Advancements in reperfusion rates and quality of care for ST-segment elevation myocardial infarction: a ten-year evaluation of Salvador's STEMI network.

Background: Continuous investment and systematic evaluation of program accomplishments are required to achieve excellence in ST-segment elevation myocardial infarction (STEMI) care, especially in resource-limited settings. Therefore, this study evaluates the impact of problem-driven interventions on reperfusion use rate in a long-term operating STEMI network from a low- to middle-income country. Methods: This is a healthcare improvement evaluation study of Salvador's public STEMI network in a quasi-experimental design, comparing data from 2009 to 2010 (pre-intervention) and 2019-2020 (post-intervention). There were evaluated all confirmed STEMI cases assisted in both periods. The interventions, implemented since 2017, included: expanding the support team, defining criteria to be a spoke, and initiating continuous education activities. The primary outcome was the rate of patients undergoing reperfusion, with secondary outcomes being time from door-to-ECG (D2E) and ECG-to-STEMI-team trigger (E2T). Results: Over ten years, the network's coverage increased by 300,000 individuals, and expanded by 1,800 km2. A total of 885 records were analyzed, 287 in the pre-intervention group (182 men [63·4%]; mean [SD] age 62·1 [12·5] years) and 598 in the post-intervention group (356 men [59·5%]; mean [SD] age 61.9 [11·8] years). It was noticed a substantial increase in reperfusion delivery rate (90 [31%] vs. 431 [73%]; P = 001) and reductions in time from D2E (159 [83-340] vs. 29 [15-63], P = 001), and E2T (31 [21-44] vs. 16 [6-40], P = 001). Conclusion: The strategies adopted by Salvador's STEMI network were associated with significant improvements in the rate of patients undergoing reperfusion and in D2E and E2T. However, the mortality rate remains high.

Stress and exhaustion among medical students: a prospective longitudinal study on the impact of the assessment period on medical education.

BACKGROUND: Stress significantly affects both the physical and emotional health of individuals, particularly students in health-related fields. Medical students in Brazil face unique challenges due to the demanding nature of their studies, especially during assessment periods, which heighten academic pressure. These pressures often lead to poor coping strategies and mental health concerns. It is crucial to understand the complex dynamics of stress within medical education to develop strategies that improve student well-being and promote a healthier academic environment. This study aims to investigate the intricate relationship between assessment periods and stress levels among medical students. It seeks to understand how academic demands and sociodemographic factors contribute to stress dynamics during these periods. METHODS: An online observational, longitudinal, and prospective study was conducted from February to October 2022. Medical students were recruited through snowball sampling and participated in surveys administered via Google Forms at two timepoints: before (T1) and during (T2) assessment periods. The surveys collected sociodemographic data and stress symptoms using Lipp's Inventory of Stress Symptoms for Adults (LSSI). RESULTS: The transition from T1 to T2 was defined by a rise in the prevalence of stress from 59.6 to 84.2% (p = 0.001) and a decline in symptom-free students from 40.4 to 15.8% (p = 0.001). There was a significant increase in exhaustion, from 12.3 to 31.6% (p = 0.0001). Higher stress levels were notably more prevalent among younger students (≤ 24 years), females, those from wealthier families, students without scholarships, those without prior degrees, and those in the clinical phase of their studies. However, non significant correlations were found between these sociodemographic and academic factors and the increase in stress. CONCLUSION: The findings highlight significant concerns regarding the mental health of medical students during assessment periods, marked by increased stress and exhaustion levels. These results emphasize the need for proactive interventions to manage stress effectively in medical education, considering its profound impact on students' well-being.

The sound of silent RNA in tuberculosis and the lncRNA role on infection.

Tuberculosis (TB) is one of the leading causes of death worldwide, and Diabetes Mellitus is one of the major comorbidities (TB/DM) associated with the disease. A total of 103 differentially expressed ncRNAs have been identified in the TB and TB/DM comparisons. A machine learning algorithm was employed to identify the most informative lncRNAs: ADM-DT, LINC02009, LINC02471, SOX2-OT, and GK-AS1. These lncRNAs presented substantial accuracy in classifying TB from HC (AUCs >0.85) and TB/DM from HC (AUCs >0.90) in the other three countries. Genes with significant correlations with the five lncRNAs enriched common pathways in Brazil and India for both TB and TB/DM. This suggests that lncRNAs play an important role in the regulation of genes related to the TB immune response.

Mentoria científica na graduação em Medicina: repercussões na satisfação, engajamento e produção discente / Scientific mentoring in undergraduate medical school: impacts on student satisfaction, engagement and production

Resumo: Introdução: A mentoria é uma estratégia acadêmica que está cada vez mais presente no curso de Medicina por promover benefícios, como a criação de ambientes de acolhimento e afetividade, e discussão de conteúdos médicos e de temas relacionados à formação profissional. Entretanto, pouco se discute acerca dessa estratégia com finalidades científicas. Objetivo: Este estudo teve como objetivos descrever a implementação do programa de mentorias científicas, investigar a percepção dos estudantes sobre a sua implantação e execução, além de mensurar indicadores de êxito. Método: Trata-se de estudo seccional descritivo, realizado em um curso de graduação em Medicina, localizado em Salvador/Bahia. Foram incluídos estudantes do terceiro ao quarto ano da graduação. Aplicou-se um questionário virtual, estruturado, anônimo, com perguntas objetivas relacionadas ao perfil discente, às percepções sobre o programa de mentorias científicas e à publicação dos trabalhos de conclusão de curso (TCC). Resultado: Dos 143 estudantes participantes, houve predominância de solteiros (90,9%), pardos (46,2%), do sexo feminino (72,0%), com idade de 25,3 ± 5,54 anos, que não participaram de programas de iniciação científica (88,8%). Dentre aqueles que participaram das mentorias (n = 101), 97,1% afirmaram que elas contribuíram para o desenvolvimento do TCC, 98,0% se mostraram favoráveis à manutenção de sua oferta e 85,0% consideraram a estratégia inovadora. No recorte temporal de dois semestres letivos, apresentaram-se 131 TCC, dos quais 27,5% foram publicados contando com a participação de 19 professores, com média de 1,89 produção/professor. Conclusão: Os estudantes de Medicina são favoráveis à implementação do sistema de mentorias científicas, tendo essa estratégia se mostrado factível e eficaz.

Abstract: Introduction: Mentoring is an academic strategy that is increasingly present in the medical course, as it promotes benefits such as the creation of welcoming and affective environments, discussion of medical content and topics related to professional training. However, little is discussed about this strategy for scientific purposes. Objectives: To describe the implementation of the scientific mentoring program, investigate the students' perception of its implementation and performance, in addition to measuring success indicators. Methods: This was a cross-sectional, descriptive study carried out in an undergraduate medical course, located in Salvador/Bahia. Students from the 3rd to the 4th year of undergraduate school were included. A virtual, structured, anonymous questionnaire was applied, with objective questions related to the students' profile, their perceptions in relation to the scientific mentorship program and the publication of the Term Paper (TP). Results: Of the 143 participating students, there was a predominance of single (90.9%), brown (46.2%), female individuals (72.0%), aged 25.3±5.54 years, those who did not participate in Undergraduate Research programs (88.8%). Among those who participated in mentorships (n=101), 97.1% considered that they contributed to the development of the TP, 98.0% are in favor of maintaining its offer and 85.0% consider the strategy to be innovative. In the time frame of two academic semesters, 131 TPs were presented, of which 27.5% were published with the participation of 19 teachers, with an average of 1.89 productions/teacher. Conclusion: Medical students are in favor of implementing the scientific mentoring system, and this strategy has shown to be feasible and effective.

Clinical and immunopathological findings during long term follow-up in Leishmania infantum experimentally infected dogs.

Canine Visceral Leishmaniasis (CVL) is caused by Leishmania infantum, which in the New World is transmitted by Lutzomyia longipalpis. While prospective clinical and immunological assessments of dogs experimentally challenged with L. infantum have been previously reported over a relatively short follow-up period, the long-term characterization of infected animals has not been performed to date. We evaluated dogs in a subclinical state for six years following experimental infection with L. infantum and Lu. longipalpis saliva, via an intradermal route, to characterize clinical, parasitological and immunological parameters arising from L. infantum experimental infection. We also assess these parameters in a group of naturally infected animals. The immune profiles of the experimentally and naturally infected animals exhibited increases of IFN-γ, IL-6 and IL-18, and decreases in TNF, IL-2, IL-8 and CXCL1, compared to controls. Our results indicate that over a six-year follow-up post-challenge, subclinically infected dogs presented low CVL clinical scores despite the persistence of Leishmania parasites in the lymph nodes, spleen and skin. Similarities observed among immune profiles in the context of experimental and natural infection seem to suggest that an enduring activation of the host immune response may lead to the control of parasite growth, thereby limiting disease severity.

Tuberculosis-immune reconstitution inflammatory syndrome in HIV: from pathogenesis to prediction.

Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is an exaggerated, dysregulated immune response against dead or viable antigens of Mycobacterium tuberculosis that frequently occurs after initiation of antiretroviral therapy despite an effective suppression of HIV viremia. Scientific advances in IRIS pathogenesis have led researchers and clinicians to postulate risk factors that could possibly predict this syndrome, in an attempt to reduce the incidence and the severity of IRIS, with appropriate anti-inflammatory therapy. This review is a summary of the available literature on pathogenic mechanisms involved from the macro to the micro level, the clinical spectrum, available predictors and the scope of these biomarkers to function as specific therapeutic targets, that could effectively modulate or ameliorate this syndrome in future.

Assessing patient satisfaction with cataract surgery under topical anesthesia supplemented by intracameral lidocaine combined with sedation / Avaliação da satisfação dos pacientes submetidos à facectomia por facoemulsificação realizada com anestesia tópica associada à lidocaína na câmara anterior combinada com sedação

PURPOSE: Ocular akinesia, the use of anticoagulants, and patient collaboration are some of the factors that must be taken into consideration when choosing the appropriate anesthesia for phacoemulsification cataract surgery. The satisfaction of patients with the use of topical anesthesia and conscious sedation for this procedure has not been enough described in Brazil. Conscious sedation allows patient walk and answer a voice command. To assess the satisfaction, pain, and perioperative hemodynamic alterations of patients subjected to phacoemulsification under conscious sedation and topical anesthesia supplemented with intracameral lidocaine. METHODS: Prospective cohort non-controlled study that included patients treated by the same surgical team over a 70-day period. Sedation was performed with midazolam at a total dose of 3 mg and topical anesthesia with 0.5% proxymetacaine chlorhydrate and 2% lidocaine gel combined with 2% lidocaine by intracameral route. The intraoperative vital parameters, scores based on the Iowa Satisfaction with Anesthesia Scale (ISAS), and the pain visual analog scale (VAS) were recorded at several time points after surgery. RESULTS: A total of 106 patients were enroled in study (73.6% female), the mean age was 65.9 years. The surgical procedures lasted 11.2 minutes on average. The hemodynamic parameters did not exhibit significant changes at any of the investigated time points. The average ISAS score was 2.67 immediately after surgery and 2.99 eight hours after the surgery; this increase was statistically significant (p<0.0001). More than two-thirds (68.9%) of the participants (73 patients) did not report any pain in the transoperative period, and 98.1% of patients denied the occurrence of pain after surgery. CONCLUSIONS: Patients that received topical anesthesia supplemented by intracameral lidocaine combined with sedation for phacoemulsification cataract surgery reported adequate level of satisfaction with the anesthetic choice. Furthermore, the patients exhibited hemodynamic parameter stability and pain control.

OBJETIVO: Acinesia ocular, uso de anticoagulantes e cooperação do paciente são fatores envolvidos na escolha da anestesia para cirurgia de catarata por facoemulsificação. A satisfação com anestesia tópica associada à sedação consciente neste procedimento foi pouco descrita no Brasil. Sedação consciente permite que o paciente sedado mantenha a capacidade de deambular e de responder ao chamado de voz. Avaliar a satisfação, dor e alterações hemodinâmicas perioperatórias de pacientes submetidos à facoemulsificação sob sedação consciente por anestesia tópica com injeção de lidocaína na câmara anterior. MÉTODOS: Estudo de coorte prospectivo, não controlado de pacientes operados pela mesma equipe em um período de 70 dias. Realizada sedação com 3 mg de midazolam, anestesia tópica com cloridrato de proximetacaína 0,5% e lidocaína gel 2%, associada à injeção de lidocaína 2% na câmara anterior. Registrados parâmetros vitais intraoperatórios, escala de satisfação com a anestesia de Iowa (ISAS) e a Escala Analógica Visual da Dor (EVA) em diferentes períodos do pós-operatório. RESULTADOS: Foram avaliados 106 pacientes (73,6% do sexo feminino), com idade média de 65,9 anos. O tempo cirúrgico médio foi de 11,2 minutos. Não houve diferença estatisticamente significante entre as variáveis hemodinâmicas nos momentos estudados. Ao final da operação, a média de escores na escala ISAS foi de 2,67 e 8 horas após foi de 2,99, apresentando aumento significativo (p<0,0001). Não houve relato de qualquer dor transoperatória em 68,9% dos casos, e 98,10% dos pacientes negaram dor pós-operatória. CONCLUSÕES: Em cirurgia de facectomia por facoemulsificação realizada sob sedação consciente associada à anestesia tópica com injeção de lidocaína 2% na câmara anterior, obtêm-se níveis adequados de satisfação com a anestesia, estabilidade de variáveis hemodinâmicas durante o procedimento e adequado controle da dor.

Analysis of theoretical knowledge and the practice of science among Brazilian otorhinolaryngologists.

UNLABELLED: Physicians from all medical specialties are required to understand the principles of science and to interpret medical literature. Yet, the levels of theoretical and practical knowledge held by Brazilian otorhinolaryngologists has not been evaluated to date. OBJECTIVE: To assess the background and level of scientific knowledge of Brazilian otorhinolaryngologists. METHOD: Participants of two national ENT meetings were invited to answer a questionnaire to assess scientific practice and knowledge. RESULTS AND CONCLUSION: This study included 73 medical doctors (52% otorhinolaryngologists and 38% residents) aged between 18 and 65 years. About two-thirds have been involved in some form of scientific activity during undergraduate education and/or reported to have written at least one scientific paper. Physicians who took part in research projects felt better prepared to interpret scientific papers and carry out research projects (p = 0.0103 and p = 0.0240, respectively). Respondents who claimed to have participated in research or to have written papers had higher scores on theoretical scientific concepts (p = 0.0101 and p = 0.0103, respectively). However, the overall rate of right answers on questions regarding scientific knowledge was 46.1%. Therefore, a deficiency was observed in the scientific education of Brazilian otorhinolaryngologists. Such deficiency may be mitigated through participation in research.

Análise do conhecimento teórico e prática científica entre otorrinolaringologistas brasileiros / Analysis of theoretical knowledge and the practice of science among Brazilian otorhinolaryngologists

A compreensão dos princípios científicos e a interpretação de artigos é necessária em qualquer especialidade médica. Entretanto, inexistem publicações sobre o conhecimento teórico e prático dos otorrinolaringologistas brasileiros. OBJETIVO: Avaliar a formação e o conhecimento científico de médicos da área de Otorrinolaringologia. MÉTODO: Durante dois congressos nacionais da especialidade, os participantes foram convidados a preencher questionário sobre prática e conhecimento científico para residentes e especialistas dessa área. RESULTADOS E CONCLUSÃO: Participaram do estudo 73 médicos (52% otorrinolaringologistas e 38% residentes), com idade entre 18 e 65 anos. Cerca de dois terços envolveram-se em alguma atividade científica durante a graduação e/ou referiram já ter escrito um artigo científico. Os médicos que já participaram de projetos de pesquisa sentem-se mais preparados para interpretar um artigo científico e conduzir um projeto de pesquisa (p = 0,0103 e p = 0,0240, respectivamente). Aqueles que participaram de projetos de pesquisa ou já escreveram um artigo tiveram melhor desempenho nos conceitos científicos teóricos (p = 0,0101 e p = 0,0103, respectivamente). Entretanto, o índice geral de acertos nas questões referentes ao conhecimento científico foi de 46,1%. Dessa forma, identificamos que há deficiências na formação científica dos otorrinolaringologistas brasileiros que podem ser atenuadas pela participação em projetos de pesquisa.

Physicians from all medical specialties are required to understand the principles of science and to interpret medical literature. Yet, the levels of theoretical and practical knowledge held by Brazilian otorhinolaryngologists has not been evaluated to date. OBJECTIVE: To assess the background and level of scientific knowledge of Brazilian otorhinolaryngologists. METHOD: Participants of two national ENT meetings were invited to answer a questionnaire to assess scientific practice and knowledge. RESULTS AND CONCLUSION: This study included 73 medical doctors (52% otorhinolaryngologists and 38% residents) aged between 18 and 65 years. About two-thirds have been involved in some form of scientific activity during undergraduate education and/or reported to have written at least one scientific paper. Physicians who took part in research projects felt better prepared to interpret scientific papers and carry out research projects (p = 0.0103 and p = 0.0240, respectively). Respondents who claimed to have participated in research or to have written papers had higher scores on theoretical scientific concepts (p = 0.0101 and p = 0.0103, respectively). However, the overall rate of right answers on questions regarding scientific knowledge was 46.1%. Therefore, a deficiency was observed in the scientific education of Brazilian otorhinolaryngologists. Such deficiency may be mitigated through participation in research.

Biomarkers of inflammation and coagulation are associated with mortality and hepatitis flares in persons coinfected with HIV and hepatitis viruses.

BACKGROUND: Hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection with human immunodeficiency virus (HIV) has a greater risk of mortality than either HCV or HBV infection alone and is frequently associated with hepatitis flares after antiretroviral therapy (ART) initiation. METHODS: We performed a retrospective cohort study of 287 HIV-positive persons coinfected with HBV and/or HCV (70 had HBV coinfection only, 207 had HCV coninfection only, and 10 had HBV and HCV coinfections) who had pre-ART plasma samples evaluated for biomarkers associated with death (within 4 years) and/or hepatitis flare (within 4 months) after ART initiation. A predictive biomarker risk score was calculated. RESULTS: Forty-eight deaths and 50 hepatitis flares occurred. Nonsurvivors were older, had more prior AIDS-defining events, and had higher pre-ART triglycerides and aspartate transaminase levels. Detectable hyaluronic acid and higher d-dimer, interleukin 6, interleukin 8, and soluble CD14 levels were associated with death in univariate models and with a composite biomarker risk score. The risk of hepatitis flares was higher with HBV coinfection only (24.3%) and with HBV and HCV coinfection (50%) than with HCV coinfection only (13.5%). Higher levels of alanine transaminase and interleukin 10 were also associated with hepatitis flares. CONCLUSIONS: Among HIV-positive patients coinfected with HBV and/or HCV who are initiating ART, biomarkers of inflammation and coagulation are associated with an increased risk of death, whereas HBV coinfection and higher pre-ART interleukin 10 levels are associated with hepatitis flares.

Assessing patient satisfaction with cataract surgery under topical anesthesia supplemented by intracameral lidocaine combined with sedation.

PURPOSE: Ocular akinesia, the use of anticoagulants, and patient collaboration are some of the factors that must be taken into consideration when choosing the appropriate anesthesia for phacoemulsification cataract surgery. The satisfaction of patients with the use of topical anesthesia and conscious sedation for this procedure has not been enough described in Brazil. Conscious sedation allows patient walk and answer a voice command. To assess the satisfaction, pain, and perioperative hemodynamic alterations of patients subjected to phacoemulsification under conscious sedation and topical anesthesia supplemented with intracameral lidocaine. METHODS: Prospective cohort non-controlled study that included patients treated by the same surgical team over a 70-day period. Sedation was performed with midazolam at a total dose of 3 mg and topical anesthesia with 0.5% proxymetacaine chlorhydrate and 2% lidocaine gel combined with 2% lidocaine by intracameral route. The intraoperative vital parameters, scores based on the Iowa Satisfaction with Anesthesia Scale (ISAS), and the pain visual analog scale (VAS) were recorded at several time points after surgery. RESULTS: A total of 106 patients were enrolled in study (73.6% female), the mean age was 65.9 years. The surgical procedures lasted 11.2 minutes on average. The hemodynamic parameters did not exhibit significant changes at any of the investigated time points. The average ISAS score was 2.67 immediately after surgery and 2.99 eight hours after the surgery; this increase was statistically significant (p<0.0001). More than two-thirds (68.9%) of the participants (73 patients) did not report any pain in the transoperative period, and 98.1% of patients denied the occurrence of pain after surgery. CONCLUSIONS: Patients that received topical anesthesia supplemented by intracameral lidocaine combined with sedation for phacoemulsification cataract surgery reported adequate level of satisfaction with the anesthetic choice. Furthermore, the patients exhibited hemodynamic parameter stability and pain control.

Metabolic adaptation to tissue iron overload confers tolerance to malaria.

Disease tolerance is a defense strategy that limits the fitness costs of infection irrespectively of pathogen burden. While restricting iron (Fe) availability to pathogens is perceived as a host defense strategy, the resulting tissue Fe overload can be cytotoxic and promote tissue damage to exacerbate disease severity. Examining this interplay during malaria, the disease caused by Plasmodium infection, we find that expression of the Fe sequestering protein ferritin H chain (FtH) in mice, and ferritin in humans, is associated with reduced tissue damage irrespectively of pathogen burden. FtH protection relies on its ferroxidase activity, which prevents labile Fe from sustaining proapoptotic c-Jun N-terminal kinase (JNK) activation. FtH expression is inhibited by JNK activation, promoting tissue Fe overload, tissue damage, and malaria severity. Mimicking FtH's antioxidant effect or inhibiting JNK activation pharmacologically confers therapeutic tolerance to malaria in mice. Thus, FtH provides metabolic adaptation to tissue Fe overload, conferring tolerance to malaria.

Biomarkers for exposure to sand flies bites as tools to aid control of leishmaniasis.

Intense research efforts so far have not been sufficient to reduce leishmaniasis burden worldwide. This disease is transmitted by bites of infected sand flies, which inject saliva in the host skin in an attempt to obtain a blood meal. Sand fly saliva has an array of proteins with diverse pharmacological properties that modulates the host homeostatic and immune responses. Some of these proteins are also immunogenic and can induce both cellular and humoral immune responses. Recently, the use of sand fly salivary proteins to estimate exposure to sand fly bites and consequently the risk of infection has emerged. Here, we review evidence that supports the use of the host immune responses against sand fly salivary proteins to estimate risk of infection. We also discuss how the use of recombinant salivary proteins can optimize serological surveys and provide guidance for the implementation of specific measures for disease control in endemic areas.

Biomarkers for susceptibility to infection and disease severity in human malaria.

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.

Biomarkers for susceptibility to infection and disease severity in human malaria

Malaria remains a major infectious disease that affects millions of people. Once infected with Plasmodium parasites, a host can develop a broad range of clinical presentations, which result from complex interactions between factors derived from the host, the parasite and the environment. Intense research has focused on the identification of reliable predictors for exposure, susceptibility to infection and the development of severe complications during malaria. Although most promising markers are based on the current understanding of malaria immunopathogenesis, some are also focused more broadly on mechanisms of tissue damage and inflammation. Taken together, these markers can help optimise therapeutic strategies and reduce disease burden. Here, we review the recent advances in the identification of malarial biomarkers, focusing on those related to parasite exposure and disease susceptibility. We also discuss priorities for research in biomarkers for severe malaria.

Can score databanks help teaching?

BACKGROUND: Basic courses in most medical schools assess students' performance by conferring scores. The objective of this work is to use a large score databank for the early identification of students with low performance and to identify course trends based on the mean of students' grades. METHODOLOGY/PRINCIPAL FINDINGS: We studied scores from 2,398 medical students registered in courses over a period of 10 years. Students in the first semester were grouped into those whose ratings remained in the lower quartile in two or more courses (low-performance) and students who had up to one course in the lower quartile (high-performance). ROC curves were built, aimed at the identification of a cut-off average score in the first semesters that would be able to predict low performances in future semesters. Moreover, to follow the long-term pattern of each course, the mean of all scores conferred in a semester was compared to the overall course mean obtained by averaging 10 years of data. Individuals in the low-performance group had a higher risk of being in the lower quartile of at least one course in the second semester (relative risk 3.907; 95% CI: 3.378-4.519) and in the eighth semester (relative risk 2.873; 95% CI: 2.495-3.308). The prediction analysis revealed that an average score of 7.188 in the first semester could identify students that presented scores below the lower quartiles in both the second and eighth semesters (p<0.0001 for both AUC). When scores conferred by single courses were compared over time, three time-trend patterns emerged: low variation, upward trend and erratic pattern. CONCLUSION/SIGNIFICANCE: An early identification of students with low performance may be useful in promoting pedagogical strategies for these individuals. Evaluation of the time trend of scores conferred by courses may help departments monitoring changes in personnel and methodology that may affect a student's performance.

Lutzomyia longipalpis saliva triggers lipid body formation and prostaglandin E2 production in murine macrophages.

BACKGROUND: Sand fly saliva contains molecules that modify the host's hemostasis and immune responses. Nevertheless, the role played by this saliva in the induction of key elements of inflammatory responses, such as lipid bodies (LB, also known as lipid droplets) and eicosanoids, has been poorly investigated. LBs are cytoplasmic organelles involved in arachidonic acid metabolism that form eicosanoids in response to inflammatory stimuli. In this study, we assessed the role of salivary gland sonicate (SGS) from Lutzomyia (L.) longipalpis, a Leishmania infantum chagasi vector, in the induction of LBs and eicosanoid production by macrophages in vitro and ex vivo. METHODOLOGY/PRINCIPAL FINDINGS: Different doses of L. longipalpis SGS were injected into peritoneal cavities of C57BL/6 mice. SGS induced increased macrophage and neutrophil recruitment into the peritoneal cavity at different time points. Sand fly saliva enhanced PGE2 and LTB4 production by harvested peritoneal leukocytes after ex vivo stimulation with a calcium ionophore. At three and six hours post-injection, L. longipalpis SGS induced more intense LB staining in macrophages, but not in neutrophils, compared with mice injected with saline. Moreover, macrophages harvested by peritoneal lavage and stimulated with SGS in vitro presented a dose- and time-dependent increase in LB numbers, which was correlated with increased PGE2 production. Furthermore, COX-2 and PGE-synthase co-localized within the LBs induced by L. longipalpis saliva. PGE2 production by macrophages induced by SGS was abrogated by treatment with NS-398, a COX-2 inhibitor. Strikingly, SGS triggered ERK-1/2 and PKC-α phosphorylation, and blockage of the ERK-1/2 and PKC-α pathways inhibited the SGS effect on PGE2 production by macrophages. CONCLUSION: In sum, our results show that L. longipalpis saliva induces lipid body formation and PGE2 production by macrophages ex vivo and in vitro via the ERK-1/2 and PKC-α signaling pathways. This study provides new insights regarding the pharmacological mechanisms whereby L. longipalpis saliva influences the early steps of the host's inflammatory response.

Research knowledge in undergraduate school in Brazil: a comparison between medical and law students / Conhecimento científico na graduação do Brasil: comparação entre estudantes de Medicina e Direito

Objective: Exposure to science education during college may affect a students profile, and research experience may be associated with better professional performance. We hypothesized that the impact of research experience obtained during graduate study differs among professional curricula and among graduate courses. Methods: A validated multiple-choice questionnaire concerning scientific concepts was given to students in the first and fourth years of medical and law school at a public Brazilian educational institution. Results: Medical students participated more frequently in introductory scientific programs than law students, and this trend increased from the first to the fourth years of study. In both curricula, fourth-year students displayed a higher percentage of correct answers than first-year students. A higher proportion of fourth-year students correctly defined the concepts of scientific hypothesis and scientific theory. In the areas of interpretation and writing of scientific papers, fourth-year students, in both curricula, felt more confident than first-year students. Although medical students felt less confident in planning and conducting research projects than law students, they were more involved in research activities. Conclusion: Medical graduation seems to favor the development of critical scientific maturity than law graduation. Specific policy in medical schools is a reasonable explanation for medical students participation in more scientific activities.

Objetivo: A exposição à educação científica durante a faculdade pode afetar o perfil do estudante, e a experiência na pesquisa pode estar associada com um melhor desempenho profissional. Hipotetizamos que o impacto da experiência na pesquisa obtida durante a graduação varia entre os currículos profissionais e entre os cursos de graduação. Métodos: Um questionário validado de múltipla escolha sobre conceitos científicos foi dado aos alunos do primeiro e quarto anos das faculdades de Medicina e Direito em uma instituição pública brasileira de ensino. Resultados: Os estudantes de Medicina participaram com mais frequência de programas de iniciação científica em relação aos estudantes de Direito, e essa tendência aumentou do primeiro ao quarto ano de faculdade. Em ambos os currículos, os alunos do quarto ano apresentaram uma maior porcentagem de acertos que os alunos do primeiro ano. A maior proporção de alunos do quarto ano definiu corretamente os conceitos de hipótese científica e teoria científica. Nas áreas de interpretação e escrita de artigos científicos, os alunos do quarto ano, em ambos os currículos, se sentiram mais confiantes do que os estudantes do primeiro ano. Embora os estudantes de Medicina tenham se sentido menos confiantes no planejamento e na realização de projetos de pesquisa que os estudantes de Direito, eles estavam mais envolvidos em atividades de pesquisa. Conclusão: A graduação em Medicina parece favorecer o desenvolvimento da maturidade crítica científica do que a graduação em Direito. A existência de políticas específicas nas escolas médicas é uma explicação razoável para a participação de estudantes de Medicina em mais atividades científicas.

Using recombinant proteins from Lutzomyia longipalpis saliva to estimate human vector exposure in visceral Leishmaniasis endemic areas.

BACKGROUND: Leishmania is transmitted by female sand flies and deposited together with saliva, which contains a vast repertoire of pharmacologically active molecules that contribute to the establishment of the infection. The exposure to vector saliva induces an immune response against its components that can be used as a marker of exposure to the vector. Performing large-scale serological studies to detect vector exposure has been limited by the difficulty in obtaining sand fly saliva. Here, we validate the use of two sand fly salivary recombinant proteins as markers for vector exposure. METHODOLOGY/PRINCIPAL FINDINGS: ELISA was used to screen human sera, collected in an area endemic for visceral leishmaniasis, against the salivary gland sonicate (SGS) or two recombinant proteins (rLJM11 and rLJM17) from Lutzomyia longipalpis saliva. Antibody levels before and after SGS seroconversion (n = 26) were compared using the Wilcoxon signed rank paired test. Human sera from an area endemic for VL which recognize Lu. longipalpis saliva in ELISA also recognize a combination of rLJM17 and rLJM11. We then extended the analysis to include 40 sera from individuals who were seropositive and 40 seronegative to Lu. longipalpis SGS. Each recombinant protein was able to detect anti-saliva seroconversion, whereas the two proteins combined increased the detection significantly. Additionally, we evaluated the specificity of the anti-Lu. longipalpis response by testing 40 sera positive to Lutzomyia intermedia SGS, and very limited (2/40) cross-reactivity was observed. Receiver-operator characteristics (ROC) curve analysis was used to identify the effectiveness of these proteins for the prediction of anti-SGS positivity. These ROC curves evidenced the superior performance of rLJM17+rLJM11. Predicted threshold levels were confirmed for rLJM17+rLJM11 using a large panel of 1,077 serum samples. CONCLUSION: Our results show the possibility of substituting Lu. longipalpis SGS for two recombinant proteins, LJM17 and LJM11, in order to probe for vector exposure in individuals residing in endemic areas.