The introduction of SARS-CoV-2 variants of concern (VOCs) in Brazil has been associated with major impacts on the epidemiological and public health scenario. In this study, 291,571 samples were ...investigated for SARS-CoV-2 variants from August 2021 to March 2022 (the highest peak of positive cases) in four geographical regions of Brazil. To identify the frequency, introduction, and dispersion of SARS-CoV-2 variants in 12 Brazilian capitals, VOCs defining spike mutations were identified in 35,735 samples through genotyping and viral genome sequencing. Omicron VOC was detected in late November 2021 and replaced the Delta VOC in approximately 3.5 weeks. We estimated viral load differences between SARS-CoV-2 Delta and Omicron through the evaluation of the RT-qPCR cycle threshold (Ct) score in 77,262 samples. The analysis demonstrated that the Omicron VOC has a lower viral load in infected patients than the Delta VOC. Analyses of clinical outcomes in 17,586 patients across the country indicated that individuals infected with Omicron were less likely to need ventilatory support. The results of our study reinforce the importance of surveillance programs at the national level and showed the introduction and faster dispersion of Omicron over Delta VOC in Brazil without increasing the numbers of severe cases of COVID-19.
Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study ...has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R. Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders. Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance. Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance. Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.
RESUMO. Polimorfismos da monoaminoxidase A (MAOA) são associados a transtornos antissociais. Menos atenção tem sido dada ao funcionamento cognitivo de indivíduos com diferentes alelos de MAOA. Nenhum estudo descreveu o fenótipo cognitivo associado ao alelo menos frequente, de baixa atividade enzimática, MAOA_LPR*2R. Objetivo: Descrevemos os correlatos cognitivos de meninos com o alelo MAOA_LPR*2R, identificados em uma amostra de escolares com inteligência normal, não encaminhados por transtornos de comportamento. Métodos: Oito meninos com o alelo MAOA_LPR*2R foram identificados entre 712 crianças genotipadas, com inteligência típica, que cursavam do 2º ao 5º ano em escolas públicas. Foram avaliados: inteligência, desempenho em matemática e ortografia, memória de trabalho verbal e visuoespacial. O desempenho foi comparado a normas publicadas, utilizando-se 1 desvio padrão (DP) abaixo da média como ponto de corte para desempenho rebaixado. Resultados: A inteligência dos meninos com alelo MAOA_LPR*2R variou de acima da média (N=2) a médio-inferior nas demais crianças. Cinco dos oito meninos com alelo MAOA_LPR*2R apresentaram desempenho rebaixado em matemática e três apresentaram dificuldades adicionais em ortografia. Quatro dos oito meninos apresentaram baixo desempenho de memória de curto prazo e de trabalho. Discussão: Este é o primeiro estudo a descrever os correlatos cognitivos e o desempenho escolar em meninos com alelo MAOA_LPR*2R. Ter esse alelo não significa necessariamente baixa inteligência ou baixo desempenho escolar. No entanto, dificuldades de aprendizagem, principalmente em matemática, e desempenho rebaixado da memória de trabalho foram observados em mais da metade dos meninos com esse alelo. Isso sugere um papel do MAOA nas dificuldades de aprendizagem.
Math anxiety (MA) seems to result from an interaction of genetic vulnerability with negative experiences learning mathematics. Although mathematics achievement does not substantially differ between ...the sexes, MA levels are usually higher in girls. Molecular genetic markers of MA vulnerability have been seldom explored. This article examines the contribution of the monoamine oxidase A gene (MAOA) to MA and to sex differences in MA. Five hundred and sixty‐eight third to fifth graders were genotyped for the MAOA‐LPR polymorphism (a repetitive element in MAOA promoter that has been associated with MAOA enzymatic activity), and assessed on general cognitive ability, mathematics achievement, and the cognitive and affective dimensions of MA. MAOA‐LPR genotypes were classified as high (MAOA‐H) or low (MAOA‐L) according to their predicted enzymatic activity. Mixed models controlling for effects of school, sex, general cognitive ability, and mathematics achievement were evaluated. The best fitting model included school, math achievement, sex, MAOA‐LPR, and the MAOA‐LPR by sex interaction. This indicated that under the MAOA‐H dominant model, anxiety toward mathematics interacted with the MAOA genotype: girls with an MAOA‐L genotype exhibited higher levels of MA, with a small but significant effect. The association between MAOA‐L genotype and MA in girls may represent an example of developmental plasticity.
Third to fifth graders self‐reported on the cognitive and affective dimensions of math anxiety (MA) and were genotyped for the MAOA‐LPR polymorphism, a repetitive element in the MAOA promoter associated with MAOA enzymatic activity. Interactions between genotype, sex, and MA were analyzed under different genetic models. Girls with the low activity (MAOA‐L), as opposed to boys and girls with the high activity (MAOA‐H) genotype, reported higher levels of affective MA.
Monoamine oxidase A (MAOA) polymorphisms have been associated with antisocial disorders. Less attention has been paid to the cognitive functioning of individuals with different MAOA alleles. No study ...has described the cognitive phenotype associated with the less frequent, low enzyme activity allele, MAOA_LPR*2R. Objective: We describe the cognitive correlates of boys having MAOA_LPR*2R allele, ascertained in a sample of school children with normal intelligence, not referred for behavioral disorders. Methods: Participants were eight boys, attending from the second to fifth grades in state-run schools. They were identified among 712 children with typical general cognitive ability, genotyped for MAOA_LPR polymorphism. Participants were assessed with general intelligence, mathematics and spelling achievement, and verbal and visuospatial working memory tests. Neuropsychological performance was compared to published standards, using 1 SD below the mean as a cutoff value for low performance. Results: Intelligence of boys with MAOA_LPR*2R allele varied from above average (N=2) to low average in the other children. Five out of eight boys with the MAOA_LPR*2R allele had low mathematics achievement, and three presented additional difficulties with spelling. Four out of eight children had low short-term and working memory performance. Discussion: This is the first study describing cognitive correlates and school performance in boys having the MAOA_LPR*2R allele. Having this allele, and therefore, probably low MAO-A activity, does not necessarily imply low intelligence or low school performance. However, learning difficulties, particularly in math, and low working memory performance were observed in boys having this allele. This suggests a role of MAOA in learning difficulties.
This study aimed to report the first case of a patient with hepatosplenic schistosomiasis mansoni, refractory ascites and portal vein thrombosis treated with a transjugular intrahepatic portosystemic ...shunt (TIPS), at the Instituto de Radiologia, Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, Brazil. After the procedure, the patient recovered favorably and progressed with portal pressure reduction and no deterioration of the liver function. Endovascular shunt modification is a conservative medical approach that often helps in reducing symptoms significantly, making it a less invasive and a safer alternative to liver transplantation for the treatment of schistosomiasis with portal hypertension.
Purpose
Bariatric endoscopy is a less invasive approach for obesity management, with better efficacy than pharmacological treatment and low morbidity. Endoscopic sleeve gastroplasty (ESG) is the ...remodeling of the stomach using a suturing device showing technical feasibility, safety, and sustained weight loss. With growing numbers of procedures worldwide, there is a need to standardize the procedure.
Materials and Methods
A consensus meeting was held in São Caetano do Sul-SP, Brazil, in June 2019, bringing together 47 Brazilian endoscopists with experience in ESG from all regions of the country. Topics on indications and contraindications of the procedure, pre-procedure evaluation and multidisciplinary follow-up, technique and post-procedure follow-up, and training requirements were discussed. An electronic voting was carried, and a consensus was defined as ≥ 70% agreement.
Results
The panel’s experience consisted of 1828 procedures, with a mean percentage total body weight loss (TBWL) of 18.2% in 1 year. Adverse events happened in 0.8% of the cases, the most common being hematemesis. The selected experts discussed and reached a consensus on several questions concerning patient selection, contraindications for the procedure, technical details such as patient preparation, procedure technique, and patient follow-up.
Conclusions
This consensus establishes practical guidelines for performance of ESG. The experience of 1828 procedures shows the expertise of the selected specialists participating in this consensus statement. The group’s experience has a satisfactory weight loss with low adverse events rate. The main points discussed in this paper may serve as a guide for endoscopists performing ESG. Practical recommendations and technique standardization are described.
Selenium (Se) is an essential element for human and animal, although considered beneficial to higher plants. Selenium application at high concentration to plants can cause toxicity decreasing the ...physiological quality of seeds. This study aimed to characterize the Se toxicity on upland rice yield, seed physiology and the localization of Se in seeds using X-ray fluorescence microanalysis (μ-XRF). In the flowering stage, foliar application of Se (0, 250, 500, 1000, 1500, 2000 g ha−1) as sodium selenate was performed. A decrease in rice yield and an increase in seed Se concentrations were observed from 250 g Se ha−1. The storage proteins in the seeds showed different responses with Se application (decrease in albumin, increase in prolamin and glutelin). There was a reduction in the concentrations of total sugars and sucrose with the application of 250 and 500 g Se ha−1. The highest intensities Kα counts of Se were detected mainly in the endosperm and aleurone/pericarp. μ-XRF revealed the spatial distribution of sulfur, calcium, and potassium in the seed embryos. The seed germination decreased, and the electrical conductivity increased in response to high Se application rates showing clearly an abrupt decrease of physiological quality of rice seeds. This study provides information for a better understanding of the effects of Se toxicity on rice, revealing that in addition to the negative effects on yield, there are changes in the physiological and biochemical quality of seeds.
•Foliar Se application above 250 g ha-1decrease rice yield and physiological seed quality.•The highest Kα counts of Se were detected mainly in the endosperm and aleurone/pericarp.•Sulfur accumulation occurred in the same tissues and in the embryo region.•The μ-XRF was a great technique to map the distribution of Se in rice seeds.
Seaweed lectins are very promising biotechnological tools that also gain prominence when applied to the pharmacology field. The purpose of the present work was to isolate and characterize lectin from ...the red algae Amansia multifida and subsequently test it in general inflammation models. The lectin was purified by ion exchange chromatography, characterized with two-dimensional electrophoresis, automated analysis of amino acid sequences and circular dichroism spectroscopy. The pharmacological tests performed were paw edema induced by carrageenan or rapid inflammatory mediators, peritonitis induced by carrageenan and myeloperoxidase leukocyte count assays, glutathione and cytokine concentration. Our results have identified a 30 KDa molecular weight protein that presents a major secondary structure arranged in β-strand elements (~43%). A fragment of 20 amino acid residues was sequenced and presented low identity to the known classes of lectins from marine alga. This lectin was able to modulate inflammatory parameters such as paw edema, leukocyte migration, oxidative stress and proinflammatory cytokines. Thus, the lectin from the seaweed Amansia multifida has evident anti-inflammatory properties because it acts by reducing the formation of edema by modulating the effect of vascular mediators, migration of neutrophils, proinflammatory cytokines and oxidative stress control.
To better understand the immune microenvironment of pancreatic ductal adenocarcinomas (PDACs), here we explored the relevance of T and B cell compartmentalisation into tertiary lymphoid structures ...(TLSs) for the generation of local antitumour immunity.
We characterised the functional states and spatial organisation of PDAC-infiltrating T and B cells using single-cell RNA sequencing (scRNA-seq), flow cytometry, multicolour immunofluorescence, gene expression profiling of microdissected TLSs, as well as in vitro assays. In addition, we performed a pan-cancer analysis of tumour-infiltrating T cells using scRNA-seq and sc T cell receptor sequencing datasets from eight cancer types. To evaluate the clinical relevance of our findings, we used PDAC bulk RNA-seq data from The Cancer Genome Atlas and the PRINCE chemoimmunotherapy trial.
We found that a subset of PDACs harbours fully developed TLSs where B cells proliferate and differentiate into plasma cells. These mature TLSs also support T cell activity and are enriched with tumour-reactive T cells. Importantly, we showed that chronically activated, tumour-reactive T cells exposed to fibroblast-derived TGF-β may act as TLS organisers by producing the B cell chemoattractant CXCL13. Identification of highly similar subsets of clonally expanded
tumour-infiltrating T cells across multiple cancer types further indicated a conserved link between tumour-antigen recognition and the allocation of B cells within sheltered hubs in the tumour microenvironment. Finally, we showed that the expression of a gene signature reflecting mature TLSs was enriched in pretreatment biopsies from PDAC patients with longer survival after receiving different chemoimmunotherapy regimens.
We provided a framework for understanding the biological role of PDAC-associated TLSs and revealed their potential to guide the selection of patients for future immunotherapy trials.
•RCB-4 is a cycle peptide with an MW of 2229.78 Dalton, and the sequence is “ARCCLVMPVPPFACVKFCSSA.”.•RCB-4 was resistant to trypsin, endo-Glu, and endo-Asp enzymes.•RCB-4 inhibited parasite growth ...by up to 50 % at 10 and 15 µg/mL (4.48 µM and 6.73 µM).•Ultrastructural studies showed that trypomastigotes incubated with natural or synthetic RCB-4 could impair T. cruzi proliferation and cause ultrastructural alterations, such as Golgi apparatus disorganization and mitochondrial swelling.•This cyclic peptides emerged as promising organic compounds with diverse pharmacological activities.•Our data allow us to prospect using RCB-4 to combat the parasites T. cruzi and T. gondii.
Chagas disease and toxoplasmosis caused by parasites Trypanosoma cruzi and Toxoplasma gondii affect more than 28 million people in poor areas of Latin America. There is an urgent need for therapeutic options as the treatments are related to efficacy, lower costs, and shorter administration time. Encouraged by the need to discover valid targets and new treatment options, we evaluated castor seed compounds against T. cruzi and T. gondii, considering their effects against proliferation, infection, and ultrastructure.
castor seed extract was fractionated by Gel-filtration chromatography using the Sephadex G-50 resin, and a fraction with MW <10 kDa, denoted LMWF, was isolated. The effect of this fraction against T. cruzi and T. gondii was investigated. LMWF was repurified by HPLC-Reverse Phase chromatography using C-18 column. The major isolated peptide, with antiprotozoal activity, denoted RCB-4, was characterized by SDS-PAGE, mass spectrometry, and “in silico” studies. To understand the mechanism of action underlying RCB-4 against T. cruzi activity, we investigated ultrastructural changes by optical and electron microscopy.
RCB-4 is a cycle peptide with an MW of 2229.78 Dalton, and the sequence is “ARCCLVMPVPPFACVKFCSSA.” RCB-4 was resistant to trypsin, endo-Glu, and endo-Asp enzymes. It inhibited parasite growth by up to 50 % at 10 and 15 µg/mL (4.48 µM and 6.73 µM), inside and outside the cells, respectively. Ultrastructural studies showed that trypomastigotes incubated with natural or synthetic RCB-4 could impair T. cruzi proliferation and cause ultrastructural alterations, such as Golgi apparatus disorganization and mitochondrial swelling.
Cyclic peptides emerged as promising organic compounds with diverse pharmacological activities. They possess superior therapeutic value due to the particular structures conferring resistance to enzymatic degradation and higher bioavailability. Our data allow us to prospect using RCB-4 to combat the parasites T. cruzi and T. gondii.
