One special question to start with: can HIF/NFkB be a target in inflammation?

Hypoxia and Inflammation are strictly interconnected with important consequences at clinical and therapeutic level. While cell and tissue damage due to acute hypoxia mostly leads to cell necrosis, in chronic hypoxia, cells that are located closer to vessels are able to survive adapting their phenotype through the expression of a number of genes, including proinflammatory receptors for alarmins. These receptors are activated by alarmins released by necrotic cells and generate signals for master transcription factors such as NFkB, AP1, etc. which control hundreds of genes for innate immunity and damage repair. Clinical consequences of chronic inflammatory reparative response activation include cell and tissue remodeling, damage in the primary site and, the systemic involvement of distant organs and tissues. Thus every time a tissue environment becomes stably hypoxic, inflammation can be activated followed by chronic damage and cell death or repair with vessel proliferation and fibrosis. This pathway can occur in cancer, myocardial infarction and stroke, diabetes, obesity, neurodegenerative diseases, chronic and autoimmune diseases and age-related diseases. Interestingly, proinflammatory gene expression can be observed earlier in hypoxic tissue cells and, in addition, in activated resident or recruited leukocytes. Herewith, the reciprocal relationships between hypoxia and inflammation will be shortly reviewed to underline the possible therapeutic targets to control hypoxia-related inflammation in a number of epidemiologically important human diseases and conditions

Bleeding jejunal varices and portal thrombosis in a splenectomized patient with hereditary spherocytosis

Bleeding from varices located in the small bowel is a very uncommon finding; nonetheless, such events accompany with a high mortality rate (1– 4). Moreover, early diagnosis of jejunal or ileal varices cannot usually be accomplished with standard diagnostic tools (ie, esophagogastroduodenoscopy, colonoscopy). Most reports in the literature relate to subjects with liver cirrhosis, often with hepatocarcinoma; in unusual anatomical situations, varices may develop beyond the ligament of Treitz in adjunct to the far more common location in the esophageal and gastric wall. Thrombosis of the portal vein is a common feature in such conditions. Portal thrombosis has also been described in association with overt or latent myeloproliferative diseases (5); its occurrence in nonneoplastic hematological conditions in subjects with normal liver function is quite uncommon. This report describes the observation of jejunal varices, with repeated episodes of “melena of unknown origin,” some of which quite severe, as their clinical presentation in a patient with portal thrombosis and with otherwise absolutely normal liver function, who had undergone splenectomy for hereditary spherocytosis in early adolescence

Kaon physics with the KLOE detector

In this paper we discuss the recent finalized analyses by the KLOE experiment at DA$\Phi$NE: the CPT and Lorentz invariance test with entangled $K^0 \bar{K}^0$ pairs, and the precision measurement of the branching fraction of the decay ${ K^+} \rightarrow \pi^+\pi^-\pi^+(\gamma)$. We also present the status of an ongoing analysis aiming to precisely measure the $K^{\pm}$ mass

A Cross-Sectional Survey on Burnout Prevalence and Profile in the Sicilian Population of Ambulance Driver-Rescuers

Introduction: Burnout is present at a high rate in emergency medicine. The ambulance driver-rescuers, who furnish first aid to the victims, are the non-medical part of the Italian 118-service staff. There is a lack of research on burnout risk in Italian Emergency Medical Services and, particularly, for this category of workers. The two Italian studies, including a little group of ambulance driver-rescuers, reported inconsistent findings. Hypothesis: This survey investigated for the first time the prevalence and exact profile of burnout in a large sample of Italian driver-rescuers. As a secondary aim, the study described how the items of the Italian version of the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) cluster in components in this sample. Methods: This cross-sectional census survey was conducted from June 2015 through May 2016 and involved all the driver-rescuers operating in Sicily, the biggest and most southern region of Italy. The subjects received a classification according to different profiles of burnout by using the Italian version of the MBI-HSS (burnout, engagement, disengagement, over-extension, and work-inefficacy). In order to explore the existence of independent factors, a Principal Component Analysis (PCA) was conducted on the survey to obtain eigenvalues >one for each component in the data. Results: The final sample comprised 2,361 responders (96.6% of the initial sample). Of them, 29.8% were in burnout (95% confidence interval [CI], 27.8% to 31.8%) and 1.7% presented a severe form (95% CI, 1.1% to 2.3%); 30.0% were engaged in their work (95% CI, 21.0% to 34.8%), 24.7% of responders were disengaged (95% CI, 22.9% to 26.5%), 1.2% presented an over-extension profile (95% CI, 0.8% to 1.7%), and 12.6% felt work-inefficacy (95% CI, 11.3% to 14.1%). The factors loaded into a five-factor solution at PCA, explaining 48.1% of the variance and partially replicating the three-factor structure. The Emotional Exhaustion (EE) component was confirmed. New dimensions from Personal Accomplishment (PA) and Depersonalization (DP) sub-scales described empathy and disengagement with patients, respectively, and were responsible for the increased risk of burnout. Conclusions: These results endorse the importance of screening and psychological interventions for this population of emergency workers, where burnout could manifest itself more insidiously. It is also possible to speculate that sub-optimal empathy skills could be related to the disengagement and work-inefficacy feelings registered

Mesothelioma incidence in the neighbourhood of an asbestos-cement plant located in a national priority contaminated site

Background. An epidemic of asbestos-related disease is ongoing in most industrialized countries, mainly attributable to past occupational exposure but partly due to environ-mental exposure. In this perspective, the incidence of pleural mesothelioma close to a former asbestos-cement plant in a national contaminated site was estimated. Methods. The census-tracts interested by atmospheric dispersion of facilities in the contaminated site were identified. Two subareas with different estimated environmental asbestos impact were distinguished. An ecological study at micro-geographic level was performed. The standardized incidence ratios (SIR) for study area and the two subareas, in comparison with region and municipality were computed. The standardized incidence rate ratio (IRR) between the two subareas was computed. Results. Mesothelioma incidence in the study area was increased: 46 cases were ob-served with respect to 22.23 expected (SIR: 2.02). The increase was confirmed in analysis considering only the subjects without an occupationally exposure to asbestos: 19 cases among men (SIR = 2.48; 95% CI: 1.49-3.88); 11 case among women (SIR = 1.34; 95% CI: 0.67-2.40). The IRR between the two subareas is less than one in overall population considering all age-classes and of 3 fold (IRR = 3.14, 95% CI: 0.65-9.17) in the age- classes below 55 years. Conclusions. The findings indicate an increased incidence of pleural mesothelioma in the neighbourhood of asbestos-cement plant, and a possible etiological contribution of asbestos environmental exposure in detected risks

Legionella control in the water system of antiquated hospital buildings by shock and continuous hyperchlorination: 5 years experience

To control the presence of Legionella in an old hospital water system, an integrated strategy of water disinfection-filtration was implemented in the university hospital Umberto I in Rome. Due to antiquated buildings, hospital water system design and hospital extension (38 buildings), shock hyperchlorination (sodium hypochlorite, 20-50 ppm of free chlorine at distal points for 1-2 h) followed by continuous hyperchlorination (0.5-1.0 mg/L at distal points) were adopted, and microbiological and chemical monitoring of the water supply was carried out in the university hospital (December 2006-December 2011). Overall, 1308 samples of cold 45°C (17.8%) water were collected, determining residual free chlorine (0.43 ± 0.44 mg/L), pH (7.43 ± 0.29) and trihalomethanes (8.97 ± 18.56 μg/L). Legionella was isolated in 102 (9.8%) out of 1.041 water samples without filters (L. pneumophila sg 1 17.6%, L. pneumophila sg 2-14 28.4%, L. non pneumophila 53.9%), and in none of the 267 samples with filters. Legionella was recovered in 23 buildings out of 38 and 29 samples (28.4%) exceeded 103 cfu/L. When considering the disinfection treatment Legionella was isolated: before shock hyperchlorination (21.1%), 15 days after shock hyperchlorination (7.8%), 30 days after shock hyperchlorination (3.5%), during continuous hyperchlorination (5.5%) and without continuous hyperchlorination (27.3%). Continuous hyperchlorination following the shock treatment achieved >70% reduction of positive samples, whereas no continuous hyperchlorination after shock treatment was more frequently associated to Legionella isolation (OR 6.41; 95% CI 3.10-13.26; p 0.5 < 1.0 mg/L) deteriorated water quality (organoleptic and chemical). However, shock and continuous hyperchlorination remains a valid-term option in old buildings with no water system rational design, managing problems due to hospital extension and absence of a proper hot water recirculation system

Secretory leukoprotease inhibitor is required for efficient quercetin-mediated suppression of TNFα secretion

Dendritic cells (DCs) are professional antigen presenting cells (APCs) that in response to microbial infections generate long-lasting adaptive immune response. Following microbial uptake, DCs undergo a cascade of cellular differentiation that ultimately leads to “mature” DCs. Mature DCs produce a variety of inflammatory cytokines, including tumor necrosis factor-α (TNFα) a key cytokine for the inflammatory cascade. In numerous studies, polyphenols, including quercetin, demonstrated their ability to suppress TNFα secretion and protect from the onset of chronic inflammatory disorders. We show that murine bone marrow derived DCs express Slpi following quercetin exposure. Slpi is known to suppress LPS mediated NFκB activation, thus, it was hypothesized that its expression could be the key step for polyphenol induced inflammatory suppression. Slpi-KO DCs poorly respond to quercetin administration failing to reduce TNFα secretion in response to quercetin exposure. Supernatant from quercetin exposed DCs could also reduce LPS-mediated TNFα secretion by unrelated DCs, but this property is lost using an anti-Slpi antibody. In vivo, oral administration of quercetin is able to induce Slpi expression. Human biopsies from inflamed tract of the intestine reveal the presence of numerous SLPI(+) cells and the expression level could be further increased by quercetin administration. We propose that quercetin induces Slpi expression that in turn reduces the inflammatory response. Our data encourages the development of nutritional strategies to improve the efficiency of current therapies for intestinal chronic inflammatory syndrome and reduce the risks of colorectal cancer development

Optimization of Laboratory Diagnostics of Primary Biliary Cholangitis: When Solid-Phase Assays and Immunofluorescence Combine

The laboratory diagnostics of primary biliary cholangitis (PBC) have substantially improved, thanks to innovative analytical opportunities, such as enzyme-linked immunosorbent assays (ELISA) and multiple immunodot liver profile tests, based on recombinant or purified antigens. This study aimed to identify the best diagnostic test combination to optimize PBC diagnosis. Between January 2014 and March 2017, 164 PBC patients were recruited at the hospitals of Parma, Modena, Reggio-Emilia, and Piacenza. Antinuclear antibodies (ANA) and anti-mitochondrial antibodies (AMA) were assayed by indirect immunofluorescence (IIF), ELISA, and immunodot assays (PBC Screen, MIT3, M2, gp210, and sp100). AMA-IIF resulted in 89.6% positive cases. Using multiple immunodot liver profiles, AMA-M2 sensitivity was 94.5%, while anti-gp210 and anti-sp100 antibodies were positive in 16.5% and 17.7% of patients, respectively. PBC screening yielded positive results in 94.5% of cases; MIT3, sp100, and gp210 were detected by individual ELISA test in 89.0%, 17.1%, and 18.9% of patients, respectively. The association of PBC screening with IIF-AMA improved the diagnostic sensitivity from 89.6% to 98.2% (p &lt; 0.01). When multiple immunodot liver profile testing was integrated with AMA-IIF, the diagnostic sensitivity increased from 89.1% to 98.8% (p &lt; 0.01). The combination of IIF with solid-phase methods significantly improved diagnostic efficacy in PBC patients