Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free ...single antiplatelet therapy (SAPT) strategy with a potent P2Y
12
inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y
12
inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y
12
inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator’s discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720)
Survivors from sepsis are in an immunosuppressed state that is associated with higher long-term mortality and risk of opportunistic infections. Whether these factors contribute to neoplastic ...proliferation, however, remains unclear. Tumor-associated macrophages (TAM) can support malignant cell proliferation, survival, and angiogenesis. We addressed the relationship between the post-sepsis state, tumor progression and TAM accumulation, and phenotypic and genetic profile, using a mouse model of sepsis resolution and then B16 melanoma in mice. In addition, we measured the serum concentrations of TNFα, TGFβ, CCL2, and CXCL12 and determined the effect of in vivo CXCR4/CXCL12 inhibition in this context. Mice that survived sepsis showed increased tumor progression both in the short and long term, and survival times were shorter. TAM accumulation, TAM local proliferation, and serum concentrations of TGFβ, CXCL12, and TNFα were increased. Naïve mice inoculated with B16 together with macrophages from post-sepsis mice also had faster tumor progression and shorter survival. Post-sepsis TAMs had less expression of MHC-II and leukocyte activation-related genes. Inhibition of CXCR4/CXCL12 prevented the post-sepsis-induced tumor progression, TAM accumulation, and TAM in situ proliferation. Collectively, our data show that the post-sepsis state was associated with TAM accumulation through CXCR4/CXCL12, which contributed to B16 melanoma progression.
Mesograzers often use macrophytes as both food and habitat and may have strong effects on primary producers. In this context, understanding the factors mediating their interaction with macrophytes, ...such as host food value, is an important step to predict the impacts of these herbivores on aquatic ecosystems. The amphipod Sunamphitoe pelagica is a mesograzer with distribution restricted to a few brown macroalgal hosts, however it is unclear if food value drives host use by this mesograzer. Herein, we investigated the distribution of S. pelagica and the food value of its hosts. For that, the abundance of S. pelagica on the macroalgae Sargassum filipendula, Padina gymnospora, and Dichotomaria marginata was evaluated seasonally in a subtidal rocky shore at Fortaleza Beach (23°32′S, 45°10′W), state of São Paulo, Brazil. Furthermore, we conducted laboratory experiments to test feeding preference and rate, as well as the performance (e.g. survival, growth, and reproductive potential) of S. pelagica using the same macroalgal hosts used in the field abundance investigation. Overall, the mesograzer was more abundant on the brown macroalgae Sargassum and Padina than on the red macroalga Dichotomaria. In both feeding preference and rate experiments, S. pelagica consumed more Sargassum and Padina than Dichotomaria. Moreover, the consumption of Padina and Sargassum resulted in high performance of this mesograzer, while juveniles raised on Dichotomaria had a low survival, perishing within few days of experiment. These results suggest the host use by S. pelagica is strongly driven by the food value of macroalgal hosts and are in accordance with the narrow host breadth of this mesograzer. Therefore, considering the vulnerability of large macroalgae to climate change and habitat alterations, the restricted host use by S. pelagica to few brown macroalgae may increase its risk of local extinction.
•Macrophytes' food value is an important factor driving the host use by mesograzers.•Sunamphitoe pelagica was more abundant on Sargassum and Padina than Dichotomaria.•Sargassum and Padina represented a better diet for S. pelagica than Dichotomaria.•The host use by S. pelagica is strongly driven by the food value of their hosts.•The restricted host use by S. pelagica may increase its risk of local extinction.
O afídeo Sipha flava (Forbes) ocasiona injúrias em capim-elefante e sua biologia é pouco conhecida. O objetivo deste trabalho foi avaliar o efeito da temperatura no desenvolvimento, sobrevivência e ...reprodução de S. flava alimentada com Pennisetum purpureum. Ninfas com até 12h de idade foram individualizadas sobre seções foliares de capim-elefante e mantidas em condições controladas (12, 16, 20, 24, 28 e 32ºC ± 1ºC, UR 70 ± 10% e fotofase de 12h). O total de 150 ninfas foi usado por tratamento, divididas em 30 repetições, em delineamento inteiramente casualizado. A temperatura base (Tb) foi de 0,83, 1,05, 3,01 e 4,98 para ninfas de primeiro, segundo, terceiro e quarto ínstares, respectivamente, indicando exigências térmicas distintas para os diferentes estádios de desenvolvimento. A Tb foi de 2,08 para a fase ninfal, verificando-se a tolerância a baixas temperaturas. Em temperaturas elevadas (28 e 32ºC), constatou-se redução significativa na sobrevivência. Embora tenha sido constatado maior período reprodutivo e longevidade a 12ºC, quando comparado às temperaturas mais altas, a fecundidade total foi substancialmente reduzida. A duração do ciclo de vida foi cerca de duas vezes maior a 12ºC em relação a 24ºC. A maior produção diária e total de ninfas foi a 24ºC. As temperaturas de 20ºC e 24ºC foram as mais favoráveis para o desenvolvimento e reprodução de S. flava.
The aphid Sipha flava (Forbes) is a pest on elephant grass, but little is known about its biology. The objective of this work was to evaluate the temperature effects on the development, survival and reproduction of S. flava fed on Pennisetum purpureum. Twelve-hour-old nymphs were individualized on sections of elephant grass blades and maintained at 12, 16, 20, 24, 28 and 32ºC ± 1ºC, UR 70 ± 10% and 12h photophase. A total of 150 nymphs were used per treatment divided in 30 replicates, using a totally random design. The lower threshold temperatures (LTT) for first, second, third and fourth instars were 0.83, 1.05, 3.01 and 4.98ºC, respectively, indicating a change in thermal requirements as the development progress. The LTT for the whole nymphal stage was 2.08ºC, pointing to the tolerance of this species to low temperatures. A significant reduction in survival was observed at high temperatures (28 and 32ºC). Although the reproductive periods were longer and insects lived longer at 12ºC as compared with those at higher temperatures, the total fecundity was substantially reduced. The overall life cycle duration was almost twice as long at 12ºC than at 24ºC. The greatest daily production of nymphs and greatest number of nymphs produced overall occurred at 24ºC. The temperatures of 20ºC and 24ºC were more suitable to S. flava development and reproduction.
The RAS oncogene is both the most frequently mutated oncogene in human cancer and the first confirmed human oncogene to be discovered in 1982. After decades of research, in 2013, the Shokat lab ...achieved a seminal breakthrough by showing that the activated KRAS isozyme caused by the G12C mutation in the KRAS gene can be directly inhibited via a newly unearthed switch II pocket. Building upon this groundbreaking discovery, sotorasib (AMG510) obtained approval by the United States Food and Drug Administration in 2021 to become the first therapy to directly target the KRAS oncoprotein in any KRAS-mutant cancers, particularly those harboring the KRAS
mutation. Adagrasib (MRTX849) and other direct KRAS
inhibitors are currently being investigated in multiple clinical trials. In this review, we delve into the path leading to the development of this novel KRAS inhibitor, starting with the discovery, structure, and function of the RAS family of oncoproteins. We then examine the clinical relevance of KRAS, especially the KRAS
mutation in human cancer, by providing an in-depth analysis of its cancer epidemiology. Finally, we review the preclinical evidence that supported the initial development of the direct KRAS
inhibitors and summarize the ongoing clinical trials of all direct KRAS
inhibitors.
Objective: To identify and describe clinical and epidemiologic profile of oral squamous cell carcinoma (OSCC) in young adults. Study Design: A systematic literature review was carried out in ...electronic databases Lilacs, SciELO, PubMed, and Periódico Capes, whose descriptors were: oral cancer, oral squamous cell carcinoma, epidemiology and young patient, in English, Spanish, and Portuguese, between January 2003 and January 2016. The review identified 348 articles, 8 of them had as main objective to evaluate clinical and epidemiologic aspects of OSCC in young adults between 20 and 45 years. Results: Tobacco use and/or alcoholism stand out among the etiologic factors related to OSCC. The tongue was the most affected region in oral cavity, followed by the lower lip and buccal floor. Regarding clinical tumor stage, it was observed, in 4 studies, that type III and IV prevailed, and regional-type metastasis was the most common. The predominant treatment associated surgery with radiotherapy, followed by isolated surgery. Conclusion: Further studies are required to define the clinical and epidemiologic characteristics of the tumor in this population and also to standardize the age group referring to the term "young adult." This information may enable the development of a primary prevention program for patients with OSCC.
Understanding the Maxam-Gilbert and Sanger sequencing as the first generation, in recent years there has been
an explosion of newly-developed sequencing strategies, which are usually referred to as ...next generation sequencing
(NGS) techniques. NGS techniques have high-throughputs and produce thousands or even millions of sequences at the
same time. These sequences allow for the accurate identification of microbial taxa, including uncultivable organisms and
those present in small numbers. In specific applications, NGS provides a complete inventory of all microbial operons and
genes present or being expressed under different study conditions. NGS techniques are revolutionizing the field of microbial
ecology and have recently been used to examine several food ecosystems. After a short introduction to the most
common NGS systems and platforms, this review addresses how NGS techniques have been employed in the study of
food microbiota and food fermentations, and discusses their limits and perspectives. The most important findings are reviewed,
including those made in the study of the microbiota of milk, fermented dairy products, and plant-, meat- and fishderived
fermented foods. The knowledge that can be gained on microbial diversity, population structure and population
dynamics via the use of these technologies could be vital in improving the monitoring and manipulation of foods and fermented
food products. They should also improve their safety.
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