BASELINE HEMATOLOGIC AND BIOCHEMICAL VALUES AND CORRELATIONS TO ENVIRONMENTAL PARAMETERS IN MANAGED JAPANESE SPIDER CRABS (MACROCHEIRA KAEMPFERI).

Although the evaluation of hematologic and biochemical parameters is a well-established diagnostic tool in vertebrate medicine, comprehensive understanding of these parameters in invertebrate species is lacking. This study provides baseline hemocyte concentrations and biochemistry values for a population of managed Japanese spider crabs (JSC; Macrocheira kaempferi) housed at six different public aquariums. The methodology for obtaining diagnostic hemolymph samples is described. Distinct hemocyte types were identified, including hyaline cells, semigranulocytes, and granulocytes, with hyaline cells as the predominant type. Correlates to exam findings and environmental parameters were evaluated and included higher absolute semigranulocyte counts (r = 0.65, P = 0.020) and triglyceride levels (r = 0.44, P = 0.014) in JSC with exoskeletal lesions; higher total protein (mean = 5.93 g/dl, P = 0.028), cholesterol (median = 18.5 mg/dl, P = 0.018), triglyceride (median = 15.5 mg/dl, P = 0.002), and amylase (median = 243 U/L, P = 0.013) in nonmolting JSC compared with JSC that have previously molted since acquisition (total protein mean = 4.83 g/dl, cholesterol median = 14 mg/dl, triglyceride median = 6.4 mg/dl, and amylase median = 131 U/L); and lower relative and absolute granulocyte counts (mean = 8.83% P = 0.030, median = 1,162 cells/µl P = 0.006, respectively) and higher albumin (median = 1.35 g/dl, P = 0.031) in JSC housed at facilities that used ozone sterilization. The data presented serve as a foundation for understanding basic clinical parameters in JSC hemolymph, as well as the potential influence of environmental stressors on those parameters.

Left shift and toxic change in heterophils and neutrophils of non-mammalian vertebrates: A comparative review, image atlas, and practical considerations.

Heterophils and neutrophils are important first cellular responders to inflammatory conditions. In addition to quantitative shifts in the numbers of these cells in blood, inflammatory disease states often have accompanying increases in immature precursor stages (left shift) and/or evidence of toxic change on blood film evaluation. Recognition of left shift and toxic change morphologies is a salient diagnostic finding with clinical relevance across species. The objectives of this report are to (a) review heterophil and neutrophil function and structure across the vertebrate animal kingdom, (b) compare morphologic features of left shift and toxic change in heterophils and neutrophils of non-mammalian vertebrates (NMV) to mammals, (c) provide an image guide demonstrating the breadth of morphologic diversity of heterophil and neutrophil lineages in health and disease across taxa, and (d) discuss practical considerations for clinical pathologists and other professionals involved in the recognition and interpretation of observations in the inflammatory leukogram of NMV.

Intraindividual Characterization of the Sleep Spindle Variability in Healthy Subjects.

Spatial and frequency characterization of sleep spindles have been extensively addressed using M/EEG or fMRI recordings. However, its intraindividual variability across time has not been addressed. Here we propose to assess the intraindividual variability of sleep spindles in a time-resolved way by means of a trial-to-trial-variability (TTV) measure. For that purpose, the EEG of 26 healthy subjects were recorded overnight. After an exhaustive preprocessing pipeline to remove artifacts, spindles were automatically detected using a complex demodulation-based method. Then, the Wavelet Scalogram was estimated to validate it. Spindle TTV of each participant was also computed for all the conventional EEG frequency bands. Root mean square (RMS) of each TTV signal was calculated as a measure of the total variability of each spindle. Results showed significant differences in the variability between frequencies. Specifically, RMS in the beta-1 frequency band showed higher values as compared to all the other frequency bands (p<0.001). TTV curves showed a dichotomic trend, with lower frequencies showing an increase in the variability before the spindle onset, and higher frequencies showing such increase after the onset. The dependence of the spindle variability with the frequency could be explained by the influence of the multiple cortical generators involved.Clinical Relevance- Sleep spindles are similarly affected in different cognitive-related disorders, which supports the relevance of assessing abnormal sleep patterns as a possible cause for such cognitive deficits.

Selecting optimal spectral bands for improved detection of autofluorescent biomarkers in multiphoton microscopy.

SIGNIFICANCE: In multiphoton microscopy, two-photon excited fluorescence (TPEF) spectra carry valuable information on morphological and functional biological features. For measuring these biomarkers, separation of different parts of the fluorescence spectrum into channels is typically achieved by the use of optical band pass filters. However, spectra from different biomarkers can be unknown or overlapping, creating a crosstalk in between the channels. Previously, establishing these channels relied on prior knowledge or heuristic testing. AIM: The presented method aims to provide spectral bands with optimal separation between groups of specimens expressing different biomarkers. APPROACH: We have developed a system capable of resolving TPEF with high spectral resolution for the characterization of biomarkers. In addition, an algorithm is created to simulate and optimize optical band pass filters for fluorescence detection channels. To demonstrate the potential improvements in cell and tissue classification using these optimized channels, we recorded spectrally resolved images of cancerous (HT29) and normal epithelial colon cells (FHC), cultivated in 2D layers and in 3D to form spheroids. To provide an example of an application, we relate the results with the widely used redox ratio. RESULTS: We show that in the case of two detection channels, our system and algorithm enable the selection of optimized band pass filters without the need of knowing involved fluorophores. An improvement of 31,5% in separating different 2D cell cultures is achieved, compared to using established spectral bands that assume NAD(P)H and FAD as main contributors of autofluorescence. The compromise is a reduced SNR in the images. CONCLUSIONS: We show that the presented method has the ability to improve imaging contrast and can be used to tailor a given label-free optical imaging system using optical band pass filters targeting a specific biomarker or application.

Performance comparison of Yb:YAG ceramics and crystal gain material in a large-area, high-energy, high average-power diode-pumped laser.

We compare for the first time the influence of different Yb:YAG gain media on the performance of a large-area, high average-power laser system with an output energy of up to 6 J. Monocrystalline slabs grown by a new technique without central growth defect are compared with ceramics. Small signal gain, maximum output energy and thermal lensing are compared for ceramic slabs with co-sintered amplified spontaneous emission (ASE) absorber cladding, monocrystalline slab with and without optically bonded ASE absorber cladding, and surface structured monocrystalline slabs. We show that these large monocrystals with optically bonded absorber cladding have similar performance to cladded ceramics, so far the only material for high-energy Yb:YAG lasers.

High-flow nasal cannula therapy versus non-invasive ventilation in children with severe acute asthma exacerbation: An observational cohort study / Oxigenoterapia de alto flujo frente a ventilación no invasiva en niños con estatus asmático: estudio observacional de cohortes

Introduction: The present study describes our experience with the high-flow humidified nasal cannula (HFNC) versus non-invasive ventilation (NIV) in children with severe acute asthma exacerbation (SA). Methods: An observational study of a retrospective cohort of 42 children with SA admitted to a Pediatric Intensive Care Unit (PICU) for non-invasive respiratory support was made. The primary outcome measure was failure of initial respiratory support (need to escalate from HFNC to NIV or from NIV to invasive ventilation). Secondary outcome measures were the duration of respiratory support and PICU length of stay (LOS). Results: Forty-two children met the inclusion criteria. Twenty (47.6%) received HFNC and 22 (52.3%) NIV as initial respiratory support. There were no treatment failures in the NIV group. However, 8 children (40%) in the HFNC group required escalation to NIV. The PICU LOS was similar in both the NIV and HFNC groups. However, on considering the HFNC failure subgroup, the median length of respiratory support was 3-fold longer (63h) and the PICU LOS was also longer compared with the rest of subjects exhibiting treatment success. Conclusions: Despite its obvious limitations, this observational study could suggest that HFNC in some subjects with SA may delay NIV support and potentially cause longer respiratory support, and longer PICU LOS (AU)

Introducción: El objetivo de este estudio es comparar nuestra experiencia con el uso de oxigenoterapia de alto flujo (OAF) frente a la ventilación no invasiva (NIV) en niños con estatus asmático (EA). Métodos: Estudio observacional de una cohorte retrospectiva de 42 niños con EA ingresados en nuestra Unidad de Cuidados Intensivos Pediátricos (UCIP) con soporte respiratorio no invasivo. El objetivo principal del estudio fue valorar el éxito/fracaso del soporte respiratorio inicial (necesidad o no de escalar a un soporte respiratorio superior). El objetivo secundario fue comparar la duración del soporte respiratorio y del ingreso en la UCIP. Resultados: Cuarenta y dos niños cumplieron con los criterios de inclusión. Veinte (47,6%) fueron tratados con OAF y 22 (52,3%) con VNI como soporte respiratorio inicial. No hubo fracaso terapéutico en el grupo VNI, si bien 8 niños (40%) del grupo OAF fueron cambiados a VNI. La duración de la estancia en la UCIP y en el hospital fue similar en ambos grupos NIV y HFNC. Sin embargo, en el subgrupo de fracaso de OAF, la duración del soporte respiratorio (el triple, 63h) y la estancia en la UCIP fueron mucho mayores en comparación con los sujetos que tuvieron éxito en el tratamiento. Conclusiones: Este estudio observacional, con sus evidentes limitaciones, podría sugerir que el uso de HFNC en algunos sujetos con EA puede retrasar el inicio de la VNI y potencialmente causar un soporte respiratorio más prolongado y una mayor estancia en la UCIP (AU)

Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation / El volumen de nutrición enteral no se correlaciona con las infecciones del tracto respiratorio inferior en pacientes con ventilación mecánica

Objective: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). Design: A retrospective secondary analysis was carried out. Setting: The Intensive Care Unit of a University Hospital. Patients or participants: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. Interventions: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. Main variables of interest: Lower respiratory tract infection episodes. Results: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. Conclusions: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV (AU)

Objetivo: Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño: Análisis secundario retrospectivo. Ámbito: La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes: Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones: Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés: Episodios de infección del tracto respiratorio inferior. Resultados: Sesenta y seis de los 185 pacientes (35,7%) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones: El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM (AU)

Enteral nutrition volume is not correlated with lower respiratory tract infection in patients on mechanical ventilation.

OBJECTIVE: To evaluate the effect of enteral nutrition volume, gastrointestinal function and the type of acid suppressive drug upon the incidence of lower respiratory tract infections in critically ill patients on mechanical ventilation (MV). DESIGN: A retrospective secondary analysis was carried out. SETTING: The Intensive Care Unit of a University Hospital. PATIENTS OR PARTICIPANTS: Patients≥18-years-old expected to need MV for more than four days, and receiving enteral nutrition by nasogastric tube within 24h of starting MV. INTERVENTIONS: We correlated enteral nutrition volume administered during the first 10 days, gastrointestinal function and the type of acid suppressive therapy with the episodes of lower respiratory tract infection up until day 28. Cox proportional hazards ratios in univariate and adjusted multivariate models were used. Statistical significance was considered for p<0.05. MAIN VARIABLES OF INTEREST: Lower respiratory tract infection episodes. RESULTS: Sixty-six out of 185 patients (35.7%) had infection; 27 patients had ventilator-associated pneumonia; and 39 presented ventilator-associated tracheobronchitis. Uninfected and infected groups were similar in terms of enteral nutrition volume (54±12 and 54±9mL/h; p=0.94) and caloric intake (19.4±4.9 and 19.6±5.2kcal/kg/d; p=0.81). The Cox proportional hazards model showed neurological indication of MV to be the only independent variable related to infection (p=0.001). Enteral nutrition volume, the type of acid suppressive therapy, and the use of prokinetic agents were not significantly correlated to infection. CONCLUSIONS: Enteral nutrition volume and caloric intake, gastrointestinal dysfunction and the type of acid suppressive therapy used were not associated to lower respiratory tract infection in patients on MV.

High-flow nasal cannula therapy versus non-invasive ventilation in children with severe acute asthma exacerbation: An observational cohort study.

INTRODUCTION: The present study describes our experience with the high-flow humidified nasal cannula (HFNC) versus non-invasive ventilation (NIV) in children with severe acute asthma exacerbation (SA). METHODS: An observational study of a retrospective cohort of 42 children with SA admitted to a Pediatric Intensive Care Unit (PICU) for non-invasive respiratory support was made. The primary outcome measure was failure of initial respiratory support (need to escalate from HFNC to NIV or from NIV to invasive ventilation). Secondary outcome measures were the duration of respiratory support and PICU length of stay (LOS). RESULTS: Forty-two children met the inclusion criteria. Twenty (47.6%) received HFNC and 22 (52.3%) NIV as initial respiratory support. There were no treatment failures in the NIV group. However, 8 children (40%) in the HFNC group required escalation to NIV. The PICU LOS was similar in both the NIV and HFNC groups. However, on considering the HFNC failure subgroup, the median length of respiratory support was 3-fold longer (63h) and the PICU LOS was also longer compared with the rest of subjects exhibiting treatment success. CONCLUSIONS: Despite its obvious limitations, this observational study could suggest that HFNC in some subjects with SA may delay NIV support and potentially cause longer respiratory support, and longer PICU LOS.

Oxigenoterapia de alto flujo frente a ventilación no invasiva en niños con estatus asmático: estudio observacional de cohortes / High-flow oxygen therapy versus non-invasive ventilation in children with asthmatic status: observational cohort study

Introducción El objetivo de este estudio es comparar nuestra experiencia con el uso de oxigenoterapia de alto flujo (OAF) frente a la ventilación no invasiva (NIV) en niños con estatus asmático (EA). Métodos Estudio observacional de una cohorte retrospectiva de 42 niños con EA ingresados en nuestra Unidad de Cuidados Intensivos Pediátricos (UCIP) con soporte respiratorio no invasivo. El objetivo principal del estudio fue valorar el éxito/fracaso del soporte respiratorio inicial (necesidad o no de escalar a un soporte respiratorio superior). El objetivo secundario fue comparar la duración del soporte respiratorio y del ingreso en la UCIP. Resultados Cuarenta y dos niños cumplieron con los criterios de inclusión. Veinte (47,6 por ciento) fueron tratados con OAF y 22 (52,3 por ciento) con VNI como soporte respiratorio inicial. No hubo fracaso terapéutico en el grupo VNI, si bien 8 niños (40 por ciento) del grupo OAF fueron cambiados a VNI. La duración de la estancia en la UCIP y en el hospital fue similar en ambos grupos NIV y HFNC. Sin embargo, en el subgrupo de fracaso de OAF, la duración del soporte respiratorio (el triple, 63h) y la estancia en la UCIP fueron mucho mayores en comparación con los sujetos que tuvieron éxito en el tratamiento. Conclusiones Este estudio observacional, con sus evidentes limitaciones, podría sugerir que el uso de HFNC en algunos sujetos con EA puede retrasar el inicio de la VNI y potencialmente causar un soporte respiratorio más prolongado y una mayor estancia en la UCIP.

El volumen de nutrición enteral no se correlaciona con las infecciones del tracto respiratorio inferior en pacientes con ventilación mecánica / The volume of enteral nutrition does not correlate with lower respiratory tract infections in patients with mechanical ventilation

Objetivo. Valorar el efecto del volumen de nutrición enteral, la función gastrointestinal y el tipo de protección gástrica en la incidencia de infección respiratoria del tracto inferior en pacientes críticos con ventilación mecánica (VM). Diseño Análisis secundario retrospectivo. Ámbito La Unidad de Cuidados Intensivos de un hospital universitario. Pacientes o participantes Pacientes con edad≥18 años que se espera que precisen de VM durante>4 días y reciban nutrición enteral en las primeras 24h. Intervenciones Correlacionamos el volumen de nutrición enteral administrado durante los primeros 10 días, la función gastrointestinal y el tipo de protección gástrica con los episodios de infección pulmonar del tracto inferior hasta el día 28. Utilizamos el modelo de regresión de Cox. Un valor de p<0,05 fue considerado estadísticamente significativo. Principal variable de interés Episodios de infección del tracto respiratorio inferior. Resultados Sesenta y seis de los 185 pacientes (35,7 por ciento) presentaron infección, 27 pacientes neumonía y 39 traqueobronquitis. Los pacientes no infectados e infectados fueron similares en el volumen de nutrición enteral (54±12 y 54±9mL/h; p=0,94) y aporte calórico (19,4±4,9 y 19,6±5,2kcal/kg/d; p=0,81). El modelo de regresión de Cox mostró que la causa neurológica de VM fue la única variable independiente asociada con infección (p=0,001). El volumen de nutrición enteral, el tipo de protección gástrica y la función gastrointestinal no se correlacionaron significativamente con la infección. Conclusiones El volumen y aporte calórico de nutrición enteral, la disfunción gastrointestinal y el tipo de protección gástrica no se asociaron a la infección del tracto respiratorio inferior en pacientes con VM.

Analysis of the non-stationarity of neural activity during an auditory oddball task in schizophrenia.

The aim of this study was to characterize brain dynamics during an auditory oddball task. For this purpose, a measure of the non-stationarity of a given time-frequency representation (TFR) was applied to electroencephalographic (EEG) signals. EEG activity was acquired from 20 schizophrenic (SCH) patients and 20 healthy controls while they underwent a three-stimulus auditory oddball task. The Degree of Stationarity (DS), a measure of the non-stationarity of the TFR, was computed using the continuous wavelet transform. DS was calculated for both the baseline [-300 0] ms and active task [150 550] ms windows of a P300 auditory oddball task. Results showed a statistically significant increase (p<;0.05) in non-stationarity for controls during the cognitive task in the central region, while less widespread statistically significant differences were obtained for SCH patients, especially in the beta-2 and gamma bands. Our findings support the relevance of DS as a means to study cerebral processing in SCH. Furthermore, the lack of statistically significant changes in DS for SCH patients suggests an abnormal reorganization of neural dynamics during an oddball task.

Novel measure of the weigh distribution balance on the brain network: graph complexity applied to schizophrenia.

The aim of this study was to assess brain complexity dynamics in schizophrenia (SCH) patients during an auditory oddball task. For this task, we applied a novel graph measure based on the balance of the node weights distribution. Previous studies applied complexity parameters that were strongly dependent on network topology. This could bias the results, as well as making correction techniques, such as surrogating process, necessary. In the present study, we applied a novel graph complexity measure derived from the information theory: Shannon Graph Complexity (SGC). Complexity patterns from electroencephalographic recordings of 20 healthy controls and 20 SCH patients during an auditory oddball task were analyzed. Results showed a significantly more pronounced decrease of SGC for controls than for SCH patients during the cognitive task. These findings suggest an important change in the brain configuration towards a more balanced network, mainly in the connections related to long-range interactions. Since these changes are significantly more pronounced in controls, a deficit in the neural network reorganization can be associated with SCH. In addition, an accuracy of 72.5% was obtained using a receiver operating characteristic curve with a leave-one-out cross-validation procedure. The independence of network topology has been demonstrated by the novel complexity measure proposed in this study, therefore, it complements traditional graph measures as a means to characterize brain networks.

Antioxidant Properties of 2-Hydroxyethyl Methacrylate-Based Copolymers with Incorporated Sterically Hindered Amine.

A series of model linear copolymers of 2-hydroxyethyl methacrylate (HEMA) and a sterically hindered amine derivative [N-(2,2,6,6-tetramethyl-piperidin-4-yl)methacrylamide (HAS)] were synthesized and characterized. Scavenging activities of the copolymers against reactive oxygen species (peroxyl and hydroxyl radicals) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals were determined. It was found that copolymers with medium HAS content (3.5-4.0 mol %) were better scavengers than copolymers with lower and higher HAS content and also than polyHEMA and polyHAS homopolymers and the HAS monomer. Importantly, these copolymers compared favorably even to established low-molecular weight antioxidant standards (BHA and dexpanthenol). Monomer reactivity ratios were determined, and the microstructure of the copolymers was assessed. Subsequently, cross-linked copolymers in the powder and film forms with optimal HAS content were synthesized. Their scavenging activities against the three types of radicals were determined, revealing that these hydrogels are potent scavengers of reactive oxygen species.

Primary cutaneous spindle cell B-cell lymphoma of follicle origin mimicking acne rosacea.

Primary cutaneous spindle cell lymphoma is a unique morphologic variant of cutaneous B-cell follicle center lymphoma characterized by a prominent population of spindle-shaped, medium, and large B lymphocytes with a poorly formed storiform pattern.We report a case of a 35-year-old woman who presented with a well-defined erythematous plaque with 2 nodular, nontender nonscaling nonulcerated lesions on her right cheek mimicking acne rosacea. Microscopic examination revealed a tumor mainly centered in the reticular dermis and mostly composed of spindle-shaped large B lymphocytes exhibiting bizarre shapes with "boomerang-like" or "spermatozoa-like" appearance. The immunohistochemical staining demonstrated neoplastic lymphocytes positive for CD20, CD79α, and BCL-6, and negative for CD3, CD43, CD10, BCL-2, and MUM-1. These results supported the diagnosis of a follicle center B-cell lymphoma with spindle cells.Although this rare variant of primary cutaneous B-cell lymphoma is not included in the recent WHO-EORTC classification, the rarity of this tumor and its unique morphologic appearance frequently leads to misdiagnosis and delays its treatment.

Assessment of neurofeedback training by means of motor imagery based-BCI for cognitive rehabilitation.

The age-related impairment is an increasing problem due to the aging suffered by the population, especially in developed countries. It is usual to use electroencephalogram (EEG)-based Brain Computer Interface (BCI) systems by means of the signal in order to assist and to improve the quality of life of people with disabilities. However, a parallel research line addresses the problem by the use of BCI systems as a way to train cognitive areas to achieve a deceleration of cognitive impairment or even an improvement. In this regard, a neurofeedback training (NFT) tool using motor imagery-based BCI, was developed. Training consists on imagery motor exercises combined with memory and logical relation tasks. In order to assess the effectiveness of the application 40 subjects, older than 59 years old, took part in this study. Our NFT application was tested by 20 subjects and their scores of a neuropsychological test were compared with the remaining 20 subjects who did not perform the NFT. Results show a significant improvement of three cognitive features after performing the NFT: visual perception, expressive speech, and immediate memory. Therefore, evidences show that the performance of a NFT tool based on motor imagery tasks could be a positive activity for slow down the aging effects.

Estradiol induces endothelial cell migration and proliferation through estrogen receptor-enhanced RhoA/ROCK pathway.

Migration and proliferation of endothelial cells are involved in re-endothelialization and angiogenesis, two important cardiovascular processes that are increased in response to estrogens. RhoA, a small GTPase which controls multiple cellular processes, is involved in the control of cell migration and proliferation. Our aim was to study the role of RhoA on estradiol-induced migration and proliferation and its dependence on estrogen receptors activity. Human umbilical vein endothelial cells were stimulated with estradiol, in the presence or absence of ICI 182780 (estrogen receptors antagonist) and Y-27632 (Rho kinase inhibitor). Estradiol increased Rho GEF-1 gene expression and RhoA (gene and protein expression and activity) in an estrogen receptor-dependent manner. Cell migration, stress fiber formation and cell proliferation were increased in response to estradiol and were also dependent on the estrogen receptors and RhoA activation. Estradiol decreased p27 levels, and significantly raised the expression of cyclins and CDK. These effects were counteracted by the use of either ICI 182780 or Y-27632. In conclusion, estradiol enhances the RhoA/ROCK pathway and increases cell cycle-related protein expression by acting through estrogen receptors. This results in an enhanced migration and proliferation of endothelial cells.

Estradiol selectively stimulates endothelial prostacyclin production through estrogen receptor-{alpha}.

Estradiol (E(2)) acts on the endothelium to promote vasodilatation through the release of several compounds, including prostanoids, which are products of arachidonic acid metabolism. Among these, prostacyclin (PGI2) and thromboxane A2 (TXA2) exert opposite effects on vascular tone. The role of different estrogen receptors (ERs) in the PGI2/TXA2 balance, however, has not been fully elucidated. Our study sought to uncover whether E(2) enhances basal production of PGI2 or TXA2 in cultured human umbilical vein endothelial cells (HUVECs), to analyze the enzymatic mechanisms involved, and to evaluate the different roles of both types of ERs (ERalpha and ERbeta). HUVECs were exposed to E(2), selective ERalpha (1,3,5-tris(4-hydroxyphenyl)-4-propyl-1h-pyrazole, PPT) or ERbeta (diarylpropionitrile, DPN) agonists and antagonists (unspecific: ICI 182 780; specific for ERalpha: methyl-piperidino-pyrazole, MPP). PGI2 and TXA2 production was measured by ELISA. Expression of phospholipases, cyclooxygenases (COX-1 and COX-2), PGI2 synthase (PGIS), and thromboxane synthase (TXAS) was analyzed by western blot and quantitative RT-PCR. E(2) (1-100 nM) dose dependently increased PGI2 production (up to 50%), without affecting TXA2 production. COX-1 and PGIS protein and gene expressions were increased, whereas COX-2, phospholipases, and TXAS expression remained unaltered. All these effects were mediated through ERalpha, since they were produced not only in the presence of E(2), but also in that of PPT, while they were abolished in the presence of MPP. In conclusion, E(2), acting through ERalpha, up-regulates COX-1 and PGIS expression, thus directing prostanoid balance toward increased PGI2 production.

Estradiol stimulates vasodilatory and metabolic pathways in cultured human endothelial cells.

Vascular effects of estradiol are being investigated because there are controversies among clinical and experimental studies. DNA microarrays were used to investigate global gene expression patterns in cultured human umbilical vein endothelial cells (HUVEC) exposed to 1 nmol/L estradiol for 24 hours. When compared to control, 187 genes were identified as differentially expressed with 1.9-fold change threshold. Supervised principal component analysis and hierarchical cluster analysis revealed the differences between control and estradiol-treated samples. Physiological concentrations of estradiol are sufficient to elicit significant changes in HUVEC gene expression. Notch signaling, actin cytoskeleton signaling, pentose phosphate pathway, axonal guidance signaling and integrin signaling were the top-five canonical pathways significantly regulated by estrogen. A total of 26 regulatory networks were identified as estrogen responsive. Microarray data were confirmed by quantitative RT-PCR in cardiovascular meaning genes; cyclooxygenase (COX)1, dimethylarginine dimethylaminohydrolase (DDAH)2, phospholipase A2 group IV (PLA2G4) B, and 7-dehydrocholesterol reductase were up-regulated by estradiol in a dose-dependent and estrogen receptor-dependent way, whereas COX2, DDAH1 and PLA2G4A remained unaltered. Moreover, estradiol-induced COX1 gene expression resulted in increased COX1 protein content and enhanced prostacyclin production. DDAH2 protein content was also increased, which in turn decreased asymmetric dimethylarginine concentration and increased NO release. All stimulated effects of estradiol on gene and protein expression were estrogen receptor-dependent, since were abolished in the presence of the estrogen receptor antagonist ICI 182780. This study identifies new vascular mechanisms of action by which estradiol may contribute to a wide range of biological processes.