Elastofibromatous changes in giant cell fibroma and amalgam tattoo: Unusual findings in common oral lesions.

Several cases of elastofibromatous lesion affecting the oral mucosa have been reported. Clinically, these lesions may appear as small exophytic lesions or less often as white lesions. Therefore, fibrous hyperplasia and leukoplakia are not uncommonly considered in clinical differential diagnosis. Microscopically, elastic and fibrous connective tissue deposition is seen. Rarely, elastofibromatous changes can be detected when assessing intraoral lesions, including cysts, salivary gland neoplasms, and epithelial dysplasia. Here we report two oral lesions showing elastofibromatous changes, expanding their clinicopathological spectrum. The first case was a 46-year-old man with a history of asymptomatic nodular lesion on the palate 1 year ago, diagnosed as giant cell fibroma with elastofibromatous changes. The second case was a 79-year-old woman who presented a pigmented and mildly symptomatic lesion on the mandibular alveolar mucosa several months ago, diagnosed as amalgam tattoo associated with elastofibromatous changes.

The Association between Gestational Diabetes and the Microbiome: A Systematic Review and Meta-Analysis.

Gestational diabetes, affecting about 10% of pregnancies, is characterized by impaired glucose regulation and can lead to complications for health of pregnant women and their offspring. The microbiota, the resident microbes within the body, have been linked to the development of several metabolic conditions. This systematic review with meta-analysis aims to summarize the evidence on the differences in microbiota composition in pregnant women with gestational diabetes and their offspring compared to healthy pregnancies. A thorough search was conducted in the PubMed, Scopus, and Web of Science databases, and data from 21 studies were analyzed utilizing 41 meta-analyses. In the gut microbiota, Bifidobacterium and Alistipes were found to be more abundant in healthy pregnancies, while Roseburia appears to be more abundant in gestational diabetes. The heterogeneity among study findings regarding the microbiota in the meconium is considerable. The placental microbiota exhibited almost no heterogeneity, with an increased abundance of Firmicutes in the gestational diabetes group and a higher abundance of Proteobacteria in the control. The role of the microbiota in gestational diabetes is reinforced by these findings, which additionally point to the potential of microbiome-targeted therapies. To completely comprehend the interactions between gestational diabetes and the microbiome, standardizing methodologies and further research is necessary.

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

The pro-proliferative effect of interferon-γ in breast cancer cell lines is dependent on stimulation of ASCT2-mediated glutamine cellular uptake.

AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for breast cancer initiation and progression. Glutamine (GLN) is a critical nutrient for cancer cells. The aim of this study was to investigate the effect of T2DM-associated compounds upon GLN uptake by breast cancer cells. MAIN METHODS: The in vitro uptake of 3H-GLN by breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-12A) cell lines was measured. KEY FINDINGS: 3H-GLN uptake in the three cell lines is mainly Na+-dependent and sensitive to the ASCT2 inhibitor GPNA. IFN-γ increased total and Na+-dependent 3H-GLN uptake in the two breast cancer cell lines, and insulin increased total and Na+-dependent 3H-GLN uptake in the non-tumorigenic cell line. GPNA abolished the increase in 3H-GLN uptake promoted by these T2DM-associated compounds. ASCT2 knockdown confirmed that the increase in 3H-GLN uptake caused by IFN-γ (in breast cancer cells) and by insulin (in non-tumorigenic cells) is ASCT2-dependent. IFN-γ (in MDA-MB-231 cells) and insulin (in MCF-12A cells) increased ASCT2 transcript and protein levels. Importantly, the pro-proliferative effect of IFN-γ in breast cancer cell lines was associated with an increase in 3H-GLN uptake which was GPNA-sensitive, blocked by ASCT2 knockdown and mediated by activation of the PI3K-, STAT3- and STAT1 intracellular signalling pathways. SIGNIFICANCE: IFN-γ and insulin possess pro-proliferative effects in breast cancer and non-cancer cell lines, respectively, which are dependent on an increase in ASCT2-mediated glutamine transport. Thus, an effective inhibition of ASCT2-mediated glutamine uptake may be a therapeutic strategy against human breast cancer in T2DM patients.

Parapharyngodon hispidus n. sp. (Nematoda: Pharyngodonidae) in Tropidurus hispidus (Spix) (Squamata: Tropiduridae) from Caatinga Biome of the Vale do São Francisco, state of Pernambuco, Brazil with a key for the Neotropical species of the genus Parapharyngodon Chatterji.

One species of Parapharyngodon Chatterji (Nematoda: Pharyngodonidae), parasitizing the large intestine of Tropidurus hispidus (Spix) (Squamata: Tropiduridae) in Caatinga biome from Brazil is described and illustrated . This new species differs from a part of its congeners by a set of characters in males: the presence of four pairs of caudal papillae, unpaired post cloacal papilla absent, and smooth anterior cloacal lip. Among the Parapharyngodon species with four pairs caudal papillae, unpaired post clocal papilla absent, and smooth cloacal lips, only P. hispidus n. sp. and P. jairaipurii Rizvi Bursey (Oriental realm), features the same characteristics including sharp pointed tip of spicule, stout terminus or spike of tail of females, and punctate ornamentation of the eggshell. However, these two species are different by the size of spicules (spicules of P. jairaipuri are around 55% of the size spicules of P. hispidus n. sp.); and the arrangement of the caudal papillae (two pairs of adcloacal papillae in P. jaraipuri which are absent in P. hispidus n. sp.). Parapharyngodon hispidus n. sp. is the 55th species assigned to the genus and the 11th species of this genus described in Neotropical hosts.

Helminths Parasitizing Procellosaurinus erythrocercus, a Little-Known Neotropical Lizard Endemic to Brazilian Semiarid Caatinga Biome.

We report the identification of helminths in Procellosaurinus erythrocercus, a lizard endemic to Brazilian Caatinga biome. Parasites that we found, such as Parapharyngodon sp. and Oochoristica sp., have not been reported in this host, which is under threat in its area of occurrence.

Development and validation of exhaled breath condensate microRNAs to identify and endotype asthma in children.

Detection and quantification of microRNAs (miRNAs) in exhaled breath condensate (EBC) has been poorly explored. Therefore we aimed to assess miRNAs in EBC as potential biomarkers to diagnose and endotype asthma in school aged children. In a cross sectional, nested case control study, all the asthmatic children (n = 71) and a random sample of controls (n = 115), aged 7 to 12 years, attending 71 classrooms from 20 local schools were selected and arbitrarily allocated to the development or validation set. Participants underwent skin-prick testing, spirometry with bronchodilation, had exhaled level of nitric oxide determined and EBC collected. Based on previous studies eleven miRNAs were chosen and analyzed in EBC by reverse transcription-quantitative real-time PCR. Principal component analysis was applied to identify miRNAs profiles and associations were estimated using regression models. In the development set (n = 89) two clusters of miRNAs were identified. After adjustments, cluster 1 and three of its clustered miRNAs, miR-126-3p, miR-133a-3p and miR-145-5p were positively associated with asthma. Moreover miR-21-5p was negatively associated with symptomatic asthma and positively associated with positive bronchodilation without symptoms. An association was also found between miR-126-3p, cluster 2 and one of its clustered miRNA, miR-146-5p, with higher FEF25-75 reversibility. These findings were confirmed in the validation set (n = 97) where two identical clusters of miRNAs were identified. Additional significant associations were observed between miR-155-5p with symptomatic asthma, negative bronchodilation with symptoms and positive bronchodilation without symptoms. We showed that microRNAs can be measured in EBC of children and may be used as potential biomarkers of asthma, assisting asthma endotype establishment.

Propriedades psicométricas do WHOQOL-HIV Bref para avaliação da qualidade de vida / Psychometric properties of the WHOQOL-HIV Bref for quality of life assessment / Propiedades psicométricas del WHOQOL-VIH Bref para evaluación de calidad de vida

Objetivo: Avaliar as propriedades psicométricas do questionário WHOQOL-HIV Bref em pessoas com HIV/AIDS. Método: O instrumento foi aplicado a 226 pessoas com HIV/AIDS do Norte de Minas Gerais. As propriedades psicométricas foram avaliadas pela validade de construto, análise da confiabilidade e validade de critério. Resultados: O modelo com seis domínios apresentou ajustamento aceitável (χ2/gl= 1,77, p <0,001, GFI = 0,85, CFI= 0,89, RMSEA = 0,058 ). O WHOQOL-HIV Bref apresentou correlações estatisticamente significativas entre os seis domínios, consistência interna e reprodutibilidade satisfatórias. Os escores dos domínios demonstraram correlação significativa com o escore da qualidade de vida geral e dos itens que avaliam a autopercepção da qualidade de vida e da saúde, correlação significativa com o resultado global da depressão e diferenças estatisticamente significativas entre subgrupos de pacientes segundo variáveis socioeconômicas e clínicas. Conclusões: O WHOQOL-HIV Bref apresentou-se válido, confiável para medir a qualidade de vida de pessoas com HIV/AIDS. (AU)

Objective: To evaluate the psychometric properties of the WHOQOL-HIV Bref questionnaire in people with HIV / AIDS. Method: The questionnaire was applied to 226 people living with HIV/AIDS in the Northern part of the state of Minas Gerais. The psychometric properties were evaluated by construct validity, reliability analysis, and criteria validity. Results: The model with six domains had an acceptable adjustment (χ2 / gl = 1.77, p <0.001, GFI = 0.85, CFI = 0.89, RMSEA = 0.058). The WHOQOL-HIV Bref showed statistically significant correlations among the six domains, satisfactory internal consistency and reproducibility. The instrument scores showed a significant correlation with the general quality of life score and the items that assess the self-perception of quality of life and health, a significant correlation with the overall result of depression, and statistically significant differences between subgroups of patients. Conclusions: The WHOQOL-HIV Bref was valid, reliable to measure the quality of life of people with HIV/AIDS. (AU)

Objetivo: Evaluar las propiedades psicométricas del cuestionario WHOQOL- HIV Bref en personas con HIV/SIDA. Método: El instrumento fue aplicado a 226 personas con HIV/SIDA del Norte de Minas Gerais. Las propiedades psicométricas fueron evaluadas por validez de constructo, análisis de confiabilidad, y validez de criterio. Resultados: El modelo con seis dominios presentó un ajuste aceptable (χ2 / gl = 1,77, p <0,001, GFI = 0,85, CFI = 0,89, RMSEA = 0,058). El WHOQOL-HIV Bref presentó correlaciones estadísticamente significativas entre los seis dominios, consistencia interna, y reproductibilidad satisfactorias. Los resultados de los dominios demostraron correlación significativa con el resultado de calidad de vida general y de los ítems que evalúan la autopercepción de calidad de vida y de la salud, correlación significativa con el resultado global de depresión y diferencias estadísticamente significativas entre subgrupos de pacientes según variables socioeconómicas y clínicas. Conclusiones: El WHOQOL- HIV Bref se presentó como válido y confiable para medir la calidad de vida de personas con HIV/SIDA. (AU)

Selective pro-apoptotic and antimigratory effects of polyphenol complex catechin:lysine 1:2 in breast, pancreatic and colorectal cancer cell lines.

Cancer is a major cause of death in both developed and developing countries. Polyphenols, abundantly found in plants, possess many anticarcinogenic properties, including inhibition of cancer cell proliferation, tumor growth, angiogenesis, metastasis and inflammation, as well as pro-apoptotic effects. Our study aimed to investigate the effects of a complex of (+)-catechin with 2 lysines (Cat:Lys) on cancer and non-cancer cells. For this, the in vitro effects of Cat:Lys on the viability, growth, proliferation, apoptosis, nutrient uptake and migration of breast, pancreatic and colorectal cancer and non-cancer cell lines was evaluated. We found that Cat:Lys exerted antiproliferative and cytotoxic effects in all breast, pancreatic and colorectal cell lines tested, but with a much less marked amplitude in non-cancer cell lines. It nevertheless interfered with nutrient (3H-deoxy-D-glucose and 3H-lactate) uptake and with lactate production in both cancer and non-cancer cell lines. Cat:Lys was found to possess selective antimigratory effects in breast, pancreatic and colorectal cancer cell lines compared to non-cancer cell lines. Cat:Lys also exerted pro-apoptotic effects in all the cancer cell lines that we tested, but not in non-cancer breast and pancreatic cell lines. The antimigratory, but not the pro-apoptotic, effects of Cat:Lys were found to be mediated by JAK2/STAT3 and Wnt pathway inhibition. In conclusion, Cat:Lys is a strong candidate for the development of new, effective anticancer agents against cancer.

Quality of life predictors for people living with HIV/AIDS in an impoverished region of Brazil.

INTRODUCTION: Quality of life (QoL) is important for people living with HIV/AIDS, particularly as the disease progresses. This study evaluated the QoL of people living with HIV/AIDS (PLWHA), as well as its predictors, in one of the most impoverished regions of Brazil. METHODS: This cross-sectional study was conducted with patients older than 18 years with HIV/AIDS from two specialized HIV/AIDS care centers in the city of Montes Claros between 2013 and 2014. Sample size was calculated considering the estimates of mean scores for various dimensions of the European Portuguese version of the World Health's Organization Quality of Life Instrument in HIV Infection (WHOQOL-HIV Bref). The following parameters were adopted: CI of 95%, estimated mean scores for QoL equal to 15, estimated variance for QoL scores equal to 16, and 5% relative margin of error. An increase of 20% was established to compensate for possible non-responses or losses, and correcting any design effect, adopting a deff equal to 2.0. Calculations revealed the need to interview at least 221 patients. Therefore, 226 patients living with HIV/AIDS were randomly selected. RESULTS: A total of 226 patients with mean age 43.7 years were evaluated: 51.8% men, 51.8% unemployed, 51.8% with low schooling level, 89.8% used antiretrovirals, and 43.3% experienced depression. Despite this, data indicated that 65% self-assessed their QoL as good and very good. Low QoL was associated with sociodemographic variables and some clinical variables. CONCLUSIONS: Depression was the main predictor of low QoL in all domains evaluated.

Quality of life predictors for people living with HIV/AIDS in an impoverished region of Brazil

Abstract INTRODUCTION: Quality of life (QoL) is important for people living with HIV/AIDS, particularly as the disease progresses. This study evaluated the QoL of people living with HIV/AIDS (PLWHA), as well as its predictors, in one of the most impoverished regions of Brazil. METHODS: This cross-sectional study was conducted with patients older than 18 years with HIV/AIDS from two specialized HIV/AIDS care centers in the city of Montes Claros between 2013 and 2014. Sample size was calculated considering the estimates of mean scores for various dimensions of the European Portuguese version of the World Health's Organization Quality of Life Instrument in HIV Infection (WHOQOL-HIV Bref). The following parameters were adopted: CI of 95%, estimated mean scores for QoL equal to 15, estimated variance for QoL scores equal to 16, and 5% relative margin of error. An increase of 20% was established to compensate for possible non-responses or losses, and correcting any design effect, adopting a deff equal to 2.0. Calculations revealed the need to interview at least 221 patients. Therefore, 226 patients living with HIV/AIDS were randomly selected. RESULTS: A total of 226 patients with mean age 43.7 years were evaluated: 51.8% men, 51.8% unemployed, 51.8% with low schooling level, 89.8% used antiretrovirals, and 43.3% experienced depression. Despite this, data indicated that 65% self-assessed their QoL as good and very good. Low QoL was associated with sociodemographic variables and some clinical variables. CONCLUSIONS: Depression was the main predictor of low QoL in all domains evaluated.

Drug-Induced HSP90 Inhibition Alleviates Pain in Monoarthritic Rats and Alters the Expression of New Putative Pain Players at the DRG.

Purinergic receptors (P2XRs) have been widely associated with pain states mostly due to their involvement in neuron-glia communication. Interestingly, we have previously shown that satellite glial cells (SGC), surrounding dorsal root ganglia (DRG) neurons, become activated and proliferate during monoarthritis (MA) in the rat. Here, we demonstrate that P2X7R expression increases in ipsilateral DRG after 1 week of disease, while P2X3R immunoreactivity decreases. We have also reported a significant induction of the activating transcriptional factor 3 (ATF3) in MA. In this study, we show that ATF3 knocked down in DRG cell cultures does not affect the expression of P2X7R, P2X3R, or glial fibrillary acidic protein (GFAP). We suggest that P2X7R negatively regulates P2X3R, which, however, is unlikely mediated by ATF3. Interestingly, we found that ATF3 knockdown in vitro induced significant decreases in the heat shock protein 90 (HSP90) expression. Thus, we evaluated in vivo the involvement of HSP90 in MA and demonstrated that the HSP90 messenger RNA levels increase in ipsilateral DRG of inflamed animals. We also show that HSP90 is mostly found in a cleaved form in this condition. Moreover, administration of a HSP90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), attenuated MA-induced mechanical allodynia in the first hours. The drug also reversed the HSP90 upregulation and cleavage. 17-DMAG seemed to attenuate glial activation and neuronal sensitization (as inferred by downregulation of GFAP and P2X3R in ipsilateral DRG) which might correlate with the observed pain alleviation. Our data indicate a role of HSP90 in MA pathophysiology, but further investigation is necessary to clarify the underlying mechanisms.

E-cadherin impairment increases cell survival through Notch-dependent upregulation of Bcl-2.

The role of E-cadherin in tumorigenesis has been attributed to its ability to suppress invasion and metastization. However, E-cadherin impairment may have a wider impact on tumour development. We have previously shown that overexpression of mutant human E-cadherin in Drosophila produces a phenotype characteristic of downregulated Notch. Hence, we hypothesized that Notch signalling may be influenced by E-cadherin and may mediate tumour development associated with E-cadherin deficiency. De novo expression of wild-type E-cadherin in two cellular models led to a significant decrease in the activity of the Notch pathway. In contrast, the ability to inhibit Notch-1 signalling was lost in cells transfected with mutant forms of E-cadherin. Increased Notch-1 activity in E-cadherin-deficient cells correlated with increased expression of Bcl-2, and increased resistance to apoptotic stimuli. After Notch-1 inhibition, E-cadherin-deficient cells were re-sensitized to apoptosis in a similar degree to wild-type E-cadherin cells. We also show that Notch-inhibiting drugs are able to significantly inhibit the growth of E-cadherin-deficient cells xenografted into nude mice. This effect was comparable with the one observed in animals treated with the chemotherapeutic agent taxol, a chemical inducer of cell death. In conclusion, our results show that aberrant Notch-1 activation, Bcl-2 overexpression and increased cell survival are likely to play a crucial role in neoplastic transformation associated with E-cadherin impairment. These findings highlight the possibility of new targeted therapeutical strategies for the treatment of tumours associated with E-cadherin inactivation.

The role of N-acetylglucosaminyltransferase III and V in the post-transcriptional modifications of E-cadherin.

It has long been recognized that E-cadherin dysfunction is a major cause of epithelial cell invasion. However, very little is known about the post-transcriptional modifications of E-cadherin and its role in E-cadherin mediated tumor progression. N-acetylglucosaminyltransferase III (GnT-III) catalyzes the formation of a bisecting GlcNAc structure in N-glycans, and has been pointed as a metastasis suppressor. N-acetylglucosaminyltransferase V (GnT-V) catalyzes the addition of beta1,6 GlcNAc branching of N-glycans, and has been associated to increase metastasis. The regulatory mechanism between E-cadherin expression and the remodeling of its oligosaccharides structures by GnT-III and GnT-V were explored in this study. We have demonstrated that wild-type E-cadherin regulates MGAT3 gene transcription resulting in increased GnT-III expression. We also showed that GnT-III and GnT-V competitively modified E-cadherin N-glycans. The GnT-III knockdown cells revealed a membrane de-localization of E-cadherin leading to its cytoplasmic accumulation. Further, the GnT-III knockdown cells also caused modifications of E-cadherin N-glycans catalyzed by GnT-III and GnT-V. Altogether our results have clarified the existence of a bidirectional crosstalk between E-cadherin and GnT-III/GnT-V that was, for the first time, reproduced in an in vivo model. This study opens new insights into the post-transcriptional modifications of E-cadherin in its biological function, in a tumor context.

Schistosoma haematobium total antigen induces increased proliferation, migration and invasion, and decreases apoptosis of normal epithelial cells.

Schistosome worms are blood-dwelling flukes that cause chronic infection in more than 200 million people and are thought to be responsible for 500,000 deaths annually. During infection with Schistosoma haematobium, eggs are deposited in the mucosa and submucosa of the bladder and lower ureters. Squamous cell carcinoma (SCC) of the bladder is a long-term sequela of chronic infection. The mechanisms underlying the association between S. haematobium and SCC of the bladder are largely unknown, with all reports to date exclusively demonstrating epidemiological evidence linking S. haematobium infection with SCC of the bladder. We hypothesised that the parasite antigens might induce alterations in epithelial cells towards cancer. For this we used Chinese Hamster Ovary (CHO) cells and treated the cells in culture with S. haematobium total antigen (Sh). Our results showed increased proliferation, increased S-phase and decreased apoptosis, as well as down-regulation of tumour suppressor p27 and up-regulation of anti-apoptotic molecule Bcl-2 in Sh-treated cells compared with controls. We also found increased migration and invasion. To our knowledge, this is the first report demonstrating alterations of normal epithelial cells as a direct effect of S. haematobium antigens.

Helicobacter and gastric malignancies.

Individuals infected with Helicobacter pylori, a stomach colonizing bacteria, have an increased risk of developing gastric malignancies. The risk for developing cancer relates to the physiologic and histologic changes that H. pylori infection induces in the stomach. In the last year numerous studies have been conducted in order to characterize the association between H. pylori infection and gastric cancer. These studies range from epidemiologic approaches aiming at the identification of environmental, host genetic, and bacterial factors associated with risk of gastric cancer, to molecular and cell biology approaches aiming at understanding the interaction between H. pylori and the transforming epithelial cell. In this review an account of the last year's research activity on the relationship between H. pylori and gastric cancer will be given.

Prevalência e características do tabagismo nos estudantes do sexto ano de medicina da Fundação Educacional Serra dos Órgãos / Prevalence and characteristics of smoking among sixth year medical students of Fundação Educacional Serra dos Órgãos

Introdução: pesquisas internacionais têm avaliado o hábito tabágico dos estudantes de medicina, mas há poucas informações disponíveis sobre os estudantes brasileiros. O objetivo foi avaliar a prevalência e características do tabagismo, nos estudantes do sexto ano de medicina, da Fundação Educacional Serra dos Órgãos. Metodologia: estudo transversal realizado entre os estudantes do sexto ano, no primeiro trimestre de 2006, utilizando questionário auto-aplicável, de caráter individual e sigiloso, com perguntas dirigidas a fumantes, ex-fumantes e não fumantes. Resultados: dos 153 estudantes, 134 responderam ao questionário, 84 (62,7%) eram do sexo masculino, com média de idade de 24,96 ±2,45 anos. Com relação ao hábito tabágico, 92 (68,7%) eram não fumantes, 18 (13,4%) ex-fumantes e 24 (17,9%) fumantes. Não houve diferença na prevalência entre os sexos. Observou-se diferença significativa em relação a história de tabagismo dos familiares. Não houve diferença entre os grupos com relação ao consumo de álcool. O fato de morar sozinho não contribuiu para que os estudantes começassem a fumar; no entanto, a metade dos fumantes fuma mais agora do que quando entrou na faculdade. A maioria dos estudantes respondeu que o fumo não deveria ser permitido em nenhum local do hospital; no entanto, 14,2% deles disseram que não se incomodariam diante de pessoas fumando na unidade, evidenciando desconhecimento ou negligência aos malefícios do tabagismo passivo. Conclusão: a prevalência de tabagismo entre os estudantes de medicina ainda é maior do que o esperado, o que demanda das escolas médicas uma maior reflexão sobre os conhecimentos transmitidos aos seus alunos no controle desta doença.

The prevalence of PIK3CA mutations in gastric and colon cancer.

A wide variety of tumours show PIK3CA mutations leading to increased phosphatidylinositol-3 kinase (PI3K) activity. We have determined the frequency of PIK3CA mutations in exons 9 and 20 that has previously been reported as mutational hotspot regions in distinct tumour models. One hundred and fifty gastrointestinal carcinomas (47 gastric and 103 colorectal) that were characterised for MSI status (76 MSI and 74 MSS) by PCR-SSCP sequencing were evaluated. We also analysed the association between PIK3CA mutations and KRAS or BRAF mutations. PIK3CA mutations in exons 9 and 20 were present in 13.6% and 10.6% of colorectal and gastric carcinomas, respectively. No differences in frequency and type of PIK3CA mutations were found between MSI and MSS colorectal carcinomas. All gastric carcinomas with PIK3CA mutations were MSI. The number of cases harbouring concomitant PIK3CA and KRAS or BRAF mutations was higher in colorectal than in gastric carcinomas (P = 0.016). In colorectal carcinoma, PIK3CA mutations occur preferentially together with activating KRAS-BRAF mutations (MSI and MSS) while in gastric carcinomas PIK3CA mutations tend to occur as isolated events (MSI).

NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease.

BACKGROUND: NOD2/CARD15 was described as the first susceptibility gene to Crohn's disease (CD). Polymorphisms in the TNFA gene and in the IL1 gene cluster, which are associated with an enhanced chronic inflammatory response, may also play a role in the development of CD. The aim of this study was to determine the association of polymorphisms in the CARD15, TNFA, IL1B, and IL1RN genes with risk of development of CD and with the clinicopathological profile of CD patients. METHODS: In a case-control study including 235 CD patients and 312 controls (929 controls for TNFA genotyping), the CARD15 (R702W, G908R, and 1007fs), TNFA (-308G/A and -857C/T), IL1B (-511C/T), and IL1RN (intron 2 variable number of tandem repeats) polymorphisms were genotyped. RESULTS: We observed a significant association between CD and the CARD15 polymorphisms, with an odds ratio (OR) of 2.9 [95% confidence interval (CI), 1.9 to 4.6] for carriers of 1 variant allele and an OR of 11.8 (95% CI, 3.5 to 40.4) for carriers of 2 variant alleles. Patients with CARD15 polymorphisms had more frequently ileal or ileocolonic disease location, stricturing phenotype, abdominal surgery, and no extraintestinal manifestations. The TNFA-308A/A genotype was associated with susceptibility to CD with an OR of 3.0 (95% CI, 1.2 to 7.2). TNFA-308A/A homozygotes showed a higher frequency of erythema nodosum and arthritis, colonic disease location, and absence of abdominal surgery. No associations were found with the TNFA-857, IL1B-511, and the IL1RN VNTR polymorphisms. CONCLUSIONS: These findings suggest that CARD15 and TNFA-308 genetic polymorphisms are associated with increased risk of CD displaying distinct clinicopathological profiles.