Processos de adaptação parental face a diferentes diagnósticos de deficiência

Nesta dissertação pretendemos analisar a validade de conteúdo da Escala Parental de Adaptação à Deficiência (EPAD) e as relações e correlações entre a Escala de Impacto na Família (EIF) e a EPAD. Pretendemos também testar diferenças na adaptação dos pais tendo em consideração diferentes diagnósticos de deficiência e diversos graus de autonomia. A amostra é constituída por 45 pais de sujeitos com diferentes diagnósticos. Os resultados mostraram que a EPAD demonstra ter validade de conteúdo e a existência de relações entre as escalas, subescalas, fatores e dimensões. Mostraram diferenças na dimensão Futuro, Depressão, Resiliência e Apoio Social, quando considerados os diagnósticos paralisia cerebral, deficiência intelectual, autismo e outro. Quando considerados os grupos de pais/mães com filhos/as com e sem autismo, verificaram-se diferenças no fator Suporte e na dimensão Apoio Social. Tendo em consideração os níveis de autonomia dos filhos/as, verificaram-se diferenças na EIF, dimensão Culpa e Resiliência; Processes of parental adaptation to different diagnoses of disability Abstract: In this dissertation we intend to analyze the content validity of the Parental Adaptation Scale for Disability (EPAD) and the relationships and correlations between the Family Impact Scale (EIF) and the EPAD. We also intend to test differences in the adaptation of the parents taking into account different diagnoses of disability and different degrees of autonomy. The sample consisted of 45 parents of subjects with different diagnoses. The results showed that the EPAD demonstrates content validity and the existence of relationships between scales, subscales, factors and dimensions. Showed differences in Future, Depression, Resilience and Social Suport dimensions, when considering the diagnoses of cerebral palsy, intelectual disability, autismo and other. When considering the groups of parents with children whit and without autism, there were differences in Suport factor and Social Suport dimension. Taking into to account the levels of autonomy of the children, there were differences in EIF, Guilt and Resilience dimensions

Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE 2 in colorectal cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC), we have characterized the transcriptional and epigenetic landscapes of the PTGS pathway genes in normal and cancer cells. [Results]: Data from four independent series of CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent normal tissues) and two series of colon mucosae from 69 healthy donors have been included in the study. Gene expression was analyzed by real-time PCR and Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing, dissociation curves, and HumanMethylation450K arrays. Most CRC patients show selective transcriptional deregulation of the enzymes involved in the synthesis of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA methylation alterations exclusively affect the tumor tissue (both adenomas and carcinomas), redirecting the transcriptional deregulation to activation of prostaglandin E 2 (PGE 2 ) function and blockade of other biologically active prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were hypermethylated in more than 40 % of all analyzed tumors. [Conclusions]: The transcriptional and epigenetic profiling of the PTGS pathway provides important clues on the biology of the tumor and its microenvironment. This analysis renders candidate markers with potential clinical applicability in risk assessment and early diagnosis and for the design of new therapeutic strategies.IC was funded by Fundação para a Ciência e a Tecnologia (SFRH/BD/28464/2006); JC was funded by a FPI fellowship. ADV was supported in part by a contract from the Ministerio de Economía y Competitividad (MINECO) (PTC2011-1091). This work was supported by the MINECO(SAF2011/23638, SAF2014/52492), the Catalan Institute of Oncology and the Instituto de Salud Carlos III (grant PI11-01439, RD12/0042/0019 and CIBERESP CB06/02/2005), the Generalitat de Catalunya (grant 2014SGR647), and the Asociación Española Contra el Cáncer (AECC).Peer Reviewe

Highlights of vitamin D supplementation in patients with COVID-19: review of scientific evidence

Introdução: A pandemia da COVID-19 tem levantado discussões acerca dos benefícios da vitamina D na prevenção e no tratamento da doença. Esta vitamina desempenha um papel eficaz no sistema imunológico, podendo contribuir para uma resposta adequada à infeção por SARS-CoV-2. Objetivos: Rever a evidência científica sobre o efeito da suplementação da vitamina D nos doentes com COVID-19. Metodologia: A pesquisa foi realizada em bases de dados eletrónicas, nomeadamente Pubmed e Web of Science, com publicações no último ano, utilizando as palavras-chave: “COVID-19” or “SARS-CoV-2” or “coronavirus”, vitamin D” and “dietary supplements”. Após aplicar os critérios de inclusão e exclusão, obtiveram-se 9 artigos. Resultados: A suplementação da vitamina D nos doentes com COVID-19 reduziu o tempo de internamento hospitalar, a necessidade de admissão nos cuidados intensivos e de ventilação mecânica invasiva, acelerando o processo de recuperação. Estudos relatam os possíveis benefícios da suplementação como medida profilática de forma a proteger contra futuras infeções víricas. Conclusões: A evidência científica existente demonstra resultados promissores do papel da vitamina D nos doentes com COVID-19 na redução da gravidade da doença e na melhoria do prognóstico. São necessários mais estudos na população humana para suportar esta hipótese e comprovar a eficácia.ABSTRACT - Introduction: The COVID-19 pandemic has raised discussions about the benefits of vitamin D in preventing and treating the disease. This vitamin plays an effective role in the immune system and can contribute to an adequate response to SARS-CoV-2 infection. The purpose of this review is to systematize the scientific evidence on the effect of vitamin D in patients with COVID-19. Objectives: Review the scientific evidence on the effect of vitamin D in patients with COVID-19. Methodology: The search was carried out in electronic databases, namely Pubmed, and Web of Science, with publications in the last year, using the keywords: “COVID-19” or “SARS-CoV-2” or “coronavirus”, vitamin D” and “dietary supplements”. After applying the inclusion and exclusion criteria, 9 articles were obtained. Results: Supplementation of vitamin D in patients with COVID-19 reduced the length of hospital stay, the need for admission to intensive care, and invasive mechanical ventilation, accelerating the recovery process. Studies report the possible benefits of supplementation as a prophylactic measure in order to protect against future viral infections. Conclusions: Scientific evidence demonstrates promising results from the role of vitamin D in patients with COVID-19 in reducing the severity of the disease and improving the prognosis. Further studies in the human population are needed to support this hypothesis and prove its effectiveness.info:eu-repo/semantics/publishedVersio

Epigenetics override pro-inflammatory PTGS transcriptomic signature towards selective hyperactivation of PGE 2 in colorectal cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Misregulation of the PTGS (prostaglandin endoperoxide synthase, also known as cyclooxygenase or COX) pathway may lead to the accumulation of pro-inflammatory signals, which constitutes a hallmark of cancer. To get insight into the role of this signaling pathway in colorectal cancer (CRC), we have characterized the transcriptional and epigenetic landscapes of the PTGS pathway genes in normal and cancer cells. [Results]: Data from four independent series of CRC patients (502 tumors including adenomas and carcinomas and 222 adjacent normal tissues) and two series of colon mucosae from 69 healthy donors have been included in the study. Gene expression was analyzed by real-time PCR and Affymetrix U219 arrays. DNA methylation was analyzed by bisulfite sequencing, dissociation curves, and HumanMethylation450K arrays. Most CRC patients show selective transcriptional deregulation of the enzymes involved in the synthesis of prostanoids and their receptors in both tumor and its adjacent mucosa. DNA methylation alterations exclusively affect the tumor tissue (both adenomas and carcinomas), redirecting the transcriptional deregulation to activation of prostaglandin E 2 (PGE 2 ) function and blockade of other biologically active prostaglandins. In particular, PTGIS, PTGER3, PTGFR, and AKR1B1 were hypermethylated in more than 40 % of all analyzed tumors. [Conclusions]: The transcriptional and epigenetic profiling of the PTGS pathway provides important clues on the biology of the tumor and its microenvironment. This analysis renders candidate markers with potential clinical applicability in risk assessment and early diagnosis and for the design of new therapeutic strategies.IC was funded by Fundação para a Ciência e a Tecnologia (SFRH/BD/28464/2006); JC was funded by a FPI fellowship. ADV was supported in part by a contract from the Ministerio de Economía y Competitividad (MINECO) (PTC2011-1091). This work was supported by the MINECO(SAF2011/23638, SAF2014/52492), the Catalan Institute of Oncology and the Instituto de Salud Carlos III (grant PI11-01439, RD12/0042/0019 and CIBERESP CB06/02/2005), the Generalitat de Catalunya (grant 2014SGR647), and the Asociación Española Contra el Cáncer (AECC).Peer Reviewe

SOX17 Enhancer Variants Disrupt Transcription Factor Binding And Enhancer Inactivity Drives Pulmonary Hypertension

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare disease characterized by remodeling of the pulmonary arteries, increased vascular resistance, and right-sided heart failure. Genome-wide association studies of idiopathic/heritable PAH established novel genetic risk variants, including conserved enhancers upstream of transcription factor (TF) SOX17 containing 2 independent signals. SOX17 is an important TF in embryonic development and in the homeostasis of pulmonary artery endothelial cells (hPAEC) in the adult. Rare pathogenic mutations in SOX17 cause heritable PAH. We hypothesized that PAH risk alleles in an enhancer region impair TF-binding upstream of SOX17, which in turn reduces SOX17 expression and contributes to disturbed endothelial cell function and PAH development. METHODS: CRISPR manipulation and siRNA were used to modulate SOX17 expression. Electromobility shift assays were used to confirm in silico–predicted TF differential binding to the SOX17 variants. Functional assays in hPAECs were used to establish the biological consequences of SOX17 loss. In silico analysis with the connectivity map was used to predict compounds that rescue disturbed SOX17 signaling. Mice with deletion of the SOX17 signal 1 enhancer region (SOX17-4593/enhKO) were phenotyped in response to chronic hypoxia and SU5416/hypoxia. RESULTS: CRISPR inhibition of SOX17-signal 2 and deletion of SOX17signal 1 specifically decreased SOX17 expression. Electromobility shift assays demonstrated differential binding of hPAEC nuclear proteins to the risk and nonrisk alleles from both SOX17 signals. Candidate TFs HOXA5 and ROR-α were identified through in silico analysis and antibody electromobility shift assays. Analysis of the hPAEC transcriptomes revealed alteration of PAH-relevant pathways on SOX17 silencing, including extracellular matrix regulation. SOX17 silencing in hPAECs resulted in increased apoptosis, proliferation, and disturbance of barrier function. With the use of the connectivity map, compounds were identified that reversed the SOX17-dysfunction transcriptomic signatures in hPAECs. SOX17 enhancer knockout in mice reduced lung SOX17 expression, resulting in more severe pulmonary vascular leak and hypoxia or SU5416/hypoxia-induced pulmonary hypertension. CONCLUSIONS: Common PAH risk variants upstream of the SOX17 promoter reduce endothelial SOX17 expression, at least in part, through differential binding of HOXA5 and ROR-α. Reduced SOX17 expression results in disturbed hPAEC function and PAH. Existing drug compounds can reverse the disturbed SOX17 pulmonary endothelial transcriptomic signature

Foliar Spraying of Solanum tuberosum L. with CaCl2 and Ca(NO3)2: Interactions with Nutrients Accumulation in Tubers

Calcium is essential for plants, yet as its mobility is limited, the understanding of the rate of Ca2+ accumulation and deposition in tissues of tubers, as well as the interactions with other critical nutrients prompted this study. To assess the interactions and differential accumulation of micro and macronutrients in the tissues of tubers, Solanum tuberosum L. varieties Agria and Rossi were cultivated and, after the beginning of tuberization, four foliar sprayings (at 8–10 day intervals) with CaCl2 (3 and 6 kg ha1) or Ca(NO3)2 (2 and 4 kg ha1) solutions were performed. It was found that both fertilizers increased Ca accumulation in tubers (mostly in the parenchyma tissues located in the center of the equatorial region). The functioning of the photosynthetic apparatus was not affected until the 3rd application but was somewhat affected when approaching the end of the crop cycle (after the 4th application), although the lower dose of CaCl2 seemed to improve the photochemical use of energy, particularly when compared with the greater dose of Ca(NO3)2. Still, none of these impacts modified tuber height and diameter. Following the increased accumulation of Ca, in the tubers of both varieties, the mean contents of P, K, Na, Fe, and Zn revealed different accumulation patterns. Moreover, accumulation of K, Fe, Mn, and Zn prevailed in the epidermis, displaying a contrasting pattern relative to Ca. Therefore, Ca accumulation revealed a heterogeneous trend in the different regions analyzed, and Ca enrichment of tubers altered the accumulation of other nutrientsinfo:eu-repo/semantics/publishedVersio

Mineral Monitorization in Different Tissues of Solanum tuberosum L. during Calcium Biofortification Process

Funding Information: This work received funding from PDR2020-101-030719 and the Fundação para a Ciência e a Tecnologia, I.P. (FCT), Portugal, through the research units UIDP/04035/2020 (GeoBioTec), UIDB/00239/2020 (CEF), and UID/FIS/04559/2013 (LIBPhys). This work was further supported by the grant of the Fundação para a Ciência e Tecnologia (FCT) UI/BD/150806/2020. Publisher Copyright: © 2022 by the authors.Calcium is one of the 16 essential elements for plants, being required as Ca2+ and being involved in several fundamental processes (namely, in the stability and integrity of the cell wall, the development of plant tissue, cell division, and in stress responses). Moreover, Ca plays an important role in potato production. In this context, this study aimed to monitor the culture development (in situ and using an unmanned aerial vehicle (UAV)) and the mineral content of four essential elements (Ca, P, K, and S) in different organs of Solanum tuberosum L. (roots, stems, leaves, and tubers) during a calcium biofortification process, carried out with two types of solutions (CaCl2 and Ca-EDTA) with two concentrations (12 and 24 kg∙ha−1). The calcium content generally increased in the S. tuberosum L. organs of both varieties and showed, after the last foliar application, an increase in Ca content that varied between 5.7–95.6% and 20.7–33%, for the Picasso and Agria varieties, respectively. The patterns of accumulation in both varieties during the biofortification process were different between the variety and mineral element. Regarding the quality analysis carried out during the development of the tubers, only the Agria variety was suitable for industrial processing after the last foliar application.publishersversionpublishe

Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes

DNA methylation variations are prevalent in human obesity but evidence of a causative role in disease pathogenesis is limited. Here, we combine epigenome-wide association and integrative genomics to investigate the impact of adipocyte DNA methylation variations in human obesity. We discover extensive DNA methylation changes that are robustly associated with obesity (N = 190 samples, 691 loci in subcutaneous and 173 loci in visceral adipocytes, P 500 target genes, and identify putative methylation-transcription factor interactions. Through Mendelian Randomisation, we infer causal effects of methylation on obesity and obesity-induced metabolic disturbances at 59 independent loci. Targeted methylation sequencing, CRISPR-activation and gene silencing in adipocytes, further identifies regional methylation variations, underlying regulatory elements and novel cellular metabolic effects. Our results indicate DNA methylation is an important determinant of human obesity and its metabolic complications, and reveal mechanisms through which altered methylation may impact adipocyte functions

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility