It Takes an Instigator, Vision and Passion, Promoting Health In Haiti: Developing a Partnership Between an Impoverished Nation and an NGO to Develop Advanced Practice Nursing Education, A Case Study

Four nurse educators went to Haiti after the 2012 earthquake to help rebuild the School of Nursing in Port-au-Prince. They were alarmed by the low level of health care in Haiti. Most people have no care, and those that do are treated by nurses who are not trained to do so. This article details the steps the nurses went through to start a family nurse practitioner program in Haiti to address the need for primary care and discusses how they created the partnerships necessary to start such an innovative program at the University of Haiti

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder

PURPOSE: Biallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype, but with limited neuroradiological data and insufficient evidence for causality of the variants. METHODS: Exome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays, and a zebrafish model. RESULTS: We report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model. CONCLUSION: We define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity

Epiregulin and EGFR interactions are involved in pain processing

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions

CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis.status: publishe

Prática Avançada de Enfermagem: uma análise conceitual

Resumo Objetivo Analisar o conceito de Prática Avançada de Enfermagem e elucidar os elementos-chave: atributos, antecedentes e consequências. Métodos O referencial metodológico para o estudo foi o modelo de análise conceitual de Walker e Avant (2011), estruturado mediante uma revisão integrativa da literatura conduzida nos meses de maio e junho de 2017. A busca foi realizada nas bases de dados Scopus, PubMed, CINAHL, Web of Science, Science Direct, Cochrane e Lilacs, considerando estudos que trataram do termo e que foram publicados em português, inglês ou espanhol. Resultados A amostra foi composta por 33 estudos conduzidos em oito países entre os anos 2000 e 2016, sendo 56% publicado no quinquênio 2011-2016. Foram identificados oito atributos: Preparação educacional em nível de mestrado ou doutorado, e especialização em área clínica; Prática baseada em evidências; Habilidade de desenvolver raciocínio clínico e pensamento crítico; Alto nível de autonomia; Avaliação avançada e ampla; Liderança; Capacidades diagnóstica, gerencial e administrativa; Promoção do ensino às outras enfermeiras. Foram identificados os antecedentes e consequências e foi desenvolvida uma definição do conceito. Conclusão Diante da expansão da ideia de enfermagem avançada pelo mundo, particularmente na América Latina, recomendam-se outros estudos relacionados à Prática Avançada de Enfermagem. É necessária uma compreensão aprofundada das questões na prática de implementação no Brasil para ajudar a determinar o conceito futuro de PAE para o país. Este estudo contribui a essa compreensão ao definir o conceito de PAE com seus antecedentes, atributos e consequências

Prática avançada de enfermagem na América Latina e Caribe: análise de contexto

Resumo Objetivo descrever os fatores que podem influenciar a implantação da PAE nos contextos dos países da América Latina e Caribe. Métodos Trata-se de uma análise de contexto realizada em outubro de 2017 mediante uma scoping review. A busca dos estudos deu-se nas bases de dados e nos portais de teses e dissertações nacionais e internacionais. A amostra compôs-se de nove pesquisas, a partir da análise e correlação dos achados dessas publicações sobre a Prática Avançada em Enfermagem na América Latina e no Caribe para com as esferas contextuais propostas por Hinds e suas especificidades. Resultados Dentre os fatores presentes nos contextos dos países da América Latina e Caribe que favorecem a implantação da Prática Avançada em Enfermagem, delimitou-se: as particularidades da Prática Avançada em Enfermagem na América Latina e no Caribe; os desafios e as potencialidades da Prática Avançada em Enfermagem na América Latina e no Caribe; as perspectivas da Prática Avançada em Enfermagem na América Latina e no Caribe; e as legislações da Prática Avançada em Enfermagem na América Latina e no Caribe. Conclusão Inferiu-se que a Prática Avançada em Enfermagem na América Latina e no Caribe apresenta potencialidade de ser implementada, mas ainda há barreiras específicas nas diversas realidades investigadas