miR-7 Controls the Dopaminergic/Oligodendroglial Fate through Wnt/\u3b2-catenin Signaling Regulation

During the development of the central nervous system, the proliferation of neural progenitors and differentiation of neurons and glia are tightly regulated by different transcription factors and signaling cascades, such as the Wnt and Shh pathways. This process takes place in cooperation with several microRNAs, some of which evolutionarily conserved in vertebrates, from teleosts to mammals. We focused our attention on miR-7, as its role in the regulation of cell signaling during neural development is still unclear. Specifically, we used human stem cell cultures and whole zebrafish embryos to study, in vitro and in vivo, the role of miR-7 in the development of dopaminergic (DA) neurons, a cell type primarily affected in Parkinson's disease. We demonstrated that the zebrafish homologue of miR-7 (miR-7a) is expressed in the forebrain during the development of DA neurons. Moreover, we identified 143 target genes downregulated by miR-7, including the neural fate markers TCF4 and TCF12, as well as the Wnt pathway effector TCF7L2. We then demonstrated that miR-7 negatively regulates the proliferation of DA-progenitors by inhibiting Wnt/\u3b2-catenin signaling in zebrafish embryos. In parallel, miR-7 positively regulates Shh signaling, thus controlling the balance between oligodendroglial and DA neuronal cell fates. In summary, this study identifies a new molecular cross-talk between Wnt and Shh signaling pathways during the development of DA-neurons. Being mediated by a microRNA, this mechanism represents a promising target in cell differentiation therapies for Parkinson's disease

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments

Open datasets wanted for tracking the insect decline: let's start from saproxylic beetles

We present six datasets of saproxylic beetles collected between 2012 and 2018 in Central and Southern Italian forests. Saproxylics represent one of the main components in forest ecosystems in terms of diversity, species richness and functional traits and, for this reason, they are an important target group for studying the modification of forests over time. The datasets consist of annotated checklists and were published on Zenodo repository.Overall, 1,171 records are published, corresponding to 918 taxa (taxonomy at species or subspecies level). The taxa are scarcely shared amongst the areas, 80.2% of them are exclusive, indicating that the beetle communities are substantially different. In consideration of the biodiversity crisis we are passing through, which is especially dramatic for the insects, we want to promotecollaboration amongst researchers for making datasets available in open repositories. This will improve the possibility for researchers and forest managers of analysing the state of species distribution that could serve for long-term studies on the variation of insect communities. We encourage repeating species assessment in the same localities in order to evaluate the trends in insect communities over time and space

Application of SLICC classification criteria in undifferentiated connective tissue disease and evolution in systemic lupus erythematosus: Analysis of a large monocentric cohort with a long-term follow-up

The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria.Objectives The objectives of this study were to analyse the performance of the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria for systemic lupus erythematosus (SLE) in a large cohort of undifferentiated connective tissue disease (UCTD) population at onset of the disease and during a long-term follow-up of 15 years (1999-2013) and to evaluate the transition from UCTD to SLE, according to American College of Rheumatology (ACR) 1997 and SLICC 2012 classification criteria. Methods A cohort of patients who met the classification criteria proposed by Mosca et al. for UCTD, were analysed. The SLICC 2012 classification criteria for SLE were retrospectively applied to each patient at the time of the diagnosis (T0) and also periodically re-applied and compared to ACR 1997 criteria at three different time points in the follow-up. Results 329 patients were enrolled. According to inclusion criteria at T0 no patient met the SLE/ACR criteria, whilst, retrospectively applying the SLE/SLICC criteria, 44 patients already satisfied this set of criteria for SLE. During the follow-up 23 new patients reached the SLE/SLICC criteria and 14 patients met the ACR criteria with a stable rate of progression to SLE over time. Acute or subacute skin rash, antiphospholipid antibody (aPL) positivity and serositis were the variables correlated to the evolution to SLE. Conclusions In our UCTD population, the application of SLICC classification criteria for SLE at disease onset allowed identification of a proportion of otherwise missed SLE cases; during follow-up, and compared with ACR criteria, SLICC criteria expanded the number of patients classifiable as SLE otherwise classified as UCTD

Setting appropriate technologies in the remediation of brownfield contaminated with hydrocarbons: The case study of the ex-Gasometer in Bari, Italy

The contribution shows a case study concerning the remediation of a disused industrial plant (Ex- Gasometer) in the central area of the city of Bari (Apulia Region, Southern Italy). The Ex-Gasometer is an area declared “at risk” by local Authorities because of it is one of the most complex, extensive (about 20,000 m2) and contaminated brownfields situated near a high population density urban area. The characterization highlighted high concentrations of heavy metals, organic pollutants and above all hydrocarbons both in groundwater and in soil. The contribution recognized and analyzed the main aspects that allowed the selection and the implementation of the most suitable remediation strategies for soils and groundwater decontamination. Furthermore, details of movable tensile structure as well as sampling procedures related to the monitoring of excavation fronts have been accurately described. In this way, the case study addressed is an example of how remediation plays an important role in the context of circular economy

Start-up of the door-to-door municipal solid waste separate collection service in a large metropolitan area

The study describes the start-up phase of the door-to-door separate collection service of municipal solid waste (MSW) in a large metropolitan area, analysing not only the performance in terms of separately collected waste but also the feedback from citizens on how to improve it. For the scope, the case study of the city of Bari (Southern Italy) was considered. The methodological approach involved primarily the subdivision of the entire municipality into eight homogeneous territorial zones (HTZ) considering population density and space availability. Additionally, each HTZ was decomposed into unitary areas, which in turn were classified according to the degree of feasibility in implementing door-to-door separate collection. During the first year of operation, results showed excellent performance in terms of separately collected waste (>80%) highlighting the goodness of the adopted technical approach as well as the convenience in acquiring feedback from users during the start-up of the service. While expressing positive satisfaction about the door-to-door system, users consider the adopted sanctioning and control system to be critical. The same was considered insufficient to deal with the well-known phenomenon of “waste tourism”

Separate collection of municipal solid waste and fate of the residual unsorted fraction: A scenario analysis

Three scenarios for the management of Municipal Solid Waste (MSW) produced in the study area of Bari (Southern Italy) were defined and evaluated in terms of separately collected material and fate of the residual fraction The first scenario represented the bring points MSW separate collection system in the current configuration with a collection rate approx. 40%. The second scenario considered the study area in the optimal configuration, with a percentage of separate collection > 80% obtained through a door-to-door system. In both scenarios, the residual/unsorted fraction of MSW was destined for conventional mechanical-biological treatment. The third scenario was an intermediate one, with a separate collection percentage equal to the legal limit (65%); the residual/unsorted fraction of MSW was destined in a Secondary Raw Material Recovery (SRMR) plant. As described in the contribution, the SRMR plant can potentially produce Secondary Recovered Fuel (SRF), homogeneous sorted waste (PET, HDPE, PP, LDPE, ferrous materials, non-ferrous materials and mixed paper) and stabilized organic fraction to be landfilled. By means of mass balances that quantify the collected fractions, scenario 3 proved to be the most promising; the amount of potentially obtainable material was higher than that of the other two scenarios. With reference only to this aspect, the study shows how the optimal configuration for a large metropolitan area is not always the one with the highest percentage of separate collection. As the incoming waste to SRMR plant contains organic, the potentially recoverable homogeneous fractions could be of low quality, resulting in decreased economic quotation or market demand. This aspect needs to be further investigated together with a more accurate economic feasibility analysis

Sustainability assessment of municipal solid waste separate collection and treatment systems in a large metropolitan area

Among different modes for municipal solid waste separate collection (SC), there is a lack of scientifically based methods for their selection available for decision-makers. This study develops and applies a methodology based on Multi-Criteria Decision Analysis (MCDA) aiming to assess and compare the sustainability of different waste management schemes. Considering the city of Bari (Southern Italy) as a supporting case study, 3 systems/visions of city waste management options are considered: (i) bring points systems with about 35% SC rate (S1, status quo); (ii) door-to-door system with an excellent (>80%) SC rate (S2); (iii) combined bring point and door-to-door system (S3, with about 70% SC rate). Scenarios differed mainly on the management of the residual fraction from SC through mechanical-biological treatment (S1 and S2) or recovery of recyclables at material recovery facility (S3). Sustainability is assessed in environmental, economic, and socio-technical terms by means of MCDA and Life Cycle Assessment (LCA). Results showed that S2 is the best solution in global, environmental, and socio-technical terms, while the weak point is the cost (65.76 € per capita). Even more interesting is the limited deviation between S3 and S2 indicators, amounting to 5.4% and 9.4% in terms of environmental and socio-technical criteria respectively, suggesting a strong competitiveness of the mixed collection mode. Methodologically, the approach proved to be robust and easy to apply by local authority decision-makers

Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis

Objective Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs). Methods Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143. Results We have included one phase I, 21 phase II, three phase II-III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage. Conclusion JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs