A Scoping Review on GIS Technologies Applied to Farmed Fish Health Management

Finfish aquaculture, one of the fastest growing intensive sectors worldwide, is threatened by numerous transmissible diseases that may have devastating impacts on its economic sustainability. This review (2010–2022) used a PRISMA extension for scoping reviews and a text mining approach to explore the extent to which geographical information systems (GIS) are used in farmed fish health management and to unveil the main GIS technologies, databases, and functions used to update the spatiotemporal data underpinning risk and predictive models in aquatic surveillance programmes. After filtering for eligibility criteria, the literature search provided 54 records, highlighting the limited use of GIS technologies for disease prevention and control, as well as the prevalence of GIS application in marine salmonid farming, especially for viruses and parasitic diseases typically associated with these species. The text mining generated five main research areas, underlining a limited range of investigated species, rearing environments, and diseases, as well as highlighting the lack of GIS-based methodologies at the core of such publications. This scoping review provides a source of information for future more detailed literature analyses and outcomes to support the development of geospatial disease spread models and expand in-field GIS technologies for the prevention and mitigation of fish disease epidemics

Involvement of NINJ2 Protein in Inflammation and Blood–Brain Barrier Transmigration of Monocytes in Multiple Sclerosis

Multiple sclerosis (MS) is an inflammatory neurodegenerative disorder of the central nervous system (CNS). The migration of immune cells into the CNS is essential for its development, and plasma membrane molecules play an important role in triggering and maintaining the inflammation. We previously identified ninjurin2, a plasma membrane protein encoded by NINJ2 gene, as involved in the occurrence of relapse under Interferon-β treatment in MS patients. The aim of the present study was to investigate the involvement of NINJ2 in inflammatory conditions and in the migration of monocytes through the blood–brain barrier (BBB). We observed that NINJ2 is downregulated in monocytes and in THP-1 cells after stimulation with the pro-inflammatory cytokine LPS, while in hCMEC/D3 cells, which represent a surrogate of the BBB, LPS stimulation increases its expression. We set up a transmigration assay using an hCMEC/D3 transwell-based model, finding a higher transmigration rate of monocytes from MS subjects compared to healthy controls (HCs) in the case of an activated hCMEC/D3 monolayer. Moreover, a positive correlation between NINJ2 expression in monocytes and monocyte migration rate was observed. Overall, our results suggest that ninjurin2 could be involved in the transmigration of immune cells into the CNS in pro-inflammatory conditions. Further experiments are needed to elucidate the exact molecular mechanisms

Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach

A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to identify a combined clinical and genetic signature of response to fingolimod that could support the prediction of drug response. Two cohorts of fingolimod-treated patients from Italy and France were enrolled and divided into training, validation, and test set. Random forest training and robust feature selection were performed in the first two sets respectively, and the independent test set was used to evaluate model performance. A genetic-only model and a combined clinical–genetic model were obtained. Overall, 381 patients were classified according to the NEDA-3 criterion at 2 years; we identified a genetic model, including 123 SNPs, that was able to predict fingolimod response with an AUROC= 0.65 in the independent test set. When combining clinical data, the model accuracy increased to an AUROC= 0.71. Integrating clinical and genetic data by means of machine learning methods can help in the prediction of response to fingolimod, even though further studies are required to definitely extend this approach to clinical application

A pharmacogenetic study implicates NINJ2 in the response to Interferon-ß in multiple sclerosis

[Background] Multiple sclerosis (MS) is a disease in which biomarker identification is fundamental to predict response to treatments and to deliver the optimal drug to patients. We previously found an association between rs7298096, a polymorphism upstream to the NINJ2 gene, and the 4-year response to interferon-β (IFNβ) treatment in MS patients.[Objectives] To analyse the association between rs7298096 and time to first relapse (TTFR) during IFNβ therapy in MS patients and to better investigate its functional role. [Methods] Survival analysis was applied in three MS cohorts from different countries (n = 1004). We also studied the role of the polymorphism on gene expression using GTEx portal and a luciferase assay. We interrogated GEO datasets to explore the relationship between NINJ2 expression, IFNβ and TTFR. [Results] Rs7298096AA patients show a shorter TTFR than rs7298096G-carriers (Pmeta-analysis = 3 × 10−4, hazard ratio = 1.41). Moreover, rs7298096AA is associated with a higher NINJ2 expression in blood (p = 7.0 × 10−6), which was confirmed in vitro (p = 0.009). Finally, NINJ2 expression is downregulated by IFNβ treatment and related to TTFR. [Conclusions] Rs7298096 could influence MS disease activity during IFNβ treatment by modulating NINJ2 expression in blood. The gene encodes for an adhesion molecule involved in inflammation and endothelial cells activation, supporting its role in MS

A multi-step genomic approach prioritized TBKBP1 gene as relevant for multiple sclerosis susceptibility

Background Over 200 genetic loci have been associated with multiple sclerosis (MS) explaining similar to 50% of its heritability, suggesting that additional mechanisms may account for the "missing heritability" phenomenon.Objective To analyze a large cohort of Italian individuals to identify markers associated with MS with potential functional impact in the disease.Methods We studied 2571 MS and 3234 healthy controls (HC) of continental Italian origin. Discovery phase included a genome wide association study (1727 MS, 2258 HC), with SNPs selected according to their association in the Italian cohort only or in a meta-analysis of signals with a cohort of European ancestry (4088 MS, 7144 HC). Top associated loci were then tested in two Italian cohorts through array-based genotyping (903 MS, 884 HC) and pool-based target sequencing (588 MS, 408 HC). Finally, functional prioritization through conditional eQTL and mQTL has been performed.Results Top associated signals overlap with already known MS loci on chromosomes 3 and 17. Three SNPs (rs4267364, rs8070463, rs67919208), all involved in the regulation of TBKBP1, were prioritized to be functionally relevant.Conclusions No evidence of novel signal of association with MS specific for the Italian continental population has been found; nevertheless, two MS loci seems to play a relevant role, raising the interest to further investigations for TBKBP1 gene

Gestione del Covid-19 in età pediatrica: documento di consenso

Coronavirus disease 2019 (Covid-19) caused by SARS-CoV-2 has rapidly spread, becoming the first pandemic of the 21st century by death toll. Children appear to be less affected than adults, with a milder clinical presentation and a significantly lower mortality rate. However, serious complica-tions can occur in childhood, such as Covid-19 temporally related multisystem inflammatory syn-drome (MIS-C). Some aspects of SARS-CoV-2 infection in children and adolescents remain un-clear and the optimal treatment has not been defined. The Working Group on Covid-19 in Paediatrics of the Emilia-Romagna Region (RE-CO-PED) has produced a consensus document with practical recommendations based on a systematic review of the literature and on the clinical experi-ence of the expert group. Evidence is reported regarding prevention measures, diagnostic tools as well as home and hospital therapeutic management of complicated cases (MIS-C). The educational and psychological effects of the pandemic in the paediatric and adolescent age are reported, with the need to define coordinated interventions (between paediatricians, neurospychiatrists, psycholo-gists and educational services) for the prevention and treatment of documented emotional, relational and educational consequences caused by the lockdown, school closures and social distances

Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses