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Abstract Background Parkinson’s disease (PD) is often accompanied by gait disorders and freezing of gait (FoG), disabling symptoms that are resistant to conventional dopamine treatments. Given the cerebellum’s connectivity with the motor cortex and basal ganglia, and its implication in PD, combining transcranial direct current stimulation targeting the cerebellum (ctDCS) with physical exercise might improve gait and balance. Objective This study aimed to evaluate the effectiveness of a novel rehabilitation approach that combines noninvasive cerebellar stimulation with motor-cognitive training via an augmented reality treadmill (C-Mill VR+) in individuals with PD and FoG. Methods Seventeen individuals with PD exhibiting FoG were enrolled in a randomized controlled trial. The participants were randomly assigned to a group receiving motor-cognitive training on the C-Mill VR+ with either ctDCS or sham ctDCS. Assessments were conducted pre-intervention (T0), post-intervention (T1) after 10 sessions, and at 4-week follow-up (T2), using various clinical scales. Additionally, C-Mill assessments of postural stability and gait were conducted at T0 and T1. Results Although no significant time*group interactions were observed for any of the clinical variables measured, some were found in the C-Mill measures. Specifically, right lower limb sway in static conditions, both with eyes open (OAD) and eyes closed (OCD), significantly improved at T1 in the ctDCS group compared with the sham group. Conclusions C-Mill outcomes indicate that the combined treatment may enhance motor control. Participants who received ctDCS along with augmented reality motor-cognitive training showed better postural stability.

Abstract Background Glioblastoma (GBM) stands as the most prevalent and aggressive form of adult gliomas. Despite the implementation of intensive therapeutic approaches involving surgery, radiation, and chemotherapy, Glioblastoma Stem Cells contribute to tumor recurrence and poor prognosis. The induction of Glioblastoma Stem Cells differentiation by manipulating the transcriptional machinery has emerged as a promising strategy for GBM treatment. Here, we explored an innovative approach by investigating the role of the depolarized resting membrane potential (RMP) observed in patient-derived GBM sphereforming cell (GSCs), which allows them to maintain a stemness profile when they reside in the G0 phase of the cell cycle. Methods We conducted molecular biology and electrophysiological experiments, both in vitro and in vivo, to examine the functional expression of the voltage-gated sodium channel (Nav) in GSCs, particularly focusing on its cell cycle-dependent functional expression. Nav activity was pharmacologically manipulated, and its effects on GSCs behavior were assessed by live imaging cell cycle analysis, self-renewal assays, and chemosensitivity assays. Mechanistic insights into the role of Nav in regulating GBM stemness were investigated through pathway analysis in vitro and through tumor proliferation assay in vivo. Results We demonstrated that Nav is functionally expressed by GSCs mainly during the G0 phase of the cell cycle, suggesting its pivotal role in modulating the RMP. The pharmacological blockade of Nav made GBM cells more susceptible to temozolomide (TMZ), a standard drug for this type of tumor, by inducing cell cycle re-entry from G0 phase to G1/S transition. Additionally, inhibition of Nav substantially influenced the self-renewal and multipotency features of GSCs, concomitantly enhancing their degree of differentiation. Finally, our data suggested that Nav positively regulates GBM stemness by depolarizing the RMP and suppressing the ERK signaling pathway. Of note, in vivo proliferation assessment confirmed the increased susceptibility to TMZ following pharmacological blockade of Nav. Conclusions This insight positions Nav as a promising prognostic biomarker and therapeutic target for GBM patients, particularly in conjunction with temozolomide treatment.

Aim of the present study was to evaluate the relationship between sensory sensitivity and autistic eating behaviours or Eating Disorders (EDs) symptomatology, in a group of 75 adults with Autism Spectrum Disorders (ASDs) without intellectual disabilities, through a series of self-report questionnaires. We found that, controlling for demographic and clinical features: (i) hypersensitivity in the vision domain predicted higher levels of both EDs symptoms and autistic eating behaviours; (ii) hyposensitivity in the taste domain predicted higher levels of EDs symptoms. This gives preliminary evidence that not only in children diagnosed with ASDs, but even in adult individuals, the threshold of sensory sensitivity is associated with dysfunctional eating behaviours.

Anorexia nervosa (AN) is an eating disorder (ED) that has seen an increase in its incidence in the last thirty years. Compared to other psychosomatic disorders, ED can be responsible for many major medical complications, moreover, in addition to the various systemic impairments, patients with AN undergo morphological and physiological changes affecting the cerebral cortex. Through immunohistochemical studies on portions of postmortem human brain of people affected by AN and healthy individuals, and western blot studies on leucocytes of young patients and healthy controls, this study investigated the role in the afore-mentioned processes of altered redox state. The results showed that the brain volume reduction in AN could be due to an increase in the rate of cell death, mainly by apoptosis, in which mitochondria, main cellular organelles affected by a decreased dietary intake, and a highly compromised intracellular redox balance, may play a pivotal role

Abstract The existing Intraductal Papillary Mucinous Neoplasm (IPMN) risk stratification relies on clinical and histological factors, resulting in inaccuracies and leading to suboptimal treatment. This is due to the lack of appropriate molecular markers that can guide patients toward the best therapeutic options. Here, we assess and confirm subtype-specific markers for IPMN across two independent cohorts of patients using two Spatial Transcriptomics (ST) technologies. Specifically, we identify HOXB3 and ZNF117 as markers for Low-Grade Dysplasia, SPDEF and gastric neck cell markers in borderline cases, and NKX6-2 and gastric isthmus cell markers in High-Grade-Dysplasia Gastric IPMN, highlighting the role of TNFα and MYC activation in IPMN progression and the role of NKX6-2 in the specific Gastric IPMN progression. In conclusion, our work provides a step forward in understanding the gene expression landscapes of IPMN and the critical transcriptional networks related to PDAC progression.

BackgroundThe increasing number of patients, the high costs of management, and the chronic progress of the disease that prevents patients from performing even simple daily activities make Parkinson disease (PD) a complex pathology with a high impact on society. In particular, patients implanted with deep brain stimulation (DBS) electrodes face a highly fragile stabilization period, requiring specific support at home. However, DBS patients are followed usually by untrained personnel (caregivers or family), without specific care pathways and supporting systems. ObjectiveThis projects aims to (1) create a reference consensus guideline and a shared requirements set for the homecare and monitoring of DBS patients, (2) define a set of biomarkers that provides alarms to caregivers for continuous home monitoring, and (3) implement an information system architecture allowing communication between health care professionals and caregivers and improving the quality of care for DBS patients. MethodsThe definitions of the consensus care pathway and of caregiver needs will be obtained by analyzing the current practices for patient follow-up through focus groups and structured interviews involving health care professionals, patients, and caregivers. The results of this analysis will be represented in a formal graphical model of the process of DBS patient care at home. To define the neurophysiological biomarkers to be used to raise alarms during the monitoring process, neurosignals will be acquired from DBS electrodes through a new experimental system that records while DBS is turned ON and transmits signals by radiofrequency. Motor, cognitive, and behavioral protocols will be used to study possible feedback/alarms to be provided by the system. Finally, a set of mobile apps to support the caregiver at home in managing and monitoring the patient will be developed and tested in the community of caregivers that participated in the focus groups. The set of developed apps will be connected to the already existing WebBioBank Web-based platform allowing health care professionals to manage patient electronic health records and neurophysiological signals. New modules in the WebBioBank platform will be implemented to allow integration and data exchange with mobile health apps. ResultsThe results of this project will provide a novel approach to long-term evaluation of patients with chronic, severe conditions in the homecare environment, based on caregiver empowerment and tailored applications developed according to consensus care pathways established by clinicians. ConclusionsThe creation of a direct communication channel between health care professionals and caregivers can benefit large communities of patients and would represent a scalable experience in integrating data and information coming from a clinical setting to those in home monitoring.

Abstract Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in the world. The neurobiology of OCD has not been completely understood and efforts are needed in order to develop new treatments. Beside the classical neurotransmitter systems and signalling pathways implicated in OCD, the possible involvement of the endocannabinoid system (ECS) has emerged in pathophysiology of OCD. We report here selective downregulation of the genes coding for enzymes allowing the synthesis of the endocannabinoids. We found reduced DAGLα and NAPE-PLD in blood samples of individuals with OCD (when compared to healthy controls) as well as in the amygdala complex and prefrontal cortex of dopamine transporter (DAT) heterozygous rats, manifesting compulsive behaviours. Also mRNA levels of the genes coding for cannabinoid receptors type 1 and type 2 resulted downregulated, respectively in the rat amygdala and in human blood. Moreover, NAPE-PLD changes in gene expression resulted to be associated with an increase in DNA methylation at gene promoter, and the modulation of this gene in OCD appears to be correlated to the progression of the disease. Finally, the alterations observed in ECS genes expression appears to be correlated with the modulation in oxytocin receptor gene expression, consistently with what recently reported. Overall, we confirm here a role for ECS in OCD at both preclinical and clinical level. Many potential biomarkers are suggested among its components, in particular NAPE-PLD, that might be of help for a prompt and clear diagnosis.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

Esta entrevista objetiva refletir sobre o processo criativo da artista Laura Anderson Barbata, nascida na Cidade do México/México e que, atualmente, vive e trabalha entre Nova Iorque/EUA e Cidade do México. Artista transdisciplinar, autora de diversos livros, transita em distintas linguagens artísticas, e já realizou exposições em países como México, Estados Unidos e Brasil. O diálogo proposto nesta entrevista com Laura Anderson Barbata, aborda os trânsitos e deslocamentos fronteiriços, o sentido de pertença, as relações entre o global e o local, entoam suas criações artísticas que combinam diversas narrativas e protagonismos. Na expectativa de contribuir para a irradiação de seu trabalho, nos lançamos a essa interlocução, numa conversação sobre sua trajetória, experiências e práticas artísticas como possibilidades de novos laços entre artistas, saberes e linguagens.

Objective. Data from trials demonstrated that abatacept (ABA) has a good safety and efficacy profile in treating rheumatoid arthritis. We have studied the retention rate of ABA in a real-life cohort of patients with rheumatoid arthritis. Methods. This is a monocentric, retrospective study including patients with rheumatoid arthritis classified by the American College of Rheumatology/European League Against Rheumatism 2010 criteria who started treatment with ABA. The Kaplan-Meier method was applied to evaluate the ABA retention rate. Results. This analysis was conducted on 161 patients [male/female 21/140, median age 65 years, interquartile range (IQR) 18.7, median disease duration 169 months, IQR 144.0]. 111 patients (68.9%) received ABA subcutaneously. ABA was associated with methotrexate in 61.9% of patients and was the first biological disease-modifying antirheumatic drug in 41%. We observed a median ABA survival of 66 months [95% confidence interval (CI) 57.3-74.7], with a retention rate of 88% at 6 months and 50.9% at 5 years. Drug survival was significantly higher in patients treated with ABA subcutaneously and in male patients (p=0.039 and p=0.018, respectively). Adjusted for main confounders, female gender was the main predictor of withdrawal (hazard ratio 5.1, 95% CI 1.2-21.3). Conclusions. Our study shows that better survival is associated with subcutaneous administration and male gender, confirming ABA effectiveness.

Aim of the present study was to evaluate the relationship between sensory sensitivity and autistic eating behaviours or Eating Disorders (EDs) symptomatology, in a group of 75 adults with Autism Spectrum Disorders (ASDs) without intellectual disabilities, through a series of self-report questionnaires. We found that, controlling for demographic and clinical features: (i) hypersensitivity in the vision domain predicted higher levels of both EDs symptoms and autistic eating behaviours; (ii) hyposensitivity in the taste domain predicted higher levels of EDs symptoms. This gives preliminary evidence that not only in children diagnosed with ASDs, but even in adult individuals, the threshold of sensory sensitivity is associated with dysfunctional eating behaviours., Author(s): Veronica Nisticò [sup.1] [sup.2] , Raffaella Faggioli [sup.3] , Roberta Tedesco [sup.1] , Barbara Giordano [sup.1] , Alberto Priori [sup.1] [sup.2] [sup.4] , Orsola Gambini [sup.1] [sup.2] [sup.3] , [...]

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy. The study of the early stages of carcinogenesis provides the opportunity for the identification of actionable pathways that underpin therapeutic resistance. Methods We analyzed 43 Intraductal papillary mucinous neoplasms (IPMN) (12 Low-grade and 31 High-grade) by Spatial Transcriptomics. Mouse and human pancreatic cancer organoids and T cells interaction platforms were established to test the role of mucins expression on T cells activity. Syngeneic mouse model of PDAC was used to explore the impact of mucins downregulation on standard therapy efficacy. Results Spatial transcriptomics showed that mucin O-glycosylation pathway is increased in the progression from low-grade to high-grade IPMN. We identified GCNT3, a master regulator of mucins expression, as an actionable target of this pathway by talniflumate. We showed that talniflumate impaired mucins expression increasing T cell activation and recognition using both mouse and human organoid interaction platforms. In vivo experiments showed that talniflumate was able to increase the efficacy of the chemotherapy by boosting immune infiltration. Conclusions Finally, we demonstrated that combination of talniflumate, an anti-inflammatory drug, with chemotherapy effectively improves anti-tumor effect in PDAC.

Background/Objectives: In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be more effective in reducing time to response. With those premises, this study aimed to evaluate a sample of TRD patients treated with standard repetitive TMS (rTMS) and accelerated rTMS (arTMS). Methods: Nine subjects were treated with standard rTMS and 19 with arTMS. Psychometric assessment was made at the baseline and one week, one month, and three months after the treatment. A linear mixed-effect regression was performed along with other appropriate statistical analyses. Results: A significant improvement over time was observed for both depressive and cognitive symptoms. Moreover, considering the reduction in the Montgomery–Asberg Depression Rating Scale scores, a better treatment response was observed in subjects treated with arTMS (p < 0.05). Conclusions: Our findings showed a significant difference between the two protocols in terms of clinical response. Although further studies are needed to confirm the superiority of arTMS, the better cost-effectiveness of this technique should be considered.

Introduction: The rapid spread of the COVID-19 pandemic has had a significant impact on the psychological well-being of millions of people around the world, and even more so among children. Contracting SARS-CoV-2, resulting in home confinement and restrictions on daily and school activities, led to negative effects on the mental health of the paediatric population. Although children suffering from COVID-19 had milder general symptoms compared to adults, impairments in cognitive, neuropsychological, and emotional-behavioural development were noted. Objective: The main aim of the present study was to detect possible changes in the neuropsychological and emotional-behavioural development of children after infection with the SARS-CoV-2 virus. The second aim was to investigate possible relationships between cognitive abilities and psychosocial characteristics. Methods: A total of 40 patients aged 8–9 years were recruited and divided into two groups: children who contracted (CG) and did not contract (NCG) SARS-CoV-2. The BVN 5–11 (Neuropsychological evaluation battery for developmental age from 5 to 11 years) instrument was administered to assess attention, memory, verbal recall, planning, phonemics, and categorical fluency domains in the paediatric population. Data on changes in emotional-behavioural profile and daily activities were collected through a questionnaire to parents. Results: The Wilcoxon signed-rank test revealed a significant change in mood after the COVID-19 period only in the CG participants (p = 0.019). However, the neuropsychological performance of the two identified groups on BVN 5–11 sub-items was below the cutoff of clinical significance. Correlations were found between sub-items of the BVN 5–11 battery, extracurricular activities, and children’s psycho-motor development. Significant positive correlations were observed between Naming on visual presentation and Reading time (p = 0.006), backward digit span and time of motor activity (p = 0.009), Visual attention and Reading time (p = 0.048), and Phonemic fluency and time observed using devices (p = 0.030). Positive statistically significant correlations were also found between Mood and Free behaviour (p = 0.000), between Mood and Structured behaviour (p = 0.005), and between Mood and peer Interaction (p = 0.013). Conclusions: SARS-CoV-2 infection negatively affected the emotional development of children contracting the virus. The neuropsychological functioning of the paediatric population was influenced by psychosocial variables and time spent on daily activities, which played a protective role in children’s cognitive development.

Introduction Motor Conversion Disorders (also called Functional Movement Disorders, FMD) are a group of neuropsychiatric conditions characterized by neurological symptoms of altered voluntary motor function that cannot be explained by typical neurological diseases or other medical conditions. In the last decade, several hypotheses have been formulated with respect to their pathophysiology, and a major line of research, trying to integrate psychological, cognitive, and neurobiological factors, focused on the subjective experience that patients feel of their own bodies. However, no study has, so far, directly investigated their Body Schema (the implicit sensorimotor representation of one’s own body) and its plasticity. Objectives To investigate the Body Schema in patients with FMD through a paradigm specifically designed to assess their perceived body metrics, through a spatial estimation of body parts length, and to compare their results with the ones obtain on a group of healthy control subjects (HC) Methods 10 patients with FMD and 11 HC underwent the Forearm Bisection Task, aimed at assessing perceived body metrics, which consists in asking the subject, blindfolded, to repeatedly point at the perceived middle point of their dominant forearm with the index finger of their contralateral hand, and a psychometric assessment for anxiety, depression, alexithymia, and tendency to dissociation. Results FMD patients bisected their forearm more proximally (with an increased shift towards their elbow equal to 7.5%) with respect to HC; average bisection point was positively associated with anxiety levels in the whole sample, and with the tendency to dissociation in the FMD group. Conclusions FMD patients seem to perceive their forearm as shorter than HC do, which might suggest an alteration of their Body Schema. The Body Schema can go through short- and long-term plastic changes in the life course, mainly related to the use of each body segment; we speculate that, despite FMD being a disorder of functional nature, characterized by variability and fluctuations in symptomatology, the lack of sense of agency over a body part might be interpreted by the nervous system as disuse and hence influence the Body Schema, as deficits of organic aetiology do. Disclosure of Interest None Declared

Objective: The search for market expansion challenges Brazilian craft breweries. Based on coopetition strategies, many join in seeking to overcome these challenges. The challenge for gypsy breweries is even more significant, as they must produce beer in a non-gypsy brewery. Some tensions emerge from this relationship, such as space availability and costs. Methods: From the actor-network theory, we analyze the relationship between gypsy and non-gypsy breweries, deepening the analysis of their tensions. Based on a case study with craft breweries in Rio de Janeiro State. Results: As the results highlighted, the tension between them starts at a level not mentioned in the literature on coopetition. Conclusions: This extension expands the existing literature on coopetition by highlighting the influence of nonhuman elements (e.g., factory, resources, equipment, and operations) in shaping inter-organizational relationships, with the factory being the main generator of this tension. The study offers insights into how actors (human and nonhuman) navigate, interact, and negotiate tensions to achieve mutual goals. By applying ANT to analyze coopetition dynamics, the study contributes to the theoretical framework by demonstrating how this approach can enhance understanding of complex mechanisms, processes, and relationships through which coopetition dynamics unfold in practice.