Metabolic Variation during Development in Culture of Leishmania donovani Promastigotes

The genome sequencing of several Leishmania species has provided immense amounts of data and allowed the prediction of the metabolic pathways potentially operating. Subsequent genetic and proteomic studies have identified stage-specific proteins and putative virulence factors but many aspects of the metabolic adaptations of Leishmania remain to be elucidated. In this study, we have used an untargeted metabolomics approach to analyze changes in the metabolite profile as promastigotes of L. donovani develop during in vitro cultures from logarithmic to stationary phase. The results show that the metabolomes of promastigotes on days 3–6 of culture differ significantly from each other, consistent with there being distinct developmental changes. Most notable were the structural changes in glycerophospholipids and increase in the abundance of sphingolipids and glycerolipids as cells progress from logarithmic to stationary phase

Situational awareness within objective structured clinical examination stations in undergraduate medical training - a literature search

Background: Medical students may not be able to identify the essential elements of situational awareness (SA) necessary for clinical reasoning. Recent studies suggest that students have little insight into cognitive processing and SA in clinical scenarios. Objective Structured Clinical Examinations (OSCEs) could be used to assess certain elements of situational awareness. The purpose of this paper is to review the literature with a view to identifying whether levels of SA based on Endsley's model can be assessed utilising OSCEs during undergraduate medical training. Methods: A systematic search was performed pertaining to SA and OSCEs, to identify studies published between January 1975 (first paper describing an OSCE) and February 2017, in peer reviewed international journals published in English. PUBMED, EMBASE, PsycINFO Ovid and SCOPUS were searched for papers that described the assessment of SA using OSCEs among undergraduate medical students. Key search terms included "objective structured clinical examination", "objective structured clinical assessment" or "OSCE" and "non-technical skills", "sense-making", "clinical reasoning", "perception", "comprehension", "projection", "situation awareness", "situational awareness" and "situation assessment". Boolean operators (AND, OR) were used as conjunctions to narrow the search strategy, resulting in the limitation of papers relevant to the research interest. Areas of interest were elements of SA that can be assessed by these examinations. Results: The initial search of the literature retrieved 1127 publications. Upon removal of duplicates and papers relating to nursing, paramedical disciplines, pharmacy and veterinary education by title, abstract or full text, 11 articles were eligible for inclusion as related to the assessment of elements of SA in undergraduate medical students. Discussion: Review of the literature suggests that whole-task OSCEs enable the evaluation of SA associated with clinical reasoning skills. If they address the levels of SA, these OSCEs can provide supportive feedback and strengthen educational measures associated with higher diagnostic accuracy and reasoning abilities. Conclusion: Based on the findings, the early exposure of medical students to SA is recommended, utilising OSCEs to evaluate and facilitate SA in dynamic environment

WNT/β-catenin pathway activation in Myc immortalised cerebellar progenitor cells inhibits neuronal differentiation and generates tumours resembling medulloblastoma

Background: Medulloblastoma is the most common malignant childhood brain tumour. Aberrant activation of the WNT/β-catenin pathway occurs in approximately 25% of medulloblastomas. However, its role in medulloblastoma pathogenesis is not understood. Methods: We have developed a model of WNT/β-catenin pathway-activated medulloblastoma. Pathway activation was induced in a Myc immortalised cerebellar progenitor cell line through stable expression of Wnt1. In vitro and in vivo analysis was undertaken to understand the effect of pathway activation and identify the potential cell of origin. Results: Tumours that histologically resembled classical medulloblastoma formed in vivo using cells overexpressing Wnt1, but not with the control cell line. Wnt1 overexpression inhibited neuronal differentiation in vitro, suggesting WNT/β-catenin pathway activation prevents cells terminally differentiating, maintaining them in a more ‘stem-like’ state. Analysis of cerebellar progenitor cell markers demonstrated the cell line resembled cells from the cerebellar ventricular zone. conclusion: We have developed a cell line with the means of orthotopically modelling WNT/β-catenin pathway-activated medulloblastoma. We provide evidence of the role pathway activation is playing in tumour pathogenesis and suggest medulloblastomas can arise from cells other than granule cell progenitors. This cell line is a valuable resource to further understand the role of pathway activation in tumorigenesis and for investigation of targeted therapies

Prevalência de dilatação da aorta abdominal em coronariopatas idosos Prevalence of abdominal aortic dilatation in patients aged 60 years or older with coronary disease

CONTEXTO: A realização de programas de triagem para o aneurisma da aorta abdominal de forma indiscriminada auxiliará uma pequena porcentagem de indivíduos, mas ao considerarmos grupos com fatores de risco relacionados à dilatação da aorta, aumentando a probabilidade da doença, este permitirá um direcionamento adequado dos recursos e um benefício maior à população. Programas direcionados pelas sociedades médicas, permitindo um diagnóstico precoce das doenças vasculares e conseqüentemente um melhor preparo do doente, promoveriam melhores taxas de sobrevida com menor morbidade. OBJETIVO: Avaliar a prevalência da dilatação da aorta abdominal em uma amostra de pacientes idosos com mais de 60 anos de idade, portadores de coronariopatia aterosclerótica diagnosticada por cineangiocoronariografia. MÉTODOS: Para a seleção dessa amostra, levou-se em consideração o fato de que a avaliação pré-operatória de cirurgia vascular não tenhasido a indicação do cateterismo. Procedeu-se então a avaliação, baseada na anamnese, exame físico e Doppler ultra-som da aorta abdominal. A análise estatística iniciou-se com o teste qui-quadrado, com a posterior análise de regressão logística multivariada e regressão logística univariada, considerando significativo um p < 0,05. RESULTADOS: Dos 180 pacientes, 57 (31,7%) dos casos pertencem ao sexo feminino, e 123 (68,3%) ao masculino. A faixa etária variou entre 60 e 80 anos, com idade média de 66,7 anos. Dos 16 indivíduos portadores de dilatação da aorta abdominal (10 aneurismas e 6 ectasias), apenas um era do sexo feminino. O risco para um indivíduo com 1 lesão aterosclerótica coronariana de apresentar dilatação da aorta abdominal foi de 0,4% no grupo avaliado. Da mesma forma, nos portadores de 2 ou 3 lesões, o risco foi de 1,7%, e naqueles com mais de 3 lesões, de 4,5%. Quando associados ao tabagismo, estes valores alteraram-se respectivamente para 6,9, 11,8 e 27,1%. CONCLUSÃO: O presente estudo permite concluir que a prevalência de dilatação da aorta abdominal foi de 8,9% (16 de 180 pacientes) nesta amostra específica. Apresentou-se de forma mais freqüente nos indivíduos do sexo masculino, tabagistas e em presença de lesões ateroscleróticas difusas das artérias coronárias.<br>BACKGROUND: Indiscriminate screening programs for abdominal aortic aneurysm will help a small percentage of individuals. However, when considering groups with risk factors associated with aortic dilatation, which increases the probability of the disease, such programs will provide an adequate allocation of resources and a greater benefit to the population. Programs guided by medical societies, providing an early diagnosis of vascular diseases and consequently a better preparation of patients, would result in better survival rates with lower morbidity. OBJECTIVE: To evaluate the prevalence of abdominal aortic dilatation in patients aged 60 years or older with atherosclerotic coronary disease diagnosed by coronary angiography. METHODS: The sample selected for this study considered the fact that preoperative assessment of vascular surgery had not been indication for catheterization. Evaluation was then performed, based on anamnesis, physical examination and ultrasound Doppler of the abdominal aorta. Statistical analysis started with chi-square test, with further multivariate logistic regression analysis and univariate logistic regression, with p < 0.05 considered significant. RESULTS: Of 180 patients, 57 (31.7%) were female and 123 (68.3%) were male. Age varied from 60 to 80 years, with mean of 66.7 years. Among the 16 individuals with abdominal aortic dilatation (10 aneurysms and six dilatations), only one was female. The risk of an individual with one atherosclerotic coronary lesion presenting abdominal aortic dilatation was 0.4%. Similarly, in those with two or three lesions the risk was 1.7, and 4.5% in those with more than three lesions. When associated with smoking, these values were 6.9, 11.8 and 27.1%, respectively. CONCLUSION: The present study leads to the conclusion that prevalence of abdominal aortic dilatation was 8.9% (16 out of 180 patients) in this specific sample. It was more prevalent in males, smokers and associated with presence of diffuse atherosclerotic lesions of the coronary arteries