University of Parma

This systematic review and meta-analysis aimed to evaluate indications, techniques, and outcomes of endovascular treatment for symptomatic hypogastric artery lesions. A systematic literature search (PubMed, Web of Science, Scopus, and Cochrane Library) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed (PROSPERO registration number CRD420251232230). Studies including at least 5 cases of symptomatic hypogastric artery lesions, treated with endovascular technique, were included. Primary outcomes were technical success (TS) and clinical success (CS). Secondary end points included patency, reintervention, and complications. Meta-analyses of proportions were performed using a random-effects model. Six studies comprising 95 patients and 117 treated hypogastric arteries were included. Mean age was 67.46 years (95% confidence interval [CI] 65.3-69.6; P = 0.018), and 89.9% of patients (95% CI 83.9-95.8; P = 0.775) were male. The hypogastric lesions were predominantly unilateral 72.5% (95% CI 53-91.9; P < 0.001) and stenosis 89.5% (95% CI 80.9-98.2; P = 0.013). Percutaneous transluminal angioplasty was used in 54.1% (95% CI 16.6-91.5; P < 0.01) of cases and stent placement in 45.9% (95% CI 8.5-83.4; P < 0.1) of cases. TS was 96.1% (95% CI 92.6-99.5; P = 0.860). Postoperative CS was achieved in 90.4% (95% CI 82.8-98.1; P = 0.114) of cases, with complete symptom resolution in 83.9% (95% CI 70.1-97.8; P < 0.001) of cases. Mean follow-up was 12.57 months (95% CI 4.39-20.7; P < 0.001). Estimated primary patency rate was 93.4% (95% CI 87.5-99.3; P = 0.081). Reintervention was required in 4.3% (95% CI 0.8-7.9; P = 0.477) of patients. No perioperative or follow-up mortality was reported. Endovascular treatment of symptomatic hypogastric steno-occlusive lesions is safe, technically feasible, and associated with high CS and excellent mid-term patency, with minimal morbidity and no reported postoperative mortality.

Postmenopausal women are approximately twice as likely to develop cardiometabolic diseases (CMDs) as premenopausal women. Plant-based diets rich in fruits and vegetables, due to their high content of bioactive compounds such as (poly)phenols, represent a promising strategy to reduce the risk of CMDs in this population. However, the cardioprotective effects of (poly)phenols depend largely on inter-individual variability, which is strongly influenced by the gut microbiota composition. Menopause is often associated with gut dysbiosis, characterized by a reduced microbial diversity and a lower abundance of beneficial bacteria. This imbalance in the gut microbiota profile of postmenopausal women could influence (poly)phenol metabolism and, consequently, the health benefits attributed to (poly)phenol-rich food (PP-rich food) consumption. Therefore, this study aimed to assess the impact of a daily consumption of PP-rich foods (dark chocolate, green tea and fruit juice) for 2 months on the urinary phenolic profile in postmenopausal women at high cardiometabolic risk. To this end, 116 urinary phenolic metabolites were determined using UHPLC-ESI-QqQ-MS/MS. Dietary intervention with PP-rich foods led to a significant increase in the urinary excretion of phenolic metabolites derived from gut microbiota activity and phase II metabolism. Notably, there was a significant increase in the excretion of glucuronidated and/or sulfated conjugates of phenyl-γ-valerolactones, phenylvaleric acids, phenylacetic acids, benzoic acids, and urolithins. It is expected that these phenolic metabolites could be the bioactive compounds responsible for the potential beneficial effects derived from the daily intake of dark chocolate, green tea, and fruit juice on the reduction of the risk of CMDs in postmenopausal women.

Fluorescent protein (FP) variants have recently emerged as promising intracellular nitric oxide (NO) sensors based on NO-induced fluorescence loss due to cysteine S-nitrosylation - the covalent addition of a nitroso group to a cysteine thiol within a protein to form an S-nitrosothiol. Here, we investigate the mechanisms underlying this fluorescence loss using a combined experimental and computational approach. We focus on mTagBFP2, a blue fluorescent protein that undergoes a 70% reduction in fluorescence quantum yield and lifetime upon exposure to micromolar NO concentrations. We discriminate, through mutagenesis, the contributions of two key cysteine residues and propose an unprecedented excitation energy transfer (EET) from the mTagBFP2 chromophore to the S-nitroso groups as a potential quenching mechanism. Our EET efficiency calculations incorporate full couplings, the effects of the surrounding protein and solvent, and molecular dynamics-based configurational flexibility. The computed EET efficiencies broadly align with experimental observations, with remaining discrepancies for which we advance potential explanations. Our findings establish a mechanistic basis for NO-induced fluorescence loss in mTagBFP2, providing guidelines for the rational design of next-generation NO-sensitive FPs. Moreover, they suggest that analogous S-nitrosylation-driven quenching mechanisms could be operative in other FPs with exposed cysteine residues, underscoring the risk of artefacts in cellular imaging under physiological NO levels.

Mental disorders and chronic pain frequently co-occur. The prevalence of this comorbidity varies widely across investigations and is certainly overestimated using screening self-reports. The main aim of this cross-sectional research was to calculate prevalence rates of mental disorders in a chronic pain population during their first consultation in an Italian specialized pain clinic using the narrow diagnostic criteria of the DSM-5. Additionally, we examined the relationship between this psychiatric comorbidity and a broad range of socio-demographic and clinical parameters related to chronic pain. 174 participants were enrolled in the Pain Therapy Service at the Parma University Hospital. They completed the Structured Clinical Interview for DSM-5 mental disorders (SCID-5) and the Brief Pain Inventory (BPI). Associations between psychiatric comorbidity and other parameters were explored using regression analyses. 57 (32.7%) subjects with chronic pain had DSM-5 psychiatric comorbidity, particularly major depression and anxiety disorders. This comorbid psychopathology showed significant associations with BPI pain severity and interference scores, as well as with the presence of widespread chronic pain (including fibromyalgia) and the prescription of anti-neuropathic medication at entry. Notably, only a minority (n=18; 31.6%) of these participants with current comorbid mental disorders were treated in psychiatric services. A large portion of chronic pain patients with comorbid psychiatric syndromes remain undiagnosed and undertreated. The presence of mental health operators in multidisciplinary chronic pain teams is justified and recommended.

The aim of this paper is to review the phenomenon of bistability, a basic working mode of NREM sleep. The perpetual oscillations between two opposite states in sleep slow waves, K-complexes as well as in the Cyclic Alternating Pattern (CAP) on a different time scale; appear spontaneously and can also be elicited by sensory stimulation, representing a response of the sleeping brain. Although there is extensive literature on bistability, its significance remains obscure. In this paper, spontaneous and elicited bistable patterns are reviewed and the global presence of bistable oscillations in NREM sleep is highlighted. We discuss the relationship of bistability with sleep homeostasis and the overlap with the CAP, with emphasis on A1 phase. We collect data along the hypothesis that bistability would provide a perpetual and flexible interface between the sleeping brain and the environment across the night, protecting the continuity of sleep and, in parallel, preserving the brain's adaptive connection with the environment.

Avelumab, pembrolizumab, and enfortumab vedotin (EV) demonstrated efficacy in mUC following platinum-based chemotherapy. However, real-world data in patients with urothelial carcinoma with squamous differentiation (UCSD) are limited. The aim of this study is to assess the real-world clinical outcomes of avelumab, pembrolizumab, or EV in mUCSD patients. The ARON-2EV study is a retrospective, international, multicenter analysis in patients with mUC treated with avelumab, pembrolizumab, or EV across 79 centers in 21 countries. Patients were divided into three cohorts: 1 (avelumab), 2 (pembrolizumab), and 3 (EV). Primary endpoints were overall survival (OS) and time on treatment (ToT). Secondary objectives included evaluating clinical factors associated with outcomes and exploring the impact of UCSD histology on response to therapy. Statistical methods included Kaplan-Meier estimates, log-rank tests, Fisher's exact and chi-square tests, and Pearson's correlation coefficients. A total of 1918 patients, 1696 with advanced pure UC (pUC) and 222 with mUCSD (36 in cohort 1, 111 in cohort 2, and 75 in cohort 3), were included. Median OS was shorter in patients with UCSD compared to patients with pUC histology in the three cohorts (1: 13.0 vs 26.8months, HR 2.66,p = 0.003; 2: 10.2 vs 18.5months, HR 1.52,p = 0.008; and 3: 7.6 vs 13.1months, HR 1.68,p = 0.011). Median ToT was shorter in patients with UCSD compared to patients with pUC histology in cohort 1 (3.5 vs 5.6months, HR 1.57,p = 0.044) and 3 (7.6 vs 13.6months, HR 1.83,p = 0.005) but not in cohort 2 (3.7 vs 4.7months, HR 1.19,p = 0.177). Response to therapy was negatively correlated with UCSD histology in cohorts 2 (correlation coefficient 0.094,p = 0.008) and 3 (correlation coefficient 0.107,p = 0.021), while response to avelumab was not correlated with UCSD (correlation coefficient 0.072,p = 0.263). UCSD is a histology with a poor prognosis and response to treatments compared to pUC. Treatments activity and effectiveness in divergent differentiations should be addressed in dedicated prospective studies. NCT05290038.