Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: A network meta-analysis

Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced nonsmall- cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection. Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis. Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38-1.00) for gefitinib, 0.28 (95% CI, 0.17-0.45) for erlotinib and 0.40 (95% CI, 0.20-0.83) for afatinib. HRs for OS were not statistically significant for any agent. Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.Logistic provision from the Cearense School of Oncology, Ceará Cancer Institute, Haroldo Juaçaba Hospital, Fortaleza, Ceará, Brazil, and The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral & Liverpool, England, United Kingdom. RAM has received honoraria from Pfizer Advisory Board, Zodiac advisory board, AstraZeneca, Novartis, National Science Centre, Krakow, Poland, and educational grant from Pierre Fabre, Amgem. RAM is ad hoc consultant at Ministry of Health, Brasília, Brazil. The other authors have no conflicts of interest in this manuscript. GM has received honoraria from Bristol Myers Squibb, Roche and AstraZeneca

Alcoóis lineares em solos arqueológicos da Amazônia.

Pôster

Study of in vitro digestion of Tenebrio molitor flour for evaluation of its impact on the human gut microbiota

Human diet has evolved to include not only nutritious foods but also health-promoting ones. Moreover, there is an increasing interest in replacing animal proteins as the main protein source. Insect based foods, e.g. Tenebrio molitor insect flour (TMIF), show potential as alternative protein sources for the human diet. This work aims to provide insights into the effect of TMIF upon the human gut microbiota and their metabolic end products by using an in vitro fecal model. Digested TMIF had a positive impact on gut microbiota, observed as an increase and/or upkeep of health promoting bacterial groups and by the production of SCFA (1.7 and 2.6 times higher acetate and propionate produced respectively than in the negative control at 48 h) and BCFA. A path is opened to acknowledge TMIF as a possible healthy nutritional source for human consumption, although in vivo trials would be necessary to confirm this

Reference values and influence of age on erythrogram of Murrah buffaloes

O eritrograma é uma avaliação que representa um auxílio ao clínico no diagnóstico de afecções que acometem os animais domésticos. No entanto, estudos hematológicos em bubalinos são escassos, havendo poucas informações na literatura a respeito de valores de referência dos constituintes sanguíneos desta espécie. Assim, este trabalho teve como objetivo a análise do eritrograma de búfalos de diferentes faixas etárias da raça Murrah, machos e fêmeas. Os animais em estudo foram distribuídos em quatro grupos experimentais, de acordo com as idades: Grupo 1: animais com idade entre o nascimento e 3 meses (n=15); Grupo 2: animais com idade entre 4 e 6 meses (n=50); Grupo 3: animais com idade entre 7 e 12 meses (n=50); e Grupo 4: animais com idade superior a 12 meses (n=50). Como resultados das análises foram encontrados os seguintes valores médios, no Grupo 1: 7,9x106 hemácias/mL de sangue (He); 13,0 g/dL de hemoglobina (Hb); hematócrito (Ht) de 38,9%; Volume Corpuscular Médio (VCM) de 49,0 fl; Concentração Hemoglobínica Corpuscular Média (CHCM) de 33,6 %, e Hemoglobina Corpuscular Média (HCM) de 16,4 pg; no Grupo 2: He: 7,1 x10(6)/mL; Hb: 12,5 g/dL; Ht: 36,8%; VCM: 52,4 fl; CHCM: 33,9%, e HCM: 17,8 pg; no Grupo 3: He: 7,9 x10(6)/mL; Hb: 12,0 g/dL; Ht: 33,8%; VCM: 43,1 fl; CHCM: 35,4%, e HCM: 15,34 pg; e no Grupo 4: He: 6,7 x10(6)/mL; Hb: 11,7 g/dL; Ht: 34,4%; VCM: 53,4 fl; CHCM: 34,4%. e HCM: 17,4 pg. A análise estatística dos resultados encontrados para as diferentes faixas etárias permitiu concluir que ocorreram variações determinadas pela evolução da idade, caracterizadas por diminuição do número médio de hemácias (He), da concentração de hemoglobina (Hb) e do valor do hematócrito (Ht). Os índices hematimétricos apresentaram variações significativas no G3.Erythrograms aid the veterinary practitioner in the diagnosis of diseases that affect domestic animals. However, hematological studies involving buffaloes are scarce, with little information in the literature on reference values for blood components in this species. Therefore, the objective of this study was analyze erythrograms of Murrah breed buffaloes of different ages, both males and females. Buffaloes in the study were distributed into four experimental groups, according to their ages: Group 1, animals from birth to 3 months of age (n=15); Group 2, animals from 4 to 6 months of age (n=50); Group 3, animals from 7 to 12 months of age (n=50); and Group 4, animals from 13 months to five years of age (n=50). The following values were obtained, for Group 1: 7.9x10(6) erythrocytes/mL (He), 13.0g/dL hemoglobin (Hb), hematocrit (Ht) 38.9%, Mean Corpuscular Volume (MCV) 49.0 fl, Mean Hemoglobin Corpuscular Concentration (MCHC) 33.6%, and Mean Corpuscular Hemoglobin (MCH) 16.4 pg; for Group 2: He7.1x10(6)/mL, Hb12.5g/dL, Ht 36.8%, MCV 52.4 fl; MCHC 33.9%; and MCH 17.8 pg; for Group 3: He 7.9x10(6)/mL, Hb12.0g/dL, Ht 33.8%, MCV 43.1 fl, MCHC 35.4%, and MCH 15.34pg; for Group 4: He 6.7x10(6)/mL, Hb 11.7g/dL, Ht 34.4%, MCV 53.4 fl, MCHC 34.4%, and MCH 17.4 pg. Statistical analysis of the results for the different age ranges permitted the conclusion that when the animals got older there was a decrease in the mean red cell counts (He), hemoglobin concentration (Hb) and hematocrit values (Ht). Although hematometric indexes showed significant variations in G3

Association between genomic daughter pregnancy rate and expected milk production on the resumption of estrus behavior in Holstein cattle

The objective of this observational study was to evaluate estrous expression at the first estrus occurring between 7 to 30 d in milk (DIM), as detected by an automated activity monitor (AAM), and its association with genomic daughter pregnancy rate (GDPR) and genomic expected milk production (GEM) in lactating dairy cows. A total of 4,119 lactations from 2,602 Holstein cows were included. Cows were enrolled as first lactation (n = 1,168), second lactation (n = 1,525) and third and greater lactation (n = 1,426). Hair samples were collected from the tail switch, and cows were genotyped using an SNP platform (Clarifide, Zoetis, São Paulo, SP, Brazil). Postpartum cows were examined daily by the farm personnel from calving until 10 DIM. Calving was classified as assisted (forced calf extraction) and unassisted (normal calving). Retained fetal membranes (RFM), hyperketonemia (KET), and left displaced abomasum (LDA) were also recorded. Mean GDPR (± SD) was −0.29 ± 1.4, and the intensity and duration of the first estrus event was 15.9 ± 13.1 x-factor (intensity unit measurement) and 11.1 ± 3.8 h, respectively. Cows that had greater GDPR had greater intensity and longer duration of estrus at the alert, independent of parity. Overall resumption of estrous expression, between 7 to 30 DIM, was 41.2% (1,695/4,119), where 58.8% (2,424/4,119) did not have an estrus event, 31.0% (1,274/4,119) of cows had one event of estrus, and 10.2% (421/4,119) of cows had 2 or more events of estrus early postpartum. Mean DIM (± SD) at first estrus event, detected by the AAM, was 19.4 ± 4.4 d. Days in milk at first event for cows with one event was 20.7 ± 1.6 d and 15.9 ± 3.1 d for cows with 2 or more events of estrus. First lactation cows were more likely to have an estrus event early postpartum when compared with second and third and greater lactation cows (45.2 ± 1.4% [530/1168] vs. 41.6 ± 1.3% [636/1525] vs. 37.2 ± 1.3% [529/1426], respectively). There was an interaction of parity and GDPR on the proportion of cows demonstrating an early postpartum estrus. There was no difference in the proportion of cows with an early postpartum estrus between those with assisted or unassisted calving, RFM, or LDA. However, cows that had KET were less likely to have an alert early postpartum when compared with cows that did not have KET. Mean genomic expected milk production (± SD) was 256.8 ± 600.1 kg. There was no interaction between GEM and parity on estrous expression (i.e., intensity and duration). There was no interaction between GEM and GDPR on the proportion of estrus early postpartum

Interaction of Ruthenium(II)-dipyridophenazine Complexes with CT-DNA: Effects of the Polythioether Ancillary Ligands

The complexes [Ru([9]aneS3)(dppz)Cl]Cl 1 and [Ru([12]aneS4)(dppz)]Cl2 2 ([9]aneS3 = 1,4,7- trithiaciclononane and [12]aneS4 = 1,4,7,10-tetrathiaciclododecane) were synthesised and fully characterised. These complexes belong to a small family of dipyridophenazine complexes with non-polypyridyl ancillary ligands . Interaction studies of these complexes with CT-DNA (UV/Vis titrations, steady-state emission and thermal denaturation) revealed their high affinity for DNA . Intercalation constants determined by UV/Vis titrations are of the same order of magnitude (106) as other dppz metallointercalators, namely [Ru(II)(bpy)2dppz]S2+. Differences between l and2 were identified by steady-state emission and thermal denaturation studies . Emission results are in accordance with structural data, which indicate how geometric distortions and different donor and/or acceptor ligand abilities affect luminescence. The possibility of noncovalent interactions between ancillary ligands and nucleobases by van der Waals contacts and H-bridges is discussed . Furthermore, complex l undergoes aquation under intra-cellular conditions and an equilibrium with the aquated form l' is attained . This behaviour may increase the diversity of available interaction modes

Dosimetric effect by shallow air cavities in high energy electron beams

This study evaluates the dosimetric impact caused by an air cavity located at 2 mm depth from the top surface in a PMMA phantom irradiated by electron beams produced by a Siemens Primus linear accelerator. A systematic evaluation of the effect related to the cavity area and thickness as well as to the electron beam energy was performed by using Monte Carlo simulations (EGSnrc code), Pencil Beam algorithm and Gafchromic EBT2 films. A home-PMMA phantom with the same geometry as the simulated one was specifically constructed for the measurements. Our results indicate that the presence of the cavity causes an increase (up to 70%) of the dose maximum value as well as a shift forward of the position of the depthedose curve, compared to the homogeneous one. Pronounced dose discontinuities in the regions close to the lateral cavity edges are observed. The shape and magnitude of these discontinuities change with the dimension of the cavity. It is also found that the cavity effect is more pronounced (6%) for the 12 MeV electron beam and the presence of cavities with large thickness and small area introduces more significant variations (up to 70%) on the depthedose curves. Overall, the Gafchromic EBT2 film measurements were found in agreement within 3% with Monte Carlo calculations and predict well the fine details of the dosimetric change near the cavity interface. The Pencil Beam calculations underestimate the dose up to 40% compared to Monte Carlo simulations; in particular for the largest cavity thickness (2.8 cm)

Optical phonon modes of wurtzite InP

Optical vibration modes of InP nanowires in the wurtzite phase were investigated by Raman scattering spectroscopy. The wires were grown along the [0001] axis by the vapor-liquid-solid method. The A1(TO), E2h, and E1(TO) phonon modes of the wurtzite symmetry were identified by using light linearly polarized along different directions in backscattering configuration. Additionally, forbidden longitudinal optical modes have also been observed. Furthermore, by applying an extended 11-parameter rigid-ion model, the complete dispersion relations of InP in the wurtzite phase have been calculated, showing a good agreement with the Raman experimental data

Consumo, comercialização e variação de preço de açaí na região estuarina do Rio Amazonas.

A crescente demanda por frutos de açaizeiro, nos mercados nacional e internacional, trouxe ganhos em renda para as famílias ribeirinhas. No entanto, isso tem suscitado preocupações socioambientais e alimentares locais, referentes à soberania alimentar e redução da diversificação produtiva. Neste estudo, objetivou- -se quantificar o consumo e a venda de frutos de açaí por famílias extrativistas da Ilha das Cinzas, Gurupá, PA

Análise da variabilidade intra-espécie dos genes pld e rpoB de Corynebacterium pseudotuberculosis por meio de marcadores PCR-RFLP.

Corynebacterium pseudotuberculosis é o agente etiológico da linfadenite caseosa em ovinos e caprinos, uma doença infectocontagiosa crônica caracterizada por abscessos em linfonodos superficiais ou internos. Os animais acometidos podem apresentar lesões internas ou externas, o que representa perdas econômicas graves na caprinovinocultura, como o comprometimento da produção de lã em ovinos, deficiência reprodutiva, condenação da carne ou morte do animal. Uma vez estabelecida a infecção no rebanho, torna-se difícil sua erradicação. Com o objetivo de avaliar a variabilidade genética intra-espécie em C. pseudotuberculosis, 31 isolados provenientes de seis municípios do Estado de Pernambuco, sendo 23 de caprinos e oito de ovinos, tiveram os seus DNAs genômicos extraídos e analisados por reação em cadeia da polimerase e análise de polimorfismos por tamanho de fragmentos de restrição (PCR-RFLP). Os locis escolhidos foram os genes pld e rpoB, cujas seqüências dos oligonucleotídeos amplificaram fragmentos de 924 e 447 pares de bases (pb), respectivamente. Os produtos da amplificação foram digeridos com as enzimas Pst I e Msp I (gene pld) e HpyCh4 IV e Msp I (gene rpoB). Os fragmentos de restrição foram corridos em gel de poliacrilamida a 15%, os quais foram corados com brometo de etídeo. Para o gene pld, digerido com a enzima Pst I, foram obtidos fragmentos de 566, 195, 91 e 72 pb; e com a enzima Msp I, fragmentos de 395, 369, 108 e 52 pb. O gene rpoB digerido com a enzima HpyCh4 IV apresentou fragmentos de 235, 126 e 86 pb; e com a enzima Msp I apresentou fragmentos de 222, 93, 78 e 54 pb. O padrão de bandas obtido para os 31 isolados de C. pseudotuberculosis, analisados neste estudo, foi monomórfico, não havendo, portanto, polimorfismo entre os diferentes isolados, independentes da espécie hospedeira ou da área geográfica estudada, o que corrobora com o padrão homogêneo da infecção para a região.bitstream/CNPGC-2009-09/12402/1/DOC167.pd