Plasma cell-free DNA concentration increases during luteolysis in beef cows.

During cell death, DNA is fragmented and reaches the bloodstream in the form of cell-free DNA (cfDNA). Luteal cells must undergo an apoptotic process during structural luteolysis to begin a new oestrous cycle. We hypothesized that cfDNA concentrations would increase when inducing luteolysis by applying prostaglandin F2α (PGF2α) analog to the cycling cow. Multiparous non-pregnant and non-lactating Angus cows (Bos taurus; n = 15) were synchronized using the 7-day CoSynch + CIDR protocol. Ten days after oestrus was detected, two treatments were applied (PGF2α, n = 10; or Con, n = 5). Twice a day, grey mode and colour Doppler ultrasonography were used to calculate area (CL-A) and luteal blood perfusion (LBP%). Additionally, we collected one blood sample for plasma progesterone (P4) and cfDNA concentrations for four consecutive days. Data analysis was performed using the GLM procedure of SAS. The luteolysis induction was demonstrated by a decrease in P4 concentrations (p ≤ .01) and CL-A (p ≤ .01) in the PGF2α group after 12 h of the PGF2α injection. Reduction of LBP% (p ≤ .01) in the PGF2α group after 36 h of the injection. The concentration of cfDNA showed a significant increase (p = .05) after 48 h of the PGF2α application in the PGF2α group. In conclusion, cfDNA showed a significantly increased concentration after luteolysis induction, which can imply that cfDNA could be used as a luteolysis biomarker in plasma.

Inovando no pensar e no agir científico: o método de Design Thinking para a enfermagem / Innovación en pensamiento y acción científica: el método de Design Thinking para enfermería / Innovation in thinking and scientific action: the method of Design Thinking for nursing

Resumo Objetivos Relatar experiências vivenciadas durante um estágio de Pós-Doutorado, o conhecimento adquirido sobre o método de Design Thinking e a socialização desse método em evento científico de Enfermagem. Método Trata-se do relato de experiência de um Pós-Doutorado realizado no Canadá e da aquisição de novos conhecimentos na área da pesquisa e do ensino. Resultados A oportunidade mais desafiadora foi a aproximação com o Design Thinking, pois esse conceito promoveu a consciência sobre a urgência de adotar um novo paradigma para pensar, colaborar, ensinar, desenhar, planejar, executar e avaliar as atividades de pesquisa. Após constantes reflexões sobre Design Thinking, houve a oportunidade de promover uma iniciativa-piloto de tradução de conhecimento do método e observar a excelente receptividade dos participantes no evento. Conclusão A experiência permitiu a aquisição de conhecimentos além da Enfermagem, estimulando o pensamento crítico e fortalecendo a destemida capacidade de pensar e inovar na produção de conhecimento. Implicações para a prática É inegável que o Design Thinking poderá revolucionar a educação, mediante sua inserção nos cursos da área da saúde, configurando uma ferramenta cognitiva que reconstrói a engenhosidade humana inspirada em valores humanísticos e empáticos, assegurando a qualidade de serviços e produtos, e respeitando o perfil do cliente.

Resumen Objetivos Informar experiencias durante una pasantía postdoctoral, como también el conocimiento adquirido sobre el método Design Thinking y la socialización de este método en un evento de enfermería científica. Método Se trata de un informe de experiencia postdoctoral realizada en Canadá y adquisición de nuevos conocimientos en investigación y docencia. Resultados La pasantía permitió la adquisición de nuevos conocimientos en el campo de la investigación y la docencia. La oportunidad más difícil fue el acercamiento al concepto de Design Thinking, porque promovía la conciencia de la urgencia de adoptar un nuevo paradigma para pensar, colaborar, enseñar, diseñar, planificar, ejecutar y evaluar actividades de investigación. Después de reflexiones constantes sobre Design Thinking, surgió la oportunidad de promover una iniciativa piloto para traducir el conocimiento del método y observar la excelente receptividad de los participantes en el evento. Conclusión La experiencia permitió la adquisición de conocimiento más allá de la enfermería, estimulando el pensamiento crítico y fortaleciendo la intrépida capacidad de pensar e innovar en la producción de conocimiento. Implicaciones para la práctica Es innegable que Design Thinking puede revolucionar la educación, a través de su inserción en los cursos del área de salud y configurarse en una herramienta cognitiva que reconstruye el ingenio humano inspirado en valores humanísticos y empáticos, asegurando la calidad de los servicios y productos, y respetando el perfil del cliente.

ABSTRACT Objectives To report experiences during a post-doctoral fellowship which included acquired knowledge about the method of Design Thinking and its dissemination in a scientific nursing event. Method A report of experience conducted in Canada and the acquisition of new knowledge in research and teaching. Results The fellowship established new knowledge in the fields of research and teaching. The most challenging opportunity was the introduction and adoption of Design Thinking. It increased awareness of the urgency to adopt a new paradigm to think, collaborate, teach, design, plan, execute and evaluate research-related activities. After participants reflected about Design Thinking, there was an opportunity to promote a pilot initiative to translate the knowledge about this concept and observe the participants' positive reception in a scientific event. Conclusion The experience allowed the acquisition of knowledge beyond nursing and the stimulation of critical thinking; this strengthened the confidence to think and innovate in the production of knowledge. Implications for practice It is undeniable that Design Thinking may revolutionize education if it is added to health courses as a cognitive tool, inspired by humanistic and empathic values, that reconstructs human inventiveness; this method assures the quality of services and products while respecting the customer's profile.

Modulation of cellular polarization and migration by ephrin/Eph signal-mediated boundary formation.

Compartment boundaries are essential for ensuring proper cell organization during embryo development and in adult tissues, yet the mechanisms underlying boundary establishment are not completely understood. A number of mechanisms, including (i) differential adhesion, (ii) differential tension, and (iii) cell signaling-mediated cell repulsion, are known to contribute and likely a context-dependent balance of each of these dictates boundary implementation. The ephrin/Eph signaling pathway is known to impact boundary formation in higher animals. In different contexts, ephrin/Eph signaling is known to modulate adhesive properties and migratory behavior of cells. Furthermore it has been proposed that ephrin/Eph signaling may modulate cellular tensile properties, leading to boundary implementation. It remains unclear however, whether, in different contexts, ephrin/Eph act through distinct dominant action modes (e.g. differential adhesion vs. cell repulsion), or whether ephrin/Eph signaling elicits multiple cellular changes simultaneously. Here, using micropatterning of cells over-expressing either EphB3 or ephrinB1, we assess the contribution of each these factors in one model. We show that in this system ephrinB1/EphB3-mediated boundaries are accompanied by modulation of tissue-level architecture and polarization of cell migration. These changes are associated with changes in cell shape and cytoskeletal organization also suggestive of altered cellular tension.

Diabetic wound regeneration using peptide-modified hydrogels to target re-epithelialization.

There is a clinical need for new, more effective treatments for chronic wounds in diabetic patients. Lack of epithelial cell migration is a hallmark of nonhealing wounds, and diabetes often involves endothelial dysfunction. Therefore, targeting re-epithelialization, which mainly involves keratinocytes, may improve therapeutic outcomes of current treatments. In this study, we present an integrin-binding prosurvival peptide derived from angiopoietin-1, QHREDGS (glutamine-histidine-arginine-glutamic acid-aspartic acid-glycine-serine), as a therapeutic candidate for diabetic wound treatments by demonstrating its efficacy in promoting the attachment, survival, and collective migration of human primary keratinocytes and the activation of protein kinase B Akt and MAPKp42/44 The QHREDGS peptide, both as a soluble supplement and when immobilized in a substrate, protected keratinocytes against hydrogen peroxide stress in a dose-dependent manner. Collective migration of both normal and diabetic human keratinocytes was promoted on chitosan-collagen films with the immobilized QHREDGS peptide. The clinical relevance was demonstrated further by assessing the chitosan-collagen hydrogel with immobilized QHREDGS in full-thickness excisional wounds in a db/db diabetic mouse model; QHREDGS showed significantly accelerated and enhanced wound closure compared with a clinically approved collagen wound dressing, peptide-free hydrogel, or blank wound controls. The accelerated wound closure resulted primarily from faster re-epithelialization and increased formation of granulation tissue. There were no observable differences in blood vessel density or size within the wound; however, the total number of blood vessels was greater in the peptide-hydrogel-treated wounds. Together, these findings indicate that QHREDGS is a promising candidate for wound-healing interventions that enhance re-epithelialization and the formation of granulation tissue.

Multiwell plate tools for controlling cellular alignment with grooved topography.

In many tissues, cells must be aligned for proper function. This alignment can occur at the cellular and/or subcellular (protein/molecular) level. The alignment of cytoskeletal components, in fact, precedes whole cell alignment. A variety of methods exist to manipulate cytoskeletal and whole cell alignment; one of the simplest and most predictable involves seeding adherent cells onto defined substrate topography. We present here two methods to create grooved multiwell plates: one involving microfabrication, which allows for custom design of substrate topography, and a simpler, inexpensive method using commercially available diffraction gratings. We also include methods for manual and automatic quantification of cell alignment.

Nonautonomous contact guidance signaling during collective cell migration.

Directed migration of groups of cells is a critical aspect of tissue morphogenesis that ensures proper tissue organization and, consequently, function. Cells moving in groups, unlike single cells, must coordinate their migratory behavior to maintain tissue integrity. During directed migration, cells are guided by a combination of mechanical and chemical cues presented by neighboring cells and the surrounding extracellular matrix. One important class of signals that guide cell migration includes topographic cues. Although the contact guidance response of individual cells to topographic cues has been extensively characterized, little is known about the response of groups of cells to topographic cues, the impact of such cues on cell-cell coordination within groups, and the transmission of nonautonomous contact guidance information between neighboring cells. Here, we explore these phenomena by quantifying the migratory response of confluent monolayers of epithelial and fibroblast cells to contact guidance cues provided by grooved topography. We show that, in both sparse clusters and confluent sheets, individual cells are contact-guided by grooves and show more coordinated behavior on grooved versus flat substrates. Furthermore, we demonstrate both in vitro and in silico that the guidance signal provided by a groove can propagate between neighboring cells in a confluent monolayer, and that the distance over which signal propagation occurs is not significantly influenced by the strength of cell-cell junctions but is an emergent property, similar to cellular streaming, triggered by mechanical exclusion interactions within the collective system.

An algorithm to quantify correlated collective cell migration behavior.

Collective cell migration is an important process that determines cell reorganization in a number of biological events such as development and regeneration. Random cell reorganization within a confluent monolayer is a popular in vitro model system for understanding the mechanisms that underlie coordination between neighboring cells during collective motion. Here we describe a simple automated C++ algorithm to quantify the width of streams of correlated cells moving within monolayers. Our method is efficient and allows analysis of thousands of cells in under a minute; analysis of large data sets is therefore possible without limitations due to computational time, a common analysis bottleneck. Furthermore, our method allows characterization of the variability in correlated stream widths among a cell monolayer. We quantify stream width in the human retinal epithelial cell line ARPE-19 and the fibroblast cell line BJ, and find that for both cell types, stream widths within the monolayer vary in size significantly with a peak width of 40 µm, corresponding to a width of approximately two cells. Our algorithm provides a novel analytical tool to quantify and analyze correlated cell movement in confluent sheets at a population level and to assess factors that impact coordinated collective cell migration.

Revisión crítica del concepto psicosomático a la luz del dualismo mente-cuerpo / Critical review of the psychosomatic concept in the context of mind/body dualism

El concepto psicosomático trae consigo una pesada carga semántica que tienesus raíces en el dualismo filosófico, acentuado en la propuesta cartesiana, que hapermeado la racionalidad moderna y con ella la concepción de la enfermedad,tanto en el campo de la medicina como de la psicología. En esta revisión teórica seexpone una breve discusión en torno al concepto “psicosomático”, esbozando lasprincipales perspectivas en el abordaje de la relación mente-cuerpo. Se concluyecomo necesaria la revisión de las posiciones dualistas y la incorporación deuna nueva mirada de las nociones de salud y enfermedad, a partir de la cual elconcepto psicosomático se hace redundante.

The concept psychosomatic brings with it a heavy semantic burden that hasits roots in the philosophical dualism, accentuated in the Cartesian proposal,which has spread through modern rationality and with it the conception of thedisease, in the medical field as well as in psychology. The following articleprovides a brief discussion of this concept, outlining the main perspectivesin addressing the mind-body connection. In conclusion, it is necessary toreview dualistic positions and the addition of a new view of notions abouthealth and illness, from which psychosomatic concept becomes redundant.

O conceito psicossomático traz consigo uma pesada carga semântica que temas suas raízes no dualismo filosófico, acentuada na proposta cartesiana, que seespalhou através da racionalidade moderna e com ela a concepção da doença, nocampo médico, assim como em psicologia. O artigo a seguir apresenta uma brevediscussão sobre este conceito, expondo as principais perspectivas para abordara conexão mente-corpo. Em conclusão, é necessário rever posições e dualista daadição de uma nova perspectiva de noções sobre saúde e doença, a partir do qualo conceito psicossomático torna-se redundante.

Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog.

OBJECTIVE: Left ventricular hypertrophy has been associated with the prolongation of QT-time, and an increased risk of ventricular arrhythmias. The renin angiotensin system has been implicated in the development of ventricular hypertrophy. At 5 weeks complete AV block (CAVB) in the dog, there is: (1) biventricular hypertrophy associated with a transient activation of components of the renin angiotensin system, (2) increased APD, more pronounced in the left than in the right ventricle leading to spatial dispersion of repolarization, and (3) enhanced susceptibility to drug-induced torsade de pointes arrhythmias. To investigate whether these remodeling processes develop in parallel, time dependency was assessed in absence or presence of the AT1 receptor-blocker Irbesartan. METHODS AND RESULTS: Dogs in sinus rhythm, 2 and 5 weeks CAVB were compared to dogs chronically treated with Irbesartan (30 mg/kg BID). Endocardial monophasic APD of left and right ventricle was measured and susceptibility to torsade de pointes was tested by infusing Dofetilide (0.025 mg/kg/5'). Hypertrophy was determined by relating heart-to-body weight at sacrifice. Left ventricular APD had increased more than right ventricular APD at 2 and 5 weeks CAVB, leading to an increase in spatial dispersion. At that time torsade de pointes were evocable in the majority of the dogs. Hypertrophy had only developed completely at 5 weeks CAVB. Irbesartan had no effect on electrical and structural parameters or on arrhythmogenicity. CONCLUSIONS: In the CAVB dog ventricular hypertrophy is not a prerequisite for electrical remodeling or drug-induced torsade de pointes, and the AT1-receptor has no dominant role in the completion of these remodeling processes.