Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinibBackground: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib. Objective: To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic-pathological features and therapeutic response. Material and methods: Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor. Results: AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC. Conclusion: AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinibtreated patients with metastatic renal cell carcinoma.this study was supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors. Rui Manuel Reis is recipient of a National Council of Technological and Scientific Development (CNPq) scholarship.info:eu-repo/semantics/publishedVersio

Stroke Correlates in Chagasic and Non-Chagasic Cardiomyopathies

BACKGROUND: Aging and migration have brought changes to the epidemiology and stroke has been shown to be independently associated with Chagas disease. We studied stroke correlates in cardiomyopathy patients with focus on the chagasic etiology. METHODOLOGY/PRINCIPAL FINDINGS: We performed a cross-sectional review of medical records of 790 patients with a cardiomyopathy. Patients with chagasic (329) and non-chagasic (461) cardiomyopathies were compared. There were 108 stroke cases, significantly more frequent in the Chagas group (17.3% versus 11.1%; p<0.01). Chagasic etiology (odds ratio [OR], 1.79), pacemaker (OR, 2.49), atrial fibrillation (OR, 3.03) and coronary artery disease (OR, 1.92) were stroke predictors in a multivariable analysis of the entire cohort. In a second step, the population was split into those with or without a Chagas-related cardiomyopathy. Univariable post-stratification stroke predictors in the Chagas cohort were pacemaker (OR, 2.73), and coronary artery disease (CAD) (OR, 2.58); while atrial fibrillation (OR, 2.98), age over 55 (OR, 2.92), hypertension (OR, 2.62) and coronary artery disease (OR, 1.94) did so in the non-Chagas cohort. Chagasic stroke patients presented a very high frequency of individuals without any vascular risk factors (40.4%; OR, 4.8). In a post-stratification logistic regression model, stroke remained associated with pacemaker (OR, 2.72) and coronary artery disease (OR, 2.60) in 322 chagasic patients, and with age over 55 (OR, 2.38), atrial fibrillation (OR 3.25) and hypertension (OR 2.12; p = 0.052) in 444 non-chagasic patients. CONCLUSIONS/SIGNIFICANCE: Chagas cardiomyopathy presented both a higher frequency of stroke and an independent association with it. There was a high frequency of strokes without any vascular risk factors in the Chagas as opposed to the non-Chagas cohort. Pacemaker rhythm and CAD were independently associated with stroke in the Chagas group while age over 55 years, hypertension and atrial fibrillation did so in the non-Chagas cardiomyopathies

Approach to Endoscopic Procedures: A Routine Protocol from a Quaternary University Referral Center Exclusively for Coronavirus Disease 2019 Patients

OBJECTIVES: The present coronavirus disease (COVID-19) pandemic has ushered in an unprecedented era of quality control that has necessitated advanced safety precautions and the need to ensure the adequate protection of healthcare professionals (HCPs). Endoscopy units, endoscopists, and other HCP may be at a significant risk for transmission of the virus. Given the immense burden on the healthcare system and surge in the number of patients with COVID-19, well-designed protocols and recommendations are needed. We aimed to systematically characterize our approach to endoscopic procedures in a quaternary university hospital setting and provide summary protocol recommendations. METHOD: This descriptive study details a COVID-19-specific protocol designed to minimize infection risks to patients and healthcare workers in the endoscopy unit. RESULTS: Our institution, located in Sa˜o Paulo, Brazil, includes a 900-bed hospital, with a 200-bed-specific intensive care unit exclusively designed for patients with moderate and severe COVID-19. We highlighted recommendations for infection prevention and control during endoscopic procedures, including appropriate triage and screening, outpatient management and procedural recommendations, role and usage of personal protective equipment (PPE), and role and procedural logistics involving COVID-19-positive patients. We also detailed hospital protocols for reprocessing endoscopes and cleaning rooms and also provided recommendations to minimize severe acute respiratory syndrome coronavirus 2 transmission. CONCLUSION: This COVID-19-specific administrative and clinical protocol can be replicated or adapted in multiple institutions and endoscopy units worldwide. Furthermore, the recommendations and summary protocol may improve patient and HCP safety in these trying times

Determinant Factors of Dividend Payments in Brazil

This study identifies factors that shaped cash disbursement distribution policies employed by Brazilian public companies listed on the Brazilian Securities, Commodities and Futures Exchange (BM&FBOVESPA) from 1995 to 2011. Relationships between Dividends/Total Assets and potential determinants discussed in the literature, including firm size, corporate governance, profitability, leverage, market to book, liquidity, investment, risk, profit growth, information asymmetry and agency conflict, are examined. The following econometric methods are employed: (1) Tobit, given the nature of the dividend data, and (2) the Generalized Method of Moments (GMM) to control for endogenous regressors. Significant positive variables found include size, return on assets (ROA), market to book, liquidity and profit growth. It can thus be inferred that larger firm size, profitability, market value, liquidity and profit growth correlate with greater firm pro pensity to distribute money to shareholders, thus supporting the theory of corporate finance. Significant negative variables found include leverage, liquidity squared, capex, beta and tag along 100%. It is thus inferred that more significantly leveraged companies that invest more heavily in fixed assets and that exhibit high liquidity, higher risk and less conflict between controlling and minority shareholders will be less likely to pay dividends to shareholders.</p

Propriedades de ZrO2 (Y2 O3) reciclado proveniente da confecção de próteses dentárias

RESUMO O objetivo deste trabalho foi a recuperação de descartes de ZrO2(Y2O3) oriundos de laboratórios de próteses dentárias, a partir do seu reprocessamento. Os descartes de ZrO2(Y2O3) foram fragmentados, peneirados e calcinados a 900ºC. Pós com tamanho menor que 32&#956;m foram prensados uniaxialmente a 100MPa e sinterizados em temperaturas entre 1400 e 1600ºC-120min. Análise de difração de raios X realizadas nos materiais calcinados indicaram a presença majoritária da fase ZrO2 tetragonal. Os compactos apresentaram densidade a verde próximo a 47% e as amostras sinterizadas tiveram sua densidade relativa variando entre 83,5% e 95%, para temperaturas de sinterização de 1400 e 1600ºC, respectivamente. Os resultados da análise de difração de raios X indicaram a presença da fase ZrO2 tetragonal, com dureza Vickers e tenacidade máxima obtidos para as amostras sinterizadas a 1600ºC, da ordem de 1100 HV e 5,7 MPa.m1/2 respectivamente

Simbióticos e monensina sódica no desempenho e na qualidade da carne de novilhas mestiças Angus confinadas

Resumo:O objetivo deste trabalho foi avaliar o efeito da inclusão de simbióticos e de monensina sódica em dietas sobre o desempenho, as características de carcaça e a qualidade da carne de novilhas mestiças Angus em confinamento. Utilizou-se um delineamento inteiramente casualizado, com 64 animais distribuídos em quatro tratamentos: controle, dieta sem suplementação; dieta suplementada com simbióticos; dieta com monensina sódica; e dieta com simbióticos e monensina sódica. A dieta com monensina sódica e a dieta com simbióticos e monensina sódica proporcionaram maior ganho de peso médio diário e ganho de peso vivo total, além de melhorar a eficiência alimentar e biológica dos animais em comparação ao controle. A dieta de simbióticos, a de monensina e a de simbióticos com monensina sódica ocasionaram a redução da ingestão de matéria seca, elevaram o peso do filé da costela e os teores de lipídeos totais na carne. A dieta com simbióticos proporcionou a redução da força de cisalhamento da carne em relação ao controle. A inclusão de simbióticos, com ou sem monensina sódica, na dieta de novilhas mestiças Angus confinadas, beneficia o desempenho animal e algumas características físico-químicas da carne

The germline mutational landscape of BRCA1 and BRCA2 in Brazil

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective.This work was supported in part by grants from Barretos Cancer Hospital (FINEP - CT-INFRA, 02/2010), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2013/24633-2 and 2103/23277-8), Fundação de Apoio à Pesquisa do Rio Grande do Norte (FAPERN), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Ministério da Saúde, the Breast Cancer Research Foundation (Avon grant #02-2013-044) and National Institute of Health/National Cancer Institute (grant #RC4 CA153828-01) for the Clinical Cancer Genomics Community Research Network. Support in part was provided by grants from Fundo de Incentivo a Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, BioComputacional 3381/2013, Rede de Pesquisa em Genômica Populacional Humana), Secretaria da Saúde do Estado da Bahia (SESAB), Laboratório de Imunologia e Biologia Molecular (UFBA), INCT pra Controle do Câncer and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). RMR and PAP are recipients of CNPq Productivity Grants, and Bárbara Alemar received a grant from the same agencyinfo:eu-repo/semantics/publishedVersio