The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.

Effects of dietary protein type on oxidized cholesterol-induced alteration in age-related modulation of lipid metabolism and indices of immune function in rats.

Exogenous oxidized cholesterol disturbs both lipid metabolism and immune functions. Therefore, it may perturb these modulations with ageing. Effects of the dietary protein type on oxidized cholesterol-induced modulations of age-related changes in lipid metabolism and immune function was examined using differently aged (4 weeks versus 8 months) male Sprague-Dawley rats when casein, soybean protein or milk whey protein isolate (WPI) was the dietary protein source, respectively. The rats were given one of the three proteins in diet containing 0.2% oxidized cholesterols mixture. Soybean protein, as compared with the other two proteins, significantly lowered both the serum thiobarbituric acid reactive substances value and cholesterol, whereas it elevated the ratio of high density lipoprotein-cholesterol/cholesterol in young rats, but not in adult. Moreover, soybean protein, but not casein and WPI, suppressed the elevation of Delta6 desaturation indices of phospholipids in both liver and spleen, particularly in young. On the other hand, WPI, compared to the other two proteins, inhibited the leukotriene B4 production of spleen, irrespective of age. Soybean protein reduced the ratio of CD4(+)/CD8(+) T-cells in splenic lymphocytes. Therefore, the levels of immunoglobulin (Ig)A, IgE and IgG in serum were lowered in rats given soybean protein in both age groups except for IgA in adult, although these observations were not shown in rats given other proteins. Thus, various perturbations of lipid metabolism and immune function caused by oxidized cholesterol were modified depending on the type of dietary protein. The moderation by soybean protein on the change of lipid metabolism seems to be susceptible in young rats whose homeostatic ability is immature. These observations may be exerted through both the promotion of oxidized cholesterol excretion to feces and the change of hormonal release, while WPI may suppress the disturbance of immune function by oxidized cholesterol in both ages. This alleviation may be associated with a large amount of lactoglobulin in WPI. These results thus showed a possibility that oxidized cholesterol-induced perturbations of age-related changes of lipid metabolism and immune function can be moderated by both the selection and combination of dietary protein.

Using self organizing maps on compositional data

Self-organizing maps (Kohonen 1997) is a type of artificial neural network developedto explore patterns in high-dimensional multivariate data. The conventional versionof the algorithm involves the use of Euclidean metric in the process of adaptation ofthe model vectors, thus rendering in theory a whole methodology incompatible withnon-Euclidean geometries.In this contribution we explore the two main aspects of the problem:1. Whether the conventional approach using Euclidean metric can shed valid resultswith compositional data.2. If a modification of the conventional approach replacing vectorial sum and scalarmultiplication by the canonical operators in the simplex (i.e. perturbation andpowering) can converge to an adequate solution.Preliminary tests showed that both methodologies can be used on compositional data.However, the modified version of the algorithm performs poorer than the conventionalversion, in particular, when the data is pathological. Moreover, the conventional ap-proach converges faster to a solution, when data is \well-behaved".Key words: Self Organizing Map; Artificial Neural networks; Compositional data

Influence of physical activity and dietary habits on lipid profile, blood pressure and BMI in subjects with metabolic syndrome

BACKGROUND The present study was determined the influence of physical activity and dietary habits on lipid profile, blood pressure (BP) and body mass index (BMI) in subjects with metabolic syndrome (MS). AIMS Identify the relationship between physical activity and proper nutrition and the probability of suffering from myocardial infarction (MI). METHODS Hundred chronically ill with MS who were active and followed a healthy diet were classified as compliant, while the remaining subjects were classified as non-compliant. RESULTS The compliant subjects show lower BMI values (30.8±4.9 vs 32.5±4.6), as well as lower levels of triacylglycerol (130.4±48.2 vs 242.1±90.1), total cholesterol (193.5±39 vs 220.2±52.3) and low-density lipoprotein cholesterol (105.2±38.3 vs 139.2±45). They show higher values in terms of high-density lipoprotein cholesterol levels (62.2±20.1 vs 36.6±15.3), with statistically significant differences. In terms of both systolic and diastolic pressure, no differences were revealed between the groups; however, those who maintain proper dietary habits show lower systolic blood pressure levels than the inactive subjects. The probability of suffering from MI greatly increases among the group of non-compliant subjects. CONCLUSIONS Our results demonstrate how performing aerobic physical activity and following an individualized, Mediterranean diet significantly reduces MS indicators and the chances of suffering from MI.

Effects of L-carnitine supplemented total parenteral nutrition on lipid and energy metabolism in postoperative stress.

During episodes of trauma carnitine-free total parenteral nutrition (TPN) may result in a reduction of the total body carnitine pool, leading to a diminished rate of fat oxidation. Sixteen patients undergoing esophagectomy were divided randomly in two equal isonitrogenous groups (0.2 g/kg.day). Both received TPN (35 kcal/kg.day; equally provided as long-chain triglycerides and glucose) over 11 days without (group A) and with (group B) L-carnitine supplementation (12 mg/kg.day = 75 mumol/kg.day). Compared with healthy controls, the total body carnitine pool prior to the operation was significantly reduced in both groups, suggesting a state of semistarvation and muscle wasting. In group A the plasma levels of total carnitine and its subfractions (free carnitine, short- and long-chain acylcarnitine) remained stable during the study whereas in group B the total plasma carnitine concentration rose mainly due to an increase in free carnitine. In group A the cumulative urinary carnitine losses were 11.5 +/- 2.6 mmol (= 15.5 +/- 3.1% of the estimated total body carnitine pool). In group B 3.1 +/- 1.9 mmol (= 11.1 +/- 7.6%) of the infused carnitine was retained in the immediate postoperative phase until day 6, but this amount was completely lost at completion of the study period. No significant differences in the respiratory quotient or in the plasma levels of triglycerides, free fatty acids, and ketone bodies were observed, between or within the groups, before the operation and after 11 days of treatment. It is concluded that the usefulness of carnitine supplementation during postoperative TPN was not apparent in the present patient material.

Effectiveness of two interventions based on improving patient-practitioner communication on diabetes self-management in patients with low educational level: study protocol of a clustered randomized trial in primary care.

BACKGROUND In the last decades the presence of social inequalities in diabetes care has been observed in multiple countries, including Spain. These inequalities have been at least partially attributed to differences in diabetes self-management behaviours. Communication problems during medical consultations occur more frequently to patients with a lower educational level. The purpose of this cluster randomized trial is to determine whether an intervention implemented in a General Surgery, based in improving patient-provider communication, results in a better diabetes self-management in patients with lower educational level. A secondary objective is to assess whether telephone reinforcement enhances the effect of such intervention. We report the design and implementation of this on-going study. METHODS/DESIGN The study is being conducted in a General Practice located in a deprived neighbourhood of Granada, Spain. Diabetic patients 18 years old or older with a low educational level and inadequate glycaemic control (HbA1c > 7%) were recruited. General Practitioners (GPs) were randomised to three groups: intervention A, intervention B and control group. GPs allocated to intervention groups A and B received training in communication skills and are providing graphic feedback about glycosylated haemoglobin levels. Patients whose GPs were allocated to group B are additionally receiving telephone reinforcement whereas patients from the control group are receiving usual care. The described interventions are being conducted during 7 consecutive medical visits which are scheduled every three months. The main outcome measure will be HbA1c; blood pressure, lipidemia, body mass index and waist circumference will be considered as secondary outcome measures. Statistical analysis to evaluate the effectiveness of the interventions will include multilevel regression analysis with three hierarchical levels: medical visit level, patient level and GP level. DISCUSSION The results of this study will provide new knowledge about possible strategies to promote a better diabetes self-management in a particularly vulnerable group. If effective, this low cost intervention will have the potential to be easily incorporated into routine clinical practice, contributing to decrease health inequalities in diabetic patients. TRIAL REGISTRATION Clinical Trials U.S. National Institutes of Health, NCT01849731.

Effect of high-intensity interval exercise on lipid oxidation during postexercise recovery.

PURPOSE: The aim of this study was to examine whether lipid oxidation predominates during 3 h of postexercise recovery in high-intensity interval exercise as compared with moderate-intensity continuous exercise on a cycle ergometer in fit young men (n = 12; 24.6 +/- 0.6 yr). METHODS: The energy substrate partitioning was evaluated during and after high-intensity submaximal interval exercise (INT, 1-min intervals at 80% of maximal aerobic power output [Wmax] with an intervening 1 min of active recovery at 40% Wmax) and 60-min moderate-intensity continuous exercise at 45% of maximal oxygen uptake (C45%) as well as a time-matched resting control trial (CON). Exercise bouts were matched for mechanical work output. RESULTS: During exercise, a significantly greater contribution of CHO and a lower contribution of lipid to energy expenditure were found in INT (512.7 +/- 26.6 and 41.0 +/- 14.0 kcal, respectively) than in C45% (406.3 +/- 21.2 and 170.3 +/- 24.0 kcal, respectively; P < 0.001) despite similar overall energy expenditure in both exercise trials (P = 0.13). During recovery, there were no significant differences between INT and C45% in substrate turnover and oxidation (P > 0.05). On the other hand, the mean contribution of lipids to energy yield was significantly higher after exercise trials (C45% = 61.3 +/- 4.2 kcal; INT = 66.7 +/- 4.7 kcal) than after CON (51.5 +/- 3.4 kcal; P < 0.05). CONCLUSIONS: These findings show that lipid oxidation during postexercise recovery was increased by a similar amount on two isoenergetic exercise bouts of different forms and intensities compared with the time-matched no-exercise control trial.

Capitalism in the classroom : the impact of self-enhancement values and normative assessment on student motivation, goals and attitudes towards cheating

Abstract The neo-liberal capitalist ideology has come under heavy fire with anecdotal evidence indicating a link between these same values and unethical behavior. Academic institutions reflect social values and act as socializing agents for the young. Can this explain the high and increasing rates of cheating that currently prevail in education? Our first chapter examines the question of whether self-enhancement values of power and açhievement, the individual level equivalent of neo-liberal capitalist values, predict positive attitudes towards cheating. Furthermore, we explore the mediating role of motivational factors. Results of four studies reveal that self-enhancement value endorsement predicts the adoption of performance-approach goals, a relationship mediated by introjected regulation, namely desire for social approval and that self-enhancement value endorsement also predicts the condoning of cheating, a relationship mediated by performance-approach goal adoption. However, self-transcendence values prescribed by a normatively salient source have the potential to reduce the link between self-enhancement value endorsément and attitudes towards cheating. Normative assessment constitutes a key tool used by academic institutions to socialize young people to accept the competitive, meritocratic nature of a sociéty driven by a neo-liberal capitalist ideology. As such, the manifest function of grades is to motivate students to work hard and to buy into the competing ethos. Does normative assessment fulfill these functions? Our second chapter explores the reward-intrinsic motivation question in the context of grading, arguably a high-stakes reward. In two experiments, the relative capacity of graded high performance as compared to the task autonomy experienced in an ungraded task to predict post-task intrinsic motivation is assessed. Results show that whilst the graded task performance predicts post-task appreciation, it fails to predict ongoing motivation. However, perceived autonomy experienced in non-graded condition, predicts both post-task appreciation and ongoing motivation. Our third chapter asks whether normative assessment inspires the spirit of competition in students. Results of three experimental studies reveal that expectation of a grade for a task, compared to no grade, induces greater adoption of performance-avoidance, but not performance-approach, goals. Experiment 3 provides an explanatory mechanism for this, showing that reduced autonomous motivation experienced in previous graded tasks mediates the relationship between grading and adoption of performance avoidance goals in a subsequent task. The above results, when combined, provide evidence as to the deleterious effects of self enhancement values and the associated practice of normative assessment in school on student motivation, goals and ethics. We conclude by using value and motivation theory to explore solutions to this problem.

Differential effects of high-fat diet on myocardial lipid metabolism in failing and nonfailing hearts with angiotensin II-mediated cardiac remodeling in mice.

Normal myocardium adapts to increase of nutritional fatty acid supply by upregulation of regulatory proteins of the fatty acid oxidation pathway. Because advanced heart failure is associated with reduction of regulatory proteins of fatty acid oxidation, we hypothesized that failing myocardium may not be able to adapt to increased fatty acid intake and therefore undergo lipid accumulation, potentially aggravating myocardial dysfunction. We determined the effect of high-fat diet in transgenic mice with overexpression of angiotensinogen in the myocardium (TG1306/R1). TG1306/R1 mice develop ANG II-mediated left ventricular hypertrophy, and at one year of age approximately half of the mice present heart failure associated with reduced expression of regulatory proteins of fatty acid oxidation and reduced palmitate oxidation during ex vivo working heart perfusion. Hypertrophied hearts from TG1306/R1 mice without heart failure adapted to high-fat feeding, similarly to hearts from wild-type mice, with upregulation of regulatory proteins of fatty acid oxidation and enhancement of palmitate oxidation. There was no myocardial lipid accumulation or contractile dysfunction. In contrast, hearts from TG1306/R1 mice presenting heart failure were unable to respond to high-fat feeding by upregulation of fatty acid oxidation proteins and enhancement of palmitate oxidation. This resulted in accumulation of triglycerides and ceramide in the myocardium, and aggravation of contractile dysfunction. In conclusion, hearts with ANG II-induced contractile failure have lost the ability to enhance fatty acid oxidation in response to increased fatty acid supply. The ensuing accumulation of lipid compounds may play a role in the observed aggravation of contractile dysfunction.

Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans.

BACKGROUND: A high dietary protein intake has been shown to blunt the deposition of intrahepatic lipids in high-fat- and high-carbohydrate-fed rodents and humans. OBJECTIVE: The aim of this study was to evaluate the effect of essential amino acid supplementation on the increase in hepatic fat content induced by a high-fructose diet in healthy subjects. DESIGN: Nine healthy male volunteers were studied on 3 occasions in a randomized, crossover design after 6 d of dietary intervention. Dietary conditions consisted of a weight-maintenance balanced diet (control) or the same balanced diet supplemented with 3 g fructose · kg(-1) · d(-1) and 6.77 g of a mixture of 5 essential amino acids 3 times/d (leucine, isoleucine, valine, lysine, and threonine) (HFrAA) or with 3 g fructose · kg(-1) · d(-1) and a maltodextrin placebo 3 times/d (HFr); there was a washout period of 4 to 10 wk between each condition. For each condition, the intrahepatocellular lipid (IHCL) concentration, VLDL-triglyceride concentration, and VLDL-[(13)C]palmitate production were measured after oral loading with [(13)C]fructose. RESULTS: HFr increased the IHCL content (1.27 ± 0.31 compared with 2.74 ± 0.55 vol %; P < 0.05) and VLDL-triglyceride (0.55 ± 0.06 compared with 1.40 ± 0.15 mmol/L; P < 0.05). HFr also enhanced VLDL-[(13)C]palmitate production. HFrAA significantly decreased IHCL compared with HFr (to 2.30 ± 0.43 vol%; P < 0.05) but did not change VLDL-triglyceride concentrations or VLDL-[(13)C]palmitate production. CONCLUSIONS: Supplementation with essential amino acids blunts the fructose-induced increase in IHCL but not hypertriglyceridemia. This is not because of inhibition of VLDL-[(13)C]palmitate production. This trial was registered at www.clinicaltrials.gov as NCT01119989.

Experimental and computational study on the synthesis and characterization of self-assembling meso/macroporous materials in highly concentrated emulsions

Report for the scientific sojourn carried out at Massachusetts General Hospital Cancer Center-Harvard Medical School, Estats Units, from 2010 to 2011. The project aims to study the aggregation behavior of amphiphilic molecules in the continuous phase of highly concentrated emulsions, which can be used as templates for the synthesis of meso/macroporous materials. At this stage of the project, we have investigated the self-assembly of diblock and triblock surfactants under the effect of a confined geometry being surrounded by the droplets of the dispersed phase. These droplets limit the growth of the aggregates, deeply modify their orientation and hence alter their spatial arrangement as compared to the self-assembly taking place far enough from any boundary surface, that is in the bulk. By performing Monte Carlo simulations, we have showed that the interface between the dispersed and continuous phases as well as its shape has a significant impact on the structural order of the resulting aggregates and hence on the potential applications of highly concentrated emulsions as reaction media, drug delivery systems, or templates for meso/macroporous materials. Due to the combined effect of symmetry breaking and morphological frustration, very intriguing structures, such as square columnar liquid crystals, twisted X-shaped aggregates, and helical phases of cylindrical aggregates, never observed in the bulk for the same model surfactant, have been found. The presence of other more conventional structures, such as micelles and cubic and hexagonal liquid crystals, formed at low and high amphiphilic concentrations, respectively, further enhance the interest on this already rich aggregation behavior.

Metabolic intervention on lipid synthesis converging pathways abrogates prostate cancer growth.

One of the most conserved features of all cancers is a profound reprogramming of cellular metabolism, favoring biosynthetic processes and limiting catalytic processes. With the acquired knowledge of some of these important changes, we have designed a combination therapy in order to force cancer cells to use a particular metabolic pathway that ultimately results in the accumulation of toxic products. This innovative approach consists of blocking lipid synthesis, at the same time that we force the cell, through the inhibition of AMP-activated kinase, to accumulate toxic intermediates, such as malonyl-coenzyme A (malonyl-CoA) or nicotinamide adenine dinucleotide phosphate. This results in excess of oxidative stress and cancer cell death. Our new therapeutic strategy, based on the manipulation of metabolic pathways, will certainly set up the basis for new upcoming studies defining a new paradigm of cancer treatment.

Finding a suitable job: the effect of the institutional context on self-perceived over-education

The current research compares the perception of over-education in four different European countries, resorting to European Household Panel Data. The results confirm that the type of educational system accounts for some of the cross-national differences in self-perceived over-education. In qualificational spaces, like Denmark, where vocational training receives more importance, self-perceived over-education is not associated as much with educational attainment as in the so-called’ organisational spaces’, like Spain, France and Italy. Yet, the results confirm that, controlling for the system of education, the traits and regulation of the labour market also have an effect on over-education. Thus, in Spain, where temporary employment has soared in recent decades, this type of contract is clearly associated with the perception of over-education, to a much higher extent than in Italy or France. Temporary contracts in Spain may not work as a steppig stone for attaining a job suitable to the training received by the individual, as they may in the case of France or Italy. In sum, not only institutions offering skills and human capital, but labour market regulation as well, have a clear impact on the incidence of over-education.

Virtual Guide On Ocular Self-Examination To Support The Self-Care Practice For People With HIV/AIDS

Objetivou-se descrever processo de desenvolvimento da cartilha virtual sobre autoexame ocular para pessoas com HIV/aids. A proposta metodológica seguiu as cinco etapas preconizadas por Falkembach: análise e planejamento, modelagem, implementação, avaliação e distribuição. A adequação da versão impressa para virtual requereu a construção de um vídeo tutorial, agregação de fotos ilustrativas para visualização de possíveis alterações oculares e ferramenta de interatividade com demonstração do resultado do exame ao usuário. Na avaliação inicial do material, foram diagnosticadas falhas no layout. Assim, comandos foram recolocados, unificados, dispostos em local de fácil visualização e foi feita a adequação da linguagem. Considera-se possível promover aproximação do usuário com métodos de prevenção na área da saúde ocular por meio de cartilha virtual, contribuindo para desenvolvimento de habilidades e divulgação do autoexame.