Alginate nanohydrogels as a biocompatible platform for the controlled release of a hydrophilic herbicide

The large-scale application of volatile and highly water-soluble pesticides to guarantee crop production can often have negative impacts on the environment. The main loss pathways are vapor drift, direct volatilization, or leaching of the active substances. Consequently, the pesticide can either accumulate and/or undergo physicochemical transformations in the soil. In this scenario, we synthesized alginate nanoparticles using an inverse miniemulsion template in sunflower oil and successfully used them to encapsulate a hydrophilic herbicide, i.e., dicamba. The formulation and process conditions were adjusted to obtain a unimodal size distribution of nanohydrogels of about 20 nm. The loading of the nanoparticles with dicamba did not affect the nanohydrogel size nor the particle stability. The release of dicamba from the nanohydrogels was also tested: the alginate nanoparticles promoted the sustained and prolonged release of dicamba over ten days, demonstrating the potential of our preparation method to be employed for field application. The encapsulation of hydrophilic compounds inside our alginate nanoparticles could enable a more efficient use of pesticides, minimizing losses and thus environmental spreading. The use of biocompatible materials (alginate, sunflower oil) also guarantees the absence of toxic additives in the formulation

REPRESENTAÇÕES DO CONCEITO “PÃO E CIRCO” EM ROMA E NO BRASIL: UM ESTUDO COMPARATIVO

Esta pesquisa teve por objetivo avaliar as diferentes apropriações do conceito “pão e circo” por mídias atuais brasileiras e comparar com o sentido dessa suposta política nas representações latinas e historiográficas. Para tanto, mediante uma abordagem qualitativa, foram utilizados os procedimentos de pesquisa bibliográfica e documental. Esta é composta por fontes primárias do período do Principado Romano, em especial documentos escritos de três autores latinos da aristocracia: Sêneca, Tácito e Juvenal. Além disso, foram analisadas cinco matérias veiculadas em sites eletrônicos de notícias, uma de cada canal selecionado, no contexto da Copa do Mundo de 2018, sendo três editoriais (Manaus Alerta, Terra, Causa Operária) e dois artigos de opinião (Gazeta do Povo, El País). Assim, foi verificado como cada matéria se apropriou e construiu significados para o panem et circenses. Por fim, como resultados, concluiu-se que há diversidade na maneira de entender o papel político e social da Copa do Mundo por parte de cada veículo midiático selecionado, relacionada às suas perspectivas políticas e ideológicas. Também pôde ser observado que muitos dos discursos presentes nas mídias examinadas possuem apropriações dos escritores latinos desta pesquisa, embora essa conexão não seja direta e consciente na maioria dos casos. Tais representações latinas serviram de base à construção da chamada “política do pão e circo” pela historiografia tradicional no século XIX, perspectiva que por vezes encontra terreno em análises sociológicas contemporâneas acerca do futebol no Brasil. Portanto, a presente pesquisa pretendeu refletir sobre as interações entre passado e presente investigando suas diversas apropriações políticas

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

DPYD c.1905+1G>A and c.2846 A>T and UGT1A1*28 allelic variants as predictors of toxicity: Pharmacogenetic translational analysis from the phase III TRIBE study in metastatic colorectal cancer.

Abstract not availabl

Tremelimumab and durvalumab combination for the non-operative management (Nom) of microsatellite instability (msi)-high resectable gastric or gastroesophageal junction cancer: The multicentre, single-arm, multi-cohort, phase ii infinity study

SIMPLE SUMMARY: The status of microsatellite instability (MSI-H) in gastric or gastroesophageal junction cancer (GC/GEJC) patients eligible for radical surgery proved to be prognostic for an improved survival outcome and predictive for poor/no benefit from the combination of adjuvant/peri-operative chemotherapy. MSI-H tumors display a high sensitivity to immunotherapy and exploratory studies showed that a pre-operative treatment with immune-checkpoint inhibitors may achieve elevated rates of pathological complete responses. The ongoing proof-of-concept INFINITY study is aimed at investigating the role of the combo-immunotherapy durvalumab plus tremelimumab as a neoadjuvant or potentially definitive treatment (avoiding surgery in case of complete clinical response) for MSI-H resectable GC/GEJC patients. ABSTRACT: In resectable gastric or gastroesophageal junction cancer (GC/GEJC), the powerful positive prognostic effect and the potential predictive value for a lack of benefit from the combination of adjuvant/peri-operative chemotherapy for the MSI-high status was demonstrated. Given the high sensitivity of MSI-high tumors for immunotherapy, exploratory trials showed that combination immunotherapy induces a high rate of complete pathological response (pCR), potentially achieving cancer cure without surgery. INFINITY is an ongoing phase II, multicentre, single-arm, multi-cohort trial investigating the activity and safety of tremelimumab and durvalumab as neoadjuvant (Cohort 1) or potentially definitive (Cohort 2) treatment for MSI-high/dMMR/EBV-negative, resectable GC/GEJC. About 310 patients will be pre-screened, to enroll a total of 31 patients, 18 and 13 in Cohort 1 and 2, at 25 Italian Centres. The primary endpoint of Cohort 1 is rate of pCR (ypT0N0) and negative ctDNA after neoadjuvant immunotherapy, of Cohort 2 is 2-year complete response rate, defined as absence of macroscopic or microscopic residual disease (locally/regionally/distantly) at radiological examinations, tissue and liquid biopsy, during non-operative management without salvage gastrectomy. The ongoing INFINITY proof-of-concept study may provide evidence on immunotherapy and the potential omission of surgery in localized/locally advanced GC/GEJC patients selected for dMMR/MSI-high status eligible for radical resection

Randomised, open-label, phase II study of Gemcitabine with and without IMM-101 for advanced pancreatic cancer

Background: Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma. Methods: Patients were randomised (2 : 1) to IMM-101 (10 mg ml−l intradermally)+GEM (1000 mg m−2 intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected. Results: IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44–1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33–0.87, P=0.01). Conclusions: IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study