Metastatic small bowel occlusion as initial presentation of squamous cell carcinoma of the lung

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Clinical communication skills and professionalism education are required from the beginning of medical training - a point of view of family physicians

Background: The Brazilian undergraduate medical course is six years long. As in other countries, a medical residency is not obligatory to practice as a doctor. In this context, this paper aims to clarify what and when competencies in communication and professionalism should be addressed, shedding light on the role of university, residency and post-residency programmes. Methods: Brazilian family physicians with diverse levels of medical training answered a questionnaire designed to seek a consensus on the competencies that should be taught (key competencies) and when students should achieve them during their medical training. The data were analysed using descriptive statistics and correlation tests. Results: A total of seventy-four physicians participated; nearly all participants suggested that the students should achieve communication and professionalism competencies during undergraduate study (twenty out of thirty competencies – 66.7%) or during residency (seven out of thirty competencies – 23.33%). When competencies were analysed in domains, the results were that clinical communication skills and professionalism competencies should be achieved during undergraduate medical education, and interpersonal communication and leadership skills should be reached during postgraduate study. Conclusion: The authors propose that attainment of clinical communication skills and professionalism competencies should be required for undergraduate students. The foundation for Leadership and Interpersonal Abilities should be particularly formed at an undergraduate level and, furthermore, mastered by immersion in the future workplace and medical responsibilities in residency.There was no direct financial support for this research. Financial support for the authors is provided by scholarships from the National Counsel of Technological and Scientific Development (CNPq), Brazil (229753/2013–2) and the Coordination for the Improvement of Higher Education Personnel (CAPES), Brazil (13271/13–0)

Insights Into the Effects of Mucosal Epithelial and Innate Immune Dysfunction in Older People on Host Interactions With Streptococcus pneumoniae

In humans, nasopharyngeal carriage of Streptococcus pneumoniae is common and although primarily asymptomatic, is a pre-requisite for pneumonia and invasive pneumococcal disease (IPD). Together, these kill over 500,000 people over the age of 70 years worldwide every year. Pneumococcal conjugate vaccines have been largely successful in reducing IPD in young children and have had considerable indirect impact in protection of older people in industrialized country settings (herd immunity). However, serotype replacement continues to threaten vulnerable populations, particularly older people in whom direct vaccine efficacy is reduced. The early control of pneumococcal colonization at the mucosal surface is mediated through a complex array of epithelial and innate immune cell interactions. Older people often display a state of chronic inflammation, which is associated with an increased mortality risk and has been termed ‘Inflammageing’. In this review, we discuss the contribution of an altered microbiome, the impact of inflammageing on human epithelial and innate immunity to S. pneumoniae, and how the resulting dysregulation may affect the outcome of pneumococcal infection in older individuals. We describe the impact of the pneumococcal vaccine and highlight potential research approaches which may improve our understanding of respiratory mucosal immunity during pneumococcal colonization in older individuals

Ovine leptospirosis in Brazil

Leptospirosis is a zoonosis distributed worldwide, endemic mainly in humid subtropical and tropical countries, with epidemic potential. It affects a range of both wild and domestic animals, including sheep, which transport leptospires in their urine and, therefore, can infect other animals and humans who deal with them. Therefore, leptospirosis is characterized as an occupational zoonosis. In individual herds leptospirosis can cause severe economic loss due to miscarriages and outbreaks of mastitis with a significant reduction of milk production. The disease is caused by Leptospira interrogans, which was reclassified into 13 pathogenic species, and distributed into more than 260 serovars classified into 23 serogroups. The clinical signs of infection may vary depending on the serovar and host. In maintenance hosts, antibody production is generally low; there are relatively mild signs of the disease, and a prolonged carrier state with organisms in the kidneys. In incidental hosts, the disease may be more severe, with high titers of circulating antibodies and a very short or nonexistent renal carrier state. In general, young animals with renal and hepatic failure have more serious infections than adults. Several diseases may produce symptoms similar to those of leptospirosis, so that laboratory confirmation, through microscopic agglutination test, for example, is required. The effectiveness of treatment depends on early diagnosis and appropriate therapy, depending on clinical features, since leptospirosis can develop into chronic liver disease and nephropathy, progressing towards death. Improvements in habitation and sanitary conditions, rodent control, vaccination, isolation and treatment of affected animals are the main measures for the control of leptospirosis

Constraining General Two Higgs Doublet Models by the Evolution of Yukawa Couplings

We study how general two Higgs doublet models can be constrained by considering their properties under renormalization group evolution of the Yukawa couplings. We take into account both the appearance of a Landau pole as well as off-diagonal Yukawa couplings leading to flavour changing neutral currents in violation with experimental constraints at the electroweak scale. We find that the latter condition can be used to limit the amount of Z2 symmetry breaking allowed in a given model.Comment: 28 pages, 10 figures, added discussion of evolution from high to low scales, to be published in JHE

Lentiviral Vector Production Titer Is Not Limited in HEK293T by Induced Intracellular Innate Immunity

Most gene therapy lentiviral vector (LV) production platforms employ HEK293T cells expressing the oncogenic SV40 large T-antigen (TAg) that is thought to promote plasmid-mediated gene expression. Studies on other viral oncogenes suggest that TAg may also inhibit the intracellular autonomous innate immune system that triggers defensive antiviral responses upon detection of viral components by cytosolic sensors. Here we show that an innate response can be generated after HIV-1-derived LV transfection in HEK293T cells, particularly by the transgene, yet, remarkably, this had no effect on LV titer. Further, overexpression of DNA sensing pathway components led to expression of inflammatory cytokine and interferon (IFN) stimulated genes but did not result in detectable IFN or CXCL10 and had no impact on LV titer. Exogenous IFN-β also did not affect LV production or transduction efficiency in primary T cells. Additionally, manipulation of TAg did not affect innate antiviral responses, but stable expression of TAg boosted vector production in HEK293 cells. Our findings demonstrate a measure of innate immune competence in HEK293T cells but, crucially, show that activation of inflammatory signaling is uncoupled from cytokine secretion in these cells. This provides new mechanistic insight into the unique suitability of HEK293T cells for LV manufacture

Lilia, A Showcase for Fast Bootstrap of Conversation-Like Dialogues Based on a Goal-Oriented System

International audienceRecently many works have proposed to cast human-machine interaction in a sentence generation scheme. Neural networks models can learn how to generate a probable sentence based on the user's statement along with a partial view of the dialogue history. While appealing to some extent, these approaches require huge training sets of general-purpose data and lack a principled way to intertwine language generation with information retrieval from back-end resources to fuel the dialogue with actualised and precise knowledge. As a practical alternative, in this paper, we present Lilia, a showcase for fast bootstrap of conversation-like dialogues based on a goal-oriented system. First, a comparison of goal-oriented and conversational system features is led, then a conversion process is described for the fast bootstrap of a new system, finalised with an on-line training of the system's main components. Lilia is dedicated to a chitchat task, where speakers exchange viewpoints on a displayed image while trying collaboratively to derive its author's intention. Evaluations with user trials showed its efficiency in a realistic setup

PCV13 induced IgG responses in serum associate with serotype-specific IgG in the lung

Pneumococcal conjugate vaccine efficacy is lower for non-invasive pneumonia than invasive disease. In this study, participants were vaccinated with PCV13 or HepA (control). Bronchoalveolar lavage samples were taken between 2-6 months and serum at 4- and 7-weeks post vaccination. In the lung, anti-capsular IgG levels were higher in the PCV13 group compared to control for all serotypes, except 3 and 6B. Systemically, IgG levels were elevated in the PCV group at 4-weeks for all serotypes, except 3. IgG in BAL and serum positively correlated for nearly all serotypes. PCV13 shows poor immunogenicity to serotype 3, implying lack of protective efficacy. Clinical trial registration with ISRCTN: 4534043

Alveolar T-helper 17 responses to streptococcus pneumoniae are preserved in ART-untreated and treated HIV-infected Malawian adults

Objective: We explored if HIV infection is associated with impaired T-Helper 17 responses against Streptococcus pneumoniae in the lung. Methods: We recruited 30 HIV-uninfected healthy controls, 23 asymptomatic HIV-infected adults not on ART, and 40 asymptomatic HIV-infected adults on ART (Median time 3.5yrs), in whom we collected bronchoalveolar lavage fluid. We measured alveolar CD4+ T cell immune responses following stimulation with pneumococcal cell culture supernatant using flow cytometry-based intracellular cytokine staining. Results: We found that the proportion of alveolar CD4+ T cells producing IL-17A following stimulation with pneumococcal cell culture supernatant (CCS) was similar between HIV-uninfected controls and ART-naïve HIV-infected adults (0.10% vs. 0.14%; p = 0.9273). In contrast, the proportion and relative absolute counts of CD4+ T cells producing IL-17A in response to pneumococcal CCS were higher in ART-treated HIV-infected adults compared HIV-uninfected controls (0.22% vs. 0.10%, p = 0.0166; 5420 vs. 1902 cells/100 ml BAL fluid; p = 0.0519). The increase in relative absolute numbers of IL-17A-producing alveolar CD4+ T cells in ART-treated individuals was not correlated with the peripheral blood CD4+ T cell count (r=–0.1876, p = 0.1785). Conclusion: Alveolar Th17 responses against S. pneumoniae are preserved in HIV-infected adults. This suggests that there are other alternative mechanisms that are altered in HIV-infected individuals that render them more susceptible to pneumococcal pneumonia