Nitric Oxide Not Apoptosis Mediates Differential Killing of Mycobacterium bovis in Bovine Macrophages

To identify the resistance phenotype against Mycobacterium bovis in cattle, we used a bactericidal assay that has been considered a marker of this trait. Three of 24 cows (12.5%) were phenotyped as resistant and 21 as susceptible. Resistance of bovine macrophages (MΦ) to BCG challenge was evaluated for its association with SLC11A1 GT microsatellite polymorphisms within 3′UTR region. Twenty-three cows (95.8%) had a GT(13) genotype, reported as resistant, consequently the SLC11A1polymorphism was not in agreement with our bactericidal assay results. MΦ of cows with resistant or susceptible phenotype were challenged in vitro with virulent M. bovis field strain or BCG, and nitric oxide production, bacterial killing and apoptosis induction were measured in resting and LPS-primed states. M. bovis field strain induced more apoptosis than BCG, although the difference was not significant. Resistant MΦ controlled better the replication of M. bovis (P<0.01), produced more nitric oxide (P<0.05) and were slightly more prone to undergo apoptosis than susceptible cells. LPS pretreatment of MΦ enhanced all the functional parameters analyzed. Inhibition of nitric oxide production with n (G)-monomethyl-L-arginine monoacetate enhanced replication of M. bovis but did not modify apoptosis rates in both resistant and susceptible MΦ. We conclude that nitric oxide production not apoptosis is a major determinant of macrophage resistance to M. bovis infection in cattle and that the influence of SLC11A1 gene 3′UTR polymorphism is not associated with this event

Coffee's beneficial effect on liver disease confirmed in NASH cohort, but only partially confirmation of in vitro pre-described differentially expressed genes in this patient cohort

This journal suppl. entitled: 2011 DDW Abstract SupplementSession - Steatosis and Steatohepatitis / Q02 Steatohepatitis: ClinicalBACKGROUND; Coffee consumption has been associated with reduced liver fibrosis. Cultured cells and animal models have been used to identify differently-regulated genes that might explain this effect. No studies evaluating the effect of coffee consumption on liver gene expression in patients with liver disease have been reported. PATIENTS AND METHODS: Patients with biopsy-proven NAFLD who completed questionnaires about coffee consumption were classified into 3 groups: none (n = 108), minimal-to moderate ( or = 7 servings/week; n = 88). Univariate and multivariate analysis were used to assess the relationship between coffee consumption, various histologic parameters (e.g., steatosis, NAS activity score, ballooning, fibrosis), and potentially-relevant demographic variables (e.g., age, gender, BMI). RNA was also isolated from the liver biopsies of 48 of these subjects and subjected to microarray analysis using Affymetrix genechip HGU133-plus 2.0 to determine changes in liver gene expression associated with coffee consumption. 37% of these 48 patients had advanced fibrosis (F3-4) and 63% had early fibrosis (F0-1). Of the 23 patients who drank more than 7 cups/week, 18 (78%) had F0-1 fibrosis and 5 (22%) had F3-4 fibrosis (p=0.06). RESULTS: Coffee consumption was inversely associated with fibrosis severity in univariate analysis (p<0.012). In multivariate analysis, advanced fibrosis was positively correlated with age (p<0.04) and negatively correlated with coffee consumption (p<0.01). Coffee consumption was also associated with lower HbA1c values (r-0.17; p=0.01). However, the association of coffee consumption and lower fibrosis was independent of HbA1c (p=0.047). Consumption of other caffeine containing beverages, such as tea and soda, was not associated with fibrosis stage. Using linear regression analysis our microarray analysis confirmed a significant relationship between daily coffee consumption and lower expression of transforming growth factor -beta1(TGFβ1) and higher expression of stearoyl-CoA desaturase 1 (SCD), Peroxisome proliferator-activated receptor alfa (PPARα) and gluthation-S-transferase (GST). CONCLUSION: Coffee consumption of at least a cup a day appears protective against fibrosis progression in NAFLD. The underlying mechanism might involve induction of protective mechanism leading to reduced fibrogenesis

When pedagogic worlds collide: Reflections on a pan-European entrepreneurship education project

Through the Entrepreneurship 2020 Action Plan launched in 2013, the European Commission set out its agenda for how entrepreneurship could help tackle the problems associated with the 2008 financial crisis. In this chapter we present how STARTIFY7, a project funded by the Commission’s Horizon 2020 initiative, sought to respond to the Entrepreneurship 2020 Action Plan. The STARTIFY7 project was created as a thematically focused and lean-training summer academy system with the aim of creating pan-European teams of young entrepreneurs in the information and communications technology (ICT) sector. The project and its underlying pedagogic approach, derived from Neck and Greene’s (2011) work on ‘worlds’ of entrepreneurship education, is discussed along with the outcomes achieved

British Association of Dermatologists guidelines for biologic therapy for psoriasis 2020: A rapid update

The overall aim of the guideline is to provide up‐to‐date, evidence‐based recommendations on the use of biologic therapies targeting TNF (adalimumab, etanercept, certolizumab pegol, infliximab), IL12/23p40 (ustekinumab), IL17A (ixekizumab, secukinumab), IL17RA (brodalumab) and IL23p19 (guselkumab, risankizumab, tildrakizumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis

British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017

The overall aim of the guideline is to provide evidence-based recommendations on the use of biologic therapies (adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis. Biologic therapies have now been in use for over 10 years, and with accrued patient-years exposure and clinical experience, many areas that were covered in previous versions of the guideline are now part of the Summary of Product Characteristics (SPC) and/or routine care so that specific recommendations are redundant (see Toolkit A: Summary of licensed indications and posology for biologic therapy, in Supporting information 2). Therefore, in this update we focus on areas where there has been a major change in the evidence base or clinical practice, where practice is very varied and/or where clear consensus or guidelines are lacking (see section 3.1 in Supporting information 1)

Geriatric rehabilitation of stroke patients in nursing homes: a study protocol.

Contains fulltext : 88482.pdf (publisher's version ) (Open Access)BACKGROUND: Geriatric patients are typically underrepresented in studies on the functional outcome of rehabilitation after stroke. Moreover, most geriatric stroke patients do probably not participate in intensive rehabilitation programs as offered by rehabilitation centers. As a result, very few studies have described the successfulness of geriatric stroke rehabilitation in nursing home patients, although it appears that the majority of these patients are being discharged back to the community, rather than being transferred to residential care. Nevertheless, factors associated with the successfulness of stroke rehabilitation in nursing homes or skilled nursing facilities are largely unknown. The primary goal of this study is, therefore, to assess the factors that uniquely contribute to the successfulness of rehabilitation in geriatric stroke patients that undergo rehabilitation in nursing homes. A secondary goal is to investigate whether these factors are similar to those associated with the outcome of stroke rehabilitation in the literature. METHODS/DESIGN: This study is part of the Geriatric Rehabilitation in AMPutation and Stroke (GRAMPS) study in the Netherlands. It is a longitudinal, observational, multicenter study in 15 nursing homes in the Southern part of the Netherlands that aims to include at least 200 patients. All participating nursing homes are selected based on the existence of a specialized rehabilitation unit and the provision of dedicated multidisciplinary care. Patient characteristics, disease characteristics, functional status, cognition, behavior, and caregiver information, are collected within two weeks after admission to the nursing home. The first follow-up is at discharge from the nursing home or one year after inclusion, and focuses on functional status and behavior. Successful rehabilitation is defined as discharge from the nursing home to an independent living situation within one year after admission. The second follow-up is three months after discharge in patients who rehabilitated successfully, and assesses functional status, behavior, and quality of life. All instruments used in this study have shown to be valid and reliable in rehabilitation research or are recommended by the Netherlands Heart Foundation guidelines for stroke rehabilitation.Data will be analyzed using SPSS 16.0. Besides descriptive analyses, both univariate and multivariate analyses will be performed with the purpose of identifying associated factors as well as their unique contribution to determining successful rehabilitation. DISCUSSION: This study will provide more information about geriatric stroke rehabilitation in Dutch nursing homes. To our knowledge, this is the first large study that focuses on the determinants of success of geriatric stroke rehabilitation in nursing home patients