeletal health, offering a sustainable strategy to enhance productivity and welfare in laying hens. Full article

Background: GSK3β is an intracellular regulatory kinase that is dysregulated in multiple tissues in Type 1 myotonic dystrophy (DM-1). Tideglusib inhibits GSK3β activity in preclinical models of DM-1 and promotes cellular maturation, normalising aberrant molecular and behavioural phenotypes. It is currently in clinical development for the treatment of paediatric and adult patients affected by congenital and juvenile-onset DM-1. Here, we summarise the development of a population pharmacokinetic model and subsequent characterisation of influential demographic and clinical factors on the systemic exposure to tideglusib. The availability of a population PK model will allow further evaluation of age-and weight-related changes in drug disposition, supporting the dose rationale and implementation of a paediatric extrapolation plan. Methods: Given the sparse pharmacokinetic sampling scheme in patients receiving tideglusib, model development was implemented in two steps. First, data from Phase I studies in healthy elderly subjects (i.e., 1832 plasma samples, n = 54) were used to describe the population pharmacokinetics of tideglusib in adults. Then, pharmacokinetic model parameter estimates obtained from healthy subjects were used as priors for the evaluation of the disposition of tideglusib in adolescent and adult DM-1 patients (51 plasma samples, n = 16), taking into account demographic and clinical baseline characteristics, as well as food intake. Secondary pharmacokinetic parameters (AUC, C_max and T_max) were derived and summarised by descriptive statistics. Results: Tideglusib pharmacokinetics was described by a two-compartment model with first-order elimination and dose-dependent bioavailability. There were no significant differences in disposition parameters between healthy subjects and DM-1 patients. Body weight was a significant covariate on clearance and volume of distribution. Median AUC_(0–12) and C_max were 1218.1 vs. 3145.7 ng/mL∙h and 513.5 vs. 1170.9 ng/mL, following once daily doses of 400 and 1000 mg tideglusib, respectively. In addition, the time of food intake post-dose or the type of meal appeared to affect the overall exposure to tideglusib. No accumulation, metabolic inhibition, or induction was observed during the treatment period. Conclusions: Even though clearance was constant over the dose range between 400 and 1000 mg, a less than proportional increase in systemic exposure appears to be caused by the dose-dependent bioavailability, which reflects the solubility properties of tideglusib. Despite large interindividual variability in the tideglusib concentration vs. time profiles, body weight was the only explanatory covariate for the observed differences. This finding suggests that the use of weight-banded or weight-normalised doses should be considered to ensure comparable exposure across the paediatric population, regardless of age or body weight. Full article

This study aims to analyze the technical and economic infrastructure of sheep farming enterprises operating in Türkiye. It assesses the demographic characteristics of enterprise owners, enterprise scales, production objectives, marketing strategies, and economic performance. Primary data were collected through face-to-face surveys conducted with 201 sheep farming enterprises during the 2023 production period. The sample was selected based on information provided by the Provincial Directorates of Agriculture and Forestry and the Breeding Sheep and Goat Breeders’ Associations. Data analysis was performed using SPSS 27. Categorical data related to enterprise characteristics and the demographic profiles of enterprise owners were examined. The findings indicate that the majority of enterprise owners are middle-aged or older individuals, have a low level of education, and operate predominantly within an extensive production system. The producers’ marketing methods rely mainly on direct sales. In conclusion, ensuring the sustainability of the sheep farming sector requires encouraging young producers to enter the industry, expanding educational programs, and adopting modern production techniques. Full article

Introduction: Hepatitis B is the most prevalent virus that causes severe liver infection worldwide. According to the current guidelines, the HBV viral load and other factors can help in treatment decisions. Therefore, the present study explores the relationship between the HBV viral load and blood-based laboratory parameters. Methods: The HBV viral load was evaluated in blood samples from 159 HBsAg-positive patients (ICT-positive). The viral load was categorized as high (above 200,000 IU/mL), moderate (between 2000 and 200,000 IU/mL), or low (below 2000 IU/mL). The viral load was then compared with laboratory parameters. Results: A significant association was observed between the Hepatitis B viral load and the patient’s age (p < 0.01). The males showed a substantially higher viral load, with 29.2% of the male patients exhibiting elevated levels, compared to 11% of the females. A statistically significant correlation was found between the viral load and liver enzymes, specifically AST (p < 0.005) and ALT (p < 0.04), as well as calcium (p < 0.01). Notably, the elevated ALT and AST levels were more pronounced in the patients with moderate and high viral loads, suggesting a potential link to liver dysfunction. A remarkable insight uncovered in our study revolves around the notable increase in the serum calcium levels (p < 0.01). Conclusions: The AST, ALT, and serum calcium levels were the most altered parameters with high HBV viral load. Though limited reports are available on altered serum calcium levels, they could serve as potential laboratory markers for assessing disease progression in HBV infection. Moreover, focusing on potential therapies to normalize the AST, ALT, and serum calcium levels could offer promising avenues for combating HBV infection. Full article

Background: Mobility plays a fundamental role in causal reasoning (causal inference or cause–effect learning), which is essential for brain development at early ages. Children naturally develop causal reasoning through interaction with their environment. Therefore, children with severe motor disabilities (GMFCS levels IV–V), who face limited opportunities for interaction, often show delays in causal reasoning. Objective: This study investigates how a wheelchair-mounted, semi-autonomous mobility platform operated via a simple switch may enhance causal learning in children with severe disabilities, compared with traditional therapies. However, due to the scarcity of participants who meet the inclusion criteria and the need for long-term evaluation, recruitment poses a significant challenge. This study aims to provide an initial assessment of the platform and collect preliminary data to estimate the required sample size and number of sessions for future studies. Methods: We conducted a pilot randomized controlled trial (RCT) to assess platform usability and its effect on reaction time and keystroke accuracy. Four children, aged 8.5 ± 2.38, participated in seven 30 min sessions. They were randomly assigned in equal numbers, with two participants in the intervention group (using the platform) and two in the control group (receiving standard therapy). Usability was evaluated through a questionnaire completed by two therapists. Key outcome measures included the System Usability Scale (SUS), reaction time (RT), and keystroke accuracy (NIS). Results: Despite the small sample size and recruitment challenges, the data allowed for preliminary estimates of the sample size and number of sessions required for future studies. Therapists reported positive usability scores. Children using the platform showed promising trends in RT and NIS, suggesting improved engagement with cause–effect tasks. Conclusions: The findings support the feasibility and usability of the mobility platform by therapists, although some improvements should be implemented in the future. No conclusive evidence was found regarding the platform’s effectiveness on causal learning, despite a positive trend over time. This pilot study also provides valuable insights for designing larger, statistically powered trials, particularly focused on NIS. Full article

Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies—particularly Mycobacterium tuberculosis—in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh–Neelsen (ZN), Periodic acid–Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at p ≤ 0.05. Results: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (p = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (p = 0.004). Conclusions: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions. Full article

Background: Functional massage is a soft tissue intervention that combines tissue compression with specific joint movements to enhance muscle function, improve joint mobility and reduce pain. The physical working capacity at the fatigue threshold (PWC_FT) uses surface electromyography to determine the highest exercise intensity that can be sustained indefinitely. The purpose of this study, therefore, was to examine the influence of FM on a multi-joint exercise such as cycle ergometry. Methods: Twelve healthy college-aged men volunteered for the current study. On two occasions, separated by seven days and in randomized order, subjects either completed a 14 min FM on both legs prior to an incremental cycle ergometer test to determine PWC_FT, or rested for 14 min before performing the same cycling test. Results: The paired samples t-tests revealed a significant (p < 0.05) difference for the absolute and relative PWC_FT values between the no-FM and FM conditions. Conclusions: These results indicate that FM may delay the onset of neuromuscular fatigue for whole-body exercise. Full article

Background/Objectives: There is still debate about students’ health in medical schools. The aim of this study was to assess the proportion of chronic diseases among medical students and analyze their predictors. Methods: We performed a secondary cross-sectional analysis using a database from a single Portuguese university. The sociodemographic/clinical variables of 309 medical students were included. Logistic regression was performed to ascertain the effects of sex, age, medical course year, financial situation, and family history of chronic diseases on the likelihood of medical students having chronic disease. Results: Median age (Q1, Q3) was 21 (17, 43) years, with females comprising 79.9% of the sample. The distribution of students by school year was similar. The majority (65.7%) reported having sufficient money. Twenty-three percent suffered from chronic disease, and around forty percent had parents or siblings with chronic disease. In the regression model, only a family history of chronic disease was associated with a personal history of chronic disease. Medical students with parents or siblings who have a chronic disease are 3.3 times more likely to have a chronic disease themselves. Conclusions: Future interventions targeting the medical student population will be needed in Portugal to reduce the prevalence and burden of chronic diseases, particularly among those with a positive family history. Full article

Lumpy skin disease virus (LSDV), a transboundary pathogen threatening cattle health in South and Southeast Asia, presents growing challenges for disease control. This study combined serological, molecular, and genomic approaches to investigate LSDV in Barura Upazila, Bangladesh. Serological screening of 424 cattle using a commercial ELISA revealed a high seroprevalence of 55.5% (95% CI: 50.7–60.3), indicating widespread exposure. Although differences were observed by age and breed, no significant associations were found with seropositivity, suggesting broad regional circulation. Real-time PCR confirmed LSDV DNA in all 20 clinically infected animals, with consistent P32 gene amplification. Two samples with low Cq values underwent whole-genome sequencing. The complete genomes of LSDV-L2/2024 and LSDV-L3/2024 showed >99.6% identity with the reference strain LSDV-29, yet carried unique genomic features, including truncated or variant ORFs and immune-related gene differences. Phylogenetic analysis of the DNA polymerase gene revealed distinct clustering: L2/2024 aligned with South Asian isolates, while L3/2024 grouped with strains from Africa, the Middle East, and Europe. These results highlight co-circulation of genetically diverse strains and possible cross-regional introductions. Overall, our findings underscore the evolutionary plasticity of LSDV and the critical need for ongoing genomic surveillance to guide targeted vaccine development and disease control strategies. Full article

Objectives: Anagrelide, an oral phosphodiesterase-3 inhibitor, is widely used to treat thrombocythemia. Evaluating the bioequivalence of low-dose formulations is essential to ensure consistent therapeutic outcomes while minimizing adverse effects, particularly cardiovascular events such as palpitations, tachycardia, and potential arrhythmias, which are known concerns with anagrelide therapy. This study aimed to compare the pharmacokinetics and bioavailability of a newly developed 0.5 mg anagrelide capsule with the reference product under fasting conditions y. Materials and Methods: In a randomized, open-label, two-period crossover design, 42 healthy Turkish male volunteers received a single oral dose (0.5 mg) of either the test or reference anagrelide capsule, with a seven-day washout period between treatments. Serial blood samples were collected over a 10 h post-dose period. Plasma concentrations of anagrelide were analyzed using a validated LC-MS/MS method. Key pharmacokinetic parameters (AUC₀–t, AUC₀–∞, Cmax, tmax, λz, t½, AUC–extrapol) were calculated and subjected to ANOVA-based bioequivalence analysis. Results: A total of 42 healthy male participants (mean age: 34.1 ± 8.9 years; BMI: 25.7 ± 2.9 kg/m²) completed the study without any protocol deviations. Pharmacokinetic analysis demonstrated that the test and reference formulations of anagrelide 0.5 mg were bioequivalent. The mean AUC₀–t values were 4533.3 ± 2379.3 pg·h/mL for the test formulation and 4515.0 ± 2392.3 pg·h/mL for the reference (p > 0.05), while the mean Cmax values were 1997.1 ± 1159.2 pg/mL and 2061.3 ± 1054.0 pg/mL, respectively (p > 0.05). The 90% confidence intervals for the geometric mean ratios of AUC₀–t (94.09–104.75%), Cmax (85.62–104.03%), and AUC₀–∞ (94.50–105.10%) were all within the predefined bioequivalence range of 80–125%, with corresponding point estimates of 99.28%, 94.37%, and 99.66%, respectively. Intra-subject variability was 14.68% for AUC₀–t and 26.98% for Cmax. No statistically significant differences were observed between the formulations for any of the primary or secondary pharmacokinetic parameters (ANOVA, p > 0.05). Regarding safety, 13 treatment-emergent adverse events were reported in 11 participants (26.2%), mostly moderate-intensity headaches, all of which resolved without complications. No serious adverse events occurred, confirming the tolerability of both formulations. Conclusions: This study demonstrates that the test and reference formulations of low-dose 0.5 mg anagrelide are bioequivalent under fasting conditions, with similar safety and tolerability profiles. The findings support the use of the test product as a safe and effective alternative. Full article

Background and Aim: Atresia is the most common congenital anomaly of the esophagus, with an increased risk of complications after surgical correction. The aim of our study was to evaluate the risk factors associated with early and late postoperative complications in neonatal patients with esophageal atresia. Methods: The study sample comprised 109 neonatal patients aged between 0 and 27 days of life who were prenatally diagnosed with esophageal atresia or diagnosed at birth. For the purpose of this study, neonatal and perinatal factors and factors associated with the mother’s medical condition were analyzed. Complications after surgical intervention were classified as early and late. Results: Patients with early postoperative complications experienced significantly more frequent complications during delivery (p = 0.002), asphyxia (p = 0.038), and postoperative sepsis (p = 0.045) and were more likely to have received medicamentous therapy (p = 0.035). Patients with late postoperative complications had significantly more frequent complications during delivery (p = 0.025), respiratory distress (p = 0.043), and postoperative sepsis (p = 0.010), were more likely to have received preoperative mechanical ventilation (p = 0.014), and showed a significantly different frequency distribution among the different classes of the Spitz classification (p = 0.008). A risk factor for early postoperative complications in patients with atresia in the upper part was complications during delivery (OR-3.09; p = 0.007). The risk factors for late postoperative complications for patients with upper atresia were preoperative mechanical ventilation (OR: 2.77; p = 0.041), postoperative sepsis (OR: 2.60; p = 0.028), and belonging to relatively high- and high-risk groups according to the Spitz classification (OR: 3.50; p = 0.022). Conclusions: In neonates who have undergone surgical intervention for esophageal atresia, a risk factor for early postoperative complications is complications during delivery, while the risk factors for late postoperative complications are preoperative mechanical ventilation, postoperative sepsis, and belonging to relatively high- and high-risk groups according to the Spitz classification. Therefore, a multidisciplinary approach and continuous monitoring are essential to reduce morbidity and mortality, as well as to improve quality of life, in these patients. Full article

Sex hormones’ and menstrual cycle’s effects on cognitive performance remain unclear. This study examined cognitive differences between women across menstrual cycle phases, sex differences between women and men, and hormone–cognition associations. In total, 71 healthy young adults, aged 20–36 (42 women, 29 men), completed standardised cognitive tests measuring attention, processing speed, working memory, and visuospatial abilities. Women were tested twice: during menstrual (low-oestradiol) and pre-ovulatory (high-oestradiol) phases; men once. Hormone levels (oestradiol, progesterone, testosterone) were measured in blood samples via electrochemiluminescence immunoassay (ECLIA). Two analytical strategies were used: (1) within-subject analysis comparing women between phases, and (2) between-group comparison across three groups—women in menstrual phase, pre-ovulatory phase, and men. Women performed better during pre-ovulatory versus menstrual phase in working memory (Digit span forward: p = 0.04; Digit span backwards max: p = 0.02) and attention switching (Trail Making Test B: p = 0.01). Sex differences in processing speed were observed only during the menstrual phase (Trail Making Test A: p = 0.03; Stroop B: p = 0.04), but not in the pre-ovulatory phase. Positive correlations between oestradiol/progesterone and cognitive performance were found in men, while complex bidirectional relationships emerged in women during the menstrual phase only. Testosterone showed no significant correlations. These findings highlight hormonal status effects on cognitive sex differences. Full article

Adipose tissue exhibits dynamic metabolic and structural changes in response to environmental stimuli, including temperature fluctuations. While continuous cold exposure has been extensively studied, the molecular effects of prolonged intermittent cold exposure (ICE) remain poorly characterized. Here, we present a proteomic analysis of inguinal white adipose tissue (IWAT) from mice subjected to a 16-week regimen of short-term daily ICE (6 °C for 6 h, 5 days per week) without compensatory caloric intake. Mass spectrometry identified 1108 proteins, with 140 differentially expressed between experimental and control groups. ICE significantly upregulated mitochondrial proteins associated with lipid and carbohydrate catabolism, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and lipogenesis, including LETM1, AIFM1, PHB, PHB2, ACOT2, NDUA9, and ATP5J. These changes reflect enhanced metabolic activity and mitochondrial remodeling. In contrast, proteins linked to oxidative stress, insulin resistance, inflammation, and extracellular matrix remodeling were downregulated, such as HMGB1, FETUA, SERPH1, RPN1, and AOC3. Notably, gamma-synuclein (SYUG), which inhibits lipolysis, was undetectable in ICE-treated samples. Our findings support the hypothesis that ICE promotes thermogenic reprogramming and metabolic rejuvenation in subcutaneous fat through activation of futile cycles and mitochondrial restructuring. This study offers molecular insights into adaptive thermogenesis and presents intermittent cold exposure as a potential strategy to mitigate adipose tissue aging. Full article

Supporting dementia carers is a global priority. As a Randomised Controlled Trial (RCT) (n = 352) of the Word Health Organization recommended, an internationally disseminated ‘iSupport’ e-health intervention was conducted, revealing no measurable benefits to the wellbeing of adult dementia carers. This process evaluation contributes original insights of the trial outcomes. Its aims were to ascertain the usability and acceptability of iSupport, participant engagement and adherence to iSupport, and contextual factors influencing its implementation and potential impact. The process evaluation followed a mixed-method design. The following data were collected from all participants randomised to iSupport (n = 175): (1) post-intervention evaluation questionnaire (n = 93) containing the 10-item System Usability Scale and bespoke items exploring acceptability, engagement, and perceived impact; (2) qualitative interviews (n = 52) with a sub-sample of participants who were purposively sampled according to age, scores on the outcome measures, and gender, as these interviews aimed to generate contextual detail and explanatory accounts; and (3) ‘Access’ data from the iSupport platform (n = 175). Descriptive statistics was used to report on the frequency of survey responses whilst a thematic analysis approach was followed to identify themes from the qualitative interview data. Data sets were analysed independently and then used with respect to one another in order to generate explanatory pathways related to the usability, acceptability, and the impact of iSupport. Despite good trial retention, 8.3% of participants (n = 32) did not spend any time on iSupport, and 54% (n = 94) spent between 30 min and 1.5 h. Factors driving this were the following: time constrains, method of delivery, and content characteristics. Positive impacts of iSupport were also described. Participants, including those with extensive caring experience, reported how iSupport had made them feel reassured, valued, and more able to ask for help. They also reported having an improved outlook on their caring role and on the needs and feelings of the person living with dementia. Research and practice should focus on exploring blended delivery, including self-directed and interactive components, such as regular contact with a health professional. These insights are critical for supporting the global implementation and adaptation of iSupport and offer valuable directions for future research. Full article

Acanthopanax senticosus is an essential medicinal herb in traditional Chinese medicine, with its pharmacological properties largely attributed to bioactive flavonoids. The types and amounts of these flavonoids act as vital quality markers for both the raw materials and the resultant products. In this work, we introduce a TiO₂@AgNP nanocomposite designed as a surface-enhanced Raman scattering (SERS) sensor aimed at the preliminary quantification and identification of flavonoids. This is achieved by leveraging the effective molecular adsorption properties of TiO₂ alongside the ‘hot spots’ generated by AgNPs. By optimizing SERS performance through adjustment of the molar ratio between TiO₂ and Ag, we can quantitatively evaluate four flavonoids—luteolin, kaempferol, quercetin, and rutin—with low detection concentrations of 10⁻⁶ M, 10⁻⁵ M, 5 × 10⁻⁶ M, and 10⁻⁶ M, respectively. Additionally, we observe a nearly linear relationship between the SERS signals and the flavonoid concentrations, allowing for dual or multiplex analysis of these compounds. Furthermore, we successfully differentiated Acanthopanax senticosus samples from six different geographical regions in China based on the detection of significant flavonoid constituents. This serves as a proof of concept for practical applications that can enhance the identification and distinction of traditional Chinese medicine, as well as assess quality and medicinal efficacy. Full article