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This study investigated how gene expression is affected by dietary fatty acids (FA) by using pigs as a reliable model for studying human diseases that involve lipid metabolism. This includes changes in FA composition in the liver, blood serum parameters and overall metabolic pathways. RNA-Seq data from 32 pigs were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Our aim was to identify changes in blood serum parameters and gene expression between diets containing 3% soybean oil (SOY3.0) and a standard pig production diet containing 1.5% soybean oil (SOY1.5). Significantly, both the SOY1.5 and SOY3.0 groups showed significant modules, with a higher number of co-expressed modules identified in the SOY3.0 group. Correlated modules and specific features were identified, including enriched terms and pathways such as the histone acetyltransferase complex, type I diabetes mellitus pathway, cholesterol metabolism, and metabolic pathways in SOY1.5, and pathways related to neurodegeneration and Alzheimer's disease in SOY3.0. The variation in co-expression observed for HDL in the groups analyzed suggests different regulatory patterns in response to the higher concentration of soybean oil. Key genes co-expressed with metabolic processes indicative of diseases such as Alzheimer's was also identified, as well as genes related to lipid transport and energy metabolism, including CCL5, PNISR, DEGS1. These findings are important for understanding the genetic and metabolic responses to dietary variation and contribute to the development of more precise nutritional strategies.

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Despite efforts to elucidate Zika virus (ZIKV) teratogenesis, still several issues remain unresolved, particularly on the molecular mechanisms behind the pathogenesis of Congenital Zika Syndrome (CZS). To answer this question, we used bioinformatics tools, animal experiments and human gene expression analysis to investigate genes related to brain development potentially involved in CZS. Searches in databases for genes related to brain development and CZS were performed, and a protein interaction network was created. The expression of these genes was analyzed in a CZS animal model and secondary gene expression analysis (DGE) was performed in human cells exposed to ZIKV. A total of 2610 genes were identified in the databases, of which 1013 were connected. By applying centrality statistics of the global network, 36 candidate genes were identified, which, after selection resulted in nine genes. Gene expression analysis revealed distinctive expression patterns for PRKDC, PCNA, ATM, SMC3 as well as for FGF8 and SHH in the CZS model. Furthermore, DGE analysis altered expression of ATM, PRKDC, PCNA. In conclusion, systems biology are helpful tools to identify candidate genes to be validated in vitro and in vivo. PRKDC, PCNA, ATM, SMC3, FGF8 and SHH have altered expression in ZIKV-induced brain malformations.

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Teratogenesis testing can be challenging due to the limitations of both in vitro and in vivo models. Test-systems, based especially on human embryonic cells, have been helping to overcome the difficulties when allied to omics strategies, such as transcriptomics. In these test-systems, cells exposed to different compounds are then analyzed in microarray or RNA-seq platforms regarding the impacts of the potential teratogens in the gene expression. Nevertheless, microarray and RNA-seq dataset processing requires computational resources and bioinformatics knowledge. Here, a pipeline for microarray and RNA-seq processing is presented, aiming to help researchers from any field to interpret the main transcriptome results, such as differential gene expression, enrichment analysis, and statistical interpretation. This chapter also discusses the main difficulties that can be encountered in a transcriptome analysis and the better alternatives to overcome these issues, describing both programming codes and user-friendly tools. Finally, specific issues in the teratogenesis field, such as time-course analysis, are also described, demonstrating how the pipeline can be applied in these studies.

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BACKGROUND: Mapping expression quantitative trait loci (eQTLs) in skeletal muscle tissue in pigs is crucial for understanding the relationship between genetic variation and phenotypic expression of carcass traits in meat animals. Therefore, the primary objective of this study was to evaluate the impact of different sets of single nucleotide polymorphisms (SNP), including scenarios removing SNPs pruned for linkage disequilibrium (LD) and SNPs derived from SNP chip arrays and RNA-seq data from liver, brain, and skeletal muscle tissues, on the identification of eQTLs in the Longissimus lumborum tissue, associated with carcass and body composition traits in Large White pigs. The SNPs identified from muscle mRNA were combined with SNPs identified in the brain and liver tissue transcriptomes, as well as SNPs from the GGP Porcine 50 K SNP chip array. Cis- and trans-eQTLs were identified based on the skeletal muscle gene expression level, followed by functional genomic analyses and statistical associations with carcass and body composition traits in Large White pigs. RESULTS: The number of cis- and trans-eQTLs identified across different sets of SNPs (scenarios) ranged from 261 to 2,539 and from 29 to 13,721, respectively. Furthermore, 6,180 genes were modulated by eQTLs in at least one of the scenarios evaluated. The eQTLs identified were not significantly associated with carcass and body composition traits but were significantly enriched for many traits in the "Meat and Carcass" type QTL. The scenarios with the highest number of cis- (n = 304) and trans- (n = 5,993) modulated genes were the unpruned and LD-pruned SNP set scenarios identified from the muscle transcriptome. These genes include 84 transcription factor coding genes. CONCLUSIONS: After LD pruning, the set of SNPs identified based on the transcriptome of the skeletal muscle tissue of pigs resulted in the highest number of genes modulated by eQTLs. Most eQTLs are of the trans type and are associated with genes influencing complex traits in pigs, such as transcription factors and enhancers. Furthermore, the incorporation of SNPs from other genomic regions to the set of SNPs identified in the porcine skeletal muscle transcriptome contributed to the identification of eQTLs that had not been identified based on the porcine skeletal muscle transcriptome alone.

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Warner-Bratzler Shear Force (WBSF) is a quantitative measurement of meat toughness that has great impact on the consumer acceptability of meat. This study was conducted to evaluate growth performance, carcass and meat quality characteristics, and fatty acids profile of longissimus lumborum (LL) intramuscular fat (IMF) of pigs that are genetically divergent for WBSF. Based on WBSF values of the LL from a previous study, 12 immunocastrated male pigs selected from 96 pigs were divided into two groups with high WBSF (53.28 to 42.50 N) and low WBSF (37.27 to 27.79 N). Although high-WBSF pigs tended to have improved (P = 0.08) gain-to-feed ratio, overall performance was similar between WBSF groups. High-WBSF pigs also tended to have higher (P = 0.09) cooling loss and lean percentage as well as decreased (P = 0.08) 10th-rib backfat depth than low-WBSF pigs. Loins from high-WBSF pigs tended to have lower (P = 0.07) IMF content and higher (P = 0.09) cooking loss than low-WBSF pigs. Compared to low-WBSF pigs, IMF of the LL from high-WBSF pigs had lower (P = 0.05) percentage of oleic acid and tended to have a decreased (P = 0.07) percentage of total monounsaturated fatty acids. Loins from pigs with high WBSF tended to have increased (P = 0.09) total polyunsaturated fatty acids (PUFA) content and had higher (P = 0.03) PUFA: saturated fatty acid ratio than low-WBSF pigs. Selecting pigs for pork tenderness could potentially conflict with lean growth efficiency and a healthier fatty acids profile for human consumption.

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Glioblastoma (GB) is the most aggressive primary malignant brain tumor and is associated with short survival. O-GlcNAcylation is an intracellular glycosylation that regulates protein function, enzymatic activity, protein stability, and subcellular localization. Aberrant O-GlcNAcylation is related to the tumorigenesis of different tumors, and mounting evidence supports O-GlcNAc transferase (OGT) as a potential therapeutic target. Here, we used two human GB cell lines alongside primary human astrocytes as a non-tumoral control to investigate the role of O-GlcNAcylation in cell proliferation, cell cycle, autophagy, and cell death. We observed that hyper O-GlcNAcylation promoted increased cellular proliferation, independent of alterations in the cell cycle, through the activation of autophagy. On the other hand, hypo O-GlcNAcylation inhibited autophagy, promoted cell death by apoptosis, and reduced cell proliferation. In addition, the decrease in O-GlcNAcylation sensitized GB cells to the chemotherapeutic temozolomide (TMZ) without affecting human astrocytes. Combined, these results indicated a role for O-GlcNAcylation in governing cell proliferation, autophagy, cell death, and TMZ response, thereby indicating possible therapeutic implications for treating GB. These findings pave the way for further research and the development of novel treatment approaches which may contribute to improved outcomes and increased survival rates for patients facing this challenging disease.

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Introdução: No mundo, um bilhão de pessoas tem algum tipo de deficiência, dentre elas a deficiência auditiva e mais de 190 milhões são mulheres surdas. É relevante tecnologias para educação inclusiva e acessível sobre o câncer de mama a surdas. Objetivo: Construir e validar vídeo educativo para mulheres surdas sobre prevenção e rastreamento do câncer de mama. Materiais e Método: Estudo metodológico com construção de vídeo educativo e validação por 11 especialistas de conteúdo e sete especialistas técnicos. Conteúdo fundamentado no Ministério da Saúde e no Instituto Nacional do Câncer. Na análise de conteúdo foi utilizado o Instrumento de Validação de Conteúdo Educativo em Saúde. A validade foi atestada pelo Índice de Validade de Conteúdo e o teste binomial. Resultados: O vídeo tem 17 minutos e 12 segundos. Na validação de conteúdo todos os itens tiveram concordância acima de 90,9% entre os participantes. O Índice de Validade de Conteúdo global foi superior a 0,90 entre os especialistas de conteúdo. Consideraram o material excelente, muito bom ou bom, 85,8% dos especialistas técnicos. Discussão: O vídeo contribui para o ensino e aprendizagem sobre o tema, ações de autocuidado e promoção da saúde às surdas. Conclusões: Vídeo construído com narração em LIBRAS, foi considerado válido quanto ao conteúdo e aspectos técnicos e poderá ser utilizado em futuras pesquisas e na educação em saúde de surdas.

Introduction: In the world, one billion people have some kind of disability, among them hearing impairment and more than 190 million are deaf women. It is relevant technologies for inclusive and accessible education about breast cancer to deaf women. Objective: To build and validate an educational video for deaf women on breast cancer prevention and screening. Materials and Method: Methodological study with construction of educational video and validation by 11 content specialists and seven technical specialists. Content based on the Ministry of Health and the National Cancer Institute. The Health Education Content Validation Instrument was used for content analysis. Validity was attested by the Content Validity Index and the binomial test. Results: The video is 17 minutes and 12 seconds long. In the content validation all items had agreement above 90.9% among participants. The overall Content Validity Index was above 0.90 among the content experts. 85.8% of the technical experts considered the material excellent, very good or good. Discussion: The video contributes to teaching and learning about the theme, self-care actions and health promotion for deaf women. Conclusions: Video constructed with narration in LIBRAS, was considered valid in terms of content and technical aspects and can be used in future research and health education for deaf women.

Introducción: En el mundo, mil millones de personas tienen algún tipo de discapacidad, entre ellas discapacidad auditiva y más de 190 millones son mujeres sordas. Se trata de tecnologías relevantes para una educación inclusiva y accesible sobre el cáncer de mama para mujeres sordas. Objetivo: Construir y validar un vídeo educativo para mujeres sordas sobre prevención y cribado del cáncer de mama. Materiales y Método: Estudio metodológico con construcción de video educativo y validación por 11 especialistas de contenido y siete especialistas técnicos. Contenido basado en el Ministerio de Salud y el Instituto Nacional del Cáncer. Se utilizó la Herramienta de Validación de Contenidos de Educación para la Salud para analizar el contenido. La validez fue atestada por el Índice de Validez de Contenido y la prueba binomial. Resultados: El vídeo tiene una duración de 17 minutos y 12 segundos. En la validación del contenido todos los ítems tuvieron un acuerdo superior al 90,9% entre los participantes. El Índice de Validez de Contenido global fue superior a 0,90 entre los expertos en contenido. El 85,8% de los expertos técnicos consideraron el material excelente, muy bueno o bueno. Discusión: El vídeo contribuye a la enseñanza y el aprendizaje sobre el tema, las acciones de autocuidado y la promoción de la salud de las mujeres sordas. Conclusiones: El video construido con narración en LIBRAS, fue considerado válido en términos de contenido y aspectos técnicos y puede ser utilizado en futuras investigaciones y educación en salud para mujeres sordas.

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INTRODUCTION: Zika virus (ZIKV) is a human teratogen that causes congenital Zika syndrome (CZS). AXL, TLR3, and STAT2 are proteins involved in the ZIKV's entry into cells (AXL) and host's immune response (TLR3 and STAT2). In this study, we evaluated the role of genetic polymorphisms in these three genes as risk factors to CZS, and highlighted which proteins that interact with them could be important for ZIKV infection and teratogenesis. MATERIALS AND METHODS: We evaluate eighty-eight children exposed to ZIKV during the pregnancy, 40 with CZS and 48 without congenital anomalies. The evaluated polymorphisms in AXL (rs1051008), TLR3 (rs3775291), and STAT2 (rs2066811) were genotyped using TaqMan® Genotyping Assays. A protein-protein interaction network was created in STRING database and analyzed in Cytoscape software. RESULTS: We did not find any statistical significant association among the polymorphisms and the occurrence of CZS. Through the analyses of the network composed by AXL, TLR3, STAT2 and their interactions targets, we found that EGFR and SRC could be important proteins for the ZIKV infection and its teratogenesis. CONCLUSION: In summary, our results demonstrated that the evaluated polymorphisms do not seem to represent risk factors for CZS; however, EGFR and SRC appear to be important proteins that should be investigated in future studies.

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Zika virus (ZIKV) is a neurotropic teratogen that causes congenital Zika syndrome (CZS), characterized by brain and eye anomalies. Impaired gene expression in neural cells after ZIKV infection has been demonstrated; however, there is a gap in the literature of studies comparing whether the differentially expressed genes in such cells are similar and how it can cause CZS. Therefore, the aim of this study was to compare the differential gene expression (DGE) after ZIKV infection in neural cells through a meta-analysis approach. Through the GEO database, studies that evaluated DGE in cells exposed to the Asian lineage of ZIKV versus cells, of the same type, not exposed were searched. From the 119 studies found, five meet our inclusion criteria. Raw data of them were retrieved, pre-processed, and evaluated. The meta-analysis was carried out by comparing seven datasets, from these five studies. We found 125 upregulated genes in neural cells, mainly interferon-stimulated genes, such as IFI6, ISG15, and OAS2, involved in the antiviral response. Furthermore, 167 downregulated, involved with cellular division. Among these downregulated genes, classic microcephaly-causing genes stood out, such as CENPJ, ASPM, CENPE, and CEP152, demonstrating a possible mechanism by which ZIKV impairs brain development and causes CZS.

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Several molecular mechanisms of thalidomide embryopathy (TE) have been investigated, from anti-angiogenesis to oxidative stress to cereblon binding. Recently, it was discovered that thalidomide and its analogs, named immunomodulatory drugs (IMiDs), induced the degradation of C2H2 transcription factors (TFs). This mechanism might impact the strict transcriptional regulation of the developing embryo. Hence, this study aims to evaluate the TFs altered by IMiDs, prioritizing the ones associated with embryogenesis through transcriptome and systems biology-allied analyses. This study comprises only the experimental data accessed through bioinformatics databases. First, proteins and genes reported in the literature as altered/affected by the IMiDs were annotated. A protein systems biology network was evaluated. TFs beta-catenin (CTNNB1) and SP1 play more central roles: beta-catenin is an essential protein in the network, while SP1 is a putative C2H2 candidate for IMiD-induced degradation. Separately, the differential expressions of the annotated genes were analyzed through 23 publicly available transcriptomes, presenting 8624 differentially expressed genes (2947 in two or more datasets). Seventeen C2H2 TFs were identified as related to embryonic development but not studied for IMiD exposure; these TFs are potential IMiDs degradation neosubstrates. This is the first study to suggest an integration of IMiD molecular mechanisms through C2H2 TF degradation.

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BACKGROUND: Kidney developmental studies have demonstrated molecular pathway changes that may be related to decreased nephron numbers in the male 17 gestational days (17GD) low protein (LP) intake offspring compared to normal protein intake (NP) progeny. Here, we evaluated the HIF-1 and components of its pathway in the kidneys of 17-GD LP offspring to elucidate the molecular modulations during nephrogenesis. METHODS: Pregnant Wistar rats were allocated into two groups: NP (regular protein diet-17%) or LP (Low protein diet-6%). Taking into account miRNA transcriptome sequencing previous study (miRNA-Seq) in 17GD male offspring kidneys investigated predicted target genes and proteins related to the HIF-1 pathway by RT-qPCR and immunohistochemistry. RESULTS: In the present study, in male 17-GD LP offspring, an increased elF4, HSP90, p53, p300, NFκß, and AT2 gene encoding compared to the NP progeny. Higher labeling of HIF-1α CAP cells in 17-DG LP offspring was associated with reduced elF4 and phosphorylated elF4 immunoreactivity in LP progeny CAP cells. In 17DG LP, the NFκß and HSP90 immunoreactivity was enhanced, particularly in the CAP area. DISCUSSION AND CONCLUSION: The current study supported that the programmed reduced nephron number in the 17-DG LP offspring may be related to changes in the HIF-1α signaling pathway. Factors that facilitate the transposition of HIF-1α to progenitor renal cell nuclei, such as increased NOS, Ep300, and HSP90 expression, may have a crucial role in this regulatory system. Also, HIF-1α changes could be associated with reduced transcription of elF-4 and its respective signaling path.

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Pork is of great importance in world trade and represents the largest source of fatty acids in the human diet. Lipid sources such as soybean oil (SOY), canola (CO), and fish oil (FO) are used in pig diets and influence blood parameters and the ratio of deposited fatty acids. In this study, the main objective was to evaluate changes in gene expression in porcine skeletal muscle tissue resulting from the dietary oil sources and to identify metabolic pathways and biological process networks through RNA-Seq. The addition of FO in the diet of pigs led to intramuscular lipid with a higher FA profile composition of C20:5 n-3, C22:6 n-3, and SFA (C16:0 and C18:0). Blood parameters for the FO group showed lower cholesterol and HDL content compared with CO and SOY groups. Skeletal muscle transcriptome analyses revealed 65 differentially expressed genes (DEG, FDR 10%) between CO vs SOY, and 32 DEG for CO vs FO, and 531 DEG for SOY vs FO comparison. Several genes, including AZGP1, PDE3B, APOE, PLIN1, and LIPS, were found to be down-regulated in the diet of the SOY group compared to the FO group. The enrichment analysis revealed DEG involved in lipid metabolism, metabolic diseases, and inflammation between the oil groups, with specific gene functions in each group and altered blood parameters. The results provide mechanisms to help us understand the behavior of genes according to fatty acids.

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BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

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Pigs (Sus scrofa) are an animal model for metabolic diseases in humans. Pork is an important source of fatty acids (FAs) in the human diet, as it is one of the most consumed meats worldwide. The effects of dietary inclusion of oils such as canola, fish, and soybean oils on pig gene expression are mostly unknown. Our objective was to evaluate FA composition, identify changes in gene expression in the liver of male pigs fed diets enriched with different FA profiles, and identify impacted metabolic pathways and gene networks to enlighten the biological mechanisms' variation. Large White male pigs were randomly allocated to one of three diets with 18 pigs in each; all diets comprised a base of corn and soybean meal to which either 3% of soybean oil (SOY), 3% canola oil (CO), or 3% fish oil (FO) was added for a 98-day trial during the growing and finishing phases. RNA sequencing was performed on the liver samples of each animal by Illumina technology for differential gene expression analyses, using the R package DESeq2. The diets modified the FA profile, mainly in relation to polyunsaturated and saturated FAs. Comparing SOY vs. FO, 143 differentially expressed genes (DEGs) were identified as being associated with metabolism, metabolic and neurodegenerative disease pathways, inflammatory processes, and immune response networks. Comparing CO vs. SOY, 148 DEGs were identified, with pathways related to FA oxidation, regulation of lipid metabolism, and metabolic and neurodegenerative diseases. Our results help explain the behavior of genes with differential expression in metabolic pathways resulting from feeding different types of oils in pig diets.

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The risk of bovine cysticercosis is mutable over time, since population habits, local infrastructure, and bovine herd size change through the years. Hence, the aim of this study was to update the risk map of bovine cysticercosis occurrence in Espírito Santo State, Brazil, by choosing the following risk factors: inadequate sewer service; bovine population per municipality; risk of flooding; and land use and occupation, examined with a mathematical model using the GIS program ArcGis 10.5. The risk map of occurrence demonstrated that the state is composed of 12.8, 24.5, 36.2 and 26.5% of areas of very high, high, medium, and low risk, respectively. The northern area stood out for areas of very high risk, with the cities of Linhares and São Mateus accounting for 99% of the area with this classification. Of the state's 78 municipalities, 15 had a portion of their territory with very high risk, 11 had over 50% of the territory with high risk and all except Irupi (100% of low risk) had some percentage of medium risk. These findings demonstrate the areas where actions to prevent bovine cysticercosis should be preferentially conducted.

O risco de cisticercose bovina é mutável ao longo do tempo, uma vez que os hábitos populacionais, a infraestrutura local e o tamanho do rebanho bovino mudam ao longo dos anos. Assim, o objetivo deste estudo foi atualizar o mapa de risco da ocorrência da cisticercose bovina no Estado do Espírito Santo, Brasil, escolhendo os seguintes fatores de risco: saneamento sanitário inadequado; população bovina por município; risco de inundação; e uso e ocupação do solo, examinados com um modelo matemático usando o programa SIG ArcGis 10.5. O mapa de risco de ocorrência demonstrou que o estado é composto por 12,8, 24,5, 36,2 e 26,5% de áreas de risco muito alto, alto, médio e baixo, respectivamente. A zona norte destacou-se como área de risco muito alto, com os municípios de Linhares e São Mateus respondendo por 99% da área com essa classificação. Dos 78 municípios do estado, 15 tinham uma parcela de seu território com risco muito alto, 11 tinham mais de 50% do território com risco alto e todos exceto Irupi (100% de risco baixo) tinham algum percentual de risco médio. Esses achados demonstram as áreas onde as ações de prevenção da cisticercose bovina devem ser preferencialmente realizadas.

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Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.

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Zika virus (ZIKV) is a teratogen that causes congenital anomalies, being linked to microcephaly in children exposed during pregnancy. Animal studies have been conducted to investigate the molecular mechanisms related to ZIKV teratogenesis. Although animal models can mimic the effects of ZIKV in human embryo development, few in vivo studies have addressed molecular changes following ZIKV infection in embryos. Moreover, few literature reviews have been conducted with these studies. The aim of this systematic review is to evaluate the molecular mechanisms of ZIKV teratogenesis determined from studies in animal models. PubMed/MEDLINE, EMBASE, Web of Science, and Scopus as well as grey literature were searched for studies that evaluated molecular alterations related to ZIKV teratogenesis which occurred during embryonic development. Nine studies were included: six with mice, one with mice and guinea pigs, one with pigs and one with chickens. In general, studies presented an unclear or high risk of bias for methodological criteria. Most of studies reported embryos exposed to ZIKV presenting microcephaly, reduced cortex thickness, and growth restriction. Different techniques were used to evaluated molecular changes in the animals following ZIKV infection: RNA sequencing, RT-qPCR, and in situ hybridization. It was found that common pathways are changed in most studies, being pathways related to immune response upregulated and those involved to neurodevelopment downregulated.

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Objetivo: Analisar o perfil dos profissionais atuantes na Atenção Primária em Saúde (APS) no cuidado a pacientes com depressão pós-parto (DPP) e as principais dificuldades na realização do diagnóstico precoce. Método: Por meio de uma pesquisa observacional, de caráter exploratório, abordagem quantitativa descritiva, com delineamento transversal, das informações colhidas através de questionário enviados por meio do aplicativo Google Forms, aplicada aos profissionais da APS, da região do Departamento Regional de Saúde de Araçatuba (DRSII). Resultado:Observa-se que 22,62% dos Agentes Comunitários de Saúde (ACS) permanecem na APS por 3 anos ou mais, enquanto 3,16% dos médicos, de 1 a 3 anos. Dos profissionais, 93,2% trabalham com protocolos de pré-natal, e destes, somente 33% são atualizados anualmente. Avaliando as consultas de pré-natal, 44,44% das gestantes com mais de 5 consultas retornam à Unidade Básica de Saúde (UBS) no puerpério. Dentre todas as categorias profissionais, 73,00% dos médicos se sentem aptos a realizarem orientações sobre a DPP. Cerca de 85% dos participantes da pesquisa identificaram os sintomas da doença e 18% o período do diagnóstico precoce corretamente. Atendimentos individuais e orientações às gestantes são realizados em 14,48% das práticas desenvolvidas pelos profissionais. Ademais, 91% dos profissionais nunca receberam capacitação a respeito do tema. Conclusão:Observou-se no estudo que há alta rotatividade dos profissionais da atenção primária de saúde, ausência do uso de protocolos de pré-natal atualizados e falta de conhecimento para a realização do diagnóstico precoce e preciso da DPP.

Objective: To analyze the profile of professionals working in Primary Health Care (PHC) in the care of patients with Postpartum Depression (PPD) and the main difficulties in carrying out an early diagnosis.Method:Through an observational, applied, exploratory research, descriptive quantitative approach, with a cross-sectional design, the information collected through a questionnaire sent through the Google Forms application, to PHC professionals, in the region of the Regional Department of Health of Araçatuba (DRSII), for the elaboration of effective strategies, aiming at the prevention, diagnosis and treatment of this pathology. Result: It is observed that 22.62% of Community Health Agents (ACS) remain in PHC for 3 years or more, while 3.16% of physicians, from 1 to 3 years. Of the professionals, 93.2% work with prenatal protocols, and of these, only 33% are updated annually. Evaluating prenatal consultations, 44.44% of pregnant women with more than 5 consultations return to the Basic Health Unit (UBS) in the puerperium. Among all professional categories, 73.00% of physicians feel able to provide guidance on PPD. About 85% of the survey participants correctly identified the symptoms of the disease and 18% the period of early diagnosis. Individual consultations and guidance for pregnant women are carried out in 14.48% of the practices developed by professionals. Furthermore, 91% of professionals have never received training on the subject. Conclusion: It was observed in the study that there is a high turnover of primary health care professionals, absence of the use of updated prenatal protocols and lack of knowledge to carry out an early and accurate diagnosis of PPD

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O estudo intenta conhecer o perfil de crianças e adolescentes atendidos em serviço comunitário para usuários de drogas e analisar as características do atendimento oferecido. Estudo quantitativo, descritivo-exploratório, com análise descritiva dos dados de 115 prontuários de um CAPSi especializado em drogas. Foi utilizada frequência válida, devido aos dados não informados. A maioria era de homens (78,2%) com idade média de 14,7 anos (dp = 1,98). Mais da metade não frequentava a escola (54,2%) e 33,7% residia com a mãe. Em 81,9% dos prontuários algum familiar fazia uso abusivo de drogas, sendo 52,9% o pai. A maconha apresentou maior prevalência e início mais precoce. O serviço dispunha de atividades que buscavam abranger diferentes necessidades, entre elas, questões escolares e familiares da clientela, justificando a proposta de um serviço comunitário especializado no cuidado a crianças e adolescentes usuários de drogas. Entretanto, observou-se como maior desafio a continuidade do atendimento no serviço.

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BACKGROUND: HAND2 is a transcription factor important for embryonic development, required for limbs and cardiovascular development. Thalidomide is a drug responsible to a spectrum of congenital anomalies known as Thalidomide Embryopathy (TE), which includes mainly limb and heart defects. It is known that HAND2 interaction with TBX5, an important protein for limbs and heart development, is inhibited by Thalidomide. The aim of this study was to evaluate and characterize HAND2 in the context of TE, and to evaluate its variability in TE individuals. METHODS: DNA from 35 TE subjects was extracted from saliva samples and PCR was performed for amplification and Sanger sequencing of HAND2 coding sequence. RESULTS: The analysis showed only one variant; a synonymous variant p.P51 (rs59621536) in exon 1 found in three individuals. Further in silico evaluation confirmed highly HAND2 conservation, being the 3'UTR the most polymorphic region of the gene. Additional computational analyses classified the variant as neutral, without alteration in splicing and miRNA sites. In silico predictions pointed to alteration of two CpG islands adjacent to the variant; however, we did not observe any alterations on the methylation pattern of HAND2 gene in our sample. Moreover, alteration of the binding site of MeCP2, a nuclear protein involved in DNA methylation, was predicted along with alteration in HAND2 mRNA structure. CONCLUSIONS: Considering HAND2 being a well conserved gene, further studies with a larger sample should be performed to evaluate the role this gene on genetic susceptibility to TE.

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