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Galectin-3 (Gal-3) is a multifunctional glycan-binding protein that participates in many pathophysiological events and has been described as a biomarker and potential therapeutic target for severe disorders, such as cancer. Several probes for Gal-3 or its ligands have been developed, however both the pathophysiological mechanisms and potential biomedical applications of Gal-3 remain not fully assessed. Molecular imaging using bioluminescent probes provides great sensitivity for in vivo and in vitro analysis for both cellular and whole multicellular organism tracking and target detection. Here, we engineered a chimeric molecule consisting of Renilla luciferase fused with mouse Gal-3 (RLuc-mGal-3). RLuc-mGal-3 preparation was highly homogenous, soluble, active, and has molecular mass of 65,870.95 Da. This molecule was able to bind to MKN45 cell surface, property which was inhibited by the reduction of Gal-3 ligands on the cell surface by the overexpression of ST6GalNAc-I. In order to obtain an efficient and stable delivery system, RLuc-mGal-3 was adsorbed to poly-lactic acid nanoparticles, which increased binding to MKN45 cells in vitro. Furthermore, bioluminescence imaging showed that RLuc-mGal-3 was able to indicate the presence of implanted tumor in mice, event drastically inhibited by the presence of lactose. This novel bioluminescent chimeric molecule offers a safe and highly sensitive alternative to fluorescent and radiolabeled probes with potential application in biomedical research for a better understanding of the distribution and fate of Gal-3 and its ligands in vitro and in vivo.

Purpose: To map and understand the influences of the hidden curriculum on the professional identity development of medical students based on the socialization process as proposed by Cruess et al. in a South American medical school. Method: Between 2014 and 2016, the authors performed 13 focus groups interviews with a total of 102 final-year medical students in Brazil and analyzed the data using thematic template analysis. Results: The authors identified three domains through which the hidden curriculum influences professional identity formation: (1) Speeding up - Repetition without reflection ends in a lack of awareness of professional identity formation; (2) Emotional dissonance in the context of negative role modeling; and (3) the conflict between personal and professional life. Discussion: As teachers “Speed up” the clinical encounters, acting as negative role models, students internalized behaviors without reflecting on their attitudes, which culminates in a state of dissonance between the physician they wanted to be and the professionals they actually are, triggering feelings of shame and guilt. Without feeling the rewards that a meaningful practice can provide, students struggled with the idea of sacrificing themselves to become physicians. Physicians/teachers who did not have a meaningful relationship with their profession, who did not cultivate the values and virtues of good medicine and did not found joy in being a physician were not able to nurture meaning and fulfillment in their students. The concepts of socialization and professional identity formation fit the purpose of grounding the local understanding of the several components of the hidden curriculum. The authors believe that this map can be used as a guide to design targeted pedagogical activities. Keywords: Emotional dissonance, Hidden curriculum, Professional identity

Aims In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models. Materials and methods DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC. HepG2 and Huh7 cells, stably transfected to overexpress SerpinB3, and respective control cells were used to assess biological and metabolic modifications of DPPIV/CD26 activity induced by this serpin. Key findings DPPIV/CD26 and SerpinB3 were localized in the same tumoral areas and both molecules were correlated with the grade of tumor differentiation, with the highest values detected in GI tumors. Cell lines over-expressing SerpinB3 displayed upregulation of DPPIV/CD26, likely as a feedback mechanism, due to the DPPIV/CD26 protease activity inhibition by SerpinB3, as confirmed by the similar behavior induced by the inhibitor Sitagliptin. Moreover, they exhibited lower glycogen storage and higher lipid accumulation, typical effects of DPPIV/CD26. Significance A close connection between SerpinB3 and DPPPIV has been identified, but further studies are required to better understand the mechanism by which these proteins communicate and exert metabolic effects in HCC.

Resume L’adhesion therapeutique demeure un defi quotidien pour les personnes vivant avec le VIH, et ce d’autant plus aupres de populations d’adolescents vivant de multiples transitions. De nombreux facteurs ont ete etudies pour expliquer l’adhesion therapeutique avec parfois des relations inconsistantes suivant les recherches. Cette etude a pour finalite de decrire les variables associees aux variations de l’adhesion therapeutique d’une cohorte d’adolescents vivant avec le VIH dans la region de Sao Paulo (Bresil). Une etude longitudinale a ete menee de mai 2011 (T0) a mai 2012 (T1) aupres d’adolescents bresiliens infectes par transmission verticale (materno-fœtale). Ainsi, 220 adolescents ont repondu aux deux temps de mesure (T0 et T1) a un questionnaire auto-administre comprenant des mesures d’adhesion et certaines variables psychosociales : le sentiment d’efficacite personnelle, le soutien social, le stress percu, la depression, la presence et l’intensite des symptomes lies a la tritherapie. Les resultats montrent que la moitie des repondants ont maintenu une adhesion therapeutique optimale au cours d’une annee (profil adherent). Ils se caracterisent, au niveau psychosocial, par une perception moins elevee du stress ( p = 0,019) mais aussi des symptomes lies a la medication autant en frequence ( p = 0,0407), qu’en intensite ( p = 0,028), ainsi que ceux lies a la depression ( p = 0,0033), avec un plus haut niveau de sentiment d’efficacite personnelle ( p

Systemic lupus erythematosus is an autoimmune disease that causes many psychological repercussions that have been studied through qualitative research. These are considered relevant, since they reveal the amplitude experienced by patients. Given this importance, this study aims to map the qualitative production in this theme, derived from studies of experiences of adult patients of both genders and that had used as a tool a semi-structured interview and/or field observations, and had made use of a sampling by a saturation criterion to determine the number of participants in each study. The survey was conducted in Pubmed, Lilacs, Psycinfo e Cochrane databases, searching productions in English and Portuguese idioms published between January 2005 and June 2012. The 19 revised papers that have dealt with patients in the acute phase of the disease showed themes that were categorized into eight topics that contemplated the experienced process at various stages, from the onset of the disease, extending through the knowledge of the diagnosis and the understanding of the manifestations of the disease, drug treatment and general care, evolution and prognosis. The collected papers also point to the difficulty of understanding, of the patients, on what consists the remission phase, revealing also that this is a clinical stage underexplored by psychological studies.

Summary Background The Pulmonary Embolism (PE) Severity Index (PESI) is a clinical prognostic rule that accurately classifies PE patients into five risk classes with increasing mortality. PESI score has been validated in studies with a relatively short-term follow-up and its accuracy in predicting long-term prognosis has never been established. Methods Consecutive patients admitted to the tertiary care hospital of Varese (Italy) with an objectively diagnosed PE between January 2005 and December 2009 were retrospectively included. Information on clinical presentation, diagnostic work-up, risk factors, treatment and mortality during a 1-year follow-up was collected. Results Five hundred and thirty-eight patients were enrolled in this study. The mean age was 70.6 years (± SD 15.2), 44.4% of patients were male, and 27.9% had known cancer. One-year follow-up was available for 96.1% of patients. The overall mortality rate was 23.2% at 3 months, 30.2% at 6 months and 37.1% at 12 months. The discriminatory power of the PESI score to predict long-term mortality, expressed as the area under the ROC curve, was 0.77 (95%CI, 0.72–0.81) at 3 months, 0.77 (95%CI, 0.73–0.81) at 6 months and 0.79 (95%CI, 0.75–0.82) at 12 months. The PESI score confirmed its accurate prediction in patients without cancer. Simplified PESI had a similar overall accuracy to the original PESI at 3 and 6 months, but this was significantly lower at 1 year. Conclusions The results of this study suggest that PESI score may also be an accurate tool to define the 6-month and 1-year mortality rates in PE patients.

Background There is little epidemiologic information from large multicenter databases on sustained monomorphic ventricular tachycardia occurring after the initial 48 hours of myocardial infarction. Methods We reassessed its incidence and short-term prognosis in 16,842 patients with a definite myocardial infarction enrolled in the Gruppo Italiano per lo Studio della Soprovvivenza nell'Infarto Miocardico (GISSI-3) trial. Results The incidence rate of late sustained ventricular tachycardia by 6 weeks was around 1%. Older age, a history of hypertension, diabetes, and myocardial infarction, nonadministration of lytic therapy, Killip class >I, ≥6 leads with ST-segment elevation, higher heart rate, and bundle branch block on admission were significantly more frequent among patients with than without late sustained ventricular tachycardia. Patients with ventricular tachycardia had a more complicated course in-hospital and posthospital to 6 weeks than the reference group did. The arrhythmia was associated with a significant excess of pump failure, atrial flutter-fibrillation, asystole, atrioventricular block, ventricular fibrillation within the first 48 hours of myocardial infarction, and recurrent ischemic events. Larger left ventricular end-systolic volumes and lower ejection fractions were more frequent among ventricular tachycardia patients than in the reference group by 6 weeks. Death rates by 6 weeks were 35% for patients with ventricular tachycardia and 5% for those without the arrhythmia. Irrespective of the stratification of patients by site and type of infarct and presence/absence of bundle branch block, the occurrence of the arrhythmia was associated with reduced 6-week survival. Conclusion In a proportional hazard regression model late sustained ventricular tachycardia was retained as a strong, independent predictor of 6-week mortality after myocardial infarction (hazard ratio 6.13, 95% confidence interval 4.56-8.25). (Am Heart J 2001;142:87-92.)

Background The year 2016 marks the bicentennial anniversary of the premiere of “The Barber of Seville” by Gioachino Rossini (1792–1868). This opera buffa, one of the most renowned in the world, puts on stage a sharp criticism against the physicians of that time in favour of empiric healers, respectively represented by the doctor Bartolo and the barber Figaro. Methods The paper analysed both the opera by Rossini and the French comedy “Le Barbier de Seville” (1775) by Pierre Beaumarchais (1732–1799), on which the Italian composer based his own play. Results The unlearned barber Figaro is portrayed as a poor but wise guy, while his rival, the graduated doctor Bartolo, is defined as an arrogant and opulent old physician. Dr. Bartolo's incompetence, lack of skill and ignorance are evident in the works by Rossini and Beaumarchais. Both plays show empiric and unskilled medicine triumphs over academic medicine, which appears weak in its scientific concepts and corrupted by money. Conclusions Arrogance, presumption and carelessness among physicians are a danger nowadays as they have been for a couple of hundred years, since they may not only lead to misjudgement and errors, but also to an increase of alternative medicines and strange healing remedies.

We have investigated the effect of pcDNA3-CpG and pcDNA-IL-12, delivered by intradermal gene gun administration, on the blood/lung eosinophilia, airway hyperresponsiveness as well as the immune response in a murine model of toxocariasis. Our results demonstrated that pcDNA-IL-12 but not pcDNA3-CpG vaccination led to a persistent lower blood/bronchoalveolar eosinophilia following Toxocara canis infection, as pcDNA3-CpG led only to an early transient blockage of eosinophil transmigration into bronchoalveolar fluid following T. canis infection. Prominent Type-1 immune response was pointed out as the hallmark of T. canis infection following pcDNA-IL-12 vaccination. Outstanding IFN-gamma/IL-4 ratio besides low levels of IgG1 with subsequent high IgG2a/IgG1 ratio further characterized a Type-1 polarized immunological profile in pcDNA-IL-12-vaccinated animals. Nevertheless, only pcDNA3-CpG was able to prevent airway hyperresponsiveness induced by T. canis infection. The persistent airway hyperresponsiveness observed in pcDNA-IL-12-vaccinated animals demonstrated that the airway constriction involved other immunological mediator than those blocked by pcDNA-IL-12. Together, these data indicated that pcDNA-IL-12 and pcDNA3-CpG vaccines have distinct therapeutic benefits regarding the eosinophilic inflammation/airway hyperresponsiveness triggered by T. canis infection, suggesting their possible use in further combined therapeutic interventions.

This is a four-step study to analyze a flood event which occurred over Friuli (north-eastern Italy) during October 1998. The first step is a synoptic analysis, in which the importance of moisture originated in the tropical Atlantic, and carried towards the Mediterranean by the remnants of a former tropical system, is emphasized. The second step analyzes the numerical forecast, as performed by the NCEP Medium range forecast (MRF) global model and by the limited area model called Eta model 1 ( Black, 1994 ; Mesinger, 1984 ; Mesinger et al., 1988 ), highlighting the importance of the large scale forcing. The third step involves multifractal modeling ( Deidda et al., 1999 ) on the rainfall forecast for two different simulations. Finally, the hydrological effects over land, produced by the predicted precipitation, are compared with the observed effects. The results suggest the importance of the correct representation of the large scale forcing for the regional models, and the crucial contribution of multifractal modeling to reproduce the spatial variability of the rainfall on a hydrologically significant scale.