Dlk1 Is Necessary for Proper Skeletal Muscle Development and Regeneration

Delta-like 1homolog (Dlk1) is an imprinted gene encoding a transmembrane protein whose increased expression has been associated with muscle hypertrophy in animal models. However, the mechanisms by which Dlk1 regulates skeletal muscle plasticity remain unknown. Here we combine conditional gene knockout and over-expression analyses to investigate the role of Dlk1 in mouse muscle development, regeneration and myogenic stem cells (satellite cells). Genetic ablation of Dlk1 in the myogenic lineage resulted in reduced body weight and skeletal muscle mass due to reductions in myofiber numbers and myosin heavy chain IIB gene expression. In addition, muscle-specific Dlk1 ablation led to postnatal growth retardation and impaired muscle regeneration, associated with augmented myogenic inhibitory signaling mediated by NF-κB and inflammatory cytokines. To examine the role of Dlk1 in satellite cells, we analyzed the proliferation, self-renewal and differentiation of satellite cells cultured on their native host myofibers. We showed that ablation of Dlk1 inhibits the expression of the myogenic regulatory transcription factor MyoD, and facilitated the self-renewal of activated satellite cells. Conversely, Dlk1 over-expression inhibited the proliferation and enhanced differentiation of cultured myoblasts. As Dlk1 is expressed at low levels in satellite cells but its expression rapidly increases upon myogenic differentiation in vitro and in regenerating muscles in vivo, our results suggest a model in which Dlk1 expressed by nascent or regenerating myofibers non-cell autonomously promotes the differentiation of their neighbor satellite cells and therefore leads to muscle hypertrophy

Wnt5a Regulates Midbrain Dopaminergic Axon Growth and Guidance

During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM) the cues that guide dopaminergic (DA) axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway). Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a−/− mice, where fasciculation of the medial forebrain bundle (MFB) as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance

The self-organizing fractal theory as a universal discovery method: the phenomenon of life

A universal discovery method potentially applicable to all disciplines studying organizational phenomena has been developed. This method takes advantage of a new form of global symmetry, namely, scale-invariance of self-organizational dynamics of energy/matter at all levels of organizational hierarchy, from elementary particles through cells and organisms to the Universe as a whole. The method is based on an alternative conceptualization of physical reality postulating that the energy/matter comprising the Universe is far from equilibrium, that it exists as a flow, and that it develops via self-organization in accordance with the empirical laws of nonequilibrium thermodynamics. It is postulated that the energy/matter flowing through and comprising the Universe evolves as a multiscale, self-similar structure-process, i.e., as a self-organizing fractal. This means that certain organizational structures and processes are scale-invariant and are reproduced at all levels of the organizational hierarchy. Being a form of symmetry, scale-invariance naturally lends itself to a new discovery method that allows for the deduction of missing information by comparing scale-invariant organizational patterns across different levels of the organizational hierarchy

Prematuridade entre recém-nascidos de mães com Amniorrexe Prematura Prematuridad entre recién nacidos de nadres com Amniorrexis Prematura Prematurity among new-borns of Mothers with Premature Amniorrexis

Estudo descritivo realizado em maternidade pública de Fortaleza-CE, com objetivo de caracterizar a prematuridade entre recém-nascidos (RNs) internados na Unidade Neonatal em decorrência da amniorrexe prematura. Analisaram-se 37 recém-nascidos e suas mães. Dos RNs, foram analisados: grau de prematuridade, Apgar e necessidade de reanimação. Das mães: idade gestacional, realização de pré-natal, patologias na gestação e tipo de parto. Verificou-se que 35,1% nasceram prematuros e 29,7% com Apgar entre 0 e 6 no 1º minuto de vida, necessitando de reanimação. Quanto à idade gestacional, 35,1% apresentaram ruptura das membranas antes da 37ª semana, 5,4% não realizaram pré-natal, 67,5% compareceram a 2 a 5 consultas e 27,1% referiram 6 ou mais; 16,2% das mães apresentaram doença hipertensiva específica da gestação (DHEG), e 51,3% tiveram parto normal. Conclui-se que a prematuridade foi elevada, podendo representar importante causa de morbimortalidade neonatal, como também acarretar complicações clínicas e obstétricas para a mãe. A DHEG ainda representa um risco para a gravidez. É preciso que novos estudos sobre a temática sejam realizados para se conhecer a verdadeira magnitude do problema.<br>Estudio descriptivo realizado en maternidad pública de Fortaleza-CE, con el objetivo de caracterizar la prematuridad entre recién nacido (RN) internados en la Unidad Neonatal debido al amniorrexis prematuro. Se analisaron 37 recién nacidos y sus madres. De los recién nacidos se analizó: el grado de la prematuridad, apgar y necesidad de reanimación. De las madres: edad gestacional, acompãnamiento pré-natal, tipo del parto y patologías de la gestación. Fué verificado que 31,1% nacieron prematuras, 29,7% con Apgar entre 0 y 6 en el primeiro minuto de vida, necesitando de reanimación. Con respecto a la edad gestational, 35,1% presentaron las rupturas de la membrana antes de la 37ª. Semana, 5,4% sin acompãnamiento pré-natal, 67,5% 2-5 consultas y 27,1% refieren 6 o más, 16,2% de las madres presentaron Dolencia Hipertensiva del Estado Gestacional (DHEG), y 51,3% tuvieran parto normal. Se concluye que la prematuridad fué elevada, representando importante causa de la morbimortalidad neonatal, como también acarretar complicaciones clínicas y obstétricas para la madre. La DHEG aún representa um risco para la gestación. És necesário que nuevos estúdios sobre la temática sean realizados para se conocer la verdadera magnitud del problema.<br>This is a descriptive study that took place in a public maternity in Fortaleza Ce, with objective to characterize the prematureness among newly born (RN) interned in the Unidade Neonatal due to the premature amniorrexe. It was analyzed 37 newborns along with their mothers. From the newborns it was analyzed: prematureness degree, Apgar and reanimation need; and from their mothers: gestational age, pre natal care, birth and gestational pathologies. It was found that 35,1% of the babies are premature and 29,7% had a 0-6 Agar during the first minute of life, needing reanimation. As for the gestational age, 35,1% presented membrane ruptures before the 37th week of birth, 5,4% did not go through pre natal care, 67,5% attended from 2 to 5 appointments and 27,1% attended to 6 or more, 16,2% of the mothers presented Gestational Specific Highblood Pressure Disease (GSHPD) and 51,3% of the mothers went through normal delivery. It was concluded that the prematureness was high, being a main cause of newborn morbid/mortality and that it also brings clinical and obstetric complications for the mothers. The GSHPD still represents a risk to pregnancy. More studies on the subject are needed in order to acknowledged the real magnitude of the problem

Validação da nomenclatura diagnóstica de enfermagem direcionada ao pré-natal: base CIPESC® em Curitiba - PR Validación de la nomenclatura diagnóstica de enfermería direccionada al periodo de embarazo: base CIPESC® en Curitiba - PR Validating the nomenclature diagnosis of pre-natal nursing: base CIPESC® in Curitiba

É de fundamental importância uma linguagem específica da profissão e a CIPESC® -Classificação Internacional para as Práticas de Enfermagem em Saúde Coletiva tem como um dos objetivos desvelar a atuação dos enfermeiros na saúde coletiva. No Brasil, a ABEn, responsável pela classificação, encontrou na Secretaria Municipal da Saúde de Curitiba - PR aliada para efetiva implantação. O objetivo deste artigo foi validar a nomenclatura dos 52 diagnósticos de enfermagem do pré-natal - base CIPESC® - Curitiba. É um estudo exploratório-descritivo, desenvolvido com enfermeiras assistenciais e com experts na área de gineco-obstetrícia e terminologia. Os resultados foram apresentados pelo Índice de Concordância por meio de freqüência absoluta, todas as definições foram validadas, porém necessitam de adequações à linguagem cotidiana. As enfermeiras apresentam dificuldades para inter-pretar intervenção de enfermagem na promoção do bem-estar, sendo premente a discussão do conceito de promoção à saúde e o processo saúde-doença na saúde coletiva.<br>Es de fundamental importancia un lenguaje específico de la profesión y la CIPESC® -Clasificación Internacional para las Prácticas de Enfermería en Salud Colectiva que tiene como uno de los objetivos desvedar la actuación de los enfermeros en la salud colectiva. En Brasil, la ABEn, responsable por la clasificación, encontró como aliada para realizar la efectiva implantación la Secretaria Municipal de la Salud de Curitiba - PR. El objetivo de este artículo fue validar la nomenclatura de los 52 diagnósticos de enfermería del periodo de embarazo - base CIPESC® - Curitiba. Es un estudio exploratorio-descriptivo, desarrollado con enfermeras asistenciales y con experts en el sector de ginecología-obstetricia y terminología. Los resultados fueron presentados por el Índice de Concordancia por medio de la frecuencia absoluta, todas las definiciones fueron validadas, sin embargo, necesitan de adecuaciones para el lenguaje cotidiano. Las enfermeras presentan dificultades para interpretar la intervención de enfermería en la promoción del bienestar, siendo apremiante la discusión del concepto de promoción a la salud y el proceso salud-enfermedad en la salud colectiva.<br>The existence of a specific language for the profession is essential, and the International Nursing Practice Classification in Collective Health (CIPESC, in the Portuguese-language acronym) has as one of its goals the classification of the work of nurses in collective health. In Brazil, the Brazilian Nursing Association (ABEn, in the Portuguese-language acronym), responsible for the classification, found in the Municipal Secretary of Health of Curitiba, in the State of Paraná, an ally for its effective implantation. The purpose of this article was to validate the nomenclature of the 52 diagnoses of pre-natal Nursing - CIPESC base - in Curitiba. It is an exploratory-descriptive study developed with assisting nurses and experts in the area of gynecology obstetrics and terminology. The results were presented through the Consonance Index through absolute frequency. All the definitions were validated, but they need to be adjusted to the daily language. The nurses show difficulty in interpret nursing intervention in the promotion of well-being, and it is urgent to discuss the concept of health promotion and the health-illness process in collective health

A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study

<p>Abstract</p> <p>Background</p> <p>Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO.</p> <p>Methods/Design</p> <p>The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in the first 60 randomized patients at 9 months to assess neointima thickness, percentage of neointima coverage, and stent strut malapposition and coverage. Personnel blinded to the allocated treatment will review all angiographic and optical coherence assessments. Secondary clinical endpoints include major adverse cardiac events, clinically driven target vessel revascularization, target vessel failure and stent thrombosis to 5-year clinical follow-up. An independent clinical event committee blinded to the allocated treatment will review all clinical events.</p> <p>Trial registration</p> <p>Clinical Trials.gov: NCT01516723. Patient recruitment started in February 2012.</p