Hepatitis C infection: eligibility for antiviral therapies

peer reviewedBackground Current treatments of chronic hepatitis C virus (HCV) are effective, but expensive and susceptible to induce significant side effects. Objectives To evaluate the proportion of HCV patients who are eligible for a treatment. Methods In a database comprising 1726 viraemic HCV patients, the files of 299 patients who presented to the same hepatologist for an initial appointment between 1996 and 2003 were reviewed. Results Patients' characteristics were age 43.1 +/- 15.6 years, 53% male and 92% Caucasian. The main risk factors were transfusion (43%) and drug use (22%). Genotypes were mostly genotype 1 (66%), genotype 3 (12%) and genotype 2 (10%). These characteristics were not different from those of the whole series of 1726 patients. A total of 176 patients (59%) were not treated, the reasons for non-treatment being medical contraindications (34%), non-compliance (25%) and normal transaminases (24%). In addition, 17% of patients declined therapy despite being considered as eligible, mainly due to fear of adverse events. Medical contraindications were psychiatric (27%), age (22%), end-stage liver disease (15%), willingness for pregnancy (13%), cardiac contraindication (7%) and others (16%). Only 123 patients (41%) were treated. A sustained viral response was observed in 41%. The treatment was interrupted in 16% for adverse events. Conclusions The majority of HCV patients are not eligible for treatment. This implies that, with current therapies, only 17% of patients referred for chronic HCV become sustained responders. Some modifications of guidelines could extend the rate of treatment (patients with normal transaminases), but an important barrier remains the patients' and the doctors' fear of adverse events

Inositol metabolism in Trypanosoma cruzi: potential target for chemotherapy against Chagas' disease

Chagas' disease is a debilitating and often fatal disease caused by the protozoan parasite Trypanosoma cruzi. The great majority of surface molecules in trypanosomes are either inositol-containing phospholipids or glycoproteins that are anchored into the plasma membrane by glycosylphosphatidylinositol anchors. The polyalcohol myo-inositol is the precursor for the biosynthesis of these molecules. In this brief review, recent findings on some aspects of the molecular and cellular fate of inositol in T. cruzi life cycle are discussed and identified some points that could be targets for the development of parasite-specific therapeutic agents

CD4+ and γδ T Cells are the main Producers of IL-22 and IL-17A in Lymphocytes from Mycobacterium bovis-infected Cattle

Gene transcription studies have identified dual roles for the cytokines IL-17A and IL-22 in bovine tuberculosis, where they show potential as both predictors of vaccine success and correlates of infection. To allow for a detailed investigation of the cell populations responsible for production of these cytokines, we have utilised a novel bovine IL-22 specific recombinant antibody for flow cytometry. Bovine tuberculin (PPDB) induced greater IL-22 and IL-17A production in Mycobacterium bovis (M. bovis)-infected cattle compared to non-infected controls, while PWM-induced cytokine levels were similar between the two groups. In M. bovis-infected animals, PPDB specific IL-22 and IL-17A responses were observed in both CD4+ T cell and γδ T cell populations. Although both cytokines were detected in both cell types, IL-22/IL-17A double producers were rare and confined mainly to the γδ T cell population. These results support previous gene transcription studies and extend the observation of increased IL-22 and IL-17A responses in M. bovis-infected animals to the level of protein production. We were also able to characterise the cell populations responsible for these disease-related cytokine responses. The data generated can be used to further our understanding of the immunopathology of bovine tuberculosis and to produce more sensitive and specific immune-diagnostic reagents

Different Strokes for Different Folks? Contrasting Approaches to Cultural Adaptation of Parenting Interventions

Relevant achievements have been accomplished in prevention science with regard to disseminating efficacious parenting interventions among underserved populations. However, widespread disparities in availability of parenting services continue to negatively impact diverse populations in high-income countries (e.g., the USA) and low- and middle-income countries. As a result, a scholarly debate on cultural adaptation has evolved over the years. Specifically, some scholars have argued that in diverse cultural contexts, existing evidence-based parenting interventions should be delivered with strict fidelity to ensure effectiveness. Others have emphasized the need for cultural adaptations of interventions when disseminated among diverse populations. In this paper, we propose that discussions on cultural adaptation should be conceptualized as a “both-and,” rather than an “either-or” process. To justify this stance, we describe three distinct parenting intervention projects to illustrate how cultural adaptation and efficacy of evidence-based interventions can be achieved using contrasting approaches and frameworks, depending on cultural preferences and available resources of local contexts. Further, we suggest the need to develop guidelines for consistent reporting of cultural adaptation procedures as a critical component of future investigations. This discussion is relevant for the broader public health field and prevention science

Characterization of alcohol dehydrogenase (ADH12) from Haloarcula marismortui, an extreme halophile from the Dead Sea

Haloarchaeal alcohol dehydrogenases are of increasing interest as biocatalysts in the field of white biotechnology. In this study, the gene adh12 from the extreme halophile Haloarcula marismortui (HmADH12), encoding a 384 residue protein, was cloned into two vectors: pRV1 and pTA963. The resulting constructs were used to transform host strains Haloferax volcanii (DS70) and (H1209), respectively. Overexpressed His-tagged recombinant HmADH12 was purified by immobilized metal-affinity chromatography (IMAC). The His-tagged protein was visualized by SDS-PAGE, with a subunit molecular mass of 41.6 kDa, and its identity was confirmed by mass spectrometry. Purified HmADH12 catalyzed the interconversion between alcohols and aldehydes and ketones, being optimally active in the presence of 2 M KCl. It was thermoactive, with maximum activity registered at 60°C. The NADP(H) dependent enzyme was haloalkaliphilic for the oxidative reaction with optimum activity at pH 10.0. It favored a slightly acidic pH of 6.0 for catalysis of the reductive reaction. HmADH12 was significantly more tolerant than mesophilic ADHs to selected organic solvents, making it a much more suitable biocatalyst for industrial application.Science Foundation IrelandIrish Research Council for Science, Engineering and TechnologyMerckIslamic Development BankEmbargo to 1 Jan 2013 --J

Positive Emotions as a Potential Mediator of a Multi-Component Positive Psychology Intervention Aimed at Increasing Mental Well-Being and Resilience

We examined mediators of a multi-component positive psychology intervention for healthy employees. We analyzed data from a randomized controlled trial involving 158 participants who were assigned to a six-session intervention program or a wait-list control group. In total, 144 participants completed baseline and post-test assessment. The mediating effects of positive emotions and psychological flexibility on treatment outcomes mental well-being and resilience at post-test assessment were examined. We also examined the influence of a range of moderators on the relationship between the intervention and the outcomes. Mediator analyses showed that these improvements possibly and partially work through increasing positive emotions. Psychological flexibility could not be considered a mediator. However, due to inability to infer causality, definite conclusions on the mediating effect of positive emotions cannot be drawn. In relation to mental well-being, a significant moderating effect for ethnicity was found in the intervention group