Farnesoid X receptor agonist for the treatment of chronic hepatitis B: a safety study

The nuclear farnesoid X receptor (FXR) regulates bile acid homeostasis and is a drug target for metabolic liver diseases. FXR also plays an important role in hepatitis B virus (HBV) DNA transcription. In vitro and in mice, FXR agonist treatment leads to inhibition of viral replication and a decline in viral proteins, pregenomic RNA (pgRNA) and HBV DNA levels. We aimed to translate this to a clinical use by primarily evaluating the safety and secondary the anti-viral effect of Vonafexor, a FXR agonist, in chronic hepatitis B (CHB) patients. In total, 73 CHB patients were enrolled in a two-part Phase Ib double-blind, placebo-controlled trial. Patients were randomized to receive oral Vonafexor (100, 200 and 400 mg once daily, or 200 mg twice daily), placebo, or entecavir (Part A, n = 48) or to receive Vonafexor (300 mg once daily or 150 mg twice daily), or placebo, combined with pegylated-interferon-alpha 2a (Part B, n = 25) for 29 days. Patients were followed up for 35 days. Enrolled CHB patients were mostly HBeAg-negative. Vonafexor was overall well tolerated and safe. The most frequent adverse events were moderate gastrointestinal events. Pruritus was more frequent with twice-daily compared with once-daily regimens (56%-67% vs. 16%, respectively, p < 0.05). Vonafexor monotherapy of 400 mg once daily decreased HBsAg concentrations (-0.1 log(10) IU/mL, p < 0.05), and Vonafexor/pegylated-IFN-alpha 2a combination therapy decreased HBcrAg and pgRNA. In conclusion, Vonafexor was safe with a decline in HBV markers observed in CHB patients suggesting a potential anti-viral effect the therapeutic potential of which has to be evaluated in larger trials.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Control de cambios / Rastrea los cambios / El camino cambia: Reflexiones sobre un mundo en transformación

“Track changes: Reflecting on a transforming world” was the theme chosen to invite panels, papers, posters and alternative presentations to be part of the 2019 international congress of SIEF that was held in Santiago de Compostela, Galicia (Spain). This introduction includes a description of the content of the congress, the rationale of the choice of plenaries and some reflections about the outcomes of the congress.El lema elegido para presentar paneles, ponencias, posters y presentaciones en formatos alternativos para el congreso internacional 2019 de SIEF -que tuvo lugar en Santiago de Compostela, Galicia (España)- fue&nbsp;“Track changes: Reflecting on a transforming world”.&nbsp;Esta introducción incluye una descripción del contenido del congreso, la idea para la elección de las plenarias y algunas reflexiones sobre los resultados del congreso. &nbsp

Pathways between childhood trauma, intimate partner violence, and harsh parenting : findings from the UN multi-country study on men and violence in Asia and the Pacific

2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordPublishe

Drivers for international innovation activities in developed and emerging countries

This paper aims to shed light on firm specific drivers that lead firms to internationalise their innovation activities. The paper draws a comprehensive picture of driving forces by including firm capabilities, characteristics of the firm’s competitive environment and the influence of innovation obstacles in the home country. In particular, the role of the potential driving forces is tested on the probability to carry out different innovative activities abroad (R&D, design/conception of new products, manufacturing of innovative products and implementation of new processes). In a second step these driving forces are used to observe their impact on the decision to locate innovation activities in various countries and regions (China, Eastern Europe, Western Europe and North America) as well as in groups of countries with similar levels of knowledge (country clubs). The analysis is based on the Mannheim Innovation Panel survey which represents the German CIS (Community Innovation Survey) contribution. Two survey waves are combined and result in a sample of about 1400 firms. The results show that the decision to perform innovation activities abroad is mainly driven by organisational capabilities such as absorptive capacities, international experience and existing technological competences of the respective firm. Innovation barriers at the German home base such as lack of labour and high innovation costs foster the set up of later-stage innovation activities abroad while the lack of demand demonstrates a barrier to the internationalisation decision for the development and manufacturing of new products. Location decisions receive the strongest influencing effects from the international experience of the firm. Firms which innovate in developing countries seem to require a more extensive level of international experience by international R&D cooperation

Unraveling the Shift to the Entrepreneurial Economy

A recent literature has emerged providing compelling evidence that a major shift in the organization of the developed economies has been taking place: away from what has been characterized as the managed economy towards the entrepreneurial economy. In particular, the empirical evidence provides consistent support that (1) the role of entrepreneurship has significantly increased, and (2) a positive relationship exists between entrepreneurial activity and economic performance. However, the factors underlying this observed shift have not been identified in a systematic manner. The purpose of this paper is to suggest some of the factors leading to this shift and implications for public policy. In particular, we find that a fundamental catalyst underlying the shift from the managed to the entrepreneurial economy involved the role of technological change. However, we also find that it was not just technological change but rather involved a number of supporting factors, ranging from the demise of the communist system, increased globalization, new competition for multinational firms and higher levels of prosperity. Recognition of the causes of the shift from the managed to the entrepreneurial economy suggests a rethinking of the public policy approach. Rather than the focus of directly and exclusively on promoting startups and SMEs, it may be that the current approach to entrepreneurship policy is misguided. The priority should not be on entrepreneurship policy but rather a more pervasive and encompassing approach, policy consistent with an entrepreneurial economy

Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Exposure to Magnetic Field

Objective: Nucleolar organizer region (NORs) is directly related to cell cycle and is an indicator of cell proliferation. We explored, in the present study, whether there was a difference in proliferation between brain tissues subjected to magnetic field for different durations.Study Design: The study comprised 5 groups with six rats each. Groups A and B were exposed to magnetic fields for 2.5 hours/day and 2.5 minutes/day, respectively, everyday for three months. Sham groups for Group A (SA) and Group B (SB) were constructed and switched-off cellular phones were left in the same environment for the same duration as their corresponding experimental groups. Rat's brains were removed, placed in 10% formalin and 3 micron thick sections were obtained following routine histological methods. Sections were stained with AgNOR stain. The number of AgNORs for each 100 cortical neurons, hippocampal neurons, ependymal and choroid plexus cells were counted on every section with an immersion microscope objective.Results: Statistical analyses revealed that mean number of AgNORs was highest in Group A (3.69 +/- 0.54), followed by Group B (3.06 +/- 0.48). Even though there was no statistically significant difference between sham groups (SA=1.76 +/- 0.56 and SB=1.84 +/- 0.65, p=0.990), mean number of AgNORs in sham groups was significantly higher than the control group (1.29 +/- 0.42) (p <= 0.05). Groups A and B differed significantly from the sham and control groups in terms of mean number of AgNORs (p <= 0.001).Conclusion: Increased proliferative activity and protein synthesis in neuronal and glial cells of the brain tissue in response to exposure to magnetic field is demonstrated by AgNORs