Medical Students’ Knowledge of Autism Compared to the General Population: A Pilot Study

Background: Historically, there has been some concern regarding the level of training in autism spectrum disorder (ASD) for medical students. Throughout medical programs in the US, there is no standardised curriculum, and therefore, to make improvements in this area of medical training, a first step is to determine the current areas of competency of medical students. This pilot study investigated whether differences exist in knowledge among third-year medical students and a general population sample. Methods: We investigated beliefs about autism among a group of third-year medical students (n = 202) and among a crowdsourced sample of the general public (n = 858). A survey assessed autism knowledge regarding sources of information, causes, age of earliest diagnosis, front-line treatment providers, and diagnostic versus non-diagnostic symptoms. The third-year medical student sample was obtained from a Health Sciences Center in the Southwest. Third-year medical students were surveyed during their paediatrics rotation. The general public sample accessed and completed the survey through Amazon’s Mechanical Turk (MTurk) platform. Results: Results suggested that although third-year medical students had lower confidence regarding their autism-knowledge base, they possessed more knowledge of autism related to sources of information, causes, and diagnostic testing options than the comparison sample. Additionally, they were significantly better at differentiating diagnostic symptoms from non-diagnostic symptoms. Conclusions: Overall, the results suggest that by their third year, medical students know more about autism than the general public. Results from the current study indicate an improvement in medical students’ knowledge with respect to autism. Treatment options and the continued need for more training to enhance medical student confidence are discussed

Produção de serapilheira em sistemas agroflorestais em Tomé-Açu, Amazônia Oriental.

A deposição de serapilheira representa um elo fundamental no fluxo de carbono entre o meio físico e o biótico, conferindo ao ecossistema do qual faz parte maior estabilidade, variando de acordo com o seu estágio sucessional e o tipo de sistema utilizado. O objetivo deste trabalho consistiu em realizar um estudo do fluxo de carbono pela deposição de serapilheira de quatro sistemas agroflorestais (SAFs) com idades e composições diferentes, no município de Tomé-Açu, Pará. O fluxo de carbono foi medido na deposição de material formador de serapilheira no período de um ano. Os SAFs foram divididos em quatro categorias, denominados SAF 1, SAF 2, SAF 3 e SAF 4, sendo (SAF 1: cacau, açaí, bananeira e seringueira, 14 anos de idade, SAF 2: cacau, açaí, bananeira, seringueira, taperebá, paricá e macacaúba, 14 anos de idade, SAF 3: cupuaçu, açaí, teca e mogno, 9 anos de idade, SAF 4:cupuaçu, açaí e paricá, 9 anos de idade). Em cada sistema, foram instaladas quatro parcelas amostrais, e dentro das parcelas foram instalados coletores para medir a deposição de material formador de serapilheira. O SAF 4 teve a maior deposição de serapilheira anual entre todos os tratamentos. A produção mensal de serapilheira apresentou uma distribuição diferenciada ao longo do ano. A estação seca foi caracterizada pela maior produção de serapilheira em todos os tratamentos. A quantidade de carbono depositada via litterfall difere significativamente em sistemas agroflorestais com idades e composições diferentes. Existe também diferença significativa entre meses dentro de um mesmo tratamento.Editores técnicos: Roberto Porro, Milton Kanashiro, Maria do Socorro Gonçalves Ferreira, Leila Sobral Sampaio e Gladys Ferreira de Sousa

Data and methods to calculate cut-off values for serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest.

The data and estimation methods presented in this article are associated with the research article, "Cut-off values of serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest: a retrospective multi-centre study" [1]. In this article we estimate recommended cut-off values for in-hospital triage with respect to extracorporeal rewarming. With only 6 survivors of 103 patients collected over a period of 20 years the ability to estimate reliable threshold values is limited. In addition, because the number of avalanche victims is also limited, a significantly larger dataset is unlikely to be obtained. We have therefore adapted two non-parametric estimation methods (bootstrapping and exact binomial distribution) to our specific needs and performed a simulations to confirm validity and reliability

HIF2α reduces growth rate but promotes angiogenesis in a mouse model of neuroblastoma

<p>Abstract</p> <p>Background</p> <p>HIF2α/EPAS1 is a hypoxia-inducible transcription factor involved in catecholamine homeostasis, vascular remodelling, physiological angiogenesis and adipogenesis. It is overexpressed in many cancerous tissues, but its exact role in tumour progression remains to be clarified.</p> <p>Methods</p> <p>In order to better establish its function in tumourigenesis and tumour angiogenesis, we have stably transfected mouse neuroblastoma N1E-115 cells with the native form of HIF2α or with its dominant negative mutant, HIF2α (1–485) and studied their phenotype <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p><it>In vitro </it>studies reveal that HIF2α induces neuroblastoma cells hypertrophy and decreases their proliferation rate, while its inactivation by the HIF2α (1–485) mutant leads to a reduced cell size, associated with an accelerated proliferation. However, our <it>in vivo </it>experiments show that subcutaneous injection of cells overexpressing HIF2α into syngenic mice, leads to the formation of tumour nodules that grow slower than controls, but that are well structured and highly vascularized. In contrast, HIF2α (1–485)-expressing neuroblastomas grow fast, but are poorly vascularized and quickly tend to extended necrosis.</p> <p>Conclusion</p> <p>Together, our data reveal an unexpected combination between an antiproliferative and a pro-angiogenic function of HIF2α that actually seems to be favourable to the establishment of neuroblastomas <it>in vivo</it>.</p

HIF-1α determines the metastatic potential of gastric cancer cells

Gastric adenocarcinoma is characterised by rapid emergence of systemic metastases, resulting in poor prognosis due to vanished curative treatment options. Better understanding of the molecular basis of gastric cancer spread is needed to design innovative treatments. The transcription factor HIF-1α (hypoxia-inducible factor 1α) is frequently overexpressed in human gastric cancer, and inhibition of HIF-1α has proven antitumour efficacy in rodent models, whereas the relevance of HIF-1α for the metastatic phenotype of gastric adenocarcinoma remains elusive. Therefore, we have conducted a comprehensive analysis of the role of HIF-1α for pivotal metastasis-associated processes of human gastric cancer. Immunhistochemistry for HIF-1α showed specific staining at the invading tumour edge in 90% of human gastric cancer samples, whereas normal gastric tissue was negative and only a minority of early gastric cancers (T1 tumours) showed specific staining. Hypoxia-inducible factor 1α-deficient cells showed a significant reduction of migratory, invasive and adhesive properties in vitro. Furthermore, the HIF-1α-inhibitor 2-methoxy-estradiol significantly reduced metastatic properties of gastric cancer cells. The accentuated expression at the invading edge together with the in vitro requirement of HIF-1α for migration, invasion and adherence argues for a pivotal role of HIF-1α in local invasion and, ultimately, systemic tumour spread. These results warrant the exploration of HIF-1α-inhibiting substances in clinical treatment studies of advanced gastric cancer

Activation of β-Catenin by Oncogenic PIK3CA and EGFR Promotes Resistance to Glucose Deprivation by Inducing a Strong Antioxidant Response

Glucose is an essential fuel for cell survival and its availability limits aberrant cellular proliferation. We have hypothesized that specific cancer mutations regulate metabolic response(s) to glucose deprivation (GD). By means of somatic knock-in cellular models, we have analyzed the response to glucose deprivation in cells carrying the frequent delE746-A750EGFR, G13DKRAS or E545KPIK3CA cancer alleles. We demonstrate that, in mammary epithelial cells, glucose has an essential antioxidant function and that these cells are very sensitive to GD. Conversely, isogenic cells carrying the delE746-A750EGFR or the E545KPIK3CA, but not the G13DKRAS allele, display high tolerance to GD by stimulating the expression of anti-oxidant genes (MnSOD and catalase). This adaptive transcriptional response is mediated by the activation of WNT/β-catenin and FOXO4 signalling. Our data highlights a new functional synergism between oncogenic EGFR and PIK3CA with WNT/β-catenin conferring high tolerance to oxidative stress generated by nutrient deprivation

Expression of DDX3 Is Directly Modulated by Hypoxia Inducible Factor-1 Alpha in Breast Epithelial Cells

DEAD box protein, DDX3, is aberrantly expressed in breast cancer cells ranging from weakly invasive to aggressive phenotypes and functions as an important regulator of cancer cell growth and survival. Here, we demonstrate that hypoxia inducible factor-1α is a transcriptional activator of DDX3 in breast cancer cells. Within the promoter region of the human DDX3 gene, we identified three putative hypoxia inducible factor-1 responsive elements. By luciferase reporter assays in combination with mutated hypoxia inducible factor-1 responsive elements, we determined that the hypoxia inducible factor-1 responsive element at position -153 relative to the translation start site is essential for transcriptional activation of DDX3 under hypoxic conditions. We also demonstrated that hypoxia inducible factor-1 binds to the DDX3 promoter and that the binding is specific, as revealed by siRNA against hypoxia inducible factor-1 and chromatin immunoprecipitation assays. Thus, the activation of DDX3 expression during hypoxia is due to the direct binding of hypoxia inducible factor-1 to hypoxia responsive elements in the DDX3 promoter. In addition, we observed a significant overlap in the protein expression pattern of hypoxia inducible factor-1α and DDX3 in MDA-MB-231 xenograft tumors. Taken together, our results demonstrate, for the first time, the role of DDX3 as a hypoxia-inducible gene that exhibits enhanced expression through the interaction of hypoxia inducible factor-1 with hypoxia inducible factor-1 responsive elements in its promoter region

Macrophages promote angiogenesis in human breast tumour spheroids in vivo

An in vivo model has been established to study the role of macrophages in the initiation of angiogenesis by human breast tumour spheroids in vivo. The extent of the angiogenic response induced by T47D spheroids implanted into the dorsal skinfold chamber in nude mice was measured in vivo and compared to that induced by spheroids infiltrated with human macrophages prior to implantation. Our results indicate that the presence of macrophages in spheroids resulted in at least a three-fold upregulation in the release of vascular endothelial growth factor (VEGF) in vitro when compared with spheroids composed only of tumour cells. The angiogenic response measured around the spheroids, 3 days after in vivo implantation, was significantly greater in the spheroids infiltrated with macrophages. The number of vessels increased (macrophages vs no macrophages 34±1.9 vs 26±2.5, P<0.01), were shorter in length (macrophages vs no macrophages 116±4.92 vs 136±6.52, P<0.008) with an increased number of junctions (macrophages vs no macrophages 14±0.93 vs 11±1.25, P<0.025) all parameters indicative of new vessel formation. This is the first study to demonstrate a role for macrophages in the initiation of tumour angiogenesis in vivo

Relation of hypoxia inducible factor 1α and 2α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival

Hypoxia inducible factors HIF1α and HIF2α are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1α and 2α protein levels, as a consequence of a redox-sensitive stabilization. The HIFαs enter the nucleus, heterodimerize with the HIF1β protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1α and HIF2α expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2α expression with HIF1α expression showed a significant association (P < 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P < 0.004), PD-ECGF (P < 0.003) and bFGF (P < 0.04) was noted. HIF1α correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2α was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2α protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2α expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1α expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2α expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1α and HIF2α overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting the HIF pathway may prove of importance in the treatment of NSCLC. © 2001 Cancer Research Campaignhttp://www.bjcancer.co