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Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modeled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

Increasing evidence suggests that early neurodevelopmental defects in Huntington’s disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organoids. Gene-expression analysis showed that control organoid overlapped with mature human fetal cortical areas, while HD organoids correlated with the immature ventricular zone/subventricular zone. We also report that defects in neuroectoderm and rosette formation could be rescued by molecular and pharmacological approaches leading to a recovery of striatal identity. These results show that mutant huntingtin precludes normal neuronal fate acquisition and highlights a possible connection between mutant huntingtin and abnormal neural development in HD.

Background This article investigates the hospital costs related to the management of COVID-19 positive patients, requiring a hospitalization (from the positivity confirmation to discharge, including rehabilitation activities). Methods A time-driven activity-based costing analysis, grounding on administrative and accounting flows provided by the management control, was implemented to define costs related to the hospital management of COVID-19 positive patients, according to real-word data, derived from six public Italian Hospitals, in 2020. Results Results reported that the higher the complexity of care, the higher the hospitalization cost per day (low-complexity = €475.86; medium-complexity = €700.20; high-complexity = €1,401.65). Focusing on the entire clinical pathway, the overall resources absorption, with the inclusion of rehabilitation costs, ranged from 6,198.02€ to 32,141.20€, dependent from the patient’s clinical condition. Conclusions Data could represent the baseline cost for COVID-19 hospital management, thus being useful for the further development of proper reimbursement tariffs devoted to hospitalized infected patients.

Interleukin 10 (IL-10) is an antiinflammatory cytokine, but also promotes B cell responses and plays a pathogenic role in systemic lupus erythematosus (SLE). CD4⁺CCR6⁺IL-7R⁺T cells from human tonsils produced IL-10 following stimulation by naïve B cells, which promoted B cell immunoglobulin G (IgG) production. These tonsillar CCR6⁺B helper T cells were phenotypically distinct from follicular helper T (TFH) cells and lacked BCL6 expression. In peripheral blood, a CCR6⁺T cell population with similar characteristics was identified, which lacked Th17- and TFH-associated gene signatures and differentiation-associated surface markers. CD4⁺CCR6⁺T cells expressing IL-10, but not IL-17, were also detectable in the spleens of cytokine reporter mice. They provided help for IgG production in vivo, and expanded systemically in pristane-induced lupus-like disease. In SLE patients, CD4⁺CCR6⁺IL-7R⁺T cells were associated with the presence of pathogenic anti-dsDNA (double-stranded DNA) antibodies, and provided spontaneous help for autoantibody production ex vivo. Strikingly, IL-10–producing CCR6⁺T cells were highly abundant in lymph nodes of SLE patients, and colocalized with B cells at the margins of follicles. In conclusion, we identified a previously uncharacterized population of extrafollicular B helper T cells, which produced IL-10 and could play a prominent pathogenic role in SLE.

Follicular helper T cells (TFHs) are a key component of adaptive immune responses as they help antibody production by B cells. Differentiation and function of TFH cells are controlled by the master gene BCL6, but it is largely unclear how this transcription repressor specifies the TFH program. Here we asked whether BCL6 controlled helper function through down-regulation of specific microRNAs (miRNAs). We first assessed miRNA expression in TFH cells and defined a TFH-specific miRNA signature. We report that hsa–miR-31–5p (miR-31) is down-regulated in TFH; we showed that BCL6 suppresses miR-31 expression by binding to its promoter; and we demonstrated that miR-31 inhibits the expression of molecules that control T-helper function, such as CD40L and SAP. These findings identify a BCL6-initiated inhibitory circuit that stabilizes the follicular helper T cell program at least in part through the control of miRNA transcription. Although BCL6 controls TFH activity in human and mouse, the role of miR-31 is restricted to human TFH cell differentiation, reflecting a species specificity of the miR-31 action. Our findings highlight miR-31 as a possible target to modulate human T cell dependent antibody responses in the settings of infection, vaccination, or immune dysregulation.

Fuel cells powered by biogas for decentralised cogeneration of heat and power are an attractive alternative to combustion technologies. However, biogas contains sulfur-based compounds (H 2 S, COS, DMS, siloxanes), which are harmful to fuel cells. This work was carried out in the framework of the European project Waste2Watts, involving the laboratories of Politecnico di Torino, ENEA, and PSI. The aim is to design and test a flexible and cost-effective cleaning unit to remove impurities for the use of biogas in high-efficiency fuel cell systems. The focus is on small- to medium-sized farms for which deep cleaning of biogas by adsorption materials is a suitable techno-economic solution to avoid intensive gas processing treatments. The ability of commercial adsorption materials (activated carbons, metal oxides, and metal hydroxides) to remove hydrogen sulphide and carbonyl sulphide was tested under different biogas compositions (oxygen and humidity). After evaluating the results, three plant configurations were proposed to optimally utilise the potential of the sorbents. Indeed, the RGM3 sorbent has proven to be an effective solution for removing H 2 S and COS under humid conditions (50% RH), whilst R7H and R8C sorbents are better suited for removing H 2 S and COS, respectively, in dry biogas conditions. Graphical abstract

The catechol- o -methyltransferase ( COMT ) genetic variations produce pleiotropic behavioral/neuroanatomical effects. Some of these effects may vary among sexes. However, the developmental trajectories of COMT -by-sex interactions are unclear. Here we found that extreme COMT reduction, in both humans (22q11.2 deletion syndrome COMT Met) and mice ( COMT −/−), was associated to cortical thinning only after puberty and only in females. Molecular biomarkers, such as tyrosine hydroxylase, Akt and neuronal/cellular counting, confirmed that COMT -by-sex divergent effects started to appear at the cortical level during puberty. These biochemical differences were absent in infancy. Finally, developmental cognitive assessment in 22q11DS and COMT knockout mice established that COMT -by-sex-dichotomous effects in executive functions were already apparent in adolescence. These findings uncover that genetic variations severely reducing COMT result in detrimental cortical and cognitive development selectively in females after their sexual maturity. This highlights the importance of taking into account the combined effect of genetics, sex and developmental stage.

To improve the use of common buckwheat (Fagopyrum esculentum), characterized by interesting nutritional properties, it could be used in pasta formulations. In particular, as buckwheat is devoid of the gluten-forming proteins, it might be an ingredient for celiac patient food. The aim of this study was to develop both fresh egg pastas integrated with buckwheat and fresh egg pasta analogues classifiable as gluten-free, based on buckwheat and rice flours. Matter loss in the cooking water and weight increase during cooking of buckwheat pasta were higher than those of a reference sample made of common wheat flour. As buckwheat integration increased, sample break strain was significantly lower, as a result of the progressive reduction in gluten content. In the production of gluten-free pasta analogues, wheat flour was substituted with rice flour, precooked rice flour or pregelatinized rice starch. Since samples containing precooked rice flour gave the best results, in terms of workability, break strain and weight increase during cooking, they were also produced on an industrial scale. Industrial gluten-free fresh egg pasta analogues were tougher and less deformable in comparison with the laboratory-produced samples. These results were determined by the presence of the double thermal pasteurisation treatment, which allows to obtain a better structure of the product, showing also a lower matter loss during cooking.

Involvement of family members is crucial to provide daily informal caring to patients in vegetative state and minimally conscious state. Previous studies showed that perceived burden is a risk factor for informal caregivers as it increases psychophysical distress. This research further investigated the relationship between these factors and aimed at providing a model that thoroughly describes this mechanism of functioning. In the frame of a national survey on people with disorders of consciousness, 487 informal caregivers of children and adult patients in vegetative and minimally conscious state were administered measures of depression, anxiety, caregiver needs, and family strain. Regression models proposed by Baron and Kenny and the Sobel test were adopted to investigate the relationship between depressive and anxiety symptoms, perceived burden and needs expressed. Our study shows that the relation between those symptoms and needs is mediated by burden, where higher burden accentuates and lower burden mitigates the needs expressed by caregivers. Our findings demonstrate that psychosocial components of the burden perceived by caregivers of patients with disorders of consciousness play a key role in shaping those caregivers’ needs, especially their needs for information and communication. We recommend implementation of comprehensive steps to meet the needs of these caregivers, steps that incorporate improved economic and public health programs, social support, and use of psychological interventions to ameliorate caregivers’ psychological distress and decrease their burden.