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Objectives: Tactile acuity is a somatosensory measure of the extent to which humans can discern tactile stimuli. It is influenced by how peripheral signals are processed centrally. In the oral cavity, Occlusal Tactile Acuity (OTA) is the ability to perceive minimal thicknesses between antagonist teeth. The aim of the current study was to assess the association between psychological traits and OTA of otherwise healthy individuals., Methods: Sixty-three volunteers (32 males; mean age ± SD: 24.6 ± 2.7 years) participated in this study. Somatosensory amplification, anxiety, depression, physical symptoms and pain catastrophizing were scored using questionnaires, and subgroups of severity were created per variable based on cut-offs. OTA was measured using 9 aluminium foils with thickness (ranging from 8 to 72 μm) and one sham test (without foil). Each thickness was tested 10 times in random order, the participants were instructed to report whether they felt the foil between their molars and the mean percentage of correct answers was computed. A linear mixed model was used with OTA as a dependent variable and psychological domain as an independent variable., Results: Significantly different OTA was observed among the anxiety subgroups (p = .003), supporting a decreased perception of thicknesses 24 and 32 μm (p = .018 and p < .001, respectively) in participants with moderate/severe anxiety compared to those with no/mild anxiety. Significantly different OTA was also observed among the pain catastrophizing subgroups (p = .008), showing decreased perception of thicknesses 32 and 40 μm (p < .001 and p = .007, respectively) in severe catastrophizing levels, compared to no/mild catastrophizing levels. No significant differences were observed for the other variables., Conclusions: Healthy adults with increased anxiety or pain catastrophizing levels show decreased interdental acuity as compared to participants with minor or no psychological impairment., (© 2024 The Author(s). Journal of Oral Rehabilitation published by John Wiley & Sons Ltd.)

Objective: The objective of this study was to describe reported adverse events (AEs) associated with elexacaftor/tezacaftor/ivacaftor (ETI) in a pediatric sample with cystic fibrosis (CF) aged 6-18 years, with at least one F508del variant, followed at multiple Italian CF centers., Study Design: This was a retrospective, multicenter, observational study. All children receiving ETI therapy from October 2019 to December 2023 were included. We assessed the prevalence and type of any reported potential drug-related AEs, regardless of discontinuation necessity. Persistent AEs were defined as those continuing at the end of the observation period., Results: Among 608 patients on ETI, 109 (17.9%) reported at least 1 AE. The majority (n = 85, 77.9%) were temporary, with a median duration of 11 days (range 1-441 days). Only 7 (1.1%) patients permanently discontinued treatment, suggesting good overall safety of ETI. The most common AEs leading to discontinuation were transaminase elevations (temporary 14.1%, persistent 25.9%) and urticaria (temporary 41.2%, persistent 7.4%). Creatinine phosphokinase elevation was uncommon. No significant differences in AEs were observed based on sex, age groups (6-11 vs 12-18 years), or genotype. Pre-existing CF-related liver disease was associated with an increased risk of transaminase elevations. We identified significant variability in the percentage of reported AEs (ANOVA P value .026)., Conclusions: This real-world study highlights significant variability in reported AEs. Our findings suggest that ETI is a safe and well-tolerated therapy in children and adolescents with CF. However, further long-term safety and effectiveness investigations are warranted., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The aim of this study was to adapt the National Aeronautics and Space Administration Task Load Index (NASA-TLX) to the home care setting and translate and validate it in Italian. An online questionnaire containing the Italian version of the NASA-TLX adapted to the home care setting was administered to home care nurses to measure workload. Content Validity Index, Exploratory, and Confirmatory Factor Analyses were used to measure the psychometric characteristics of the modified NASA-TLX. The modified Italian version of NASA-TLX&#95;HC-IT showed good psychometric characteristics in measuring the workload of home care nurses, with excellent fit indices. The reliability, calculated with Cronbach's alpha, was 0.73, indicating adequate reliability. A negative correlation between workload and job satisfaction among home care nurses, as well as a positive association between high workload and intention to leave the workplace, was verified. The modified Italian version of the NASA-TLX&#95;HC-IT was confirmed to be a valid and reliable instrument to measure workload in home care nursing. Furthermore, the correlation between workload and the intention to leave the workplace among home care nurses was an important result that community nursing managers should consider preventing the shortage of home care nurses., (© 2024 The Author(s). Public Health Nursing published by Wiley Periodicals LLC.)

Introduction: Stroke negatively impacts both patients and their families, who must face multiple changes after the onset of the disease. Family caregivers must face new problems with a possible sense of inadequacy, stress and burden. Our retrospective study aimed to assess the burden of caregivers during the rehabilitation process of patients with Stroke., Material and Method: This study included patients with a diagnosis of stroke and their caregiver, who attended the Day Hospital of the IRCCS Neurolesi Center "Bonino-Pulejo", Messina, Italy, between January 2018 and October 2019, using electronic recovery system data. The final sample consisted of 30 patients and their caregivers., Results: Significant improvements were observed in patients' cognitive and mood scores, reflecting the efficacy of rehabilitation therapies. Additionally, a correlation emerged between patients' reported anxiety levels and caregivers' reported depression levels, highlighting a dynamic interaction between the emotional states of the two groups., Conclusion: The study highlights the intricate interplay between caregiver characteristics, patient outcomes, and family dynamics in the context of caregiving. Targeted interventions aimed at improving family resilience and coping mechanisms are crucial to optimizing the well-being of both caregivers and patients., (© 2024. The Author(s).)

Background: Alternating hemiplegia of childhood (AHC) is a rare disorder with both neurologic and cardiac manifestations. The ATP1A3-D801N variant is associated with a pathologically short QT interval and risk of ventricular arrhythmia following bradycardia; however, the mechanism of this remains unknown. We investigated the relationship between heart rate (HR), QT, and QTc, hypothesizing that individuals with ATP1A3-D801N have abnormal, impaired shortening of QT and QTc at lower HR leading to arrhythmia predisposition., Methods: We performed a retrospective observational study of individuals who underwent clinical evaluation, Holter monitoring, and genetic testing for AHC at Duke University Hospitals. We also compiled a group of healthy individuals as a control cohort. A larger, worldwide cohort of individuals with ATP1A3 -related phenotypes was compiled to investigate sinus node dysfunction. Linear regression analysis was then performed., Results: The cohort consisted of 44 individuals with ATP1A3 -related phenotypes with 81 Holter recordings (52.27% female; mean age at first Holter 8.04 years, range 0.58 - 33 years), compared to 36 healthy individuals with 57 Holter recordings (52.78% female; mean age at first Holter 9.84 years, range 0.08 - 38 years). Individuals with ATP1A3-D801N had reduced prolongation of QT at lower HR, manifest as a significantly lower slope for HR vs QT compared to healthy (P<0.0001). This resulted in a significantly higher slope of the relationship for HR vs QTc compared to healthy (P<0.0001). Individuals with ATP1A3 -related phenotypes and baseline QTc <350 milliseconds (ms) had increased shortening of QT and QTc at lower HR compared to those with normal QTc (P=0.003; P=0.001). Among worldwide cases, 3 out of 131 individuals with ATP1A3 -related phenotypes required device implantation and/or had sinus pauses >4 seconds., Conclusions: Individuals with the ATP1A3-D801N variant exhibit paradoxical shortening of QT and QTc at lower HR, which contributes to an increased risk of arrhythmias during bradycardia. This is exacerbated by an underlying risk of sinus node dysfunction., Clinical Perspective: What is Known:Individuals with ATP1A3-D801N have a short baseline QTc.Two individuals with AHC experienced ventricular fibrillation following bradycardia.What the Study Adds:The QT and QTc shorten to a greater extent at lower heart rate in individuals with ATP1A3-D801N than in healthy individuals. Individuals with ATP1A3 -related phenotypes and QTc <350ms show greater impairment of QT and QTc dynamics than those with normal QTc. There is low prevalence of device implantation and significant sinus pauses in individuals with ATP1A3 -related phenotypes, with a relatively greater prevalence in those with ATP1A3-D801N.

We developed a flow cytometry (FC) assay enabling the rapid and accurate identification of bacterial and viral infections using whole blood samples. The streamlined flow cytometry assay is designed to be user-friendly, making it accessible even for operators with limited experience in FC techniques. The key components of the assay focus on the expression levels of specific surface markers-CD64 on polymorphonuclear neutrophils (PMN) as a marker for bacterial infection, and CD169 on monocytes (MO) for viral infection. The strong performance indicated by an area under the receiver operating characteristic (ROC) curve of 0.94 for both PMN CD64 positive predictive value (PPV) 97.96% and negative predictive value (NPV) 76.67%, and MO CD169 PPV 82.6% and NPV 86.9%, highlight the assay's robustness in differentiating between bacterial and viral infections accurately. The FC assay includes the assessment of immune system status through HLA-DR and IL-1R2 modulation in MO, providing a useful insight into the patients' immune response. The significant increase in the frequency of MO exhibiting reduced HLA-DR expression and elevated IL-1R2 levels in infected patients (compared to healthy controls) underscores the potential of these markers as indicators of infection severity. Although the overall correlation between HLA-DR and IL-1R2 expression levels was not significant across all patients, there was a trend in patients with more severe disease suggesting that these markers may have the potential to assist in stratifying patient risk. The present FC assay has the potential to become routine in the clinical microbiology laboratory community and to be helpful in guiding clinical decision making.

IgG4-related disease is a rare fibroinflammatory condition. Prompt recognition is fundamental to initiate treatment and to prevent organ damage. Diagnostic and classification criteria are primarily intended for use by clinicians with established expertise in IgG4-related disease. Absence of disease awareness among primary care physicians and specialists without expertise in IgG4-related disease remains the main cause of diagnostic delay. We aimed to identify red flags that might increase the suspicion of IgG4-related disease in primary and secondary care settings. A task force of experts in IgG4-related disease from the European Reference Network for Rare Connective Tissue Diseases (ERN-ReCONNET), patient representatives, and primary care physicians derived potential red flags for IgG4-related disease through a systematic literature search and a level of agreement exercise. Five red flags reached 100% agreement among experts: swelling in one or more organ system; pancreatic and biliary tree involvement; increased serum IgG4; IgG4 + plasma cell tissue infiltration; and obliterative phlebitis. Red flags for IgG4-related disease are intended for use in primary and secondary care to improve referral to centres of expertise and prompt early diagnosis., Competing Interests: Declaration of interests GPG received funding from The European Commission within the contract SANTE/2018/B3/030-SI2·813822 to support collaboration with European Reference Network (ERN) ReCONNET as a methodologist in the systematic review on red flags for IgG4-related disease. FF received honoraria from GSK for lectures and plenary presentations at educational events. TA received travel grants from AbbVie and Neovil; declares study support from Janssen; and received honoraria from AbbVie, Amgen, AstraZeneca, GSK, and Neovil for lectures and plenary presentations at educational events. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Prolonged treatment with anti-CD20 antibodies can lead to hypogammaglobulinemia and increased infection risk in multiple sclerosis (MS). We investigated switch from anti-CD20 to cladribine as a strategy to prevent immunoglobulin reduction while preserving efficacy. We prospectively analysed serum IgG, IgM, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in 44 patients, 14 who were switched from anti-CD20 to cladribine and 30 continuing anti-CD20. Over 1 year, serum IgG, IgM, NfL and GFAP remained stable after switch and similar to patients continuing anti-CD20. More than 90 % of patients remained free of disease activity. Cladribine should be further explored as de-escalating agent from anti-CD20 in MS., Competing Interests: Declaration of competing interest The employer (Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland) receives financial support from Abbvie, Biogen Idec, Lundbeck, Merck, Novartis Roche, Sanofi, Teva. The submitted work is not related to these agreements., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objectives: Autism Spectrum Disorder (ASD) involves challenges in social communication and daily functioning. Emerging research highlights that virtual reality (VR) interventions can significantly improve social skills in adults with ASD by providing immersive, controlled practice environments. This systematic review will assess the effectiveness of VR-based interventions for improving social skills in adults with ASD. Materials and Methods: Studies were identified from an online search of PubMed, Web of Science, Cochrane Library, and Embase databases without any search time range. This review was registered on Open OSF ( n ) P4SM5. Results: Recent studies show that VR interventions significantly enhance job interview skills, social abilities, and practical tasks in adults with ASD, with improvements in confidence, social understanding, and everyday skills. VR has been shown to be user-friendly and effective in providing immersive, adaptable training experiences. Conclusions: The review highlights VR's promising role in improving social skills, job interview abilities, and daily functioning in adults with ASD. It emphasizes the need for broader studies, standardized interventions, and exploration of VR's integration with other therapies to enhance long-term effectiveness and address comorbidities like anxiety and depression.

Temporomandibular disorders (TMDs) are a common musculoskeletal condition, presenting treatment challenges due to their non-specific nature. Categorizing patients with TMDs into clusters based on neurobiological pain mechanisms could provide a promising approach to facilitate targeted treatments. This observational study (1) used a network analysis (NA) to explore the complexity of TMDs by investigating relationships among biopsychosocial variables, and (2) validated potential TMD subgroups based on mechanism-specific pain categories. One hundred and two patients with TMD were included. Biopsychosocial variables covered: general health, psychosocial features, TMD pain, and TMD characteristics. A NA evaluated the associations between variables and determined the role of each feature within the network. Hierarchical clustering was used to identify TMD subgroups. The NA revealed significant correlations primarily within the same feature domains, indicating a strong interplay between symptoms and psychological factors. Cluster analysis identified two subgroups driven by nociceptive and nociplastic pain mechanisms; the nociplastic group exhibited higher levels of anxiety, depression, pain catastrophization, central sensitization, pain duration, and more pain locations, along with poorer sleep quality, quality of life, and health status. In contrast, the nociceptive group exhibited restricted maximal mouth opening (MMO), heightened pain during TMJ palpation and mouth opening, and a greater positive response to manual therapy. Across all features, psychological factors, pain locations, and MMO primarily contributed to the separation of subgroups. By adopting a data-driven approach, these results support the significant role of considering the neurobiological basis of pain to improve patient classification. This knowledge may facilitate clinical reasoning and personalized treatments. PERSPECTIVE: This study used a network analysis to explore the complex biopsychosocial interactions present in people with TMDs, identifying important variables such as the Central Sensitization Inventory and pain-free maximal mouth opening. The findings distinguish potential nociceptive and nociplastic pain subgroups, offering important insights for targeted therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to its critical role in neurogenesis, brain-derived neurotrophic factor (BDNF) modulates pain and depressive behaviors., Methods: In a translational perspective, we tested the anti-migraine activity of highly purified and characterized recombinant human BDNF (rhBDNF) in an animal model of cephalic pain based on the chronic and intermittent NTG administration (five total injections over nine days), used to mimic recurrence of attacks over a given period. To achieve this, we assessed the effects of two doses of rhBDNF (40 and 80 µg/kg) administered intranasally to adult male Sprague-Dawley rats, on trigeminal hyperalgesia (by orofacial formalin test), gene expression (by rt-PCR) of neuropeptides and inflammatory cytokines in specific areas of the brain related to migraine pain. Serum levels of CGRP, PACAP, and VIP (by ELISA) were also evaluated. The effects of rhBDNF were compared with those of sumatriptan (5 mg/kg i.p), administered 1 h before the last NTG administration., Results: Both doses of rhBDNF significantly reduced NTG-induced nocifensive behavior in Phase II of the orofacial formalin test. The anti-hyperalgesic effect of intranasal high-dose rhBDNF administration in the NTG-treated animals was associated with a significant modulation of mRNA levels of neuropeptides (CGRP, PACAP, VIP) and cytokines (IL-1beta, IL-10) in the trigeminal ganglion, medulla-pons, and hypothalamic area. Of note, the effects of rhBNDF treatment were comparable to those induced by the administration of sumatriptan. rhBDNF administration at both doses significantly reduced serum levels of PACAP, while the higher dose also significantly reduced serum levels of VIP., Conclusions: The findings suggest that intranasal rhBDNF has the potential to be a safe, non-invasive and effective therapeutic approach for the treatment of primary headache, particularly migraine., (© 2024. The Author(s).)

ALK5 inhibitors represent an attractive therapeutic approach for the treatment of a variety of pathologies, including cancer and fibrosis. Herein, we report the design and in vitro characterization of a novel series of ALK5 modulators featuring a 4,6-disubstituted pyridazine core. A knowledge-based scaffold-hopping exploration was initially conducted on a restricted set of heteroaromatic cores using available ligand- and structure-based information. The most potent structurally novel hit compound 2A was subsequently subjected to a preliminary optimization for the inhaled delivery, applying physicochemical criteria aimed at minimizing systemic exposure to limit the risk of adverse side effects. The resulting inhibitors showed a marked boost in potency against ALK5 and in vitro ADME properties, potentially favoring lung retention. The optimized hits 20 and 23 might thus be considered promising starting points for the development of novel inhaled ALK5 inhibitors., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Background: this study was performed under the umbrella of the Health Extended Alliance for Innovative Therapies, Advanced Lab Research, and Integrated Approaches of Precision Medicine (HEAL ITALIA) partnership and funded under the National Recovery and Resilience Plan, Mission 4 Component 2 Investment 1.3, and by the European Union., Objectives: the overall objective of the HEAL project is to identify innovative and effective therapeutic approaches to reduce disease burden. The present research falls within Spoke 7: Prevention Strategies: Integrated and gender medicine approaches for prevention strategies based on environmental, lifestyle, and clinical biometric data. Obesity represents a primary risk factor worldwide for the onset of numerous life-threatening diseases, including metabolic, cardiovascular, and neurological diseases. Environmental and gender-related factors influence obesity development. However, the molecular mechanisms underlying the effects of those agents on different organs of the human body are not fully understood yet., Methods: here, we present a study protocol aimed at shedding light on (i) the complex interplays among adipose tissue, brain and gut in obesity, and (ii) the effects of specific dietary components and environmental metabolism-disrupting compounds on those interactions. To this purpose, we combined ex vivo, in vitro, and in vivo approaches to gain additional knowledge about the molecular mechanisms underlying connections between organs., Conclusions: the data provided by this study will contribute to defining new targets for therapeutic and/or preventive interventions, thereby allowing more personalized approaches to nutrition.

Bifidobacteria are recognized as health-promoting bacteria that reside in the human gut, helping in the digestion of fiber, preventing infections, and producing essential compounds like vitamins. To date, Bifidobacterium animalis subsp. lactis , together with Bifidobacterium adolescentis , Bifidobacterium bifidum , Bifidobacterium breve, and Bifidobacterium longum , represents one of the species that are used as probiotic bacteria. Despite the extensive and detailed scientific research conducted on this microbial taxon, the molecular mechanisms by which B. animalis subsp. lactis exerts health benefits to its host are still largely unknown. Thus, we dissected the genetic repertoire and phylogenetic relationship of 162 strains of B. animalis subsp. lactis to select a representative reference strain of this taxon suitable for investigating its interaction with the host. The B. animalis subsp. lactis PRL2013 strain, which was isolated by a mucosal sample of a healthy adult, was chosen as the reference of the monophyletic cluster of human origin and revealed a greater adhesion index than that observed for another B. animalis subsp. lactis strain used in the industry as a probiotic supplement. Transcriptomics analyses of PRL2013 strain, when exposed to human cell monolayers, revealed 291 significantly upregulated genes, among which were found genes predicted to encode extracellular structures that may directly interact with human cells, such as extracellular polymeric substances, wall teichoic acids, and pili., Importance: To date, many Bifidobacterium animalis subsp. lactis strains have been isolated from human fecal samples. However, their presence in these samples does not necessarily suggest an ability to colonize the human gut. Furthermore, probiotics of non-human origin may not effectively interact with the gut epithelium, resulting in transient bacteria of the gut microbiota. In vitro experiments with human cells revealed that B. animalis subsp. lactis PRL2013, an autochthonous member of the human gut, shows colonization capability, leading to future applications in functional foods., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE)., Design: Observational cohort analysis based on a multicentre international registry., Setting: Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries., Participants: A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins., Methods: Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use., Results: From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76)., Conclusions: In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Perampanel is a selective non-competitive antagonist of AMPA receptors, and the first agent of this class to become available for the treatment of epilepsy. It could be a useful tool for treatment of refractory status epilepticus (RSE)., Methods: We describe a series of eight RSE cases treated with Perampanel., Results: Perampanel was successful in terminating SE in all the described cases. Only in one patient a severe psychomotor agitation occurred, but without needing PER discontinuation. No other adverse events were observed., Conslusion: Our case series of eight patients, albeit small, broadens the clinical experiences on the efficacy and safety of PER as a treatment for RSE. It may also support the early use of PER, considering the role of AMPA receptors in sustaining epileptic firing in SE. Further studies are warranted to clarify the potential of Perampanel in the treatment of status epilepticus and, in particular, in RSE., (© 2024. Fondazione Società Italiana di Neurologia.)

Introduction: Parkinson's disease (PD) is one the most common neurodegenerative movement disorder, leading to motor and non-motor symptoms, including deficits in executive functions (EF), memory, visuospatial abilities, and psychomotor speed. Current treatments are primarily symptomatic, involving pharmacological, surgical strategies. Neurologic Music Therapy (NMT) has gained recognition for its effectiveness in neurorehabilitation of PD patients and improving motor and cognitive domains, such as EF. This study combines NMT with the virtual reality (VR) platform Computer-Assisted Rehabilitation Environment (CAREN), offering customizable environments for rhythmic cue practice to provide an innovative approach to Parkinson's rehabilitation., Methods: In our single-blind quasi-randomized controlled trial, forty patients were assigned to either an experimental group (EG = 20) or a control group (CG = 20). Both groups underwent two months of training with CAREN scenarios (three times a week for 24 sessions). The experimental group additionally received NMT applied to the selected scenarios. Participants were evaluated by a neuropsychologist at baseline and immediately after training., Results: Intra-group analysis showed significant improvements in the EG for MOCA (p = 0.007), FAB (p = 0.008), Stroop Error (p = 0.003), Stroop Time (p < 0.001), and Visual Search (p < 0.001). The CG showed a significant difference only in Stroop Error (p = 0.02)., Conclusions: This pilot study is the first to combine NMT with CAREN in PD patients. Our findings suggest that NMT, within an immersive VR environment, effectively improves cognitive and EF in PD. Music structured within NMT techniques, coupled with advanced audio-visual feedback from VR, offers an innovative and potentially more effective approach for managing cognitive and executive deficits associated with PD., Competing Interests: The authors declare no conflicts of interest regarding the research, authorship, or publication of this article., (© 2024 The Author(s).)

Background/Objectives : Empowerment in medicine and psychiatry involves patients gaining control over health-related decisions, improving treatment adherence, outcomes, and satisfaction. This concept is especially significant in psychiatric care due to the complex challenges of mental health conditions, including stigma and impairment of emotional and cognitive functioning. We aim to investigate the correlations between patient trust, decision-making involvement, symptom severity, and perceived empowerment among individuals with Major Depression. Methods : Patients with Major Depressive Disorder were recruited in the "Policlinico G. Rodolico" psychiatry outpatient clinic from November 2022 to June 2023. Inclusion criteria: ages 18-65, ability to consent, stable condition, psychiatric medication history, and recent consultation. Exclusion criteria: psychotic features, bipolar disorder, substance abuse, high suicide risk, and severe comorbidities. Measures included the User Scale for Measuring Empowerment in Mental Health Services (SESM), Trust in Oncologist Scale (TiOS), Clinical Decision-Making Style for Patients (CDMS-P), and Hamilton Depression Rating Scale (HAM-D). Analysis used Kendall's Tau correlation and Two-One-Sided Tests procedure. Results : Seventy-three patients completed the study. No relationship was found between decision-making involvement and perceived empowerment (τ = -0.0625; p = 0.448), or between trust in psychiatrists and empowerment (τ = 0.0747; p = 0.364). An inverse correlation existed between patient involvement in therapy management and trust (τ = -0.2505; p = 0.002). Depression severity inversely correlated with empowerment (τ = -0.2762; p = <.001), but not with trust or decision-making involvement. Conclusions : The lack of significant correlations suggests that decision-making involvement and trust alone may not suffice to enhance empowerment. Trust may encourage patient passivity, while skepticism might drive active involvement. Higher empowerment is associated with less depressive symptoms, highlighting its potential connection with patient outcomes.

Objectives: The COVID-19 pandemic has negatively impacted child and adolescent mental health. The study outcome was the evaluation of the pandemic impact on adolescents' hospitalizations in an acute psychiatric ward., Methods: With an observational and retrospective design, we collected selected variables among adolescents hospitalized in an acute psychiatric ward from 01/07/2017 to 30/06/2022. Data were statistically processed., Results: Our sample consisted of 118 minors with an average age of 15.7 ± 1.2 SD, mostly represented by females (61 %) and Italians (60.2 %), who made 204 hospitalizations in the study period. The admissions by years drastically decreased in 2020 concomitantly with the lockdown and increased in the first half of 2022. The admission rate was higher in winter and spring, except in 2020 when all admissions decreased (p=0.000). Females more frequently were hospitalized for suicidal behavior and acute anxiety (p=0.000) and were discharged with acute stress reactions, eating disorders, and mood disorder diagnoses (p=0.000). Differently, males more frequently were hospitalized for aggressive behavior (p=0.000) and discharged with ADHD diagnosis (p=0.000). At multiple linear regression, the duration of hospitalization (dependent variable) was negatively associated with "the pandemic period" (p=0.017) and "absent aggressive behavior" (p=0.003), and positively with "autism" diagnosis (p=0.000)., Conclusions: We highlighted the more stressful impact of COVID-19 pandemic on female adolescents, who required more frequently psychiatric hospitalizations due to suicidal behavior, anxiety and mood disorders., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

This study investigates P. ostreatus and A. bisporus biodegradation capacity of low density polyethylene (LDPE) oxidised to simulate environmental weathering. Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM) were used to analyse the degradation of LDPE treated with fungal cultures. Molecular implications of LDPE degradation by P. ostreatus and A. bisporus were evaluated by Reverse transcription followed by quantitative PCR (qRT-PCR) of lac, mnp and lip genes expression. After 90 days of incubation, FT-IR analysis showed, for both fungal treatments, an increasing in the intensity of peaks related to the asymmetric C-C-O stretching (1160 to 1000 cm -1 ) and the -OH stretching (3700 to 3200 cm -1 ) due to the formation of alcohols and carboxylic acid, indicating depolymerisation of LDPE. This was confirmed by the SEM analysis, where a widespread alteration of the surface morphology was observed for treated LDPE fragments. Results revealed that the exposure of P. ostreatus to oxidised LDPE treatment led to a significant increase in the expression of the lac6, lac7, lac9, lac10 and mnp2 genes, while A. bisporus showed an over-expression in lac2 and lac12 genes. The obtained results offer new perspectives for a biotechnological use of P. ostreatus and A. bisporus for plastic bioremediation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In the aging process, skin morphology might be affected by wrinkle formation due to the loss of elasticity and resilience of connective tissues linked to the cleavage of elastin by the enzymatic activity of elastase. Little information is available about the structural requirements to efficiently inhibit elastase 1 (EC 3.4.21.36) expressed in skin keratinocytes. In this study, a structure-based approach led to the identification to the pharmacophoric hypotheses that described the main structural requirements for binding to porcine pancreatic elastase as a valuable tool for the development of skin therapeutic agents due to its similarity with human elastase 1. The obtained models were subsequently refined through the application of computational alanine-scanning mutagenesis to evaluate the effect of single residues on the binding affinity and protein stability; in turn, molecular dynamic simulations were carried out; these procedures led to a simplified model bearing few essential features, enabling a reliable collection of chemical features for their interactions with elastase. Then, a virtual screening campaign on the in-house library of synthetic compounds led to the identification of a nonpeptide-based inhibitor (IC 50 = 60.4 µM) belonging to the class of N -substituted-1 H -benzimidazol-2-yl]thio]acetamides, which might be further exploited to obtain more efficient ligands of elastase for therapeutic applications.

Introduction: Evidence from randomised controlled trials on anti-tumour necrosis factor (TNF) agents in patients with Behçet's syndrome (BS) is low., Method: We conducted a phase 3, multicentre, prospective, randomised, active-controlled, parallel-group study to evaluate the efficacy and safety of either infliximab (IFX) or adalimumab (ADA) in patients with BS. Adults patients with BS presenting with active mucocutaneous manifestations, occurring while on therapy with either azathioprine or cyclosporine for at least 3 months prior to study entry, were eligible. Participants were randomly assigned (1:1) to receive IFX or ADA for 6 months. The primary study outcome was the time to response of manifestations over 6-month anti-TNF alpha agents' treatment., Results: 42 patients underwent screening visits, of whom 40 were randomly assigned to the IFX group (n=22) or to the ADA group (n=18). All patients at the time of randomisation had active mucocutaneous manifestations and a smaller proportion had concomitant vital organ involvement (ie, six and three patients with ocular and neurological involvement, respectively). A total of 14 (64%) responders in the IFX group and 17 (94%) in the ADA group were observed. Retention on treatment was 95% and 94% in the IFX and in the ADA group, respectively. Quality of life resulted to be significantly improved in both groups from baseline, as well as Behçet's Disease Current Activity Form assessment. We registered two adverse events (one serious) in the ADA group and three non-serious adverse events in the IFX group., Discussion: The overall results of this study confirm the effectiveness of both IFX and ADA in achieving remission in patients with BS affected by mucocutaneous involvement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ on behalf of EULAR.)

Introduction: The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial., Aim: The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population., Materials and Methods: A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T 3mo ), 6 months (T 6mo ) and 12 months (T 12mo ) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del)., Results: Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T 3mo and T 6mo , but not at T 12mo , whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly., Conclusion: We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment.

A simple and sustainable propylphosphonic anhydride (T3P)-assisted methodology for the synthesis of N -acyl tryptamines, an interesting class of gut microbiota-derived endocannabinoid-like lipid mediators, was proposed. This protocol is characterized by great operational simplicity, and all products were obtained at room temperature, without the use of an inert atmosphere and by using limited amounts of non-halogenated solvents. Finally, the possibility to realize the reaction under mechanochemical conditions was explored with interesting results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Villano and Di Marzo.)

Objective: To optimise the organisation of care and encourage the adoption of good clinical practices, the RarERN Path © methodology was designed within ERN ReCONNET. The aim of our work was to report the application of RarERN Path © on systemic sclerosis within the ERN ReCONNET centres, providing a feasible and flexible organisational reference model for optimising the systemic sclerosis care pathway in different countries., Methods: RarERN Path © is a six-phase methodology which enables the creation of a reference organisational model co-designed on the basis of the expertise of different stakeholders. It foresees six phases, ranging from the map of existing patients' care pathways and patients' stories, to the consensus on a common organisational patient care pathways, and its key performance indicators definition., Results: The agreed reference model highlights the importance of having an organisational flow for referrals that foresees how patients may access directly the specialised unit from the different referrals. Specific specialised visits were considered as mandatory to be organised and they included cardiologist, pneumologist, gastroenterologist, psychologist, nephrologist, dermatologist, wound care specialist/nurses and other healthcare professionals (such as nurses, social workers and nutritional counselling). Moreover, specific services related to therapy were highlighted as strongly recommended to be organised, mainly represented by infusion therapy and wound care, as well as occupation therapy and physiotherapy., Conclusion: The organisational model emerged from our investigation emphasises that the organisation of specific services for systemic sclerosis treatment should be organised as a solid support for implementing the existing recommendations on systemic sclerosis management in real life., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2024.)

The present study describes a small library of peptides derived from a potent and selective CXCR4 antagonist (3), wherein the native disulfide bond is replaced using a side-chain to tail macrolactamization technique to vary ring size and amino acid composition. The peptides were preliminary assessed for their ability to interfere with the interaction between the receptor and anti-CXCR4 PE-conjugated antibody clone 12G5. Two promising candidates (13 and 17) were identified and further evaluated in a 125 I-CXCL12 competition binding assay, exhibiting IC 50 in the low-nanomolar range. Furthermore, both candidates displayed high selectivity towards CXCR4 with respect to the cognate receptor CXCR7, ability to block CXCL12-dependent cancer cell migration, and receptor internalization, albeit at a higher concentration compared to 3. Molecular modeling studies on 13 and 17 produced a theoretical model that may serve as a guide for future modifications, aiding in the development of analogs with improved affinity. Finally, the study provides valuable insights into developing therapeutic agents targeting CXCR4-mediated processes, demonstrating the adaptability of our lead peptide 3 to alternative cyclization approaches and offering prospects for comprehensive investigations into the receptor region's interaction with its C-terminal region., Competing Interests: Declaration of competing interest On behalf of all the authors of the manuscript titled “Disulfide Bond Replacement with Non-Reducible Side Chain to Tail Macrolactamization for the Development of Potent and Selective CXCR4 Peptide Antagonists Endowed with Flanking Binding Sites,” I confirm that A. M. T. and S. S. declare a conflict of interest as they hold a patent on one of the compounds mentioned in the article (compound 3) (WO2021130329A1). The remaining authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Cardiovascular diseases are a major cause of death worldwide. Advanced in vitro models can be the key stone for a better understanding of the mechanisms at the basis of the different pathologies, supporting the development of novel therapeutic protocols. In particular, the implementation of induced pluripotent stem cell (iPSC) technology allows for the generation of a patient-specific pluripotent cell line that is able to differentiate in several organ-specific cell subsets while retaining the patient genetic background, thus putting the basis for personalized in vitro modeling toward personalized medicine. The design of iPSC-based models able to recapitulate the complexity of the cardiac environment is a critical goal. Here, we review some of the published efforts to exploit three dimensional (3D) iPSC-based methods to recapitulate the relevant cardiomyopathies, including genetically and non-genetically determined cardiomyopathies and cardiotoxicity studies. Finally, we discuss the actual method limitations and the future perspectives in the field.

Objective: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR)., Methods: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points., Results: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment., Conclusions: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements.

Background and Objectives: Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method that modulates cortical excitability and shows promising results for treating disorders of consciousness (DoCs). Robotic verticalization training (RVT) has been shown to enhance motor and cognitive recovery. This study evaluates the effects of an innovative approach combining RVT with tDCS in individuals with DoCs., Methods: Twenty-four subjects with DoCs, particularly those with chronic minimally conscious state (MCS) due to vascular or traumatic brain injury, participated in a quasi-randomized study at the Neurorehabilitation Unit, IRCCS Neurolesi (Messina, Italy). Participants were divided into either a control group (CG) receiving RVT alone or an experimental group (EG) receiving combined tDCS and RVT. Both groups underwent treatments five times weekly for four weeks, with tDCS/sham sessions over the dorsolateral prefrontal cortex (DLPFC) lasting 20 min before Erigo training sessions, which lasted 45 min., Results: The findings indicate that combining tDCS with Erigo ® Pro RTT could lead to greater improvements in cognitive functioning and P300 latency compared to the CG., Conclusions: These results suggest that the integrated approach of tDCS with RVT could offer significant benefits for patients with MCS, highlighting its potential to enhance cognitive recovery, such as reducing P300 latency.

COVID-19 vaccination recommendations include healthcare workers (HCWs). We measured COVID-19 vaccine effectiveness (CVE) of the autumn 2023 dose against laboratory-confirmed SARS-CoV-2 infection in a prospective cohort study of 1,305 HCWs from 13 European hospitals. Overall CVE was 22% (95% CI: -17 to 48), 49% (95% CI: -8 to 76) before and -11% (95% CI: -84 to 34) after the start of BA.2.86/JN.1 predominant circulation. Autumn 2023 COVID-19 vaccination led to a moderate-to-low reduction in SARS-CoV-2 infection incidence in HCWs. Monitoring of CVE is crucial for COVID-19 prevention.

The aim of this review is to provide a critical summary of studies published during 2023 that contribute to our understanding of Behçet's syndrome. An increase in the incidence of BS was reported in Northern Spain after 2014.Studies on patient perspectives showed the impact of Behçet's syndrome on quality of life, daily activities, education, work, and relationships. Differences in genetics among Behçet's syndrome patients with different types of organ involvement were reported and an association between HLA-B/MICA and SLCO4A1 polymorphisms and eye involvement and between DDX60L polymorphisms and nervous system involvement were observed. It was suggested that Integrin α9β1 plays a crucial role in the neutrophil-mediated inflammatory pathways underlying this syndrome and the dysfunction of the PDL1/PD-1 pathway may be associated with the hyperactivity of the Th-1/Th-17 axis. Vein wall thickness seems to be increased in patients with Behçet's syndrome, but its pathogenetic and clinical implications are not clear. There is growing evidence regarding the efficacy of TNF inhibitors in different types of organ involvement. A number of small case series point out to the potential role of TCZ and JAK inhibitors.

Background and Aims: CCN4/WISP-1 regulates various cell behaviours that contribute to atherosclerosis progression, including cell adhesion, migration, proliferation and survival. We therefore hypothesised that CCN4 regulates the development and progression of atherosclerotic plaques., Methods: We used a high fat fed ApoE -/- mouse model to study atherosclerotic plaque progression in the brachiocephalic artery and aortic root. In protocol 1, male ApoE -/- mice with established plaques were given a CCN4 helper-dependent adenovirus to see the effect of treatment with CCN4, while in protocol 2 male CCN4 -/- ApoE -/- were compared to CCN4 +/+ ApoE -/- mice to assess the effect of CCN4 deletion on plaque progression., Results: CCN4 overexpression resulted in reduced occlusion of the brachiocephalic artery with less apoptosis, fewer macrophages, and attenuated lipid core size. The amount of plaque found on the aortic root was also reduced. CCN4 deficiency resulted in increased apoptosis and occlusion of the brachiocephalic artery as well as increased plaque in the aortic root. Additionally, in vitro cells from CCN4 -/- ApoE -/- mice had higher apoptotic levels. CCN4 deficiency did not significantly affect blood cholesterol levels or circulating myeloid cell populations., Conclusions: We conclude that in an atherosclerosis model the most important action of CCN4 is the effect on cell apoptosis. CCN4 provides pro-survival signals and leads to reduced cell death, lower macrophage number, smaller lipid core size and reduced atherosclerotic plaque burden. As such, the pro-survival effect of CCN4 is worthy of further investigation, in a bid to find a therapeutic for atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aim: Ductal carcinoma in situ is considered a local disease with no metastatic potential, thus sentinel lymph node biopsy (SLNB) may be deemed an overtreatment. SLNB should be reserved for patients with invasive cancer, even though the risk of upstaging rises to 25 %. We aimed to identify clinicopathological predictors of post-operative upstaging in invasive carcinoma., Methods: We retrospectively analyzed patients with a pre-operative diagnosis of DCIS subjected to breast surgery between January 2017 to December 2021, and evaluated at the Breast Unit of PTV (Policlinico Tor Vergata, Rome)., Results: Out of 267 patients diagnosed with DCIS, 33(12.4 %) received a diagnosis upstaging and 9(3.37 %) patients presented with sentinel lymph node (SLN) metastasis. In multivariate analysis, grade 3 tumor (OR 1.9; 95 % CI 1.2-5.6), dense nodule at mammography (OR 1.3; 95 % CI 1.1-2.6) and presence of a solid nodule at ultrasonography (OR 1.5; 95 % CI 1.2-2.6) were independent upstaging predictors. Differently, the independent predictors for SLNB metastasis were: upstaging (OR 2.1.; 95 % CI 1.2-4.6; p = 0.0079) and age between 40 and 60yrs (OR 1.4; 95 % CI 1.4-2.7; p = 0.027). All 9 patients with SLN metastasis received a diagnosis upstaging and were aged between 40 and 60 years old., Conclusion: We identified pre-operative independent predictors of upstaging to invasive ductal carcinoma. The combined use of different predictors in an algorithm for surgical treatments of DCIS could reduce the numbers of unnecessary SLNB., Competing Interests: Declaration of competing interest All the authors declare that they have no potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Childhood maltreatment, particularly emotional abuse (EA), has been identified as a significant risk factor for the development of eating disorders (EDs). This study investigated the association between EA and ED symptoms while considering multiple potential mediators., Methods: Participants included 151 individuals with Anorexia Nervosa (AN), 115 with Bulimia Nervosa (BN), and 108 healthy controls. The Childhood trauma questionnaire, the Toronto Alexithymia scale, the Behavioral inhibition System, and the Eating Disorder Inventory 2 scale were completed before treatment. A mediator path model was conducted in each group: EA was set as independent variable, eating symptoms as dependent variables and ineffectiveness, sensitivity to punishment, alexithymia, and impulsivity as mediators., Results: In individuals with AN, impulsivity emerged as a significant mediator between EA and desire for thinness and bulimic behaviors. Conversely, in individuals with BN, sensitivity to punishment was found to mediate the association between EA and dissatisfaction with one's body. Ineffectiveness and difficulty identifying emotions were identified as transdiagnostic mediators in both clinical groups. No mediation effect was found in healthy individuals., Discussion: The simultaneous assessment of multiple mediators in a unique model outlines the complex interplay between childhood EA and ED psychopathology. Improving ineffectiveness, emotion identification, sensitivity to punishment and impulsivity and exploring their relations with early emotional abuse may represent treatment targets in individuals with EDs and childhood trauma., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To examine studies involving the impact of telerehabilitation (TLR), tele-training and tele-support on the dyad stroke survivor and caregiver in relation to psychological, physical, social and health dimensions., Design: A systematic review was conducted., Data Sources: The following electronic databases were consulted until September 2023: PsycInfo, CINAHL, Eric, Ovid, PubMed, Scopus, Cochrane Central and Web of Science., Review Methods: It was conducted and reported following the checklists for Reviews of PRISMA 2020 Checklist. Critical evaluation of the quality of the studies included in the review was performed with the Joanna Briggs Institute Checklists., Data Synthesis: A total of 2290 records were identified after removing duplicates, 501 articles were selected by title and abstract and only 21 met the inclusion criteria. It included 4 quasi-experimental studies, 7 RCTs, 1 cohort study and 9 qualitative studies. The total number of participants between caregivers and stroke survivors was 1697, including 858 stroke survivors and 839 caregivers recruited from 2002 to 2022. For a total of 884 participants who carried out TLR activities in the experimental groups,11 impact domains were identified: cognitive/functional, psychological, caregiver burden, social, general health and self-efficacy, family function, quality of life, healthcare utilization, preparedness, quality of care and relationship with technology., Conclusions: The results support the application of telehealth in the discharge phase of hospitals and rehabilitation centres for stroke survivors and caregivers. TLR could be considered a substitute for traditional rehabilitation only if it is supported by a tele-learning programme for the caregiver and ongoing technical, computer and health support to satisfy the dyad's needs., Impact: Designing a comprehensive telemedicine programme upon the return home of the dyad involved in the stroke improves the quality of life, functional, psychological, social, family status, self-efficacy, use of health systems and the dyad's preparation for managing the stroke., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Few data are available regarding vaccine induced SARS-CoV-2 specific T cell responses over time and after booster doses in multiple sclerosis (MS) patients on different disease modifying treatments. We measured SARS-CoV-2 specific CD4 + T cell responses in 72 samples collected from 36 MS patients. The percentage of CD4 + CTV low CD25 + ICOS + T cells after stimulation with Spike Recombinant Protein was 29.9 (17.0-43.6) on teriflunomide, 32.4 (11.9-42.5) on ocrelizumab, but much lower (0.6 [0.3-5.9]) on sphingosine-1-phospate receptor modulators (β = -26.35, p = 0.003). SARS-CoV-2 specific T cells were mainly of Th1 type and stable over time and after booster vaccine doses. mRNA vaccines elicit strong and persistent CD4+ T cell responses against SARS-CoV-2 in MS patients on anti-CD20 and teriflunomide, but not in those on sphingosine-1-phospate receptor modulators., Competing Interests: Declaration of competing interest The employer (Department of Neurology, Regional Hospital Lugano (EOC), Lugano, Switzerland) receives financial support from Abbvie, Biogen Idec, Lundbeck, Merck, Novartis Roche, Sanofi, Teva. The submitted work is not related to these agreements., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Here, we report new 2-nitro and/or 4-trifluoromethylphenyl-based small molecules developed as inhibitors of alpha-Syn fibril formation. The set of eighteen compounds was inspired by well-known alpha-Syn aggregation modulators retrieved from literature. The preliminary biochemical data suggested that the two molecules out of eighteen compounds exerted activity comparable to that of reference compound SynuClean-D (SC-D, 5-nitro-6-(3-nitrophenyl)-2-oxo-4-(trifluoromethyl)-1H-pyridine-3-carbonitrile), according to Thioflavin T kinetics. Pharmacophore modelling deciphered the main structural requirements for alpha-Syn aggregation modulators. Moreover, docking and molecular dynamics simulations depicted the binding mode with the targeted alpha-Syn fibrils. The structural data of these new potential α-Syn binders might furnish additional information for understanding the mechanism of action of the ligands that specifically target the NAC domain as theranostic agents for α-synucleopathies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Polymetabolic syndrome achieved pandemic proportions and dramatically influenced public health systems functioning worldwide. Chronic vascular complications are the major contributors to increased morbidity, disability, and mortality rates in diabetes patients. Nitric oxide (NO) is among the most important vascular bed function regulators. However, NO homeostasis is significantly deranged in pathological conditions. Additionally, different hormones directly or indirectly affect NO production and activity and subsequently act on vascular physiology. In this paper, we summarize the recent literature data related to the effects of insulin, estradiol, insulin-like growth factor-1, ghrelin, angiotensin II and irisin on the NO regulation in physiological and diabetes circumstances., Competing Interests: Declaration of competing interest The authors declare that there are no competing interests to declare regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although several studies have analyzed the effects of spirituality on stroke survivors' physical functioning and their caregiver's outcomes, no systematic review or meta-synthesis was found to identify the lived experiences of stroke survivors and caregivers regarding spirituality. For these reasons, this study aimed to analyze quantitively and qualitatively research relating to stroke survivors' and caregivers' experiences. The included studies were RCT studies, quasi-experimental studies, qualitative, descriptive, ethnographic, and phenomenological studies, and cross-sectional studies (n = 37), with a total of 6850 stroke survivors and 1953 caregivers enrolled. Spirituality appears to play an important role in improving the quality of life and decreasing anxiety and depression of both stroke survivors and their caregivers., (© 2024. The Author(s).)

Behçet's syndrome (BS) is a rare multisystem vasculitis involving blood vessels of any size. BS aetiology is still unclear to date, and the heterogeneity of clinical expression among ethnics and genders make early diagnosis challenging. However, so far, considerable efforts have been made toward the understanding of BS, leading researchers to agree that the coexistence of some environmental triggers and a genetical susceptibility both underlie BS aetiopathogenesis. In particular, viral agents, oral microbial flora, and mucosal microbiota have been widely explored in this regard, but still no specific microorganism has been definitely linked to the disease aetiology. Likewise, the concept that some environmental factors may play a role in BS clinical presentation has emerged based on the growing evidence that disease severity is usually higher in male patients, and that diet and fatigue may be involved in disease recurrence, especially in mucocutaneous manifestations. Moreover, smoke cessation is acknowledged as a risk factor for oral ulcerations, although the underlying mechanism is still not clear. All those environmental factors play their effects through epigenetic mechanisms. The aim of this review is to discuss the evidence on the role of environmental factors in BS aetiopathogenesis and clinical course.

Purpose: To describe which needs and difficulties are experienced by stroke patients and caregivers regarding their return to work and to synthesise the lived experiences of stroke patients and caregivers., Materials and Methods: A systematic review and metasynthesis was conducted on PubMed, CINAHL, Scopus, Web of Sciences and PsycInfo, in according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research. Studies eligible for the review had to fulfil the following inclusion criteria: qualitative studies, stroke patients and their caregivers in a working age (approximately from 18 to 65 years old), discharged from the hospital., Results: Thirty-eight studies involving stroke patients and caregivers were included in this review. For the stroke patients' group, three main themes were identified: (a) Towards the future; (b) Professional support in return to work; and (c) return to work and employment perspective, while for caregivers two main themes were: (a) daily life challenges and role overload; and (b) employment challenges., Conclusions: Integrating public employment, social and health services, support for job placement, return to work, and social participation of stroke patients should be more supported in individual rehabilitation programs to help stroke survivors and caregivers in their return-to-work process.

We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVD DD-DI ) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVD DD-DI without uneven late toxicities., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: In the arms of patients with Amyotrophic lateral sclerosis (ALS) two peculiar patterns of dissociated muscular atrophy have been described: the split-hand sign (with predominant atrophy of the lateral aspect of the hand, compared to hypothenar eminence) and the split-hand-plus sign (SHPS), a predominant abductor pollicis brevis (ABP) atrophy with sparing of flexor pollicis longus (FPL)., Aims: In this case-control study, we evaluated the diagnostic utility of a neurophysiological indicator of SHPS and assessed its association with clinical features., Methods: We prospectively studied 59 incident ALS patients, 61 patients with ALS-mimic disorders (OND) and 61 non-neurological controls (NNCs). ABP and FPL compound muscle action potentials (CMAP) amplitudes were obtained by supramaximal stimulation of median nerve at elbow. Split-hand plus index (SHPI) was calculated according to the formula: APB-CMAP/FPL-CMAP., Results: SHPI was significantly lower in ALS compared to OND patients and NNCs (p < 0.0001). SHPI value < 1 was observed in 2% of NNCs and 9% of OND patients and demonstrated an accuracy of 71% in differentiating ALS from OND and an accuracy of 74% in differentiating ALS from NNC. SHPI was associated with higher LMN score, and higher disease severity as quantified by the ALSFRS-r., Conclusion: Our results indicate that SHPI is a reliable indicator to distinguish ALS patients from ONDs and NNCs. SHPI was significantly associated to the degree of lower motor neuron impairment but showed no association with upper motoneuron impairment., (© 2024. Fondazione Società Italiana di Neurologia.)