Discovering common pathogenetic processes between COVID-19 and diabetes mellitus by differential gene expression pattern analysis.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the newly discovered coronavirus, SARS-CoV-2. Increased severity of COVID-19 has been observed in patients with diabetes mellitus (DM). This study aimed to identify common transcriptional signatures, regulators and pathways between COVID-19 and DM. We have integrated human whole-genome transcriptomic datasets from COVID-19 and DM, followed by functional assessment with gene ontology (GO) and pathway analyses. In peripheral blood mononuclear cells (PBMCs), among the upregulated differentially expressed genes (DEGs), 32 were found to be commonly modulated in COVID-19 and type 2 diabetes (T2D), while 10 DEGs were commonly downregulated. As regards type 1 diabetes (T1D), 21 DEGs were commonly upregulated, and 29 DEGs were commonly downregulated in COVID-19 and T1D. Moreover, 35 DEGs were commonly upregulated in SARS-CoV-2 infected pancreas organoids and T2D islets, while 14 were commonly downregulated. Several GO terms were found in common between COVID-19 and DM. Prediction of the putative transcription factors involved in the upregulation of genes in COVID-19 and DM identified RELA to be implicated in both PBMCs and pancreas. Here, for the first time, we have characterized the biological processes and pathways commonly dysregulated in COVID-19 and DM, which could be in the next future used for the design of personalized treatment of COVID-19 patients suffering from DM as comorbidity.

Wearable Technologies and AI at the Far Edge for Chronic Heart Failure Prevention and Management: A Systematic Review and Prospects.

Smart wearable devices enable personalized at-home healthcare by unobtrusively collecting patient health data and facilitating the development of intelligent platforms to support patient care and management. The accurate analysis of data obtained from wearable devices is crucial for interpreting and contextualizing health data and facilitating the reliable diagnosis and management of critical and chronic diseases. The combination of edge computing and artificial intelligence has provided real-time, time-critical, and privacy-preserving data analysis solutions. However, based on the envisioned service, evaluating the additive value of edge intelligence to the overall architecture is essential before implementation. This article aims to comprehensively analyze the current state of the art on smart health infrastructures implementing wearable and AI technologies at the far edge to support patients with chronic heart failure (CHF). In particular, we highlight the contribution of edge intelligence in supporting the integration of wearable devices into IoT-aware technology infrastructures that provide services for patient diagnosis and management. We also offer an in-depth analysis of open challenges and provide potential solutions to facilitate the integration of wearable devices with edge AI solutions to provide innovative technological infrastructures and interactive services for patients and doctors.

White matter substrates of functional connectivity dynamics in the human brain.

The contribution of structural connectivity to functional connectivity dynamics is still far from being elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.

Effects of diffusion signal modeling and segmentation approaches on subthalamic nucleus parcellation.

The subthalamic nucleus (STN) is commonly used as a surgical target for deep brain stimulation in movement disorders such as Parkinson's Disease. Tractography-derived connectivity-based parcellation (CBP) has been recently proposed as a suitable tool for non-invasive in vivo identification and pre-operative targeting of specific functional territories within the human STN. However, a well-established, accurate and reproducible protocol for STN parcellation is still lacking. The present work aims at testing the effects of different tractography-based approaches for the reconstruction of STN functional territories. We reconstructed functional territories of the STN on the high-quality dataset of 100 unrelated healthy subjects and on the test-retest dataset of the Human Connectome Project (HCP) repository. Connectivity-based parcellation was performed with a hypothesis-driven approach according to cortico-subthalamic connectivity, after dividing cortical areas into three groups: associative, limbic and sensorimotor. Four parcellation pipelines were compared, combining different signal modeling techniques (single-fiber vs multi-fiber) and different parcellation approaches (winner takes all parcellation vs fiber density thresholding). We tested these procedures on STN regions of interest obtained from three different, commonly employed, subcortical atlases. We evaluated the pipelines both in terms of between-subject similarity, assessed on the cohort of 100 unrelated healthy subjects, and of within-subject similarity, using a second cohort of 44 subjects with available test-retest data. We found that each parcellation provides converging results in terms of location of the identified parcels, but with significative variations in size and shape. All pipelines obtained very high within-subject similarity, with tensor-based approaches outperforming multi-fiber pipelines. On the other hand, higher between-subject similarity was found with multi-fiber signal modeling techniques combined with fiber density thresholding. We suggest that a fine-tuning of tractography-based parcellation may lead to higher reproducibility and aid the development of an optimized surgical targeting protocol.

In Vivo Super-Resolution Track-Density Imaging for Thalamic Nuclei Identification.

The development of novel techniques for the in vivo, non-invasive visualization and identification of thalamic nuclei has represented a major challenge for human neuroimaging research in the last decades. Thalamic nuclei have important implications in various key aspects of brain physiology and many of them show selective alterations in various neurologic and psychiatric disorders. In addition, both surgical stimulation and ablation of specific thalamic nuclei have been proven to be useful for the treatment of different neuropsychiatric diseases. The present work aimed at describing a novel protocol for histologically guided delineation of thalamic nuclei based on short-tracks track-density imaging (stTDI), which is an advanced imaging technique exploiting high angular resolution diffusion tractography to obtain super-resolved white matter maps. We demonstrated that this approach can identify up to 13 distinct thalamic nuclei bilaterally with very high inter-subject (ICC: 0.996, 95% CI: 0.993-0.998) and inter-rater (ICC:0.981; 95% CI:0.963-0.989) reliability, and that both subject-based and group-level thalamic parcellation show a fair share of similarity to a recent standard-space histological thalamic atlas. Finally, we showed that stTDI-derived thalamic maps can be successfully employed to study structural and functional connectivity of the thalamus and may have potential implications both for basic and translational research, as well as for presurgical planning purposes.

Feasibility, Usability, and Customer Satisfaction of the Tele-COVID19 Project, Sicilian Model.

Background and Objectives: In March 2020, COVID-19 pandemic affected the world. All countries, to limit viral transmission, imposed quarantine. This emergency exerted personal, social, economic, and psychological impact on people. For health systems, was needed to create alternative care pathways. Telemedicine can be helpful to reduce isolation, provide health care services, and monitor virus infections. Italian regions, including Sicily, have activated telemedicine services for management of patients with COVID-19. Objective: The purpose of study is to describe a Sicilian telemedicine model for management of COVID-19 patients, showing results on feasibility, usability and quality of service and patient satisfaction. Materials and Methods: This is a descriptive exploratory study on a telemedicine service for residents in Messina infected by COVID-19. It included monitoring of vital signs and specialist consultations (i.e., doctor, psychologists, social workers, and nutritionist biologists). Results: More than twenty percent (23.8%) of participants used tele-monitoring and tele-counselling services; 14.3% were only telemonitored. Participants judged positively telemedicine service (30% were quiet and 50% were very satisfied), as well as tool (70% were quiet and 10% were very satisfied). Telemonitoring had a low agreement (10% were slightly satisfied and 50% were neutral); tele-counselling had a high rate of satisfaction (40% quiet and 60% were very satisfied). Conclusions: This study showed that telemedicine model for Sicilian population affected by COVID-19 was feasible, easy to use and appreciated by patients. Our promising results allow us to assume that if in Sicily there was a return of the emergency, we would be ready to manage it This system can be the solution to remote management of these patients, to reduce isolation, provide health services, and monitor virus infections. The use of this technology should encourage future research to change the health care system and provides opportunities to ensure health and care for oneself and others.

Ventral intermediate nucleus structural connectivity-derived segmentation: anatomical reliability and variability.

The Ventral intermediate nucleus (Vim) of thalamus is the most targeted structure for the treatment of drug-refractory tremors. Since methodological differences across existing studies are remarkable and no gold-standard pipeline is available, in this study, we tested different parcellation pipelines for tractography-derived putative Vim identification. Thalamic parcellation was performed on a high quality, multi-shell dataset and a downsampled, clinical-like dataset using two different diffusion signal modeling techniques and two different voxel classification criteria, thus implementing a total of four parcellation pipelines. The most reliable pipeline in terms of inter-subject variability has been picked and parcels putatively corresponding to motor thalamic nuclei have been selected by calculating similarity with a histology-based mask of Vim. Then, spatial relations with optimal stimulation points for the treatment of essential tremor have been quantified. Finally, effect of data quality and parcellation pipelines on a volumetric index of connectivity clusters has been assessed. We found that the pipeline characterized by higher-order signal modeling and threshold-based voxel classification criteria was the most reliable in terms of inter-subject variability regardless data quality. The maps putatively corresponding to Vim were those derived by precentral and dentate nucleus-thalamic connectivity. However, tractography-derived functional targets showed remarkable differences in shape and sizes when compared to a ground truth model based on histochemical staining on seriate sections of human brain. Thalamic voxels connected to contralateral dentate nucleus resulted to be the closest to literature-derived stimulation points for essential tremor but at the same time showing the most remarkable inter-subject variability. Finally, the volume of connectivity parcels resulted to be significantly influenced by data quality and parcellation pipelines. Hence, caution is warranted when performing thalamic connectivity-based segmentation for stereotactic targeting.

Cognitive impairment in obstructive sleep apnea syndrome: a descriptive review.

PURPOSE: Obstructive sleep apnea syndrome is a clinical sleep disorder defined by total or partial airflow restraint during sleep that results in fragmented sleep and hypoxemia, impacting negatively with cognitive functioning. This review was conducted on studies investigating structural brain alteration and cognitive impairment in obstructive sleep apnea syndrome. METHOD: We searched on PubMed databases and screening references of included studies and review articles for additional citations. From initial 190 publications, only 17 met search criteria and described the cognitive impairment in obstructive sleep apnea syndrome. RESULTS: Findings showed that patients with this syndrome had worse performance than healthy controls in attention, memory, and executive functions, showing specific neuroanathomical features. Cognitive impairment is also related to the severity of pathology. Treatment could improve certain cognitive aspects. CONCLUSIONS: Cognitive deficits seem to be mainly attributable to decreased daytime vigilance and nocturnal hypoxemia.

Cognitive Decline in Rheumatoid Arthritis: Insight into the Molecular Pathogenetic Mechanisms.

Cognitive decline refers to a deterioration of intellectual and learning abilities and related memory problems, and is often associated with behavioral alterations, which prevents sufferers from carrying out the most common daily activities, such as maintaining normal productive interpersonal relationships, communicating, and leading an autonomous life. Numerous studies have highlighted the association between cognitive decline and autoimmune disorders, including rheumatoid arthritis (RA). RA is a chronic, inflammatory, autoimmune disease that involves systems and organs other than the bones and joints, with varying severity among patients. Here, we review the studies investigating the link between cognitive decline and RA, focusing on the main molecular pathogenetic mechanisms involved. The emerging body of data suggests that clinical, psychological, and biological factors may contribute to the pathogenesis of cognitive decline in RA, including cardiovascular complications, chronic pain, depression, inflammatory factors, changes in hormone levels, drug side effects, and genetics. Further studies are warranted in order to fully clarify the basis underlying the association between cognitive decline and RA and to find new possible diagnostic strategies and therapeutic targets for RA patients.

A multidisciplinary Telehealth approach for community dwelling older adults.

Telemedicine may be used for the continuity of care in several chronic conditions. Sixty frail old people were enrolled along with their primary caregivers, and randomly divided into two groups: 30 of them received a multi-specialist telemedicine care, whilst the other 30 were treated in their usual territory care. All of the patients were evaluated through a clinical and psychometric battery at baseline (T0), after 6 months (T1), and at the end of the study (T2). It was found that telemedicine was more effective than the traditional approach in mood improvement (p < 0.001), behaviour (p < 0.01) and ADL/IADL (p < 0.01/0.04), as well as nutritional status. These changes increased over time (from T0 to T1), the caregivers' burden decreased, and system usability was rated as good. Telemedicine could be considered an important tool to improve the psychological health and quality of the life of older frail patients living at home.

How patients with mild dementia living in a nursing home benefit from dementia cafés: a case-control study focusing on psychological and behavioural symptoms and caregiver burden.

BACKGROUND: Dementia is a syndrome, mainly due to neurodegeneration, affecting cognition, behaviour, feelings and relationships. Pharmacological treatment is still challenging and thus different ways to improve/slow down the disease are necessary. METHODS: Twenty-five subjects with mild dementia, living in a nursing home, and their relatives were invited to attend a dementia cafe, a community group which provides support for families affected by dementia. Each patient was evaluated by a neuropsychologist, through the administration of a specific neuropsychological battery, before and at the end of the study. Their outcomes were compared to a matched group of patients with dementia receiving psycho-counselling. RESULTS: After the dementia cafe meetings, patients showed higher significant changes in mood (P < 0.01), behavioural symptoms (P < 0.001), quality of life (P < 0.001), and caregiver burden (P < 0.001). The control group significantly improved only in quality of life with a reduction of caregiver burden. CONCLUSIONS: Our findings confirm that patients with dementia may benefit from the dementia cafe, especially concerning behavioural symptoms. Moreover, caregivers find these cafés to be welcoming, relaxed places to socialise and access support and information. Future dementia cafés should create programs and comfortable environments answering to the different needs of the patients.

Spatially coherent and topographically organized pathways of the human globus pallidus.

Internal and external segments of globus pallidus (GP) exert different functions in basal ganglia circuitry, despite their main connectional systems share the same topographical organization, delineating limbic, associative, and sensorimotor territories. The identification of internal GP sensorimotor territory has therapeutic implications in functional neurosurgery settings. This study is aimed at assessing the spatial coherence of striatopallidal, subthalamopallidal, and pallidothalamic pathways by using tractography-derived connectivity-based parcellation (CBP) on high quality diffusion MRI data of 100 unrelated healthy subjects from the Human Connectome Project. A two-stage hypothesis-driven CBP approach has been carried out on the internal and external GP. Dice coefficient between functionally homologous pairs of pallidal maps has been computed. In addition, reproducibility of parcellation according to different pathways of interest has been investigated, as well as spatial relations between connectivity maps and existing optimal stimulation points for dystonic patients. The spatial organization of connectivity clusters revealed anterior limbic, intermediate associative and posterior sensorimotor maps within both internal and external GP. Dice coefficients showed high degree of coherence between functionally similar maps derived from the different bundles of interest. Sensorimotor maps derived from the subthalamopallidal pathway resulted to be the nearest to known optimal pallidal stimulation sites for dystonic patients. Our findings suggest that functionally homologous afferent and efferent connections may share similar spatial territory within the GP and that subcortical pallidal connectional systems may have distinct implications in the treatment of movement disorders.

Impaired Recognition of Facial Emotion in Patients With Parkinson Disease Under Dopamine Therapy.

INTRODUCTION: Parkinson disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms. The impaired ability to recognize facial emotion expressions represents an important nonmotor symptom. The aim of this study is to investigate the ability in recognizing facial emotion expressions in patients with PD under dopamine replacement therapy. METHODS: Thirty medicated patients with PD and 15 healthy controls (HC) were enrolled. All participants performed the Ekman 60-Faces test for emotional recognition. All patients underwent a neuropsychological evaluation for global cognitive functioning, depression, and anxiety. RESULTS: Patients with PD were impaired in recognizing emotions. Significant differences between PD and HC were found in Ekman 60-Faces test scores (P < .001), and in Ekman 60-Faces test subscales, in particular, sadness, fear, disgust, anger, and surprise (P < .001). CONCLUSIONS: The nigrostriatal dopaminergic depletion seems to determine emotional information processing dysfunction. This relevant nonmotor symptom could have consequences in daily living reducing interactions and social behavioral competence.

Improving motor performance in Parkinson's disease: a preliminary study on the promising use of the computer assisted virtual reality environment (CAREN).

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by various motor symptoms including balance and gait impairment. Several studies have shown that physiotherapy, cueing techniques, treadmill training, and cognitive movement strategies are useful in improving balance and gait in patients with PD. Devices employing virtual reality (VR) have been shown to be promising in neurorehabilitation as they can provide the patients with multisensory stimulation creating a realistic environment and improve the motivation and the adhesion of patients to the rehabilitation program. This preliminary study is aimed at testing the efficacy and feasibility of gait training based on the computer-assisted virtual reality environment (CAREN) in a sample of PD. METHODS: In this preliminary study, 22 outpatients affected by PD who attended the Behavioral and Robotic Neurorehab Laboratory of the IRCCS Neurolesi between August 2017 and October 2018 were enrolled. All PD patients underwent 20 conventional physiotherapy sessions followed by 3-month of rest. Then, the patients were provided with 20 sessions of CAREN training. Gait and balance performances were rated before, after each training protocol, and 3 months later. Gait analysis was also performed before and after CAREN training. RESULTS: All patients completed both of the rehabilitation trainings without any adverse event. All considered scales improved significantly at the end of both rehabilitation treatments. However, patients presented with a greater clinical improvement after the CAREN training, compared with conventional physiotherapy. In particular, patients walked faster and with more stability, with wider, longer steps. CONCLUSIONS: Even though further neurophysiological details are required to identify the patients who may benefit from CAREN training, our findings suggest that this innovative device is an effective and feasible tool to train balance and gait in patients with PD.

Neuropsychological functions and psychiatric symptoms in late-onset manifestation of pantothenate kinase-associated neurodegeneration: a clinical case report.

Purpose of the study: Pantothenate Kinase-associated Neurodegeneration (PKAN) is a form of Neurodegeneration with brain iron accumulation (NBIA) due to gene mutations. Classical phenotype showed progressive neurological symptoms associated to a characteristic pattern of basal ganglia iron deposits. The atypical case, with adult-onset manifestation, could have neuropsychiatric symptoms with behavioral deficits. We described an adult-onset case of Pantothenate Kinase-associated Neurodegeneration.Materials and methods: The patient underwent neuropsychological and psychiatric evaluation and Magnetic Resonance Imaging, respectively for cognitive and behavioral assessment and to confirm the characteristic findings of this syndrome.Results: The patient showed atypical phenotype of Pantothenate Kinase-associated Neurodegeneration, characterized by language deficits, dixesecutive, and psychiatric manifestations, such as obsessive ideation, impulsivity, and disinhibition.Conclusions: This description could be helpful to a more correct diagnosis and clinical management.

Role of visual P300 in cognitive assessment of subacute stroke patients: a longitudinal study.

Aim: The aim of this study was to assess if pre- and post- event related potentials (ERPs) components after visual stimulation training admitted differences exist in subacute stroke patients and to observe the outcome markers of cognitive functions recovery by using Neurowave system.Materials and Methods: Eighteen ischemic subacute stroke patients were enrolled and underwent to neuropsychological evaluation and ERPs recording at two time points, at baseline (T0) and after 3 months from (T1). All patients were stimulated with customized images for three days a week.Findings: Intra group analysis showed a significance difference in ERPs parameters and neuropsychological tests. Correlation analysis showed a significant relation between neuropsychological and ERP values.Conclusion: Our findings confirm that P300 ERPs' component could be a predictive marker for cognitive recovery of ischemic subacute stroke patients. Intensive programs of neurosensory stimulation could facilitate recovery of cognitive and attentive functions in subacute cerebrovascular disease.

Effects of Combined Admistration of Imatinib and Sorafenib in a Murine Model of Liver Fibrosis.

Liver fibrosis is defined as excessive extracellular matrix deposition in the hepatic parenchyma as a consequence of complex interactions among matrix-producing hepatic stellate cells (HSCs) and liver-resident and infiltrating cells. In addition to the liver, the process of fibrosis may represent end-stage disease of several diseases including kidneys, lungs, spleens, heart, muscles and at certain extent, the central nervous system and the peripheral nerves. To date, antifibrotic treatment of fibrosis represents an unconquered area for drug development. The aim of the present study was to test the efficacy of a new drug combination for the treatment of hepatic fibrosis in order to provide a proof-of-concept for the use of therapeutic agents in clinical practice. For this purpose, we have studied the effects of the PDGF inhibitor imatinib and the angiogenesis inhibitor sorafenib, administered alone or in combination, in reducing the progression of the fibrogenetic process in a pre-clinical model of liver damage induced in mice by repeated administration of Concanavalin A (ConA), resembling long-tern autoimmune hepatitis. Our results suggest that treatments with imatinib and sorafenib can modulate potently and, in a superimposable fashion, the fibrinogenic process when administered alone. However, and in agreement with the computational data presently generated, they only exert partial overlapping antifibrotic effects in modulating the main pathways involved in the process of liver fibrosis, without significant additive or synergist effects, when administered in combination.

Teleassistance for frail elderly people: A usability and customer satisfaction study.

Scientific advances and new information and communication technologies have facilitated the development of services that allow older people to stay at home as long as possible. In this study, we evaluated the usability and the patient satisfaction of a novel telemedicine system. All enrolled participants underwent a teleassistance program, which included remote surveillance and tele-counselling services with different health-care professionals, including nurses. We administered a specific questionnaire to assess the quality of the service and the patient satisfaction, whereas the System Usability Scale was used to evaluate the patient's usability of the system. Our findings showed that telemedicine might be useful in improving health and quality of life of disadvantaged older people, especially if affected by severe comorbidity and living far from health services. Moreover, the patient satisfaction concerning the service was rated as good by the majority of the participants, although the usability rate was not so high.

Anatomical Characterization of the Human Structural Connectivity between the Pedunculopontine Nucleus and Globus Pallidus via Multi-Shell Multi-Tissue Tractography.

Background and objectives: The internal (GPi) and external segments (GPe) of the globus pallidus represent key nodes in the basal ganglia system. Connections to and from pallidal segments are topographically organized, delineating limbic, associative and sensorimotor territories. The topography of pallidal afferent and efferent connections with brainstem structures has been poorly investigated. In this study we sought to characterize in-vivo connections between the globus pallidus and the pedunculopontine nucleus (PPN) via diffusion tractography. Materials and Methods: We employed structural and diffusion data of 100 subjects from the Human Connectome Project repository in order to reconstruct the connections between the PPN and the globus pallidus, employing higher order tractography techniques. We assessed streamline count of the reconstructed bundles and investigated spatial relations between pallidal voxels connected to the PPN and pallidal limbic, associative and sensorimotor functional territories. Results: We successfully reconstructed pallidotegmental tracts for the GPi and GPe in all subjects. The number of streamlines connecting the PPN with the GPi was greater than the number of those joining it with the GPe. PPN maps within pallidal segments exhibited a distinctive spatial organization, being localized in the ventromedial portion of the GPi and in the ventral-anterior portion in the GPe. Regarding their spatial relations with tractography-derived maps of pallidal functional territories, the highest value of percentage overlap was noticed between PPN maps and the associative territory. Conclusions: We successfully reconstructed the anatomical course of the pallidotegmental pathways and comprehensively characterized their topographical arrangement within both pallidal segments. PPM maps were localized in the ventromedial aspect of the GPi, while they occupied the anterior pole and the most ventral portion of the GPe. A better understanding of the spatial and topographical arrangement of the pallidotegmental pathways may have pathophysiological and therapeutic implications in movement disorders.

Structural Connectivity-Based Parcellation of the Dopaminergic Midbrain in Healthy Subjects and Schizophrenic Patients.

Background and objectives: Functional deregulation of dopaminergic midbrain regions is a core feature of schizophrenia pathophysiology. Anatomical research on primates suggests that these regions may be subdivided into distinct, topographically organized functional territories according to their connectivity to the striatum. The aim of the present work was the reconstruction of dopaminergic midbrain subregions in healthy subjects and schizophrenic patients and the evaluation of their structural connectivity profiles. Materials and Methods: A hypothesis-driven connectivity-based parcellation derived from diffusion tractography was applied on 24 healthy subjects and 30 schizophrenic patients to identify distinct territories within the human dopaminergic midbrain in vivo and non-invasively. Results: We identified a tripartite subdivision of dopaminergic midbrain, including limbic, prefrontal and sensorimotor territories. No significant differences in structural features or connectivity were found between subjects and patients. Conclusions: The parcellation scheme proposed herein may help to achieve detailed characterization of structural and functional anomalies of the dopaminergic midbrain in schizophrenic patients.