Search Results (43)

Background: The present study aimed to investigate the clinical correlates of treatment response to mood stabilizers in patients with bipolar disorder (BD), with a specific focus on trait-related characteristics such as impulsivity and affective temperaments. Methods: In- and outpatients diagnosed with BD were recruited at the Section of Psychiatry of the General Hospital/University of Perugia. Socio-demographic, clinical, and current psychopathological characteristics were collected. The treatment response was retrospectively assessed using the Alda Scale. Trait characteristics were evaluated through the Barratt Impulsiveness Scale (BIS-11) and the Brief Temperament Evaluation of Memphis, Pisa, and San Diego—Münster version (briefTEMPS-M). Bivariate analyses and a general linear model were employed to analyze the correlates of treatment response to mood stabilizers. Results: Among the investigated variables, trait impulsivity showed a significant negative association with treatment response. A similar effect was observed for depressive temperament, while other affective temperaments were not significantly associated with treatment outcomes. Patients with good treatment responses exhibited higher illness duration and lower severity of BD, higher prevalence of comorbid anxiety disorders, lower diurnal variation in depressive symptoms, and lower functional impairment in autonomy and occupational domains. The main limitations of this study were represented by the small sample size, the retrospective assessment of treatment response, and the inclusion of patients from a single center. Conclusions: The present findings suggest that impulsivity and depressive temperament should be investigated as potential predictors of poor response to mood stabilizers in BD. These trait dimensions, together with other clinical markers, may serve as useful targets for patient stratification and the development of personalized treatment strategies. Full article

Background: Colds are widespread infectious diseases that affect daily life, increasing healthcare costs and limiting productivity. Objectives: The aim of this study was to investigate the effects of a dietary supplement containing specific probiotic strains (L. plantarum PBS067, L. acidophilus PBS066, B. lactis BL050) on cold symptom relief, immune response enhancement, and quality of life. Methods This randomized, double-blind, placebo-controlled trial included 65 healthy volunteers (age range: 18–44 years), divided into two groups: 40 received the probiotic treatment (with vitamins and bulking agents), and 25 received placebo (vitamins and bulking agents only) for 12 weeks. Cold symptoms and systemic inflammation were assessed at three time points (baseline T0, post-treatment T1, and 6 weeks after treatment T2). Results: Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7% for Placebo, p < 0.05). At T1, fever and muscle pain occurred in 20% of participants in the Probiotic group vs. 28% and 44% in the Placebo group, respectively (p < 0.05 for muscle pain vs. Placebo). For muscle pain, a trend was maintained also at T2 (17.5% vs. 20%). The pro-inflammatory cytokine IFN-γ levels significantly decreased in the Probiotic group vs. T0 (p < 0.0001 at T1 and p < 0.01 at T2), while they increased in the Placebo group (22.279 ± 3.538 vs. 19.432 ± 3.143 pg/mL, p = NS). Although not statistically significant, at T1 the Probiotic group had higher levels of IL-10 vs. T0 (266.98 ± 78.432 vs. 240.967 ± 70.238, pg/mL p = NS). Conclusions: The probiotic mix effectively alleviated cold symptoms and reduced pro-inflammatory cytokine levels, suggesting anti-inflammatory effects. Full article

Background/Objectives: Vaginal laser therapy is a promising treatment for menopausal vulvovaginal atrophy (VVA). This study evaluates the efficacy of a dual-wavelength diode laser (980 + 1470 nm) in treating VVA. Methods: Thirty postmenopausal patients with moderate-to-severe VVA were recruited, and twenty-nine completed the study. Patients underwent a screening visit (T0); three laser sessions at 4-week intervals (T1, T2, and T3); and a follow-up visit 4 weeks after the last treatment (T4). At T0 and T4, the Schiller test and Vaginal Maturation Index (VMI) were performed; sexual function was assessed through the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R). At each visit, the Vaginal Health Index (VHI) and the Visual Analog Scale (VAS) for dyspareunia were administered. Potential side effects were investigated, and the VAS for the pain associated with the procedure was assessed. Data analysis included the overall group and two subgroups: women with (group A) and without (group B) a history of breast cancer (BC). Results: Significant improvements in the VHI and reduced dyspareunia were observed at T4 compared to T0 in all groups. The improvement was already seen after the first procedure, with further improvement after the other procedures, being persistent at the 1-month follow-up. The Schiller test showed significant improvements from T0 to T4 in all groups. The VMI showed a significant improvement from T0 to T4 in the overall group and group B. The FSFI questionnaires showed a significant improvement in all areas for the whole population, whereas the FDSF-R questionnaire showed an improvement only in the overall group. Procedural pain was low (mean VAS 1.6), and no side effects were reported. Conclusions: The dual-wavelength diode laser is an effective and safe option for the treatment of VVA in patients with and without a history of BC. Full article

Background: Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). Methods: A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle–Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger’s test and funnel plots. Results: Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = −0.143, 95% CI: −0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: −0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). Conclusion: This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression. Full article

An important geological risk to which many towns in Puglia are exposed is sinking cavities in urban areas. For urban centers, studying, mapping, providing geological and speleological descriptions, classifying, and cataloging the forms and types of cavities is essential because cavities are linked to past local anthropic and natural processes at different sites. These circumstances could lead to the enhancement of existing underground cavities in urban areas through conservation and continuous monitoring. Unfortunately, in many cases, these underground cavities have been used as landfills and subsequently abandoned. In late March 2007, one of these cavities collapsed inside Gallipoli’s inhabited center, causing damage to the structures but fortunately not human lives. In the area surrounding the collapsed cavity, a series of geophysical investigations were undertaken using ground penetrating radar in an attempt to delimit the area of collapse and develop possible interventions for restoration. In the same area, these measures were repeated 16 years later in December 2022 due to another collapse. The comparison between data acquired in these two periods shows that there were no strong changes apart from an increased presence of subsoil moisture in 2022. Full article

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea, consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three-inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module also includes calibration instruments and electronics for power, readout, and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and ten prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, which total 828 as of October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. The validation of a pre-production series has been completed, and a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure safe operation at the bottom of the Mediterranean Sea throughout the observatory’s lifespan. Full article

Digital technologies have greatly developed and impacted several aspects of life, including health and lifestyle. Activity tracking, mobile applications, and devices may also provide messages and goals to motivate adopting healthy behaviors, namely physical activity and dietary changes. This review aimed to assess the effectiveness of digital resources in supporting behavior changes, and thus influencing weight loss, in people with overweight or obesity. A systematic review was conducted according to the PRISMA guidelines. The protocol was registered in PROSPERO (CRD42023403364). Randomized Controlled Trials published from the database’s inception to 8 November 2023 and focused on digital-based technologies aimed at increasing physical activity for the purpose of weight loss, with or without changes in diet, were considered eligible. In total, 1762 studies were retrieved and 31 met the inclusion criteria. Although they differed in the type of technology used and in their design, two-thirds of the studies reported significantly greater weight loss among electronic device users than controls. Many of these studies reported tailored or specialist-guided interventions. The use of digital technologies may be useful to support weight-loss interventions for people with overweight or obesity. Personalized feedback can increase the effectiveness of new technologies in motivating behavior changes. Full article

Hydroxylysine glycosylations are post-translational modifications (PTMs) essential for the maturation and homeostasis of fibrillar and non-fibrillar collagen molecules. The multifunctional collagen lysyl hydroxylase 3 (LH3/PLOD3) and the collagen galactosyltransferase GLT25D1 are the human enzymes that have been identified as being responsible for the glycosylation of collagen lysines, although a precise description of the contribution of each enzyme to these essential PTMs has not yet been provided in the literature. LH3/PLOD3 is thought to be capable of performing two chemically distinct collagen glycosyltransferase reactions using the same catalytic site: an inverting beta-1,O-galactosylation of hydroxylysines (Gal-T) and a retaining alpha-1,2-glucosylation of galactosyl hydroxylysines (Glc-T). In this work, we have combined indirect luminescence-based assays with direct mass spectrometry-based assays and molecular structure studies to demonstrate that LH3/PLOD3 only has Glc-T activity and that GLT25D1 only has Gal-T activity. Structure-guided mutagenesis confirmed that the Glc-T activity is defined by key residues in the first-shell environment of the glycosyltransferase catalytic site as well as by long-range contributions from residues within the same glycosyltransferase (GT) domain. By solving the molecular structures and characterizing the interactions and solving the molecular structures of human LH3/PLOD3 in complex with different UDP-sugar analogs, we show how these studies could provide insights for LH3/PLOD3 glycosyltransferase inhibitor development. Collectively, our data provide new tools for the direct investigation of collagen hydroxylysine PTMs and a comprehensive overview of the complex network of shapes, charges, and interactions that enable LH3/PLOD3 glycosyltransferase activities, expanding the molecular framework and facilitating an improved understanding and manipulation of glycosyltransferase functions in biomedical applications. Full article

The church of Santa Chiara with its adjacent convent, whose foundations date back to the 13th century, is a monastic complex in the city of Nardò in the province of Lecce. The current church was built ex novo between the 17th and 18th centuries under the direction of Bishop Orazio Fortunato. Currently, there is no information about the presence of crypts or burials in the church and in the adjacent area. For this reason, a campaign of geophysical investigations was undertaken using electromagnetic, electrical resistivity and ground-penetrating radar methods. Geophysical investigations were carried out both inside and in the courtyard of the church. The results showed the presence of a series of anomalies, whose interpretation suggests important structures of probable archaeological interest. Full article

The Castle of Melfi is placed on a hilltop overlooking the modern town and it includes many buildings that have been modified and expanded over time. Its Norman-era core was probably built between the end of the 11th and the start of the 12th century on top of an earlier Byzantine castrum; it was enlarged during the reign of Frederick II and additional alterations were undertaken during the reigns of the Angevin and Aragonese. Integrated ground-penetrating radar (GPR) and electrical resistivity tomography (ERT) surveys were carried out inside two courtyards of the westernmost part of the castle, the Cortile degli Armigeri and the Cortile del Mortorio, and in an external eastern wall area in order to identify ancient buried structures through two different methods of investigation and to compare the results. Full article

α-Synucleinopathies are spreading neurodegenerative disorders characterized by the intracellular accumulation of insoluble aggregates populated by α-Synuclein (α-Syn) fibrils. In Parkinson’s disease (PD) and dementia with Lewy bodies, intraneuronal α-Syn aggregates are referred to as Lewy bodies in the somata and as Lewy neurites in the neuronal processes. In multiple system atrophy (MSA) α-Syn aggregates are also found within mature oligodendrocytes (OLs) where they form Glial Cytoplasmic Inclusions (GCIs). However, the origin of GCIs remains enigmatic: (i) mature OLs do not express α-Syn, precluding the seeding and the buildup of inclusions and (ii) the artificial overexpression of α-Syn in OLs of transgenic mice results in a burden of soluble phosphorylated α-Syn but fails to form α-Syn fibrils. In contrast, mass spectrometry of α-Syn fibrillar aggregates from MSA patients points to the neuronal origin of the proteins intimately associated with the fibrils within the GCIs. This suggests that GCIs are preassembled in neurons and only secondarily incorporated into OLs. Interestingly, we recently isolated a synthetic human α-Syn fibril strain (1B fibrils) capable of seeding a type of neuronal inclusion observed early and specifically during MSA. Our goal was thus to investigate whether the neuronal α-Syn pathology seeded by 1B fibrils could eventually be transmitted to OLs to form GCIs in vivo. After confirming that mature OLs did not express α-Syn to detectable levels in the adult mouse brain, a series of mice received unilateral intra-striatal injections of 1B fibrils. The resulting α-Syn pathology was visualized using phospho-S129 α-Syn immunoreactivity (pSyn). We found that even though 1B fibrils were injected unilaterally, many pSyn-positive neuronal somas were present in layer V of the contralateral perirhinal cortex after 6 weeks. This suggested a fast retrograde spread of the pathology along the axons of crossing cortico-striatal neurons. We thus scrutinized the posterior limb of the anterior commissure, i.e., the myelinated interhemispheric tract containing the axons of these neurons: we indeed observed numerous pSyn-positive linear Lewy Neurites oriented parallel to the commissural axis, corresponding to axonal segments filled with aggregated α-Syn, with no obvious signs of OL α-Syn pathology at this stage. After 6 months however, the commissural Lewy neurites were no longer parallel but fragmented, curled up, sometimes squeezed in-between two consecutive OLs in interfascicular strands, or even engulfed inside OL perikarya, thus forming GCIs. We conclude that the 1B fibril strain can rapidly induce an α-Syn pathology typical of MSA in mice, in which the appearance of GCIs results from the pruning of diseased axonal segments containing aggregated α-Syn. Full article

In the last decades, there has been a huge increase in the consumption of both Energy Drinks (EDs) and alcohol and, concurrently, these two trends generated the additional practice of mixing ED with alcohol, known as Alcohol mixed with Energy Drink (AmED). One of the most important group of AmED consumers is represented by young. Indeed, the study population of the researches in this field are mainly represented by college students and the results evidence a great range of negative consequences for health. The purpose of the systematic review was to explore the prevalence of AmED consumption among undergraduate students, together with motivations to their use, adverse effects and health-related behaviors associated to AmEDs use. The review was conducted according to the PRISMA Statement and PubMed, Scopus and Web of Science were interrogated. 42 articles, published from 2008 to 2021, were included in the review. An overall prevalence rate of 37% was estimated for AmEDs use in undergraduates, with geographical differences. Although a decrease in consumption was observed throughout the studied period, a continuous monitoring on this phenomenon is needed for identifying those risk groups that could develop risky behaviors related to AmEDs consumption and provide them targeted educational interventions. Full article

Objective: This paper illustrates the results of a mono-institutional registry trial, aimed to test whether gastrointestinal (GI) and genitourinary (GU) toxicity rates were lower in localized prostate cancer patients treated with image-guided volumetric modulated arc therapy (IG-VMAT) compared to those treated with IG-3D conformal radiation therapy (IG-3DCRT). Materials and Methods: Histologically proven prostate cancer patients with organ-confined disease, treated between October 2008 and September 2014 with moderately hypofractionated radiotherapy, were reviewed. Fiducial markers were placed in the prostate gland by transrectal ultrasound guide. The prescribed total dose was 70 Gy in 28 fractions. The mean and median dose volume constraints for bladder and rectum as well as total volume of treatment were analyzed as potentially prognostic factors influencing toxicity. The Kaplan–Meier method was applied to calculate survival. Results: Overall, 83 consecutive patients were included. Forty-two (50.6%) patients were treated with 3D-CRT and 41 (49.4%) with the VMAT technique. The median follow-up for toxicity was 77.26 months for the whole cohort. The VMAT allowed for a dose reduction to the rectum and bladder for the large majority of the considered parameters; nonetheless, the only parameter correlated with a clinical outcome was a rectal dose limit V66 > 8.5% for late GI toxicity G ≥ 2 (p = 0.045). Rates of G ≥ 2 toxicities were low among the whole cohort of these patients treated with IGRT. The analysis for rectum dose volume histograms (DVHs) showed that a severe (grade ≥ 2) late GI toxicity was related with the rectal dose limit V66 > 8.5% (p = 0.045). Conclusions: This study shows that moderate hypofractionation is feasible and safe in patients with intermediate and high-risk prostate cancer. Daily IGRT may decrease acute and late toxicity to organs at risk and improve clinical benefit and disease control rate, cutting down the risk of PTV geographical missing. The adoption of VMAT allows for promising results in terms of OAR sparing and a reduction in toxicity that, also given the small sample, did not reach statistical significance. Full article

Introduction: Androgen receptor pathway inhibitors (ARPIs) have been increasingly offered to older patients with prostate cancer (PC). However, prognostic factors relevant to their outcome with ARPIs are still little investigated. Methods and Materials: The Meet-URO network ADHERE was a prospective multicentre observational cohort study evaluating and monitoring adherence to ARPIs metastatic castrate-resistant PC (mCRPC) patients aged ≥70. Cox regression univariable and multivariable analyses for radiographic progression-free (rPFS) and overall survival (OS) were performed. Unsupervised median values and literature-based thresholds where available were used as cut-offs for quantitative variables. Results: Overall, 234 patients were enrolled with a median age of 78 years (73–82); 86 were treated with abiraterone (ABI) and 148 with enzalutamide (ENZ). With a median follow-up of 15.4 months (mo.), the median rPFS was 26.0 mo. (95% CI, 22.8–29.3) and OS 48.8 mo. (95% CI, 36.8–60.8). At the MVA, independent prognostic factors for both worse rPFS and OS were Geriatric G8 assessment ≤ 14 (p < 0.001 and p = 0.004) and PSA decline ≥50% (p < 0.001 for both); time to castration resistance ≥ 31 mo. and setting of treatment (i.e., post-ABI/ENZ) for rPFS only (p < 0.001 and p = 0.01, respectively); age ≥78 years for OS only (p = 0.008). Conclusions: Baseline G8 screening is recommended for mCRPC patients aged ≥70 to optimise ARPIs in vulnerable individuals, including early introduction of palliative care. Full article

The progressive accumulation of misfolded α-synuclein (α-syn) in the brain is widely considered to be causal for the debilitating clinical manifestations of synucleinopathies including, most notably, Parkinson’s disease (PD). Immunotherapies, both active and passive, against α-syn have been developed and are promising novel treatment strategies for such disorders. To increase the potency and specificity of PD vaccination, we created the ‘Win the Skin Immune System Trick’ (WISIT) vaccine platform designed to target skin-resident dendritic cells, inducing superior B and T cell responses. Of the six tested WISIT candidates, all elicited higher immune responses compared to conventional, aluminum adjuvanted peptide-carrier conjugate PD vaccines, in BALB/c mice. WISIT-induced antibodies displayed higher selectivity for α-syn aggregates than those induced by conventional vaccines. Additionally, antibodies induced by two selected candidates were shown to inhibit α-syn aggregation in a dose-dependent manner in vitro. To determine if α-syn fibril formation could also be inhibited in vivo, WISIT candidate type 1 (CW-type 1) was tested in an established synucleinopathy seeding model and demonstrated reduced propagation of synucleinopathy in vivo. Our studies provide proof-of-concept for the efficacy of the WISIT vaccine technology platform and support further preclinical and clinical development of this vaccine candidate. Full article