Resumo: O objetivo foi estimar a prevalência do atraso nas três doses da vacina tetravalente (DTP+Hib) em crianças de 12 a 23 meses de idade, no Brasil, por meio dos dados da Pesquisa Nacional de Saúde (PNS) de 2013 e descrever o atraso em cada uma das doses segundo variáveis sociodemográficas, utilização de serviços e intervenções públicas de saúde. Foram utilizados dados da PNS, estudo transversal realizado em 2013. O desfecho foi o atraso pelo menos em uma das três doses da vacina tetravalente. Considerou-se como atraso a dose recebida pelo menos 30 dias após a data preconizada, segundo informação da caderneta de vacinação. A prevalência do atraso foi descrita segundo variáveis sociodemográficas e utilização de serviços de saúde. Realizou-se análise descritiva obtendo-se frequências absolutas e relativas e seus respectivos intervalos de 95% de confiança. Das 2.016 crianças com informações coletadas, 1.843 foram analisadas. A prevalência de atraso de pelo menos uma dose da vacina foi de 44%. Observou-se atraso de 14,8% na primeira, 28,8% na segunda e 45,4% na terceira dose, sendo que 10% das crianças tiveram atraso nas três doses. Maiores prevalências de atraso foram encontradas em crianças do sexo masculino, de cor da pele parda, pertencentes ao quintil mais pobre de riqueza, moradores da zona rural e da Região Norte do Brasil. Evidenciou-se alta prevalência de atraso na vacina tetravalente (DTP+Hib) em crianças de 12 a 23 meses do Brasil, sendo maior na terceira dose.

Background/Objectives: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety. Methods: Thirty-seven healthy volunteers, enrolled after rigorous health assessments, received a single dose of etodolac (Flancox^® 500 mg). Pharmacokinetic profiles were determined using tandem mass spectrometry analysis, and the metabolomic profiling was conducted using baseline samples (pre-dose) and samples at maximum drug concentration (post-dose) via liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Network analysis was employed to interpret the data. Results: Correlations were observed between metabolomic profiles and pharmacokinetic parameters as well as clinical characteristics. Notably, metabolites derived from arachidonic acid, such as prostaglandins and leukotrienes, were linked to etodolac’s pharmacokinetics. Other metabolites involved in pathways like cholesterol biosynthesis, bile salts, riboflavin, and retinoic acid signaling were correlated with hematological and liver function parameters. These findings are consistent with the infrequent adverse events reported by participants, including hematological and biochemical changes in liver function. Conclusions: A set of metabolites was identified in possible associations between specific pathways and unusual side effects, comparing the metabolic profiles before and after doses of etodolac. Our results highlight the importance of optimizing drug therapy and minimizing adverse events by taking into account individual metabolic profile information.

Analysis of the CFTR gene in Venezuelan cystic fibrosis patients, identification of six novel cystic fibrosis-causing genetic variants Karen Sánchez,1 Elizabeth de Mendonca,1 Xiorama Matute,2 Ismenia Chaustre,2 Marlene Villalón,3 Howard Takiff4 1Unit of Genetic and Forensic Studies, Venezuelan Institute for Scientific Research (IVIC), 2Hospital JM de los Ríos, 3Hospital José Ignacio Baldo, Algodonal, National Reference Unit, 4Laboratory of Molecular Genetics, Venezuelan Institute for Scientific Research (IVIC), Caracas, Venezuela. The mutations in the CFTR gene found in patients with cystic fibrosis (CF) have geographic differences, but there are scant data on their prevalence in Venezuelan patients. This study determined the frequency of common CFTR gene mutations in a group of Venezuelan patients with CF. The 27 exons of the CFTR gene from 110 Venezuelan patients in the National CF Program were amplified and sequenced. A total of 36 different mutations were identified, seven with frequencies greater than 1%: p.Phe508del (27.27%), p.Gly542* (3.18%), c.2988+1G.A (3.18%), p.Arg334Trp (1.36%), p.Arg1162* (1.36%), c.1-8G.C (1.36%), and p.[Gly628Arg;Ser1235Arg](1.36). In 40% of patients, all with a clinical diagnosis of CF, no mutations were found. This report represents the largest cohort of Venezuelan patients with CF ever examined, and includes a wider mutation panel than has been previously studied in this population. Mutations common in Southern European populations predominate, and several new mutations were discovered, but no mutations were found in 40% of the cohort. Keywords: c.49_50dupTT, c.3963+1G.A, p.Asp373Asn, p.Glu815*, p.Asn900Lys, p.Trp277*

We aimed to test the association between sleep-related polygenic scores (PGSs) and accelerometer-based sleep metrics among Brazilian adolescents and to evaluate potential mechanisms underlying the association through the enrichment of obesity, and cortisol pathway-specific polygenic scores (PRSet). Utilizing data from The 2004 Pelotas (Brazil) Birth Cohort, sleep time window and sleep efficiency were measured at the 11-year-old follow-up using ActiGraph accelerometers. Three sleep PGSs were developed based on the most recent genome-wide association study of accelerometer-based sleep measures. PRSet, calculated using variants linked to body mass index (BMI) and plasmatic cortisol concentration, aimed to assess pleiotropic effects. Linear regression models, adjusted for sex and the first 10 principal components of ancestry, were employed to explore the impact of sleep PGS and specific-PRSet on sleep phenotypes. The number of nocturnal sleep episodes-PGS was positively associated with sleep time window (β = 2.306, SE: 0.92, p = .011). Nocturnal sleep episodes were also associated with sleep time window when restricted to BMI-PRSet (β = 2.682, SE: 0.912, competitive p = .003). Both the number of sleep episodes and sleep time window cortisol-PRSets were associated (β = .002, SE: 0.001, p = .013; β = .003, SE: 0.001, p = .003, respectively) and exhibited enrichment in molecular pathways (competitive p = .011; competitive p = .003, respectively) with sleep efficiency. Sleep polygenetic components observed in European adults may partially explain the accelerometer-based sleep time window in Brazilian adolescents. Specific BMI molecular pathways strengthened the association between sleep PGS and sleep time window, while the cortisol concentration pathway had a significant impact on the genetic liability for sleep efficiency. Our results suggest genetic overlap as a potential etiological pathway for sleep-related comorbidities, emphasizing common genetic mechanisms.