Reverse Myocardial Remodeling in Hypertrophic Cardiomyopathy: Little Explored Benefit of Exercise

International Journal of Exercise Science 14(2): 1018-1026, 2021. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disease that causes myocardial remodeling. Physical exercise (PE) is a therapeutic resource used in Supervised Cardiac Rehabilitation (SCR) to improve Quality of Life (QL), reducing cardiovascular morbidity and mortality. Therefore, the aim of this study is to report how SCR using a personalized exercise prescription, promoted Reverse Myocardial Remodeling (RMR), improved functionality and QL of a patient with HCM. This is a case report of a 43-year-old sedentary female patient with a Body Mass Index (BMI) of 24.7 kg/m2. The patient was diagnosed with Septal Type Asymmetric HCM. Heart Failure (HF) grade III / IV, according to the New York Heart Association (NYHA), was initially treated with 40mg of Propranolol Hydrochloride twice a day, and presented with excessive fatigue, and angina. The echocardiogram showed a final diastolic volume (FDV) of 130 ml, a final systolic volume (FSV) of 44 ml, a left ventricular mass (LVM) of 236 g, interventricular septum thickness of 14 mm, left ventricular posterior wall (LVPW) thickness of 9 mm, left atrium diameter 46 mm, left ventricular end diastolic diameter of 52mm, septum/left ventricular wall ratio of 1.55 mm, and ejection fraction (EF) of 66% (Teicholz). It was obtained as a result of decreased FDV 130 vs. 102ml, decreased FSV 44 vs. 32 ml, decreased LVM 236 vs. 201 g, increased EF 66 vs. 69%, 26% improvement in QL, and 50% reduction in the dosage of Propranolol Hydrochloride. These results suggest that a personalized SCR program is an adjuvant treatment capable of promoting RMR and improving QL and functionality in a patient with HCM

Design and Synthesis of CNS-targeted Flavones and Analogues with Neuroprotective Potential Against H2O2- and Aβ1-42-Induced Toxicity in SH-SY5Y Human Neuroblastoma Cells

With the lack of available drugs able to prevent the progression of Alzheimer’s disease (AD), the discovery of new neuroprotective treatments able to rescue neurons from cell injury is presently a matter of extreme importance and urgency. Here, we were inspired by the widely reported potential of natural flavonoids to build a library of novel flavones, chromen-4-ones and their C-glucosyl derivatives, and to explore their ability as neuroprotective agents with suitable pharmacokinetic profiles. All compounds were firstly evaluated in a parallel artificial membrane permeability assay (PAMPA) to assess their effective permeability across biological membranes, namely the blood-brain barrier (BBB). With this test, we aimed not only at assessing if our candidates would be well-distributed, but also at rationalizing the influence of the sugar moiety on the physicochemical properties. To complement our analysis, logD7.4 was determined. From all screened compounds, the p-morpholinyl flavones stood out for their ability to fully rescue SH-SY5Y human neuroblastoma cells against both H2O2- and Aβ1-42-induced cell death. Cholinesterase inhibition was also evaluated, and modest inhibitory activities were found. This work highlights the potential of C-glucosylflavones as neuroprotective agents, and presents the p-morpholinyl C-glucosylflavone 37, which did not show any cytotoxicity towards HepG2 and Caco-2 cells at 100 μM, as a new lead structure for further development against AD.Fundação para a Ciência e a Tecnologia-UID/Multi/0612/2019Unión Europea-D3i4AD), FP7-PEOPLE-2013-IAPP, GA 61234

Seqüência nucleotídica completa do genoma de Pepper mild mottle virus isolado no Distrito Federal, Brasil

Occurrence of Pepper mild mottle virus (PMMoV) on Capsicum plants has become common in Brazil. Despite the importance of this virus, genome information is still lacking for South American isolates. In this report, the first complete genome sequence of a Brazilian isolate of PMMoV (BR-DF01) was elucidated and compared with other PMMoV sequences. The nucleotide sequence of the complete genome of BR-DF01 isolate shared the highest nucleotide identity (99.54%) with the Japanese isolate JP-J, which does not overcome L3 resistance gene of Capsicum plants, as also observed for BR-DF01. The coat protein (CP) amino acid sequence of these two isolates was identical, which suggested that CP is the key factor for L-based resistance breaking. Phylogenetic analysis implied that BR-DF01 and PMMoV isolates belonging to Cluster I, including JP-J isolate, may share a common ancestral origin.A ocorrência do Pepper mild mottle virus (PMMoV) em plantas de Capsicum tornou-se frequente no Brasil. Apesar da importância desse vírus, informações genômicas de isolados sul-americanos são ainda escassos. Neste trabalho, foi elucidada a sequência do genoma completo de um isolado brasileiro de PMMoV (BR-DF01) e esta foi comparada a outras sequências de PMMoV. A sequência de nucleotídeos do genoma completo do isolado BR-DF01 apresentou a maior identidade (99,54%) com o isolado japonês JP-J, que é capaz de contornar a resistência do gene L3 de plantas de Capsicum, como foi também observado para BR-DF01. A sequência de amino ácidos da capa protéica (CP) desses dois isolados foi idêntica, sugerindo que a CP é o fator-chave para a quebra de resistência baseada no gene L. Análises filogenéticas indicaram que BR-DF01 e isolados de PMMoV pertencentes ao agrupamento I, incluindo o isolado JP-J, podem compartilhar de um ancestral em comum

Formação de professores e o atendimento ao público-alvo da Educação Especial

El trabajo en cuestión se desarrolló a partir de una encuesta de carácter exploratorio - donde matrices curriculares y programas de estudio relacionadas con Educación Especial y / o Educación Inclusiva, Lengua de Signos Brasileña (Libras) y prácticas en Educación Especial y / o Educación Inclusiva de IES en el Estado de Río de Janeiro - y los relatos de experiencia de un maestro de Educación Especial. Buscamos comprender cómo la formación inicial, a un nivel superior, ha preparado a los futuros profesores de educación básica para trabajar con estudiantes con discapacidad. Entendiendo la asistencia escolar a clases regulares como un derecho de este público, atendiendo a sus necesidades específicas, merece atención la preparación de los profesionales que los recibirán en las escuelas públicas. A través de las experiencias presentadas, reflexionamos y hacemos recomendaciones sobre el proceso de formación docente y los desafíos que enfrentan estos profesionales para brindar asistencia educativa al público objetivo de Educación Especial. Los resultados apuntan a una formación aún deficiente de los futuros docentes en esta área, aunque ya estén actuando durante la graduación como mediadores de estos estudiantes en la educación básica

Skin picking treatment with the Rothbaum cognitive behavioral therapy protocol : a randomized clinical trial

Introduction: Although behavioral therapies can effectively treat skin picking disorder (SPD), there is no standardized treatment for improving SPD and its comorbidities and there is no group intervention option. This trial aimed to adapt the Rothbaum trichotillomania protocol to SPD (Study 1) and test its efficacy for treating SPD and comorbidities in individual and group formats (Study 2). Methods: The adapted protocol was applied to 16 SPD patients, who were allocated to group or individual treatment (Study 1). Afterwards, 54 patients were randomly allocated to treatment in an individual (n=27) or group format (n=27) (Study 2). In both studies, assessments of SPD severity, anxiety, depression, clinical status and skin lesion severity were performed at baseline and the endpoint. Results: The adapted protocol was feasible in both treatment modalities (Study 1) and led to high SPD remission rates (individual 63%; group 52%), with no significant difference between intervention types (p = 0.4) (Study 2). SPD, anxiety, and depression symptoms and objective patient lesion measures improved after treatment. There was large effect size for SPD symptom improvement in both treatment types (Cohen’s d: group = 0.88; individual = 1.15) (Study 2). Conclusion: The adapted Rothbaum protocol was effective for SPD remission, comorbidities, and skin lesions, both in individual and group formats

Padrões de variação genética em loci sob selecção na abelha ibérica: comparação da selecção balanceada e direccional

A Península Ibérica tem sido reconhecida como um "hotspot" de diversidade c endemismo para diversas espécies quer animais quer vegetais. Em parte esta grande diversidade encontrada na Península Ibérica deve-se ao flicto de este local ter sido utilizado como refúgio por diferentes espécies durante as glaciaçôes A abelha é um dos muitos casos onde este processo aconteceu. Na verdade, a Península Ibérica é umas das regiões da Europa onde esta espécie apresenta uma maior diversidade c complexidade genética. A abelha ibérica que está distribuída pela Península Ibérica é o fruto de uma hibridação natural entre a linhagem Africana c a linhagem da Europa ocidental. O estudo de zonas híbridas tem sido muito importante para compreender os processos evolutivos que levaram à complexidade genética tão característica dos refúgios O objectivo deste trabalho é fazer uma abordagem inicial para perceber como é que os diferentes tipos de selecção (balanceadora e direccional) influenciam a diversidade genética das abelhas na Península Ibérica e tentar perceber qual o papel da selecção na divergência adaptativa das populações. Para tal foram calculadas algumas cstatisticas sumárias e também toram utilizados diversos sothvares que implementam algoritmos Bayesianos de forma a verificar que estrutura é captada ao utilizar-se as regiões do genoma sob diferentes tipos de selecção (balanceadora ou direccional). No total foram detectados 22 loci sob selecção usando o Bayescan, 9 dos quais apresentavam aparentam estar sob de uma selecção balanceada c 13 sob selecção direccional. Neste trabalho é representado o padrão obtido utilizado software "STRUCTURE

2,4,5-Triaminopyrimidines as blue fluorescent probes for cell viability monitoring: synthesis, photophysical properties, and microscopy applications

Monitoring cell viability is critical in cell biology, pathology, and drug discovery. Most cell viability assays are cell-destructive, time-consuming, expensive, and/or hazardous. Herein, we present a series of newly synthesized 2,4,5-triaminopyrimidine derivatives able to discriminate between live and dead cells. To our knowledge, these compounds are the first fluorescent nucleobase analogues (FNAs) with cell viability monitoring potential. These new fluorescent molecules are synthesized using highly efficient and cost- effective methods and feature unprecedented photophysical properties (longer absorption and emission wavelengths, environment-sensitive emission, and unprecedented brightness within FNAs). Using a live– dead Saccharomyces cerevisiae cell and theoretical assays, the fluorescent 2,4,5-triaminopyrimidine derivatives were found to specifically accumulate inside dead cells by interacting with dsDNA grooves, thus paving the way for the emergence of novel and safe fluorescent cell viability markers emitting in the blue region. As the majority of commercially available viability dyes emit in the green to red region of the visible spectrum, these novel markers might be useful to meet the needs of blue markers for co-staining combinations

Effects of proteasome inhibitor MG-132 on the parasite Schistosoma mansoni

Proteasome is a proteolytic complex responsible for intracellular protein turnover in eukaryotes, archaea and in some actinobacteria species. Previous work has demonstrated that in Schistosoma mansoni parasites, the proteasome inhibitor MG-132 affects parasite development. However, the molecular targets affected by MG-132 in S. mansoni are not entirely known. Here, we used expression microarrays to measure the genome-wide changes in gene expression of S. mansoni adult worms exposed in vitro to MG-132, followed by in silico functional analyses of the affected genes using Ingenuity Pathway Analysis (IPA). Scanning electron microscopy was used to document changes in the parasites' tegument. We identified 1,919 genes with a statistically significant (q-value <= 0.025) differential expression in parasites treated for 24 h with MG-132, when compared with control. Of these, a total of 1,130 genes were up-regulated and 790 genes were down-regulated. A functional gene interaction network comprised of MG-132 and its target genes, known from the literature to be affected by the compound in humans, was identified here as affected by MG-132. While MG-132 activated the expression of the 26S proteasome genes, it also decreased the expression of 19S chaperones assembly, 20S proteasome maturation, ubiquitin-like NEDD8 and its partner cullin-3 ubiquitin ligase genes. Interestingly, genes that encode proteins related to potassium ion binding, integral membrane component, ATPase and potassium channel activities were significantly down-regulated, whereas genes encoding proteins related to actin binding and microtubule motor activity were significantly up-regulated. MG132 caused important changes in the worm tegumentpeeling, outbreaks and swelling in the tegument tubercles could be observed, which is consistent with interference on the ionic homeostasis in S. mansoni. Finally, we showed the down-regulation of Bax pro-apoptotic gene, as well as up-regulation of two apoptosis inhibitor genes, IAP1 and BRE1, and in contrast, down-regulation of Apaf-1 apoptotic activator, thus suggesting that apoptosis is deregulated in S. mansoni exposed to MG-132. A considerable insight has been gained concerning the potential of MG-132 as a gene expression modulator, and overall the data suggest that the proteasome might be an important molecular target for the design of new drugs against schistosomiasis.Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto, SP, BrazilUniv Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo, SP, BrazilAdolfo Lutz Inst, Ctr Parasitol & Micol, Nucleo Enteroparasitas, Sao Paulo, SP, BrazilUniv Franca, Nucleo Pesquisa Ciencias Exatas & Tecnol, Grp Pesquisa Prod Nat, Franca, SP, BrazilInst Butantan, Lab Expressao Genica Eucariotos, Sao Paulo, SP, BrazilUniv Fed Uberlandia, Inst Genet Bioquim, Campus Patos de Minas, Patos De Minas, MG, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Discipline Parasitol, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Inst Biol, Ctr Ciencias & Saude, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Discipline Parasitol, Sao Paulo, SP, BrazilWeb of Scienc