A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, genome sequencing (GS), RNA-seq, and optical genome mapping (OGM). A complex 9p24 SV was hinted at by CMA results, showing three interspersed duplicated segments. Combined GS and OGM analyses revealed that the 9p24 duplications constitute a complex SV, on which a set of breakpoints matches the boundaries of the CMA duplicated sequences. The proposed structure for this complex rearrangement implies three duplications associated with an inversion of ~ 2 Mb region on chromosome 9 and a SINE element insertion at the more distal breakpoint. Interestingly, this genomic structure of rearrangement forms a chimeric transcript of the KANK1/DMRT1 loci, which was confirmed by both RNA-seq and Sanger sequencing on blood samples from 9p24 rearrangement carriers. Altogether with breakpoint amplification and FISH analysis, this combined approach allowed a deep characterization of this complex rearrangement. Although the genotype-phenotype correlation remains elusive from the molecular mechanism point of view, this study identified a large genomic rearrangement at 9p24 segregating with a familial congenital heart defect, revealing a genetic biomarker that was successfully applied for embryo selection, changing the reproductive perspective of affected individuals.

A web-based educational therapy intervention associated with physical exercise to promote health in fibromyalgia in Brazil: the Amigos De Fibro (Fibro Friends) study protocol.

BACKGROUND: Health education is one of the main items to enable health promotion to patients with fibromyalgia. The objective of the study "Amigos de Fibro (Fibro Friends)" is to evaluate the impact of an educational intervention associated with physical exercise based on the web in promoting health and quality of life of patients with fibromyalgia in Brazil. METHODS: A study with a randomized controlled trial approach will be carried out. The sample will consist of 24 participants, divided into two groups, with 12 individuals each. The experimental group will participate in meetings with lectures, debates, conversation rounds and exercises by a multidisciplinary team. Physical exercises will also be performed in an online environment. On the other hand, the control group will receive an e-book of education and self-care. Primary outcomes will be quality of life. The secondary outcomes will be sociodemographic and health profile, pain intensity, sleep quality, self-care agency, usage and costs of health and social care services, viability of the program and program participation. In addition, a qualitative evaluation process will be carried out with the participants. After the intervention, the data of both groups will be collected again, as well as after 3, 6, and 12 months to verify the effect and the maintenance of the intervention. DISCUSSION: The results will provide data for studies to consider the use of this tool in the future by professionals working in the field of rheumatology. TRIAL REGISTRATION: The protocol was registered in the Brazilian Registry of Clinical Trials RBR-3rh759 ( https://trialsearch.who.int/Trial2.aspx?TrialID=RBR-3rh759 ). Date of registration: 07/02/2020].

The effects of the healthcare line in a stroke unit: three years' experience of a center in the Northeast of Brazil.

BACKGROUND: Treatment at an organized stroke unit center (SUC) improves survival after stroke. Stroke mortality has decreased worldwide in recent decades. OBJECTIVE: This study shows the experience of a SUC in the Northeast of Brazil, comparing its first, second, and third years. METHODS: We compared data on the SUC prospectively collected from 31 July 2018 to 31 July 2019 (year 1), August 1st, 2019, to July 31st, 2020 (year 2), and August 1st to July 31st, 2021 (year 3). RESULTS: There was an expertise evolution through the years, with good outcomes in spite of the coronavirus disease 2019 pandemic in the 3rd year. Also, in the 1st year, the median (interquartile range) door-to-needle time was 39.5 (29.5-60.8) minutes evolving to 22 (17-30) minutes, and then to 17 (14-22) minutes in the last year. CONCLUSION: This was the first report on a SUC's outcome in the Brazil's Central Arid Northeast countryside, and it shows the improvement in care for patients with stroke through an effective healthcare line.

ANTECEDENTES: O tratamento em um centro organizado com Unidade de acidente vascular cerebral (AVC) melhora a sobrevida após o AVC. A mortalidade por AVC diminuiu em todo o mundo nas últimas décadas. OBJETIVO: Este estudo mostra a experiência de um centro de AVC no Nordeste brasileiro, comparando o primeiro, segundo e terceiro anos do serviço. MéTODOS: Nós comparamos dados coletados prospectivamente na Unidade de AVC de 31 de julho de 2018 a 31 de julho 2019 (ano 1), 1° de agosto de 2019 a 31 de julho de 2020 (ano 2) e 1° de agosto a 31 de julho de 2021 (ano 3). RESULTADOS: Houve uma evolução na conhecimento especializado ao longo dos anos, com bons desfechos apesar da pandemia de coronavirus disease 2019 no terceiro ano. Além disso, no primeiro ano a mediana do tempo porta­agulha foi de 39.5 (29.5­60.8) minutos, evoluindo para 22 (17­30) minutos, e então 17 (14­22) minutos no último ano. CONCLUSãO: Este foi o primeiro relato sobre o desempenho de um serviço de AVC do interior do Nordeste brasileiro e evidencia a melhoria assistencial aos pacientes com AVC por meio de uma efetiva linha de cuidado em saúde.

The effects of the healthcare line in a stroke unit: three years' experience of a center in the Northeast of Brazil / Efeitos da linha de cuidado em saúde em uma unidade de AVC: três anos de experiência de um centro no nordeste do Brasil

Abstract Background Treatment at an organized stroke unit center (SUC) improves survival after stroke. Stroke mortality has decreased worldwide in recent decades. Objective This study shows the experience of a SUC in the Northeast of Brazil, comparing its first, second, and third years. Methods We compared data on the SUC prospectively collected from 31 July 2018 to 31 July 2019 (year 1), August 1st, 2019, to July 31st, 2020 (year 2), and August 1st to July 31st, 2021 (year 3). Results There was an expertise evolution through the years, with good outcomes in spite of the coronavirus disease 2019 pandemic in the 3rd year. Also, in the 1st year, the median (interquartile range) door-to-needle time was 39.5 (29.5-60.8) minutes evolving to 22 (17-30) minutes, and then to 17 (14-22) minutes in the last year. Conclusion This was the first report on a SUC's outcome in the Brazil's Central Arid Northeast countryside, and it shows the improvement in care for patients with stroke through an effective healthcare line.

Resumo Antecedentes O tratamento em um centro organizado com Unidade de acidente vascular cerebral (AVC) melhora a sobrevida após o AVC. A mortalidade por AVC diminuiu em todo o mundo nas últimas décadas. Objetivo Este estudo mostra a experiência de um centro de AVC no Nordeste brasileiro, comparando o primeiro, segundo e terceiro anos do serviço. Métodos Nós comparamos dados coletados prospectivamente na Unidade de AVC de 31 de julho de 2018 a 31 de julho 2019 (ano 1), 1° de agosto de 2019 a 31 de julho de 2020 (ano 2) e 1° de agosto a 31 de julho de 2021 (ano 3). Resultados Houve uma evolução na conhecimento especializado ao longo dos anos, com bons desfechos apesar da pandemia de coronavirus disease 2019 no terceiro ano. Além disso, no primeiro ano a mediana do tempo porta-agulha foi de 39.5 (29.5-60.8) minutos, evoluindo para 22 (17-30) minutos, e então 17 (14-22) minutos no último ano. Conclusão Este foi o primeiro relato sobre o desempenho de um serviço de AVC do interior do Nordeste brasileiro e evidencia a melhoria assistencial aos pacientes com AVC por meio de uma efetiva linha de cuidado em saúde.

A germline chimeric KANK1-DMRT1 transcript derived from a complex structural variant is associated with a congenital heart defect segregating across five generations.

Structural variants (SVs) pose a challenge to detect and interpret, but their study provides novel biological insights and molecular diagnosis underlying rare diseases. The aim of this study was to resolve a 9p24 rearrangement segregating in a family through five generations with a congenital heart defect (congenital pulmonary and aortic valvular stenosis, and pulmonary artery stenosis), by applying a combined genomic analysis. The analysis involved multiple techniques, including karyotype, chromosomal microarray analysis (CMA), FISH, whole-genome sequencing (WGS), RNA-seq and optical genome mapping (OGM). A complex 9p24 SV was hinted at by CMA results, showing three interspersed duplicated segments. Combined WGS and OGM analyses revealed that the 9p24 duplications constitute a complex SV, on which a set of breakpoints match the boundaries of the CMA duplicated sequences. The proposed structure for this complex rearrangement implies three duplications associated with an inversion of ~ 2Mb region on chromosome 9 with a SINE element insertion at the more distal breakpoint. Interestingly, this hypothesized genomic structure of rearrangement forms a chimeric transcript of the KANK1/DMRT1 loci, which was confirmed by RNA-seq on blood from 9p24 rearrangement carriers. Altogether with breakpoint amplification and FISH analysis, this combined approach allowed a deep characterization of this complex rearrangement. Although the genotype-phenotype correlation remains elusive from the molecular mechanism point of view, this study identified a large genomic rearrangement at 9p segregating with a familial congenital clinical trait, revealing a genetic biomarker that was successfully applied for embryo selection, changing the reproductive perspective of affected individuals.

Generation of genetically modified human induced pluripotent stem cell lines harboring haploin sufficient or dominant negative variants in the FBN1 gene.

Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene. To investigate the molecular mechanisms of pathogenesis for the syndrome, we genetically modified the FBN1 gene in a line of induced pluripotent stem cells (hiPSCs) derived from a healthy donor using the CRISPR/Cas9 gene editing technology. The sublines described here were characterized according to established criteria and were shown to maintain pluripotency, three germ layer differentiation potential and genomic integrity. These clones can now be used to better understand the pathogenesis of MFS in different cell types.

Generation of 6 lines of human pluripotent stem cells from hypertensive patients and 3 lines of human pluripotent stem cell from normotensive patients.

Hypertension is a complex multifactorial disease characterized by a chronic increase of arterial pressure. Ninety percent of the cases are idiopathic and thus classified as essential hypertension. Uncontrolled arterial pressure has devasting consequences including cardiac insufficiency, stroke, dementia, chronic renal disease, ischemic heart disease and death. The hiPSC lines described here from six hypertensive patients and three controls were characterized according to established criteria and were shown to maintain pluripotency, differentiation into the three germ layers and genomic integrity. These cell lines can contribute to the understanding of the molecular mechanisms involved in hypertension in different cell types.

Dynamic sex chromosome expression in Drosophila male germ cells.

Given their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, based on measuring all genes or a set of broadly expressed genes in testis we identified. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5.

Implantação da puericultura e desafios do cuidado na estratégia saúde da família em um município do estado do Ceará / Implementation of childcare and care challenges in the Family Health Strategy in a city of the Ceará state / Implantación de la puericultura y los desafíos del cuidado de la Estrategia de Salud de la Familia de un municipio del Estado de Ceará

OBJETIVO: Relatar a experiência da implantação da puericultura e desafios do cuidado na Estratégia Saúde da Família em um município do Estado do Ceará. Síntese dos dados: Trata-se de um estudo de abordagem qualitativa, com caráter descritivo, do tipo relato de experiência, desenvolvido no contexto de uma das Unidades Básicas de Saúde do município de Aracati, Ceará. A sistematização do relato se deu a partir dos registros realizados pela enfermeira residente em um diário de campo, no período compreendido entre os meses de junho de 2013 e abril de 2015. Com a implantação da consulta em puericultura, pode-se perceber a importância de se realizar um acompanhamento sistemático desde o pré-natal, perpassando o momento do puerpério e alcançando o foco principal deste estudo, a saúde da criança. Destaca-se a contribuição do Núcleo de Apoio à Saúde da Família nas consultas e o uso das tecnologias simples favorecendo a interação entre profissionais, comunidade e serviços de saúde. Além disso, algumas fragilidades do processo de trabalho precisaram ser superadas, tais como: obstáculos estruturais, falta de compromisso de alguns profissionais, divergências de condutas, profissionais desmotivados devido à sobrecarga de trabalho e poucos cursos ofertados para qualificação da equipe de saúde. CONCLUSÃO: A tarefa não é fácil, os desafios são contínuos, mas a recompensa consegue ser maior e mais gratificante do que qualquer dificuldade vivenciada. Espera-se que este relato possa promover reflexões críticas acerca do trabalho que se tem produzido junto à Estratégia Saúde da Família.

OBJECTIVE: To report the experience of childcare implementation and care challenges in the Family Health Strategy in a city of the Ceará state. Data synthesis: Experience report study with a descriptive, qualitative approach, developed within one the Primary Health Care Units in the city of Aracati, Ceará. The report systematization was carried out from the records made in a field diary by a nurse resident, in the period between the months of June 2013 and April 2015. With the implementation of the childcare consultation, one can realize the importance of conducting a systematic follow-up since the prenatal period, including the puerperium and reaching the main focus of this study, the child's health. It highlights the contribution of the Family Health Support Center in the consultations and the use of simple technologies favoring the interaction between professionals, community and health services. Additionally, some weaknesses of the work process had to be overcome, such as: structural barriers; lack of commitment on the part of some professionals; divergences of conducts; unmotivated professionals due to work overload and shortage of training courses offered for qualification of the health team. CONCLUSION: The task is not easy, the challenges are ongoing, but the benefits can be greater and more rewarding than any experienced difficulty. It is hoped that this report can promote critical thinking about the work that has been produced within the Family Health Strategy

OBJETIVO: Relatar la experiencia de implantación de la puericultura y los desafíos del cuidado de la Estrategia de Salud de la Familia de un municipio del Estado de Ceará. Síntesis de los datos: Se trata de un estudio de abordaje cualitativo, de carácter descriptivo, del tipo relato de experiencia que se há desarrollado en el contexto de una de las Unidades Básicas de Salud del municipio de Aracati, Ceará. La sistematización del relato se dio a partir de los registros de un diario de campo de la enfermera residente entre los meses de junio de 2013 y abril de 2015. Tras la implantación de la consulta de puericultura, se percibe la importancia de un seguimiento sistemático a partir del prenatal pasando por el momento del puerperio y alcanzando el foco principal de este estudio que es la salud del niño. Se destaca la contribución del Núcleo de Apoyo a la Salud de la Familia em las consultas y el uso de las tecnologías simples que favorezcan la interacción entre los profesionales, la comunidad y los servicios de salud. Además, algunas fragilidades del proceso de trabajo precisan ser superadas tales como los problemas estructurales, la falta de compromiso de algunos profesionales, las divergencias de conductas, la falta de motivación de los profesionales por la sobrecarga de trabajo y pocos cursos ofertados para la calificación del equipo de salud. CONCLUSIÓN: La tarea no es fácil, los desafíos son continuos pero la recompensa es mayor y más gratificante que cualquier dificultad vivida. Se espera que este relato promueva reflexiones críticas sobre el trabajo que se produce con la Estrategia de Salud de la Familia