Detection of cytokines in cervicovaginal lavage in HIV-infected women and its association with high-risk human papillomavirus.

Background: Women living with HIV/AIDS (WLHA) have an increased prevalence of high-risk HPV infection (HR-HPV) and cervical intraepithelial neoplasia (CIN) and a greater risk of cervical cancer despite access to a new generation of antiretroviral therapy. The aim of this study is to evaluate the concentrations of different cytokines involved in the local immune response in WLHA, which is fundamental for understanding the pathogenesis of HPV-related cancer in this population. Methods: IL-1ß, IL-2, IL-4, IL-6, IL-10, IFN-γ, TNF-α, IP-10, GM-CSF, and MIP-1α were investigated in the cervicovaginal lavage (CVL) of 106 WLHA attending at Hospital Universitario Professor Edgard Santos in Salvador, Bahia, Brazil, during the period December 2019 to April 2023 by Luminex®. All participants were also tested for Chlamydia trachomatis and Neisseria gonorrhoeae and underwent colposcopy, Pap smear, and Nugent score. HIV plasma viral load (VL) and CD4 cell count were performed for all WLHA. Results: In this study, 22.6% (24/106) of WLHA were infected with HR-HPV. A higher proportion of patients with HR-HPV (66.7%) had detectable levels of IL-10 than those negative ones (40.2%, p = 0.02). More premenopausal women had either IL-6 (51.4%) or IP-10 (58.3%) than those in menopausal status (26.5% for IL-6 and 32.4% for IP-10, p = 0.013 and p = 0.011, respectively). Vaginosis was negatively associated with detection of IP-10 (24.2% vs. 61.4%, p < 0.001) and INF-γ (39.4% vs. 68.6%, p = 0.005). A positive association was detected for IL-1ß (66.7 vs. 37.1%, p = 0.005) and IL-10 (63.6% vs. 37.1%, p = 0.01). VL and CD4 were not associated with the studied cytokines. Conclusion: We demonstrated a positive association between IL-10 and HPV infection in CVL, suggesting the predominance of the Th2 response in HIV/HPV co-infected patients. However, further studies with longer follow-up will be needed to evaluate the association of IL-10 with HPV infection, CIN, and cervical cancer in WLHA.

Predictive genetic panel for adult asthma using machine learning methods.

Background: Asthma is a chronic inflammatory disease of the airways that is heterogeneous and multifactorial, making its accurate characterization a complex process. Therefore, identifying the genetic variations associated with asthma and discovering the molecular interactions between the omics that confer risk of developing this disease will help us to unravel the biological pathways involved in its pathogenesis. Objective: We sought to develop a predictive genetic panel for asthma using machine learning methods. Methods: We tested 3 variable selection methods: Boruta's algorithm, the top 200 genome-wide association study markers according to their respective P values, and an elastic net regression. Ten different algorithms were chosen for the classification tests. A predictive panel was built on the basis of joint scores between the classification algorithms. Results: Two variable selection methods, Boruta and genome-wide association studies, were statistically similar in terms of the average accuracies generated, whereas elastic net had the worst overall performance. The predictive genetic panel was completed with 155 single-nucleotide variants, with 91.18% accuracy, 92.75% sensitivity, and 89.55% specificity using the support vector machine algorithm. The markers used range from known single-nucleotide variants to those not previously described in the literature. Our study shows potential in creating genetic prediction panels with tailored penalties per marker, aiding in the identification of optimal machine learning methods for intricate results. Conclusions: This method is able to classify asthma and nonasthma effectively, proving its potential utility in clinical prediction and diagnosis.

Thr92Ala-DIO2 heterozygosity is associated with skeletal muscle mass and myosteatosis in patients with COVID-19.

INTRODUCTION: The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and COVID-19. OBJECTIVE: To identify a potential association between Thr92Ala-DIO2 polymorphism and body composition (appendicular muscle mass, myosteatosis, and fat distribution) and to determine whether they reflect the severity or mortality associated with the disease. METHODS: In this prospective cohort study (June-August 2020), 181 patients hospitalized with moderate-to-severe COVID-19 underwent a non-contrast-enhanced computed tomography (CT) of the thorax to assess body composition, laboratory tests, and genotyping for the Thr92Ala-DIO2 polymorphism. RESULTS: 181 consecutive patients were stratified into three subgroups according to the genotype: Thr/Thr (n = 64), Thr/Ala (n = 96), and Ala/Ala (n = 21). The prevalence of low muscle area (MA) (< 92 cm²) was 52.5 %. Low MA was less frequent in Ala/Thr patients (44.8%) than in Thr/Thr (60.9%) or Ala/Ala patients (61.9%) (p = 0.027). Multivariate logistic regression analysis confirmed that the Thr/Ala allele was associated with a reduced risk of low MA (41% to 69%) and myosteatosis (62% to 72%) compared with Thr/Thr + Ala/Ala (overdominant model). Kaplan-Meier curves showed that patients with low muscle mass and homozygosity had lower survival rates than the other groups. Notably, the heterozygotes with MA ≥ 92 cm² exhibited the best survival rate. CONCLUSION: Thr92Ala-DIO2 heterozygosity is associated with increased skeletal MA and less myosteatosis in patients with COVID-19. The protective effect of Thr92Ala-DIO2 heterozygosity on COVID-19 mortality is restricted to patients with reduced MA.

The Thr92Ala polymorphism in the type 2 deiodinase gene is linked to depression in patients with COVID-19 after hospital discharge.

Background: The Thr92Ala-DIO2 polymorphism has been associated with clinical outcomes in hospitalized patients with COVID-19 and neuropsychiatric diseases. This study examines the impact of the Thr92Ala-DIO2 polymorphism on neuropsychological symptoms, particularly depressive symptoms, in patients who have had moderate to severe SARS-CoV-2 infection and were later discharged. Methods: Our prospective cohort study, conducted from June to August 2020, collected data from 273 patients hospitalized with COVID-19. This included thyroid function tests, inflammatory markers, hematologic indices, and genotyping of the Thr92Ala-DIO2 polymorphism. Post-discharge, we followed up with 68 patients over 30 to 45 days, dividing them into depressive (29 patients) and non-depressive (39 patients) groups based on their Beck Depression Inventory scores. Results: We categorized 68 patients into three groups based on their genotypes: Thr/Thr (22 patients), Thr/Ala (41 patients), and Ala/Ala (5 patients). Depressive symptoms were less frequent in the Thr/Ala group (29.3%) compared to the Thr/Thr (59.1%) and Ala/Ala (60%) groups (p = 0.048). The Thr/Ala heterozygous genotype correlated with a lower risk of post-COVID-19 depression, as shown by univariate and multivariate logistic regression analyses. These analyses, adjusted for various factors, indicated a 70% to 81% reduction in risk. Conclusion: Our findings appear to be the first to show that heterozygosity for Thr92Ala-DIO2 in patients with COVID-19 may protect against post-COVID-19 depression symptoms up to 2 months after the illness.

Multi-omics in nasal epithelium reveals three axes of dysregulation for asthma risk in the African Diaspora populations.

Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10-9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10-16 and CPA3; p = 2.39 × 10-14) and wound healing (FN1; p = 7.63 × 10-9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora.

Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma.

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.

Mother's smoking habits affects IL10 methylation but not asthma in Ecuadorian children.

There is no evidence evaluating the IL10 epigenetic upregulation among mestizo children in a high-altitude Andean city in Latin America. OBJECTIVE: To identify polymorphisms and methylation profiles in the IL10 gene associated with asthma in children aged 5 to 11. METHODS: A case-control study was conducted with asthmatic and non-asthmatic children aged 5 to 11 years in Cuenca-Ecuador. Data on allergic diseases and risk factors were collected through a questionnaire for parents. Atopy was measured by skin prick test (SPT) to relevant aeroallergens. Three IL10 single nucleotide polymorphisms were evaluated in all participants, and methylation analysis was performed in 54 participants. Association between risk factors, allergic diseases and genetic factors were estimated using multivariate logistic regression. RESULTS: The results of polymorphisms showed no differences between cases and controls when comparing the SNPs rs3024495, rs3024496, rs1800896 allelic and genotypic frequencies. In the methylation analysis, no differences in the IL10 methylation profile were found between cases and controls; however, the multivariate analysis showed an association between the mother's smoking habits and the IL10 methylation profile. CONCLUSION: Smoking habit could be essential as an environmental exposure factor in regulating gene expression in children with asthma.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

The role of IL10 and IL17 gene polymorphisms in treatment response in children and adolescents with severe asthma.

OBJECTIVE: To determine whether polymorphisms of the IL10 and IL17 genes are associated with severe asthma control and bronchodilator reversibility in children and adolescents with severe asthma. METHODS: This was a cross-sectional study, nested within a prospective cohort study of patients with severe asthma. Two outcomes were evaluated: asthma control and bronchodilator reversibility. We extracted DNA from peripheral blood and genotyped three single nucleotide polymorphisms: rs3819024 and rs2275913 in the IL17A gene; and rs3024498 in the IL10 gene. For the association analyses, we performed logistic regression in three genetic models (allelic, additive, and dominant). RESULTS: The rs3024498 C allele in the IL10 gene was associated with failure to achieve asthma control despite regular treatment (p = 0.02). However, the G allele of the IL17A rs3819024 polymorphism was associated with failure to respond to stimulation with a b2 agonist. The rs2275913 polymorphism of the IL17A gene showed no relationship with asthma control or bronchodilator reversibility. CONCLUSIONS: In pediatric patients with severe asthma, the IL10 polymorphism appears to be associated with failure to achieve clinical control, whereas the IL17A polymorphism appears to be associated with a worse bronchodilator response. Knowledge of the involvement of these polymorphisms opens future directions for pharmacogenetic studies and for the implementation of individualized therapeutic management of severe asthma in pediatric patients.

Relationship between permanent upper anterior teeth and anthropometric facial measures in different populations: a narrative review

Aim: The main purpose of this study was to conduct a narrative review investigating the possible relationship between permanent maxillary anterior teeth and anthropometric facial parameters in different populations. Methods: Searches were performed in the PubMed, BVS (Biblioteca Virtual em Saúde) and SciELO databases to identify relevant scientific articles using the following search terms: "maxillary anterior teeth", "facial measurements" and "anthropometry", in such a way that 218 publications were found. After application of inclusion and exclusion criteria, 13 publications remained for full-text reading. Results: All studies involved male and female samples and it was notorious that male measurements were unanimously higher than those obtained in the opposite sex. The age of the analyzed participants ranged from 17 to 60 years; however, a mean age of 18 to 25 years was the most investigated in literature. In addition, facial measurements including the bizygomatic width, interpupillary distance, intercanthal distance, interalar width and intercommissural width have been proposed to help determine the correct size of anterior teeth. Conclusion: It was concluded that despite the limited number of studies, some factors that influence dental and facial dimensions, such as sex and age, can be identified. However, there is no standardization of the facial or dental parameters used in the studies, a fact that makes it difficult to establish a universal ratio for clinical dental practice

Repercussões da COVID-19 na morbidade e mortalidade de crianças indígenas: revisão integrativa / Repercussions of COVID-19 on the morbidity and mortality of indigenous children: integrative review

A doença causada pelo COVID-19 repercutiu na saúde de comunidades indígenas, com taxas de internação e óbitos, principalmente, no segmento infantil. O objetivo do estudo foi identificar evidências científicas acerca das repercussões da COVID-19 na morbidade e mortalidade de crianças indígenas. Trata-se de um estudo de revisão integrativa com a questão de pesquisa: Quais as repercussões da pandemia de COVID-19 nas crianças indígenas? Foram acessadas as fontes de dados PUBMED, WEB OF SCIENCE, LILACS e SCOPUS durante o mês de dezembro de 2023 com as estratégias de busca: "indigenous population" AND "child" AND "coronavirus infections" e "native" AND "child" AND "coronavirus infections" com recorte temporal a partir de 2020. A partir dos critérios de inclusão selecionou-se nove produções científicas. Após a interpretação dos resultados, identificou-se que crianças indígenas apresentam maior risco de mortalidade comparada às crianças não indígenas da mesma idade. Isto pode estar relacionado ao aumento da vulnerabilidade, dificuldade de acesso a alimentos e à prematuridade. Concluiu-se que crianças indígenas apresentaram maiores taxas de mortalidade e outras implicações relacionadas à COVID-19 e repercussões relacionadas às desigualdades sociais já existentes e às vulnerabilidades que aumentaram com a pandemia. Destaca-se a escassa produção científica acerca da população indígena, em especial, às crianças.

The disease caused by COVID-19 had an impact on the health of indigenous communities, with hospitalization and death rates, mainly in the children's segment. The objective of the study was to identify scientific evidence about the repercussions of COVID-19 on the morbidity and mortality of indigenous children. This is an integrative review study with the research question: What are the repercussions of the COVID-19 pandemic on indigenous children? The PUBMED, WEB OF SCIENCE, LILACS and SCOPUS data sources were accessed during the month of December 2023 with the search strategies: "indigenous population" AND "child" AND "coronavirus infections" and "native" AND "child" AND "coronavirus infections", taking 2020 as the epidemiological milestone. Based on the inclusion criteria, nine scientific productions were selected. After interpreting the results, it was identified that indigenous children have a higher risk of mortality compared to non-indigenous children of the same age. This may be related to increased vulnerability, difficulty accessing food and prematurity. It was concluded that indigenous children had higher mortality rates and other implications related to COVID-19 and repercussions related to existing social inequalities and vulnerabilities that increased with the pandemic. The scarce scientific production regarding the indigenous population stands out, especially with regard to children.

MTOR gene variants are associated with severe COVID-19 outcomes: A multicenter study.

BACKGROUND: The worst outcomes linked to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been attributed to the cytokine storm, which contributes significantly to the immunopathogenesis of the disease. The mammalian target of rapamycin (mTOR) pathway is essential for orchestrating innate immune cell defense including cytokine production and is dysregulated in severe Coronavirus Disease 2019 (COVID-19) individuals. The individual genetic background might play a role in the exacerbated immune response. OBJECTIVE: In this study, we aimed to investigate the association between MTOR genetic variants and COVID-19 outcomes. METHODS: This study enrolled groups of individuals with severe (n = 285) and mild (n = 207) COVID-19 from Brazilian states. The MTOR variants, rs1057079 and rs2536, were genotyped. A logistic regression analysis and Kaplan-Meier survival curves were performed. We applied a genotyping risk score to estimate the cumulative contribution of the risk alleles. Tumor necrosis factor (TNF) and interleukin-6 (IL-6) plasma levels were also measured. RESULTS: The T allele of the MTOR rs1057079 variant was associated with a higher likelihood of developing the most severe form of COVID-19. In addition, higher levels of IL-6 and COVID-19 death was linked to the T allele of the rs2536 variant. These variants exhibited a cumulative risk when inherited collectively. CONCLUSIONS: These results show a potential pathogenetic role of MTOR gene variants and may be useful for predicting severe outcomes following COVID-19 infection, resulting in a more effective allocation of health resources.

Genetic variants associated with SARS-CoV-2 infection also affect lung function and asthma severity.

Background: Host genetic factors may be associated with COVID-19 unfavourable outcomes. The first genome-wide association study (GWAS) conducted in individuals with respiratory failure due to COVID-19 revealed susceptibility loci close to six genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1) and the ABO blood-group gene. We aimed to investigate how polymorphisms in those genes could relate to lung function and severe asthma in a Brazilian population. Methods: DNA samples of 784 individuals following the ProAR (Programa para Controle da Asma e Rinite Alérgica da Bahia) were genotyped by the Multi-Ethnic Global Array panel with ∼2 million polymorphisms (Illumina). Polymorphisms in SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6, XCR1 and the ABO blood-group gene were evaluated. Logistic regression for severe asthma, airway obstruction and lack of FEV1 reversibility was performed using PLINK software 1.9, in the additive model and was adjusted for sex, age and PCA-1. Pairwise Linkage disequilibrium analyses were performed using Haploview 4.2. The haplotypes and gene score analyses were performed in the SNPstat tool. In silico functions of polymorphisms were analysed using rSNPbase and RegulomeDB plataforms. Results: We identified the rs8176733 (G allele) and rs8176725 (A allele) in the ABO blood-group gene as risk factors for severe asthma, lower pulmonary obstruction and lack of FEV1 reversibility. Polymorphisms in CCR9 are risk factors for both severe asthma (A allele of rs34338823) and airway obstruction (A allele of rs6806802). The markers rs13079478 (A allele) and rs75817942 (A allele) in FYCO1 are related to more severe asthma and a lack of FEV1 reversibility, respectively. We identified the A allele of both rs35731912 and rs34338823 in LZTFL1 as risk factors for severe asthma. The marker rs6806802 (C allele) was associated with airway obstruction and rs7614952 (A allele), rs7625839 (G allele) and rs112509260 (A allele) are related to a lack of FEV1 reversibility. The A allele of rs2531747 in the SLC6A20 gene is also associated with severe asthma. Conversely, polymorphisms in XCR1 play a protective role in relation to severe asthma (A allele of rs2036295) and airway obstruction (A allele of rs2036295). Additionally, we found that individuals with a higher number of risk alleles have a greater risk of severe asthma, airway obstruction and FEV1 reversibility. Conclusion: Our study suggests that polymorphisms in genes associated with respiratory failure in SARS-CoV-2-infected individuals are associated with greater susceptibility to severe asthma and reduced lung function in subjects with asthma.

PDE4D gene variants and haplotypes are associated with asthma and atopy in Brazilian children.

PDE4D (Phosphodiesterase 4D) gene encodes a hydrolase of cyclic AMP. PDE4D genetic variants have been associated with asthma susceptibility. Therefore, this study aimed to investigate the association between PDE4D variants (and haplotypes) with asthma and atopy in a Brazilian population. The study comprised 1,246 unrelated participants from the SCAALA (Social Changes Asthma and Allergy in Latin America) program. Genotyping was performed using the Illumina 2.5 Human Omni bead chip. Multivariate logistic regression was used to investigate the association between PDE4D variants and asthma/atopy phenotypes in PLINK 1.09 software. Twenty-four SNVs in PDE4D were associated with atopy or asthma. The rs6898082 (A) variant increased asthma susceptibility (OR 2.76; CI 99% 1.26-6.03) and was also related to a greater PDE4D expression in the GTEx database. Also, the variant rs6870632 was further associated with asthma in meta-analysis with a replication cohort. In addition, the variants rs75699812 (C), rs8007656 (G), and rs958851 (T) were positively associated with atopy. Moreover, these variants formed an atopy risk haplotype (OR 1.82; CI 99% 1.15-2.88). Also, these variants were related to lower levels of IL-10. Functional in silico assessment showed that some PDE4D SNVs may have an impact on gene regulation and expression. Variants in the PDE4D are positively associated with asthma and allergy markers. It is possible that these variants lead to alteration in PDE4D expression and therefore impact immunity and pulmonary function.

The rs2601796 variant in ADCY9 gene is associated with severe asthma and less bronchodilator response.

Asthma is a respiratory disease caused by the interaction of genetic and environmental factors. The adenylyl cyclase type 9 (ADCY9) enzyme produces the cyclic-adenosinemonophosphate (cAMP), important mediator involved in bronchodilation and immunomodulatory response. The aim of this study was to investigate if rs2601796 and rs2532019 variants in the ADCY9 gene are associated with asthma and lung function. The study comprised 1,052 subjects. Logistic regressions were done using PLINK 1.9 adjusted by sex, age, BMI, smoke and principal components. Bronchodilator responsiveness was assessed using the percentage of difference in FEV1 before and after the bronchodilator use. The in silico analysis for gene expression was performed in the GTEx Portal. The variant rs2601796 (AA/AG genotype) was positively associated with asthma severity (OR: 1.60 IC95%: 1.08-2.39) and with obstruction in individuals with severe asthma (OR: 3.10, IC95%: 1.11-8.62). Individuals with severe asthma and the AA/AG genotype of rs2601796 had less responsiveness to bronchodilators and also a lower expression of ADCY9 in lung and whole blood. The variant rs2532019 (TT/GT genotype) also downregulated the ADCY9 gene expression, but no significant association with the studied phenotypes was found. Thus, the variant in ADCY9 was associated with worse asthma outcomes, including a lower response to bronchodilators, likely due to the impact on its gene expression rate. This variant may be useful in the future to assist in personalized management of patients with asthma.

Genome-wide association study of Helicobacter pylori serological status in Latin American children.

BACKGROUND: Few genome-wide association studies (GWAS) on Helicobacter pylori infection susceptibility have been conducted for admixed populations from developing countries. Here, we performed a GWAS to identify genetic factors associated with H. pylori serostatus in a cohort of admixed children from a large Latin American urban center. METHODS: A cross-sectional study involving 1161 children from 4 to 11 years old living in poor areas of Salvador, in northeastern Brazil. Logistic regression analysis was performed to detect associations between single-nucleotide variants (SNVs) and H. pylori seropositivity, assuming an additive genetic model. Enrichment analyses were conducted using the MAGMA v1.10 software. RESULTS: We found 22 SNVs to be suggestively associated (p < 10-5 ) with H. pylori seropositivity. The most suggestive SNV was the rs77955022 (p = 4.83e-07) located in an intronic region of EXOC3 at 5p15.33. The second most suggestively associated SNV was rs10914996 (p = 8.97e-07), located in an intergenic region at 1p34.3. Furthermore, we were able to replicate three SNVs (p < 0.05) in the Study of Health in Pomerania (SHIP) cohort: the rs2339212 and rs4795970, both located at 17q12 near TMEM132E, as well as the rs6595814, an intronic variant of FBN2 at 5q23.3. The enrichment analysis indicated the participation of genes and metabolic pathways related to the regulation of the digestive system and gastric acid secretion in the risk of seropositivity for H. pylori. CONCLUSIONS: Additional studies are required to validate these association findings in larger population samples and to get insight into the underlying physiological mechanisms.

Direct antitumoral effects of sulfated fucans isolated from echinoderms: a possible role of neuropilin-1/ß1 integrin endocytosis and focal adhesion kinase degradation.

Hypercoagulability, a major complication of metastatic cancers, has usually been treated with heparins from natural sources, or with their synthetic derivatives, which are under intense investigation in clinical oncology. However, the use of heparin has been challenging for patients with risk of severe bleeding. While the systemic administration of heparins, in preclinical models, has shown primarily attenuating effects on metastasis, their direct effect on established solid tumors has generated contradictory outcomes. We investigated the direct antitumoral properties of two sulfated fucans isolated from marine echinoderms, FucSulf1 and FucSulf2, which exhibit anticoagulant activity with mild hemorrhagic potential. Unlike heparin, sulfated fucans significantly inhibited tumor cell proliferation (by ~30-50%), and inhibited tumor migration and invasion in vitro. We found that FucSulf1 and FucSulf2 interacted with fibronectin as efficiently as heparin, leading to loss of prostate cancer and melanoma cell spreading. The sulfated fucans increased the endocytosis of ß1 integrin and neuropilin-1 chains, two cell receptors implicated in fibronectin-dependent adhesion. The treatment of cancer cells with both sulfated fucans, but not with heparin, also triggered intracellular focal adhesion kinase (FAK) degradation, with a consequent overall decrease in activated focal adhesion kinase levels. Finally, only sulfated fucans inhibited the growth of B16-F10 melanoma cells implanted in the dermis of syngeneic C57/BL6 mice. FucSulf1 and FucSulf2 arise from this study as candidates for the design of possible alternatives to long-term treatments of cancer patients with heparins, with the advantage of also controlling local growth and invasion of malignant cells.

Permanent health education actions in pandemic times: priorities in state and national contingency plans. / Ações de educação permanente em saúde em tempos de pandemia: prioridades nos planos estaduais e nacional de contingência.

OBJECTIVE: to assess permanent health education actions regarding the national and state contingency plans to face the COVID-19 pandemic in Brazil. METHOD: documentary research, using 54 plans in the initial and final versions, published between January 2020 and May 2021. The content analysis included the identification and systematization of proposals aimed at training and reorganizing the work process, as well as physical and mental health care of health workers. RESULTS: the actions were focused on training workers with an emphasis on flu syndrome, infection risk control measures and knowledge about biosafety. Few plans addressed the teams' working hours and work process, promotion and assistance to the workers' mental health, mainly in the hospital environment. CONCLUSION: the superficiality regarding the approach to permanent education actions in contingency plans need to include actions in the strategic agenda of the Ministry of Health and State and Municipal Health Secretariats, with the qualification of workers to face this and other epidemics. They propose the adoption of health protection and promotion measures in daily health work management within the scope of the SUS.

OBJETIVO: analisar ações de educação permanente em saúde nos Planos Nacional e Estaduais de Contingência para enfrentamento à pandemia de COVID-19 no Brasil. METODOLOGIA: pesquisa documental, com utilização de 54 planos nas versões iniciais e finais, publicados entre janeiro de 2020 e maio de 2021. A análise do conteúdo contemplou identificação e sistematização das propostas voltadas para capacitação e reorganização do processo de trabalho e cuidados à saúde física e mental dos trabalhadores de saúde. RESULTADOS: as ações voltaram-se à capacitação dos trabalhadores com ênfase em síndrome gripal, medidas de controle de riscos de infeção e conhecimento sobre biossegurança. Poucos planos abordaram jornadas e processo de trabalho das equipes, promoção e assistência à saúde mental dos trabalhadores principalmente no âmbito hospitalar. CONCLUSÃO: superficialidade nas abordagens das ações de educação permanente nos planos de contingência, necessidade de inclusão de ações na agenda estratégica do Ministério da Saúde e das secretarias estaduais e municipais de saúde com qualificação dos trabalhadores para enfrentar esta e outras epidemias. Propõe adoção de medidas de proteção e promoção da saúde no cotidiano da gestão do trabalho em saúde no âmbito do SUS.

Ações de educação permanente em saúde em tempos de pandemia: prioridades nos planos estaduais e nacional de contingência / Permanent health education actions in pandemic times: priorities in state and national contingency plans

Resumo Objetivo: analisar ações de educação permanente em saúde nos Planos Nacional e Estaduais de Contingência para enfrentamento à pandemia de COVID-19 no Brasil. Metodologia: pesquisa documental, com utilização de 54 planos nas versões iniciais e finais, publicados entre janeiro de 2020 e maio de 2021. A análise do conteúdo contemplou identificação e sistematização das propostas voltadas para capacitação e reorganização do processo de trabalho e cuidados à saúde física e mental dos trabalhadores de saúde. Resultados: as ações voltaram-se à capacitação dos trabalhadores com ênfase em síndrome gripal, medidas de controle de riscos de infeção e conhecimento sobre biossegurança. Poucos planos abordaram jornadas e processo de trabalho das equipes, promoção e assistência à saúde mental dos trabalhadores principalmente no âmbito hospitalar. Conclusão: superficialidade nas abordagens das ações de educação permanente nos planos de contingência, necessidade de inclusão de ações na agenda estratégica do Ministério da Saúde e das secretarias estaduais e municipais de saúde com qualificação dos trabalhadores para enfrentar esta e outras epidemias. Propõe adoção de medidas de proteção e promoção da saúde no cotidiano da gestão do trabalho em saúde no âmbito do SUS.

Abstract Objective: to assess permanent health education actions regarding the national and state contingency plans to face the COVID-19 pandemic in Brazil. Method: documentary research, using 54 plans in the initial and final versions, published between January 2020 and May 2021. The content analysis included the identification and systematization of proposals aimed at training and reorganizing the work process, as well as physical and mental health care of health workers. Results: the actions were focused on training workers with an emphasis on flu syndrome, infection risk control measures and knowledge about biosafety. Few plans addressed the teams' working hours and work process, promotion and assistance to the workers' mental health, mainly in the hospital environment. Conclusion: the superficiality regarding the approach to permanent education actions in contingency plans need to include actions in the strategic agenda of the Ministry of Health and State and Municipal Health Secretariats, with the qualification of workers to face this and other epidemics. They propose the adoption of health protection and promotion measures in daily health work management within the scope of the SUS.

Genetic polymorphism (rs6587666) in FLG protects from eczema in admixed Brazilian children population with high African ancestry.

Genetic variants in filaggrin (FLG) are key in eczema and are less common in Africans than in Europeans and Asians. Here we examined the association between FLG Single Nucleotide Polymorphisms (SNPs) and eczema in a population of admixed Brazilian children and whether African ancestry modifies this association. We included 1010 controls and 137 cases and ran logistic regressions between SNPs in FLG and eczema in the studied population and also stratified the analyses according to the degree of African ancestry. In addition, we tested the replication of the findings on an independent set of individuals, as well as, we verified the impact on FLG expression according to each SNP genotype. The T allele of SNP rs6587666 was negatively associated with eczema in additive model (OR: 0.66, 95% CI: 0.47-0.93, P: 0.017). Moreover, African ancestry modifies the association between rs6587666 and eczema. The effect of the T allele was higher among individuals with higher African ancestry and the association with eczema was lost in individuals with lower African ancestry. In our analyses the expression of FLG in skin was slightly downregulated by the presence of the T allele of rs6587666. In our population, the T allele of rs6587666 in FLG was associated with protection to eczema and the degree of African ancestry was able to modify the observed association.