Search Results (112)

Glioblastoma (GBM) is a highly aggressive brain tumor marked by invasive growth and therapy resistance. Tumor cells adapt to hostile conditions, such as hypoxia and nutrient deprivation, by activating survival mechanisms including autophagy and metabolic reprogramming. Among GBM-associated changes, hypersialylation, particularly, the aberrant expression of polysialic acid (PSA), has been linked to increased plasticity, motility, and immune evasion. PSA, a long α2,8-linked sialic acid polymer typically attached to the NCAM, is abundant in the embryonic brain and re-expressed in cancers, correlating with poor prognosis. Here, we investigated how PSA expression was regulated in GBM cells under nutrient-limiting conditions. Serum starvation induced a marked increase in PSA-NCAM, driven by upregulation of the polysialyltransferase ST8SiaIV and an autophagy-dependent recycling of sialic acids from degraded glycoproteins. Inhibition of autophagy or sialidases impaired PSA induction, and PSA regulation appeared dependent on p53 function. Immunohistochemical analysis of GBM tissues revealed co-localization of PSA and LC3, particularly around necrotic regions. In conclusion, we identified a novel mechanism by which GBM cells sustain PSA-NCAM expression via autophagy-mediated sialic acid recycling under nutrient stress. This pathway may enhance cell migration, immune escape, and stem-like properties, offering a potential therapeutic target in GBM. Full article

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article

Gender-specific cardiology has gained increasing recognition in recent years, emphasizing the need for tailored management strategies for women with cardiovascular disease. Among these, cardiomyopathies—dilated, arrhythmogenic, hypertrophic, and restrictive—pose unique challenges throughout a woman’s reproductive life, affecting contraception choices, pregnancy outcomes, and breastfeeding feasibility. Despite significant advances in cardiovascular care, there is still limited guidance on balancing maternal safety and neonatal well-being in this complex setting. This review provides a comprehensive overview of the current evidence on reproductive counseling, pregnancy management, and postpartum considerations in women with cardiomyopathies. We discuss the cardiovascular risks associated with each cardiomyopathy subtype during pregnancy, highlighting risk stratification tools and emerging therapeutic strategies. Additionally, we address the safety and implications of breastfeeding, an often overlooked but increasingly relevant aspect of postpartum care. A multidisciplinary approach involving cardiologists, gynecologists, obstetricians, and anesthesiologists is crucial to optimizing maternal and fetal outcomes. Improved risk assessment, tailored patient counseling, and careful management strategies are essential to ensuring safer reproductive choices for women with cardiomyopathy. From now on, greater attention is expected to be given to bridging existing knowledge gaps, promoting a more personalized and evidence-based approach to managing these patients throughout different stages of reproductive life. Full article

Background: Patients with obesity seeking bariatric surgery often display high rates of depressive symptoms, which are linked to worse clinical and surgical outcomes. A comprehensive evaluation of depression-related features in this population is lacking. Therefore, this study investigated clinical and psychopathological factors associated with depressive symptoms’ severity in 946 outpatients with obesity undergoing pre-surgical evaluation. Methods: The sample (45.1 ± 12 years) was subdivided according to Patient Health Questionnaire-9 (PHQ-9) into ‘absent’, ‘mild’, and ‘moderate-to-severe depression’ groups, which were compared for sociodemographic characteristics, childhood trauma, and emotional dysregulation. Assessments included the Childhood Trauma Questionnaire-Short-Form (CTQ-SF) and Difficulties in Emotion Regulation Scales (DERS). Inflammatory levels were evaluated through the Systemic Immune-inflammatory Index (SII). Multinomial logistic regression and correlations were performed to evaluate predictors of depression severity and their interrelationship. Results: Beyond sociodemographic and clinical differences, patients with moderate-to-severe depression displayed higher childhood trauma, emotional dysregulation, and inflammatory levels. Logistic regression with 95% confidence intervals showed that higher CTQ-SF scores were significantly associated with moderate-to-severe vs. absent depression (p = 0.005, 95% CI: 1.02–1.09), while elevated DERS scores were a risk factor for both moderate-to-severe vs. mild (p < 0.001, 95% CI: 1.04–1.11) and vs. absent depression (p < 0.001, 95% CI: 1.11–1.18). Additionally, PHQ-9 was significantly correlated with CTQ-SF, DERS, and SII. Conclusions: A worse clinical picture was observed in patients with moderate-to-severe depression, and significant interactions were found between psychopathology and inflammatory indexes. Emotional dysregulation was primarily associated with depression severity. These preliminary results support the implementation of rigorous pre-operative screening to identify and deliver targeted psychotherapeutic/pharmacological interventions aimed at improving clinical and post-surgical outcomes. Full article

The topical administration of drugs on the skin by nanovesicular systems can represent a tool to treat skin pathologies. The study of nanovesicle biodistribution after skin administration is crucial to understanding their transdermal potential. A formative study enabled us to investigate the influence of some methods in the production of nanovesicles based on phosphatidylcholine, differing in their ethanol amount. Particularly, both liposomes and ethosomes produced by different methods, i.e., microfluidics and solvent injection, were considered. The evaluation of size distribution, shape and internal morphology was performed using photon correlation spectroscopy, cryogenic electron microscopy, hyperspectral dark-field microscopy and small-angle X-ray scattering. Transmission electron microscopy was then used to observe and compare the transdermal passage of selected liposomes and ethosomes applied to human skin explants in a bioreactor. The mean diameters of nanovesicles prepared by the ethanol injection method were smaller with respect to those obtained by microfluidics, measuring roughly 140 and 230 nm, respectively. The uni- or multilamellar ultrastructure of the vesicles was influenced by the solvent injection procedure. Ultrastructural analysis of skin penetration revealed (i) the ability of intact vesicles to cross the different skin layers, with ethosomes produced by the water injection method showing greater transdermal potential and (ii) the role of ethanol as a penetration enhancer. Full article

Enterovirus (EV) infections in neonates can be transmitted vertically or horizontally, with symptoms ranging from mild to severe, including myocarditis, meningoencephalitis, and hepatitis. Neonates with EV-induced myocarditis may present severe cardiovascular disease with sudden onset of arrhythmia. Neonatal arrhythmias, particularly in low birth weight or critically ill infants, can impair cardiac function and worsen outcomes. EV targets cardiomyocyte receptors, inducing apoptosis pathways and triggering cardiac conduction disturbances. We present an extremely low-birth-weight preterm infant (GW 27 + 6) who developed EV-induced myocarditis, complicated with a sudden onset of supraventricular tachycardia (SVT), pericardial effusion and bi-atrial enlargement. Despite multi-agent regimen, including propranolol, flecainide, and amiodarone, the infant showed persistent junctional rhythm until seven months of age, later transitioning to atrial rhythm with stable cardiac function. A review of previously published rhythm disturbances due to EV-induced myocarditis is presented. Newborns with EV-induced arrhythmia may require a multi-modal treatment such as a multi-agent medical regimen or, in severe non-responsive cases, an electrophysiological approach. EV infections may cause long-term cardiovascular comorbidities (such as left ventricular dysfunction or mitral valve regurgitation), necessitating continuous monitoring through echocardiography and ECG. Collaboration between neonatologists and pediatric cardiologists is crucial for effective treatment and follow-up. Full article

Background: Cancer survivors who do not engage in regular physical activity often experience persistent psychological distress and fatigue, which can significantly impact their quality of life. While handgrip strength (HGS) is recognized as an indicator of overall health and physical resilience, the combined role of HGS and physical inactivity in predicting psychological distress and fatigue in this population remains unclear. This study aimed to examine the relationships between self-reported physical inactivity, HGS, and psychological distress, specifically depressive symptoms, anxiety, and cancer-related fatigue (CRF), in physically inactive cancer survivors. Methods: This cross-sectional study included 42 physically inactive cancer survivors (mean age = 63.2 years, SD = 8.96) recruited from the Cancer Institute (IRCCS) in Bari, Italy. Physical inactivity was quantified based on self-reported weekly physical activity minutes, with all participants engaging in less than 150 min per week. The participants underwent HGS assessment and completed validated psychological measures, including the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI-Y1 and STAI-Y2), and the Fatigue Severity Scale (FSS). Results: Bivariate correlations were examined via Spearman’s rank correlation coefficients, and multiple linear regression analyses were performed to identify independent predictors of psychological distress and fatigue, adjusting for covariates such as age, sex, cancer type, and time since treatment completion. Both lower HGS and greater physical inactivity were significantly correlated with greater depressive symptoms (HGS: ρ = −0.524, p < 0.001; physical inactivity: ρ = −0.662, p < 0.001), greater fatigue severity (HGS: ρ = −0.599, p < 0.001; physical inactivity: ρ = −0.662, p < 0.001), and increased trait anxiety (HGS: ρ = −0.532, p < 0.001; physical inactivity: ρ = −0.701, p < 0.001). No significant associations were found between physical inactivity or HGS and state anxiety (p > 0.05). Multiple regression analyses confirmed that both HGS and physical inactivity independently predicted depressive symptoms (HGS: β = −0.435, p = 0.009; physical inactivity: β = −0.518, p = 0.002), trait anxiety (HGS: β = −0.313, p = 0.038; physical inactivity: β = −0.549, p < 0.001), and fatigue (HGS: β = −0.324, p = 0.033; physical inactivity: β = −0.565, p < 0.001), even after adjusting for covariates. Low physical activity and reduced muscle strength independently predict psychological distress and fatigue in cancer survivors. Conclusions: These findings highlight the potential exacerbating role of physical inactivity in both physical and psychological vulnerability, underscoring the need for interventions promoting regular exercise. Integrating strength assessments and structured physical activity programs may be key strategies in survivorship care to improve mental well-being and overall quality of life. Full article

Background: Approximately 25.0% of metastatic prostate cancer patients harbour DNA damage repair mutations, including BRCA1 and BRCA2, which are actionable targets for poly(ADP-ribose) polymerase (PARP) inhibitors. Accurate detection of BRCA1/2 mutations is critical for guiding targeted therapies, but crucial pre-analytical factors, such as tissue storage duration and DNA fragmentation, drastically affect the reliability of next-generation sequencing (NGS) using real-world diagnostic specimens. Methods: This multicentre study analysed 954 formalin-fixed paraffin-embedded tissue samples from 11 centres, including 559 biopsies and 395 surgical specimens. This study examined the impact of storage duration (<1 year, 1–2 years, and >2 years) and DNA parameters (concentration and fragmentation index) on NGS success rates. Logistic regression and Cox regression analyses were used to assess correlations between these factors and sequencing outcomes. Results: NGS success rates decreased significantly with longer storage, from 87.8% (<1 year) to 69.1% (>2 years). Samples with higher DNA concentrations and fragmentation indexes had higher success rates (p < 0.001). Surgical specimens had superior success rates (83.3%) compared with biopsies (72.8%) due to better DNA quality. The DNA degradation rate was more pronounced in older samples, underscoring the negative impact of extended storage. Conclusions: Timely testing of BRCA1/2 mutations is critical for optimizing the identification of prostate cancer patients eligible for PARP inhibitors. Surgical specimens provide more reliable results than biopsies and minimizing the storage duration significantly enhances testing outcomes. Standardizing pre-analytical and laboratory procedures across centres is essential to ensure personalized treatments and improve patient outcomes. Full article

Background and Objectives: Mitral valve transcatheter edge-to-edge repair (TEER) is a widely adopted therapeutic approach for managing significant mitral regurgitation (MR) in high-risk surgical candidates. While procedural safety and efficacy have been demonstrated, the impact of institutional expertise on outcomes remains unclear. We aimed at evaluating whether the institutional monthly volume of TEER influences short- and long-term clinical results. Materials and Methods: This analysis from the multicenter, prospective GIOTTO trial study evaluated the impact of institutional monthly volume on outcomes of TEER to remedy significant mitral regurgitation. Centers were stratified into tertiles based on monthly volumes (≤2.0 cases/month, 2.1–3.5 cases/month, >3.5 cases/month), and key clinical, echocardiographic, and procedural outcomes were analyzed. Statistical analysis was based on standard bivariate tests as well as unadjusted and multivariable adjusted Cox models. Results: A total of 2213 patients were included, stratified into tertiles based on institutional procedural volume: 645 (29.1%) patients in the first tertile, 947 (42.8%) patients in the second tertile, and 621 (28.1%) patients in the third tertile. Several baseline differences were found, with some features disfavoring less busy centers (e.g., functional class and surgical risk, both p < 0.05), and others suggesting a worse risk profile in those treated in busier institutions (e.g., frailty and history of prior mitral valve intervention, both p < 0.05). Procedural success rates were higher in busier centers (p < 0.001), and hospital stay was also shorter there (p < 0.001). Long-term follow-up (median 14 months) suggested worse outcomes in patients treated in less busy centers at unadjusted analysis (e.g., p = 0.018 for death, p = 0.015 for cardiac death, p = 0.014 for death or hospitalization for heart failure, p < 0.001 for cardiac death or hospitalization for heart failure), even if these associations proved no longer significant after multivariable adjustment, except for cardiac death or hospitalization for heart failure, which appeared significantly less common in the busiest centers (p < 0.05). Similar trends were observed when focusing on tertiles of overall center volume and when comparing for each center the first 50 cases with the following ones. Conclusions: High institutional monthly volume of TEER mitral valve repair appears to correlate with an improved procedural success rate and shorter hospitalizations. Similarly favorable results were found for long-term rates of cardiac death or hospitalization for heart failure. These findings inform on the importance of operator experience and center expertise in achieving state-of-the-art results with TEER, while confirming the usefulness of the proctoring approach when naïve centers begin a TEER program. Full article

Quantum computing gives direct access to the study of the real-time dynamics of quantum many-body systems. In principle, it is possible to directly calculate non-equal-time correlation functions, from which one can detect interesting phenomena, such as the presence of quantum scars or dynamical quantum phase transitions. In practice, these calculations are strongly affected by noise, due to the complexity of the required quantum circuits. As a testbed for the evaluation of the real-time evolution of observables and correlations, the dynamics of the ${\mathbb{Z}}_n$ Schwinger model in a one-dimensional lattice is considered. To control the computational cost, we adopt a quantum–classical strategy that reduces the dimensionality of the system by restricting the dynamics to the Dirac vacuum sector and optimizes the embedding into a qubit model by minimizing the number of three-qubit gates. The time evolution of particle-density operators in a non-equilibrium quench protocol is both simulated in a bare noisy condition and implemented on a physical IBM quantum device. In either case, the convergence towards a maximally mixed state is targeted by means of different error mitigation techniques. The evaluation of the particle-density correlation shows a well-performing post-processing error mitigation for properly chosen coupling regimes. Full article

Background/Objectives: The UbcH10 protein plays an important role in a variety of human malignancies, including thyroid, breast, ovarian, and colorectal carcinomas. It has been previously reported that UbcH10 is overexpressed in non-small cell lung cancer (NSCLC) compared to normal lungs and that its expression is directly and inversely correlated with the mutational status of p53 and EGFR, respectively. Methods: We transfected lung cancer cells with wild-type and mutant forms of EGFR, modulated the expression of UbcH10 and p53, and treated these cells with tyrosine kinase inhibitor (TKI) erlotinib. Using Western blotting, we evaluated the expression of UbcH10 induced by EGFR and p53. Finally, we employed immunohistochemistry to assess the levels of UbcH10 expression in a subset of NSCLC patients receiving TKI therapy. Results: We reported a possible modulation of UbcH10 expression by the overexpression of wild-type and mutant EGFR in H460 lung cancer cells, potentially through p53. The enforced expression of UbcH10 in cells transfected with mutant EGFR suggested a potential increase in resistance to erlotinib treatment. Finally, immunohistochemical analysis of samples from NSCLC patients with mutant EGFR indicated a possible connection between UbcH10 expression levels and progression-free survival. Conclusions: In NSCLC, UbcH10 may play a role in the regulation of TKI response via a molecular pathway potentially involving p53 and EGFR. However, further research is needed to fully understand this mechanism. Full article

Introduction: Meniscus injuries are common among endurance athletes, requiring structured rehabilitation to restore function and facilitate a safe return to sport. Traditional in-person rehabilitation may not always be accessible or feasible for high-performance athletes. Telerehabilitation, incorporating virtual reality, motion tracking, and telemonitoring, offers an innovative approach to guided recovery. However, evidence supporting its effectiveness in elite athletes remains limited. Case presentation: This case report explores the application of an innovative telerehabilitation program for a 49-year-old triathlete recovering from partial meniscectomy following a medial meniscus tear. The program was structured into three progressive phases over 12 weeks, focusing on restoring range of motion (ROM), muscle strength, and functional stability while gradually reintroducing sports-specific activities. Results: By the end of the rehabilitation, the patient achieved full ROM and muscle strength (scoring 5/5 on the Medical Research Council scale for the vastus medialis), along with a pain-free state in both static and dynamic conditions. The integration of telemonitoring devices facilitated detailed monitoring and feedback, enabling personalized adjustments to the rehabilitation protocol. Key milestones included a return to swimming and cycling in Phase 2, reintroduction of running in Phase 3, and a full resumption of triathlon training by week 12. Conclusions: Despite the positive results, the study highlights the need for further research to validate these findings across larger cohorts and establish standardized telerehabilitation protocols for athletes. This case underscores the potential of digital health technologies in enhancing recovery trajectories for high-demand athletes post-meniscus surgery, paving the way for supervised, accelerated, and effective sports reintegration. Full article

We examine the physical limitations and performance of spatially coherent imaging systems under defocused conditions using a modified two-point resolution criterion. By comparing coherent and incoherent illumination regimes, in defocused conditions, we highlight the peculiar advantages of coherent systems in resolving closely spaced features while maintaining a high depth of field. The analysis identifies two primary contributions to image degradation in coherent defocused systems: image broadening and interference-related contrast reduction. Through a specifically designed analytical framework, this study confirms that resolution degradation in coherent imaging is characterized by a square root dependence on defocusing distance, irrespective of the numerical aperture. This behavior starkly contrasts with incoherent imaging, where the resolution deteriorates linearly with defocusing and exhibits a strong dependence on the system’s numerical aperture. Furthermore, we provide explicit analytical expressions for contrast loss and minimum resolvable object size under defocused coherent conditions, offering deeper insights into their relation with system parameters. These results corroborate the superior performance of coherent imaging in resolving fine details in defocused environments, challenging conventional optical paradigms. Our findings not only extend the theoretical understanding of coherent imaging but also establish practical guidelines to optimize optical systems for high-resolution applications. Full article

Vector-borne diseases represent a serious threat to human and animal health, especially where environmental conditions favor pathogen-carrying vectors. Dogs serve as natural hosts for two tick-borne pathogens: Ehrlichia canis, which causes canine monocytic ehrlichiosis, and spotted fever group (SFG) Rickettsia spp., a zoonotic threat in the Mediterranean region. Rhipicephalus sanguineus is the primary vector for these pathogens. Shelter dogs, due to increased exposure to ticks and confined living conditions, facilitate the spread of vector-borne pathogens, raising the risk of zoonotic transmission. This study conducted a serological survey of 1287 dogs from two shelters, assessing exposure to Rickettsia spp. and E. canis and examining the influence of demographic and environmental factors. Seroprevalence rates were 41.8% for Rickettsia spp. and 24.5% for E. canis, with 14% of dogs positive for both pathogens. No significant association was found with sex or breed. A higher seroprevalence was observed in dogs older than 12 months and in those from the shelter on the Mediterranean coast compared to those from the Tyrrhenian coast, likely due to climatic differences. The study highlights the role of climate in disease spread and the need for public health interventions, supporting One Health initiatives to prevent zoonotic disease transmission. Full article

Introduction: Colorectal cancer screening programs are effective in reducing incidence and mortality. In Europe, every FIT+ patient is referred to colonoscopy. The available data show that ~75.0% of these patients are negative. It is desirable to select patients at a greater risk of having a positive colonoscopy. Materials and Methods: 711 subjects, aged 50–74, attending the screening program of ASL-NA-3-SUD (Naples, Italy), were enrolled in a cross-sectional study to evaluate the performance of the QuantiDNA™ test and the non-inferiority of an alternative approach (AAP). This evaluation is based on FIT+ and QuantiDNA™+ patients referred to colonoscopy, compared to Standard of Care (SOC) colonoscopy following a FIT+ test alone. A non-inferiority margin (NIM) for colorectal neoplasia (CN) and advanced adenomas (AA) was set at −10% and at −3.8% for CRC. Results: The odds ratio was 1.76 (p-value = 0.009). The detection rate of AAP was 15.9% for colorectal neoplasia, 13.0% for advanced adenoma, and 3.0% for CRC. The risk difference between AAP and SOC was −5.07% (95% C.I. −9.23, −0.90) for colorectal neoplasia, −4.02% (95% C.I. −7.89, −0.16) for advanced adenomas, and −1.04% (95% C.I. −3.16, 1.07) for CRC. This data suggests that AAP is non-inferior to SOC for detecting CN, AA, and CRC. The expected decrease in colonoscopies is 33.4%. Conclusions: The QuantiDNA™ test is straightforward, non-invasive, and well-tolerated. Data from this study indicate that it is effective in the reduction of the need for colonoscopy examinations (−33.4%) and is non-inferior to SOC in the detection of significant colorectal lesions. Full article