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Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19.Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used.Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events.Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.Financial Support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper. [ABSTRACT FROM AUTHOR]

Background: Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.Objectives: The objective of this paper, part of the MAPEC_LIFE project, is to describe the frequency of micronuclei and meta-nuclear alterations in exfoliated buccal cells of 6-8year-old Italian children recruited in five Italian towns (i.e., Brescia, Torino, Pisa, Perugia and Lecce) with different air pollution levels.Methods: About 200 children per town were recruited from primary schools. Biological samples were collected twice from the same children, in two different seasons (winter 2014-15 and late spring 2015). Cytogenetic damage was evaluated by the buccal micronucleus cytome assay.Results: Overall,n = 1046 children represent the final cohort of the MAPEC_LIFE study. On the whole, the results showed a higher mean MN frequency in winter (0.42 ± 0.54‰) than late-spring (0.22 ± 0.34‰). MN frequency observed among the five Italian towns showed a trend that follows broadly the levels of air pollution in Italy: the highest MN frequency was observed in Brescia during both seasons, the lowest in Lecce (winter) and Perugia (late-spring).Conclusions: To the best of our knowledge, the number of recruited children included in the analysis (n = 1046) is the highest compared to previous studies evaluating the frequency of MN in exfoliated buccal cells so far. MN frequency was associated with winter season and living in towns at various levels of air pollution, suggesting an important role of this exposure in determining early cytogenetic effects. [ABSTRACT FROM AUTHOR]

Objective: To examine knowledge displays (KDs), a practice by which Therapeutic Community (TC) professionals exhibit previous knowledge about their clients' circumstances and experiences.Methods: Conversation analysis is used to examine 12 staff-led meetings recorded in Italy (8 in a drug addiction TC; 4 in a mental health TC).Results: The TC professionals use KDs within broader sequences of talk where they solicit their clients to share personal information and where the clients provide insufficient or inconsistent responses. In these circumstances, the staff members employ KDs to pursue responses that redress emerging knowledge gaps and discrepancies regarding the clients' experiences or circumstances.Conclusion: KDs allow the staff members to achieve a balance between respecting their clients' right to report their own experiences and influencing the ways in which they report them. KDs help to reinforce the culture of openness that is central to many forms of therapeutic interaction, to forward the therapeutic agenda and to expand the staff members' knowledge of the clients' experiences and circumstances.Practice Implications: KDs can be used to solicit clients to share personal information. This paper illustrates core features that underlie the function of KDs (where they are used and how they are constructed). [ABSTRACT FROM AUTHOR]

Multiple layers of dealers connect international drug traffickers to users. The fundamental activity of these dealers is buying from higher-level dealers and re-selling in smaller quantities at the next lower market level. Each instance of this can be viewed as completing a drug dealing "cycle". This paper introduces an approach for combining isolated accounts of such cycles into a coherent model of the structure, span, and profitability of the various layers of the domestic supply chain for illegal drugs. The approach is illustrated by synthesizing data from interviews with 116 incarcerated dealers to elucidate the structure and operation of distribution networks for cocaine and heroin in Italy and Slovenia. Inmates' descriptions of cycles in the Italian cocaine market suggest fairly orderly networks, with reasonably well-defined market levels. The Italian heroin market appears to have more "level-jumpers" who skip a market level by making a larger number of sales per cycle, with each sale being of a considerably smaller weight. Slovenian data are sparser, but broadly consistent. Incorporating prices allows calculation of how much of the revenue from retail sales is retained by dealers at each market level. In the Italian cocaine market, both retail sellers and the international supply chain outside of Italy each appear to receive about 30-40% of what users spend, with the remaining 30% going to higher-level dealers operating in Italy (roughly 10% to those at the multi-kilo level and 20% to lower level wholesale dealers). Factoring in cycle frequencies permits rough estimation of the number of organizations at each market level per billion euros in retail sales, and of annual net revenues for organizations at each level. These analyses provide an approach to gaining insight into the structure and operation of the supply chain for illegal drugs. They also illustrate the value of two new graphical tools for describing illicit drug supply chains and hint at possible biases in how respondents describe their drug dealing activities. [ABSTRACT FROM AUTHOR]

Background: A growing body of literature aims to improve understanding of the operations of drug trafficking markets through conducting interviews with dealers and traffickers. Insight into how these individuals conduct business can provide evidence to inform the efforts by policy makers, law enforcement and practitioners to disrupt illicit markets. This paper aims to make a contribution to this evidence base by extending the number of European countries in which interviews have been conducted with incarcerated drug dealers and traffickers.Methods: It draws on interviews with 135 men convicted of offences related to the distribution or sale of heroin or cocaine and imprisoned in Italy, Slovenia and Germany. The research was conducted as part of the Reframing Addictions Project (ALICE-RAP) funded by the European Commission. The sample was diverse. It included a range of nationalities and some individuals who were members of organised crime groups. The majority of the interviewees were dealers who sold at the retail and street level, but there were some who were importers and wholesalers.Findings: Most dealers in each of the three countries reported having more than one regular supplier, and were able to respond to periods of over and under supply without losing customers. Supply arrangements varied in terms of frequency and quantities bought. Dealers engaged in repeated transactions and their relationships with customers were based on trust and reputation. Dealers aimed to sell to regular customers and to provide drugs of good quality. While dealers sought to maximise their profits by cutting drugs with cutting agents, the quality of drugs that they sold could affect their reputation and thus their profits and position in the market. Lastly, while there are some significant differences in the approach between those involved in organised crime groups and those who are not, and between street dealers and those operating at higher levels of the market, there were striking similarities in terms of the day-to-day operational concerns and modes of relationship management.Conclusions: Interviewees' arrangements for securing supplies of drugs provide support to the notion that drug markets are resilient and flexible. Our findings correspond with other empirical research in relation to the centrality of trust in the practical operation of supply and sale of drugs. The research highlights some differences, but important similarities between dealers who were part of organised crime groups and those who were not; dealers all faced some common challenges and adopted some common responses to these. [ABSTRACT FROM AUTHOR]

Background: Duodenal fistula (DF) after gastrectomy continues to be a life-threatening problem. We performed a retrospective multicenter study analyzing the characteristics of DF after elective gastrectomy for malignant disease.Methods: Three thousand seven hundred eighty-five patients who had undergone gastrectomy with duodenal stump in 11 Italian surgical units were analyzed.Results: Sixty-eight DFs occurred, with a median frequency of 1.6% and a mortality rate of 16%. Complications were mainly septic but fistulas or bleeding of surrounding organs accounted for about 30%. Reoperation was performed in 40% of patients. We observed a correlation between mortality and age (hazard ratio 1.09; 95% CI 1.00-1.20) and serum albumin (hazard ratio 0.90; 95% CI 0.83-0.99). The appearance of further complications was associated with reoperation (P < 0.001) and death (P = 0.054), while the preservation of oral feeding was related to DF healing (P < 0.001).Conclusions: This paper represents the largest series ever published on DF and shows that its features have changed in the last 20 years. DF alone no longer leads to death and some complications observed in the past have disappeared, while new ones are emerging. Nowadays, medical therapy is preferred and surgery is indicated only in cases of abdominal sepsis or bleeding. [ABSTRACT FROM AUTHOR]

This paper investigates the price variability of standardized medical devices purchased by Italian Public Buyers (PBs). A semiparametric approach is used to recover the marginal cost of each device. Average prices vary substantially between PBs; we show that most of the difference between the purchase prices and estimated costs is associated with a PB fixed effect, which, in turn, is related to the institutional characteristics and size of the PB. Repeating the main estimation using device fixed effects yields similar results. Finally, an exogenous policy change, i.e. the termination of the mandatory reference price regime, is used to assess how discretion affects medical device procurement given the skills of each PB. Our results show that less PB discretion - i.e. when mandatory reference prices apply - determines efficiency gains and losses for low- and high-skilled PBs, respectively. [ABSTRACT FROM AUTHOR]

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta-chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research. [ABSTRACT FROM AUTHOR]

Evidence of negative health effects of solid waste management is uncertain. Available reviews suggests the use of biomarkers in human biomonitoring (HBM) to detect low exposure levels. In September 2013, a waste-to-energy plant located in the Turin (Italy) went into operation. The SPoTT (acronym for Population health Surveillance in the Turin incinerator's area) monitoring program was set up to assess the potential health impact caused by the plant. The paper illustrates the results of HBM of metals in the workers before the plant went into operation and then at 1 year and 3 years. This study is one of the few focusing on workers with a longitudinal design (the first in Italy). Eighteen metals in urine and lead in blood were determined by sector field inductively coupled plasma mass spectrometry. Information on participant habits and other characteristics that could potentially affect metals concentrations were collected via a structured questionnaire. Subjects were classified according to their work role at the facility: administrative staff workers (AW); plant workers (PW). Nonparametric methods were used to evaluate the changes in metals concentration over time. Comparison of the metals concentration in the samples taken at baseline and at the following two-time points shows a general decrease in levels: urinary concentration of beryllium (Be), cobalt (Co), mercury (Hg), Ir, nickel (Ni), tin (Sn), thallium (Tl), and blood level of lead (Pb) among the PW and Ir and Pd among the AW were significantly lower at T2 versus baseline. A decrease was also recorded in arsenic (As) among the PW and in cadmium (Cd), chromium (Cr), palladium (Pd), rhodium (Rh), and zinc (Zn) for both groups, whereas the levels of copper (Cu) and vanadium (V) remained unchanged over time. The downward trend remained also after taking confounding factors into account. The only exceptions were Mn, Pt, Sb among the PW: increase levels between T0 and T2 were recorded, which cannot be specifically attributable to the plant activity. The median urinary and blood concentrations of the metals were lower than those reported in the literature and were below the occupational reference values at all three-time points. Our results are consistent with those reported for the cohort of local residents and with the ambient air measurements. [ABSTRACT FROM AUTHOR]

Neurological disorders can be mis-diagnosed as psychiatric ones. This might happen to pedophilia emerging as a symptom of brain insult (i.e. acquired pedophilic behavior). This paper aims to delineate a behavioral profile that might help to identify defendants whose pedophilic behavior is likely to be the consequence of a neurological disorder. Through a systematic review of the literature, seventeen clinical and behavioral variables of the modus operandi and victimology that can distinguish between acquired and developmental pedophilic behavior have been collected. Seven of these were found to be consistent behavioral indicators (i.e. red flags) for acquired pedophilia. Cluster hierarchical analysis on the seventeen variables collected through the systematic review of the literature on cases of acquired pedophilic behavior was applied to a new dataset including 66 Italian closed cases of pedophilia. Stepwise regression and correlation analyses were carried out to further examine the differences between the clusters identified in the cluster analysis. Results revealed that the new sample was partitioned into two clusters. Individuals with ascertained acquired pedophilia were grouped together. The clusters widely differed for the prevalence of red flags (mean number of red flags in each cluster: 2.14 ± 0.79 vs 4.96 ± 0.93, p < 0.001), while no between cluster difference emerged for the other clinical and behavioral variables. Regression analysis provided a robust model that included the three most significant red flags that explain over 64.5% of the variance (absence of masking, spontaneous confession and offenders older age). An organic origin of pedophilic behavior should be suspected if red flags are present in a defendant charged with pedophilia. In those cases, an in depth trans-disciplinary neuroscientific investigation is advocated. The behavioral profile identified might help to provide a proper assessment of defendants. [ABSTRACT FROM AUTHOR]

Besides hyperglycaemia and insulin resistance, several factors are associated with a higher cardiovascular risk in type 2 diabetes mellitus (T2DM), many of them being closely related to each other owing to common origins or pathways. The pathophysiological mechanisms underlying vascular dysfunctions in diabetes include reduced bioavailability of nitric oxide, increased ROS and prothrombotic factors production, as well as activation of receptors for advanced glycation end-products. These alterations contribute to create a pro-inflammatory/thrombotic state that ultimately leads to plaque formation and complication. This study aimed at identifying differentially expressed plasma proteins between T2DM and non-diabetic patients undergoing carotid endarterectomy, by means of two-dimensional electrophoresis coupled with LC-MS/MS. Before analysis, plasma samples were enriched in low-expression proteins through combinatorial hexapeptide ligand libraries. Both mono- and two-dimensional western blotting were performed for data validation. Differentially expressed proteins were mapped onto STRING v10 to build a protein-protein interaction network. Sixteen differentially expressed spots were identified with a high score. Among them, there were fibrinogen beta and gamma chains, complement C1r, C3 and C4-B subcomponents, alpha-1-antitrypsin (AAT), vitronectin and CD5 antigen-like. Protein-Protein interaction analysis evidenced a network among differentially expressed proteins in which vitronectin seems to represent a potentially pivotal node among fibrinolysis, complement dependent immune responses and inflammation in accordance with a number of in vitro and in vivo evidences for a contributory role of these proteins to the development of diabetic atherosclerosis. [ABSTRACT FROM AUTHOR]