Predictores del estado post-ictus en el alta hospitalaria. Importancia en enfermería / Predictors of the post-stroke status in the discharge from the hospital. Importance in nursing

A menudo, por parte del paciente y de la familia, se solicita a los profesionales de enfermería que predigan los factores que influyen en el estado post-ictus. Se han realizado numerosos estudios para determinar los factores que influyen en el estado neurológico post-ictus en el momento del alta hospitalaria. Sin embargo, las técnicas de aprendizaje automático no se han utilizado para este propósito. Con el objetivo de obtener reglas de asociación del pronóstico neurológico, se ha llevado a cabo un doble análisis, tanto clínico como con técnicas de aprendizaje automático, de las posibles asociaciones de factores que influyen en el estado neurológico de los pacientes post-ictus. El algoritmo Apriori detectó varias reglas de asociación con alta confianza (≥ 95%), con el siguiente patrón: En pacientes en el rango de edad de 50-80 años, la asociación de un NIHSS entre 11 y 15 puntos (NIHSS intermedio/bajo), junto con la trombectomía, conduce a la recuperación ad integrum al alta. Con la técnica de remuestreo SMOTE, se alcanzó el 100% de confianza para la asociación de NIHSS elevado (>20) y afectación de las arterias carótida y basilar, con pronóstico nefasto (exitus). Estas reglas confirman, por primera vez con aprendizaje automático, la importancia de la asociación de algunos predictores, en el pronóstico post-ictus. El conocimiento por parte de las enfermeras de estas reglas puede mejorar los resultados del ictus. Adicionalmente, el papel de la enfermería en los programas de educación sobre los factores de riesgo, y pronóstico de un ictus se torna imprescindible. (AU)

Nurses are often asked to predict factors that influence post-stroke outcome by the patient and family. Many studies have been carried out in order to determine the factors that influence the neurological status of the post-stroke patient at the moment of the discharge from the hospital. However, machine learning techniques have not been used for this purpose. Therefore, with the objective of obtaining association rules of neurological prognosis, a double analysis, both clinical and with machine learning techniques of the possible associations of factors that influence the neurological status of the post-stroke patients has been carried out. The Apriori algorithm detected several association rules with high confidence (≥ 95%), from which the following pattern: In patients in the age range of 50-80 years, the association of a NIHSS between 11 and 15 points (intermediate/low NIHSS), along with thrombectomy, leads to recovery ad integrum at discharge. With the SMOTE resampling technique, the 100% confidence was reached for the association of high NIHSS (>20) and involvement of the carotid and basilar arteries, with a dire prognosis (exitus). These rules confirm, for the first time with machine learning, the importance of the association of some predictors, in the post-stroke prognosis. The knowledge by the nurses of these association rules can successfully improve stroke outcome. In addition, the role of nurses in education programs that teach knowledge of risk factors and stroke prognosis becomes essential. (AU)

Effect of Vagus Nerve Stimulation on the GASH/Sal Audiogenic-Seizure-Prone Hamster.

Vagus nerve stimulation (VNS) is an adjuvant neuromodulation therapy for the treatment of refractory epilepsy. However, the mechanisms behind its effectiveness are not fully understood. Our aim was to develop a VNS protocol for the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) in order to evaluate the mechanisms of action of the therapy. The rodents were subject to VNS for 14 days using clinical stimulation parameters by implanting a clinically available neurostimulation device or our own prototype for laboratory animals. The neuroethological assessment of seizures and general behavior were performed before surgery, and after 7, 10, and 14 days of VNS. Moreover, potential side effects were examined. Finally, the expression of 23 inflammatory markers in plasma and the left-brain hemisphere was evaluated. VNS significantly reduced seizure severity in GASH/Sal without side effects. No differences were observed between the neurostimulation devices. GASH/Sal treated with VNS showed statistically significant reduced levels of interleukin IL-1ß, monocyte chemoattractant protein MCP-1, matrix metalloproteinases (MMP-2, MMP-3), and tumor necrosis factor TNF-α in the brain. The described experimental design allows for the study of VNS effects and mechanisms of action using an implantable device. This was achieved in a model of convulsive seizures in which VNS is effective and shows an anti-inflammatory effect.

Impacto de la endoglina y de otros marcadores de angiogénesis en las varices recurrentes. Resultados preliminaries / Impact of endoglin and other angiogenesis markers on recurrent varicose veins. Preliminary results

Introducción: después de una cirugía convencional de las varices (crosectomía y stripping de la safena interna) existe un importante porcentaje de recidivas que ocasiona un problema clínico, social y económico. Su etiopatogenia no está bien esclarecida. Objetivo: investigar en pacientes con varices (no recidivadas y recidivadas) la expresión de diferentes moléculas implicadas en los procesos de neovascularización, infl amación e hipoxia. Métodos: 41 pacientes sometidos a cirugía convencional de varices divididos en dos grupos: varices no recidivadas (n = 24) y varices recidivadas (n = 17). En ambos grupos se determinaron en la pared de la vena safena interna a nivel del cayado safenofemoral mediante RT-PCR a tiempo real los siguientes marcadores angiogénicos: endoglina, factor de crecimiento del endotelio vascular (VEGF-A), sus receptores 1 y 2 (VEGFR1 o FLTI), (VEGFR2 o KDR) y el factor inducible por hipoxia (HIF-1A). Todos los pacientes fi rmaron por escrito un consentimiento para participar en el estudio. Resultados: en los pacientes con recidiva varicosa se aprecia, a nivel de la pared venosa, una superior expresión de endoglina (p < 0,05), VEGF-A (p < 0,05), FLT1 (p < 0,001) y KDR (p < 0,001) respecto del grupo de varices no recidivadas. No se observaron diferencias signifi cativas respecto a HIF-1A. Conclusión: existe un aumento de los marcadores de angiogénesis, incluida la endoglina, en las muestras de pacientes portadores de varices con recidivas

Introduction: after conventional surgery for varicose veins (crosectomy and stripping of the internal saphenous)there is a significant percentage of recurrences which cause a clinical, social and economic problem. Its etiopathogenesis is not clear.Objective: to investigate in patients with varicose veins (non-recurrent and recurrent), the expression of differentmolecules involved in the processes of neovascularization, inflammation and hypoxia.Methods: 41 patients undergoing conventional varicose vein surgery, divided into two groups: non-recurrentvaricose veins (n = 24) and recurrent varicose veins (n = 17). In both groups, the following angiogenic markers weredetermined in the wall of the internal saphenous vein at the level of the saphenous-femoral arch, by means of realtime RT-PCR: endoglin, vascular endothelial growth factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLTI), (VEGFR2or KDR), and hypoxia-inducible factor (HIF-1A). All patients signed a written consent to participate in the study.Results: in patients with varicose recurrence, a higher expression of endoglin (p < 0.05), VEGF-A (p < 0.05), FLT1(p < 0.001) and KDR (p < 0.001) is appreciated in respect to the group of non-recurrent varicose veins. No significantdifferences were observed with respect to HIF-1A.Conclusion: there is an increase in angiogenesis markers, including endoglin, in samples from patients with recurrent varicose veins

Stromal SNAI2 Is Required for ERBB2 Breast Cancer Progression.

SNAI2 overexpression appears to be associated with poor prognosis in breast cancer, yet it remains unclear in which breast cancer subtypes this occurs. Here we show that excess SNAI2 is associated with a poor prognosis of luminal B HER2+/ERBB2+ breast cancers in which SNAI2 expression in the stroma but not the epithelium correlates with tumor proliferation. To determine how stromal SNAI2 might influence HER2+ tumor behavior, Snai2-deficient mice were crossed with a mouse line carrying the ErbB2/Neu protooncogene to generate HER2+/ERBB2+ breast cancer. Tumors generated in this model expressed SNAI2 in the stroma but not the epithelium, allowing for the role of stromal SNAI2 to be studied without interference from the epithelial compartment. The absence of SNAI2 in the stroma of HER2+/ERBB2+ tumors is associated with: (i) lower levels of cyclin D1 (CCND1) and reduced tumor epithelium proliferation; (ii) higher levels of AKT and a lower incidence of metastasis; (iii) lower levels of angiopoietin-2 (ANGPT2), and more necrosis. Together, these results indicate that the loss of SNAI2 in cancer-associated fibroblasts limits the production of some cytokines, which influences AKT/ERK tumor signaling and subsequent proliferative and metastatic capacity of ERBB2+ breast cancer cells. Accordingly, SNAI2 expression in the stroma enhanced the tumorigenicity of luminal B HER2+/ERBB2+ breast cancers. This work emphasizes the importance of stromal SNAI2 in breast cancer progression and patients' prognosis. SIGNIFICANCE: Stromal SNAI2 expression enhances the tumorigenicity of luminal B HER2+ breast cancers and can identify a subset of patients with poor prognosis, making SNAI2 a potential therapeutic target for this disease. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/23/5216/F1.large.jpg.

Consumo de la mezcla tabaco-betel-hidróxido cálcico entre estudiantes españoles / Consumption of the tobacco-betel-calcium hidroxyde mixture, among Spanish students

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Cardiotrophin-1 Improves Kidney Preservation, Graft Function, and Survival in Transplanted Rats.

BACKGROUND: Cold ischemia-reperfusion injury is unavoidable during organ transplantation, and prolonged preservation is associated with poorer function recovery. Cardiotrophin-1 (CT-1) is an IL-6 family cytokine with cytoprotective properties. This preclinical study in rats tested whether CT-1 mitigates cold renal ischemia-reperfusion injury in the context of the transplantation of long-time preserved kidneys. METHODS: Kidneys were flushed with cold (4°C) University of Wisconsin solution containing 0.2 µg/mL CT-1 and stored for several periods of time at 4°C in the same solution. In a second approach, kidneys were first cold-preserved for 6 hours and then were perfused with University of Wisconsin solution containing CT-1 (0, 16, 32, or 64 µg/mL) and further cold-preserved. Organ damage markers were measured in the kidneys at the end of the storage period. For renal transplantation, recipient consanguineous Fischer rats underwent bilateral nephrectomy and received a previously cold-preserved (24 hours) kidney as described above. Survival and creatinine clearance were monitored over 30 days. RESULTS: Cardiotrophin-1 in perfusion and preservation fluids reduced oxidative stress markers (superoxide anion and inducible nitric oxide synthase), inflammation markers (NF-κB and tumor necrosis factor-α), and vascular damage (vascular cell adhesion molecule-1) and activated leukemia inhibitory factor receptor and STAT-3 survival signaling. Transplantation of kidneys cold-preserved with CT-1 increased rat survival and renal function (ie, lower plasma creatinine and higher creatinine clearance) and improved kidney damage markers after transplantation (ie, lower superoxide anion, tumor necrosis factor-α, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 and higher NF-κB). CONCLUSIONS: Cardiotrophin-1 represents a novel therapeutic strategy to reduce ischemia-reperfusion and cold preservation injury to rescue suboptimal kidneys and, consequently, to improve the clinical outcomes of renal transplantation.

Peri-implant and Paracrestal Inflammatory Biomarkers at Failing Versus Surviving Implant Sites in a Beagle Dog Study.

PURPOSE: This study sought to quantify three biochemical mediators of inflammation (tumor necrosis factor alpha [TNF-α], superoxide anion [SOA], and myeloperoxidase [MPO]) by analyzing crestal (peri-implants) and paracrestal gingival biopsy samples obtained from an experimental study on beagle dogs treated with implants inserted immediately into fresh sockets with circumferential defects. MATERIALS AND METHODS: In 10 beagle dogs, 4 roughened titanium implants (3.8 mm wide × 8 mm high) were placed in the distal sockets of the third and fourth premolars, where a circumferential defect (5 mm wide and 5 mm deep) had been previously created by trephination. After varying follow-up periods, ranging from 80 to 190 days, the dogs were explored clinically to assess implant survival, peri-implant pocket depth, and implant stability. The levels of three biochemical mediators of inflammation (MPO, TNF-α, and SOA) were investigated using the crestal and paracrestal gingival biopsy samples with ELISA tests. RESULTS: It was found that 37.5% of the implants were either absent or mobile. Higher levels of the inflammatory mediators were found in the crestal samples than in the paracrestal samples. The final implant stability values were significantly correlated with the final probing depth (r = -0.83, P < .01), but neither of the clinical measures were significantly correlated with any biochemical marker. The risk of implant failure was significantly proportional to the level of MPO (odds ratio: 1.1) and TNF-α (odds ratio: 1.1) in both the crestal and paracrestal regions. CONCLUSION: All the inflammatory mediators studied were higher in the crestal areas than in the paracrestal regions, but only the values of MPO and TNF-α were significant predictors of implant failure.

Unraveling heterogeneous susceptibility and the evolution of breast cancer using a systems biology approach.

BACKGROUND: An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account the underlying heterogeneity at different molecular levels. RESULTS: Here, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers. Our model is based on our analyses of a cohort of mice that are characterized by heterogeneous susceptibility to ERBB2-positive breast cancers. Our analysis reveals that there are similarities between ERBB2 tumors in humans and those of backcross mice at clinical, genomic, expression, and signaling levels. We also show that mice that have tumors with intrinsically high levels of active AKT and ERK are more resistant to tumor metastasis. Our findings suggest for the first time that a site-specific phosphorylation at the serine 473 residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we present two predictive models that can explain the heterogeneous behavior of the disease in the mouse population when we consider simultaneously certain genetic markers, liver cell signaling and serum biomarkers that are identified before the onset of the disease. CONCLUSIONS: Considering simultaneously tumor pathophenotypes and several molecular levels, we show the heterogeneous behavior of ERBB2-positive breast cancer in terms of disease progression. This and similar studies should help to better understand disease variability in patient populations.

Effect of adenosine in extracellular matrix synthesis in human and rat mesangial cells.

Adenosine (ADO) is an intermediary metabolite of adenosine trisphosphate degradation and a vasoactive mediator. We showed previously that ADO induces contraction and proliferation in rat mesangial cells by a mechanism involving A1 and A2 receptors. The studies concerning the effect of ADO on extracellular matrix (ECM) accumulation in mesangial cells are scarce. The purpose of our study was to evaluate the effect of ADO and the effect of the selective stimulation of A1 and A2 ADO receptors on the expression of ECM components fibronectin and collagen type I, in human and rat renal mesangial cells. Cultured human and rat renal mesangial cells were subjected to selective stimulation of A1 and A2 ADO receptors for 24 and 48 h. Fibronectin and collagen type I expression was evaluated by Western blot; total collagen synthesis was measured by [3H]-proline incorporation into collagen proteins. ADO, A1 and A2 receptor stimulation induce increases in fibronectin expression in rat mesangial cells, and A1 receptor stimulation partially inhibits fibronectin expression in serum-stimulated rat mesangial cells, without any effect in human mesangial cells. A2 receptor stimulation reduces collagen type I expression in serum-stimulated mesangial cells. Neither ADO nor A1 or A2 receptor stimulation induce significant changes in total collagen synthesis. These data suggest that ADO is not a major regulator of ECM synthesis in rat and human mesangial cells.

Involvement of H- and N-Ras isoforms in transforming growth factor-beta1-induced proliferation and in collagen and fibronectin synthesis.

Transforming growth factor beta1 (TGF-beta1) has a relevant role in the origin and maintenance of glomerulosclerosis and tubule-interstitial fibrosis. TGF-beta and Ras signaling pathways are closely related: TGF-beta1 overcomes Ras mitogenic effects and Ras counteracts TGF-beta signaling. Tubule-interstitial fibrosis is associated to increases in Ras, Erk, and Akt activation in a renal fibrosis model. We study the role of N- and H-Ras isoforms, and the involvement of the Ras effectors Erk and Akt, in TGF-beta1-mediated extracellular matrix (ECM) synthesis and proliferation, using embrionary fibroblasts from double knockout (KO) mice for H- and N-Ras (H-ras(-/-)/N-ras(-/-)) isoforms and from heterozygote mice (H-ras(+/-)/N-ras(+/-)). ECM synthesis is increased in basal conditions in H-ras(-/-)/N-ras(-/-) fibroblasts, this increase being higher after stimulation with TGF-beta1. TGF-beta1-induced fibroblast proliferation is smaller in H-ras(-/-)/N-ras(-/-) than in H-ras(+/-)/N-ras(+/-) fibroblasts. Erk activation is decreased in H-ras(-/-)/N-ras(-/-) fibroblasts; inhibition of Erk activation reduces fibroblast proliferation. Akt activation is higher in double KO fibroblasts than in heterozygotes; inhibition of Akt activation also inhibits ECM synthesis. We suggest that H- and N-Ras isoforms downregulate ECM synthesis, and mediate proliferation, in part through MEK/Erk activation. PI3K-Akt pathway activation may be involved in the increase in ECM synthesis observed in the absence of H- and N-Ras.