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Metabolic syndrome (MS), a cluster of metabolic risk factors, ranging from abdominal obesity, dyslipidaemia, hypertension, type 2 diabetes and non-alcoholic fatty liver disease [...]

Continual mapping and monitoring of impervious surfaces are crucial activities to support sustainable urban management strategies and to plan effective actions for environmental changes. In this context, impervious surface coverage is increasingly becoming an essential indicator for assessing urbanization and environmental quality, with several works relying on satellite imagery to determine it. However, although satellite imagery is typically available with a frequency of 3–10 days worldwide, imperviousness maps are released at most annually as they require a huge human effort to be produced and validated. Attempts have been made to extract imperviousness maps from satellite images using machine learning, but (i) the scarcity of reliable and detailed ground truth (ii) together with the need to manage different spectral bands (iii) while making the resulting system easily accessible to the end users is limiting their diffusion. To tackle these problems, in this work we introduce a deep-learning-based approach to extract imperviousness maps from multi-spectral Sentinel-2 images leveraging a very detailed imperviousness map realised by the Italian department for environment protection as ground truth. We also propose a scalable and portable inference pipeline designed to easily scale the approach, integrating it into a web-based Geographic Information System (GIS) application. As a result, even non-expert GIS users can quickly and easily calculate impervious surfaces for any place on Earth (accuracy >95%), with a frequency limited only by the availability of new satellite images.

Background: The aim was to verify whether the density of particulate matter (PM10), the climate, and the mobility of people can influence the pandemic in the 19 regions and in the two autonomous Italian provinces as incidence rate and lethality. Design and Methods: The incidence rates per 100,000 inhabitants and the case fatality ratio (CFR) (dependent variables) in all Italian regions were calculated in January 2021 at John Hopkins University Coronavirus Center. The independent variables were: -Minimum average temperatures in the same month (January) of 2020, -Average pollution of PM10 in the air in each region in the last year available reported on a 0-10 scale to 0 = total absence of PM10 to 10 maximum pollutions. -Number of places in hotels occupied per inhabitants in 2020. Linear regression and Multiple Regression Analysis were carried out. Results: The spread of the COVID-19 in the Italian regions seems to be related to pollution of PM10, the number of beds occupied in hotels (as an index of mobility and temperature (indirect correlation). On the contrary, the CFR correlates inversely with temperature but not with pollution. Measuring the concomitant effect of two independent variables by means of Multiple Regression Analysis, temperature and pollution show a synergistic effect on COVID-19 incidence. Conclusions: The study seems to confirm the literature on the influence of temperature on the lethality of COVID-19 but adds the new results of an inverse relationship between the spread of the virus and low temperature in regions between the Mediterranean area (which includes southern Italy and Sicily and Sardinia islands) and the cold European temperate zone which includes the northern regions under the Alps. A new date also concerns the summation effect of the risk between cold weather and PM10 air pollution was found. Due to several methodic weakness the study has an exploratory than conclusive relevance.

Abstract Background Family and friends (carer) involvement in the treatment of people with mental illness is widely recommended. However, the implementation remains poor, especially during hospital treatment, where carers report being excluded from care decisions. Methods We developed structured clinical procedures to maximise carer involvement in inpatient treatment. The aim of this study was to test their feasibility across four inpatient wards in East London and explore experiences of the participants. The intervention was delivered by clinicians (social therapists, nurses and psychiatrists) who were trained by the research team. Thirty patients and thirty carers received the intervention and completed research assessments and qualitative interviews after the intervention. 80% of the patients were followed up after six weeks of admission to complete quantitative questionnaires. Six clinicians were interviewed to explore their views on the intervention. Thematic analysis was used to analyse qualitative data. Results The intervention was found to be feasible to be delivered within the first week of admission in more than a half of the patients (53%) who provided consent. The main reasons why the interventions was not delivered in the remaining 47% of patients included staff or carers not being available, withdrawal of consent from the patient or patient being discharged prior to the intervention. Two themes were identified through thematic analysis. The first captured participant experiences of the intervention as facilitating a three-way collaborative approach to treatment. The second covered how patients’ mental states and practicalities of inpatient care acted as barriers and facilitators to the intervention being implemented. Conclusions Carer involvement in hospital treatment for mental illness is more difficult to implement than is commonly thought. This study has shown that a simple structured approach can facilitate a trialogue and that patients, clinicians and carers appreciate this approach to care. Our intervention provides clear and simple manualised clinical procedures that clinicians can follow. However, even the implementation of such procedures may be challenging in the absence of wider organisational support. The involvement of senior managers and clinical leaders might play a key role in overcoming barriers and support front-line clinicians to prioritise and implement carer involvement.

Abstract Background Synaptic dysfunction, named synaptopathy, due to inflammatory status of the central nervous system (CNS) is a recognized factor potentially underlying both motor and cognitive dysfunctions in neurodegenerative diseases. To gain knowledge on the mechanistic interplay between local inflammation and synapse changes, we compared two diverse inflammatory paradigms, a cytokine cocktail (CKs; IL-1β, TNF-α, and GM-CSF) and LPS, and their ability to tune GABAergic current duration in spinal cord cultured circuits. Methods We exploit spinal organotypic cultures, single-cell electrophysiology, immunocytochemistry, and confocal microscopy to explore synaptic currents and resident neuroglia reactivity upon CK or LPS incubation. Results Local inflammation in slice cultures induced by CK or LPS stimulations boosts network activity; however, only CKs specifically reduced GABAergic current duration. We pharmacologically investigated the contribution of GABAAR α-subunits and suggested that a switch of GABAAR α1-subunit might have induced faster GABAAR decay time, weakening the inhibitory transmission. Conclusions Lower GABAergic current duration could contribute to providing an aberrant excitatory transmission critical for pre-motor circuit tasks and represent a specific feature of a CK cocktail able to mimic an inflammatory reaction that spreads in the CNS. Our results describe a selective mechanism that could be triggered during specific inflammatory stress.

Abstract Background Severe mental illness (SMI) presents a major burden to societies worldwide. Low- and middle-income countries (LMICs) often do not have sufficient financial resources and qualified staff to provide extensive specialised services for outpatients with SMI. Our research therefore aims to explore and test low-cost interventions that use existing resources in routine patient-clinician meetings, families and communities. Methods In Bosnia-Herzegovina, Colombia and Uganda, three psychosocial interventions will be tested, i.e. making patient-clinician meetings therapeutically effective through DIALOG+, family involvement in multi-family group meetings, and support for patients in befriending schemes with volunteers. All interventions will be provided to patients with SMI, delivered over a six-month period and evaluated with assessments at baseline and after six and 12 months. We will conduct nine trials including non-controlled trials, non-randomised controlled trials and randomised controlled trials (RCTs). Core outcome criteria will be used across all studies. However, details of study delivery and additional outcome criteria vary to accommodate local contexts, interests and priorities. The studies will be analysed separately, but with the option to compare and combine findings. Discussion The approach provides the opportunity to learn from commonalities and differences in the results and experiences across the three resource-oriented approaches and the three countries. If successfully implemented the studies can lead to more extensive research and are expected to inform health policies and clinical practice of community care for patients with SMI in the three participating countries and other LMICs. Trial registration All RCTs were registered prospectively and non-randomised trials retrospectively within the ISRCTN Registry. DIALOG+ in Uganda: ISRCTN25146122 (Date of Registration: 20/11/2018, prospective); DIALOG+ in Colombia: ISRCTN83333181 (Date of Registration: 20/11/2018, prospective); DIALOG+ in Bosnia-Herzegovina: ISRCTN13347129 (Date of Registration: 20/11/2018, prospective); Volunteer Support in Uganda: ISRCTN86689958 (Date of Registration: 04/03/2019, retrospective); Volunteer Support in Colombia: ISRCTN72241383 (Date of Registration: 04/03/2019, retrospective);Volunteer Support in Bosnia-Herzegovina: ISRCTN51290984 (Date of Registration: 20/11/2018, prospective); Family Involvement in Uganda: ISRCTN78948497 (Date of Registration: 04/03/2019, retrospective); Family Involvement in Colombia: ISRCTN11440755 (Date of Registration: 04/03/2019, retrospective); Family Involvement in Bosnia-Herzegovina: ISRCTN13347355 (Date of Registration: 20/11/2018, prospective).

Abstract Background People participation teams are being established in many British NHS Trusts. They support active service user involvement in staff recruitment interviews, in evaluations of care and in programmes to improve services. No studies exploring experience of people involved in these activities are available in published mental health literature. In this project we explored benefits experienced and suggestions for improvement provided by service users. Methods The design, materials and methods of the project were developed in workshops including N = 15 service users. Three service user researchers were trained to carry out research interviews and qualitative analysis of the data. They were responsible for the management of the project on a day-to-day basis with weekly supervision by academic researchers and authored this paper. The service user researchers interviewed people with at least 1 year of experience of being involved in a People Participation team activities. Interviews were based on a topic guide, which was developed in workshops with a larger number of service users (N = 15) and explored reasons for joining the group, how participation helped recovery and suggestions for service improvement. Results Fifteen service users were recruited and interviewed. Reasons for joining the group were identified: to “give back” to the service, to influence service change, curiosity, desire to meet like-minded people and to structure the day. Benefits reported included: sharing experiences, improving self-confidence, feeling valued, having a better understanding of services, overcoming personal fears, and developing better coping mechanisms for psychological difficulties. Being involved in People Participation activities helped to gain or refresh listening and interpersonal skills, communication skills, public speaking and creative skills and to develop better ways to cope with conflict. Suggestions for improvement were focused on changing staff attitudes, further promoting participation (e.g. through websites), simplifying payment procedures and establishing a moving-on support system to help people to access regular employment and gain full social inclusion. Conclusions Our findings showed that People Participation initiatives can have benefits at least for some patients and help their recovery through a positive effect on self-confidence, providing room for feeling valued and for obtaining or refreshing personal skills. This provides support for the development and refinement of People Participation Teams and for larger scale research to test their effects.

Introduction Hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) or with normal C1-INH is characterized by recurrent swellings due to uncontrolled production of vasoactive mediators, among which bradykinin (BK) is crucial. Through the binding and activation of the two human BK-receptors, kinins may have dual beneficial and deleterious effects in vascular and inflammation physiopathology by inducing oxidative stress. We aimed to assess the serum concentrations of advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs) in patients affected by HAE. Material and methods Blood samples were collected to measure the serum concentrations of AGEs and AOPPs by spectrofluorimetric and spectrophotometric methods in patients affected by C1-INH-HAE and FXII-HAE during the remission state. Results We showed that the circulating levels of AOPPs observed on control group (0.94 (0.36) nmol/mg) were significantly lower than those observed on the C1-INH-HAE group (1.68 (0.47) nmol/mg; p = 0.002) and FXII-HAE (1.50 (0.27) nmol/mg; p = 0.001). Moreover, the circulating levels of AGEs were significantly higher in C1-INH-HAE group (211.58 (151.05) AU/g; p = 0.02) than the FXII group (141.48 (89.59) AU/g), thus demonstrating a state of heightened oxidative stress. Conclusions Our observations show additional underlying events involved in HAE and are of central importance for further investigations of differences in bradykinin receptors signaling among the two disease subgroups.

Background: Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) is a severe non-infectious complication of Common Variable Immunodeficiency (CVID), often associated with extrapulmonary involvement. Due to a poorly understood pathogenesis, GLILD diagnosis and management criteria still lack consensus. Accordingly, it is a relevant cause of long-term loss of respiratory function and is closely associated with a markedly reduced survival. The aim of this study was to describe clinical, immunological, laboratory and functional features of GLILD, whose combination in a predictive model might allow a timely diagnosis.Methods: In a multicenter retrospective cross-sectional study we enrolled 73 CVID patients with radiologic features of interstitial lung disease (ILD) associated to CVID (CVID-ILD) and 125 CVID patients without ILD (controls). Of the 73 CVID-ILD patients, 47 received a definite GLILD diagnosis while 26 received a clinical-radiologic diagnosis of CVID related ILD defined as uILD.Results: In GLILD group we found a higher prevalence of splenomegaly (84.8 vs. 39.2%), autoimmune cytopenia (59.6 vs. 6.4%) and bronchiectasis (72.3 vs. 28%), and lower IgA and IgG serum levels at CVID diagnosis. GLILD patients presented lower percentage of switched-memory B cells and marginal zone B cells, and a marked increase in the percentage of circulating CD21lo B cells (14.2 vs. 2.9%). GLILD patients also showed lower total lung capacity (TLC 87.5 vs. 5.0%) and gas transfer (DLCO 61.5 vs. 5.0%) percent of predicted. By univariate logistic regression analysis, we found IgG and IgA levels at CVID diagnosis, presence of splenomegaly and autoimmune cytopenia, CD21lo B cells percentage, TLC and DCLO percent of predicted to be associated to GLILD. The joint analysis of four variables (CD21lo B cells percentage, autoimmune cytopenia, splenomegaly and DLCO percent of predicted), together in a multiple logistic regression model, yielded an area under the ROC curve (AUC) of 0.98 (95% CI: 0.95-1.0). The AUC was only slightly modified when pooling together GLILD and uILD patients (0.92, 95% CI: 0.87-0.97).Conclusions: we propose the combination of two clinical parameters (splenomegaly and autoimmune cytopenia), one lung function index (DLCO%) and one immunologic variable (CD21lo%) as a promising tool for early identification of CVID patients with interstitial lung disease, limiting the use of aggressive diagnostic procedures.

Background and aims: Severe asthma is burdened by frequent exacerbations and use of oral corticosteroids (OCS) which worsen patients’ health and increase healthcare spending. Aim of this study was to assess the clinical and economic effect of adding mepolizumab (MEP) for the treatment of these patients. Methods: Patients >18 years old, referred to 8 asthma clinics, starting MEP between May 2017 and December 2018, were enrolled and followed-up for 12 months. Information in the 12 months before mepolizumab were collected retrospectively. The evaluation parameters included: OCS use, number of exacerbations/hospitalizations, concomitant therapies, comorbidity, and annual number of working days lost due to the disease. The primary objective was to compare the annual total cost per patient pre- and post-MEP. Secondary outcomes included rates of exacerbations and number of OCS-dependent patients. Results: 106 patients were enrolled in the study: 46 male, median age 58 years. Mean annual cost pre- and post-MEP (cost of biologic excluded) was €3996 and €1,527, respectively. Total savings due to MEP resulted in €2469 (95%CI 1945–2993), 62% due to exacerbations reduction and 33% due to productivity increase. Such savings could fund about 22% of the total cost of MEP for one year. The introduction of MEP induced a clinical benefit by reducing both OCS-dependent patients (OR = 0.12, 95%CI 0.06–0.23) and exacerbation rate (RR = 0.19, 95%CI 0.15–0.24). Conclusions: Patients with severe eosinophilic asthma experienced a clinical benefit in asthma control adding MEP to standard therapy. Biologic therapy can be, partially, funded by the savings produced by patients’ improvement.

Dans l’histoire de la musique occidentale, le statut de l’atelier – comme lieu du faire et lieu de transmission – semble inexistant. À première vue, il n’y a pas d’équivalent en musique des ateliers de sculpture et de peinture de la Renaissance, du baroque ou du XIXe siècle qui, progressivement, deviendront à la fois des lieux d’exposition et de fabrique de l’oeuvre. Cette histoire des ateliers d’artistes ne traverse pas de façon aussi visible celle de la fabrique des oeuvres musicales. Notre hypothèse est que cette histoire invisible de l’atelier musical est en partie due à la nature même de la musique, éclatée en plusieurs lieux et points d’écoute.

Background The diversity in the clinical course of COVID-19 has been related to differences in innate and adaptative immune response mechanisms. Natural killer (NK) lymphocytes are critical protagonists of human host defense against viral infections. It would seem that reduced circulating levels of these cells have an impact on COVID-19 progression and severity. Their activity is strongly regulated by killer-cell immuno-globulin-like receptors (KIRs) expressed on the NK cell surface. The present study’s focus was to investigate the impact of KIRs and their HLA Class I ligands on SARS-CoV-2 infection. Methods KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 396 Sardinian patients with SARS-CoV-2 infection. Comparisons were made between 2 groups of patients divided according to disease severity: 240 patients were symptomatic or paucisymptomatic (Group A), 156 hospitalized patients had severe disease (Group S). The immunogenetic characteristics of patients were also compared to a population group of 400 individuals from the same geographical areas. Results Substantial differences were obtained for KIR genes, KIR haplotypes and KIR-HLA ligand combinations when comparing patients of Group S to those of Group A. Patients in Group S had a statistically significant higher frequency of the KIR A/A haplotype compared to patients in Group A [34.6% vs 23.8%, OR = 1.7 (95% CI 1.1–2.6); P = 0.02, Pc = 0.04]. Moreover, the KIR2DS2/HLA C1 combination was poorly represented in the group of patients with severe symptoms compared to those of the asymptomatic-paucisymptomatic group [33.3% vs 50.0%, OR = 0.5 (95% CI 0.3–0.8), P = 0.001, Pc = 0.002]. Multivariate analysis confirmed that, regardless of the sex and age of the patients, the latter genetic variable correlated with a less severe disease course [ORM = 0.4 (95% CI 0.3–0.7), PM = 0.0005, PMC = 0.005]. Conclusions The KIR2DS2/HLA C1 functional unit resulted to have a strong protective effect against the adverse outcomes of COVID-19. Combined to other well known factors such as advanced age, male sex and concomitant autoimmune diseases, this marker could prove to be highly informative of the disease course and thus enable the timely intervention needed to reduce the mortality associated with the severe forms of SARS-CoV-2 infection. However, larger studies in other populations as well as experimental functional studies will be needed to confirm our findings and further pursue the effect of KIR receptors on NK cell immune-mediated response to SARS-Cov-2 infection.

AimSARS-CoV-2 infection is a world-wide public health problem. Several aspects of its pathogenesis and the related clinical consequences still need elucidation. In Italy, Sardinia has had very low numbers of infections. Taking advantage of the low genetic polymorphism in the Sardinian population, we analyzed clinical, genetic and immunogenetic factors, with particular attention to HLA class I and II molecules, to evaluate their influence on susceptibility to SARS-CoV-2 infection and the clinical outcome.Method and MaterialsWe recruited 619 healthy Sardinian controls and 182 SARS-CoV-2 patients. Thirty-nine patients required hospital care and 143 were without symptoms, pauci-symptomatic or with mild disease. For all participants, we collected demographic and clinical data and analyzed the HLA allele and haplotype frequencies.ResultsMale sex and older age were more frequent in hospitalized patients, none of whom had been vaccinated during the previous seasonal flu vaccination campaignes. Compared to the group of asymptomatic or pauci-symptomatic patients, hospitalized patients also had a higher frequency of autoimmune diseases and glucose-6-phosphate-dehydrogenase (G6PDH) deficiency. None of these patients carried the beta-thalassemia trait, a relatively common finding in the Sardinian population. The extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 [OR 0.1 (95% CI 0–0.6), Pc = 0.015] was absent in all 182 patients, while the HLA-C*04:01 allele and the three-loci haplotype HLA-A*30:02, B*14:02, C*08:02 [OR 3.8 (95% CI 1.8–8.1), Pc = 0.025] were more frequently represented in patients than controls. In a comparison between in-patients and home care patients, the HLA-DRB1*08:01 allele was exclusively present in the hospitalized patients [OR > 2.5 (95% CI 2.7–220.6), Pc = 0.024].ConclusionThe data emerging from our study suggest that the extended haplotype HLA-A*02:05, B*58:01, C*07:01, DRB1*03:01 has a protective effect against SARS-CoV-2 infection in the Sardinian population. Genetic factors that resulted to have a negative influence on the disease course were presence of the HLA-DRB1*08:01 allele and G6PDH deficiency, but not the beta-thalassemic trait. Absence of influenza vaccination could be a predisposing factor for more severe disease.

Much is known, but there is also much more to discover, about the actions that thyroid hormones (TH) exert on metabolism. Indeed, despite the fact that thyroid hormones are recognized as one of the most important regulators of metabolic rate, much remains to be clarified on which mechanisms control/regulate these actions. Given their actions on energy metabolism and that mitochondria are the main cellular site where metabolic transformations take place, these organelles have been the subject of extensive investigations. In relatively recent times, new knowledge concerning both thyroid hormones (such as the mechanisms of action, the existence of metabolically active TH derivatives) and the mechanisms of energy transduction such as (among others) dynamics, respiratory chain organization in supercomplexes and cristes organization, have opened new pathways of investigation in the field of the control of energy metabolism and of the mechanisms of action of TH at cellular level. In this review, we highlight the knowledge and approaches about the complex relationship between TH, including some of their derivatives, and the mitochondrial respiratory chain.