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Psychosocial problems, daily functioning and help-seeking behaviour of international migrant workers in the Netherlands: A qualitative study to inform the adaptation of a scalable stepped-care intervention
Full text linkInternational migrant workers (IMWs) may face insecure work and housing, limited access to healthcare and increased risk of psychological problems. Two scalable, evidence-based interventions to support individuals experiencing psychological distress are Doing What Matters in Times of Stress (DWM) and Problem Management Plus (PM+). This study aimed to explore IMWs' problems, daily functioning and help-seeking behaviour, to inform cultural adaptation of the DWM/PM+ stepped-care intervention in the Netherlands. Following the Design, Implementation, Monitoring, and Evaluation (DIME) model, we conducted various qualitative interviews and a focus group discussion with IMWs (n = 30) and professionals (n = 18). Data were analysed thematically, and findings informed adaptations. Participants described problems related to work, housing, administration, finances, healthcare access and the COVID-19 pandemic. Daily routines focused on practical needs. Help-seeking was hindered by stigma, fear of job loss, low trust and reliance on informal or cross-border healthcare. Based on these results, the intervention was adapted to the needs of Polish IMWs in the Netherlands, regarding content and examples, which were tailored to their context; the intervention was offered remotely and collaboration with employers was avoided. These findings highlight the structural vulnerabilities of IMWs and demonstrate how qualitative insights can guide the cultural adaptation of a psychological intervention
Telehealth-delivered exercise and nutrition intervention to improve outcomes in patients with early stage non-small cell lung cancer: protocol for the multicentre STARLighT phase II (neoadjuvant) and phase III (adjuvant) trial
No full textIntroduction: In early stage non-small cell lung cancer (NSCLC), recurrence is frequent despite surgery and systemic treatments. Observational studies suggest that physical exercise and nutrition could improve outcomes, such as survival and treatment tolerance; however, solid evidence is lacking. The STARLighT trial aims to assess the effects of a telehealth-delivered combined exercise and nutrition intervention on clinical, biological and patient-reported outcomes in early stage NSCLC. Methods and analysis: STARLighT is a multicentre master protocol study conducted in Italy, comprising two cohorts of patients affected by early stage NSCLC (stages IB-IIIA) epidermal growth factor receptor and anaplastic lymphoma kinase wild type. Cohort A will include 46 patients with resectable NSCLC receiving neoadjuvant treatment and will exploit a single-arm phase II design. Cohort B will enrol 268 patients undergoing adjuvant treatment (including as a part of a perioperative strategy) and proposes a randomised controlled phase III design. Patients in Cohort A and those allocated to the interventional arm in Cohort B will receive a tailored telehealth-delivered exercise and nutritional intervention. The control group will receive the usual care plus educational material. For cohort A, two coprimary endpoints are set: pathological complete response and quality of life, whereas the primary endpoint for cohort B is 2-year disease-free survival. Secondary and exploratory endpoints include a series of clinical (eg, overall survival and safety), biological (immune-inflammatory markers, gut microbiota and transcriptomics) and patient-reported outcomes (eg, sleep habits, physical activity, anxiety and depression and distress) evaluations. Ethics and dissemination: The study is approved by the Ethics Committee of the University of Verona (Prot. No. 33979) and registered on ClinicalTrials.gov (NCT07042724). Findings will be disseminated through peer-reviewed journals, scientific meetings, public forums and guideline updates. Trial registration number: Clinicaltrial.gov: NCT07042724
Comparison of antidepressant deprescribing strategies in individuals with clinically remitted depression: a systematic review and network meta-analysis
No full textBackground: Antidepressants are recommended for moderate-to-severe depression and anxiety, but concerns exist around overprescribing, long-term use, and paucity of evidence-based deprescribing strategies. We aimed to compare the effectiveness of different deprescribing approaches in individuals with clinically remitted depression or anxiety. Methods: For this systematic review and network meta-analysis, we searched PubMed, PsycINFO, Web of Science, CENTRAL, CINAHL, and online trial registries from inception to April 6, 2025, for randomised controlled trials comparing abrupt discontinuation, fast tapering (≤4 weeks), slow tapering (>4 weeks), dose reduction (≤50% of the minimal effective dose), or continuation, with or without psychological support in adults with fully or partially remitted depressive or anxiety disorders on antidepressant treatment. The primary outcome was relapse rate by trial end. For each study, we extracted summary-level data on study characteristics, participant demographics, intervention details, and outcome measures. We did random-effects pairwise meta-analysis, and random-effects frequentist network meta-analysis to obtain relative risks (RRs) and standardised mean differences with 95% CIs. We assessed risk of bias using the Cochrane Risk-of-Bias-2 tool and the certainty of pooled estimates using the Confidence in Network Meta-Analysis approach. Individuals with lived experiences contributed to the interpretation of results. The study was registered with Open Science Framework, https://osf.io/9bsxz/. Findings: Of 13 011 records, we included 76 trials comprising 17 379 participants. The mean age of individuals was 45·2 years (SD 15·2, IQR 34·9-55·5); 11 731 (67·5%) were female and 5648 (32·5%) male; the mean follow-up was 45·9 weeks (SD 29·7). Individuals were predominantly White (mean 87·9% [SD 8·1]). 60 (79%) of 76 studies investigated depression and 16 (21%) investigated anxiety. Separate analyses by diagnosis showed consistent baseline characteristics or treatment effects, although most comparisons were informed primarily by studies of participants with depression. After pooling data across conditions, the following strategies outperformed abrupt discontinuation for relapse prevention: continuation at standard dose plus psychological support (RR 0·40, 95% CI 0·26-0·61; number needed to treat [NNT] 4·3; moderate certainty), continuation at standard dose (0·51, 0·46-0·58; NNT 5·3; moderate certainty), slow tapering plus psychological support (0·52, 0·38-0·72; NNT 5·4; moderate certainty), and continuation at reduced dose (0·62, 0·42-0·92; NNT 6·8; low certainty). These strategies also outperformed fast tapering (point estimates ranging from 0·39 to 0·52; the first three supported by moderate certainty, the last by low certainty). Compared with abrupt discontinuation, the following strategies made no difference in relapse prevention: fast tapering plus psychological support (0·52, 0·27-1·01; low certainty), abrupt stopping plus psychological support (0·73, 0·30-1·78; very low certainty), and slow tapering alone (0·81, 0·56-1·18; low certainty). Moderate heterogeneity emerged (τ2=0·07), without evidence of inconsistency. Sensitivity, subgroup, and secondary outcomes provided consistent results. Tolerability was comparable across strategies. Interpretation: In remitted depression, slow tapering plus psychological support is as effective as antidepressant continuation in preventing relapse and superior to abrupt or rapid discontinuation. In remitted anxiety, despite consistent population characteristics and effect estimates, limited evidence warrants cautious generalisation. Guidelines should promote individualised deprescribing with gradual tapering and structured psychological support. Funding: None
Targeting PGC-1α axis Rescues Aberrant Development from Thyroid Hormone Defect in Brain Organoids
No full text: Thyroid hormone (T3) deficiency during central nervous system development leads to severe and often incurable human pathologies, including intellectual disability and motor dysfunction. Using murine dorsal forebrain organoids, we showed that T3 is required to activate mitochondrial β-oxidation and OXPHOS biogenesis to sustain neuronal development, while its absence caused profound neurodevelopmental defects such as defective maturation, astrogliosis, and reduced spontaneous activity. Mechanistically, we identified the transcriptional coactivator PGC-1α as a central mediator of the T3 effect. Pharmacological inhibition of β-oxidation in T3-supplemented organoids recapitulated the T3-deficient phenotype, whereas Ppargc1a gene augmentation rescued neuronal development under T3-deprived conditions. Most importantly, pharmacological stimulation of the PGC-1α axis with Nicotinamide Riboside or Bezafibrate rescues mitochondrial bioenergetics and neuronal development, effectively correcting aberrant brain organoid maturation despite T3 deficiency. These findings reveal for the first time the role of T3 in supporting neurodevelopment via activation of mitochondrial β-oxidation and OXPHOS biogenesis, and identify the PGC-1α axis as a promising therapeutic avenue for otherwise intractable disorders linked to thyroid hormone deficiency
Higher post-prandial glucose excursions in youth with type 1 diabetes and celiac disease: Time to change the bolus?
No full textNewer gluten-free products have been improved in terms of glyce-
mic index and glycemic load; however, they may have a higher intake
of saturated fat and a lower intake of fibre,6 which could influence
postprandial glucose control. Therefore, we highlight the importance of
an educational reinforcement on the size and timing of insulin bolus at
each meal, in individuals on GFD. Slightly larger boluses (for the same
carbohydrate content) when consuming GFD high-GI foods, along with
a longer waiting time to reduce peak spikes, should be effective strate-
gies for these youths who are monitored with FGM/CGM, as well as
increasing fibre intake, which helps slow meal absorption. Other possi-
bilities include splitting the bolus: part immediately, part over time
(or have a square/dual wave over 1–2 h) to cover both the fast spike
and slower tail; or to add a correction bolus after some time (e.g., 1–2 h
post-meal) if bolus plus meal leads to earlier spike
Socio-Emotional Learning and Human Flourishing [Aprendizaje socioemocional y florecimiento humano]
No full textThe development of social and emotional competences is a crucial aspect of human flourishing. These competences, including self-awareness, self-management, social awareness, interpersonal skills and responsible decision-making, have been found to demonstrate effective improvements through social and emotional learning (SEL) programs. An analysis of the recent literature on emerging SEL approaches was conducted to provide an overview of current educational proposals, highlighting their strong and critical areas and outlining the lingering challenges, particularly in terms of the necessity to define the theoretical foundations of the programs with utmost clarity and conduct rigorous research on their effectiveness. In light of the aforementioned considerations, this article presents an innovative SEL program entitled The Nous Project that responds to the recommendations highlighted in the literature. Developed for primary school children, The Nous Project is based on a philosophically-grounded theory of socio-emotional education, which primarily focuses on the role of emotional self-understanding. Consequently, the primary objective of The Nous Project is to foster students’ knowledge of their own emotional dimensions and their ability to understand their own emotions. This is achieved by involving them in keeping a reflective diary, where they write down their emotions and analyse them on the basis of a metaphor. The effectiveness of this activity will be discussed starting from the presentation of the findings emerged from the qualitative analysis of the diaries collected during the pilot implementation of the program
Strength training in the gym versus specific strength training on the bike in young off-road cyclists
Full text linkBackground: The benefits of strength training in cyclists are still a topic of debate. The aim of this study was to compare the effects of strength training performed in the gym with specific strength training performed on the bike in young off-road cyclists. Sources of data: Nineteen participants were divided into the following two groups: (i) the group A performed 12 weeks of endurance training combined with two sessions/week of strength training in the gym; (ii) the group B performed 12 weeks of endurance training combined with two sessions/week of specific strength training on the bike. Incremental test, 30 s Wingate test, and countermovement jump test were conducted at pre (T0) and post (T1) training programs. Areas of agreement: The findings are in line with previous research showing that heavy strength training in cyclists has significant improvements in some aerobic and anaerobic performance outcomes. Indeed, our results showed that in the group A, the Mean Power Output (MPO) of the 30 s Wingate test increased significantly between T0 and T1 (P = .002). In the group B, no significant differences were found in the MPO of the 30 s Wingate test between T0 and T1 (P = .276). In the group A, the Maximum Power Achieved (MPA) increased significantly between T0 and T1 (P < .001). In the group B, no significant differences were found in the MPA between T0 and T1 (P = .889). Areas of controversy: Strength training in the gym for cyclists has not been widely investigated, and, in fact, the literature shows conflicting results on the topic, with some research groups highlighting the importance of sport-specific strength training. In this way, in both groups, no significant differences in the vertical jump height between T0 and T1 (P = .331 and P = .184, for groups A and B, respectively) were detected. However, the small sample size and the numerical heterogeneity between males and females in the recruited sample do not allow to generalize findings. Growing points: As the group of cyclists who performed strength training in the gym showed significant improvements, this study suggests integrating heavy strength sessions in the gym into the usual endurance training program. Areas timely for developing research: Further studies should investigate the effectiveness of strength training in the gym both in all off-road cycling categories as well as in other cycling specialities
Association between plasma glucosylsphingosine levels and dyskinesia burden in GBA1-related Parkinson's disease
Full text linkBackground: GBA1 mutation is the most significant genetic risk factor for Parkinson's disease (PD). It encodes glucocerebrosidase (GCase), whose dysfunction - seen in Gaucher disease - leads to the accumulation of glucosylceramide and its derivate glucosylsphingosine (GlcSph). However, it remains unclear whether GCase and GlcSph are relevant in PD patients carrying no or monoallelic GBA1 variants, and what their clinical impact might be. Objective: Investigating the relationships between GBA1 mutations, GCase, GlcSph, and clinical features in a large PD cohort. Methods: We performed a cross-sectional study of PD patients screened for GBA1 mutations, GCase activity, and GlcSph via dried blood spot tests. Patients were classified as heterozygous mutation carriers (GBA1-PD) or non-carriers (nonGBA1-PD). Collected data included motor and non-motor parameters. Molecular and clinical differences were compared between GBA1-PD and nonGBA1-PD. Distinctive clinical features were further investigated through multivariate models to test their correlations with biochemical data. Results: The cohort included 611 subjects (225 GBA1-PD, 386 nonGBA1-PD). GBA1-PD presented earlier onset, lower cognitive scores, higher incidence of mood disturbances and more advanced stage. Motor assessment revealed a higher frequency and severity of dyskinesias, independently from disease duration and LEDD. GlcSph levels showed an independent correlation with dyskinesia severity and time at onset in GBA1-PD patients, which was independent of sex, LEDD, UPDRS-III, disease duration and GBA1 mutation class. Conclusions: This study reveals an association between GlcSph and dyskinesias in GBA1-PD, that should prompt further investigation to assess the GlcSph role as a possible biomarker and target to tackle dyskinesias in GBA1-PD
In vitro interactions of sulbactam/durlobactam in combination with meropenem, ceftazidime/avibactam, piperacillin/tazobactam, cefiderocol and fosfomycin against carbapenem-resistant Acinetobacter baumannii (CRAB) clinical isolates
No full text: We evaluated in vitro activity of sulbactam/durlobactam in combination with different antimicrobials against Carbapenem-Resistant Acinetobacter baumannii (CRAB) clinical isolates with different susceptibility profiles, including sulbactam/durlobactam-resistant strains. The genomes of 13 CRAB clinical isolates were characterized by whole-genome sequencing and synergy testing was performed with MIC Test Strips. Sulbactam/durlobactam, when combined with piperacillin/tazobactam or ceftazidime/avibactam, showed synergistic activity against 53.8% (7/13) of CRAB isolates and restored meropenem MIC values below the clinical breakpoint in 46.2% (6/13) of them. Our results demonstrate that sulbactam-durlobactam in combination with β-lactams exhibited high in vitro synergistic activity against CRAB strains
Aspects textuels: le cas des bornes milliaires réécrites
No full textThis study examines re-engraved milestones from northern Italy dating to the fourth century, pinpointing the possible reasons behind their reuse