The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Recomendaciones en el abordaje del hematoma intracerebral espontáneo durante la internación / Recommendations for the management of spontaneous intracerebral hemorrhage during hospitalization

Resumen El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neuro- lógico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualiza- das del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.

Abstract Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracere- bral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.

[Recommendations For The Management Of Spontaneous Intracerebral Hemorrhage During Hospitalization]. / Recomendaciones en el Abordaje del Hematoma Intracerebral Espontáneo Durante la Internación.

Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracerebral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.

El accidente cerebrovascular (ACV) constituye la principal causa de discapacidad de origen neurológico en los adultos mayores a 40 años y la cuarta causa de muerte en Argentina. En los últimos diez años las publicaciones indexadas relacionadas al tratamiento del ACV isquémico fueron más numerosas que las de ACV hemorrágico. El objetivo de este material es proporcionar recomendaciones locales y actualizadas del abordaje de pacientes con hematoma intraparenquimatoso espontáneo durante la internación. Para la redacción de este manuscrito se convocó a especialistas en esta enfermedad que conformaron grupos de trabajo. Se plantearon 10 tópicos centrales expresados como epidemiologia, atención inicial, imágenes, tratamiento de la presión arterial, reversión de antitrombóticos, indicación de cirugía, profilaxis anticonvulsivante, pronóstico, prevención de complicaciones y reinicio de antitrombóticos. De cada tópico se plantearon mediante preguntas PICO los interrogantes más frecuentes de la práctica diaria. Luego de una revisión sistemática de la literatura, se generaron recomendaciones evaluadas mediante sistema GRADE y consensuadas entre autores y pacientes.

Crop management and its effects on weed occurrence

The objective was to evaluate weed phytosociology and similarities between crop management systems in the Chapadões region. The experiment was conducted at in agricultural area located in the municipality of Chapadão do Sul, MS, during the 2016/17 harvest. Three crop managements strategies were used: (1) cotton/soybean/Urochloa, (2) millet/soybean/millet and (3) millet/soybean/crotalaria. A phytosociological survey of weeds was carried out during soybean cultivation and cover crops growth, in succession. The evaluation area for each management strategy was 0.5 ha. Soybean surveys were carried out in October and January, while the cover crop surveys were performed in February and May. The relative frequency (RF), relative density (RD), relative abundance (AR), and relative importance (RI) of weeds, Venn diagram, and Jaccard and Sorenson similarity indices were evaluated. The management area represented by the cotton/soybean/Urochloa rotation had fewer weed species than others. The species Cenchrus echinatus, Digitaria insularis, Digitaria sanguinalis, Eleusine indica and Commelina benghalensis had the highest phytosociological indeces among the monocotyledons. Attention is required for managing the dicotyledons Amaranthus deflexus, Conyza canadensis and Senna obtusifolia despite their low indices because of herbicide resistant cases. The highest indeces of similarity were found between managements areas 2 and 3, which did not rely on cotton cultivation prior to soybeans.

Effect of trinexapac-ethyl on sugarcane varieties / Efeito do trinexapac-ethyl em variedades de cana-de -açúcar

Growth regulators have been widely employed as maturation inducers in the sugarcane crop, as an agricultural strategy. However, the response of varieties to the use of these compounds has been poorly studied, mainly in cerrado (savannah-like biome) areas occupied by the crop. This study was carried out to examine the effects of trinexapac-ethyl on important morphological characteristics of sugarcane varieties. The experiment was set up as a randomized block design with a 4 × 2 factorial arrangement consisting of four varieties (RB83-5054, SP80-1816, RB96-6928, and RB85-5156) associated or unassociated with application of trinexapac-ethyl (375 g L­1 of the a.i. ha­1), with four replicates. The ripener was applied at 126, 178, and 228 days after planting (DAP) the first-cycle sugarcane, using the dose of 125 g L­1 a.i. ha­1 per application. Upon harvest, which occurred at 243 DAP, we determined the number of stalks per meter, weight of 30 stalks without top, internode length, number of internodes per stalk, and yield of sugarcane stalks. Ripener application increased the number of stalks in varieties RB96-6928 and RB83-5054 and the weight of 30 stalks in varieties RB96-6928 and RB83-5054 and SP80-1816; reduced internode length in varieties RB85-5156 and RB83-5054; and increased stalk yield per hectare in varieties RB96-6928 and RB83-5054, but did not increase the number of internodes per stalk in any of the tested varieties. The variables number of stalks, stalk weight, internode length, and stalk yield responded in a genotype-dependent manner to the application of trinexapac-ethyl.

O uso de reguladores de crescimento como indutores da maturação em cana-de-açúcar tem sido uma prática agrícola bastante empregada. Entretanto, a resposta das variedades à utilização desses compostos tem sido pouco estudada, principalmente em áreas de cerrado ocupadas pela cultura. O objetivo deste estudo foi avaliar os efeitos do trinexapac-ethyl em características morfológicas importantes para a produtividade de variedades de cana-de-açúcar. O delineamento experimental utilizado foi o de blocos casualizados em esquema fatorial 4 x 2, sendo quatro variedades (RB83-5054, SP80-1816, RB96-6928 e RB85-5156), combinadas com e sem aplicação de trinexapac-ethyl (375 g L-1 do i.a. ha-1) e quatro repetições. A aplicação do maturador ocorreu aos 126, 178 e 228 dias após o plantio (DAP) da cana planta, com dose de 125 g L-1 i.a. ha-1 por vez. Por ocasião da colheita, realizada aos 243 DAP, foram avaliados o número de colmos por metro, massa de 30 colmos sem ponteiro, comprimento de entrenós, número de entrenós por colmo e produtividade de colmos de cana-de-açúcar. Verificou-se que a aplicação do maturador incrementou o número de colmos para as variedades RB96-6928 e RB83-5054, a massa de 30 colmos para as variedades RB96-6928 e RB83-5054 e SP80-1816, maior redução no comprimento de entrenós para as variedades RB85-5156 e RB83-5054 e maior aumento na produção de colmos por hectare para as variedades RB96-6928 e RB83-5054, mas não aumentou o número de entrenós por colmo nas variedades testadas. A resposta das variáveis: número de colmos, massa de colmos, comprimento dos entrenós e produtividade de colmos à aplicação do trinexapac-ethyl mostrou-se genótipo dependente.

Drying and storage of corn grains for ethanol production in Brazil / Secagem e armazenamento de grãos de milho para produção de etanol no Brasil

The aim of the present research was to evaluate the effects of drying air temperature and storage conditions used in Brazil on the quality of corn grains (Zea mays L.) for ethanol production. The experiment was set up in a completely randomized design in a (3x2x2) factorial arrangement (drying air temperatures of 80, 100 and 120 ºC vs. ambient storage conditions of 23 ºC / 60% RH and cooled to 10 ºC / 40% RH vs. storage time of zero and six months). The corn grains were harvested with a water content of 18.0% (w.b.). Then, they were dried in a convection/forced-air oven at different temperatures, until water content reached 12% (w.b.). After that, the grains were stored. It was concluded that the increase in drying air temperature reduced lipid content and starch percentage, decreasing ethanol yield to 38.74 L ton-1 of grains. Storage under refrigeration at 10 °C was favorable for the maintenance of lipid levels (+2%), starch percentage (6%) and ethanol yield (33 L ton-1 of grains). Thus, considering production conditions and weather in Brazil, grains should be dried at air temperatures up to 80 °C, and storage must be performed under refrigerated air up to 10 °C for quality assurance of maize grains in the dry season and, therefore, increased ethanol production in the industry.

O objetivo do presente trabalho foi avaliar os efeitos da secagem e as condições de temperatura do ar e armazenamento utilizadas no Brasil na qualidade de grãos de milho (Zea mays L.) para a produção de etanol. O experimento foi instalado em delineamento inteiramente casualizado, em arranjo fatorial (3x2x2) (secagem a temperatura do ar de 80, 100 e 120 ºC vs. condições de ambiente de armazenamento de 23 ºC / 60% RH e resfriamento de 10 ºC / 40% RH vs. tempo de armazenamento de zero e seis meses). Os grãos de milho foram colhidos com um teor de água de 18,0% (w.b.). Em seguida, os grãos foram secos em estufa de convecção / forçada de ar a diferentes temperaturas, até que o teor de água atingiu 12% (w.b.). Em seguida, os grãos foram armazenados. Concluiu-se que o aumento da temperatura do ar de secagem reduziu os teores de lípidos e a percentagem de amido, diminuindo o rendimento de etanol a 38,74 L ton-1 de grãos. O armazenamento sob refrigeração, a 10 °C foi favorável para a manutenção dos níveis de lípidos (+2%), percentagem de amido (6%) e rendimento de etanol (33 L ton-1 de grãos). Assim, considerando as condições de produção e clima no Brasil, os grãos devem ser secos nas temperaturas do ar de até 80 °C e o armazenamento deve ser realizado sob refrigeração do ar até 10 °C para garantir a qualidade dos grãos de milho na estação seca e, portanto, um aumento da produção de etanol na indústria.

Acute viral bronchiolitis: Physician perspectives on definition and clinically important outcomes.

BACKGROUND: Two key limitations hamper intervention research in bronchiolitis: the absence of a clear definition of disease, and the heterogeneous choice of outcome measures in current clinical trials. We assessed how paediatricians and general practitioners (GPs) perceived definition and clinically important outcomes in bronchiolitis. METHODS: A nationwide online survey (ABBA study) was conducted through the Portuguese Society of Paediatrics and GPs' mailing lists. We assessed agreement with statements on bronchiolitis definition, and participants were asked to score the relative importance of several outcomes. Principal component analysis (PCA) explored dimensions underlying disease definition. Outcomes were ranked by mean score and proportion given highest score. RESULTS: We included 514 paediatricians and 165 GPs (overall 59% were board-certified). Most paediatricians (76.5%) agreed with a definition based on coryza, wheezing and/or crackles/rales, compared to 38.1% GPs (P < 0.001). Less than 5% physicians agreed with a definition commonly used in clinical trials (<12 months, first episode of wheeze). We retained three dimensions on PCA: one based on coryza, rales/crepitations and no sudden onset; another on number of episodes and age; and a third on wheeze. Dimensions varied by physician specialization and training (P < 0.01). Hospital admission and respiratory distress were top rated outcomes by both groups of physicians. CONCLUSIONS: Physician definitions of bronchiolitis have considerable variability and often mismatch those of clinical trials. Rating of important outcomes was consistent. Our results highlight the need for a robust standardized definition of acute bronchiolitis in infants and support the development of a core outcome set for future clinical trials. Pediatr Pulmonol. 2016;51:724-732. © 2015 Wiley Periodicals, Inc.