Search Results (7,372)

The annual congress of the Italian Association of Plastic Aesthetic Surgery (AICPE), with more than 700 members, represents one of the most relevant conference meetings in Europe relating to Aesthetic Plastic Surgery due to the number of participants and due to the faculty of invited speakers chosen for their renowned scientific value. The 13th meeting was held in Rome (Italy) from 10 to 12 April 2026. Key focus areas of the scientific program concerned breast (reduction, lifting supported or not by mesh, implant surfaces, augmentation), face and neck (lifting, blepharoplasty, malar implants, feminization), body (abdominoplasty and torsoplasty, post-partum and ex-obesity surgery, body and limb contouring, complication treatments) and nose surgery combined with medical innovations in energy devices, threads and aesthetic medicine procedures. Special attention was also given to the theme of the therapeutic role of aesthetic surgery, which is increasingly becoming an integral part of a clinical pathway useful for restoring the patient’s psycho-physical balance. Presented here is a report of the abstracts accepted due to their innovative or cutting-edge content that were selected to be given as oral presentations during the congress sessions. The 2nd edition of the Saccomanno memorial award for the best abstract presented by a young surgeon has been organized with the endorsement of Surgical Techniques Development by MDPI. Full article

Nectin-4 has emerged as a clinically relevant target in muscle-invasive bladder cancer (MIBC), primarily because of its role in antibody–drug conjugate-based therapies. However, the broader biological context of Nectin-4 expression and its association with tumor-promoting signaling pathways in MIBC remain insufficiently characterized. In this single-institution study, Nectin-4 expression (H-score 0–300) was assessed by immunohistochemistry in two independent MIBC cohorts. Associations between Nectin-4 expression and key markers related to growth signaling, metabolic regulation, and inflammation were analyzed alongside clinicopathological characteristics. Nectin-4 expression was significantly higher in malignant tissue than in non-malignant tissue (p = 0.0016 and p = 0.0302, respectively). Nectin-4 expression was not associated with demographic or clinicopathological parameters; however, a trend toward lower expression in more advanced disease stages was observed. Significant positive correlations were identified between Nectin-4 expression and protein kinase B (p = 0.0004), cytoplasmic (p = 0.0115) and membranous somatostatin receptor 2 (p = 0.0125), insulin receptor substrate 1 (p = 0.03), and interleukin-1 receptor antagonist (IL-1RA; p = 0.0045). In contrast, a negative correlation was observed with the IL-1β/IL-1RA ratio (p = 0.0246). Although Nectin-4 expression was not significantly associated with cancer-specific or overall survival, a trend toward shorter relapse-free survival was observed in patients with lower Nectin-4 expression (p = 0.0531). In multivariate analysis, patient age, but not Nectin-4 expression, emerged as an independent prognostic factor. Although Nectin-4 expression does not appear to have independent prognostic value, its biological associations suggest that it reflects an integrated tumor-related signaling context. These findings support further investigation of Nectin-4 as part of rational, biology-driven therapeutic strategies in bladder cancer. Full article

Diabetes mellitus remains a major metabolic disorder requiring the development of new and effective α-glucosidase inhibitors. The present study aimed to identify, design, and optimize novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-α]pyrimidine derivatives with promising inhibitory activity against the α-glucosidase enzyme using a comprehensive in silico strategy. Approximately 300 molecular descriptors were calculated to characterize a dataset of 32 compounds (Peytam et al.) and to investigate the structural factors governing their biological activity. Based on these descriptors, a multiple linear regression model was developed to predict the inhibitory activities of the compounds against alpha-glucosidase. The developed model demonstrated satisfactory predictive performance and was internally and externally validated to ensure its accuracy, robustness, and reproducibility. In addition, the applicability domain analysis confirmed the reliability of the predictions. Using the validated QSAR model, seven new derivatives were designed with predicted pIC₅₀ values exceeding the maximum activity of the parent compounds. The leverage analysis demonstrated that all newly designed compounds were located within the applicability domain of the model, supporting the reliability of the predictions. To further evaluate their inhibitory potential, molecular docking studies were performed to investigate the interactions between the designed compounds and the α-glucosidase active site. The docking results revealed favorable binding interactions comparable to those reported for known α-glucosidase inhibitors. Furthermore, ADMET analysis indicated generally favorable pharmacokinetic properties, although potential CYP3A4 inhibition-related pharmacokinetic risks were identified and discussed. Molecular dynamics simulations, including replicated runs and MM/GBSA binding free energy calculations, confirmed the stability of the most promising protein–ligand complexes throughout the simulation period. In conclusion, this study proposes a robust and integrated computational workflow combining descriptor generation, QSAR modeling, applicability domain analysis, molecular docking, ADMET prediction, and molecular dynamics simulations for the rational design of potential α-glucosidase inhibitors. The findings highlight the therapeutic potential of the designed derivatives and provide a valuable in silico framework for the future development of antidiabetic agents. Full article

Secreted frizzled-related protein 4 (sFRP4) has traditionally been regarded as a Wnt antagonist with tumor-suppressive properties. However, growing evidence indicates that its role in cancer is far more complex and highly context-dependent. Depending on tumor type, molecular subtype, epigenetic state, and microenvironmental conditions, sFRP4 may exert either inhibitory or tumor-promoting effects. This functional heterogeneity has important implications for understanding cancer biology and for evaluating the clinical relevance of sFRP4. In this review, we summarize current knowledge of the structural features, regulatory mechanisms, and signaling functions of sFRP4, and discuss how these factors shape its diverse roles across malignancies. We further examine its potential significance in diagnosis, prognosis, therapeutic stratification, and systemic metabolic regulation. A clearer understanding of the context-specific behavior of sFRP4 may help refine its value as a biomarker and support the development of more precise and mechanism-informed therapeutic strategies. Full article

Background/Objectives: Schistosomiasis, a parasitic disease caused by Schistosoma worms with freshwater snails as intermediate hosts, affects over 250 million people. The current control relies solely on praziquantel, which raises concerns on drug resistance and highlights the need for new therapeutic alternatives. Our bioprospection studies have focused on marine macroalgae as an unexplored source of antischistosomal metabolites with promising results. Guided by WHO recommendations to target both the parasite and its transmission vectors, this study aimed to investigate Ochtodes secundiramea to: (i) isolate active metabolites; (ii) evaluate the isolated compounds against adult worms and oviposition to identify leads for drug development; and (iii) perform an independent screening of their effects against the environmental transmission stages on cercariae and B. glabrata embryos. Methods: A dichloromethane extract of O. secundiramea was submitted to an NMR–biomonitored guided fractionation against Schistosoma mansoni adult worms. Active fractions were further purified through HPLC and characterized by ¹H and ¹³C NMR spectroscopy to identify the isolated compounds. Results: Three halogenated monoterpenes were isolated: ochtodene 1 (4-bromo-1,6,8-trichloro-2,3-ochtodene), ochtodene 2 (2-chloro-1,6,8-tribromo-3,8-ochtodene), and the novel natural product ochtodene 3 [2,6-dibromo-4-(2-chloroethylidene)-1,1dimethylcyclohexane]. Ochtodene 1 was the primary active metabolite against Schistosoma mansoni adult worms, with IC₅₀/96 h values of 47.2 and 46.1 µM for male and female worms respectively, and totally suppressed egg laying with 60 µM, while showing no toxicity toward human fibroblasts. Notably, all metabolites, including the novel ochtodene 3, caused 100% mortality in cercariae and embryos at low concentrations. Conclusions: The discovery of the novel ochtodene 3 and the identification of distinct leads for host treatment and transmission elimination position O. secundiramea as a promising source for integrated schistosomiasis control. Full article

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy characterized by variable clinical behavior and diverse molecular phenotypes. Although immune checkpoint inhibitors and targeted therapies have transformed the treatment landscape of advanced RCC, clinically validated biomarkers capable of improving risk stratification, therapeutic-decision making and disease monitoring remain lacking. Kidney injury molecule-1 (KIM-1), also known as hepatitis A virus cellular receptor-1 (HAVCR1) or T-cell immunoglobulin and mucin domain-containing protein-1 (TIM-1), has emerged as a biologically compelling investigational biomarker e because of its close relationship to proximal tubular epithelial injury and renal carcinogenesis. KIM-1 is a transmembrane glycoprotein minimally expressed in normal kidney tissue but markedly upregulated in dedifferentiated proximal tubular epithelial cells following injury, and in clear cell RCC, where its extracellular domain can be shed into plasma and urine. Beyond its role as a marker of tubular injury, KIM-1 participates in immune regulation, phagocytosis, inflammatory signaling and tissue remodeling, supporting its potential relevance to tumor biology. Clinical studies have demonstrated associations between elevated circulating KIM-1 levels and RCC diagnosis, recurrence risk, and survival outcomes, particularly in localized and postoperative disease settings. KIM-1 has additionally been investigated as a therapeutic target through antibody–drug conjugate approaches. Despite promising translational data, important limitations yet remain. Current evidence is predominantly prognostic rather than predictive, and substantial analytical and biological challenges continue to limit implementation. Assay standardization, clinically meaningful cutoffs, specimen selection, timing of sampling, and confounding by chronic kidney disease or nonmalignant renal injury remain incompletely resolved. Furthermore, evidence supporting incremental value beyond established clinicopathologic models remains limited. This review critically evaluates the biological rationale, analytical considerations and clinical evidence supporting KIM-1 in RCC. Particular emphasis is placed on distinguishing prognostic, predictive, pharmacodynamic, and therapeutic applications, as well as defining the evidentiary gaps that must be addressed before clinical implementation. Current evidence is derived predominantly from retrospective and exploratory analyses, and important limitations remain regarding assay standardization, biological specificity, chronic kidney disease-related confounding, and prospective validation. The review concludes with a summary of the evolving landscape of KIM-1-directed biomarker strategies in RCC, which may ultimately contribute to improved biologic risk stratification and biomarker-driven clinical investigation in RCC. Full article

Hydroperoxides (R–OOH, organic hydroperoxides) constitute a relatively small but structurally diverse class of natural metabolites occurring in higher plants, fungi, and marine organisms. Their formation is closely associated with oxidative processes involving redox-active metal ions, particularly iron and copper, which promote reactive oxygen species (ROS) generation and the oxidative transformation of steroids and triterpenoids. In the present study, approximately 1500 naturally occurring steroids and triterpenoids were screened using the PASS (Prediction of Activity Spectra for Substances) platform to identify compounds with potential relevance to neurodegenerative disorders. Among the analyzed compounds, only 17 hydroperoxide-containing steroids and triterpenoids exhibited notable predicted anti-dementia activity and were selected for detailed evaluation. The selected compounds displayed a broad spectrum of predicted biological activities, including antineoplastic, anti-inflammatory, antiulcerative, antithrombotic, hepatoprotective, and neuroprotective effects. Several hydroperoxide-containing triterpenoids demonstrated particularly high predicted anti-dementia activity, with a norlupane-type hydroperoxide exhibiting the highest probability of activity (Pa = 0.972). The biological significance of these compounds may be related to the unique redox properties of the hydroperoxide functionality, which can participate in both oxidative and adaptive signaling processes. Because hydroperoxides interact with transition metal ions and reactive oxygen species, they occupy a complex position at the interface between oxidative stress, cellular defense mechanisms, and neurodegeneration. The present analysis highlights hydroperoxide-containing steroids and triterpenoids as an underexplored class of natural products with potential relevance to dementia research. However, the reported activities are based primarily on computational predictions and should be interpreted as indicators of pharmacological potential rather than experimentally validated therapeutic effects. Further investigations involving blood–brain barrier permeability assessment, biochemical studies, cellular assays, animal models, and clinical evaluation will be required to determine the true therapeutic value of these compounds in neurodegenerative diseases. Full article

Irritable bowel syndrome (IBS) is a prevalent disorder of gut–brain interaction, characterized by a substantial symptom burden, impaired quality of life, and increased healthcare use. Despite advances in diagnostic criteria and treatment strategies, many patients feel dismissed, inadequately informed, or uncertain about the nature and meaning of their symptoms; these experiences may undermine trust and reduce engagement with healthcare professionals. The aim of this narrative review is to synthesize clinical and ethical considerations and propose a patient-centered ethical framework for IBS management, positioning communication as a core therapeutic intervention. We highlight how validation, clear and non-stigmatizing explanations, transparency about uncertainty, and recognition of patient values can strengthen the therapeutic alliance, support relational autonomy, and enable shared decision-making. These elements can promote supported self-management and improve adherence to individualized dietary, behavioral, and pharmacologic strategies. In response to the central role of nutrition in IBS care, we further integrate dietary management into the ethical framework, addressing dietary assessment, first-line dietary advice, soluble fiber, the structured low-FODMAP approach, and the risks of excessive or unsupported food restriction. We further discuss how the incorporation of patient-reported outcomes (PROs) can translate patient priorities into measurable outcomes, monitor clinically meaningful changes over time, and reduce discrepancies between clinical assessment and patients’ lived experiences. Finally, we underscore the impact of stigma and uncertainty and provide practical communication approaches to support a stronger therapeutic alliance in IBS care. The integration of ethical communication, PROs, and nutrition-sensitive self-management may improve patient experience, strengthen adherence, and support individualized therapeutic strategies in IBS care. Full article

This study aimed to investigate the selective anticancer activity of the curcumin analog PAC (3,5-Bis-4-hydroxy-3-methoxybenzylidene)-N-methyl-4-piperidone). Normal gingival epithelial cells (GECs), cancerous gingival cells (Ca9-22) and tongue squamous carcinoma cells (CAL27) were exposed to increasing concentrations of PAC (0–10 µM) for 24 h. Cell viability and cytotoxicity were evaluated using MTT and LDH assays, while apoptosis and caspase activation were analyzed by Annexin V/PI staining and flow cytometry. Gene-expression profiling was performed using RT² Profiler PCR arrays. PAC significantly inhibited Ca9-22 and CAL27 cell proliferation in a concentration-dependent manner, with an IC₅₀ value of 5 µM, while exerting no noticeable cytotoxic effects on normal GEC. PAC treatment induced significant early and late apoptosis associated with increased caspase activity in both oral cancer cell lines. Transcriptomic analyses revealed extensive modulation of apoptosis-related genes. In Ca9-22 cells, PAC predominantly suppressed anti-apoptotic and survival-associated genes, including BCL2, BIRC3, BIRC5, XIAP, CFLAR, and NFKB1. In contrast, CAL27 cells exhibited a more pronounced pro-apoptotic transcriptional profile characterized by upregulation of TP53, APAF1, CASP1, BID, and TNF. Gene interaction network analyses further demonstrated that PAC targets highly interconnected apoptotic signaling pathways. Collectively, these findings demonstrate that PAC exerts potent selective anticancer activity against OSCC cells through modulation of intrinsic and extrinsic apoptotic pathways. These results further support the therapeutic potential of PAC as a promising multitarget candidate for oral cancer treatment. Full article

Background and Clinical Significance: Carcinoid heart disease (CHD) is an uncommon valvular manifestation of neuroendocrine tumours, usually affecting right-sided cardiac valves. Left-sided involvement is rare and is generally associated with bronchopulmonary carcinoid, right-to-left shunting, or markedly elevated circulating vasoactive substances. Therapeutic decision-making is particularly challenging in advanced disease when severe tricuspid regurgitation occurs in patients at prohibitive surgical risk. Case Presentation: We report the case of a 61-year-old male patient with progressive dyspnoea, abdominal distension, lower-limb oedema, facial flushing, and 15 kg of unintentional weight loss. Transthoracic and transoesophageal echocardiography demonstrated torrential tricuspid regurgitation caused by thickened, retracted, and immobile leaflets, with additional mitral and aortic valve involvement, raising strong suspicion of CHD. An agitated-saline contrast study demonstrated delayed right-to-left shunting without patent foramen ovale, suggesting an extracardiac, likely intrapulmonary, shunt. Somatostatin receptor PET/CT identified a pancreatic lesion with metastatic disease, and bone marrow biopsy confirmed neuroendocrine tumour infiltration. Owing to prohibitive surgical risk, as reflected by a Tricuspid Regurgitation Impact Score (TRI-SCORE) with an estimated in-hospital mortality of 65%, unfavourable tricuspid anatomy for repair, and refractory venous congestion, heterotopic bicaval valve implantation was performed (TricValve system -P&F). Discussion: This case highlights the role of echocardiography in recognising the characteristic phenotype of CHD, detecting occult right-to-left shunting, and supporting selection of a palliative transcatheter intervention. It also illustrates the value of a multimodality diagnostic strategy integrating echocardiography, functional oncological imaging, and histopathology in tumour-related cardiac disease. Conclusions: In selected inoperable patients with advanced carcinoid-related tricuspid regurgitation, heterotopic bicaval valve implantation may represent a feasible strategy for reducing venous congestion and improving functional status. Full article

Background: Live music, understood as real-time musical performance delivered in the physical presence of patients or other participants, is increasingly incorporated into healthcare settings as an arts-based, non-pharmacological practice intended to support well-being and humanize care. While previous reviews have examined a broad range of music-based interventions in healthcare, limited attention has been given specifically to live music, its contextual characteristics, and the values attributed to its use within hospital environments. Objectives: This scoping review aims to map and synthesize the literature on live music in healthcare settings, focusing on clinical contexts, populations involved, and the therapeutic, psychosocial, and environmental values reported. Methods: A scoping review was conducted following the framework of Arksey and O’Malley. Searches were performed in Web of Science, Scopus and Pubmed using terms related to live music and healthcare settings. Studies published in English or Spanish over the past 20 years were considered. After screening titles, abstracts, and full texts, 81 studies met the inclusion criteria. Results: The studies covered diverse hospital units and patient groups, particularly oncology, neonatal and intensive care, palliative care, and haemodialysis. Reported outcomes were mainly psychological and emotional, including reductions in anxiety, stress, and distress, alongside improvements in mood, well-being, and quality of life. Cognitive, physiological, and environmental benefits were also identified, emphasizing the role of live music in creating supportive and humanized care environments. Most studies were conducted in Europe and North America. Conclusions: Live music is widely implemented in healthcare settings and is associated with benefits extending beyond symptom reduction to experiential and humanizing dimensions of care. This scoping review provides an overview of the existing evidence base and identifies directions for future research in arts and health. Full article

Introduction: The uric acid-to-albumin ratio (UAR) is a novel cardiovascular biomarker, but its prognostic value in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) remains unknown. Materials and Methods: This retrospective study enrolled 1513 consecutive patients who underwent successful CTO-PCI at a single center from February 2011 to December 2023. Patients were stratified by baseline UAR tertiles. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), and the secondary endpoint was all-cause mortality. Multivariable Cox regression and restricted cubic spline (RCS) analyses were performed. Results: During a median follow-up of 810 days, patients in the highest UAR tertile had significantly higher rates of MACCE (18.5%, 10.1%, and 7.5% across tertiles; p < 0.001) and all-cause mortality (10.7%, 3.8%, and 2.0%; p < 0.001). After multivariable adjustment, each one-unit increase in UAR was associated with a 6% higher risk of MACCE (HR 1.06; 95% CI 1.02–1.10; p = 0.002) and a 9% higher risk of all-cause mortality (HR 1.09; 95% CI 1.04–1.14; p < 0.001). Patients in the highest UAR tertile had significantly increased risks of MACCE (HR 1.90; 95% CI 1.25–2.90; p = 0.003) and all-cause mortality (HR 3.40; 95% CI 1.62–7.12; p = 0.001) compared with those in the lowest UAR tertile. RCS analysis showed significant overall associations between UAR and both MACCE and all-cause mortality, with no significant evidence of nonlinearity. Conclusions: Elevated baseline UAR was independently associated with long-term MACCE and all-cause mortality after successful CTO-PCI. These findings support UAR as a readily available prognostic marker but do not establish causality or support UAR-guided therapeutic decision-making. Prospective studies are needed for validation. Full article

Background/Objectives: Enzalutamide and abiraterone acetate are commonly used androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC), including after docetaxel. However, real-world outcomes remain heterogeneous, and simple prognostic markers may help describe this variability. This study aimed to describe survival outcomes with enzalutamide and abiraterone acetate after docetaxel and to explore the prognostic value of a routine clinical-inflammatory risk classification. Methods: This retrospective single-center study included 136 patients with mCRPC treated with enzalutamide or abiraterone acetate after docetaxel. A composite risk classification was defined using four routinely available variables: pan-immune-inflammation value (PIV) > 457.99, time to castration resistance < 12 months, baseline hemoglobin ≤ 12 g/dL, and Gleason score ≥ 8. One point was assigned for each adverse factor, and patients were classified as low, moderate, or high risk. Overall survival (OS) was assessed using Kaplan–Meier estimates and Cox regression. The prognostic score and Cox regression-based nomogram were evaluated as exploratory tools. Results: Of the 136 patients, 8 (5.9%) were classified as low risk, 67 (49.3%) as moderate risk, and 61 (44.9%) as high risk. Median OS was not reached in the low-risk group, compared with 33.84 months in the moderate-risk group and 9.66 months in the high-risk group. In multivariable analysis, high-risk status was independently associated with worse OS (HR = 9.87; 95% CI: 2.38–40.92; p = 0.002). No statistically significant OS difference was observed between enzalutamide and abiraterone acetate in this non-randomized cohort (HR = 1.36; 95% CI: 0.90–2.06; p = 0.142). Conclusions: In this real-world post-docetaxel mCRPC cohort, no statistically significant OS difference was observed between enzalutamide and abiraterone acetate; however, the study was not designed to establish comparative effectiveness or therapeutic equivalence. The exploratory risk classification based on routine clinical and inflammatory variables was associated with distinct survival outcomes. External validation is required before clinical application. Full article

As the core molecular chaperones of the cellular stress response, the heat shock protein (HSP) family has gained extensive attention for its role in the occurrence, development, and target organ damage of hypertension. This review aimed to comprehensively summarize the research progress of the HSP family in the field of hypertension, and to analyze its key roles in the pathogenesis of hypertension, including its regulatory effects on key pathological processes such as endothelial dysfunction, proliferation and migration of vascular smooth muscle cells, oxidative stress, and inflammatory responses. It also summarized the potential value of HSPs as biomarkers in the early diagnosis, condition monitoring, and prognostic evaluation of hypertension. Moreover, it discussed in depth the efficacy and safety of intervention strategies targeting HSPs, including the regulation of HSPs by gene editing, the targeted effects of small-molecule inhibitors, and the modulatory effects of natural products. We need to strengthen interdisciplinary collaboration mechanisms, accelerate the transformation of basic research results into clinical applications, carry out large-scale clinical trials, and develop specific modulators in the future, so as to ultimately provide solid scientific theoretical support and a practical clinical basis for the precise prevention and treatment of hypertension. The findings of this review not only provide novel insights into the pathogenesis of hypertension but also lay a theoretical foundation for the development of HSP-based biomarkers and targeted therapeutic strategies. Full article