Search Results (310,976)

Background: Reintervention after mitral valve repair represents a relevant clinical challenge, yet the mechanisms and timing of repair failure remain incompletely defined. Understanding how the interval between index repair and reoperation affects failure mechanisms and the feasibility of repeat repair may help refine surgical strategies. Methods: We retrospectively analyzed 194 patients undergoing repeat mitral valve surgery between 2010 and 2025 after prior repair. Median age was 70 years and 61.3% were male. Patients were stratified by time to reoperation: 0–5 years (n = 91), 6–10 years (n = 42), and >10 years (n = 61). Median left ventricular ejection fraction was 58%, atrial fibrillation prevalence 32.5%, minimally invasive approach 21.6%, and EuroSCORE II 4.8%. Results: Baseline characteristics and operative risk were comparable across groups. However, mechanisms of repair failure differed significantly. Early failures were more commonly due to recurrent leaflet prolapse (47.8%), whereas late failures showed a higher incidence of mitral stenosis (63.9%). The rate of repeat mitral repair decreased over time, being higher in early failures compared with intermediate and late failures (17.6% vs. 14.3% vs. 8.2%). Conclusions: Timing of mitral repair failure is associated with distinct mechanisms and influences surgical management. Early failures are more frequently related to prolapse recurrence and are more amenable to re-repair, whereas late failures are characterized by structural degeneration and more often require valve replacement. Full article

Background/Objectives: Attitudes toward health conditions involving physical dysfunction may differ between healthcare professionals (HCPs) and the general public. This study compared affective responses to stroke, femoral neck fracture (FNF), and spinal cord injury (SCI) across both groups within a unified framework. Methods: We conducted an online cross-sectional survey of 400 members of the general public (stratified by age and gender) and 400 HCPs representing 18 professions. Affective responses were measured using scales assessing negative affect, interpersonal avoidance, and impressions (physical strength, mental resilience, and mental strength). A 2 × 3 mixed-model ANOVA (group × condition) and correlation analyses were conducted. Results: Negative affect showed a significant group × condition interaction (p < 0.001, ηp² = 0.030). HCPs scored lower than the general public for stroke and FNF, with no significant difference for SCI. HCPs also reported lower interpersonal avoidance across all conditions. Impression scales showed no interaction; however, HCPs rated higher physical strength and mental strength, while mental resilience showed no group difference. Condition effects were significant, with a consistent hierarchy of SCI > stroke > FNF for both negative affect and interpersonal avoidance. Negative affect and interpersonal avoidance were moderately correlated in both groups. Among HCPs, FNF-related interpersonal avoidance negatively correlated with years of clinical experience. Conclusions: HCPs generally report less negative affect and interpersonal avoidance and hold more positive perceptions of patient capability than the general public. However, both groups share a negativity hierarchy across conditions, suggesting persistent perceptions associated with specific health labels. Full article

Tau is a protein associated with microtubules principally expressed in neuronal cells, where it plays a fundamental role in cytoskeleton stabilization and axonal transport. Several diseases collectively named tauopathies, such as Alzheimer’s disease, have been associated with an imbalance in the expression of alternative spliced Tau transcripts and the accumulation of hyperphosphorylated Tau, causing dysfunction and death of neuronal cells. Therefore, understanding the Tau exon splicing mechanisms may contribute to elucidating molecular factors that could underlie the development of neurodegenerative disorders. The aim of this study was to define the role of selected splicing factors in regulating Tau exon expression in cell lines and neuronal organoids. We demonstrated the role of the RNA-binding motif protein 20 (RBM20) splicing factor in regulating Tau exon 6 and exon 10, applying RNA-binding assay and qPCR analyses. Furthermore, we demonstrated that Tau expression was regulated during cerebral organoid differentiation, recapitulating in vivo Tau expression. These results suggest the feasibility of using brain organoid technology to study Tau alternative splicing during neural development, confirming that 3D cellular models could be used to study and characterize pathological processes taking place in Tau-related pathologies. Full article

The C-terminal binding protein 1 (CTBP1) is a transcriptional corepressor with a major role in nervous system growth and development. There are only 20 published cases with CTBP1 mutations, displaying a phenotype of Hypotonia, Ataxia, Developmental Delay and Tooth enamel defect Syndrome (HADDTS). Histochemical evidence of decreased mitochondrial respiratory chain activity has been previously reported, but comprehensive data on the metabolic phenotype assessed by various cellular respiration parameters are still missing. We present a 10-year-old female with typical HADDTS features, harboring the most reported de novo heterozygous CTBP1 mutation c.991C>T. To elucidate her metabolic phenotype, we quantified mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) utilizing an analyzer for assessing mitochondrial function (Seahorse XFp). Real-time metabolic assays revealed profound mitochondrial dysfunction with significantly attenuated maximal respiration and spare respiratory capacity compared to neurotypical controls. Following mitochondria-targeted nutritional support for one-year measurable bioenergetic improvements and reduced number of respiratory infections were registered. However, neurological recovery and new skill acquisition were not observed. We present a novel case of CTBP1-related neurodevelopmental disorder and demonstrate, for the first time, the application of non-invasive, real-time mitochondrial functional assessment in this setting, providing additional evidence for mitochondrial dysfunction in HADDTS. Full article

Lotus rectus L. is an underexplored forage legume with reported traditional uses in skin-related conditions. This study aimed to characterize the phytochemical profile of its aqueous leaf extract (LRAE) and to explore its bioactivity in vitro. Phytochemical characterization was carried out using spectrophotometric assays and UHPLC-HRMS/MS. Cytocompatibility was assessed by the resazurin assay in HaCaT keratinocytes and NIH/3T3 fibroblasts, while wound-healing potential was evaluated using a scratch assay. Enzyme inhibitory activities (xanthine oxidase, collagenase, hyaluronidase, and tyrosinase) were determined spectrophotometrically. Antioxidant capacity was assessed using chemical assays (DPPH and ABTS), biologically relevant reactive oxygen species, and metal chelation assays. Antifungal activity was evaluated against clinically relevant yeasts and dermatophytes using standardized macrodilution methods. LRAE showed a relatively high content of flavonoids and proanthocyanidins, particularly flavonol glycosides. The extract was cytocompatible at all tested concentrations and showed an increased closure of the scratched area in vitro. It exhibited antioxidant activity and inhibited xanthine oxidase, while more moderate effects were observed for collagenase and tyrosinase, and minimal activity was detected against hyaluronidase. Antifungal activity was limited, with modest effects observed only against selected dermatophytes at high concentrations. Overall, these findings provide preliminary in vitro evidence of bioactivity associated with the traditional use of this species, supporting further investigation to better characterize the biological relevance of this understudied species. Full article

Objective: Given the increasing use of outpatient parenteral antimicrobial therapy (OPAT) and the clinical challenges posed by Pseudomonas aeruginosa infections, this study aimed to evaluate the effectiveness and safety of OPAT for the treatment of P. aeruginosa infections in a real-world cohort. Methods: We conducted a prospective observational study with retrospective analysis including adult patients with P. aeruginosa infections treated within a multidisciplinary OPAT program shared by two tertiary hospitals between November 2012 and December 2024. Clinical characteristics, infection type, antimicrobial therapy, resistance patterns, source control, and clinical outcomes were recorded. Primary outcomes were treatment failure during OPAT and within 30 days after OPAT completion. Secondary outcomes included adverse events and vascular access complications. Bivariate and multivariable logistic regression analyses were performed to identify factors associated with treatment failure. Results: A total of 290 patients were included. The most frequent infections were bronchiectasis exacerbations (39.7%) and complicated urinary tract infections (15.2%). Most patients received monotherapy (72.8%), mainly ceftazidime, while 27.2% received combination therapy with a beta-lactam plus an aminoglycoside. Treatment failure occurred in 7.6% of patients during OPAT and in 15.5% within 30 days after OPAT completion, with an overall clinical success rate of 77%. Male sex and chronic obstructive pulmonary disease (COPD) were independently associated with failure during OPAT. At 30 days, higher Charlson comorbidity index, COPD exacerbation, and endovascular infection were associated with failure, whereas combination therapy was associated with a lower risk of failure. Antimicrobial-related adverse events were rare (3.2%). Conclusions: Our results support OPAT as an effective and safe strategy for managing P. aeruginosa infections in clinically stable patients. Patients with COPD, either as a comorbidity or during an exacerbation, and those with a higher Charlson score may require closer follow-up. Full article

Myocardial infarction initiates complex remodeling processes involving the renin–angiotensin system, through activation of the angiotensin II type 1 receptor (AT₁R). This study correlated AT₁R expression with fibrosis and cardiac function in the heart and kidneys following cardiac ischemic injury in animal models. Male Sprague-Dawley rats underwent Sham surgery, Ischemia/Reperfusion (I/R, 20-min ligation) or Permanent Ligation (PL) of the left anterior descending artery. Cardiac function was assessed by echocardiography. AT₁R expression was measured in the heart (infarct and remote areas) and kidneys (cortex, medulla) via [¹²⁵Iodine]Sarcosine¹-Isoleucine⁸-Angiotensin II autoradiography. Collagen deposition was evaluated through picrosirius red staining. Left ventricular (LV) ejection fraction declined in PL models but remained stable following I/R. Post-I/R, a transient increase in cardiac AT₁R (day-3 to week-5) correlated with an increase in collagen, whereas after PL, elevations persisted through week-12. Infarct areas consistently displayed higher AT₁R and collagen than remote areas. Renal AT₁R and collagen levels were unchanged across groups. In analyses with pooled animals, cardiac AT₁R expression correlated with collagen and inversely correlated with LV Fractional Shortening (LVFS), whereas LVFS inversely correlated with collagen deposition. These findings suggest that cardiac AT₁R levels may serve as a target of cardiac remodeling, while changes in renal AT₁R appear less pronounced. Full article

Plaque-disclosing agents are widely used to enhance visualization of dental biofilm. However, their chromogenic components may adhere to enamel surfaces, resulting in transient extrinsic discoloration. This study evaluated the extent and short-term recovery of such discoloration and compared three removal modalities in terms of enamel color change (CIEDE2000, ΔE₀₀), surface roughness (Ra), and gloss (GU). Extracted human anterior teeth with intact buccal enamel were stained using an erythrosine-based disclosing agent and randomly allocated into three groups (n = 15): manual brushing with conventional toothpaste, rubber-cup polishing with a perlite-containing paste (1000 rpm, 5 s), or erythritol-based air-polishing (5 s; 50% power/100% water). ΔE₀₀ was measured at baseline, immediately after cleaning, and after 1 week of storage in artificial saliva. Ra and GU were recorded at baseline and post-cleaning. Data were analyzed using appropriate tests (p < 0.05). All modalities were associated with a reduction in visible discoloration without significantly affecting Ra or GU (p > 0.05). Immediate ΔE₀₀ values remained above commonly reported acceptability thresholds, indicating residual discoloration. Partial color recovery occurred after artificial saliva storage. Within the limitations of this study, the findings indicate no statistically significant differences among the tested procedures, without evidence of superiority of any single modality. Full article

Oncogenic driver mutations in non-small cell lung cancer (NSCLC) activate defined signaling pathways that sustain tumor growth and influence the immune landscape. Yet, how coordinated interactions among diverse cell populations within the tumor immune microenvironment (TIME) contribute to this process remains largely unresolved. To address this, we profiled approximately 200,000 single cells from 45 treatment-naïve NSCLC patients representing seven major driver mutations. This analysis uncovered five multicellular modules (CM1–5) with distinct functional properties, each linked to specific malignant regulatory programs. Among them, CM2 and CM5 exhibited pronounced invasive features and were associated with unfavorable clinical outcomes. CM2 was predominantly observed in EGFR- and MET-driven brain metastases and was defined by strong crosstalk between astrocytes and myofibroblasts. Factors such as SPP1, PTN, and PSAP, together with metabolic alterations, contributed to a microenvironment supportive of metastatic colonization in the brain. By contrast, CM5 was enriched in ROS1-, KRAS-, and EGFR-mutant tumors and consisted of diverse myeloid and endothelial subsets characterized by immunosuppressive and pro-angiogenic signaling, including MIF, GALECTIN, and RETN, collectively facilitating immune escape and vascular remodeling. We further constructed and validated a driver mutation-specific prognostic signature (DMSP.sig) model integrating receptor–ligand interactions and core transcription factors, which effectively stratified patient survival. Leveraging this model, we also identified potential therapeutic candidates linked to these prognostic features, highlighting opportunities for clinical intervention. In summary, our study delineates how oncogenic drivers give rise to distinct TIME architectures, providing a framework for prognostic assessment and precision immunotherapy in high-risk NSCLC. Full article

In the saline–alkaline lake (SAL) systems of the Nhecolândia region, Brazilian Pantanal, soils exhibit complex mineralogical assemblages controlled by sediment inheritance, pedogenesis, and hydrogeochemical gradients. This study investigates the distribution and transformation of 2:1 phyllosilicates along representative SAL toposequences. Soil samples were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD), supported by granulometry and adjustment of the FTIR spectra. Mineralogical data were integrated with geochemical (Al, K, Mg, Ca, Na) and pH data and examined using principal component analysis (PCA). Greenish loamy horizons act as key morphological controls on hydrogeochemistry, regulating solute retention along mid- to downslope transitions. Illite is more strongly associated with upslope positions, whereas downslope alkaline environments are associated with smectitic phases (e.g., montmorillonite and Mg-rich varieties such as saponite) and mixed-layer minerals structures (e.g., illite–smectite and montmorillonite–vermiculite structures). These assemblages are consistent with non-linear transformation pathways, with illite as a possible transitional phase between micas and expandable structures. The PCA results suggest a primary mineral distribution structured by fine-material content and depth, while pH and alkalinity emerge as key geochemical controls that differentiate mineral stability fields and reinforce the hydrogeochemical compartmentalization of the profiles. Geochemical data show strong associations of Al, Mg, and K with fine-fraction accumulation. The integration of these approaches highlights that a 2:1 phyllosilicate assemblage results from multiple superimposed pedogenetic pathways, offering a conceptual framework for studying complex soil–lake systems. Full article

Regulation of all-trans retinoic acid (ATRA) signaling is crucial to early embryonic development. Embryonic stem (ES) cell-derived gastruloids mimic normal development in response to the Wnt/β-catenin agonist CHIR9901, and this study has examined the importance of the activities of RAR (retinoic acid receptor) α and γ to gastruloid development. Expression of retinoic acid receptor (RAR)γ within developing gastruloids was spatially restricted to primitive cells that co-expressed ES cell and early progenitor cell markers, i.e., Nanog, Sox2, and Oct4. In contrast, RARα expression was ubiquitous. mRNAs for the key enzymes involved in ATRA synthesis (Aldh1a2) and degradation (Cyp26a1) were not seen in cells that expressed RARγ. Treatment of ES cell-derived gastruloids with physiologically relevant (10 nM) levels of ATRA or with a highly selective RARγ agonist blocked normal developmental processes, preventing symmetry-breaking and axial elongation. This was not seen following treatments with an RARα agonist, where there was a tendency for enhanced axial elongation. Brachyury (TBXT) immuno-positive cells localized in the posterior end of elongated gastruloids in control- and RARα agonist-treated cultures, with Sox2 immuno-positive cells seen more widely, whilst both TBXT and Sox2 immuno-positive cells were randomly distributed throughout ATRA- and RARγ agonist-treated gastruloids. Concurrent treatment of gastruloids with 10 nM ATRA and 100 nM of an RARγ antagonist partially abrogated the ATRA-mediated block to axial elongation. Conversely, 10 nM RARγ antagonist treatments were associated with the formation of multi-axis gastruloid elongations, with comparatively little effect seen after treatments with an RARα antagonist. These findings reveal that RARγ plays a crucial role in the development of embryonic tissues. Full article

Background: Osteoporosis is a chronic bone disease characterized by reduced bone mass and structural deterioration, increasing fracture risk and affecting patients’ quality of life (QoL). Pharmacological treatments are essential in managing osteoporosis; however, suboptimal prescribing patterns and poor medication adherence can limit therapeutic outcomes. This study primarily aimed to assess medication adherence among patients with osteoporosis using the MMAS-8, as well as prescribing patterns and patient beliefs. Methods: We conducted a single-center cross-sectional observational study at Saqr Hospital, Ras al Khaimah, UAE, between October 2024 and May 2025, enrolling 300 adults with clinically diagnosed osteoporosis and/or a bone mineral density T-score ≤ −2.5. Data were collected through structured interviews and medical-record review. Medication adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8), and beliefs about medicines were measured using the Beliefs about Medicines Questionnaire (BMQ). Prescribing patterns were characterized by drug class, dose, and frequency, and prescribing appropriateness was evaluated using prescribed daily dose/defined daily dose (PDD/DDD) ratios based on WHO ATC/DDD standards. Predictors of adherence were examined using univariate and multivariable Firth penalized logistic regression. Results: The median age was 70 years (IQR 63–76), 89.0% of participants were female, and 32.0% had a prior fracture history. Denosumab was the most frequently prescribed anti-osteoporotic therapy (59.0%), followed by romosozumab (30.7%), whereas bisphosphonates and parathyroid hormone analogues were infrequently used (2.7% and 4.7%, respectively). Prescribed dosing closely aligned with WHO standards for all evaluated agents. Overall, 40.7% of patients were classified as adherent and 59.3% as non-adherent. Adherence was not significantly associated with age, gender, nationality, fracture history, polypharmacy, or most comorbidities. In contrast, medication beliefs demonstrated a strong relationship with adherence. In multivariable Firth regression, stronger medication concerns were independently associated with lower odds of adherence (adjusted OR 0.033, 95% CI 0.003–0.355; p = 0.0049), while having more than two comorbidities was also associated with reduced adherence (adjusted OR 0.076, 95% CI 0.008–0.688; p = 0.022). Conclusions: In this UAE real-world cohort, osteoporosis pharmacotherapy was dominated by injectable biologic agents and was prescribed in close agreement with standard dosing recommendations. However, medication adherence remained suboptimal. Patient beliefs, particularly treatment-related concerns, emerged as a more important determinant of adherence than demographic or most clinical characteristics. These findings highlight the need for belief-sensitive, patient-centered adherence interventions alongside optimized pharmacotherapy to improve osteoporosis outcomes in routine practice. Full article

Low birth weight (LBW) is associated with neonatal morbidity, mortality and long-term health complications. Global studies report an association between air pollution, such as tropospheric ozone, and LBW. This study aims to analyze the association between ozone exposure during pregnancy and LBW in 130 municipalities in rural and semi-urban Spain. We conducted a retrospective population-based cohort study using data from the Instituto Nacional de Estadística (INE) and air quality data from the Spanish Government for the 2001–2017 period. We performed descriptive analysis, logistic regression and linear regression analyses adjusted for various covariates. In addition, we fitted generalized additive models (GAMs) to estimate non-linear relationships. An association between decreased neonatal weight and high ozone exposure was found, especially in the first and second trimester. An increase in ozone concentration could lower neonatal weight but not enough evidence demonstrates an association with LBW. More research is needed to understand the impact of ozone exposure on neonates during pregnancy. Full article

Gambling disorder (GD) is a behavioral addiction associated with significant psychosocial consequences and high psychiatric comorbidity, including anxiety, depression, and impulsivity; however, the role of physical activity (PA) as a potential modulator of these alterations remains unclear. The aim of this study was to examine the relationship between PA levels and symptoms of anxiety, depression, and impulsivity in patients with GD. An observational study was conducted with 62 adults diagnosed according to DSM-5 criteria, recruited from AJUPAREVA (Valladolid, Spain). PA was assessed using the International Physical Activity Questionnaire (IPAQ), Personality trails where evaluated with CEPER III, impulsivity with the Barratt Impulsiveness Scale (BIS-11) and the Plutchik Impulsivity Scale, and anxiety and depression with the Hamilton Anxiety (HAM-A) and Depression (HAM-D) scales. Participants were predominantly male (91.5%) and reported moderate-to-high PA levels. No significant differences were found in total impulsivity across PA levels; however, motor impulsivity was higher in highly active individuals, while non-planning impulsivity was greater in those with low PA. Anxiety and depression were highly prevalent (~65%) with no significant associations with PA. In conclusion, PA was not significantly associated with psychiatric outcomes in this clinical sample, highlighting the need for larger, longitudinal studies to clarify its potential role within multidisciplinary interventions for GD. Full article

Background/Objectives: Pest management strategies rely on insecticides such as deltamethrin (DM), a commonly applied type II pyrethroid. As a natural component of food-associated microflora, Saccharomyces cerevisiae inevitably encounters DM residues in crops used for fermentation processes, including dough leavening and winemaking. However, the prolonged effect of DM exposure on yeast fermentation performance and its capacity to remove DM remained unclear. Methods: In this study, S. cerevisiae was continuously exposed to a non-lethal concentration (10 mg/L) and a low-inhibition toxic concentration (30 mg/L) of DM for 30 days. Results: Yeast exhibited high removal capacity, removing 98.05 ± 1.2% and 98.28 ± 0.4% of DM at 10 mg/L and 30 mg/L, respectively. Prolonged exposure to DM at both concentrations did not significantly affect biomass formation, glucose consumption, ethanol production, or acetic acid levels. In contrast, glycerol production increased markedly, reaching 1.1 g/L and 1.5 g/L in cultures exposed to 10 mg/L and 30 mg/L DM, respectively. Consistent with these changes, the expression levels of GPD1 and GPD2, which encode rate-limiting enzymes in glycerol biosynthesis, were upregulated in a dose-dependent manner. Conclusions: Given the fact that Saccharomyces cerevisiae is a workhorse for the biotechnological industry and has a wide range of applications, including in the food industry, elevated glycerol production in yeast under DM exposure is noteworthy in terms of yeast-based applications. Full article