Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. METHODS: Wild type, inducible nitric oxide synthase (iNOS)-/- and endothelial nitric oxide synthase (eNOS)-/- mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). RESULTS: SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS-/- PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS-/- PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS-/- or iNOS-/- mice. Thalidomide acutely increased plasma NOx in wild type and eNOS-/- mice but not iNOS-/- mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS-/- and iNOS-/- PVL mice, after which time levels returned to the respective baseline. CONCLUSION: Thalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism

Universality from disorder in the random-bond Blume-Capel model

Using high-precision Monte Carlo simulations and finite-size scaling we study the effect of quenched disorder in the exchange couplings on the Blume-Capel model on the square lattice. The first-order transition for large crystal-field coupling is softened to become continuous, with a divergent correlation length. An analysis of the scaling of the correlation length as well as the susceptibility and specific heat reveals that it belongs to the universality class of the Ising model with additional logarithmic corrections observed for the Ising model itself if coupled to weak disorder. While the leading scaling behavior in the disordered system is therefore identical between the second-order and first-order segments of the phase diagram of the pure model, the finite-size scaling in the ex-first-order regime is affected by strong transient effects with a crossover length scale $L^{\ast} \approx 32$ for the chosen parameters

Wang-Landau study of the 3D Ising model with bond disorder

We implement a two-stage approach of the Wang-Landau algorithm to investigate the critical properties of the 3D Ising model with quenched bond randomness. In particular, we consider the case where disorder couples to the nearest-neighbor ferromagnetic interaction, in terms of a bimodal distribution of strong versus weak bonds. Our simulations are carried out for large ensembles of disorder realizations and lattices with linear sizes $L$ in the range $L=8-64$. We apply well-established finite-size scaling techniques and concepts from the scaling theory of disordered systems to describe the nature of the phase transition of the disordered model, departing gradually from the fixed point of the pure system. Our analysis (based on the determination of the critical exponents) shows that the 3D random-bond Ising model belongs to the same universality class with the site- and bond-dilution models, providing a single universality class for the 3D Ising model with these three types of quenched uncorrelated disorder.Comment: 7 pages, 7 figures, to be published in Eur. Phys. J.

Superspreading: Mechanisms and Molecular Design

The intriguing ability of certain surfactant molecules to drive the superspreading of liquids to complete wetting on hydrophobic substrates is central to numerous applications that range from coating flow technology to enhanced oil recovery. Despite significant experimental efforts, the precise mechanisms underlying superspreading remain unknown to date. Here, we isolate these mechanisms by analyzing coarse-grained molecular dynamics simulations of surfactant molecules of varying molecular architecture and substrate affinity. We observe that for superspreading to occur, two key conditions must be simultaneously satisfied: the adsorption of surfactants from the liquid–vapor surface onto the three-phase contact line augmented by local bilayer formation. Crucially, this must be coordinated with the rapid replenishment of liquid–vapor and solid–liquid interfaces with surfactants from the interior of the droplet. This article also highlights and explores the differences between superspreading and conventional surfactants, paving the way for the design of molecular architectures tailored specifically for applications that rely on the control of wetting

Stability of Repulsive Bose-Einstein Condensates in a Periodic Potential

The cubic nonlinear Schr\"odinger equation with repulsive nonlinearity and an elliptic function potential models a quasi-one-dimensional repulsive dilute gas Bose-Einstein condensate trapped in a standing light wave. New families of stationary solutions are presented. Some of these solutions have neither an analog in the linear Schr\"odinger equation nor in the integrable nonlinear Schr\"odinger equation. Their stability is examined using analytic and numerical methods. All trivial-phase stable solutions are deformations of the ground state of the linear Schr\"odinger equation. Our results show that a large number of condensed atoms is sufficient to form a stable, periodic condensate. Physically, this implies stability of states near the Thomas-Fermi limit.Comment: 12 pages, 17 figure

Balancing the dilution and oddity effects: Decisions depend on body size

Background Grouping behaviour, common across the animal kingdom, is known to reduce an individual's risk of predation; particularly through dilution of individual risk and predator confusion (predator inability to single out an individual for attack). Theory predicts greater risk of predation to individuals more conspicuous to predators by difference in appearance from the group (the ‘oddity’ effect). Thus, animals should choose group mates close in appearance to themselves (eg. similar size), whilst also choosing a large group. Methodology and Principal Findings We used the Trinidadian guppy (Poecilia reticulata), a well known model species of group-living freshwater fish, in a series of binary choice trials investigating the outcome of conflict between preferences for large and phenotypically matched groups along a predation risk gradient. We found body-size dependent differences in the resultant social decisions. Large fish preferred shoaling with size-matched individuals, while small fish demonstrated no preference. There was a trend towards reduced preferences for the matched shoal under increased predation risk. Small fish were more active than large fish, moving between shoals more frequently. Activity levels increased as predation risk decreased. We found no effect of unmatched shoal size on preferences or activity. Conclusions and Significance Our results suggest that predation risk and individual body size act together to influence shoaling decisions. Oddity was more important for large than small fish, reducing in importance at higher predation risks. Dilution was potentially of limited importance at these shoal sizes. Activity levels may relate to how much sampling of each shoal was needed by the test fish during decision making. Predation pressure may select for better decision makers to survive to larger size, or that older, larger fish have learned to make shoaling decisions more efficiently, and this, combined with their size relative to shoal-mates, and attractiveness as prey items influences shoaling decisions

Measuring Inequalities in the Distribution of Health Workers: The case of Tanzania.

The overall human resource shortages and the distributional inequalities in the health workforce in many developing countries are well acknowledged. However, little has been done to measure the degree of inequality systematically. Moreover, few attempts have been made to analyse the implications of using alternative measures of health care needs in the measurement of health workforce distributional inequalities. Most studies have implicitly relied on population levels as the only criterion for measuring health care needs. This paper attempts to achieve two objectives. First, it describes and measures health worker distributional inequalities in Tanzania on a per capita basis; second, it suggests and applies additional health care needs indicators in the measurement of distributional inequalities. We plotted Lorenz and concentration curves to illustrate graphically the distribution of the total health workforce and the cadre-specific (skill mix) distributions. Alternative indicators of health care needs were illustrated by concentration curves. Inequalities were measured by calculating Gini and concentration indices.\ud There are significant inequalities in the distribution of health workers per capita. Overall, the population quintile with the fewest health workers per capita accounts for only 8% of all health workers, while the quintile with the most health workers accounts for 46%. Inequality is perceptible across both urban and rural districts. Skill mix inequalities are also large. Districts with a small share of the health workforce (relative to their population levels have an even smaller share of highly trained medical personnel. A small share of highly trained personnel is compensated by a larger share of clinical officers (a middle-level cadre) but not by a larger share of untrained health workers. Clinical officers are relatively equally distributed. Distributional inequalities tend to be more pronounced when under-five deaths are used as an indicator of health care needs. Conversely, if health care needs are measured by HIV prevalence, the distributional inequalities appear to decline. The measure of inequality in the distribution of the health workforce may depend strongly on the underlying measure of health care needs. In cases of a non-uniform distribution of health care needs across geographical areas, other measures of health care needs than population levels may have to be developed in order to ensure a more meaningful measurement of distributional inequalities of the health workforce

Identifying dyspepsia in the Greek population: translation and validation of a questionnaire

BACKGROUND: Studies on clinical issues, including diagnostic strategies, are considered to be the core content of general practice research. The use of standardised instruments is regarded as an important component for the development of Primary Health Care research capacity. Demand for epidemiological cross-cultural comparisons in the international setting and the use of common instruments and definitions valid to each culture is bigger than ever. Dyspepsia is a common complaint in primary practice but little is known with respect to its incidence in Greece. There are some references about the Helicobacter Pylori infection in patients with functional dyspepsia or gastric ulcer in Greece but there is no specific instrument for the identification of dyspepsia. This paper reports on the validation and translation into Greek, of an English questionnaire for the identification of dyspepsia in the general population and discusses several possibilities of its use in the Greek primary care. METHODS: The selected English postal questionnaire for the identification of people with dyspepsia in the general population consists of 30 items and was developed in 1995. The translation and cultural adaptation of the questionnaire has been performed according to international standards. For the validation of the instrument the internal consistency of the items was established using the alpha coefficient of Chronbach, the reproducibility (test – retest reliability) was measured by kappa correlation coefficient and the criterion validity was calculated against the diagnosis of the patients' records using also kappa correlation coefficient. RESULTS: The final Greek version of the postal questionnaire for the identification of dyspepsia in the general population was reliably translated. The internal consistency of the questionnaire was good, Chronbach's alpha was found to be 0.88 (95% CI: 0.81–0.93), suggesting that all items were appropriate to measure. Kappa coefficient for reproducibility (test – retest reliability) was found 0.66 (95% CI: 0.62–0.71), whereas the kappa analysis for criterion validity was 0.63 (95% CI: 0.36–0.89). CONCLUSION: This study indicates that the Greek translation is comparable with the English-language version in terms of validity and reliability, and is suitable for epidemiological research within the Greek primary health care setting

Psychological determinants of whole-body endurance performance

Background: No literature reviews have systematically identified and evaluated research on the psychological determinants of endurance performance, and sport psychology performance-enhancement guidelines for endurance sports are not founded on a systematic appraisal of endurance-specific research. Objective: A systematic literature review was conducted to identify practical psychological interventions that improve endurance performance and to identify additional psychological factors that affect endurance performance. Additional objectives were to evaluate the research practices of included studies, to suggest theoretical and applied implications, and to guide future research. Methods: Electronic databases, forward-citation searches, and manual searches of reference lists were used to locate relevant studies. Peer-reviewed studies were included when they chose an experimental or quasi-experimental research design, a psychological manipulation, endurance performance as the dependent variable, and athletes or physically-active, healthy adults as participants. Results: Consistent support was found for using imagery, self-talk, and goal setting to improve endurance performance, but it is unclear whether learning multiple psychological skills is more beneficial than learning one psychological skill. The results also demonstrated that mental fatigue undermines endurance performance, and verbal encouragement and head-to-head competition can have a beneficial effect. Interventions that influenced perception of effort consistently affected endurance performance. Conclusions: Psychological skills training could benefit an endurance athlete. Researchers are encouraged to compare different practical psychological interventions, to examine the effects of these interventions for athletes in competition, and to include a placebo control condition or an alternative control treatment. Researchers are also encouraged to explore additional psychological factors that could have a negative effect on endurance performance. Future research should include psychological mediating variables and moderating variables. Implications for theoretical explanations of endurance performance and evidence-based practice are described