Atomistic simulation of biaxial liquid crystals and mixtures of liquid crystals

In this thesis molecular dynamics (MD) simulations at a fully-atomistic level have been undertaken to study the biaxiality and the structure of the liquid crystalline phase formed by the para-heptylbenxoate diester of 2.5-bis-(p-hydroxyphenyl)-1,3,4-oxadiazole (ODBP-Ph-C(_7)), which is a bent-core mesogen. This has been the first time the transition between isotropic and liquid crystalline phases has been achieved using a fully atomistic (all-atom) potential. Simulations at five different temperatures covering the nematic range of ODBP-Ph-C(_7) have been undertaken to study the temperature dependence of the biaxial ordering. Ferroelectric domains have been observed in all the systems. Simulations started from the biaxial nematic phase have been performed with the partial charges turned off to study the influence of the electrostatic interactions on the behaviour of the system. A system composed of ODBP-Ph-C(_7) and the deuterated molecule hexamethylbenzoate-d10 (HMB) has also been simulated to check the validity of the (^)2HNMR method, which is often employed to study biaxiality. MD simulations at a fully-atomistic level have been also performed for the mixture of liquid crystals E7， commercialized by Merck. The nematic phase for this mixture is grown from an isotropic phase using an fully atomistic (all-atom) potential, and in order to study the temperature dependence of the order parameter simulations at six different temperatures covering the nematic range have been performed. The internal structure of the mixture, alongside some of its material properties such as rotational viscosity and flexoelectric coefficients have been studied. Finally, ab initio calculations involving several molecular fragments which are components of some of the most common mesogens have been carried out to calculate torsional energies of key dihedral angles. Subsequently, torsional energies have been fitted using a Fourier series expansion to obtain torsional parameters for an atomistic force field. These will be used in future atomistic simulations of liquid crystals

Study of the impact of the kink instability in heliospheric magnetic flux ropes

Les Ejeccions de Massa Coronals (CMEs) tenen un impacte significatiu en la meteorologia espacial en transportar massa i energia solar cap a l'Heliosfera. Aquesta investigació se centra en comprendre les seves configuracions magnètiques internes, fonamentalment les Cordes de Flux Magnètic (MFRs), que són crucials per predir el comportament de les CMEs. L'estudi es concentra en la inestabilitat de tipus kink, un fenomen que podria induir rotacions de les MFRs heliosfèriques. Emprant el mètode de la velocitat de creixement, la investigació avalua l'estabilitat de les MFRs sota pertorbacions utilitzant principis magnetohidrodinàmics i models de simetria cilíndrica. Aquest estudi s'ha aplicat a dades de sondes espacials en un intent d'augmentar la nostra capacitat de predir quan aquestes pertorbacions podrien causar canvis en l'estructura, la dinàmica i la trajectòria d'una CME.Las Eyecciones de Masa Coronal (CMEs) tienen un impacto significativo en la meteorología espacial al transportar masa y energía solar hacia la Heliosfera. Esta investigación se centra en comprender sus configuraciones magnéticas internas, fundamentalmente las Cuerdas de Flujo Magnético (MFRs), que son cruciales para predecir el comportamiento de las CMEs. El estudio se concentra en la inestabilidad de tipo kink, un fenómeno que podría inducir rotaciones en las MFRs heliosféricas. Utilizando el método de la velocidad de crecimiento, la investigación evalúa la estabilidad de las MFRs bajo perturbaciones utilizando principios magnetohidrodinámicos y modelos de simetría cilíndrica. Este estudio se ha aplicado a datos de sondas espaciales en un intento de aumentar nuestra capacidad de predecir cuándo estas perturbaciones podrían causar cambios en la estructura, la dinámica y la trayectoria de una CME.Coronal Mass Ejections (CMEs) significantly impact space weather by transporting solar mass and energy into the Heliosphere. This research focuses on understanding their internal magnetic configurations, fundamentally Magnetic Flux Ropes (MFRs), which are crucial for predicting CME behavior. The study concentrates on the kink instability, a phenomenon that could induce heliospheric MFR rotations. Employing the growth rate method, the research assesses MFR stability under perturbations using magnetohydrodynamic principles and cylindrical symmetry models. This study has been applied to spacecraft data in an attempt to enhance our ability to predict when these perturbations might cause changes in the structure, dynamics, and trajectory of a CME.Outgoin

Phylogenetic analysis of an epidemic outbreak of acute hepatitis C in HIV-infected patients by ultra-deep pyrosequencing

Background: The incidence of acute hepatitis C (AHC) among HIV-infected men who have sex with men (MSM) has increased significantly in the last 10 years. Several studies point to a social and sexual network of HIV-positive MSM that extends internationally. Objectives: The aim of our study was to investigate the dynamics of HCV transmission in an outbreak of AHC in HIV-infected MSM in Barcelona by ultra-deep pyrosequencing. Study design: Between 2008 and 2013, 113 cases of AHC in HIV-infected MSM were diagnosed in the Infectious Diseases Unit, Hospital Clínic, Barcelona. Massive sequencing was performed using the Roche 454 GS Junior platform. To define possible transmission networks, maximum likelihood phylogenetic trees were constructed, and levels of genetic diversity within and among patients were compared. Results: Among the 70 cases analyzed, we have identified 16 potential clusters of transmission: 8 for genotype 1a (23 cases involved), 1 for genotype 1b (3 cases) and 7 for genotype 4d (27 cases). Although the initial phylogenetic reconstruction suggested a local transmission cluster of HCV gt4d, our approach based on low genetic differentiation did not corroborate it. Indeed, gt4d strains formed 4 independent groups related to patients from other countries. Conclusions: Frequent clustering of HIV-positive MSM shows that HCV infection has spread through a local network in Barcelona. This outbreak is related to a large international HCV transmission network among MSM. Public health efforts are needed to reduce HCV transmission among this high-risk group

Direct-acting antivirals for hepatitis C virus induce a rapid clinical and biochemical remission of porphyria cutanea tarda

Sporadic porphyria cutanea tarda (PCT) is strongly associated with hepatitis C virus (HCV) infection in our population. 1-4 Therapeutic options for PCT include phlebotomies and low-dose 4-aminoquinolines, which show high rates of disease remission. However, some patients with PCT may present frequent relapses attributable to resistance, intolerability or poor adherence to conventional treatments and/or persistence of risk factors. In 2014, we reported the first case of a patient with active PCT and HCV-HIV coinfection cured with direct antiviral agents (DAAs).5 Herein, we present a cohort of patients demonstrating rapid and persistent remission of PCT with DAA regimes administered for HCV infection

The influence of HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV-positive individuals

<p>Abstract</p> <p>Objective</p> <p>This study was performed to investigate the impact of HAART versus no HAART and nucleoside free versus nucleoside containing HAART on the efficacy and safety of pegylated interferon and ribavirin therapy for the treatment of chronic HCV infection in HIV/HCV co-infected patients. In addition a control group of HCV mono-infected patients undergoing anti-HCV therapy was evaluated.</p> <p>Methods</p> <p>Multicenter, partially randomized, controlled clinical trial. HIV-negative and -positive patients with chronic HCV infection were treated with pegylated interferon alfa-2a and ribavirin (800 - 1200 mg/day) for 24 - 48 weeks in one of four treatment arms: HIV-negative (A), HIV-positive without HAART (B) and HIV-positive on HAART (C). Patients within arm C were randomized to receive open label either a nucleoside containing (C1) or a nucleoside free HAART (C2).</p> <p>Results</p> <p>168 patients were available for analysis. By intent-to-treat analysis similar sustained virological response rates (SVR, negative HCV-RNA 24 weeks after the end of therapy) were observed comparing HIV-negative and -positive patients (54% vs. 54%, p = 1.000). Among HIV-positive patients SVR rates were similar between patients off and on HAART (57% vs. 52%, p = 0.708). Higher SVR rates were observed in patients on a nucleoside free HAART compared to patients on a nucleoside containing HAART, though confounding could not be ruled out and in the intent-to-treat analysis the difference was not statistically significant (64% vs. 46%, p = 0.209).</p> <p>Conclusions</p> <p>Similar response rates for HCV therapy can be achieved in HIV-positive and -negative patients. Patients on nucleoside free HAART reached at least equal rates of sustained virological response compared to patients on standard HAART.</p

Intususcepción ileo-cólica en paciente adulto, secundaria a lipoma

Mujer de 58 años, sin antecedentes y una colonoscopia normal 3 años antes, intervenida de apendicitis, que acudió a urgencias por dolor en epigastrio de 6 horas de evolución sin otros síntomas.&nbsp; Presentaba buen estado general. El abdomen era doloroso en fosa ilíaca derecha con defensa a ese nivel, sin masas y ruidos abdominales normales. No presentaba alteraciones analíticas. Se realizó radiografía de abdomen (Imagen 1) y TC abdominal con contraste intravenoso

Ideal cardiovascular health in women with systemic lupus erythematosus: Association with arterial stiffness, inflammation, and fitness

Methods This cross-sectional study included 76 women with SLE (age 43.4±13.8 years old). Ideal levels of 7 health metrics (smoking, body mass index, physical activity, healthy diet, blood pressure, cholesterol, and glucose) were used to define the ICH score (ranging from 0 to 7 ideal metrics) and the ICH status ( defined as presenting ≥4 ideal metrics). Arterial stiffness was measured through pulse wave velocity (PWV) and inflammation through serum high sensitivity C-reactive protein (hs-CRP). Cardiorespiratory fitness (CRF) was measured by 6-min walk test (6MWT), and Siconolfi step test and muscular strength by handgrip strength and 30-s chair stand, and range of motion (ROM) by the back-scratch test. Results Higher ICH score was associated with lower PWV (β = −0.122, p = 0.002), lower hs-CRP (β = −0.234, p = 0.056), higher CRF [6MWT (β = 0.263, p = 0.041); Siconolfi step test (β = 0.330, p < 0.001)], higher ROM (β = 0.278, p = 0.013) and higher relative handgrip strength (β = 0.248, p = 0.024). Women with ICH status presented lower PWV (mean difference 0.40 m/s, 95% CI 0.17 to 0.63, p = 0.001), and higher CRF [assessed by 6MWT (mean difference 43.9 m, 95% CI 5.0 to 82.7, p = 0.028)], than women with non-ICH status. Sensitivity analyses using ICH score ranging 0–14 and considering ICH status with ≥5 metrics revealed consistent results. Conclusion ICH is associated with lower arterial stiffness, lower inflammation, and higher fitness in women with SLE. Although these results extend current knowledge about the potential role of ICH for primordial prevention of CVD in SLE, they are yet to be confirmed in future prospective researchThisworkwas funded by the Consejería de Salud, Junta de Andalucía (grant numbers: PI-0525-2016 and PIER-0223-2019). AHM was supported by Plan Propio, ""Gerty Cori progra"" from University of Almería, Spain. BGCwas supported by the SpanishMinistry of Education (FPU15/00002)

Effects of 12-week Aerobic Exercise on Arterial Stiffness, Inflammation, and Cardiorespiratory Fitness in Women with Systemic LUPUS Erythematosus: Non-Randomized Controlled Trial

This study assessed the effect of 12-week aerobic exercise on arterial stiffness (primary outcome), inflammation, oxidative stress, and cardiorespiratory fitness (secondary outcomes) in women with systemic lupus erythematosus (SLE). In a non-randomized clinical trial, 58 women with SLE were assigned to either aerobic exercise (n = 26) or usual care (n = 32). The intervention comprised 12 weeks of aerobic exercise (2 sessions X 75 min/week) between 40–75% of the individual’s heart rate reserve. At baseline and at week 12, arterial stiffness was assessed through pulse wave velocity (PWV), inflammatory (i.e., high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TFN- α], and inteleukin 6 [IL-6]) and oxidative stress (i.e., myeloperoxidase [MPO]) markers were obtained from blood samples, and cardiorespiratory fitness was assessed (Bruce test). There were no between-group differences in the changes in arterial stiffness (median PWV difference -0.034, 95% CI -0.42 to 0.36 m/s; p = 0.860) or hsCRP, TNF-α, IL-6, and MPO (all p > 0.05) at week 12. In comparison to the control group, the exercise group significantly increased cardiorespiratory fitness (median difference 2.26 minutes, 95% CI 0.98 to 3.55; p = 0.001). These results suggest that 12 weeks of progressive treadmill aerobic exercise increases cardiorespiratory fitness without exacerbating arterial stiffness, inflammation, or oxidative stress in women with SLE.This work was supported by Fundación para la Investigación Biosanitaria de Andalucía Oriental (grant number: PI-0525-2016) and the Ilustre Colegio Oficial de Médicos de Granada (Premios de Investigación 2017). BG-C was supported by the Spanish Ministry of Education (FPU15/00002)

Association of physical fitness components and health-related quality of life in women with systemic lupus erythematosus with mild disease activity

To study the association of different components of physical fitness [flexibility, muscle strength and cardiorespiratory fitness (CRF)] and a clustered fitness score with healthrelated quality of life (HRQoL) in women with systemic lupus erythematosus (SLE) and to analyze whether participants with high fitness level have better HRQoL. This cross-sectional study included 70 women with SLE (aged 42.5; SD 13.9 years). The back-scratch test assessed flexibility, the 30-sec chair stand and handgrip strength tests assessed muscle strength, and the 6-min walk test (n = 49) assessed CRF. HRQoL was assessed through the 36-item Short-Form Health Survey (SF-36). Our study suggests that muscle strength and CRF are positively associated with HRQoL, while flexibility showed contradictory results. These findings highlight the importance of maintaining adequate fitness levels in women with SLE.This work was supported by the Consejería de Salud, Junta de Andalucía (grant number: PI-0525-2016) and the Ilustre Colegio Oficial de Médicos de Granada (Premios de Investigación 2017). BG-C was supported by the Spanish Ministry of Education (FPU15/00002)

Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.

Background and Aims This was a safety and efficacy pharmacogenetic study of a previously performed randomized trial which compared the effectiveness of treatment of hepatitis C virus infection with pegylated interferon alpha (pegIFNα) 2a vs. 2b, both with ribavirin, for 48 weeks, in HCV-HIV coinfected patients. Methods The study groups were made of 99 patients (efficacy pharmacogenetic substudy) and of 114 patients (safety pharmacogenetic substudy). Polymorphisms in the following candidate genes IL28B, IL6, IL10, TNFα, IFNγ, CCL5, MxA, OAS1, SOCS3, CTLA4 and ITPA were assessed. Genotyping was carried out using Sequenom iPLEX-Gold, a single-base extension polymerase chain reaction. Efficacy end-points assessed were: rapid, early and sustained virological response (RVR, EVR and SVR, respectively). Safety end-points assessed were: anemia, neutropenia, thrombocytopenia, flu-like syndrome, gastrointestinal disturbances and depression. Chi square test, Student's T test, Mann-Whitney U test and logistic regression were used for statistic analyses. Results As efficacy is concerned, IL28B and CTLA4 gene polymorphisms were associated with RVR (p<0.05 for both comparisons). Nevertheless, only polymorphism in the IL28B gene was associated with SVR (p = 0.004). In the multivariate analysis, the only gene independently associated with SVR was IL28B (OR 2.61, 95%CI 1.2-5.6, p = 0.01). With respect to safety, there were no significant associations between flu-like syndrome or depression and the genetic variants studied. Gastrointestinal disturbances were associated with ITPA gene polymorphism (p = 0.04). Anemia was associated with OAS1 and CTLA4 gene polymorphisms (p = 0.049 and p = 0.045, respectively), neutropenia and thromobocytopenia were associated with SOCS3 gene polymorphism (p = 0.02 and p = 0.002, respectively). In the multivariate analysis, the associations of the SOCS3 gene polymorphism with neutropenia (OR 0.26, 95%CI 0.09-0.75, p = 0.01) and thrombocytopenia (OR 0.07, 95%CI 0.008-0.57, p = 0.01) remained significant. Conclusions In HCV-HIV coinfected patients treated with PegIFNα and ribavirin, SVR is associated with IL28B rs8099917 polymorphism. HCV treatment-induced neutropenia and thrombocytopenia are associated with SOCS3 rs4969170 polymorphism