Comparison of Non-Invasive Methods for the Detection of Coronary Atherosclerosis

BACKGROUND: Non-invasive detection of atherosclerosis is critical for its prevention. OBJECTIVE: To correlate non-invasively detectable indicators of coronary atherosclerosis, or Coronary Artery Disease (i.e., classical risk factors, hs-CRP test results, carotid intima-media thickness, endothelial function, ankle-brachial index and calcium score by computed tomography) with the extent of coronary disease assessed by the Friesinger index from conventional coronary angiography. METHODS: We conducted a prospective study of 100 consecutive patients, mean age 55.1 ± 10.7 years, 55% men and 45% women. Patients with acute coronary syndrome, renal dialytic insufficiency, collagen disease and cancer were not included. All patients were subjected to clinical evaluation and laboratory tests. Endothelial function of the brachial artery and carotid artery were evaluated by high-resolution ultrasound; ankle-brachial index and computed tomography for coronary determination of calcium score were also performed, and non-HDL cholesterol and TG/HDL-c ratio were calculated. All patients were subjected to coronary angiography at the request of the assistant physician. We considered patients without an obstructive lesion (< 29% stenosis) demonstrated by coronary angiography to be normal. RESULTS: Univariate analysis showed that calcium score, HDL-c, TG/HDL ratio and IMT were significantly correlated with the Friesinger index. However, multivariate analysis indicated that only calcium score and low HDL-c levels correlated significantly with the extension of CAD. On the other hand, hs-CRP, LDL-c, flow-mediated dilation, and Framingham score did not correlate with the Friesinger index. ROC analysis showed that calcium score, HDL-c and TG-HDL ratio accurately predicted extensive CAD in a statistically significant manner. CONCLUSION: It is possible to approximately determine the presence and extent of CAD by non-invasive methods, especially by calcium score, HDL-c and TG/HDL-c ratio assays

Effects of desiccation with glyphosate on two common bean cultivars: Physiology and cooking quality of the harvested product

The aim of this work was to evaluate the effect of glyphosate when used on two bean cultivars for the desiccation of weeds during the pre-harvest period and the consequences on the physiologic characteristics and cooking quality of the harvested product. Treatments consisted of four doses of glyphosate used as a desiccant: 180, 360, 720, and 1,080 g a.i. ha-1, ammonium gluphosinate at 360 g a.i. ha-1, as well as a control without application of desiccant, applied to two bean cultivars (Pérola and IPR Juriti). For each of the cultivars, the experimental design was a completely randomized design with five replicates. The desiccants were applied during phenological stage R9 of the crop (maturation), which occurred 74 days after sowing (DAS). The harvest was performed 13 days after application (87 DAS). The treatments did not affect productivity, 100-bean weight, electric conductivity, accelerated aging, cooking time, or bean hydration. However, higher glyphosate doses negatively affected first count value, index of emergence speed, and seedling dry mass. The use of the herbicide glyphosate up to a rate of 1,080 g a.e. ha-1 as a desiccant against weeds in the pre-harvest period is possible for the bean market. However, if the harvested product is destined for the planting of a new crop, caution should be observed with the use of this herbicide

Physical Activity, Exercise, and Sports in Individuals with Skeletal Dysplasia: What Is Known about Their Benefits?

here is a lack of knowledge about the practice of physical activity, exercise, and sports in people with skeletal dysplasia (SD). This study aimed to characterize the physical fitness of people with SD; investigate the benefits of physical activity, exercise, or sports programs for people with SD; identify the adapted physical activities that can be prescribed to individuals with SD; and identify the most common and effective structural characteristics and guidelines for the evaluation of individuals with SD and corresponding activity prescriptions. Electronic searches were carried out in the PubMed, Scopus, SPORTDiscus, Psycinfo, and Web of Science databases in October 2021 and March 2022 and included papers published until 3 March 2022. The search strategy terms used were “dwarfism”, “dwarf”, “skeletal dysplasia”, “achondroplasia”, “pseudoachondroplasia”, “hypochondroplasia”, “campomelic dysplasia”, “hair cartilage hypoplasia”, “x-linked hypophosphatemia”, “metaphyseal chondrodysplasia schmid type”, “multiple epiphyseal dysplasia”, “three M syndrome”, “3-M syndrome”, “hypophosphatasia”, “fibrodysplasia ossificans progressive”, “type II collagen disorders”, “type II collagenopathies”, “type II collagenopathy”, “physical activity”, “exercise”, “sport”, “training”, and “physical fitness”, with the Boolean operators “AND” or “OR”. After reading the full texts of the studies, and according to previously defined eligibility criteria, fifteen studies met the inclusion criteria; however, there was not a single intervention study with physical exercise. Several cross-sectional, review, or qualitative studies presented a set of essential aspects that future intervention studies can consider when evaluating, prescribing, and implementing physical exercise programs, as they allowed the physical characterization of the SD population. This study demonstrated an apparent scarcity in the literature of experimental studies with physical exercise implementation in the SD population.info:eu-repo/semantics/publishedVersio

Optical coherence tomography in conjunction with bronchoscopy

OBJETIVO: Avaliar a viabilidade e o potencial do uso da tomografia de coerência óptica em conjunto com um broncoscópio convencional na avaliação das vias aéreas. MÉTODOS: Estudo piloto baseado em um modelo experimental ex vivo com três animais: um coelho adulto da raça Nova Zelândia e dois suínos da raça Landrace. Um cateter de imagem de tomografia de coerência óptica foi inserido no canal de trabalho de um broncoscópio flexível para alcançarmos a traqueia distal dos animais. As imagens foram obtidas sistematicamente em toda a traqueia ao longo das paredes, partindo da porção distal para a proximal. RESULTADOS: O cateter de imagem se adaptou com facilidade ao canal de trabalho do broncoscópio. Imagens em alta resolução de cortes transversais da traqueia foram obtidas em tempo real, sendo delineadas microestruturas, tais como epitélio, submucosa, cartilagem e camada adventícia nas paredes anteriores e laterais da traqueia. As camadas correspondentes do epitélio, mucosa e cartilagens foram claramente diferenciadas. Na parede posterior, foi possível identificar mucosa, submucosa e musculatura traqueal. CONCLUSÕES: O uso de tomógrafo de coerência óptica em conjunto com um broncoscópio flexível é viável. A tomografia de coerência óptica produz imagens de alta resolução que permitem visualizar a microanatomia da traqueia, inclusive estruturas que normalmente são visualizadas somente na histologia convencional

Identificação de novos fármacos contra a doença de Chagas através de estratégia de genômica e bioinformática

Chagas disease, caused by the protozoan parasite Trypanosomacruzi, is a major cause of mortality and morbidity in tropical and subtropical regions. In the absence of an effective vaccine, its control is highly dependent on the treatment of infected patients. However, only two drugs, nifurtimox and benzinidazole, are officially used for treating Chagas disease. Also, these drugs are incapable of generating radical cure and display high toxicity. Under this perspective, this study aimed to identify new therapies against Chagas disease, making use of a bioinformatics approach. Thus, theT. cruzi genome database was initially employed for selecting potential therapeutic targets (proteins) involved in intracellular transport mechanisms. In the second phase, each of the selected therapeutic targets was used to interrogate two databases that are able to identify inhibitors (drugs) based on homology with proteins from other species for which effective drugs are already available. This process, called "drug repositioning", allowed the identification of ten (10) new compounds with the potential to eliminate or inhibit the growth of T. cruzi parasites. The identification of these drugs may open new perspectives for the treatment of Chagas disease.Keywords: Chagas; Trypanosoma cruzi; Drugs; Genomics; Bioinformatics.A doença de Chagas, causada peloTrypanosoma cruzi, acarreta elevada mortalidade e morbilidade em regiões tropicais e subtropicais. Na ausência de uma vacina eficaz, o seu controle é dependente do tratamento de pacientes.Entretanto, apenas dois fármacos, benzinidazole e nifurtimox, são oficialmente utilizados. Contudo, estes são incapazes de gerar cura e apresentam elevada toxicidade. Neste sentido, o trabalhoteve como objetivo identificar novas terapias contra a doença de Chagas, fazendo-se uso de uma aproximação bioinformática. Foi primariamente utilizada a base de dados do genoma doT.cruzi para selecionar potenciais alvos terapêuticos envolvidos em mecanismos de transporte intracelular. Depois cada um dos alvos terapêuticos selecionados foi introduzido em duas bases de dados que permitiram identificarfármacos baseando-se no critério de homologia com proteínas de outras espécies paraas quais já existem drogas eficazes. Este processo permitiu identificar dez novas drogas com o potencial de eliminar ou inibir o crescimento do parasita.Palavras chave: Chagas; Trypanosoma cruzi; Fármacos; Genômica; Bioinformática

Endothelial and Non-Endothelial Coronary Blood Flow Reserve and Left Ventricular Dysfunction in Systemic Hypertension

OBJECTIVES: We evaluated the impairment of endothelium-dependent and endothelium-independent coronary blood flow reserve after administration of intracoronary acetylcholine and adenosine, and its association with hypertensive cardiac disease. INTRODUCTION: Coronary blood flow reserve reduction has been proposed as a mechanism for the progression of compensated left ventricular hypertrophy to ventricular dysfunction. METHODS: Eighteen hypertensive patients with normal epicardial coronary arteries on angiography were divided into two groups according to left ventricular fractional shortening (FS). Group 1 (FS >0.25): n=8, FS=0.29 ± 0.03; Group 2 (FS <0.25): n=10, FS= 0.17 ± 0.03. RESULTS: Baseline coronary blood flow was similar in both groups (Group 1: 80.15 ± 26.41 mL/min, Group 2: 100.09 ± 21.51 mL/min, p=NS). In response to adenosine, coronary blood flow increased to 265.1 ± 100.2 mL/min in Group 1 and to 300.8 ± 113.6 mL/min (p <0.05) in Group 2. Endothelium-independent coronary blood flow reserve was similar in both groups (Group 1: 3.31 ± 0.68 and Group 2: 2.97 ± 0.80, p=NS). In response to acetylcholine, coronary blood flow increased to 156.08 ± 36.79 mL/min in Group 1 and to 177.8 ± 83.6 mL/min in Group 2 (p <0.05). Endothelium-dependent coronary blood flow reserve was similar in the two groups (Group 1: 2.08 ± 0.74 and group Group 2: 1.76 ± 0.61, p=NS). Peak acetylcholine/peak adenosine coronary blood flow response (Group 1: 0.65 ± 0.27 and Group 2: 0.60 ± 0.17) and minimal coronary vascular resistance (Group 1: 0.48 ± 0.21 mmHg/mL/min and Group 2: 0.34 ± 0.12 mmHg/mL/min) were similar in both groups (p= NS). Casual diastolic blood pressure and end-systolic left ventricular stress were independently associated with FS. CONCLUSIONS: In our hypertensive patients, endothelium-dependent and endothelium-independent coronary blood flow reserve vasodilator administrations had similar effects in patients with either normal or decreased left ventricular systolic function

CONTAGEM MICROBIANA, ATIVIDADE DE β-GLICOSIDASE E ISOLAMENTO DE FUNGOS TERMOFÍLICOS/TERMOTOLERANTES EM SOLOS COM CULTIVO CONVENCIONAL E AGROECOLÓGICO

A busca por alimentos mais saudáveis e com produção sustentável fez com que nos últimos anos houvesse uma grande expansão dos sistemas agroecológicos de produção, contrapondo-se ao uso de defensivos agrícolas, característico dos sistemas convencionais. Este trabalho teve como objetivo avaliar se os sistemas de manejo e tipos de cultura afetam a quantidade de fungos e bactérias, bem como a atividade de β-glicosidase e a presença de fungos termofílicos/termotolerantes produtores dessa enzima, no solo. Foram feitas oito coletas em uma área com sistemas convencional e agroecológico/orgânico de produção, no município de Fronteira/MG, em três pontos (horta agroecológica; cultivo convencional de abacaxi e cultivo convencional de cana-de-açúcar). Como indicadores da qualidade do solo, foram avaliadas a população de bactérias e fungos, bem como a atividade da enzima β-glicosidase. Além disso, foram isoladas linhagens de fungos termotolerantes/termofílicos do solo e analisado o potencial de produção de β-glicosidase pelos fungos. Verificou-se que os solos provenientes da horta agroecológica e com cultivo convencional de cana-de-açúcar propiciaram quantidades significativamente maiores de fungos e bactérias e também atividades mais elevadas da enzima β-glicosidase, em relação ao solo com cultivo convencional de abacaxi. O solo que propiciou a maior quantidade de fungos com potencial de produção da enzima foi o com cultivo agroecológico de hortaliças, seguido dos solos com cultivo de cana-de-açúcar e abacaxi. Assim, conclui-se que tanto a microbiota quanto a atividade de β-glicosidase foram bons indicadores de qualidade do solo na área estudada

Cosmeceutical potential of grateloupia turuturu: using low-cost extraction methodologies to obtain added-value extracts

The invasive macroalga Grateloupia turuturu is known to contain a diversity of bioactive compounds with different potentialities. Among them are compounds with relevant bioactivities for cosmetics. Considering this, this study aimed to screen bioactivities with cosmeceutical potential, namely, antioxidant, UV absorbance, anti-enzymatic, antimicrobial, and anti-inflammatory activities, as well as photoprotection potential. Extractions with higher concentrations of ethanol resulted in extracts with higher antioxidant activities, while for the anti-enzymatic activity, high inhibition percentages were obtained for elastase and hyaluronidase with almost all extracts. Regarding the antimicrobial activity, all extracts showed to be active against E. coli, S. aureus, and C. albicans. Extracts produced with higher percentages of ethanol were more effective against E. coli and with lower percentages against the other two microorganisms. Several concentrations of each extract were found to be safe for fibroblasts, but no photoprotection capacity was observed. However, one of the aqueous extracts was responsible for reducing around 40% of the nitric oxide production on macrophages, showing its anti-inflammatory potential. This work highlights G. turuturu’s potential in the cosmeceutical field, contributing to the further development of natural formulations for skin protection.info:eu-repo/semantics/publishedVersio

Medidas de distanciamento social podem ter reduzido as mortes estimadas relacionadas à COVID-19 no Brasil

Social distancing was planned as a preventive measure to control the extensive spread of COVID-19. COVID-19-related deaths in Brazil were analyzed during the period of social distancing measures. Mortality data for COVID-19 was obtained from the Worldometer website. Deaths were estimated up to the 31st day after the occurrence of the 5th COVID-19-related death in Brazil. Social distance was measured using Google's community mobility reports. The Brazilian epidemic curves were interconnected, and mathematical models were evaluated to fit the mortality estimation curves. The optimistic model was defined in the opening period of social distancing and, therefore, in the lower mobility (40-60%). The realistic model was calculated according to relaxed social distance measures (&lt;40%) and the pessimistic model was calculated based on the transmission rate between 2-3. Thus, the equations of the mathematical models provided the outcomes for the date of June 9, 2020, as follows: realistic model with 40,623 deaths, pessimistic model with 64,310 deaths and the optimistic model with a projection of 31,384 deaths. As a result of these analyzes, on May 24, 2020, there were a total of 22,965 deaths related to COVID-19, and those deaths included within the proposed mathematical models were 17,452 for the optimistic model, 22,623 for the realistic model and 32,825 for the pessimistic model. Thus, it is concluded that social distancing measures promoted by the Brazilian public managers contributes to the reduction in approximately ten thousand deaths related to COVID-19 in the current pandemic scenario.O distanciamento social foi planejado como uma medida preventiva para controlar a disseminação extensiva da COVID-19. Foi analisado as mortes relacionadas à COVID-19 no Brasil durante o período de medidas de distanciamento social. Os dados de mortalidade do COVID-19 foram obtidos no site da Worldometer. As mortes foram estimadas até o 31º dia após a ocorrência da 5ª morte relacionada à COVID-19 no Brasil. O distanciamento social foi medido por meio dos relatórios de mobilidade comunitária do Google. As curvas epidêmicas brasileiras foram interligadas e os modelos matemáticos foram avaliados para se ajustarem às curvas de estimativa de mortalidade. O modelo otimista foi definido no período de abertura do distanciamento social e, portanto, na menor mobilidade (40-60%). O modelo realista foi calculado de acordo com medidas de distanciamento social relaxado (&lt;40%) e o modelo pessimista foi calculado com base na taxa de transmissão entre 2-3. Assim, as equações dos modelos matemáticos proveram os desfechos para a data de nove de junho de 2020, conforme seguem: modelo realista com 40.623 mortes, modelo pessimista com 64.310 mortes e o modelo otimista com projeção de 31.384. Como resultados dessas análises, na data de 24 de maio de 2020 obteve um total de 22.965 mortes relacionadas com a COVID-19, sendo que essas mortes inseridas dentro dos modelos matemáticos propostos foram de 17.452 para o modelo otimista, 22.623 para o modelo realista e 32.825 para o modelo pessimista. Assim, conclui-se que a medida de distanciamento social promovida pelos gestores públicos brasileiros contribui para a redução em aproximadamente dez mil mortes relacionadas com a COVID-19 no atual cenário pandêmico

Novel scFv against Notch Ligand JAG1 Suitable for Development of Cell Therapies toward JAG1-Positive Tumors

Funding Information: This research was funded by the Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) grant PTDC/BBB-BMD/4497/2014 (to A.B.), through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020), and the Associate Laboratory LS4FUTURE (LA/P/0087/2020). Publisher Copyright: © 2023 by the authors.The Notch signaling ligand JAG1 is overexpressed in various aggressive tumors and is associated with poor clinical prognosis. Hence, therapies targeting oncogenic JAG1 hold great potential for the treatment of certain tumors. Here, we report the identification of specific anti-JAG1 single-chain variable fragments (scFvs), one of them endowing chimeric antigen receptor (CAR) T cells with cytotoxicity against JAG1-positive cells. Anti-JAG1 scFvs were identified from human phage display libraries, reformatted into full-length monoclonal antibodies (Abs), and produced in mammalian cells. The characterization of these Abs identified two specific anti-JAG1 Abs (J1.B5 and J1.F1) with nanomolar affinities. Cloning the respective scFv sequences in our second- and third-generation CAR backbones resulted in six anti-JAG1 CAR constructs, which were screened for JAG1-mediated T-cell activation in Jurkat T cells in coculture assays with JAG1-positive cell lines. Studies in primary T cells demonstrated that one CAR harboring the J1.B5 scFv significantly induced effective T-cell activation in the presence of JAG1-positive, but not in JAG1-knockout, cancer cells, and enabled specific killing of JAG1-positive cells. Thus, this new anti-JAG1 scFv represents a promising candidate for the development of cell therapies against JAG1-positive tumors.publishersversionpublishe