Effects of dietary supplementation with inactivated Lactobacillus plantarum on growth performance, haemato-biochemical parameters, liver fatty acids profile and intestinal microbiome of Nile tilapia.

This study investigated the effects of dietary supplementation with inactivated Lactobacillus plantarum for Nile tilapia (Oreochromis niloticus). Three treatments, in quintuplicate, were established: a control group, fish fed a diet without additives; LP group, fish fed a diet supplemented with live probiotic; and IP group, fish fed a diet supplemented with inactivated probiotic. Final weights (49.40 ± 3.15 g) and weight gains (38.20 ± 3.23 g) were increased in tilapia in the IP group. Feed conversion (1.32 ± 0.04) decreased significantly in the IP group. Haemato-biochemical parameters were significantly influenced by dietary supplementation. Erythrocyte count (262.74 ± 69.28 × 106 µL-1) was significantly low, while albumin (1.79 ± 1.12 g dL-1) and cholesterol (254.14 ± 98.49 mg dL-1) were high in the control group. Dietary supplementation modified the tilapia microbiome. Rhodobacter was abundant in fish intestines from the control and IP groups. Phreatobacter was abundant in the IP and LP groups, while Aurantimicrobium and Bosea were abundant in the LP group. Oleic acid (C18:1n9) was significantly increased in the LP (3.25 ± 0.49%) and IP (3.02 ± 0.30%) groups. Hexadecatrienoic acid (C16:3n4) was significantly increased (0.04 ± 0.01%) in the IP group, while Cis 11,14,17-eicosatrienoic acid (C20:3n3) (0.31 ± 0.03%) and adrenic acid (C22:4n6) (0.11 ± 0.02%) were significantly decreased in the LP group. Additionally, monounsaturated fatty acids (MUFA) were significantly increased (4.83 ± 0.35%) in the LP group compared to that in the control group. Collectively, these results indicate the potential of inactivated L. plantarum for use in commercial feed, leading to the conclusion that both inactivated and live L. plantarum can improve the Nile tilapia metabolism, altering haematological and biochemical markers.

Efeito da fotobiomodulação na reabilitação de pacientes com patologias traumato-ortopédicas: revisão integrativa / Efectos de la fotobiomodulación en la rehabilitación de pacientes con patologías traumatoortopédicas: revisión integrativa / Effects of photobiomodulationin the rehabilitation of patients with traumato-orthopedic pathologies: integrative review

Introdução: Fotobiomodulação corresponde à exposição de tecidos biológicos a baixos níveis de luz vermelha e infravermelha, esta terapia favorece a reabilitação de diferentes tecidos e que pode ser utilizada para a melhora da prática clínica nas diferentes atuações da fisioterapia, como por exemplo, no tratamento dos acometimentos musculoesqueléticos e inflamatórios. Objetivo: Identificar os benefícios da fotobiomodulação empregados na reabilitação de pacientes nas diferentes patologias traumato-ortopédicas. Metodologia:Trata-se de uma revisão integrativa com busca online nas plataformas de dados: Medline e PubMed. Os descritores foram: fotobiomodulação, taumato-ortopedia e reabilitação. As línguas selecionadas foram: Português, Inglês e Espanhol, entre os anos de 2018 a 2022.Resultados:A descrição dos achados nos ensaios clínicos analisados mostra que a terapia de fotobiomodulação apresenta diferentes usos na prática clínica e que seu uso produz efeito analgésico, anti-inflamatório e regenerativo nos distúrbios musculoesqueléticos. Conclusões:De acordo com a revisão dos artigos, pôde-se perceber que a terapia por fotobiomodulação confirma seus benefícios e eficácia, portando, se fazendo positiva na atuação traumato-ortopédica, gerando resultados significativos quando comparada a outros recursos (AU).

Introduction: Photobiomodulationcorresponds to the exposure of biological tissues to low levels of red and infrared light, this therapy favors the rehabilitation of different tissues and can be used to improve clinical practice in different actions of physiotherapy, such as, for example, in the treatment of musculoskeletal and inflammatory disorders. Objective: To identify the benefits of photobiomodulation used in the rehabilitation of patients with different traumato-orthopedic pathologies. Methodology:This is an integrative review with online search on data platforms: Medline and PubMed. The descriptors were: photobiomodulation, thaumato-orthopedics and rehabilitation. The selected languages were: Portuguese, English and Spanish, from 2018 to 2022. Results: The description of the discovers in the analyzed clinical trials shows that photobiomodulation therapy has different uses in clinical practice and that its use produces analgesic, anti-inflammatory and regenerative effects in musculoskeletal disorders. Conclusions:According to the review of the articles, it could be seen that photobiomodulation therapy confirms its benefits and effectiveness, therefore, becoming positive in the trauma-orthopedic performance, generating significant results when compared to other resources (AU).

Introducción: La fotobiomodulacióncorresponde a la exposición de tejidos biológicos a bajos niveles de luz roja e infrarroja, esta terapia estimula la rehabilitación de diferentes tejidos y puede ser utilizada para mejorar la práctica clínica en diferentes áreas de fisioterapia, como por ejemplo, en tratamiento de Trastornos musculoesqueléticos e inflamatorios. Objetivo: Identificar los beneficios de la fotobiomodulación utilizada en la rehabilitación de pacientes con diferentes patologías traumato-ortopédicas. Metodología: Esta es una revisión integradora con búsqueda en línea en plataformas de datos: Medline y PubMed. Los descriptores fueron: fotobiomodulación, taumato-ortopedia y rehabilitación. Los idiomas seleccionados fueron: portugués, inglés y español, entre los años 2018 a 2022. Resultados: La descripción de los hallazgos en los ensayos clínicos analizados muestra que la terapia de fotobiomodulación tiene diferentes usos en la práctica clínica y que su uso produce efectos analgésicos, antiinflamatorios y regenerador en trastornos musculoesqueléticos. Conclusiones: De acuerdo con la revisión de los artículos, se pudo apreciar que la terapia de fotobiomodulación confirma sus beneficios y efectividad, por lo tanto, tornándose positiva en el desempeño trauma-ortopédico, generando resultados significativos cuando se compara con otros recursos (AU).

Resultado da mobilização precoce sobre as repercussões clínicas e funcionais de cirurgias torácicas: revisão integrativa / Resultados de la temprana movilización sobre las repercusiones clínicas y funcionales de cirugíatorácica: revisión integrativa / Results of early mobilization on the clinical and functional repercussions of patients submitted to thoracic surgery: integrative review

Introdução: O período de internação os pacientes passam por um longo período de imobilização no leito, acompanhada de complicações e comorbidades que podem ocorrer no período pós-operatório. A fisioterapia aturará prevenindo os efeitos da imobilidade no leito, além de melhorar a independência funcional do paciente. Objetivo: Diante o exposto, o objetivo desse estudo é analisar as repercussões clínicas e funcionais da reabilitação precoce em pacientes submetidos à cirurgia torácica. Metodologia: Trata-se de uma revisão integrativa. Critérios de inclusão: ensaios clínicos randomizados, artigos completos, dos idiomas português, inglês e espanhol, publicados entre 2012 e 2022. Critérios de exclusão: protocolos de ensaios, ensaios não finalizados, estudos inferiores ao ano de 2012 e outras línguas. Descritores: Cirurgia torácica; Deambulação precoce; Modalidades de Fisioterapia. Com seus respectivos termos na língua inglesa. Resultados: Foram encontrados 51 artigos. Com os critérios estabelecidos foram selecionados 06 artigos. Os estudos dos autores avaliados se mostraram benéficos para a terapia de deambulação precoce combinada e exercícios. Conclusões: Os achados resultam na minimização das alterações de fluxo e volume pulmonar, otimização da mecânica do movimento tóraco-abdominal e aumento da amplitude do movimento dos músculos respiratórios, facilitando a reexpansão pulmonar e melhorando osparâmetros de função pulmonar (AU)>

Introduction: During hospitalization, patients go through a long period of immobilization in bed, accompanied by complications and comorbidities that may occur in the postoperative period. Physical therapy will help prevent the effects of immobility in bed, in addition to improving the patient's functional independence. Objective:Given the above, the objective of this study is to analyze the clinical and functional repercussions of early rehabilitation in patients undergoing thoracic surgery. Methodology:It is a systematic review. Inclusion criteria: randomized clinical trials, complete articles, in Portuguese, English and Spanish, published between 2012 and 2022. Exclusion criteria: trial protocols, unfinished trials, studies smaller than 2012 in other languages. Descriptors: Thoracic surgery; Early ambulation; Physiotherapy modalities. Results:51 articles were found. With the established criteria, 06 articles were selected. The evaluated authors' studies have shown benefit for combined early ambulation therapy and exercise. Conclusions:The findings result in the minimization of changes in lung flow and volume, optimization of the mechanics of thoracoabdominal movement and increased range of motion of the respiratory muscles, facilitating lung re-expansion and improving lung function parameters (AU).

Introducción: A lo largo de la hospitalización, los pacientes pasan por un largo período de inmovilización en cama, acompañado de complicacionesy comorbilidades que pueden presentarse en el postoperatorio. La fisioterapia ayudará a prevenir los efectos de la inmovilidad en cama, además de mejorar la independencia funcional del paciente. Objetivo:Teniendo en cuenta lo anterior, el objetivo de este estudio es analizar las repercusiones clínicas y funcionales de la rehabilitación temprana en pacientes sometidos a cirugía torácica.Metodología: Esta es una revisión sistemática. Criterios de inclusión: ensayos clínicos aleatorizados, artículos completos, en portugués, inglés y español, publicados entre 2012 y 2022. Criterios de exclusión: protocolos de ensayos, ensayos inconclusos, estudios menores a 2012 y otros idiomas. Descriptores: Cirugía torácica; Deambulación temprana; Modalidades de fisioterapia. Con sus respectivos términosen inglés.Resultados: Se encontraron 51 artículos. Fueron seleccionados 06 artículos, con los criterios establecidos. Los estudios de los autores evaluados han demostrado beneficios para la combinación de terapia de deambulación temprana y ejercicio.Conclusiones: Los hallazgos resultan en la minimización de alteraciones en el flujo y volumen pulmonar, optimización de la mecánica del movimiento toracoabdominal y aumento en el rango de movimiento de los músculos respiratorios, facilitando la reexpansión pulmonar y mejorando los parámetrosde la función pulmonar (AU).

Climatic zoning of yerba mate and climate change projections: a CMIP6 approach.

Yerba mate (Ilex paraguariensis) is renowned for its nutritional and pharmaceutical attributes. A staple in South American (SA) culture, it serves as the foundation for several traditional beverages. Significantly, the pharmaceutical domain has secured numerous patents associated with this plant's distinctive properties. This research delves into the climatic influence on yerba mate by leveraging the CMIP6 model projections to assess potential shifts brought about by climate change. Given its economic and socio-cultural significance, comprehending how climate change might sway yerba mate's production and distribution is pivotal. The CMIP6 model offers insights into future conditions, pinpointing areas that are either conducive or adverse for yerba mate cultivation. Our findings will be instrumental in crafting adaptive and mitigative strategies, thereby directing sustainable production planning for yerba mate. The core objective of this study was to highlight zones optimal for Ilex paraguariensis cultivation across its major producers: Brazil, Argentina, Paraguay, and Uruguay, under CMIP6's climate change forecasts. Our investigation encompassed major producing zones spanning the North, Northeast, Midwest, Southeast, and South of Brazil, along with the aforementioned countries. A conducive environment for this crop's growth features air temperatures between 21 to 25 °C and a minimum precipitation of 1200 mm per cycle. We sourced the current climate data from the WorldClim version 2 platform. Meanwhile, projections for future climatic parameters were derived from WorldClim 2.1, utilizing the IPSL-CM6A-LR model with a refined 30-s spatial resolution. We took into account four distinct socio-economic pathways over varying timelines: 2021-2040, 2041-2060, 2061-2081, and 2081-2100. Geographic information system data aided in the spatial interpolation across Brazil, applying the Kriging technique. The outcomes revealed a majority of the examined areas as non-conducive for yerba mate cultivation, with a scanty 12.25% (1.5 million km2) deemed favorable. Predominantly, these propitious regions lie in southern Brazil and Uruguay, the present-day primary producers of yerba mate. Alarming was the discovery that forthcoming climatic scenarios predominantly forecast detrimental shifts, characterized by escalating average air temperatures and diminishing rainfall. These trends portend a decline in suitable cultivation regions for yerba mate.

Climate and disease: tackling coffee brown-eye spot with advanced forecasting models.

BACKGROUND: Climate influences the interaction between pathogens and their hosts significantly. This is particularly evident in the coffee industry, where fungal diseases like Cercospora coffeicola, causing brown-eye spot, can reduce yields drastically. This study focuses on forecasting coffee brown-eye spot using various models that incorporate agrometeorological data, allowing for predictions at least 1 week prior to the occurrence of disease. Data were gathered from eight locations across São Paulo and Minas Gerais, encompassing the South and Cerrado regions of Minas Gerais state. In the initial phase, various machine learning (ML) models and topologies were calibrated to forecast brown-eye spot, identifying one with potential for advanced decision-making. The top-performing models were then employed in the next stage to forecast and spatially project the severity of brown-eye spot across 2681 key Brazilian coffee-producing municipalities. Meteorological data were sourced from NASA's Prediction of Worldwide Energy Resources platform, and the Penman-Monteith method was used to estimate reference evapotranspiration, leading to a Thornthwaite and Mather water-balance calculation. Six ML models - K-nearest neighbors (KNN), artificial neural network multilayer perceptron (MLP), support vector machine (SVM), random forests (RF), extreme gradient boosting (XGBoost), and gradient boosting regression (GradBOOSTING) - were employed, considering disease latency to time define input variables. RESULTS: These models utilized climatic elements such as average air temperature, relative humidity, leaf wetness duration, rainfall, evapotranspiration, water deficit, and surplus. The XGBoost model proved most effective in high-yielding conditions, demonstrating high precision and accuracy. Conversely, the SVM model excelled in low-yielding scenarios. The incidence of brown-eye spot varied noticeably between high- and low-yield conditions, with significant regional differences observed. The accuracy of predicting brown-eye spot severity in coffee plantations depended on the biennial production cycle. High-yielding trees showed superior results with the XGBoost model (R2 = 0.77, root mean squared error, RMSE = 10.53), whereas the SVM model performed better under low-yielding conditions (precision 0.76, RMSE = 12.82). CONCLUSION: The study's application of agrometeorological variables and ML models successfully predicted the incidence of brown-eye spot in coffee plantations with a 7 day lead time, illustrating that they were valuable tools for managing this significant agricultural challenge. © 2024 Society of Chemical Industry.

Agroclimatic mapping for olive cultivation in Brazil: pinpointing optimal growing regions.

BACKGROUND: This research aimed to identify the agroclimatic zones in Brazil, excluding Rio Grande do Sul, that are suitable for olive (Olea europaea L.) cultivation, considering both climatic and topographical factors. Olives require specific conditions: moderate winter temperatures (7-15 °C), warmer summers (25-35 °C) and sufficient water during growth and fruit maturation. They can endure some drought, making them a viable option for agricultural diversification. Using daily meteorological data from 1989 to 2023 from NASA-POWER, this study analyzed variables like air temperature (minimum and maximum) and rainfall. Key climate variables were the mean air temperature in winter (T_w), spring (T_s), summer (T_su) and autumn (T_a) and total annual precipitation (Prec). Criteria for suitability included: T_w between 5 and 20 °C, T_s between 15 and 23 °C, T_su between 15 and 30 °C, T_a between 15 and 22 °C, annual precipitation over 900 mm and altitude below 900 m. Geographic information system software and Python 3.8 were employed for data analysis and zoning. RESULTS: Results indicated that only 1.92% of the analyzed area, mainly in Minas Gerais, was suitable for olive cultivation. High temperatures and low rainfall in Brazil, particularly in the North and Midwest, make 59.56% of the country unsuitable for olive farming. Additionally, 18.58% of the land, mainly in the Northeast, faces challenges due to extreme heat (T_w) and insufficient water supply. © 2023 Society of Chemical Industry.

Climate zoning: identifying suitable regions for the occurrence of Alternaria Brown spot in tangerine trees in Brazil.

BACKGROUND: Brazilian citrus farming has been migrating to nontraditional citrus-growing regions, which can be considered a challenge for citrus growers, as not all these areas are suitable for tangerine cultivation. Thus, the mapping of regions exhibiting favorable climatic conditions for Alternaria brown spot has become crucial in the selection of appropriate locations for the establishment of new orchards. This mapping enables the implementation of an avoidance strategy, which entails steering clear of areas where the disease is prevalent, aligning with fundamental principles of disease control. RESULTS: Thus, this study seeks to zone areas with high and low climatic favorability for the occurrence of Alternaria brown spot in tangerine trees in Brazil. Historical climate data series from the NASA-POWER database were used for all municipalities in Brazil. Agrometeorological variables used to determine the development of Alternaria brown spot were average monthly air temperature (Tmean) and duration of leaf wetness period (LWD). Areas were considered unsuitable climatically when Tmean was <17 °C or >33 °C, relatively suitable when Tmean was between 13 °C and 33 °C and LWD <10%, and climatically suitable when Tmean was between 13 °C and 33 °C and LWD >10%. The states of Paraná, Santa Catarina and Rio Grande do Sul showed greater thermal amplitude within months and throughout the year. The southern region of the country has harsher winters, with minimum temperatures below 15 °C, which is unfavorable for the disease incidence. CONCLUSION: The states with the greatest favorability for Alternaria brown spot were Paraná, Santa Catarina, and Rio Grande do Sul, mainly from May to September. Rio Grande do Sul was the state in this region that showed the greatest favorability, as a consequence of leaf wetness exceeding 10 h. The main tangerine-producing regions in Brazil, including the southern part of Minas Gerais, the state of São Paulo and the metropolitan region of Porto Alegre, were mostly classified as relatively favorable areas for the occurrence of Alternaria brown spot. It is recommended that when establishing new tangerine orchards, regions with lower favorability for the occurrence of Alternaria brown spot, such as the North and Central-West regions of Brazil, particularly the states of Amazonas, Pará and Mato Grosso, should be selected. © 2023 Society of Chemical Industry.

Climate risk zoning for wheat crops in the southeastern region of Brazil.

BACKGROUND: Wheat (Triticum aestivum L.) is the second most consumed food in the world. One way to meet this demand is the expansion of wheat cultivation to the Brazilian Cerrado in the southeastern region. However, one of the major limitations is that there are few studies related to wheat climate risk zoning. Thus, this study aimed to determine the agroclimatic zoning of wheat by estimating the water needs satisfaction index (ISNA) in the southeastern region of Brazil. For this purpose, a 60-year historical series of meteorological data was used to calculate the potential evapotranspiration, crop evapotranspiration, and climatological water balance values. To define the agroclimatic zones of wheat and sowing date, the ISNA method was used. The data were analyzed using descriptive statistics to determine the variations. To obtain the agroclimatic zoning of wheat, the geostatistical method of kriging interpolation was used. RESULTS: The regions with the highest rainfall are the south of Minas Gerais and the coast of São Paulo. The sowing period directly impacts the development of the crop, the available water capacity and the ISNA values indicated the spring and summer had better cultivation conditions, and the best window for wheat cultivation is concentrated in the fall due to the limitation of biotic factors. CONCLUSION: In terms of altitude (>700 m), Minas Gerais has 39.4% of the area suitable for wheat cultivation. Thus, climatic variations within and between the states of the southeastern region should be considered for the positioning of wheat cultivars in these regions to obtain the maximum yield. © 2023 Society of Chemical Industry.

PARP1 Characterization as a Potential Biomarker for BCR::ABL1 p190+ Acute Lymphoblastic Leukemia.

Detection of t(9;22), and consequent BCR::ABL1 fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of BCR::ABL1 p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets. Overall, we demonstrate the effectiveness of PARPi in the treatment of BCR::ABL1 p190+ ALL cell models and that PARP1 is differentially expressed in patient samples. We hope our findings help expand the characterization of molecular profiles in ALL settings and guide future investigations into novel biomarker detection and pharmacological choices in clinical practice.

Saberes e Práticas Sobre Prevenção e Tratamento de Queimaduras no Ambiente Domiciliar / Knowledge and Practices About Prevention and Treatment of Burns in the Home Environment / Conocimientos y Prácticas Sobre Prevención y Tratamiento de Quemaduras en el Ambiente Domiciliario

Objetivos:Demonstrar os saberes e as práticas de indivíduos sobre prevenção e tratamento de queimaduras no ambiente domiciliar e descrever o cuidado educativo de enfermagem na prevenção e tratamento de queimaduras no ambiente domiciliar. Método: Pesquisa convergente-assistencial realizada de maneira virtual, no período de junho a agosto de 2021, com pessoas residentes na cidade de Macaé (RJ). Resultados: A pesquisa incluiu 16 participantes, sendo 81,25% (n = 13) do sexo feminino, com idades entre 19 e 59 anos. Na análise das entrevistas, foi possível identificar saberes e práticas equivocados sobre a prevenção e o tratamento de queimaduras, a serem discutidos neste estudo. Conclusão: Embora haja conhecimento acerca dos saberes e práticas adequados sobre prevenção e tratamento de queimaduras no ambiente domiciliar, houve identificação de práticas equivocadas que podem prejudicar o correto tratamento e prevenção de agravos. Os achados deste estudo apontam para a necessidade de construir materiais e de realizar práticas educativas com essa população para reforço de medidas preventivas de queimaduras.

Objectives:To demonstrate the knowledge and practices of individuals on the prevention and treatment of burns in the home environment and to describe the educational nursing care in the prevention and treatment of burns in the home environment. Method: Convergent care research was carried out virtually, from June to August 2021, with people residing in the city of Macaé/RJ, Brazil. Results: The survey included 16 participants, 81.25% (n = 13) female, aged between 19 and 59 years old. In the analysis of the interviews, it was possible to identify mistaken knowledge and practices about the prevention and treatment of burns, to be discussed in this study. Conclusion: Although there is knowledge about adequate knowledge and practices on the prevention and treatment of burns in the home environment, there was identification of wrong practices that can harm the correct treatment and prevention of injuries. The findings of this study point to the need to build materials and carry out educational practices with this population to reinforce preventive measures for burns.

Objetivos:Demostrar los conocimientos y prácticas de los individuos sobre la prevención y tratamiento de quemaduras en el ambiente domiciliario y describir el cuidado educativo de enfermería en la prevención y tratamiento de quemaduras en el ambiente domiciliario. Método: Investigación de Atención Convergente (PCA) realizada virtualmente, de junio a agosto de 2021, con personas residentes en la ciudad de Macaé/RJ. Resultados: La encuesta contó con 16 participantes, 81,25% (n=13) mujeres, con edades entre 19 y 59 años. En el análisis de las entrevistas, fue posible identificar conocimientos y prácticas erróneas sobre la prevención y el tratamiento de las quemaduras, para ser discutidas en este estudio. Conclusión: Si bien existe conocimiento sobre los saberes y prácticas sobre la prevención y tratamiento de quemaduras en el ámbito domiciliario, se identificaron prácticas incorrectas que pueden perjudicar el correcto tratamiento y prevención de lesiones. Los hallazgos de este estudio apuntan para la necesidad de construir materiales y realizar prácticas educativas con esta población para reforzar las medidas preventivas de quemaduras.

Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect in vivo.

Introduction: Natural killer 92 (NK-92) cells are an attractive therapeutic approach as alternative chimeric antigen receptor (CAR) carriers, different from T cells, once they can be used in the allogeneic setting. The modest in vivo outcomes observed with NK-92 cells continue to present hurdles in successfully translating NK-92 cell therapies into clinical applications. Adoptive transfer of CAR-NK-92 cells holds out the promise of therapeutic benefit at a lower rate of adverse events due to the absence of GvHD and cytokine release syndrome. However, it has not achieved breakthrough clinical results yet, and further improvement of CAR-NK-92 cells is necessary. Methods: In this study, we conducted a comparative analysis between CD19-targeted CAR (CAR.19) co-expressing IL-15 (CAR.19-IL15) with IL-15/IL-15Rα (CAR.19-IL15/IL15Rα) to promote NK cell proliferation, activation, and cytotoxic activity against B-cell leukemia. CAR constructs were cloned into lentiviral vector and transduced into NK-92 cell line. Potency of CAR-NK cells were assessed against CD19-expressing cell lines NALM-6 or Raji in vitro and in vivo in a murine model. Tumor burden was measured by bioluminescence. Results: We demonstrated that a fourth- generation CD19-targeted CAR (CAR.19) co-expressing IL-15 linked to its receptor IL-15/IL-15Rα (CAR.19-IL-15/IL-15Rα) significantly enhanced NK-92 cell proliferation, proinflammatory cytokine secretion, and cytotoxic activity against B-cell cancer cell lines in vitro and in a xenograft mouse model. Conclusion: Together with the results of the systematic analysis of the transcriptome of activated NK-92 CAR variants, this supports the notion that IL-15/IL-15Rα comprising fourth-generation CARs may overcome the limitations of NK-92 cell-based targeted tumor therapies in vivo by providing the necessary growth and activation signals.

Caloric restriction improves inflammation in different tissues of the Wistar rats with obesity and 2K1C renovascular hypertension.

Renovascular hypertension (RHV) is the cause of high blood pressure due to left renal ischemia, and obesity and hypertension cause an inflammatory response. This work analyzed the inflammatory and tissue repair profile in renal, hepatic, and cardiac tissues in an animal model of RVH associated with a high-fat diet and caloric restriction. The expressions of RORγ-t, IL-17, T-bet, and TNF-α decreased and IFN-γ increased in the right kidney. In relation to the left kidney, caloric restriction decreased the expression of IFN-γ. In the liver, caloric restriction decreased RORγ-t, IL-17, and T-bet. Hypertension associated with obesity decreased the expression of IFN-γ, while caloric restriction increased. In the right kidney, hypertension and obesity, associated or not with caloric restriction, increased the area of collagen fibers. In the heart and liver, caloric restriction reduced the area of collagen fibers. Caloric restriction increased vascular endothelial growth factor, reduced levels of growth transformation factor-ß1 (TGF-ß), and increased collagen I in the left kidney. Hypertension/obesity, submitted or not having caloric restriction, increased TGF-ß in liver. The results suggest that caloric restriction has beneficial effects in lowering blood pressure and regulating tissue proinflammatory cytokines. However, there was no change in the structure and composition of tissue repair markers.

Telomeric repeat-containing RNA is dysregulated in acute myeloid leukemia.

TERRA (telomeric repeat-containing RNA) is a class of long noncoding RNAs transcribed from subtelomeric and telomeric regions. TERRA binds to the subtelomeric and telomeric DNA-forming R-loops (DNA-RNA hybrids), which are involved in telomere maintenance and telomerase function, but the role of TERRA in human cells is not well characterized. Here, we comprehensively investigated for the first time TERRA expression in primary human hematopoietic cells from an exploratory cohort of patients with acute myeloid leukemia (AML), patients with acute lymphoblastic leukemia (ALL), patients with telomere biology disorder (TBD), and healthy subjects. TERRA expression was repressed in primary human hematopoietic cells, including healthy donors, patients with ALL, and patients with TBD, irrespective of their telomere length, except for AML. A second cohort comprising 88 patients with AML showed that TERRA was overexpressed in an AML subgroup also characterized by higher R-loop formation, low TERT and RNAseH2 expression, and a paucity of somatic splicing factor mutations. Telomere length did not correlate with TERRA expression levels. To assess the role of TERRA R-loops in AML, we induced R-loop depletion by increasing RNAseH1 expression in 2 AML cell lines. Decreased TERRA R-loops in AML cell lines resulted in increased chemosensitivity to cytarabine. Our findings indicate that TERRA is uniformly repressed in primary human hematopoietic cells but abnormally expressed in an AML subset with low telomerase.

Genome Editing for Engineering the Next Generation of Advanced Immune Cell Therapies.

Our current genetic engineering capacity through synthetic biology and genome editing is the foundation of a revolution in biomedical science: the use of genetically programmed cells as therapeutics. The prime example of this paradigm is the adoptive transfer of genetically engineered T cells to express tumor-specific receptors, such as chimeric antigen receptors (CARs) or engineered T-cell receptors (TCR). This approach has led to unprecedented complete remission rates in patients with otherwise incurable hematological malignancies. However, this approach is still largely ineffective against solid tumors, which comprise the vast majority of neoplasms. Also, limitations associated with the autologous nature of this therapy and shared markers between cancer cells and T cells further restrict the access to these therapies. Here, we described how cutting-edge genome editing approaches have been applied to unlock the full potential of these revolutionary therapies, thereby increasing therapeutic efficacy and patient accessibility.

BCR-ABL promotes hematopoietic stem and progenitor cell formation in embryonic stem cells.

Generating hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) has been a long-lasting quest in the field of hematopoiesis. Previous studies suggested that enforced expression of BCR-ABL, the unique oncogenic driver of chronic myelogeneous leukemia (CML), in embryonic stem cells (ESCs)-derived hematopoietic cells is sufficient to confer long-term in vivo repopulating potential. To precisely uncover the molecular events regulated by the tyrosine kinase activity of BCR-ABL1 (p210) during the course of hematopoietic differentiation, we engineered a Tet-ON inducible system to modulate its expression in murine ESCs (mESCs). We showed in unique site-directed knock-in ESC model that BCR-ABL expression tightly regulated by doxycycline (dox) controls the formation and the maintenance of immature hematopoietic progenitors. Interestingly, these progenitors can be expanded in vitro for several passages in the presence of dox. Our analysis of cell surface markers and transcriptome compared with wild-type fetal and adult HSCs unraveled a similar molecular signature. Long-term culture initiating cell (LTC-IC) assay confirmed their self-renewal capacities albeit with a differentiation bias toward erythroid and myeloid cells. Collectively, our novel Tet-ON system represents a unique in vitro model to shed lights on ESC-derived hematopoiesis, CML initiation, and maintenance.

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy that occurs due to alterations such as genetic mutations, chromosomal translocations, or changes in molecular levels. These alterations can accumulate in stem cells and hematopoietic progenitors, leading to the development of AML, which has a prevalence of 80% of acute leukemias in the adult population. Recurrent cytogenetic abnormalities, in addition to mediating leukemogenesis onset, participate in its evolution and can be used as established diagnostic and prognostic markers. Most of these mutations confer resistance to the traditionally used treatments and, therefore, the aberrant protein products are also considered therapeutic targets. The surface antigens of a cell are characterized through immunophenotyping, which has the ability to identify and differentiate the degrees of maturation and the lineage of the target cell, whether benign or malignant. With this, we seek to establish a relationship according to the molecular aberrations and immunophenotypic alterations that cells with AML present.

Hybrid lipid-biopolymer nanocarrier as a strategy for GBM photodynamic therapy (PDT).

Glioblastoma (GBM) is the most common brain cancer characterized by aggressive and infiltrated tumors. For this, hybrid biopolymer-lipid nanoparticles coated with biopolymers such as chitosan and lipidic nanocarriers (LN) loaded with a photosensitizer (AlClPc) can be used for GBM photodynamic therapy. The chitosan-coated LN exhibited stable physicochemical characteristics and presented as an excellent lipid nanocarrier with highly efficiently encapsulated photosensitizer chloro-aluminum phthalocyanine (AlClPc). LN(AlClPc)Ct0.1% in the presence of light produced more reactive oxygen species and reduced brain tumor cell viability and proliferation. Confirm the effects of in vivo LN applications with photodynamic therapy confirmed that the total brain tumor area decreased without systemic toxicity in mice. These results suggest a promising strategy for future clinical applications to improve brain cancer treatment.

[Scribbling and doodling: social representations by children expressed in drawings, regarding the experience of blood sampling]. / Risco e rabisco: representações sociais de crianças expressas em desenhos acerca do procedimento de coleta sanguínea.

The scope of this article was to identify the social representations of children in a municipal public school in Rio de Janeiro, with respect to the blood sampling procedure and to discuss the social representations that emerge, in the light of the performance of the family health team in carrying out this procedure. Moscovisci's method/theory of analysis of social representations based on a qualitative approach was used. For data collection, the projective technique of the esthetic production scene and the student's speech was used. The results were grouped into four categories: 1) structural dimensions involved in the blood sampling procedure; 2) dimension of the human component and its interface in the blood sampling procedure; 3) the psycho-emotional dimension portrayed in the blood sampling procedure; and 4) blood sampling: the importance for student health. With respect to the importance of blood sampling, we highlight the perception of students regarding the importance of actions aimed at prevention and health care promotion.

Objetivou-se identificar as representações sociais de crianças de uma escola pública municipal do Rio de Janeiro acerca do procedimento de coleta sanguínea e discutir as representações sociais emergidas, à luz da atuação da equipe de saúde da família na realização desse procedimento. Utilizou-se o método e a teoria de análise das representações sociais fundamentadas por Moscovisci e Jodelet, numa abordagem qualitativa. Para a coleta de dados, empregou-se a técnica projetiva de cena de produção estética e do discurso do escolar. Os resultados foram agrupados em quatro categorias: 1) dimensões estruturais que envolvem o procedimento de coleta sanguínea; 2) dimensão do componente humano e sua interface no procedimento de coleta sanguínea; 3) a dimensão psicoemocional retratada no procedimento de coleta sanguínea e 4) a coleta de sangue: a importância para a saúde do escolar. No que diz respeito à importância da coleta sanguínea, evidenciamos a percepção de escolares para a importância de ações voltadas à prevenção e promoção da saúde.

Risco e rabisco: representações sociais de crianças expressas em desenhos acerca do procedimento de coleta sanguínea / Scribbling and doodling: social representations by children expressed in drawings, regarding the experience of blood sampling

Resumo Objetivou-se identificar as representações sociais de crianças de uma escola pública municipal do Rio de Janeiro acerca do procedimento de coleta sanguínea e discutir as representações sociais emergidas, à luz da atuação da equipe de saúde da família na realização desse procedimento. Utilizou-se o método e a teoria de análise das representações sociais fundamentadas por Moscovisci e Jodelet, numa abordagem qualitativa. Para a coleta de dados, empregou-se a técnica projetiva de cena de produção estética e do discurso do escolar. Os resultados foram agrupados em quatro categorias: 1) dimensões estruturais que envolvem o procedimento de coleta sanguínea; 2) dimensão do componente humano e sua interface no procedimento de coleta sanguínea; 3) a dimensão psicoemocional retratada no procedimento de coleta sanguínea e 4) a coleta de sangue: a importância para a saúde do escolar. No que diz respeito à importância da coleta sanguínea, evidenciamos a percepção de escolares para a importância de ações voltadas à prevenção e promoção da saúde.

Abstract The scope of this article was to identify the social representations of children in a municipal public school in Rio de Janeiro, with respect to the blood sampling procedure and to discuss the social representations that emerge, in the light of the performance of the family health team in carrying out this procedure. Moscovisci's method/theory of analysis of social representations based on a qualitative approach was used. For data collection, the projective technique of the esthetic production scene and the student's speech was used. The results were grouped into four categories: 1) structural dimensions involved in the blood sampling procedure; 2) dimension of the human component and its interface in the blood sampling procedure; 3) the psycho-emotional dimension portrayed in the blood sampling procedure; and 4) blood sampling: the importance for student health. With respect to the importance of blood sampling, we highlight the perception of students regarding the importance of actions aimed at prevention and health care promotion.

Is There a Dose-Response Relationship between High-Intensity Interval Exercise (HIIE) Intensity and Affective Valence? Analysis of Three HIIE Sessions Performed with Different Amplitudes.

The inverse relationship between exercise intensity and affective valence is well established for continuous exercise but not for high-intensity interval exercise (HIIE). The objective was to verify the dose-response relationship between exercise intensity and affective valence in HIIE sessions. Eleven young men underwent a vigorous-intensity continuous exercise (VICE) and three HIIE sessions at the same average intensity (70% of peak power-WPeak) and duration (20 min) but with different amplitudes: 10 × [1 min at 90% WPeak/1 min at 50% WPeak]-HIIE-90/50; 10 × [1 min at 100% WPeak/1 min at 40% WPeak]-HIIE-100/40; 10 × [1 min at 110% WPeak/1 min at 30% WPeak]-HIIE-110/30. During the exercise sessions, psychophysiological variables were recorded (VO2, VCO2, heart rate, perceived exertion CR10, and Feeling Scale (FS)). Higher correlations were found between CR10 and FS for all conditions (VICE = -0.987; HIIE-90/50 = -0.873; HIIE-100/40 = -0.908; HIIE-110/30 = -0.948). Regarding the physiological variables, the %HRMax presented moderate inverse correlations with FS for all exercise conditions (VICE = -0.867; HIIE-90/50 = -0.818; HIIE-100/40 = -0.837; HIIE-110/30 = -0.828) while the respiratory variables (%VO2Peak and %VCO2Peak) presented low-to-moderate correlations only for VICE, HIIE-90/50, and HIIE-100/40 (ranging from -0.523 to -0.805). Poor correlations were observed between the %VO2Peak (r = -0.293) and %VCO2Peak (r = -0.020) with FS. The results indicated that perceived exertion is more sensible than physiological variables to explain the intensity-affective valence relationship in HIIE sessions. RPE should be used for HIIE prescription with a focus on affect.