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Item does not contain fulltext, Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

To assess the propensity of Russian and Italian fashion consumers to use Product-Service Systems (PSSs), the study identifies the drivers and barriers for their adoption to improve decision-making and targeting of consumers when launching PSSs in markets with different socio-cultural and economic characteristics. After providing a comprehensive list of the services that are currently implemented in the fashion industry, the study also compares the level of interest in PSSs for Russian and Italian consumers, as well as their willingness to recommend, actual usage of, and attitude towards PSSs. The methodology relies on a comparative quantitative study between Russian and Italian consumers, using a survey leading to a final sample of 328 participants. From the findings, it emerges that the national context plays a pivotal role in determining the propensity of fashion consumers to adopt PSSs. We find that Italian consumers are more inclined to adopt PSSs vis-a-vis their counterparts. Further, by identifying the key drivers and barriers, we also highlight potential opportunities and threats for the adoption of PSSs in the future. Given that the widespread adoption at an international level of PSSs is strictly related to their potential in terms of scalability, the findings have highly significant implications for both theory and practice.

BACKGROUNDSevere forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODSWe performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid-dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTSSixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults.In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusionCONCLUSIONTreatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.TRIAL REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.

COVID-19 is a viral infection, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized by a complex inflammatory process and clinical immunophe-notypes. Nowadays, several alterations of immune response within the respiratory tracts as well as at the level of the peripheral blood have been well documented. Nonetheless, their effects on COVID-19-related cell heterogeneity and disease progression are less defined. Here, we performed a single-cell RNA sequencing of about 400 transcripts relevant to immune cell function including surface markers, in mononuclear cells (PBMCs) from the peripheral blood of 50 subjects, infected with SARS-CoV-2 at the diagnosis and 27 healthy blood donors as control. We found that patients with COVID-19 exhibited an increase in COVID-specific surface markers in different subsets of immune cell composition. Interestingly, the expression of cell receptors, such as IFNGR1 and CXCR4, was reduced in response to the viral infection and associated with the inhibition of the related signaling pathways and immune functions. These results highlight novel immunoreceptors, selectively expressed in COVID-19 patients, which affect the immune functionality and are correlated with clinical outcomes.

This paper outlines the characteristics of scientific leadership and the role of Scientific Associations with their specific activities. The recent activities of the Lombard Academy of Public Health are subsequently described, including the creation, in 2019, of the Academy of young leaders in public health. Comparing to other sectors, scientific leadership dynamics take into consideration different aspects. Besides awards (Nobel Prize or several other) and prestigious affiliations, eventual indicators might be academic roles, fundraising abilities, relevant positions among scientific associations, editors of prestigious journals or editorial series and, more recently, high bibliometric indicators. The peculiar topics of public health encompass interactions with institutions, authorities, politicians, involved in different levels in health policies. Recently, in Italy, the Ministry of Health has identified parameters to be accreditated as a scientific and technical association. The role of SItI (Italian Society of Hygiene), EUPHA, ASPHER, and WFPHA appears relevant in PH, in national and international contexts, with Italian praiseworthy members constantly achieving leading roles. Considering that few training opportunities aimed to improve research and leadership skills are available, Accademia Lombarda di Sanità Pubblica (ALSP) designed the AYLPH (Academy of Young Leaders in Public Health) program. AYLPH program is a 1-year training to shape leadership skills among young professionals. A set of didactic, theoretical and practical methods was offered and evaluated.

Tra l’agosto del 1953 e il giugno del 1954 Arnold Leonard Epstein condusse un’indagine antropologica a Luanshya, città mineraria del Copperbelt (attuale Zambia), con l’intento di analizzare la formazione di alcune istituzioni giuridico-amministrative locali. Tra la fine degli anni Ottanta e i primi anni Duemila, Loïc Wacquant ha condotto una serie di ricerche teoriche ed empiriche volte a comprendere fenomeni riconducibili alla frammentazione sociale e alla povertà urbana tra Chicago e Parigi. I testi qui presentati sono frammenti dei frutti di queste inchieste etnografiche, i risultati delle quali, certamente lontani gli uni dagli altri, sono in grado, tuttavia, di mostrare un ipotetico percorso che l’antropologia ha intrapreso nel suo relazionarsi alle realtà urbane, mettendo in luce le continuità e le discontinuità da un punto di vista sia metodologico sia teorico sia del posizionamento del ricercatore nei confronti dei contesti indagati.

The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer– BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3’ regulatory region 1 (3’RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects. Taken together, these results suggest that favorable genetic backgrounds and immune profiles support the progression of an effective response to BNT162b2 vaccination.