168 research outputs found
Associations between variants in SERPINA1, SLC6A14 e SLC26A9 genes and cystic fibrosis.
No full textIntroduction: Cystic fibrosis (CF) is an autosomal recessive, multisystemic and potentially lethal disease, which incidence is higher in Caucasian population. CF aetiology is characterized by the presence of pathogenic variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes a homonymous protein. CF heterogeneity is high in frequency and complexity of its clinical manifestations and modifier genes are described as one of the factors that regulates the phenomenon. Objective: To establish the frequency of allelic variants in SERPINA1, SLC6A14 and SLC26A9 genes and to analyze their influence on the heterogeneity of clinical manifestations in individuals with CF. Materials and Methods: The study is cross-sectional. Genomic DNA samples from 56 individuals were subjected to real-time PCR (qPCR) technique in order to identify the genotypes of rs28929474 (SERPINA1), rs3788766 (SLC6A14) and rs7512462 (SLC26A9) variants. The Gene-Calc, dbSNP (NCBI), RegulomeDB 2.0.3 and HaploReg 4.1 platforms were consulted for determining the Hardy-Weinberg Equilibrium and obtaining genetic and functional data on the analyzed variants. The association between variants and CF-related clinical variables was determined by binomial logistic regression which was performed in RStudio 2022.07.0 software, in which four genetic models were considered: allelic, dominant, recessive and additive. Results: The minor alleles frequencies (MAF) for the rs3788766 and rs7512462 variants were A (0.41) and C (0.4), respectively. All of the alleles in rs28929474 variant were represented by nucleotide C. The rs3788766 variant was significantly associated with dornase alfa use in the recessive (OR = 0.23; p = 0.04) and additive (OR = 0.23; p = 0.04) models, occurrence of pulmonary exacerbations in dominant model (OR = 9.09; p = 0.04), nutritional risk of overweight in the allelic (OR = 4.48; p = 0.03), recessive (OR = 16.03; p = 0.02), and additive (OR = 19.73; p = 0.03) models, and nutritional risk of malnutrition in the allelic (OR = 0.22; p = 0.03), recessive (OR = 0.06; p = 0.02), and additive (OR = 0.05; p = 0.03) models. No significant associations were observed for the rs7512462 variant. Conclusions: The A and C alleles related to rs3788766 and rs7512462 variants, respectively, were frequent among the people in the study. The rs3788766 variant was associated with markers of lung disease (use of dornase alfa and episodes of lung exacerbations) and, especially, nutritional risk of overweight and malnutrition.Fundação de Amparo à Pesquisa do Estado da BahiaIntrodução: A fibrose cística é uma doença autossômica recessiva, multissistêmica e potencialmente letal, com maior incidência em populações de origem caucasiana. A sua etiologia é caracterizada pela presença de variantes patogênicas no gene CFTR, o qual codifica uma proteína homônima. Ela apresenta grande heterogeneidade na frequência e na complexidade das suas manifestações clínicas e os genes modificadores são descritos como um dos fatores que regulam este fenômeno. Objetivo: Estabelecer a frequência de variantes alélicas nos genes SERPINA1, SLC6A14 e SLC26A9 e analisar a sua influência na heterogeneidade das manifestações clínicas de indivíduos acometidos pela doença. Materiais e Métodos: Trata-se de um estudo de corte transversal. As amostras de DNA genômico de 56 indivíduos foram submetidas à técnica da PCR em tempo real (qPCR) para a identificação dos genótipos das variantes rs28929474 (SERPINA1), rs3788766 (SLC6A14) e rs7512462 (SLC26A9). As plataformas Gene-Calc, dbSNP (NCBI), RegulomeDB 2.0.3 e HaploReg 4.1 foram consultadas para a determinação do Equilíbrio de Hardy-Weinberg e para a obtenção de dados genéticos e funcionais sobre as variantes analisadas. A associação entre as variantes e as variáveis clínicas relacionadas à fibrose cística foi determinada por uma regressão logística binomial realizada no software RStudio 2022.07.0, na qual quatro modelos genéticos foram considerados: alélico, dominante, recessivo e aditivo. Resultados: Os alelos de menores frequências para as variantes rs3788766 e rs7512462 foram o A (0,41) e C (0,4), respectivamente. Todos os alelos da variante rs28929474 foram representados pelo nucleotídeo C. A variante rs3788766 foi associada significativamente ao uso de dornase alfa nos modelos recessivo (OR = 0,23; p = 0,04) e aditivo (OR = 0,23; p = 0,04), à ocorrência de exacerbação pulmonar no modelo dominante (OR = 9,09; p = 0,04), ao risco nutricional para sobrepeso nos modelos alélico (OR = 4,48; p = 0,03) recessivo (OR= 16,03; p = 0,02) e aditivo (OR = 19,73; p = 0,03), e ao risco nutricional para desnutrição nos modelos alélico (OR = 0,22; p = 0,03), recessivo (OR = 0,06; p = 0,02) e aditivo (OR= 0,05; p = 0,03). Não foram observadas associações significativas para a variante rs7512462. Conclusões: Os alelos A e C relacionados às variantes rs3788766 e rs7512462, respectivamente, foram frequentes entre os sujeitos incluídos no estudo. A variante rs3788766 foi associada aos marcadores da doença pulmonar (uso de dornase alfa e episódios de exacerbação pulmonar) e, principalmente, ao risco nutricional para sobrepeso e desnutrição
O CENÁRIO DOS DADOS EPIDEMIOLÓGICOS DESCRITIVOS E A IMPORTÂNCIA PARA O CONTROLE DA PANDEMIA DA COVID-19 NO BRASIL
No full textJustificativa e objetivos: No Brasil o acesso aos dados epidemiológicos da COVID-19 é escasso. Dessa forma, descrevemos aspectos que poderiam ser divulgados para o uso nas tomadas de decisão de saúde pública. Métodos: Foram coletados dados do censo sobre o número de casos e de óbitos, letalidade, incidência e mortalidade por cem mil habitantes, SRAG causada pelo SARS-CoV-2 ou outro vírus, % de ocupação de UTI e de isolamento social, número de testes de RT-PCRs e % de testes realizados perante o total de amostras coletadas. Resultados: Houve um aumento no número de SRAG em 2020 se comparado aos casos de anos anteriores. O número de testes de RT-PCRs foi realizado, principalmente em pacientes graves com a COVID-19. Alguns estados do Brasil realizaram a análise do material coletado para a RT-PCR de apenas uma parcela de indivíduos. No Brasil, existe uma aparente subnotificação de casos da doença e que pode compreender ~44 mil indivíduos em estado grave ou de óbitos, bem como, mais de ~700 mil indivíduos com gravidade leve ou assintomáticos. Conclusão: No Brasil, temos limitado acesso a informações que caracterizem a realidade do momento em que vivemos perante a pandemia da COVID-19. Os dados epidemiológicos, principalmente, referentes ao número de novos casos, de óbitos e de internações pela COVID-19 e a análise da adesão ao isolamento social são de extrema importância para viabilizar na tomada de decisões para o melhor manejo da COVID-19 em caráter nacional no setor de saúde pública e privada do Brasil e do mundo
Forgetting what shouldn't be forgotten: the new normal after the COVID-19 pandemic in Brazil
No full textPolymorphisms on key genes of the inflammatory response in allergic asthma, and their role in cystic fibrosis and severe acute viral bronchiolitis
No full textOrientador: José Dirceu RibeiroTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: Introdução: Variantes genéticas em genes relacionados a resposta inflamatória atuam na presença e/ou gravidade da asma alérgica, fibrose cística (FC) e bronquiolite viral aguda grave (BVAG). Objetivo: Descrever e verificar as associações entre variáveis clínicas e laboratoriais de pacientes com asma alérgica, FC e BVAG. Comparar a presença e a gravidade destas doenças com o genótipo de 251 polimorfismos em 125 genes distintos. Método: Foram incluídos 244 pacientes com asma alérgica, 273 com FC, 186 com BVAG e 536 controles saudáveis. Realizou-se a técnica de OpenArray para a triagem do genótipo dos polimorfismos. As variáveis clínicas e laboratoriais foram obtidas nos prontuários dos pacientes, entrevista com pais e/ou responsáveis, exame clínico e/ou exame laboratorial. A avaliação de marcadores clínicos e laboratoriais foram 44, 34 e 32 na asma alérgica, FC e BVAG, respectivamente. Para análise estatística utilizou-se o software SPSS versão 22.0, considerando ?=0,05. Resultados: A apresentação dos resultados está descrita pelo número de genes e polimorfismos, respectivamente, associados para cada variável entre parênteses. Asma alérgica: presença da doença (56/79); gravidade da doença (11/12); comparação de asma persistente com intermitente (18/20); grau de controle da doença (16/20); graus de gravidade da doença versus controles saudáveis [intermitente (35 genes, cinco exclusivos); persistente leve (39 genes, cinco exclusivos); persistente moderada (44 genes, três exclusivos); persistente grave (34 genes, oito exclusivos)]; graus de controle da doença versus controles saudáveis [não controlada (38 genes, cinco exclusivos); parcialmente controlada (23 genes, três exclusivos); controlada (54 genes, 22 exclusivos)]; CVF% (14/15); VEF1% (6/7); CVF/VEF1 (12/20); FEF25-75% (12/19); pneumonia de repetição (9/9); índice de massa corpórea (IMC) (12/14); atopia (19/19); e tempo para início dos sintomas (14/14). FC: comparação com controles saudáveis (42/53), idade do paciente (19/42), início dos sintomas (geral e pulmonar) (11/13), tempo para diagnóstico (13/14); IMC (24/28); polipose nasal (10/12); identificação de bactérias [tempo para identificação de Pseudomonas aeruginosa (8/10); presença de P. aeruginosa mucoide (6/8) e não mucoide (11/11); Achromobacter xylosoxidans (9/9); Burkholderia cepacia (8/9) e Staphylococcus aureus (5/5)]; escores de gravidade [Bhalla (10/11), Kanga (15/16) e Shwachman-Kulczcki (17/18)]; função pulmonar pré-broncodilatador inalatório [SaO2 (9/11), CVF% (10/10), VEF1% (12/13), VEF1/CVF (4/5) e FEF25-75% (7/8)] e função pulmonar pós broncodilatador inalatório [CVF% (10/10), VEF1% (12/13), VEF1/CVF (4/5) e FEF25-75% (7/8)]. BVAG: comparação com controles saudáveis (51/65); tempo de internação (6/9); oxigenoterapia (4/7); ventilação mecânica (6/6); necessidade de UTI (4/4); vírus identificado [VSRA (11/14), VSRB (8/10), Rinovírus (12/12) e coinfecção (9/10)] e óbito (4/5). Na comparação da frequência genotípica dos polimorfismos com a presença de asma alérgica + FC + BVAG, em comparação aos controles saudáveis houve diferença para 47 polimorfismos, em 40 genes distintos; em contrapartida, quando agrupamos asma alérgica + BVAG versus controles saudáveis houve associação com 86 polimorfismos, em 60 genes distintos. A análise descritiva dos dados, associações entre as variáveis clínicas e laboratoriais entre si, e a associação das mutações no gene CFTR com os marcadores de gravidade da FC não estão apresentados no resumo. Conclusão: As variantes genéticas avaliadas atuam na presença e/ou gravidade da asma alérgica, FC e BVAGAbstract: Introduction: Genetic variants of genes involved in the inflammatory response act in the presence and/or severity of allergic asthma, cystic fibrosis (CF), severe acute viral bronchiolitis (SAVB). Objective: To describe and verify the associations between clinical and laboratory variables of patients with allergic asthma, CF and SAVB. Comparing the presence and severity of these diseases with the genotype of 251 polymorphisms of 125 genes. Methods: In the present study was enrolled 244 patients with allergic asthma, 273 with CF, 186 with SAVB and 536 healthy controls. The polymorphisms genotypes were achieved by OpenArray technique. Clinical and laboratory data were obtained from medical records of patients, interviews with parents and/or guardians, clinical and/or laboratory tests. The clinical and laboratory markers evaluated were 44, 34 and 32 in allergic asthma, CF and SAVB, respectively. Statistical analysis was performed using SPSS version 22.0 considering ? = 0.05. Results: The presentation of results are described, respectively, by the number of genes and polymorphisms associated to each variable, in parentheses. Allergic asthma: presence of disease (56/79); disease severity (11/12); persistent asthma compared with intermittent (18/20); degree of disease control (16/20); degrees of severity of the disease versus healthy controls [intermittent (35 genes, five unique); mild persistent (39 genes, five unique); moderate persistent (44 genes, three unique); severe persistent (34 genes, eight unique)]; degrees of control of the disease versus healthy controls [uncontrolled (38 genes, five unique); partially controlled (23 genes, three unique); controlled (54 genes, 22 unique); FVC% (14/15); FEV1% (6/7); FVC/FEV1 (12/20); FEF25-75% (12/19); recurrent pneumonia (9/9); body mass index (BMI) (12/14); atopy (19/19); and time of onset of symptoms (14/14). CF: compared with healthy controls (42/53); age of patients (19/42); onset of symptoms (combined and lung disease) (11/13); time for diagnosis (13/14); BMI (24/28); nasal polyposis (10/12); bacteria identification [time to identification for the first Pseudomonas aeruginosa (8/10); presence of mucoid P. aeruginosa (6/8) and non-mucoid P. aeruginosa (11/11); Achromobacter xylosoxidans (9/9); Burkholderia cepacia (8/9) and Staphylococcus aureus (5/5)]; severity scores [Bhalla (10/11), Kanga (15/16) and Shwachman-Kulczcki (17/18 )]; pulmonary function pre-inhaled bronchodilator [SaO2 (9/11), FVC% (10/10), FEV1% (12/13), FEV1/FVC (4/5) and FEF25-75% (7/8)] and lung function post inhaled bronchodilator [FVC% (10/10), FEV1% (12/13), FEV1/FVC (4/5) and FEF25-75% (7/8)]. SAVB: compared with healthy controls (51/65); hospitalization time (6/9); oxygen therapy (4/7); mechanical ventilation (6/6); need for ICU (4/4); identified virus [RSVA (11/14), RSVB (8/10), rhinovirus (12/12) and coinfection (9/10)] and death (4/5). Comparing the genotypic frequency of polymorphisms in the presence of allergic asthma + CF + SAVB, compared to healthy controls there were difference for 47 polymorphisms in 40 different genes; however, when we grouped allergic asthma + SAVB versus healthy controls there was association with 86 polymorphisms in 60 different genes. The descriptive data analysed, associations between clinical and laboratory variables each other, and the association of mutations in the CFTR gene with the markers of severity are not presented in the final abstract. Conclusion: Genetic variants evaluated act in the presence and/or severity of allergic asthma, CF and SAVBDoutoradoSaude da Criança e do AdolescenteDoutor em Ciências2011/12939-4FAPES
Classification of CFTR mutation classes
No full textsem informação48E37E38sem informaçãosem informaçã
The hindrances to perform the COVID-19 vaccination in Brazil
No full textINTRODUCTION: Brazil is one of the epicenters of COVID-19 pandemic and faces several hindrances to make his COVID-19 vaccination plan efficient. METHODS: The Brazilian COVID-19 vaccination plan was evaluated and the hindrances to make the COVID-19 vaccination plan efficient were described and discussed. RESULTS: High territorial extension might contribute to a delay on the COVID-19 vaccination, due to difficulty in delivering vaccines to furthest Brazilian states and to all the interior cities. The choice among the vaccines should be done based on the type of storage and must consider the transport conditions necessary to maintain its effectiveness. The indigenous individuals were included with health-care workers as the first group to be vaccinated, inflaming the number of vaccines doses distributed in states where the indigenous population have higher prevalence. The antivaccine movement and the politicization of the vaccine are also hindrances to be overcome in Brazil. The COVID-19 incidence or mortality rate and the distribution of intensive care units (ICUs) are not a criterion to distribute the vaccines, as we did not identify a correlation between these markers and the number of vaccines. However, a strong or very strong correlation occurred between the number of COVID-19 vaccines and the number of COVID-19 cases, deaths by COVID-19, gross domestic product, as well as populational density. A total of 83,280,475 doses of COVID-19 vaccines were distributed in Brazil. In the first dose, the Coronavac (Sinovac™), AZD1222 (AstraZeneca/Oxford™), and BNT162b (Pfizer/BioNTech™) vaccines were responsible to vaccinate, respectively, 9.61%, 6.69%, and 0.35% of the Brazilian population. In the second dose, the Coronavac, AZD1222, and BNT162b vaccines were responsible to vaccinate, respectively, 7.52%, 0.53%, and <0.01% of the Brazilian population. CONCLUSIONS: The Federal Government must evaluate the hindrances and propose solutions to maximize the immunization against COVID-19 on Brazil
Human Development Index Is Associated with COVID-19 Case Fatality Rate in Brazil: An Ecological Study
No full textThe Human Development Index measures a region’s development and is a step for development debate beyond the traditional, economic perspective. It can also determine the success of a country’s response to the COVID-19 pandemic, mainly affecting the case fatality rate among severe cases of SARS-CoV-2 infection. We aimed to associate the Human Development Index with the case fatality rate due to COVID-19 in each Brazilian state and the Federal District, taking into account comorbidities and the need for invasive mechanical ventilation. We also evaluated the influence of the GINI index, number of intensive care unit beds, and occupied households in subnormal clusters on the case fatality rate. We performed an ecological study including two populations: COVID-19 individuals that did not require the mechanical ventilation protocol; and COVID-19 individuals under invasive mechanical ventilation. We performed a Pearson correlation test and a univariate linear regression analysis on the relationship between Human Development Index, Human Development Index—Education Level, Human Development Index—Life Expectancy, and Human Development Index—Gross National Income per capita and COVID-19 deaths. The same analyses were performed using the other markers. We grouped the patients with COVID-19 according to comorbidities and the need for invasive mechanical ventilation. Alpha = 0.05. We included 848,501 COVID-19 individuals, out of which 153,710 needed invasive mechanical ventilation and 314,164 died, and 280,533 COVID-19 individuals without comorbidity, out of which 33,312 needed invasive mechanical ventilation and 73,723 died. We observed a low negative Pearson correlation between the Human Development Index and death and a moderate negative Pearson correlation between the Human Development Index and deaths of individuals on invasive mechanical ventilation, with or without comorbidity. The univariate linear analysis showed the case fatality rate depends on at least 20–40% of the Human Development Index. In Brazil, regions with a low Human Development Index demonstrated a higher case fatality rate due to COVID-19, mainly in individuals who needed invasive mechanical ventilation, than regions with a higher Human Development Index. Although other indexes studied, such as intensive care unit beds and GINI, were also associated with the COVID-19 case fatality rate, they were not as relevant as the Human Development Index. Brazil is a vast territory comprising cultural, social, and economic diversity, which mirrors the diversity of the Human Development Index. Brazil is a model nation for the study of the Human Development Index’s influence on aspects of the COVID-19 pandemic, such as its impact on the case fatality rate
Retraction of Clinical Trials about the SARS-CoV-2 Infection: An Unaddressed Problem and Its Possible Impact on Coronavirus Disease (COVID)-19 Treatment
No full textWe are presenting an overview of the retracted clinical trials about the Coronavirus Disease (COVID)-19 published in PubMed using the descriptors ((COVID-19 OR SARS-CoV-2) AND (Clinical Trial)). We collected the information for i) the first author’s country; ii) the journal name where the study was published; iii) the impact factor of the journal; iv) the main objective of the study; v) methods including population, intervention, study design, and outcomes; and vi) results and conclusions. We collected complete information from the retraction notes published by the journals and the number of publications/retractions related to non-COVID-19 clinical trials published simultaneously. We also included the Altmetric index for the clinical trials and the retraction notes about COVID-19 to compare the accessibility to both studies’ indexes. The retraction of clinical trials occurred in four countries (one in Lebanon, one in India, one in Brazil, and five in Egypt) and six journals (one in Viruses, one in Archives of Virology, one in Expert Review of Anti-infective Therapy, one in Frontiers in Medicine, two in Scientific Reports, and two in The American Journal of Tropical Medicine and Hygiene). Eight drugs were tested (Ivermectin, Vitamin D, Proxalutamide, Hydroxychloroquine, Remdesevir, Favipiravir, and Sofosbuvir + Daclatasvir) in the studies. One of the retractions was suggested by the authors due to an error in the statistical analysis, which compromised their results and conclusions. Also, the methods, mainly the allocation, were not well conducted in the two studies, and the studies were retracted. In addition, the studies performed by Dabbous et al. presented several issues, mainly including several raw datasets that did not prove their findings. Moreover, two studies were retracted due to data overlap and copying. Significant concerns were raised about the integrity of the data and reported results in another article. We identified a higher Altmetric index for the original studies, proving that the retracted studies were accessed more than the retraction notes. Interestingly, the impact of the original articles is much higher than their retraction notes. The different Altmetric indexes show that possibly people who read those retracted articles are not reading their retraction notes and are unaware of the erroneous information they share. COVID-19- related clinical trials were ~two-time times more retracted than the other clinical trials performed during the same time
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