RAG Recombinase as a Selective Pressure for Genome Evolution.

The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an ongoing discussion, in particular regarding the counter-selection of sequences resembling the RSS and the modifications of epigenetic regulation at these potential cryptic sites. Here, we describe a new bioinformatics tool to map potential RAG targets in all jawed vertebrates. We show that our REcombination Classifier (REC) outperforms the currently available tool and is suitable for full genomes scans from species other than human and mouse. Using the REC, we document a reduction in density of potential RAG targets at the transcription start sites of genes co-expressed with the rag genes and marked with high levels of the trimethylation of the lysine 4 of the histone 3 (H3K4me3), which correlates with the retention of functional RAG activity after the horizontal transfer.

A new highly discriminatory multiplex capillary-based MLVA assay as a tool for the epidemiological survey of Pseudomonas aeruginosa in cystic fibrosis patients.

Multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) has been shown to provide a high level of information for epidemiological investigations and the follow-up of Pseudomonas aeruginosa chronic infection. In the present study, an automatized MLVA assay has been developed for the analysis of 16 VNTRs in two multiplex polymerase chain reactions (PCRs), followed by capillary electrophoresis. The result in the form of a code is directly usable for clustering analyses. This MLVA-16(Orsay) scheme was applied to the genotyping of 83 isolates from eight cystic fibrosis patients, demonstrating that the same genotype persisted during eight years of chronic infection in the majority of cases. Comparison with pulsed-field gel electrophoresis (PFGE) analysis showed that both methods were congruent, MLVA providing, in some cases, additional informativity. The evolution of strains during long-term infection was revealed by the presence of VNTR variants.

High-throughput typing method to identify a non-outbreak-involved Legionella pneumophila strain colonizing the entire water supply system in the town of Rennes, France.

Two legionellosis outbreaks occurred in the city of Rennes, France, during the past decade, requiring in-depth monitoring of Legionella pneumophila in the water network and the cooling towers in the city. In order to characterize the resulting large collection of isolates, an automated low-cost typing method was developed. The multiplex capillary-based variable-number tandem repeat (VNTR) (multiple-locus VNTR analysis [MLVA]) assay requiring only one PCR amplification per isolate ensures a high level of discrimination and reduces hands-on and time requirements. In less than 2 days and using one 4-capillary apparatus, 217 environmental isolates collected between 2000 and 2009 and 5 clinical isolates obtained during outbreaks in 2000 and 2006 in Rennes were analyzed, and 15 different genotypes were identified. A large cluster of isolates with closely related genotypes and representing 77% of the population was composed exclusively of environmental isolates extracted from hot water supply systems. It was not responsible for the known Rennes epidemic cases, although strains showing a similar MLVA profile have regularly been involved in European outbreaks. The clinical isolates in Rennes had the same genotype as isolates contaminating a mall's cooling tower. This study further demonstrates that unknown environmental or genetic factors contribute to the pathogenicity of some strains. This work illustrates the potential of the high-throughput MLVA typing method to investigate the origin of legionellosis cases by allowing the systematic typing of any new isolate and inclusion of data in shared databases.

Selective training and cross-year clinical tutoring as educational influences on generalist career choice.

CONTEXT: This study was undertaken with all 299 graduates of 12 consecutive classes (in 6 years) of a Brazilian medical school. PURPOSE: To appraise the relationships of gender, early preference for a career, the experience of selective training (a form of elective clerkship) and student preceptorship (cross-year clinical tutoring by peers), with the career choices of graduates. METHOD: Data were obtained at three points: at the beginning of medical studies, on career preference; at the end of medical studies, on selective traineeship and student preceptorship; and after graduation, on medical residency selected. Chi-square tests and logistic regression analysis were done on the data of the graduates, grouped in terms of choice, or not, of frontline care specialties (internal medicine, pediatrics or obstetrics-gynecology). RESULTS: Findings are presented on 299 graduates, of whom 48.5% were female, and 53.8% preferred frontline care (FC) specialties at the beginning of the program. After graduation, 50.2% of the subjects chose FC specialties, among which two-thirds had kept their early preference for a specific specialty. Logistic regression analysis predicted 86.7% of the graduates' choices of FC specialties. Female gender, early preference, student preceptorship and, mostly, selective traineeship in the same broad area were significant factors. CONCLUSION: In this study a strong association was found between selective traineeship and career choice of FC specialties in relation to three additional predictive factors. It also revealed student preceptorship as a factor of potential educational significance in the career decision process and as a matter of institutional concern.

An appraisal of medical students' reflection-in-learning.

INTRODUCTION: How do students reflect as they strive for some control of learning early in their clinical activities? The purpose of this study was to examine the reflection-in-learning profile of medical students as they started their clinical apprenticeship. METHODS: A measure of reflection-in-learning was used to appraise the level and direction of change of reflection in relation to a course experience. The study involved 103 medical students of both sexes who were beginning clinical activities. Assessments of self-regulation of learning, of the meaningfulness of the learning experience, and of diagnostic thinking were also obtained. RESULTS: The results showed that 81% of the students had an increase in scores for reflection-in-learning between the beginning and the end of a course. At the end of the course, the level of reflection-in-learning was significantly associated with self-perceived competence for self-regulated learning and with the meaningfulness of the learning experience. In the following term, students who had high reflection-in-learning scores at the end of the course had higher grade-point averages and greater self-reported diagnostic ability in comparison with those with low scores. CONCLUSIONS: There was some evidence of an improved quality of reflection as the students strive for some control of learning. Overall, the findings support the idea that a greater effort at reflection is associated with a more positive learning experience. They also suggest that reflection-in-learning is related to readiness for self-regulation of learning and may be conducive to enhanced diagnostic ability. In conclusion, measuring reflection-in-learning may be a useful tool in the appraisal of medical students' learning profiles.

[Career in medicine and elective internship: a cohort study]. / Escolha de carreira em medicina e internato eletivo: um estudo de coortes.

A study of career choice was undertaken with students of the new curriculum of the University of Brasilia Medical program that graduated from 1994 to 1997. The purpose was to assess the impact of selective training during the internship on the choice of medical residency and the relationships with some selected personal and academic factors. Data from 196 participants were obtained at the beginning of the medical program, after registration for the elective, and after the medical residency examination. Chi-square tests and logistic regression analysis were applied to the data. Results showed that about 74% of the choices for medical residency favor four specialties: internal medicine, general surgery, pediatrics and obstetrics-gynecology and define a demand profile compatible with the offer profile. Regression analysis with three predictor variables revealed that selective training was the strongest influence in each case. The other variables showed independent but weaker association: sex (general surgery and internal medicine) and initial preference (general surgery and pediatrics). Another analysis verified that initial preference was the main influence in the choice of selective training. Three other factors (learning style, self-confidence as a learner, and grade point average) showed weak association with some areas of selective training or specialty choice. In conclusion, the study confirmed the hypothesis of the prediction power of the selective training on career choice and revealed other distinct influences.

[Curriculum renewal and quality of the educational process]. / Renovamento curricular e qualidade do processo educativo.

Curriculum renewal may be one good way for the betterment of medical education in the perspective of educational development. The article identifies three otmization lines for curriculum renewal, in the sense of criteria of relevance, efficacy, and efficiency. They are: 1) anchoring the renewal in the vision of a three-dimension concept of competence; 2) emphasis on quality of learning; and 3) a quest for restructuring the learning settings. Implication and examples of, and some barriers against such moves are noticed. The author points out that curriculum renewal may be effective only when it is fostering the quality of learning.

[Brazilian multicenter study of sotalol effectiveness in ventricular arrhythmias]. / Estudo multicêntrico Brasileiro da eficácia do sotalol em arritmias ventriculares.

PURPOSE: To evaluate the effects of sotalol in patients with nonsustained ventricular tachyarrhythmia (NSVT). METHODS: Ninety patients were enrolled. Patients were submitted to a double-blind crossover randomized study (placebo x 320 ms/po/d/sotalol; 4 weeks, after a wash-out control period. Holter recordings were performed in control (Ct), placebo (Pb) and drug (Dg) periods. Eligible patients had > 50/h isolated ventricular premature beats (VPB), in control, with or without pairs (P) or nonsustained VT (NSVT; > 3 beats, > 100bpm). Drug efficacy criteria were; > or = 75% reduction in isolated VPB, reduction > or = 90% of P and NSVT. The effects of the Dg were evaluated in the global population, in patients with Chagas' disease, idiopathic arrhythmias and ischemic/hypertensive patients. RESULTS: Differences between control and placebo were NS. Isolated VPB; Dg was effective in 42% (38/90 patients) with a mean of Pb and Dg respectively of 11,770 +/- 13,818 and 1,043 +/- 1,554 (p < 0.001). Pairs: drug was effective in 48% (32/67 patients) with a mean of Pb and Dg respectively of 439 +/- 586 and 27 +/- 52 (p < 0.001). NSVT: drug effectiveness was 53% (19/36 patients) with a mean of Pb and Dg respectively of 445 +/- 1,148 and 2.5 +/- 5.8 (p < 0.102). In patients with Chagas' disease, the reduction in VPB was 33% (13/39 patients), in pairs was 42+ (14/34) and in NSVT was 64% (12/22). In idiopathic patients the reduction of VPB was 53% (17/32 patients), in pairs was 50% (10/20) and in NSVT was 36% (4/11). In ischemic and hypertensive patients the reduction of VPB was 47% (7/15 patients) and 73% in pairs (8/11). CONCLUSION: In the present study, sotalol was effective in the control of nonsustained ventricular tachyarrhythmia, with minimal side-effects.

Estudo multicêntrico brasileiro da eficácia do sotalol em arritmias ventriculares / Brazilion Multicenter Study of Sotalol Effectiveness in Ventricular Arrhythmias

Objetivo - Avaliar através de ensaio clínico prospectivo, randomizado, duplo-cego cruzado contra placebo, a eficácia do sotalol na dose oral de 320 miligramas diários em reduzir taquiarritmias ventriculares näo sustentadas (TVNS). Métodos - Foram avaliados em condiçöes de controle (Ct), placebo (Pb) e droga (Dg), 90 portadores de um número médio maior ou igual a 50 extra-sístole horárias (EV), com ou sem respostas pareadas (RP) e TVNS, registradas no Holter. Considerou-se a droga como efetiva, fren a uma reduçäo maior ou igual a 75 por cento das EV e maior ou igual a 90 por cento das RP e TVNS. Avaliaram-se os resultados globais e os observados em doenças específicas, incluindo a cardiopatia chagásica crônica, arritmias ventriculares idiopáticas e doença coronariana e hipertensiva sistêmica. Resultados - Näo ocorreram diferenças significativas entre Ct e Pb. Globalmente, a droga reduziu as EV em 42 por cento (38/90 pacientes), as RP em 48 por cento (32/67 e as TVNS em 53 por cento (19/36), com méis respectivas entre Pb e Dg de 11.770 mais ou menos 13.818 para 1.043 mais ou menos 1.554 nas EV (p menor a 0,001); de 439 mais ou menos 586 para 27 mais ou menos 52 nas RP (p menor a 0,001) e de 445 mais ou menos 1.147 para 2,5 mais ou menos 5,8 nas TVNS (p menor a 0,102). Nos chagásicos, reduçäo das EV de 33 por cento (13/39 pacientes), das RP em 42 por cento (14/34) e das TVNS em 64 por cento (12/22). Nos indiopáticos, a reduçäo das EV foi de 53 por cento (17/32 pacientes), das RP de 50 por cento (0/0) e das TVNS de 36 por cento (4/11). Nos isquêmicos e/ou hipertensos, a reduçào das EV foi de 47 por cento (7/15 pacientes) e de 73 por cento nas RP (8/11). Conclusäo - Na populaçäo estudada e na dose indicada, o sotalol mostrou ser um fármaco efetivo para controle de TVNS, apresentando mínimos efeitos colaterais.

Diagnostic ability of medical students in relation to their learning characteristics and preclinical background.

Is the diagnostic ability of medical students--as appraised by the Diagnostic Thinking Inventory (DTI) --influenced by the learners' characteristics, or the way they acquired basic knowledge? This question was explored in a 4-year consecutive sampling of clinical clerkship students. DTI inventory scores (flexibility in thinking and structure in memory), learners' characteristics (learning style, self-confidence as a learner, and motivation to learn), together with knowledge scores (grade-point) average and problem-solving test) were measured and analysed for their relationships and the differences between groups. Results revealed that higher scores of the DTI measures were associated with students' high self-confidence, high motivation to learn, and abstract learning types. Correlation coefficients showed significant relationships between the DTI scores and both knowledge measures. In addition, t-tests showed that students with an integrated teaching background and problem-based learning (PBL) experience obtained significantly higher scores for structure in memory. The findings suggest that the inventory scores are sensitive to both cognitive and non-cognitive factors. The inventory may be useful detecting subtle influences on diagnostic ability differentiation in medical students.

Peer tutoring and student outcomes in a problem-based course.

Does peer-tutoring affect students' educational outcomes in problem-based learning? Students' characteristics and outcomes were compared along 14 successive classes of a problem-based learning course in the University of Brasilia medical programme. In the first stage of this time series, 26 teacher-tutored groups were formed; in the second stage, 50 groups had both teacher- and peer-tutoring. Both groups had equivalent characteristics in stages one and two as regards membership size and composition (students' learning style, self-confidence and motivation to learn). Results showed that scores for problem-solving tests and self-evaluation of skills were not significantly different between first and second stage groups. However, scores of meaningfulness of course experience and group work usefulness were significantly higher in the peer-tutoring stage. Significant positive correlations were found between scores of meaningfulness of course experience and both self-evaluation and group work usefulness but not between the first measure and group size or motivation to learn. The findings suggest that peer-tutoring can facilitate group work without sustained loss of cognitive achievement in long range conditions of problem-based learning experience.

[Availability optimization: an alternative vision]. / Otimização de disponibilidades: uma visão alternativa.

Optimization of available resources is defined by the author as a guideline for characterization of institutional values with the intention to improves professional work. Important factors are referred by which the institutional resources may find a better use.

[Preference for general practice in the medical course: relationship with changes in the clinical environment]. / Preferência por medicina geral num curso de medicina: relação com mudança na ambiência clínica.

Career preferences were investigated before and after a major change of clinical training setting at the University of Brasilia. The inquiry addressed to pre-clinical students for a total of 15 cohort years (N = 1107). Data were gathered through self-report questionnaires on main preference, its inducing factor (a priori, theme study, task experience) and on learning style. The results showed a significant difference between student-pool career preference profiles, before and after change, which was mostly due to a decrease (from 24% to 10%) in preference for general practice. Lesser proportions of aprioristic induction, active learning style and male students were featured in the after-change student-pool. Relation-ships were found between preference for general practice and aprioristic induction, active learning style and male sex. Decline in preference for general practice is ascribed more to factors reducing access to course than to reorientation of the curriculum.

[Digestive symptoms in young individuals: survey among medical students]. / Sintomas digestivos em jovens: inquérito em estudantes de medicina.

The purpose of this study was to assess the frequency patterns of 8 digestive symptoms and related features, with regard to functional disorders, in young adults. A sample of 279 subjects, representing the student body at the Medical School of Brasília, filled up the self-report questionnaire. From 20% to 27% of subjects reported more than 6 episodes of one more of the following symptoms, within a 12-month period: indigestion, distension, constipation, heartburn, abdominal pain, and diarrhea. A higher prevalence of constipation in women was a significant (p < 0.05) difference between the sexes. Dyspepsia and irritable bowel syndrome (IBS) were identified by clinical criteria in 25% and 9% of subjects, respectively, while 4% disclosed the occurrence of an organic disease. About 30% of the subjects volunteered perceptions on the meaning of the symptoms, while 22% reported days of restricted activities ascribed to the symptoms. Days of restricted activities were significantly (p < 0.05) related to the number, the type (diarrhea, nausea and vomiting, and abdominal pain), and the IBS pattern of symptoms (but not to the dyspepsia pattern). In conclusion, a substantial proportion of subjects in this student group, contacted at the workplace, showed indexes of clinical dysfunction (recurrence of multiple symptoms), and of social dysfunction (days of restricted activity), which indicate persistent limitations on the digestive health status.

[Interdisciplinarity in medical education: 3 aspects of analysis]. / A interdisciplinaridade no ensino médico: três aspectos de análise.

The author defines and analyses the concept of an interdisciplinary approach to basic medical education. Thereby, this educational strategy is examined in reference to three features: the expected outcomes with regard to the dimensions of competence of the graduate; the parameters of interdisciplinary integration; and the limiting factors for the development of interdisciplinarity in medical education. The case of pre-clinical teaching at the University of Brasilia is reviewed to illustrate comments on the conditionalities pending the adoption of the interdisciplinary approach.

Learning the educator role: a course for medical students.

The design and evaluation of a revised course on educational skills for medical students is described. The overall aim of this elective was to help students develop a working concept of their educator role regarding themselves, their peers, and their patients. The programme comprised 15 2-hour weekly meetings consisting of small-group discussion and exercises around issues of self-learning skills, peer teaching, and the process of patient education. Advanced preparation was promoted by readings and special assignments. Self-assessment, peer-assessment, and continuous assessment based on course-work were used to help student learning and to provide a basis for final grading. During a 3-year study period, the Course Valuing Inventory (CVI) and a goal-oriented questionnaire were used for course evaluation. Evaluation done on five consecutive classes showed favourable indices of course attractiveness. It also showed broad progress of most students in the course goals and high positive CVI scores for cognitive, personal and behavioural learnings, in addition to course valuing. Students' perceptions of improvement in self-appraisal, communication skills and personal growth were related findings. Significant, moderate correlations were found between CVI learning scores and both the self-ratings of progress in the course goals and of attitude towards the educator role. Reinforcement of the positive attitude towards this role was a valuable finding related to a lasting effect: a significant increase in the choice of undergraduate preceptorships by the participants when compared to the control sample of students not exposed to this learning experience.

Relevancia da aprendizagem do papel educativo na formacao medica. / The relevance of learning of the educator role in medical education

Descricao da concepcao da funcao educativa na missao do medico. Caracteristicas da funcao educativa: natureza e ambito. Aprendizagem da funcao educativa: condicoes e processos; importancia da receptividade do aprendiz e das estrategias de controle, organizacao e provisao. Exemplos do impacto potencial dos produtos do aprendizado, em termos da relevancia para o manejo de problemas medicos