Search Results (255)

Background/Objectives: The COVID-19 pandemic severely impacted healthcare systems globally, with Italian healthcare professionals experiencing heightened stress, organizational challenges, and a significant psychological burden. This study investigates the frequency of depressive symptoms and health-related quality of life (H-QoL) among outpatient healthcare workers in Italy, comparing pre-pandemic (2017) and post-pandemic (2025) periods. Methods: A cross-sectional study was conducted in 2025, including 97 healthcare professionals from five outpatient departments at the University Hospital of Cagliari. Participants completed demographic surveys, the Short Form Health Survey (SF-12), and the Patient Health Questionnaire (PHQ-9) to assess H-QoL and depressive symptoms. Data were compared with previously published data from the same facility collected in 2017 and with pre-pandemic Italian community surveys. Results: Compared to 2017, there was a statistically significant increase in depressive episodes (38.1% vs. 33.2%, p = 0.01) and a higher proportion of individuals with low H-QoL (62.9% vs. 43.5%, p < 0.0001) in 2025. After age- and sex-standardization, both depressive symptoms and low H-QoL were significantly more prevalent among healthcare professionals in 2025 compared with the general population before the pandemic. Within the 2025 sample, non-medical healthcare workers showed a significantly higher prevalence of depressive symptoms than medical doctors, while female healthcare workers were more likely to report low H-QoL. Conclusions: Despite the pandemic’s end, healthcare workers, especially those in outpatient settings, continue to face elevated psychological distress. Specific professional and gender-related vulnerabilities persist, and structural challenges, such as staff shortages and organizational issues, may exacerbate this burden. Sustained mental health support and targeted systemic interventions remain crucial to mitigate the long-term impact on the healthcare workforce. Full article

Peritoneal metastases represent one of the most dreadful manifestations of gastric cancer and continue to drive poor outcomes despite significant advances in systemic therapy. Accurate staging—beginning with laparoscopy—remains essential for avoiding non-beneficial surgery and ensuring appropriate allocation to systemic or locoregional treatment pathways. Although modern systemic agents, including immunotherapy and targeted therapies, have transformed the broader management of metastatic disease, their impact in the peritoneal compartment remains limited, reflecting its unique biological and pharmacokinetic constraints. Locoregional approaches such as CRS–HIPEC, PIPAC, and NIPS have expanded the therapeutic armamentarium and have shown encouraging signals in selected populations. Recent randomized studies, including ESTOK01 and PERISCOPE II, emphasize the importance of careful patient selection, technical standardization, and optimal sequencing, while ongoing trials—such as PREVENT, GASTRICHIP, and CONVERGENCE—seek to refine the integration of systemic and intraperitoneal strategies. Yet the field continues to advance without the benefit of validated predictive biomarkers capable of guiding therapeutic decisions. This limitation constrains clinical progress and underscores the need for a stronger translational framework. Future improvement in the management of gastric cancer with peritoneal metastases will depend on the identification of robust biological predictors of response, enabling more rational patient selection and the development of truly personalized multimodal approaches. Full article

Background and Aims: Gastric cancer (GC) remains a leading cause of cancer-related mortality, frequently diagnosed at advanced stages. High-risk features—tumor size ≥ 40 mm, cT3/cT4, nodal involvement, diffuse histology, and Borrmann type III/IV—are associated with peritoneal metastasis (PM). Staging laparoscopy with peritoneal washing (PW) is superior to conventional preoperative imaging modalities, including contrast-enhanced CT, MRI, PET/CT and endoscopic ultrasound, in detecting occult peritoneal disease. In this era of personalized medicine and expanding loco-regional strategies such as cytoreductive surgery (CRS)/Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) and Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC), accurate staging is crucial. This study assessed the impact of SL and PW in high-risk GC. Methods: We retrospectively analyzed 113 consecutive high-risk GC patients who underwent SL and PW between 2014 and 2024 at our institution. The primary endpoint was detection of PM or positive cytology (CY+). Secondary endpoints were treatment modification, eligibility for loco-regional therapy, and safety. Results: SL/PW identified PM or CY+ in 26 patients (23%), including 16 with CY+ only. None had radiologic signs of peritoneal disease. SL findings altered treatment in all cases: 21 patients (81%) with Peritoneal Cancer Index (PCI) < 6 underwent induction chemotherapy followed by CRS + HIPEC; 5 patients (PCI > 6) were spared non-therapeutic laparotomy and treated with bidirectional systemic chemotherapy and PIPAC. In 10 patients, systemic therapy was shifted from FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) to FOLFOX (fluorouracil, leucovorin, and oxaliplatin) ± nivolumab. No perioperative complications occurred; all patients were discharged within 24 h without delay in systemic treatment. Conclusions: SL with PW is safe and significantly improves staging accuracy in high-risk GC, enabling personalized therapeutic planning. Routine integration of SL should be considered essential in treatment algorithms to guide systemic and loco-regional strategies. Full article

Background/Objectives: Metabolic syndrome (MetS) and even closely related metabolic and anthropometric alterations require timely intervention to reduce associated risks. Neo-Policaptil^® Gel Retard has shown potential in managing both established MetS and early imbalances. To further characterize its real-world impact, a large post-marketing survey was conducted to assess perceived effectiveness, safety, quality of life (QoL), and patterns of use. Methods: Between December 2021 and May 2025, patients/child caregivers, pharmacists, and physicians completed online questionnaires via a dedicated web platform. Patients reported their direct experience, while healthcare professionals (HCPs) provided observations on patient use. Results: The survey included 2204 patients, 57 child caregivers, 455 physicians, and 387 pharmacists. Overall, 97.7% of patients reported an improvement in their condition. Most physicians (94.3%) and pharmacists (89.1%) rated the overall effectiveness of the product as “good” or “excellent”. The safety profile was judged “good” or “excellent” by 84.4% of patients and by over 93% of HCPs. The product was mainly used as monotherapy or in combination with dietary measures and/or physical exercise. Conclusions: These findings underscore the product’s effectiveness, safety, tolerability, and positive influence on QoL in both adults and children affected by MetS or by related metabolic and anthropometric imbalances. Full article

Background/Objectives: Children with hearing loss (HL) could experience significant fatigue which compromises their performance. The effort related to the combination of HL and visual impairment in children affected by Usher syndrome (USH) could compromise mental health, socio-emotional behavior and academic achievement. The aim of the present study was to analyse the listening effort in USH cases types 1 and 2 and its relation to age, molecular diagnosis, visual field, visual acuity, degree of HL, vestibular impairment and spatial orientation. Methods: This was a retrospective monocentric study. Twenty children with genetically confirmed USH (USH2 in 15/20–75% and USH1 in 5/20–25%), age range 3–17 years (mean 9.6 ± 4.7), underwent: the Vanderbilt fatigue scale questionnaire (VFS), audiological and vestibular assessment including the Oldenburg Matrix test in Italian and video head impulse test (VHIT), sound localization test and ophthalmologic examination. Results: We observed a more pronounced HL and deteriorated vestibular function in those with USH1. They also employed significantly more time and head movements to localize sounds compared to USH2 and had the worst visual field on eye examination. The VFS did not show significant differences between the two groups, with the exception of the physical fatigue reported by parents. Mean VFS was linearly related to age, the hearing threshold of the worse ear, data logging hours of hearing device, time and head movements of the localization test, VHIT asymmetry and balance problems referred by parents and the visual field. USH type 1 had no greater risk of fatigue than USH2. Profound hearing loss, data logging of hearing device < 8 h a day, difficult localization test, balance problems and low retinal sensitivity represented risk factors for listening effort measured with VFS. Conclusions: Listening effort in difficult environments such as school rooms in USH patients is not only associated to hearing function but also to the spatial awareness determined in part by vestibular and visual function. Teachers should be informed and made aware of multiple comorbidities in order to facilitate learning. Full article

Background/Objectives: We measured hepatic T2*, T1, and T2 values in N = 81 transfusion-dependent thalassemia (TDT) patients to assess and compare their reproducibility, evaluate their correlations with demographics and clinical parameters, and explore their association with disease-related complications. Methods: All TDT patients (52 females, 38.13 ± 10.79 years), were enrolled in the Extension-Myocardial Iron Overload in Thalassaemia Network. The magnetic resonance imaging protocol (1.5 T) included: multi-echo gradient echo sequences for T2* relaxometry, modified look-locker inversion recovery (MOLLI) sequences for T1 mapping, and multi-echo fast-spin-echo (MEFSE) sequences for T2 mapping. Results: All three relaxation times demonstrated good intra- and inter-observer reproducibility and were significantly correlated with each other. Of the 59 patients with reduced T2*, 45 (76.3%) also had reduced T1, and 42 (71.2%) had reduced T2 values. Among 22 patients with normal T2*, 3 (13.6%) exhibited reduced T1. No patients showed increased T1, and only one had elevated T2. Liver relaxation times were not associated with gender or splenectomy status. All relaxation times inversely correlated with serum ferritin levels, while T2 and T2* inversely correlated with mean alanine aminotransferase levels. Cirrhosis and glucose metabolism alterations were associated with lower relaxation times. All three relaxation times effectively discriminated between the absence and presence of cirrhosis [areas under the curve (AUCs) with 95% confidence intervals (CIs): 0.85 (0.75–0.92) for T2*, 0.78 (0.68–0.87) for T1, and 0.92 (0.84–0.97) for T2]. T2* showed comparable accuracy to T1 and T2, while a significant difference was observed between T1 and T2 values. All liver relaxation times demonstrated similar diagnostic performance in identifying glucose metabolism alterations [AUCs with 95% CIs: 0.67 (0.55–0.77) for T2*, 0.69 (0.57–0.79) for T1, and 0.67 (0.56–0.77) for T2]. Conclusions: In TDT, a comprehensive assessment of hepatic relaxation times may enhance clinical monitoring and management of iron overload and its related complications. Full article

As a versatile shrub, sea buckthorn (Hippophae rhamnoides L.) plays a significant role in restoring degraded ecosystems and supporting regional economies. However, its cultivation faces increasing risks from climate change and pest infestations, particularly from Rhagoletis batava and Cossus cossus. This study aimed to evaluate potential suitable planting areas for H. rhamnoides under current and future climate conditions while accounting for pest risks. The MaxEnt model was employed to predict species distributions and their overlap with pest habitats across multiple climate scenarios (SSP126, SSP245, and SSP585) for the periods 2041–2060 and 2081–2100. The results indicate that currently, 61.95% of the suitable areas for H. rhamnoides face threats from pests. Under future scenarios, the total suitable area showed an increasing trend under SSP126 and SSP245, but a significant decrease under SSP585 by the 2090s. Notably, the area severely threatened by both pests was projected to reduce dramatically, by up to 85.40% under the high-emission scenario (SSP585–2090s), suggesting a potential ecological window for cultivation expansion in certain regions. The study introduces a dual-constraint model incorporating both climate and pest variables, providing a more accurate assessment of optimal planting areas. These findings offer critical insights for the sustainable management of H. rhamnoides cultivation by highlighting regions where pest control strategies should be prioritized and informing future policy and management decisions. Full article

Osteosarcoma (OSA) is an aggressive primary bone cancer mainly affecting the pediatric population. Despite intensive multimodal treatments, therapeutic progress has remained limited for decades, resulting in high recurrence rates, poor prognosis driven by metastatic progression, and severe chemotherapy-associated toxicities. To advance the development of more effective and safer therapeutic strategies, our recent studies identified Chondroitin Sulfate Proteoglycan (CSPG)4 as a relevant mediator of the malignant behavior of OSA cells. Targeting CSPG4 DNA-based vaccine demonstrated encouraging antitumor activity against OSA. Nevertheless, since single-agent immunotherapies are often constrained by tumor immune escape, the need for rational combinatorial strategies is of utmost importance. In this perspective, we broaden our analysis to include other potentially complementary targets beyond CSPG4, which may contribute to OSA pathogenesis. Among these, the cystine/glutamate antiporter xCT and Toll-like Receptor 2 (TLR2) emerge as particularly promising due to their established role in tumor progression, therapy resistance, and immune modulation. We discuss the contribution of all these molecules in major hallmarks of OSA—(1) proliferative and survival advantages, (2) metastasis and angiogenesis, and (3) immune evasion—and examine potential strategies for their combined targeting. By leveraging knowledge gained from other cancer models and integrating it with the distinct biological and clinical features of OSA, this perspective seeks to outline rational and innovative combinatorial strategies that may overcome current therapeutic limitations and ultimately improve patient outcomes. Full article

Cryptorchidism is a genital defect in which ram testicles fail to descend, causing azoospermia, while maintaining normal behavior towards females. We investigated whether cryptorchid rams can induce a ram-effect in ewes that would then be subjected to artificial insemination (AI). Therefore, ewes were isolated from any contact with rams for 6 weeks, then exposed to cryptorchid rams for 14 days. From day 15 to day 24, estrus was checked using a cryptorchid teaser four times daily (at 08:00, 12:00, 16:00, 20:00). Ewes detected in estrus were inseminated 24 h later. Experiment 1 included ewes (n = 31) all exposed to the cryptorchid ram-effect (CRE): 70.9% showed estrus, lambing rate after AI was 45.5%, and prolificacy was 1.40. Experiment 2 compared CRE (n = 80) with a control group with no prior exposure to males (n = 39). Estrus occurrence differed significantly (75.0% vs. 23.1%, respectively, p ≤ 0.001). Lambing rate from AI was 44.1% and prolificacy 1.27. These results show that cryptorchid rams effectively induce and synchronize estrus in Sarda ewes. AI fertility results on natural estrus following CRE yields outcomes comparable to those previously reported after hormonal synchronization for this breed. Full article

Background/Objectives: Healthcare workers (HCWs) experienced marked psychological distress during and after the COVID-19 pandemic, including high levels of burnout, depression, and suicidal ideation. Italy, one of the first Western countries to be severely affected, recorded high mortality, even among healthcare staff. Emerging evidence suggests that suicidal ideation may also occur in the absence of major depressive episodes, possibly linked to subthreshold mood dysregulation and circadian rhythm disturbances, described within the construct of Dysregulation of rhythms and hyper-energy Syndrome (DYMERS). This study examined the prevalence of suicidal ideation and/or death-related thoughts among Italian HCWs, with particular attention to clinically relevant signs emerging in the absence of a full depressive episode. Methods: A cross-sectional analysis was conducted on 97 HCWs at the University Hospital of Cagliari, Italy, compared with a pre-pandemic community sample from the same region. Depressive symptoms and suicidal ideation or death-related thoughts were assessed with the Patient Health Questionnaire-9 (PHQ-9), considering their presence both in individuals with and without a depressive episode. Daily activation and energy were measured using item 10 of the 12-Item Short Form Health Survey (SF-12), while circadian rhythm dysregulation was evaluated with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). Results: HCWs showed a significantly higher prevalence of suicidal or death-related thoughts than the community sample (14.4% vs. 5.7%, p = 0.001; OR = 2.81, 95% CI 1.4–4.4). Notably, 8.2% of HCWs without probable depression reported such thoughts; given the very small number of events (n = 4), this estimate is exploratory, and inferential statistics should be interpreted with caution. Based on descriptive data, these individuals appeared to show higher perceived activation (SF-12, item 10) and rhythm dysregulation (BRIAN). This observation is exploratory and consistent with the DYMERS heuristic framework. Conclusions: Subthreshold symptoms and DYMERS may represent critical risk factors in suicide prevention strategies for HCWs. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers, largely due to late diagnosis and the lack of reliable non-invasive biomarkers. Altered trace element homeostasis has been implicated in tumor biology and systemic inflammation, but comprehensive metallomic profiling in PDAC is still limited. Methods: Using inductively coupled plasma mass spectrometry (ICP-MS), we quantified 20 serum and 15 urinary metals in 71 PDAC patients and 69 matched controls. Statistical analyses included univariate Wilcoxon testing, correlation with systemic inflammatory indices (NLR, MLR, SIRI, AISI, HGB/RDW, PCT), and multivariate chemometric modeling (PCA-LDA). K-means clustering was applied to identify patient subgroups with distinct biochemical signatures. Results: PDAC patients showed significantly elevated urinary antimony, chromium, cadmium, and vanadium, whereas controls exhibited higher serum selenium, zinc, barium, vanadium, and cobalt (all p < 10⁻⁵). The PCA-LDA model achieved 99% classification accuracy (Monte Carlo cross-validation, 1000 iterations), highlighting complementary diagnostic contributions of serum and urinary profiles. Serum selenium was inversely associated with SIRI and NLR, while urinary cobalt correlated positively with NLR. Clustering revealed three PDAC subgroups with different inflammatory and metallomic patterns, suggesting underlying biological heterogeneity. Conclusions: PDAC is characterized by opposite serum-urine metal signatures, indicating altered absorption-excretion dynamics. Selenium depletion may represent a protective biomarker, whereas urinary cobalt excretion reflects systemic inflammation. This integrative ICP-MS–chemometric approach provides a promising diagnostic tool for improving early detection and patient stratification in clinical practice. Full article

Colorectal cancer (CRC) is among the most prevalent malignancies worldwide, representing the second leading cause of cancer-related mortality and accounting for approximately 2 million new cases and nearly half a million deaths annually. Global age-standardized incidence rates are highest in Australia/New Zealand and other Western countries, and lowest in parts of sub-Saharan Africa and South Asia, reflecting variations in demographics, lifestyle exposures, and screening practices. Colon cancer constitutes the larger fraction of CRC cases, with rectal cancer contributing substantially, and early-onset CRC (<50 years) is increasing across both high-income and emerging regions. Established risk factors include age, hereditary syndromes, obesity, sedentary behavior, dietary patterns, metabolic disorders, and chronic inflammation, with notable distinctions between colon and rectal subsites. This narrative review provides a comprehensive overview of CRC epidemiology, molecular and genetic pathogenesis, staging, and modern therapeutic approaches, addressing colon and rectal cancers separately due to their distinct biology, clinical behavior, and treatment strategies. By integrating current knowledge on genetic drivers, systemic and local therapies, and patient stratification, the review aims to inform clinical practice, support clinical trial design, discuss ongoing challenges and future perspectives, and foster further research toward precision-guided management of CRC. Full article

Salmonella enterica subsp. enterica serovar Typhimurium is a major foodborne pathogen whose ability to form biofilms contributes to persistent contamination in food-processing and clinical environments. This study investigated the anti-biofilm activity of the biosurfactant surfactin, produced by Bacillus subtilis, against S. Typhimurium wild type (LT2) and its lipopolysaccharide (LPS)-modified mutants on commonly used plastic surfaces such as polypropylene (PP) and polystyrene (PS). Biofilm formation was quantified using the crystal violet assay, revealing significantly higher biomass on PS compared to PP (p < 0.0001). Surfactin at 5 µg/mL was identified as the minimum biofilm inhibitory concentration (MBIC), significantly reducing biofilm formation in the wild-type and LPS mutants rfaL, rfaJ, rfaF (all p < 0.0001), and rfaI (p < 0.01). Further analysis using fluorescence microscopy and SYPRO^® Ruby staining confirmed a significant reduction in extracellular polymeric substances (EPSs) on PP surfaces following surfactin treatment, particularly in strains LT2 (p < 0.0001), rfa (p < 0.01), rfaL (p < 0.0001), rfaG (p < 0.05), and rfaE (p < 0.0001). These findings highlight the influence of LPS structure on biofilm development and demonstrate surfactin’s potential as an eco-friendly antimicrobial agent for controlling S. Typhimurium biofilms on food-contact surfaces. Analysis of mutants revealed that disruption of the rfa gene, which is involved in the biosynthesis of the outermost region of the lipopolysaccharide (LPS), significantly reduced bacterial attachment to polypropylene. This suggests that interactions between the external LPS layer and the plastic surface are important for colonisation. In contrast, mutants in core LPS biosynthesis genes such as rfaE and rfaD did not show any notable differences in attachment compared to the wild-type strain. This highlights the specific importance of outer LPS components, particularly under surfactant conditions, in mediating interactions with plastic surfaces. This work supports the application of biosurfactants in food safety strategies to reduce the risk of biofilm-associated contamination. Full article

Background/Objectives: Adolescence is a sensitive developmental window shaped by both vulnerabilities and adaptive potential. From an evolutionary standpoint, mental health difficulties in this period may represent functional responses to environmental stressors rather than mere dysfunctions. Despite increasing interest, integrative models capturing the dynamic interplay of risk and protective factors in adolescent mental health remain limited. This study presents a holistic, multi-level framework grounded in ecological and evolutionary theories to improve understanding and intervention strategies. Methods: A two-round Delphi method was used to develop and validate the framework. Twelve experts in adolescent mental health evaluated a preliminary draft derived from the literature. In Round 1, 12 items were rated across five criteria (YES/NO format), with feedback provided when consensus thresholds were not met. Revisions were made using consensus index scores. In Round 2, the revised draft was assessed across eight broader dimensions. A consensus threshold of 0.75 was used in both rounds. Results: Twelve out of thirteen experts (92%) agreed to join the panel. Round 1 item scores ranged from 0.72 to 0.85, with an average consensus index of 0.78. In Round 2, ratings improved significantly, ranging from 0.82 to 1.0, with an average of 0.95. The Steering Committee incorporated expert feedback by refining the structure, deepening content, updating sources, and clarifying key components. Conclusions: The final framework allows for the clustering of indicators across macro-, medium-, and micro-level domains. It offers a robust foundation for future research and the development of targeted, evolutionarily informed mental health interventions for adolescents. Full article

Background: Hemorrhoidal disease (HD) is a common anorectal condition characterized by symptoms such as bleeding, pain, discomfort and itching. While often underdiagnosed due to patient reluctance to seek care, HD significantly impacts quality of life (QoL). Conservative treatments are preferred for low-grade HD, with increasing interest in natural substance-based therapies. Materials and Methods: A large-scale survey was conducted using a digital platform to collect real-world data (RWD) from patients, pharmacists and physicians. The research assessed perceived effectiveness, safety, tolerability, quality of life (QoL) and usage patterns of NeoFitoroid BioOintment. Quantitative analysis was also performed using a global score (GS) based on Likert scale ratings and their distribution. Results: A total of 2618 participants were included. A strong concordance across the three participating cohorts in the answers provided for all items of the questionnaire was observed. The descriptive analysis revealed high grades of effectiveness, safety and tolerability. Indeed, over 90% of respondents rated the product as “good” or “excellent” in terms of effectiveness and safety. Conclusions: These findings underscore the treatment’s effectiveness, safety, tolerability and positive influence on QoL in HD patients. Full article