Neutral Atom Imaging of the Solar Wind-Magnetosphere-Exosphere Interaction Near the Subsolar Magnetopause.

Energetic neutral atoms (ENAs) created by charge-exchange of ions with the Earth's hydrogen exosphere near the subsolar magnetopause yield information on the distribution of plasma in the outer magnetosphere and magnetosheath. ENA observations from the Interstellar Boundary Explorer (IBEX) are used to image magnetosheath plasma and, for the first time, low-energy magnetospheric plasma near the magnetopause. These images show that magnetosheath plasma is distributed fairly evenly near the subsolar magnetopause; however, low-energy magnetospheric plasma is not distributed evenly in the outer magnetosphere. Simultaneous images and in situ observations from the Magnetospheric Multiscale (MMS) spacecraft from November 2015 (during the solar cycle declining phase) are used to derive the exospheric density. The ~11-17 cm-3 density at 10 RE is similar to that obtained previously for solar minimum. Thus, these combined results indicate that the exospheric density 10 RE from the Earth may have a weak dependence on solar cycle.

Postoperative analgesia with continuous wound infusion of local anaesthesia vs saline: a double-blind randomized, controlled trial in colorectal surgery.

AIM: The aim of this prospective double-blind randomized clinical trial was to determine whether preperitoneal continuous wound infusion (CWI) of the local anaesthetic ropivacaine after either laparotomy or video-assisted laparoscopy for colorectal surgery would reduce patient consumption of morphine. METHOD: Patients scheduled for colorectal surgery randomly received a 48-h preperitoneal CWI of either 0.38% ropivacaine or 0.9% saline at rates of 5 ml/h after laparotomy or 2 ml/h after laparoscopy. The primary end-point was total morphine consumption in surgery and afterwards through a patient-controlled analgesia device. Results in the laparotomy and laparoscopy subgroups were also compared. RESULTS: Sixty-seven patients were included, 33 in the ropivacaine CWI group and 34 in the saline group. Median [interquartile range (IQR)] morphine consumption was lower in the ropivacaine group [23.5 mg (11.25-42.75)] than in the saline group [52 mg (24.5-64)] (P = 0.010). Morphine consumption was also lower in the laparotomy subgroup receiving ropivacaine [21.5 (15.6-34.7)] than in the saline group [52.5 (22.5-65) ml] (P = 0.041). Consumption was statistically similar in laparoscopy patients on ropivacaine or saline. No side effects were observed. Sixteen patients had a surgical wound infection (23.9%); 11 (16.4%) presented wound infection and five (7.5%) organ space infection. Forty-six catheter cultures were obtained; 10 (21.7%) were positive, assessed to be due to contamination. CONCLUSION: Preperitoneal CWI of ropivacaine is a good, safe addition to a multimodal analgesia regimen for colorectal surgery. CWI can reduce morphine consumption without increasing adverse effects.

Overproduction of cyclo-oxygenase-2 (COX-2) is involved in the resistance to apoptosis in vascular smooth muscle cells from diabetic patients: a link between inflammation and apoptosis.

AIMS/HYPOTHESIS: Inflammation is a common feature in cardiovascular diseases, including diabetes mellitus. In addition to the well-known inflammatory role of cyclo-oxygenase-2 (COX-2), this protein has also been implicated in apoptosis resistance in tumour cells. Vascular smooth muscle cells (VSMC) from diabetic patients are also resistant to apoptosis because of an increased abundance of B cell lymphoma 2 protein (BCL2). In this work, we investigated whether overproduction of COX-2 was involved in the resistance to apoptosis in VSMC from diabetic patients. METHODS: VSMC were obtained from internal mammary arteries from patients who had undergone coronary artery bypass graft surgery. Apoptosis was measured by DNA fragmentation, BCL2 degradation and cytochrome c release. RESULTS: Apoptosis induced by C-reactive protein in cells from non-diabetic patients was mediated by COX-2. VSMC from diabetic patients showed higher basal levels of COX-2 compared with those from non-diabetic patients. Transfection of VSMC from non-diabetic patients with a plasmid containing COX-2 (also known as PTGS2) increased basal production of COX-2 and BCL2 and mimicked the resistance to apoptosis that occurs in diabetic patients. We also found a significant correlation (R = 0.846, p = 0.016) between COX-2 and BCL2 production in arterial rings from diabetic patients measured by confocal microscopy. However, inhibition of COX-2 production by small interfering RNA proved unable to reverse BCL2 production in diabetic VSMC. CONCLUSIONS/INTERPRETATION: These results suggest a link between inflammation (COX-2) and apoptosis resistance (BCL2) in the arteries of diabetic patients. This relationship is not causative and the common production of these two proteins may be co-regulated by shared regulatory elements in diabetes.

Determining EMIC Wave Vector Properties Through Multi-Point Measurements: The Wave Curl Analysis.

Electromagnetic ion cyclotron (EMIC) waves play important roles in particle loss processes in the magnetosphere. Determining the evolution of EMIC waves as they propagate and how this evolution affects wave-particle interactions requires accurate knowledge of the wave vector, k. We present a technique using the curl of the wave magnetic field to determine k observationally, enabled by the unique configuration and instrumentation of the Magnetospheric MultiScale (MMS) spacecraft. The wave curl analysis is demonstrated for synthetic arbitrary electromagnetic waves with varying properties typical of observed EMIC waves. The method is also applied to an EMIC wave interval observed by MMS on October 28, 2015. The derived wave properties and k from the wave curl analysis for the observed EMIC wave are compared with the Waves in Homogenous, Anisotropic, Multi-component Plasma (WHAMP) wave dispersion solution and with results from other single- and multi-spacecraft techniques. We find good agreement between k from the wave curl analysis, k determined from other observational techniques, and k determined from WHAMP. Additionally, the variation of k due to the time and frequency intervals used in the wave curl analysis is explored. This exploration demonstrates that the method is robust when applied to a wave containing at least 3-4 wave periods and over a rather wide frequency range encompassing the peak wave emission. These results provide confidence that we are able to directly determine the wave vector properties using this multi-spacecraft method implementation, enabling systematic studies of EMIC wave k properties with MMS.

Major diet-drug interactions affecting the kinetic characteristics and hypolipidaemic properties of statins.

Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. This paper reviews major interactions between statins and dietary compounds. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment. Grapefruit juice components inhibit cytochrome P-4503A4, reducing the presystemic metabolism of drugs such as Simvastatin, Lovastatin and Atorvastatin. Follow-up studies on the therapeutic effect of statins in patients consuming a Mediterranean-style diet are necessary to assure the correct prescription because the oil-statin and minor oil compound-statin possible interactions have been only briefly studied. Preliminary study suggests that olive oil can increase the hypolipaemiant effect of Simvastatin with respect sunflower oil. The consumption of polyunsaturated rich oils, throughout the cytochrome P- 450 activation could decrease the half-life of some statins and therefore their hypolipaemic effects. The statins and n-3 fatty acids combined therapy gives rise to pharmacodinamic interaction that improves the lipid profile and leads greater cardioprotection. Although statins are more effective in high endogenous cholesterol production subjects and plant sterols are more effective in high cholesterol absorption efficacy subjects, plant esterols-statins combined therapy generates very positive complementary effects. This review ends suggesting possible diet-stain interactions that require further investigations (e.g. types of olive oils, fruit juices other than grapefruit, fibre or consumption of alcoholic beverages rich in polyphenols or ethanol).

Electron Bernstein waves driven by electron crescents near the electron diffusion region.

The Magnetospheric Multiscale (MMS) spacecraft encounter an electron diffusion region (EDR) of asymmetric magnetic reconnection at Earth's magnetopause. The EDR is characterized by agyrotropic electron velocity distributions on both sides of the neutral line. Various types of plasma waves are produced by the magnetic reconnection in and near the EDR. Here we report large-amplitude electron Bernstein waves (EBWs) at the electron-scale boundary of the Hall current reversal. The finite gyroradius effect of the outflow electrons generates the crescent-shaped agyrotropic electron distributions, which drive the EBWs. The EBWs propagate toward the central EDR. The amplitude of the EBWs is sufficiently large to thermalize and diffuse electrons around the EDR. The EBWs contribute to the cross-field diffusion of the electron-scale boundary of the Hall current reversal near the EDR.

Endometrioid adenocarcinoma of the ovary and endometriosis.

OBJECTIVE: We present a retrospective analysis of 22 cases of endometrioid ovarian carcinoma, reviewed to identify endometriosis and its malignant transformation. STUDY DESIGN: Twenty-two patients with endometrioid ovarian cancer were included in the review. Their clinical and histological data were retrospectively reviewed. The origin of the tumours was considered endometriosis-related when the presence of malignant changes in endometriosis glands leading to endometrioid carcinoma were found. RESULTS: Endometriosis was detected in three cases (3/22=14%). One of them presented a clearly benign to malignant transformation area. In another patient, the transition zone was abrupt and present in both ovaries. In the third, a pre-menopausal woman, ovarian endometriosis with only focal endometrioid carcinoma was observed. The three of them had a clear-cell carcinoma component. The presence of a clear-cell component was significantly greater in patients with endometriosis than in patients without endometriosis Each patient had a different clinical presentation: increase in abdominal perimeter, post-menopausal vaginal haemorrhage and hypermenorrhea. Preoperative CA 125 levels were avalaible in 15 of the patients (15/22=68%). Endometriosis was found in two of these 15 patients, both with the highest CA 125 measured levels, exceeding 1700 U/ml. In the remaining of the patients, CA 125 value did not exceed 35 U/ml. CONCLUSION: Although this association is not very frequent, patients with ovarian endometriosis and a high CA 125 serum level should be managed with special care, regardless of their pre-menopausal or post-menopausal status.

ALDH1A3 is epigenetically regulated during melanocyte transformation and is a target for melanoma treatment.

Despite the promising targeted and immune-based interventions in melanoma treatment, long-lasting responses are limited. Melanoma cells present an aberrant redox state that leads to the production of toxic aldehydes that must be converted into less reactive molecules. Targeting the detoxification machinery constitutes a novel therapeutic avenue for melanoma. Here, using 56 cell lines representing nine different tumor types, we demonstrate that melanoma cells exhibit a strong correlation between reactive oxygen species amounts and aldehyde dehydrogenase 1 (ALDH1) activity. We found that ALDH1A3 is upregulated by epigenetic mechanisms in melanoma cells compared with normal melanocytes. Furthermore, it is highly expressed in a large percentage of human nevi and melanomas during melanocyte transformation, which is consistent with the data from the TCGA, CCLE and protein atlas databases. Melanoma treatment with the novel irreversible isoform-specific ALDH1 inhibitor [4-dimethylamino-4-methyl-pent-2-ynthioic acid-S methylester] di-methyl-ampal-thio-ester (DIMATE) or depletion of ALDH1A1 and/or ALDH1A3, promoted the accumulation of apoptogenic aldehydes leading to apoptosis and tumor growth inhibition in immunocompetent, immunosuppressed and patient-derived xenograft mouse models. Interestingly, DIMATE also targeted the slow cycling label-retaining tumor cell population containing the tumorigenic and chemoresistant cells. Our findings suggest that aldehyde detoxification is relevant metabolic mechanism in melanoma cells, which can be used as a novel approach for melanoma treatment.

Chronic myeloid leukaemia in Spain: Its presentation characteristics have changed. Spanish section of the EUTOS population-based registry. / Leucemia mieloide crónica en España: sus características de presentación han cambiado. Sección española del registro poblacional EUTOS.

OBJECTIVES: To provide more reliable data on the epidemiology of chronic myeloid leukaemia (CML) in Spain than are currently available. MATERIAL AND METHODS: The EUTOS population-based project of European LeukemiaNet is a population registry of new CML cases in patients 18 years of age or older from 22 European areas. The Spanish section included the autonomous communities of Madrid, Castilla-La Mancha and Aragon, from 1-2-2010 to 31-12-2012. RESULTS: A total of 250 cases were recorded in 35 months. The overall incidence was 1.08 cases/10(5) inhabitants-year, with a predominance of men (58%) and clear differences among the communities. The incidence standardised by age was similar (overall, 1.04; men, 1.31; women, 0.81). The median age was 54 years. The incidence increased with age, reaching a peak at>65 years, although 31.7% of cases appeared between the ages of 20 and 44 years. Four percent of cases were diagnosed in advanced stages (2.4% in accelerated phase, 1.6% in blast crisis), 56% were asymptomatic, 38% had splenomegaly, and the Sokal score was high in 11% (lower than what was previously reflected in the literature). CONCLUSIONS: The current incidence of CML in Spain is higher than previously reported and similar to that of the European studies. Unlike the classical descriptions, CML presented mostly in asymptomatic form, with no splenomegaly, less leucocytosis and in stages with better prognosis.

The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia.

AIMS: The purpose of this study was to establish the relevance of several clinical factors associated with parenteral nutrition (PN) hypertriglyceridemia and to construct a predictive model for this complication. METHOD: This multicenter study included all patients with initial serum triglyceridemia <3 mmol and receiving a minimum of 7 days' PN therapy. The study ended for each patient when hypertriglyceridemia developed or PN was terminated. Two multivariate models were constructed, one to study the clinical factors and the second to predict plasma triglyceridemia. A total of 22 clinical factors studied as independent variables were included in the multiple-step regression models only when they showed a P-value over 0.1. Statistical significance was determined by the confidence interval of the odds ratio (OR) and the partial regression coefficient (b). RESULTS: The study included 260 patients from 14 hospitals. Lipid administration was 0.83+/-0.37 g/kg/day. Among the total, 68 patients (26.2%) showed hypertriglyceridemia. Variables included in both models were serum glucose (OR, 2.63; b, 0.06), renal failure (OR, 10.56; b, 1.70), corticoid administration >0.5 mg/kg (OR, 7.98; b, 0.97), pancreatitis (OR, 4.38; b, 0.64), sepsis (OR, 4.48; b, 0.24), lipids infused (OR, 3.03; b, 0.24) and heparin administration >3 mg/kg/day (OR, 0.11; b, -1.21). CONCLUSION: Although the rate of lipid infusion was low, certain clinical factors modified triglyceridemia. Nevertheless, relatively fast plasma clearance of lipids infused indicates that a reduction in lipid supply could be a quick, effective measure for controlling hypertriglyceridemia. Thus, careful monitoring of patients with clinical factors predicting risk in the model studied, with adjustment of lipid perfusion rates accordingly, is suggested to avoid hypertriglyceridemia.

[Evaluation of the Andalusia Public Health System hospital websites in the period 2010-2012]. / Evaluación de la calidad de las páginas webs de los hospitales del Sistema Sanitario Público de Andalucía.

OBJECTIVES: Evaluate the quality, accessibility and presence of Web 2.0 tools in the Andalusia Public Health System hospitals websites METHODS: Observational, descriptive study carried out between 2010 and 2012. The variables analyzed were: quality, accessibility and innovation. The quality was evaluated using a Bermudez-Tamayo questionnaire. Accessibility was measured using the Web Accessibility Test (TAW) tool. Web 2.0 tools were identified by direct observation. RESULTS: A total of 31 of the 45 hospitals (68.9%) had a website in the year 2010, increasing to 34 (75.5%) in 2012. The average score+standard deviation (SD) of the Bermudez-Tamayo quality questionnaire was 11.1+3.8 points in 2010, and 12.3+3.9 points in 2012, observing a statistically significant difference of 0.25 being observed between the means (P=.007), 95% CI; 0.00 to 0.50) In the accessibility evaluation only 7 websites (n=31) in 2010, and 10 (n=34) in 2012, fulfilled the legal criteria for accessibility. The use of Web 2.0 tools has increased throughout the study. In 2010, 19.4% (n=6) of the hospital websites had this type of tool, in comparison to 58.8% (n=20) in 2012. CONCLUSIONS: In general, the quality of the websites studied is good. However, current legislation regarding accessibility is not fulfilled and must be revised and adapted to the current legal rules. There is an incipient use of Web 2.0 resources as education and communication strategies with regard to health.

Nanocomposites of iridium oxide and conducting polymers as electroactive phases in biological media.

Much effort is currently devoted to implementing new materials in electrodes that will be used in the central nervous system, either for functional electrostimulation or for tests on nerve regeneration. Their main aim is to improve the charge capacity of the electrodes, while preventing damaging secondary reactions, such as peroxide formation, occurring while applying the electric field. Thus, hybrids may represent a new generation of materials. Two novel hybrid materials are synthesized using three known biocompatible materials tested in the neural system: polypyrrole (PPy), poly(3,4-ethylenedioxythiophene) (PEDOT) and iridium oxide (IrO2). In particular, PPy-IrO2 and PEDOT-IrO2 hybrid nanocomposite materials are prepared by chemical polymerization in hydrothermal conditions, using IrO2 as oxidizing agent. The reaction yields a significant ordered new hybrid where the conducting polymer is formed around the IrO2 nanoparticles, encapsulating them. Scanning electron microscopy and backscattering techniques show the extent of the encapsulation. Both X-ray photoelectron and Fourier transform infrared spectroscopies identify the components of the phases, as well as the absence of impurities. Electrochemical properties of the final phases in powder and pellet form are evaluated by cyclic voltammetry. Biocompatibility is tested with MTT toxicity tests using primary cultures of cortical neurons grown in vitro for 6 and 9days.

Non-institutionalized nonagenarians health-related quality of life and nutritional status: is there a link between them?

INTRODUCTION: Nonagenarian population, clearly increasing, shows different characteristics from the rest of elderly people. Health-related quality of life is a way to study population health in physical, psychological and social dimensions. OBJECTIVES: To examine the relationship between nutritional status and health-related quality of life in a group of free-living nonagenarians. Differences with octogenarians were also studied. METHODS: Within Villanueva Older Health Study, 20 non-institutionalised people (92.5 ± 3.5 years; 80% women) make the nonagenarian subsample. Nutritional risk was assessed by Mininutritional Assessment questionnaire, dietary intake by a 24-hour dietary recall and health-related quality of life by EuroQoL-5D questionnaire. SPSS was used for statistical analysis. RESULTS: 40% nonagenarians were at risk of malnutrition. Dietary assessment showed magnesium, zinc, potassium, folic acid, vitamin D and vitamin E deficiencies. Problems in mobility were more frequently reported (80%). EQ-5Dindex was associated with MNA(p<0.05). Self-care dimension was associated with calcium and niacin(p<0.05), retinol and cholesterol(p<0.01) intake. Usual activities dimension was associated with niacin(p<0.01) and cholesterol(p<0.05) intake. Pain/discomfort dimension was associated with protein(p<0.01), energy, selenium and niacin(p<0.05) intake. Anxiety/depression was associated with protein(p<0.01) and selenium(p<0.05) intake. CONCLUSIONS: Risk of malnutrition is a factor associated to health-related quality of life. Results suggest that energy and some nutrient intakes could be possibly associated to health-related quality of life but further research on this influence is required.

Introducción: La población nonagenaria, en claro crecimiento, muestra características diferentes del resto de la población anciana. La calidad de vida relacionada con la salud es una forma de estudiar la salud de la población en sus dimensiones física, psicológica y social. Objetivos: Observar la relación entre el estado nutricional y la calidad de vida relacionada con la salud en un grupo de nonagenarios de vida independiente. También se estudian las diferencias con los octogenarios. Método: Dentro del Estudio sobre Salud en Mayores de Villanueva de la Cañada, 20 personas (92,5±3,5 años; 80% mujeres) forman la submuestra de nonagenarios. El riesgo nutricional fue valorado mediante el Mininutritional Assessment, la ingesta dietética mediante un recuerdo de 24 horas y la calidad de vida relacionada con la salud usando el cuestionario EuroQoL-5D (EQ-5D). Para el análisis estadístico se utilizó el programa SPSS. Resultados: 40% de los nonagenarios presentaban riesgo de malnutrición. Se detectaron posibles deficiencias de magnesio, cinc, potasio, ácido fólico, vitamina D y vitamina E. Los problemas de movilidad fueron los más frecuentes (80%). El EQ-5Dindice se asoció con el MNA(p.

Influence of nutritional status on health-related quality of life of non-institutionalized older people.

OBJECTIVES: Health-related quality of life (HRQoL) is a multidimensional health measurement and a key to optimal aging. The aim of this study was to examine the association of nutritional status with HRQoL in the elderly. DESIGN: Cross-sectional study. SETTING: Villanueva Older Health Study, a community-based study in Villanueva de la Cañada (Madrid, Spain). PARTICIPANTS: 83 (53 women) non-institutionalized inhabitants aged 80 years and above. MEASUREMENT: HRQoL was assessed by EuroQoL-5D (EQ-5D) questionnaire, nutritional risk by Mini Nutritional Assessment (MNA) questionnaire and dietary intake by 24-hour dietary recall. Statistical significance was evaluated at 95% confidence level (P<0.05). RESULTS: EQ-5D pointed out differences between men and women (0.782±0.235 and 0.633±0.247; p=0.02). Problems in mobility (total sample) and pain/discomfort (women) dimensions were most frequently reported. MNA (26.5±3.2 men and 24.3±3.2 women; p=0.03) revealed malnutrition in 3.3% of men and 1.9% of women, and risk of malnutrition in 6.7% and 37.7%, respectively. Total sample was at risk of folic acid, zinc, magnesium, vitamin D and vitamin E deficiency. EQ-5D was associated with MNA (p<0.001). EQ-5Dindex was associated with energy intake (p=0.04) and EQ-5Dvas was negatively correlated with body mass index (p=0.02). EQ-5D pain/discomfort dimension was associated with energy (p=0.006), protein (p=0.005), lipid (p=0.03), magnesium (p=0.032), phosphorus (p=0.012), selenium (p=0.043) and niacin (p=0.004) intake. CONCLUSIONS: Women showed poorer HRQoL and higher malnutrition risk. A relationship between HRQoL and risk of malnutrition was observed. Results suggest that when energy and protein, lipid, phosphorus, magnesium, selenium and niacin intake increase, HRQoL is promoted, although the increase does not seem to have a strong direct effect on it. The limited influence of energy and nutrient intake on HRQoL observed requires further research.

GABAergic pharmacological activity of propofol related compounds as possible enhancers of general anesthetics and interaction with membranes.

Phenol compounds, such as propofol and thymol, have been shown to act on the GABAA receptor through interaction with specific sites of this receptor. In addition, considering the high lipophilicity of phenols, it is possible that their pharmacological activity may also be the result of the interaction of phenol molecules with the surrounding lipid molecules, modulating the supramolecular organization of the receptor environment. Thus, in the present study, we study the pharmacological activity of some propofol- and thymol-related phenols on the native GABAA receptor using primary cultures of cortical neurons and investigate the effects of these compounds on the micro viscosity of artificial membranes by means of fluorescence anisotropy. The phenol compounds analyzed in this article are carvacrol, chlorothymol, and eugenol. All compounds were able to enhance the binding of [(3)H]flunitrazepam with EC50 values in the micromolar range and to increase the GABA-evoked Cl(-) influx in a concentration-dependent manner, both effects being inhibited by the competitive GABAA antagonist bicuculline. These results strongly suggest that the phenols studied are positive allosteric modulators of this receptor. Chlorothymol showed a bell-type effect, reducing its positive effect at concentrations >100 µM. The concentrations necessary to induce positive allosteric modulation of GABAA receptor were not cytotoxic. Although all compounds were able to decrease the micro viscosity of artificial membranes, chlorothymol displayed a larger effect which could explain its effects on [(3)H]flunitrazepam binding and on cell viability at high concentrations. Finally, it is suggested that these compounds may exert depressant activity on the central nervous system and potentiate the effects of general anesthetics.