Comportamento de cópula de Spodoptera eridania (Walker) (Lepidoptera: Noctuidae).

Pouco se conhece sobre o comportamento de cópula de Spodoptera eridania (Walker) (Lepidoptera: Noctuidae), praga que tem ganhado importância nos últimos anos em vários cultivos agrícolas. Para tanto, foram estudados 61 casais virgens, durante oito noites após a emergência, em intervalos de 15 min, durante 14 horas. Os casais foram transferidos para tubo de PVC transparente e alimentados com solução de mel a 10%. Foi determinado a idade da primeira cópula, o número de cópulas por casal, o número de espermatóforos transferidos para cada fêmea e o horário de cópula. Os adultos copularam desde a primeira até a sétima noite após a emergência. Na primeira noite mais de 76% dos casais realizaram a primeira cópula, e até a quarta noite mais de 95% do total de cópulas foi observado. A partir da quarta noite, além da redução no número de cópulas, 50% das mesmas que ocorreram neste período tiveram duração inferior a 15 min, não caracterizando uma cópula duradoura onde pudesse haver a transferência de espermatóforos. Quando foram correlacionados o número de cópulas por casal com o número de espermatóforos transferido para a fêmea (correlação de 0,77), notou-se que nos casais onde houve estas cópulas rápidas, o número de espermatóros foi menor que o número de cópulas, sugerindo que não houve a transferência de espermatóforos, caracterizando este comportamento como tentativa de cópula e não como cópula efetiva. Outro aspecto observado no comportamento de S. eridania foi que 56% dos casais realizaram apenas uma cópula ao longo dos oito dias de avaliação, evidenciando uma tendência a "monoandria". O horário das cópulas foi predominantemente na oitava e nona hora da escotofase, se estendendo até a 11ª hora

The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis

Background: Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors. Methods: By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs. Results: The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction <0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p < 0.001 for both) and higher platelets (p = 0.004 and p < 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p < 0.001 for both) and other known prognostic variables. Conclusions: Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions

Gemcitabine with or without ramucirumab as second-line treatment for malignant pleural mesothelioma (RAMES): a randomised, double-blind, placebo-controlled, phase 2 trial

Background: There is a preclinical rationale for inhibiting angiogenesis in mesothelioma. We aimed to assess the efficacy and safety of the anti-VEGFR-2 antibody ramucirumab combined with gemcitabine in patients with pretreated malignant pleural mesothelioma. Methods: RAMES was a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial done at 26 hospitals in Italy. Eligible patients were aged 18 years or older, had Eastern Cooperative Oncology Group performance status 0\u20132, and histologically proven malignant pleural mesothelioma progressing during or after first-line treatment with pemetrexed plus platinum. Patients were randomly assigned (1:1) to receive intravenous gemcitabine 1000 mg/m2 on days 1 and 8 every 3 weeks plus either intravenous placebo (gemcitabine plus placebo group) or ramucirumab 10 mg/kg (gemcitabine plus ramucirumab group) on day 1 every 3 weeks, until tumour progression or unacceptable toxicity. Central randomisation was done according to a minimisation algorithm method, associated with a random element using the following stratification factors: ECOG performance status, age, histology, and first-line time-to-progression. The primary endpoint was overall survival, measured from the date of randomisation to the date of death from any cause. Efficacy analyses were assessed in all patients who had been correctly randomised and received their allocated treatment, and safety analyses were assessed in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03560973, and with EudraCT, 2016-001132-36. Findings: Between Dec 22, 2016, and July 30, 2018, of 165 patients enrolled 161 were correctly assigned and received either gemcitabine plus placebo (n=81) or gemcitabine plus ramucirumab (n=80). At database lock (March 8, 2020), with a median follow-up of 21\ub79 months (IQR 17\ub77\u201328\ub75), overall survival was longer in the ramucirumab group (HR 0\ub771, 70% CI 0\ub759\u20130\ub785; p=0\ub7028). Median overall survival was 13\ub78 months (70% CI 12\ub77\u201314\ub74) in the gemcitabine plus ramucirumab group and 7\ub75 months (6\ub79\u20138\ub79) in the gemcitabine plus placebo group. Grade 3\u20134 treatment-related adverse events were reported in 35 (44%) of 80 patients in the gemcitabine plus ramucirumab group and 24 (30%) of 81 in the gemcitabine plus placebo group. The most common treatment-related grade 3\u20134 adverse events were neutropenia (16 [20%] for gemcitabine plus ramucirumab vs ten [12%] for gemcitabine plus placebo) and hypertension (five [6%] vs none). Treatment-related serious adverse events were reported in five (6%) in the gemcitabine plus ramucirumab group and in four (5%) patients in the gemcitabine plus placebo group; the most common was thromboembolism (three [4%] for gemcitabine plus ramucirumab vs two [2%] for gemcitabine plus placebo). There were no treatment-related deaths. Interpretation: Ramucirumab plus gemcitabine significantly improved overall survival after first-line standard chemotherapy, with a favourable safety profile. This combination could be a new option in this setting. Funding: Eli Lilly Italy. Translation: For the Italian translation of the abstract see Supplementary Materials section

Mutational profile of malignant pleural mesothelioma (MPM) in the phase II RAMES study

Purpose: Malignant pleural mesothelioma (MPM) is an aggressive cancer. Data are not available in prospective trials on correlations between genetic alterations and outcomes of therapies. In this study, we assessed the genetic profile of MPM patients (pts) in tissue samples. Patients and Methods: From December 2016 to July 2018 (end of enrolment), 164 pts were enrolled. We evaluated by targeted sequencing the mutational profile of a panel of 34 genes: ACTB, ACTG1, ACTG2, ACTR1A, BAP1, CDH8, CDK4, CDKN2A, CDKN2B, COL3A1, COL5A2, CUL1, DHFR, GOT1, KDR, KIT, MXRA5, NF2, NFRKB, NKX6-2, NOD2, PCBD2, PDZK1IP1, PIK3CA, PIK3CB, PSMD13, RAPGEF6, RDX, SETDB1, TAOK1, TP53, TXNRD1, UQCRC1, XRCC6. Genetic profiling was correlated with clinical and pathological variables. Results: Overall, 110 pts (67%) from both treatment arms had samples available for molecular analysis. Median age was 63 years (45\u201381), 25.5% (n = 28) were females, and 74.5% (n = 82) were males. Tumor histotype was 81.8% (n = 90) epithelioid and 18.2% (n = 20) non-epithelioid; 28.5% of the tumors (n = 42) were stage IV, 71.5% (n = 68) were stage III. Targeted sequencing of tissue specimens identified 275 functional somatic mutations in the 34 genes analyzed. The number of mutated genes was positively associated with higher stage and metastatic disease (p = 0.025). RDX (42%), MXRA5 (23%), BAP1 (14%), and NF2 (11%) were the most frequently mutated genes. Mutations in RAPGEF6 (p = 0.03) and ACTG1 (p = 0.02) were associated with the non-epithelioid subtype, and mutations in BAP1 (p = 0.04) were related to progression-free survival (PFS) > 6 months. Conclusions: In the Ramucirumab Mesothelioma clinical trial (RAMES), mutation of the gene BAP1 is related to a prolonged PFS for patients treated with platinum/pemetrexed regimens (p = 0.04)

Synthetic sex pheromone of citrus leafminer in Brazilian citrus groves Feromônio sexual sintético do minador-dos-citros em pomares brasileiros de citros

The objective of this work was to determine the best conditions of use of the synthetic sex pheromone of Phyllocnistis citrella Stainton for monitoring this species in citrus groves in northeastern Brazil. Pheromone doses (0.0, 0.1, 1, 10 and 100 &#956;g) and longevity (1, 15, 29, 43 and 57-day-old lures) and trap height (0.5, 1.5 and 2.5 m), color (green, red, and white) and model influence on P. citrella males capture were evaluated. The doses of 10 and 100 &#956;g of the synthetic sex pheromone - a 3:1 blend of (Z,Z,E)-7,11,13-hexadecatrienal and (Z,Z)-7,11-hexadecadienal - attracted the greatest number of P. citrella males. Traps baited with these two both dosages continued to capture P. citrella males at a comparable rate for over eight weeks in citrus groves. Although there was no significant decrease in activity of both dosages until 57 days of exposure to the environment, the higher dose, as time passed, attracted significantly more P. citrella males than the lower dose. There were no significant differences in male capture in traps with synthetic sex pheromone placed at 1.5 and 2.5 m height, wich had the better results. Trap color and model did not affect male capture.<br>O objetivo deste trabalho foi determinar as melhores condições de uso do feromônio sexual sintético de Phyllocnistis citrella Stainton para o monitoramento dessa espécie em pomares de citros no Nordeste do Brasil. Foram avaliados: doses (0,0, 0,1, 1, 10 e 100 &#956;g), duração (1, 15, 29, 43 e 57 dias de exposição do feromônio sexual sintético), altura de instalação (0,5, 1,5 e 2,5 m), cor (verde, vermelha e branca) e modelo de armadilha na captura de machos de P. citrella. As doses de 10 e 100 &#956;g do feromônio sintético - proporção de 3:1 da mistura de Z,Z,E-7,11,13-hexadecatrienal e (Z,Z)-7,11-hexadecadienal - atraíram o maior número de machos de P. citrella. Armadilhas contendo a mistura feromonal nessas duas doses capturaram machos de P. citrella por mais de oito semanas em pomares de citros. Embora nenhuma das duas doses tenha sofrido decréscimo na atividade por até 57 dias de exposição ao ambiente, com o passar do tempo a maior dose atraiu significativamente mais machos de P. citrella que a menor dose. Não houve diferença significativa na captura de machos nas armadilhas com o feromônio sexual instaladas a 1,5 e 2,5 m de altura, as quais apresentaram os melhores resultados. O modelo e a cor das armadilhas não afetaram a captura dos machos

Inflammatory indices and clinical factors in metastatic renal cell carcinoma patients treated with nivolumab: the development of a novel prognostic score (Meet-URO 15 study)

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations