Search Results (2,565)

Background: Vitamin D has been increasingly investigated for its pleiotropic immunomodulatory and antimicrobial effects, which may influence periodontal inflammation and healing. This systematic review aimed to evaluate the impact of serum vitamin D levels and vitamin D supplementation as an adjunct to non-surgical periodontal therapy (NSPT) on clinical and microbiological outcomes in patients with periodontitis. Methods: An electronic search was conducted in MEDLINE and other major databases up to September 2025. Randomized controlled trials assessing the relationship between vitamin D status or supplementation and periodontal outcomes following NSPT were included. Data were synthesized qualitatively, focusing on changes in serum 25(OH)D levels and periodontal parameters, including probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and gingival inflammation. Results: Four studies met the inclusion criteria. In patients with sufficient baseline vitamin D levels, supplementation provided limited additional clinical benefits beyond NSPT alone. Conversely, in vitamin D-deficient patients, supplementation regimens capable of restoring serum 25(OH)D levels above 30 ng/mL were consistently associated with greater reductions in PPD, improved CAL, and decreased plaque and bleeding indices. Microbiological analyses also revealed a reduction in red complex periodontal pathogens in supplemented groups. Conclusions: Vitamin D supplementation enhances the clinical effectiveness of NSPT primarily in patients with documented vitamin D deficiency. Its adjunctive benefits appear to be mediated by immunomodulatory and antimicrobial mechanisms that complement mechanical debridement. While current evidence supports targeted supplementation in deficient individuals, long-term randomized trials are required to establish standardized protocols and confirm sustained clinical benefits. Full article

Background/Objectives: Iron deficiency (ID) is a critical comorbidity in chronic heart failure (CHF) that impairs myocardial energy metabolism and clinical outcomes. Despite its significance, data regarding ID prevalence in Southeast Asian CHF populations remain insufficient. This study aimed to determine the prevalence of ID and identify its independent clinical correlates among CHF patients at a leading tertiary hospital in Vietnam using high-precision automated diagnostic platforms. Methods: A descriptive cross-sectional study was conducted on 138 adult CHF patients. Serum iron and ferritin were quantified using photometric and electrochemiluminescence immunoassay (ECLIA) methods on cobas c702 and e602 systems. ID was defined according to 2021 ESC guidelines (ferritin < 100 ng/mL or ferritin 100–299 ng/mL with TSAT < 20%). Multivariable logistic regression identified independent factors associated with ID. Results: The overall ID prevalence was 75.4%, consisting of functional (39.9%) and absolute ID (35.5%). A significant gender disparity was observed (p = 0.0326): absolute ID was more prevalent in females (44.4%), while functional ID predominated in males (47.4%). Multivariable analysis revealed that NT-proBNP (aOR = 2.29; 95% CI: 1.13–4.66; p = 0.021) and C-reactive protein (aOR = 2.17; 95% CI: 1.07–4.43; p = 0.031) were independent correlates of ID status. The association with anemia was borderline non-significant (p = 0.055). Conclusions: ID is nearly ubiquitous among Vietnamese CHF patients in this tertiary setting, driven by hemodynamic severity and systemic inflammation. These findings advocate for integrating routine iron status screening into the standard diagnostic workup for all CHF patients, regardless of hemoglobin levels. Full article

Background/Objectives: Chronic Spontaneous Urticaria (CSU) is a skin disorder marked by recurrent wheals and itching, with or without angioedema, which can greatly affect the quality of life. Vitamin D has been implicated in the pathophysiology of various immune-mediated conditions, including CSU. The connection between vitamin D levels, patients’ perceived symptoms, and life impact remains unexplored. This study aims to elucidate vitamin D levels and their correlation with perceived disease-related burden in individuals with CSU. Methods: PROM-based questionnaires, serum 25(OH)D levels, and BMI were statistically analyzed in high-disease-activity CSU, among hospitalized and outpatients who attended the main tertiary hospital center during a 1-year period. These data were compared with a control group, after obtaining their consent. Results: The study included 104 patients, 74 (71.15%) females, mean age 43.17 ± 18.26 years, and 23 controls, 12 (52.17%) females, mean age 44.61 ± 12.77 years. Levels of 25(OH)D were significantly lower in patients compared to controls and in the hospitalized versus the outpatient group (p < 0.05). Suboptimal 25(OH)D was found in 94.23% of patients (mean level 18.29 ± 6.74 ng/mL) and 82.61% of controls (mean 24.01 ± 7.44 ng/mL). A BMI > 25 kg/m² was found in 71 (68.3%) patients and 11 (47.83%) controls. Age was not significantly correlated with vitamin D levels. A significant positive correlation was found between vitamin D levels and the perceived bothersomeness score of urticarial elements and pruritus. Age was negatively correlated with perceived bothersomeness of pruritus. Irrespective of 25(OH)D levels, perceived bothersomeness of urticarial elements positively correlated with scores for angioedema, pruritus, and the impact of CSU on life and daily activities. Life and daily activities impact scores were also positively correlated with angioedema and pruritus. Conclusions: Suboptimal levels of 25(OH)D were common in CSU patients, especially among hospitalized patients, and were significantly lower compared with controls, suggesting a potential link between low vitamin D status and high disease activity. PROMs did not show a significant association between lower vitamin D levels and worse scores for perceived bothersomeness of urticarial elements, angioedema, pruritus, or impact on life and daily activities. Full article

Quinolone antibiotic (QA) residues in various natural environments have recently received massive scientific attention. Nevertheless, there is limited information on the distribution characteristics and potential hazards of antibiotics in coastal wetlands. Here, the occurrence, spatial and seasonal distribution, and ecological risk assessment of eight QAs including pipemidic acid (PPA), ofloxacin (OFL), enrofloxacin (ENR), ciprofloxacin (CIP), sarafloxacin (SAL), lomefloxacin (LOM), flumequine (FLU), and oxolinic acid (OA) in coastal wetland were investigated through collected water, sediment, benthos, and plant samples along the Jiangsu coastline in four seasons. The results demonstrated that all selected QAs were detected with varying frequencies and degrees, and their mean concentrations in water, sediment, plants, and benthos ranged from n.d. to 6.11 ng L⁻¹, 3.10 μg kg⁻¹, 6.14 μg kg⁻¹, and 17.13 μg kg⁻¹, respectively. The seasonal differences in antibiotic concentration indicated higher values in winter and significantly lower values in summer, while no significant variations were observed between spring and autumn. Based on the risk quotient (RQ) method, the ecological risk assessment revealed medium risks for OFL, ENR, CIP, and LOM, and low or no risks of other QAs. It is suggested that the differences in PNEC values between seasons and toxicity of antibiotic mixtures should be considered in future studies for better illustration of actual risk levels. This research provides fundamental data and an assessment pattern that governments and other scientific groups all over the world could use as reference to evaluate QA residues in coastal wetlands. Full article

Bud sport mutations are valuable sources of citrus germplasm innovation and provide an ideal system to dissect genetic regulation of specific traits. The Ponkan mandarin (Citrus reticulata Blanco cv. Ponkan) bud sport mutant “Pumpkin mandarin” displays a Pumpkin-shaped, ribbed peel protrusion phenotype with elevated soluble sugars, but its molecular basis remains unclear. Here, wild-type Ponkan (PG) and Pumpkin mandarin (NG) were compared across six developmental stages (90–240 days after flowering, DAF) for fruit appearance and internal quality, peel firmness, and tissue morphology; RNA-seq was performed on mature peel at 240 DAF. Peel protrusion was detectable as early as flowering. NG showed significantly lower mature fruit weight and consistently higher soluble sugar content throughout development. Peel firmness exhibited a stage-dependent reversal: NG exceeded PG before 180 DAF, PG exceeded NG at 180–210 DAF, and NG again exceeded PG at 240 DAF. RNA-seq generated 41.38 Gb of high-quality data and identified 580 differentially expressed genes (DEGs; 411 upregulated, 169 downregulated). DEGs were enriched in cell wall organization/modification, phenylpropanoid biosynthesis, starch and sucrose metabolism, cutin/wax biosynthesis, and photosynthesis. Expansin (EXP) and GH18 genes were upregulated, while NAM genes encoding NAC transcription factors were downregulated, suggesting an imbalance between cell wall loosening and structural maintenance in protrusion formation. Peel DEGs also included upregulated sucrose synthase (SUS) and sugar transporter (SUT) genes, indicating carbohydrate-related reprogramming in mutant peel. We propose a preliminary network in which NAM may function upstream, cell wall remodeling represents a principal effector module, and the peel carbohydrate metabolism acts as an accompanying module. Full article

The aim of the study was to investigate the relationship between air pollution exposure and gut microbiota-related biomarkers among a cohort of healthy school-age children. A cross-sectional biomonitoring study was conducted among 11-year-old healthy children living in central Italy. Selected urinary (u) volatile organic compounds (VOCs) (benzene, toluene, ethylbenzene, xylenes, methyl tertbutyl ether, ethyl tert-butyl ether, 2-methyl-2-butyl methyl ether, and diisopropyl ether) were measured as exposure biomarkers while u-indican and faecal (f) zonulin were assessed as indicators of gut dysbiosis and intestinal permeability, respectively. Socio-demographic and lifestyle data were collected through questionnaires. u-VOCs showed higher geometric means among children exposed to environmental tobacco smoke, living in urban areas, and those spending a longer time in motor vehicles. u-Ethylbenzene and u-toluene were the most abundant compounds (mean ± SD: 307 ± 118 ng/L and 188 ± 94 ng/L, respectively). Mean f-zonulin and mean u-indican were, respectively, 49.09 ± 18.41 ng/mL and 5.97 ± 3.50 mg/dL. A statistically significant positive correlation was observed between u-ethylbenzene and u-indican (p = 0.02) and between u-toluene and f-zonulin (p = 0.05). These findings provide preliminary evidence that air pollution may influence gut microbial metabolic activity and intestinal barrier regulation in children, supporting the need for larger longitudinal studies. Full article

As men age, systemic inflammation increases, whereas grip strength (GS) and testosterone levels tend to fall. This rate of decline is known to be influenced by gut microbial health, lifestyle and diet but the role for interventions to slow this decline are less well established. This double-blind randomised controlled trial evaluated the impact, and explored the synergistic potential, of boosting phytochemical rich foods and Lactobacillus probiotics on these physical and biological markers. Two hundred and eight men with untreated early prostate cancer managed with observation only (average age 74 years) received a phytochemical rich supplement (PRS) containing concentrated broccoli, green tea, pomegranate, ginger, cranberries and turmeric (YourPhyto). In addition, they were randomised to either a 5-blend Lactobacillus probiotic (PB) capsule (YourGutplus) or a placebo (P). Average GS improved by 2.5 kg from baseline to trial completion, at 4 months in men taking PRS +P (95% CI 1.8–3.4, p < 0.001). In the PRS+PB arm, GS improved by 4.4 kg (95% CI 3.6–5.2, p < 0.001). The odds of grip strength improving was 11.8% greater (p = 0.002, OR = 1.11, 95% CI 1.04–1.20) in the PRS+PB arm. Improvements in systemic inflammation were better in the PRS+PB arm (−0.41 vs. +0.39, p = 0.04). Four-month testosterone levels were greater in the PRS+PB arms (14.75 vs. 13.02 ng/L, 95% CI 0.23 to 3.33 ng/L p = 0.046). In conclusion, boosting dietary phytochemicals was associated with improved GS. The addition of this blend of Lactobacillus further enhanced GS, and reduced markers of inflammation. These data justify longer studies exploring the synergy between phytochemicals and probiotics, on more objective markers of longevity. Full article

The Kupa River (Croatia), a tributary of the Danube basin forming part of the Slovenian border, was heavily contaminated with polychlorinated biphenyls (PCBs) between 1962 and 1985 due to improper handling and downstream transport via the Krupa and Lahinja rivers. This study evaluated the occurrence, interspecific distribution, and human health implications of PCBs and polycyclic aromatic hydrocarbons (PAHs) in fish (Northern pike, Common carp, Grass carp, Pike-perch, Wels catfish, Bream, and Chub) from the Croatian Kupa River. PCB concentrations were consistently higher than PAH levels across all species. In 30% of samples, Σ6 non-dioxin-like PCBs exceeded the European Commission maximum permissible level for freshwater fish (125 ng⋅g⁻¹ wet weight). Of the 11 PAHs analyzed, only fluoranthene and pyrene were detected. Self-Organizing Map identified distinct pollutant patterns, with chub showing the highest variability and accumulation. PCB concentrations position the Kupa River among moderately to highly impacted European freshwater systems affected by legacy industrial contamination. Health risk assessment, incorporating updated national consumption data, indicates that long-term, uncontrolled consumption of Kupa River fish may pose risks due to PCB exposure, while PAH-related risks appear negligible. These findings highlight the persistence of legacy PCB pollution and the need for integrated sediment–biota monitoring. Full article

Background: Transperineal magnetic resonance (MRI)/ultrasound (US) fusion-guided prostate biopsy has emerged as a promising alternative to the transrectal approach by improving lesion targeting and reducing infectious complications. However, real-world data addressing factors that influence the detection of clinically significant prostate cancer (csPCa), including imaging characteristics and procedural experience, remain limited. Objective: To evaluate the diagnostic performance, safety profile, and independent predictors of csPCa detection in patients who underwent transperineal MR/US fusion-guided prostate biopsy, with particular emphasis on PIRADS category, prostate-specific antigen (PSA) level, and procedural learning curve. Methods: In this study, patient data were prospectively recorded in a routinely maintained institutional database, while the present analysis was conducted retrospectively. A total of 136 patients with clinical suspicion of prostate cancer—defined as elevated prostate-specific antigen (PSA), abnormal digital rectal examination, or PIRADS ≥3 on multiparametric MRI—underwent transperineal MR/US fusion-guided biopsy between January 2023 and October 2024. Results: Prostate cancer was detected in 45.5% of patients, whereas csPCa was identified in 32.3%. The PIRADS category emerged as the strongest independent predictor of csPCa detection, with PIRADS-5 lesions showing a significantly greater likelihood of csPCa than PIRADS-3 lesions (OR 6.70, p = 0.006). The PSA level was also independently associated with csPCa detection (OR 1.06 per ng/mL increase, p = 0.033). Although csPCa detection rates increased across learning curve groups, procedural experience was not an independent predictor after adjustment. The procedure demonstrated a favorable safety profile, with a low rate of infectious and noninfectious complications despite minimal use of antibiotic prophylaxis. The multivariable model showed moderate explanatory power and acceptable overall classification accuracy. Conclusions: Transperineal MR/US fusion-guided prostate biopsy provides reliable detection of clinically significant prostate cancer with a low complication rate and consistent performance across different stages of institutional experience. The PIRADS category and PSA level remain key determinants of csPCa detection, supporting the integration of MRI-based risk stratification into contemporary prostate cancer diagnostic methods. Full article

Background/Objectives: Non-classical congenital adrenal hyperplasia (NCCAH) due to 21-hydroxylase deficiency represents the mildest form of congenital adrenal hyperplasia and is frequently diagnosed only after the onset of clinical signs in childhood. Newborn screening programs for CAH are primarily designed to detect classical forms and show limited sensitivity for NCCAH. The clinical significance of neonatal 17-hydroxyprogesterone (17-OHP) values below recall thresholds remains incompletely defined. Methods: We retrospectively analyzed clinical, auxological, hormonal, and genetic data from pediatric patients diagnosed with NCCAH between 2018 and 2023 at a tertiary referral center. Neonatal screening 17-OHP concentrations, basal and ACTH-stimulated 17-OHP levels at diagnosis, bone age advancement, pubertal status, and hydrocortisone treatment were evaluated. Correlations between hormonal parameters, age at onset, and treatment dose were assessed. Results: Thirty-five patients (30 females) were included, with a mean age at clinical onset of 7.52 ± 0.36 years for females and 6.25 ± 0.29 years for males. Premature pubarche was the most frequent presenting sign (94.3%), and central precocious puberty was diagnosed in 31.4% of cases. The mean neonatal screening 17-OHP level was 4.53 ± 0.7 ng/mL; only two patients exceeded the screening recall cut-off. At diagnosis, mean basal and ACTH-stimulated 17-OHP levels were 15.1 ± 3.35 and 55.2 ± 11.3 ng/mL, respectively. Age at clinical onset was inversely correlated with both basal and stimulated 17-OHP levels, while hydrocortisone dose correlated positively with biochemical severity. Bone age advancement was observed in all patients. Conclusions: Most children with NCCAH display mildly elevated neonatal 17-OHP values that do not trigger screening recall. Higher biochemical severity is associated with earlier clinical presentation and higher glucocorticoid requirements. Neonatal 17-OHP concentrations, even when below cut-off values, may represent an early indicator of disease severity and warrant further investigation. Full article

The detection of biological markers is critical not only for the early diagnosis of cancer but also for adjustments in antitumor therapy. Rapid, sensitive, and selective detection and monitoring of the content of specific biomarkers in real time are key to point-of-care testing diagnostics. We report the detection of heat shock proteins by fluorescence immunoassay with the appropriate phage antibodies, with a minimum detection limit of 1 ng/mL. The fluorescence immunoassay data were confirmed by dot immunoassay and by circular dichroism studies. The results of the study may help in the adaptation of the fluorescence immunoassay to cancer diagnostics. Full article

Background/Objectives: Population aging has been accompanied by increased institutionalization of older adults and a high prevalence of vitamin D deficiency in this group. Although the literature suggests a possible relationship between vitamin D and cognition, findings remain inconsistent, particularly in institutional settings. This cross-sectional study aimed to investigate factors associated with vitamin D deficiency in institutionalized older adults, emphasizing the role of vitamin D supplementation and length of institutionalization, as well as to evaluate the association between serum vitamin D levels, cognitive decline, and dementia. Methods: A total of 104 older adults living in different long-term care institutions (LTCFs) in the city of Pelotas, RS, Brazil, were evaluated. Sociodemographic, clinical, and nutritional data were collected via interviews and medical record review. Serum 25-hydroxyvitamin D levels were categorized according to the Institute of Medicine cutoffs (<20 ng/mL and ≥20 ng/mL). Cognitive decline was assessed using the Mini-Mental State Examination, and dementia was evaluated with the Clinical Dementia Rating scale. Analyses included bivariate tests and binary logistic regression. Results: A high prevalence of vitamin D deficiency (52.9%), cognitive decline (83.6%), and questionable or mild dementia (79.4%) was observed. In multivariate analysis, vitamin D supplementation remained independently associated with vitamin D deficiency, whereas no significant association was observed between vitamin D levels and cognitive decline or dementia. Conclusions: Vitamin D deficiency in institutionalized older adults is predominantly associated with contextual and care-related factors rather than cognitive impairment, highlighting the importance of systematic nutritional monitoring and vitamin D supplementation strategies in institutional settings. Full article

Background: The clinical intra-anesthetic changes of perioperative hypersensitivity (POH) are not specific and require a thorough differential diagnosis with other mimicking conditions. Biomarkers such as tryptase and histamine provide supportive evidence for POH. From the suggested cutoffs, a common decision threshold has not been validated for use in daily practice. The aim of this systematic review and meta-analysis is to identify biomarkers investigated for POH and to evaluate their diagnostic performance. Methods: This meta-analysis included original diagnostic accuracy studies comparing patients with clinically suspected POH and controls with no signs of intraoperative hypersensitivity reactions, in whom allergy biomarkers were evaluated, aiming to investigate diagnostic performance of the assays. Data was pooled to evaluate sensitivity and specificity. Results: In seven studies on tryptase and three studies on histamine dosing for the diagnosis of POH/POA, different fixed or dynamic thresholds for positivity were proposed. For tryptase, fixed thresholds had 59.8% sensitivity and 95.2% specificity for an optimal cutoff of 12.68 ng/mL, while dynamic thresholds yielded 77.2% sensitivity and 88.5% specificity. For histamine, fixed cutoffs presented 78% sensitivity and 85% specificity, while dynamic thresholds investigated in a single study yielded 78.2% sensitivity and 91.1% specificity. Estimates for histamine are unreliable due to limited data. Conclusions: From published data, tryptase is clearly the most robust biomarker, dynamic thresholds boost sensitivity without major specificity loss and confirm the added diagnostic value of relative changes over fixed absolute cutoffs. Preliminary results suggest that histamine might have optimal diagnostic performance, but estimates are severely limited by small sample sizes. Full article

Background/Objectives: The excessive use of antibiotics in the intensive care unit (ICU) is driving antimicrobial resistance and poor clinical results. Therefore, the aim of this study was to assess antibiotic exposure and clinical results stratified by baseline procalcitonin (PCT) levels in critically ill ICU patients with suspected bacterial infections. Methods: A retrospective observational cohort study was conducted at a tertiary referral center in Bali, Indonesia. This study included adult ICU patients with suspected bacterial infections and documented baseline PCT levels. Participants were stratified into two cohorts based on a baseline PCT threshold, namely <0.5 ng/mL and ≥0.5 ng/mL. Comprehensive clinical data, antibiotic utilization, and patient results were extracted from electronic medical records. Comparative statistics and multivariable logistic regression were used to identify independent association after adjustment for relevant clinical confounders. Results: In this study, a total of 84 patients were analyzed. Patients in the elevated PCT group (≥0.5 ng/mL) were significantly older and had higher APACHE II scores, suggesting greater baseline illness severity at ICU admission. The median duration of antibiotic therapy was significantly longer in the elevated PCT than the normal group (8 vs. 5 days; p < 0.001). After adjustment for age, APACHE II score, and other relevant clinical variables, elevated baseline PCT levels remained independently associated with prolonged antibiotic exposure and in-hospital mortality. Incremental increases in PCT levels were associated with higher odds of mortality, along with advanced age and higher SOFA scores. Furthermore, the presence of multidrug-resistant (MDR) pathogens was independently associated with prolonged antibiotic use. Conclusions: Elevated baseline PCT levels upon ICU admission were associated with prolonged antibiotic exposure and increased in-hospital mortality. Baseline PCT levels likely reflect underlying illness severity and the magnitude of the host inflammatory response. Within antimicrobial stewardship frameworks, they should be interpreted alongside clinical assessment and severity scores rather than as a standalone determinant of antibiotic duration. Full article

Accurate measurement of androgen receptor pathway inhibitors (ARPIs) and their active metabolites is essential for pharmacokinetic studies and therapeutic drug monitoring (TDM) in patients with prostate cancer (PC). However, their simultaneous determination in human plasma is analytically challenging because of the wide concentration ranges. This study aimed to develop and validate a sensitive and robust LC–MS/MS method for the quantification of abiraterone, Δ4-abiraterone, enzalutamide, N-desmethyl enzalutamide, darolutamide, keto-darolutamide, apalutamide, and N-desmethyl apalutamide in human plasma. Sample preparation was performed by protein precipitation, followed by chromatographic separation and detection using multiple reaction monitoring with isotopically labeled internal standards (total run time 6.5 min). The method was validated in accordance with regulatory guidelines by assessing selectivity, linearity, sensitivity, accuracy, precision, recovery, matrix effects, and stability. The assay demonstrated good linearity (≥0.997) across clinically relevant concentration ranges, with lower limits of quantification between 0.1 and 40 ng/mL, depending on the analyte. Intra- and inter-day precision and accuracy were within acceptable limits, and recovery and matrix effects were consistent across different plasma matrices. Stability experiments conducted in plasma and whole blood provided practical guidance for sample handling. The method was successfully applied to 79 plasma samples from 61 patients with metastatic PC. Measured concentrations were generally consistent with published pharmacokinetic data, while unexpectedly high ABI levels were observed. Sample collection occurred between 1 and 28 h after the last drug intake, enabling assessment of the analytical method across the entire pharmacokinetic profile. Full article