Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation

A comparative evaluation of regional subsidies for collaborative and individual R&D in small and medium-sized enterprises

We analyse whether public subsidies supporting collaborative research and development (R&D) projects in small and medium-sized enterprises (SMEs) are able to encourage persistent R&D investment and interorganisational networking more than subsidies supporting individual R&D projects. Adopting a counterfactual approach to policy evaluation, we compare subsidies for collaborative R&D and for individual R&D implemented in the same Italian region in the same period. Our findings suggest that, once public support is no longer available, the two subsidies have different effects on different types of SMEs. If the policymakers’ objective is to increase the number of R&D-performing SMEs over time, they should provide subsidies for collaborative R&D to firms with modest R&D experience. If their objective is to increase the amount of spontaneous R&D investment over time, they should target SMEs with some prior R&D experience, using either subsidy. Finally, if their objective is to induce SMEs to network with external organisations, subsidies for collaborative R&D projects should be preferred to subsidies for individual R&D projects

Epithelial V-like Antigen (EVA), a Novel Member of the Immunoglobulin Superfamily, Expressed in Embryonic Epithelia with a Potential Role as Homotypic Adhesion Molecule in Thymus Histogenesis

Thymus development depends on a complex series of interactions between thymocytes and the stromal component of the organ. To identify regulated genes during this codependent developmental relationship, we have applied an RNA fingerprinting technique to the analysis of thymus expansion and maturation induced in recombinase-deficient mice injected with anti-CD3 antibodies. This approach led us to the identification of a gene encoding a new member of the immunoglobulin superfamily, named epithelial V-like antigen (EVA), which is expressed in thymus epithelium and strongly downregulated by thymocyte developmental progression. This gene is expressed in the thymus and in several epithelial structures early in embryogenesis. EVA is highly homologous to the myelin protein zero and, in thymus-derived epithelial cell lines, is poorly soluble in nonionic detergents, strongly suggesting an association to the cytoskeleton. Its capacity to mediate cell adhesion through a homophilic interaction and its selective regulation by T cell maturation might imply the participation of EVA in the earliest phases of thymus organogenesis

Serum antibody response to Human papillomavirus (HPV) infections detected by a novel ELISA technique based on denatured recombinant HPV16 L1, L2, E4, E6 and E7 proteins

BACKGROUND: Human papillomaviruses (HPVs) are the primary etiological agents of cervical cancer and are also involved in the development of other tumours (skin, head and neck). Serological survey of the HPV infections is important to better elucidate their natural history and to disclose antigen determinants useful for vaccine development. At present, the analysis of the HPV-specific antibodies has not diagnostic value for the viral infections, and new approaches are needed to correlate the antibody response to the disease outcome. The aim of this study is to develop a novel ELISA, based on five denatured recombinant HPV16 proteins, to be used for detection HPV-specific antibodies. METHODS: The HPV16 L1, L2, E4, E6 and E7 genes were cloned in a prokaryotic expression vector and expressed as histidine-tagged proteins. These proteins, in a denatured form, were used in ELISA as coating antigens. Human sera were collected from women with abnormal PAP smear enrolled during an ongoing multicenter HPV-PathogenISS study in Italy, assessing the HPV-related pathogenetic mechanisms of progression of cervical cancer precursor lesions. Negative human sera were collected from patients affected by other infectious agents. All the HPV-positive sera were also subjected to an avidity test to assess the binding strength in the antigen-antibody complexes. RESULTS: Most of the sera showed a positive reactivity to the denatured HPV16 proteins: 82% of the sera from HPV16 infected women and 89% of the sera from women infected by other HPV genotypes recognised at least one of the HPV16 proteins. The percentages of samples showing reactivity to L1, L2 and E7 were similar, but only a few serum samples reacted to E6 and E4. Most sera bound the antigens with medium and high avidity index, suggesting specific antigen-antibody reactions. CONCLUSION: This novel ELISA, based on multiple denatured HPV16 antigens, is able to detect antibodies in women infected by HPV16 and it is not genotype-specific, as it detects antibodies also in women infected by other genital HPVs. The assay is easy to perform and has low cost, making it suitable for monitoring the natural history of HPV infections as well as for detecting pre-existing HPV antibodies in women who receive VLP-based HPV vaccination

The frail patient undergoing cardiac surgery: lessons learned and future perspectives

Frailty is a geriatric condition characterized by the reduction of the individual's homeostatic reserves. It determines an increased vulnerability to endogenous and exogenous stressors and can lead to poor outcomes. It is an emerging concept in perioperative medicine, since an increasing number of patients undergoing surgical interventions are older and the traditional models of care seem to be inadequate to satisfy these patients' emerging clinical needs. Nowadays, the progressive technical and clinical improvements allow to offer cardiac operations to an older, sicker and frail population. For these reasons, a multidisciplinary team involving cardiac surgeons, clinical cardiologists, anesthesiologists, and geriatricians, is often needed to assess, select and provide tailored care to these high-risk frail patients to optimize clinical outcomes. There is unanimous agreement that frailty assessment may capture the individual's biological decline and the heterogeneity in risk profile for poor health-related outcomes among people of the same age. However, since commonly used preoperative scores for cardiac surgery fail to capture frailty, a specific preoperative assessment with dedicated tools is warranted to correctly recognize, measure and quantify frailty in these patients. On the contrary, pre-operative and post-operative interventions can reduce the risk of complications and support patient recovery promoting surgical resilience. Minimally invasive cardiac procedures aim to reduce surgical trauma and may be associated with better clinical outcome in this specific sub-group of high-risk patients. Among postoperative adverse events, the occurrence of delirium represents a risk factor for several unfavorable outcomes including mortality and subsequent cognitive decline. Its presence should be carefully recognized, triggering an adequate, evidence based, treatment. There is evidence, from several cross-section and longitudinal studies, that frailty and delirium may frequently overlap, with frailty serving both as a predisposing factor and as an outcome of delirium and delirium being a marker of a latent condition of frailty. In conclusion, frail patients are at increased risk to experience poor outcome after cardiac surgery. A multidisciplinary approach aimed to recognize more vulnerable individuals, optimize pre-operative conditions, reduce surgical invasivity and improve post-operative recovery is required to obtain optimal long-term outcome

Glucose transport in brain and retina: implications in the management and complications of diabetes

Neural tissue is entirely dependent on glucose for normal metabolic activity. Since glucose stores in the brain and retina are negligible compared to glucose demand, metabolism in these tissues is dependent upon adequate glucose delivery from the systemic circulation. In the brain, the critical interface for glucose transport is at the brain capillary endothelial cells which comprise the blood–brain barrier (BBB). In the retina, transport occurs across the retinal capillary endothelial cells of the inner blood–retinal barrier (BRB) and the retinal pigment epithelium of the outer BRB. Because glucose transport across these barriers is mediated exclusively by the sodium-independent glucose transporter GLUT1, changes in endothelial glucose transport and GLUT1 abundance in the barriers of the brain and retina may have profound consequences on glucose delivery to these tissues and major implications in the development of two major diabetic complications, namely insulin-induced hypoglycemia and diabetic retinopathy. This review discusses the regulation of brain and retinal glucose transport and glucose transporter expression and considers the role of changes in glucose transporter expression in the development of two of the most devastating complications of long-standing diabetes mellitus and its management. Copyright © 1999 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35242/1/43_ftp.pd

Sistema Integrato Multicentrico di Indicatori. Rapporto 2005. Provincia di Parma.

The SIMI (Integrated System of Indicators multicenter) Project contributes to the development of an integrated management of informative data streams related to drug addicted persons. This report analyzes the phenomenon of addiction on the territory of the Parma Province through a description of the network services that provide care and rehabilitation of those addicted. Besides the characteristics of users of local services for addictions, has been developed the analysis of the subjects reported to the prefectures for use of illegal drugs and any action taken. Standard methods of estimation were also applied to quantify the proportion of users of substances that do not relate to services and to identify certain characteristics.Il Progetto SIMI (Sistema Integrato Multicentrico di Indicatori) intende contribuire allo sviluppo di una gestione integrata e sinergica dei flussi informativi relativi ai consumatori di sostanze stupefacenti afferenti alle diverse amministrazioni dello Stato. In linea con quanto proposto dall\u27Osservatorio europeo di Lisbona, per la descrizione e analisi del fenomeno connesso all\u27uso/abuso di sostanze, risulta di fondamentale importanza la possibilit? di ottenere informazioni esaustive e comparabili sulle persone che usano e/o abusano di sostanze psicotrope. Il presente rapporto analizza il fenomeno delle dipendenze sul territorio della provincia di Parma attraverso la descrizione della rete dei servizi preposti alla cura e riabilitazione dei soggetti tossicodipendenti. Accanto alle caratteristiche degli utenti dei servizi territoriali per le dipendenze, ? stata sviluppata l\u27analisi dei soggetti segnalati alle Prefetture per uso di sostanze illegali e degli eventuali provvedimenti adottati. Sono state inoltre applicate metodologie standard di stima per quantificare la quota parte di utilizzatori di sostanze che non afferiscono ai servizi e per identificarne alcune caratteristiche

Ceftolozane/Tazobactam for Treatment of Severe ESBL-Producing Enterobacterales Infections: A Multicenter Nationwide Clinical Experience (CEFTABUSE II Study)

Background. Few data are reported in the literature about the outcome of patients with severe extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) infections treated with ceftolozane/tazobactam (C/T), in empiric or definitive therapy.Methods. A multicenter retrospective study was performed in Italy (June 2016-June 2019). Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to ESBL-E infection and lack of microbiological evidence of infection. The primary end point was to identify predictors of clinical failure of C/T therapy.Results. C/T treatment was documented in 153 patients: pneumonia was the most common diagnosis (n = 46, 30%), followed by 34 cases of complicated urinary tract infections (22.2%). Septic shock was observed in 42 (27.5%) patients. C/T was used as empiric therapy in 46 (30%) patients and as monotherapy in 127 (83%) patients. Favorable clinical outcome was observed in 128 (83.7%) patients; 25 patients were considered to have failed C/T therapy. Overall, 30-day mortality was reported for 15 (9.8%) patients. At multivariate analysis, Charlson comorbidity index >4 (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.9-3.5; P = .02), septic shock (OR, 6.2; 95% CI, 3.8-7.9; P < .001), and continuous renal replacement therapy (OR, 3.1; 95% CI, 1.9-5.3; P = .001) were independently associated with clinical failure, whereas empiric therapy displaying in vitro activity (OR, 0.12; 95% CI, 0.01-0.34; P < .001) and adequate source control of infection (OR, 0.42; 95% CI, 0.14-0.55; P < .001) were associated with clinical success.Conclusions. Data show that C/T could be a valid option in empiric and/or targeted therapy in patients with severe infections caused by ESBL-producing Enterobacterales. Clinicians should be aware of the risk of clinical failure with standard-dose C/T therapy in septic patients receiving CRRT