DETECÇÃO DE FORMAÇÃO EROSIVA (VOÇOROCA) POR MEIO DE CLASSIFICAÇÃO HIERÁRQUICA E POR ÁRVORE DE DECISÃO

Este estudo teve por objetivo verificar a possibilidade de reconhecimento de feiçõeserosivas do tipo voçoroca utilizando análise orientada a objeto (OBIA - Object-Based Image Analysis). A área de estudo está localizada no município deUberlândia, em Minas Gerais. Em função do objetivo, definiu-se uma redesemântica hierárquica multinível para representação do conhecimento especialista.Foram usados dados espectrais oriundos de imagem IKONOS e dados deintensidade e altimétricos provenientes de perfilamento com ALS (Airborne LaserScanner). Os objetos foram gerados por meio de segmentação multirresolução(FNEA-Fractal Net Evolution Approach) aplicada aos dados espectrais ealtimétricos. O reconhecimento das feições foi realizado por classificaçãohierárquica e por árvores de decisão (algoritmo CART-Classification AndRegression Trees). A metodologia permitiu a identificação da relevância dos dadosde entrada, parâmetros de segmentação e atributos a serem usados para classificaçãodas voçorocas. Os resultados obtidos com a classificação hierárquica e com CARTforam bastante similares, os quais evidenciaram a possibilidade do uso do métodosemiautomatizado a partir dos parâmetros previamente identificados e analisados

Participação de um agente adrenérgico não peptídico na ação inotrópica positiva da fração polar da Bryopsis pennata

As algas marinhas representam uma rica fonte de compostos bioativos, algumas delas precursoras de ferramentas farmacológicas e de substâncias potencialmente úteis para o desenvolvimento de novos fármacos. A macroalga Bryopsis pennata, Cloroficea pertencente à ordem Caulerpales, sin. Bryopsidales é uma espécie tropical encontrada em diversos costões rochosos. Essa espécie produz uma defesa química tóxica para organismos herbívoros e potencial de se tornar invasiva e dominante em condições ambientais favoráveis. Este trabalho é uma investigação do efeito cardiotônico da fração polar da B. pennata .O cultivo, em ambiente controlado destituído de contaminantes, foi realizado no intuito de comparar seus efeitos com os efeitos da alga coletada. O efeito cardiotônico cronotrópico positivo em tiras ventriculares de anuros ficou fortemente evidenciado nos testes com frações polares de algas coletadas e cultivadas, não apresentando diferenças significativas entre as frações. O propranolol antagonizou o efeito cardiotônico e enzimas endopeptidases não reagiram com a fração polar da B. pennata. Testes bioquímicos demonstraram que a fração com efeito cardiotônico é de caráter ácido e apresenta peso molecular menor que 10.000 daltons.Marine algae are a rich source of bioactive compounds and some of them have shown to be useful for the development of new pharmacological tools and medicines. Bryopsis pennata, (Clorofícea, Caulerpales, sin. Bryopsidales) is a marine algae that can be found in the Southeastern Brazilian coast and elsewhere. The species produces a toxic chemical defense to the herbivorous organisms and possesses a potential to become invasive and dominant in favorable environmental conditions.The present study is about the investigation of the cardiotonic effect of the polar extract of B. pennata. The cultive in laboratory without any contaminants was made to compare studies performed with the collected algae extracts and the ones cultivated effect. The cardiotonic effect in the anurou's ventricular strips was strongly unequivocal when it was tested with the polar extracts from the collected and cultivated algae. The propranolol antagonized polar effects of these algae and the endopeptidase enzyme did not change the effects of polar extracts of Bryopsis pennata. Biochemical tests showed that the polar fraction presenting the inotropic cardiac activity weighs less than 10.000 Daltons and has an acid character

Efeito da administração do citrato de clomifeno durante o período perinatal no comportamento sexual, peso dos órgãos e concentração hormonal de ratos Wistar machos e fêmeas

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation – DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered.Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação – DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente

Formyl Peptide Receptors and Annexin A1: Complementary Mechanisms to Infliximab in Murine Experimental Colitis and Crohn's Disease

Non-responsiveness to anti-TNF-α therapies presents relevant rates in inflammatory bowel disease patients, presenting the need to find biomarkers involved in therapeutic efficacy. Herein, we demonstrate that higher levels of colonic formyl peptide receptor 1 and annexin A1 correlate with histological recovery in Crohn’s disease patients under remission. Using the dextran sulfate sodium colitis model in mice, we suggest that infliximab induces annexin A1 expression and secretion in activated intestinal leukocytes. Conversely, this mechanism might stimulate epithelial formyl peptide receptors, inducing wound healing and consequent histological remission. Our data indicate that assessing intestinal expressions of formyl peptide receptors and annexin A1 might provide precious information on the disease activity and responsiveness to infliximab in inflammatory bowel disease patients

Epidemiology and clinical course of severe acute respiratory syndrome coronavirus 2 infection in cancer patients in the Veneto Oncology Network: The Rete Oncologica Veneta covID19 study

Introduction: Coronavirus disease 2019 (COVID-19) pandemic started in Italy with clusters identified in Northern Italy. The Veneto Oncology Network (Rete Oncologica Veneta) licenced dedicated guidelines to ensure proper care minimising the risk of infection in patients with cancer. Rete Oncologica Veneta covID19 (ROVID) is a regional registry aimed at describing epidemiology and clinical course of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer. Materials and methods: Patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on cancer diagnosis, comorbidities, anticancer treatments, as well as details on SARS-CoV-2 infection (hospitalisation, treatments, fate of the infection), have been recorded. Logistic regression analysis was applied to calculate the association between clinical/laboratory variables and death from any cause. Results: One hundred seventy patients have been enrolled. The median age at time of the SARS-CoV infection was 70 years (25-92). The most common cancer type was breast cancer (n = 40). The majority of the patients had stage IV disease. Half of the patients had two or more comorbidities. The majority of the patients (78%) presented with COVID-19 symptoms. More than 77% of the patients were hospitalized and 6% were admitted to intensive care units. Overall, 104 patients have documented resolution of the infection. Fifty-seven patients (33%) have died. In 29 cases (17%), the cause of death was directly correlated to SARS-CoV-2 infection. Factors significantly correlated with the risk of death were the following: Eastern Cooperative Oncology Group performance status (PS), age, presence of two or more comorbidities, presence of dyspnoea, COVID-19 phenotype ≥ 3, hospitalisation, intensive care unit admission, neutrophil/lymphocyte ratio and thrombocytopenia. Conclusions: The mortality rate reported in this confirms the frailty of this population. These data reinforce the need to protect patients with cancer from SARS-CoV-2 infection

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

Background & aims: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. Methods: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. Results: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. Conclusions: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.publishedVersionPeer reviewe

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers

Abstract Introduction Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). Methods To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. Results Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 &#215; 10-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 &#215; 10-5, P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df-P = 0.007; rs1292011 2df-P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 &#215; 10-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). Conclusions The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers