Interleukin-12 treatment reduces tumor growth and modulates the expression of CASKA and MIR-203 in athymic mice bearing tumors induced by the HGC-27 gastric cancer cell line.

Gastric cancer (GC) is one of the most common malignant tumors in the digestive system and due to its poor prognosis, there is an increase in the demand for more effective anticancer therapies. Interleukins are potential anticancer agents which can modulate expression of cancer related genes and have therapeutic effects. Interleukin 12 (IL-12) exhibits potent anti-tumor, anti-angiogenic and anti-metastatic activities and represents the ideal candidate for tumor immunotherapy, due to its ability to activate both innate and adaptive immunities. The aim of this study was to evaluate the effect of IL-12 administration on GC tumor growth induced in the cancer xenograft nude mouse model. Tumor development was analyzed weekly and after 8 weeks, the animals were sacrificed for cytokine analysis (IL-4, TNF-alfa, IL-2, INF-gamma, IL-12, IL-10, TGF-beta) by ELISA. The tumor cells in the implanted areas of the animals that developed solid growth of the tumor (anatomopathological analysis was performed). We have also evaluated CASK and miR203 expression, two related cell invasion factors, in the induced tumors after administration of 6 n/kg IL-12. The development of tumor masses was observed in all groups of animals inoculated with HGC-27 neoplastic cells. In animals treated with 6 n/kg IL-12, there was no tumor development confirmed by anatomopathological analysis. Changes in the levels of pro and anti-inflammatory cytokines were also observed. Our results indicated that miR203 expression was elevated while CASK was downregulated. These results suggest that IL-12 treatment repress the tumor growth by induction of miR203 expression which in turn repress CASK expression.

A Comparison of the Academic Achievement at the End of the Medicine Undergraduate Degree Program Between Students Who Only Used the University Admission Test and Those Who Used the University Admission Test Plus Marks from the High School National Exam (ENEM) at a Single Brazilian Center.

Purpose: The role of marks in the University Admission Test (UAT) plus the marks from pre-university academic records in predicting academic achievement at the end of the Medicine undergraduate degree program is not completely known. This study was undertaken to compare the performance of marks in the UAT alone with those of the UAT plus marks from the National High School Exam (ENEM in Brazil) regarding students' outcomes at the end of the Medicine undergraduate degree program. Methods: Fifty-one (51) students from the last semester (12th) of our Medicine undergraduate degree program were included in the study. They were divided into a group of those who used the marks obtained in the UAT plus the marks obtained in the ENEM (ENEM group, n=9), and those who only used the marks in the UAT (non-ENEM group, n=42). We compared the academic achievement of the non-ENEM group with that of the ENEM group regarding the mean marks obtained in the clerkship, in the Progress Test (PT), and in the Objective Structured Clinical Examination (OSCE). Results: The mean scores obtained in the disciplines of the clerkship were higher in the non-ENEM group compared to the ENEM group (7.32 ± 0.41 vs 6.98 ± 0.31, p= 0.01). Both groups obtained similar mean marks in the OSCE and in the PT. A moderate correlation was observed between the marks in the clerkship with those of the UAT from the non-ENEM group (p=0.00006; r=0.45). Conclusion: Marks of the UAT alone appear to be associated with a higher academic achievement in the clerkship than marks of the UAT plus scores obtained from the ENEM at the end of the Medicine undergraduate degree program.

Nonpharmaceutical public health interventions to curb the COVID-19 pandemic: a narrative review.

Nonpharmaceutical Interventions (NPI) consist of compulsory (isolation, quarantine, stay-at-home orders, banning public gatherings, nonessential business closures, school closures), and voluntary (social distancing, handwashing, respiratory etiquette, and universal mask wearing) measures. The aim of this narrative review is to evaluate the different forms of NPI and their effectiveness in combating the pandemic. Isolation can be indicated for symptomatic and asymptomatic infected people at home or at hospitals depending on the patient's clinical picture. Quarantine is a social distancing intervention in asymptomatic uninfected people who had contact with SARS-CoV-2 infected individuals. Stay-at-home orders refer to statewide mandates imposing nonessential business closures, prohibition of public events and gatherings, and travel restrictions. Studies have suggested that stay-at-home orders may be associated with a reduction in the incidence of COVID-19 in some countries. Mask wearing decreases the risk of COVID-19 in the community, especially when the surgical masks are used for vulnerable people. N-95 respirators protect health workers from COVID-19. NPI may be helpful to curb the COVID-19 pandemic while mass vaccination worldwide is not attainable, and the threat of SARS-COV-2 variants remain on the horizon.

The history of the evolution of the knowledge about the diagnosis and the pathogenetic aspects of heart failure: From the Egyptians to James Mackenzie.

The recognition of the syndrome of heart failure (HF) dates back to the Egyptians, although it is still a mystery how they did that because they had an erroneous notion of the blood flow. Some cardinal aspects of the clinical picture of HF were associated with cardiac disease 1600 years later. Dyspnea was associated with cardiac disease in 1000 CE by Avicenna; pedal edema was associated with cardiac disease by Pawl in 1615. Lower associated dyspnea with pedal edema in 1669, and Bonet associated ascites with cardiac disease in 1679. Lancisi associated the jugular venous distention with right ventricular dilatation in 1728. However, it was only in 1748 that Albertini associated pedal edema and dyspnea with the myocardial disease. The evolution of the understanding that myocardial contractility abnormality was the mechanism behind HF partially started with Lower in 1669, it was clearly pointed out by Albertini in 1748 and refined by Mackenzie in 1908. At that time, it was clear that the exhausted myocardial would lead to the appearance of HF. However, the full understanding of the pathogenesis of HF had to wait for the hemodynamic studies which would appear in the second decade of the 20th century, and for the neurohormonal theory of the 90's.

University Admission Test Associates with Academic Performance at the End of Medical Course in a PBL Medical Hybrid Curriculum.

PURPOSE: Most studies assessing the value of the university admissions test (UAT) to predict academic performance at the end of a medical course were carried out on lecture-based medical courses. However, the association between performance in the UAT with academic achievement at the end of medical course in a problem-based learning (PBL) medical hybrid curriculum remains controversial. The aim of this study was to correlate marks in the UAT with those obtained in the Organized Structured Clinical Examination (OSCE), in the progress testing (PT), and in the final marks of the clerkship (FMC). METHODS: We used data from 48 medical students. A single and a multiple dependency studies were performed to assess bivariate and multiple correlation between the UAT or the essay scores (dependent variables) and the OSCE, PT, and FMC (independent variables). Pearson test, multiple linear regression, and ANOVA tests were used and a p-value < 0.05 was considered significant. RESULTS: In the bivariate analysis, only the UAT and FMC marks were correlated (r=0.34; p=0.02). However, the multiple dependency study showed a moderate correlation among UAT, OSCE, PT, and FMC marks (r=0.46; p=0.01). No correlation was found between the essay scores and PT, FMC, and OSCE scores. CONCLUSION: Our study shows that UAT marks, but not essay scores, can predict academic achievement, particularly in terms of clinical competence (FMC) at the end of a medical course in a PBL hybrid curriculum.

Formative assessment scores in tutorial sessions correlates with OSCE and progress testing scores in a PBL medical curriculum.

BACKGROUND: Effective assessments programs are a challenge in problem-based learning (PBL). One of the main principles of this educational setting is the Formative Assessment (FA). We hypothesized that students' performance assessed by FA in tutorial sessions in a PBL curriculum is related to other summative assessments. OBJECTIVE: To investigate the correlation among FA in tutorial sessions with grades obtained in Objective Structured Clinical Evaluation (OSCE) and Progress Testing (PT) to better understand the assessment process in PBL medical teaching approach and to predict student's future performance. DESIGN: An observational cross-sectional study was conducted comparing FA, OSCE and PT scores from 4th to 8th semester medical students. Correlation analyses were performed using pooled and separate data from the 4th and 8th semesters. RESULTS: From the 5th to 8th semester, OSCE scores were smaller compared to the FA, while PT scores were lower in all stages. In the pooled data, the correlation analysis showed a significant positive relationship between grades on FA and OSCE, FA and PT and OSCE and PT. A significant correlation among the three assessments strategies was also detected in the 8th semester, but not in the 4th semester. CONCLUSIONS: Assessment strategies in PBL approach, including FA, OSCE and PT, have positive correlations, which increases as the medical course becomes more complex.

Assessment test before the reporting phase of tutorial session in problem-based learning.

PURPOSE: In our context, problem-based learning is not used in the preuniversity environment. Consequently, students have a great deal of difficulty adapting to this method, particularly regarding self-study before the reporting phase of a tutorial session. Accordingly, the aim of this study was to assess if the application of an assessment test (multiple choice questions) before the reporting phase of a tutorial session would improve the academic achievement of students at the preclinical stage of our medical course. METHODS: A test consisting of five multiple choice questions, prepared by tutors of the module at hand and related to the problem-solving process of each tutorial session, was applied following the self-study phase and immediately before the reporting phase of all tutorial sessions. The questions were based on the previously established student learning goals. The assessment was applied to all modules from the fifth to the eighth semesters. The final scores achieved by students in the end-of-module tests were compared. RESULTS: Overall, the mean test score was 65.2±0.7% before and 68.0±0.7% after the introduction of an assessment test before the reporting phase (P<0.05). Students in the sixth semester scored 67.6±1.6% compared to 63.9±2.2% when they were in the fifth semester (P<0.05). Students in the seventh semester achieved a similar score to their sixth semester score (64.6±2.6% vs 63.3±2%, respectively, P>0.05). Students in the eighth semester scored 71.8±2.3% compared to 70±2% when they were in the seventh semester (P>0.05). CONCLUSION: In our medical course, the application of an assessment test (a multiple choice test) before the reporting phase of the problem-based learning tutorial process increases the overall academic achievement of students, especially of those in the sixth semester in comparison with when they were in the fifth semester.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease.

The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Could Carlos Chagas' assumption on the relationship between goiter and chronic Chagas heart disease be correct? A historical reappraisal.

In 1910, Chagas divided the clinical manifestations of the chronic form of Chagas disease according to heart, Central Nervous System, and thyroid involvement, particularly the presence of goiter. Chagas emphasized the association of goiter with poor houses infested with kissing bugs, the similarity of the clinical picture with that of patients underwent partial thyroidectomy, and with the presence of thyroid sclerosis (inflammation) on histological examination. In addition, Chagas observed that all people living in poor houses infested by sucking bugs had goiter, contrasting with persons who lived in the same region, drinking the same water, but living in good houses, which did not have goiter. Furthermore, Chagas stressed the fact that people without any evidence of thyroid disease that migrated to live in poor houses in areas infested by sucking bugs developed thyroid disease some time later. Finally, and more importantly, Chagas emphasized the association of goiter with cardiac abnormalities in 80% of patients with chronic Chagas heart disease. Despite this, other authors working in different regions did not confirm such an association. A reappraisal of data from a work published in 1949 clearly shows that the presence of goiter was statistically associated with chronic Chagas heart disease and with chronic Chagas disease. Our paper highlights once more the grandiosity of Chagas' work, which has been proved to be correct even in the history of goiter, and justifies our claim for a posthumous Nobel Prize inasmuch as his work was not perceived by the Karolinska Institute.

Antiophidian properties of the aqueous extract of Mikania glomerata.

Aqueous extracts, prepared from dried or fresh roots, stems or leaves of Mikania glomerata, a plant found in Mata Atlântica in Southeastern Brazil, were able to efficiently neutralize different toxic, pharmacological, and enzymatic effects induced by venoms from Bothrops and Crotalus snakes. Phospholipase A(2) activity and the edema induced by Crotalus durissus terrificus venom were inhibited around 100 and approximately 40%, respectively, although this inhibition was only partial for Bothrops venoms. The hemorrhagic activity of Bothrops venoms (Bothrops altenatus, Bothrops moojeni, Bothrops neuwiedi, and Bothrops jararacussu) was significantly inhibited by this vegetal species, while the clotting activity of Crotalus durissus terrificus, Bothrops jararacussu, and Bothrops neuwiedi venoms was totally inhibited. Although, the mechanism of action of Mikania glomerata extract is still unknown, the finding that no visible change was detected in the electrophoretic pattern of snake venom after incubation with the extract excludes proteolytic degradation as a potential mechanism. Since the extract of Mikania glomerata significantly inhibited the studied snake venoms, it may be used as an alternative treatment to serumtherapy and, in addition, as a rich source of potential inhibitors of PLA(2)s, metalloproteases and serineproteases, enzymes involved in several physiopathological human and animal diseases.

Brazilian medical students' perceptions of expert versus non-expert facilitators in a (non) problem-based learning environment.

BACKGROUND: In problem-based learning (PBL), the facilitator plays an important role in guiding the student learning process. However, although content expertise is generally regarded as a useful but non-essential prerequisite for effective PBL facilitation, the perceived importance of content knowledge may be subject to cultural, contextual, and/or experiential influences. AIM: We sought to examine medical students' perceptions of subject-matter expertise among PBL facilitators in a region of the world (Brazil) where such active learning pedagogies are not widely used in university or pre-university settings. RESULTS: Of the 252 Brazilian medical students surveyed, significantly (p≤0.001) greater proportions viewed content expert facilitators to be more effective than their non-expert counterparts at building knowledge (95% vs. 6%), guiding the learning process (93% vs. 7%), achieving cognitive learning (92% vs. 18%), generating learning goals (87% vs. 15%), and motivating self-study (80% vs. 15%). DISCUSSION/CONCLUSION: According to Brazilian medical students, subject-matter expertise among PBL facilitators is essential to the learning process. We believe this widespread perception is due, in large part, to the relative lack of prior educational exposure to such pedagogies.

Development of anatomophysiologic knowledge regarding the cardiovascular system: from Egyptians to Harvey.

Our knowledge regarding the anatomophysiology of the cardiovascular system (CVS) has progressed since the fourth millennium BC. In Egypt (3500 BC), it was believed that a set of channels are interconnected to the heart, transporting air, urine, air, blood, and the soul. One thousand years later, the heart was established as the center of the CVS by the Hippocratic Corpus in the medical school of Kos, and some of the CVS anatomical characteristics were defined. The CVS was known to transport blood via the right ventricle through veins and the pneuma via the left ventricle through arteries. Two hundred years later, in Alexandria, following the development of human anatomical dissection, Herophilus discovered that arteries were 6 times thicker than veins, and Erasistratus described the semilunar valves, emphasizing that arteries were filled with blood when ventricles were empty. Further, 200 years later, Galen demonstrated that arteries contained blood and not air. With the decline of the Roman Empire, Greco-Roman medical knowledge about the CVS was preserved in Persia, and later in Islam where, Ibn Nafis inaccurately described pulmonary circulation. The resurgence of dissection of the human body in Europe in the 14th century was associated with the revival of the knowledge pertaining to the CVS. The main findings were the description of pulmonary circulation by Servetus, the anatomical discoveries of Vesalius, the demonstration of pulmonary circulation by Colombo, and the discovery of valves in veins by Fabricius. Following these developments, Harvey described blood circulation.

When a misperception favors a tragedy: Carlos Chagas and the Nobel Prize of 1921.

Carlos Chagas, the discoverer of Chagas' disease was nominated to the Nobel Prize in 1921, but none did win the prize in that year. As a leader of a young scientist team, he discovered all aspects of the new disease from 1909 to 1920. It is still obscure why he did not win the Nobel Prize in 1921. Chagas was discarded by Gunnar Hedrèn on April 16, 1921. Hedrèn should have made a written report about the details of his evaluation to the Nobel Committee. However, such a document has not been found in the Nobel Committee Archives. No evidence of detractions made by Brazilian scientists on Chagas was found. Since Chagas nomination was consistent with the Nobel Committee requirements, as seen in the presentation letter by until now unknown Cypriano de Freitas, it become clear that Chagas did not win the Nobel Prize exclusively because the Nobel Committee did not perceive the importance of his discovery. Thus, it would be fair a posthumous Nobel Prize of 1921 to Carlos Chagas. A diploma of the Nobel Prize, as precedent with Dogmack in 1947, would recognize the merit of the scientist who made the most complete medical discovery of all times.

Evaluation of the Hypoglycemic Properties of Anacardium humile Aqueous Extract.

The antihyperglycemic effects of several plant extracts and herbal formulations which are used as antidiabetic formulations have been described and confirmed to date. The main objective of this work was to evaluate the hypoglycemic activity of the aqueous extract of Anacardium humile. Although the treatment of diabetic animals with A. humile did not alter body weight significantly, a reduction of the other evaluated parameters was observed. Animals treated with A. humile did not show variation of insulin levels, possibly triggered by a mechanism of blood glucose reduction. Levels of ALT (alanine aminotransferase) decreased in treated animals, suggesting a protective effect on liver. Levels of cholesterol were also reduced, indicating the efficacy of the extract in reestablishing the balance of nutrients. Moreover, a kidney protection may have been achieved due to the partial reestablishment of blood glucose homeostasis, while no nephrotoxicity could be detected for A. humile. The obtained results demonstrate the effectiveness of A. humile extracts in the treatment of alloxan-induced diabetic rats. Therefore, A. humile aqueous extract, popularly known and used by diabetic patients, induced an improvement in the biochemical parameters evaluated during and following treatment of diabetic rats. Thus, a better characterization of the medicinal potential of this plant will be able to provide a better understanding of its mechanisms of action in these pathological processes.

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease / Descobertas de Carlos Chagas como Pano de Fundo para a Construção Científica da Cardiopatia Chagásica Crônica

Abstract The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

Resumo A construção científica da doença de Chagas crônica (DCC) começou em 1910, quando Carlos Chagas salientou a presença de arritmia cardíaca em exames físicos de pacientes com doença de Chagas crônica, e descreveu um caso de insuficiência cardíaca associada à inflamação do miocárdio e à presença de ninhos de parasitas durante a autópsia. Ele descreveu morte súbita cardíaca associada a arritmias em 1911, e sua associação ao bloqueio AV total detectado com o polígrafo de Jacquet, conforme reportou em 1912. Chagas mostrou a presença de fibrose do miocárdio como subjacente ao quadro clínico da DCC em 1916, e apresentou uma caracterização completa dos aspectos clínicos da DCC em 1922. Em 1928, Chagas detectou fibrose do sistema condutor, e apontou a presença de cardiomegalia acentuada no raio X do tórax, associada a sintomatologia mínima. O uso da reação sorológica no diagnóstico de DCC foi posta em prática clínica em 1936, após a morte de Chagas, e juntamente com o ECG de 12 derivações, revelou a importância epidemiológica da DCC em 1945. Em 1953, ficou comprovado o longo período de tempo entre a infecção inicial e o aparecimento de DCC, enquanto que a incidência anual de DCC na forma indeterminada da doença foi estabelecida em 1956. Os aspectos clínicos fundamentais de DCC descritos por Carlos Chagas foram complementados pelo uso de cateterismo cardíaco em 1965, teste ergométrico em 1973, Holter em 1973, teste eletrofisiológico em 1975, ecocardiografia em 1975, biópsia endomiocárdica em 1981 e ressonância magnética em 1995.