Feasibility of a Manualized Mindful Yoga Intervention for Patients With Chronic Mood Disorders

Chronic mood disorders pose an important mental health problem. Individuals with these disorders experience a significant impairment, often fail to seek help, and their illnesses frequently do not respond to treatment. It is therefore important to develop innovative and attractive treatments for these disorders. Mindful yoga represents a promising treatment approach. This pilot study tested the feasibility of a 9-week manualized mindful yoga intervention for patients with chronic mood disorders. Eleven patients receiving standard treatment were recruited to complete a 9-week mindful yoga intervention. Qualitative methods were used to assess patients' experiences of the intervention and quantitative methods were used to assess psychological distress and mechanisms that play a role in chronic mood disorders. Eight patients completed the intervention and rated the overall quality of the intervention with a mean score of 8.8 (range of 8 to 9, using a scale of 1 to 10). All participants reported a reduction in psychological distress and no adverse events. Among the mechanisms that play a role in chronic mood disorders, the most potentially promising effects from the intervention were found for worry, fear of depression and anxiety, rumination, and areas related to body awareness, such as trusting bodily experiences and not distracting from sensations of discomfort. A 9-week mindful yoga intervention appears to be a feasible and attractive treatment when added to treatment as usual for a group of patients with chronic mood disorders. A randomized controlled trial to study the effects of mindful yoga is recommended

The temporal dynamics of daily stress, affect, and several affect regulation processes, in patients with chronic mood and anxiety disorders before and after a mindful yoga intervention

Background and Objectives: Patients with chronic mood and anxiety disorders experience many life stressors and are more reactive to these stressors. Although mindful yoga might reduce stress reactivity, little is known about the affect regulation mechanisms involved, such as repetitive negative thinking, fear of emotion, acting with awareness and body awareness. Design and Methods: Using experience sampling methodology, 12 patients with chronic mood and anxiety disorders completed five daily assessments for 15 days before and after a 9-week mindful yoga intervention. Interrupted time-series analyses were used to assess mean-level change from pre-to-post intervention and vector autoregressive models to assess change in the temporal associations. Results: Most individuals experienced positive changes in affect and the proposed affect regulation processes. Fear of emotion showed changes from pre-to-post intervention for most individuals (67%), followed by acting with awareness (58%), body awareness (58%) and repetitive negative thinking (50%). In the dynamic relationships between stressors, the four affect regulation processes and affect, there were individual differences in which pathways changed and how they changed. Conclusions: After a mindful yoga intervention, affect and several affect regulation processes improve in most individuals. Achieving this in the context of daily life stress, seems to be more complicated. Trial registration: ISRCTN register (study ID ISRCTN13612864).</p

The IFIT2–IFIT3 antiviral complex targets short 5’ untranslated regions on viral mRNAs for translation inhibition

Recognition of foreign RNA is critical for the innate immune response to viruses. Interferon (IFN)-induced proteins with tetratricopeptide repeats (IFIT) 2 and 3 are highly upregulated following viral infection, but mechanistic insight into their antiviral role is lacking. Here we demonstrate that short 5’ untranslated regions (UTRs), a characteristic of many viral mRNAs, can serve as a molecular pattern for innate immune recognition via IFIT2 and IFIT3. Structure determination of the IFIT2–IFIT3 complex at 3.2 Å using cryo-EM reveals a domain-swapped heterodimer that is required for recognition of the viral mRNA 5’ end, translation inhibition and antiviral activity. Critically, viral or host 5’ UTR lengths less than 50 nucleotides are necessary and sufficient to enable translation inhibition by the IFIT2–IFIT3 complex. Accordingly, diverse viruses whose mRNAs contain short 5’ UTRs, such as vesicular stomatitis virus and parainfluenza virus 3, are sensitive to IFIT2–IFIT3-mediated antiviral activity. Our work thus reveals a pattern of antiviral nucleic acid immune recognition that takes advantage of the inherent constraints on viral genome size

A Multi-Variant, Viral Dynamic Model of Genotype 1 HCV to Assess the in vivo Evolution of Protease-Inhibitor Resistant Variants

Variants resistant to compounds specifically targeting HCV are observed in clinical trials. A multi-variant viral dynamic model was developed to quantify the evolution and in vivo fitness of variants in subjects dosed with monotherapy of an HCV protease inhibitor, telaprevir. Variant fitness was estimated using a model in which variants were selected by competition for shared limited replication space. Fitness was represented in the absence of telaprevir by different variant production rate constants and in the presence of telaprevir by additional antiviral blockage by telaprevir. Model parameters, including rate constants for viral production, clearance, and effective telaprevir concentration, were estimated from 1) plasma HCV RNA levels of subjects before, during, and after dosing, 2) post-dosing prevalence of plasma variants from subjects, and 3) sensitivity of variants to telaprevir in the HCV replicon. The model provided a good fit to plasma HCV RNA levels observed both during and after telaprevir dosing, as well as to variant prevalence observed after telaprevir dosing. After an initial sharp decline in HCV RNA levels during dosing with telaprevir, HCV RNA levels increased in some subjects. The model predicted this increase to be caused by pre-existing variants with sufficient fitness to expand once available replication space increased due to rapid clearance of wild-type (WT) virus. The average replicative fitness estimates in the absence of telaprevir ranged from 1% to 68% of WT fitness. Compared to the relative fitness method, the in vivo estimates from the viral dynamic model corresponded more closely to in vitro replicon data, as well as to qualitative behaviors observed in both on-dosing and long-term post-dosing clinical data. The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied