Modulating Stress Susceptibility and Resilience: Insights from miRNA Manipulation and Neural Mechanisms in Mice.

This study explored the impact of microRNAs, specifically mmu-miR-1a-3p and mmu-miR-155-5p, on stress susceptibility and resilience in mice of different strains. Previous research had established that C57BL/6J mice were stress-susceptible, while NET-KO and SWR/J mice displayed stress resilience. These strains also exhibited variations in the serum levels of mmu-miR-1a-3p and mmu-miR-155-5p. To investigate this further, we administered antagonistic sequences (Antagomirs) targeting these microRNAs to C57/BL/6J mice and their analogs (Agomirs) to NET-KO and SWR/J mice via intracerebroventricular (i.c.v) injection. The impact of this treatment was assessed using the forced swim test. The results showed that the stress-susceptible C57/BL/6J mice could be transformed into a stress-resilient phenotype through infusion of Antagomirs. Conversely, stress-resilient mice displayed altered behavior when treated with Ago-mmu-miR-1a-3p. The study also examined the expression of mmu-miR-1a-3p in various brain regions, revealing that changes in its expression in the cerebellum (CER) were associated with the stress response. In vitro experiments with the Neuro2a cell line indicated that the Antago/Ago-miR-1a-3p and Antago/Ago-miR-155-5p treatments affected mRNAs encoding genes related to cAMP and Ca2+ signaling, diacylglycerol kinases, and phosphodiesterases. The expression changes of genes such as Dgkq, Bdnf, Ntrk2, and Pde4b in the mouse cerebellum suggested a link between cerebellar function, synaptic plasticity, and the differential stress responses observed in susceptible and resilient mice. In summary, this research highlights the role of mmu-miR-1a-3p and mmu-miR-155-5p in regulating stress susceptibility and resilience in mice and suggests a connection between these microRNAs, cerebellar function, and synaptic plasticity in the context of stress response.

Cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: protocol for the randomised, single-blinded, parallel-group Sleep-RA trial.

BACKGROUND: More than half of patients with rheumatoid arthritis complain of insomnia, which is predominantly treated with hypnotic drugs. However, cognitive behavioural therapy for insomnia is recommended as the first-line treatment in international guidelines on sleep. Patients with rheumatoid arthritis suffer from debilitating symptoms, such as fatigue and pain, which can also be linked to sleep disturbance. It remains to be determined whether cognitive behavioural therapy for insomnia can be effective in patients with rheumatoid arthritis. The aim of the Sleep-RA trial is to investigate the efficacy of cognitive behavioural therapy for insomnia on sleep and disease-related symptoms in patients with rheumatoid arthritis. The primary objective is to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep efficiency from baseline to week 7 in patients with rheumatoid arthritis. The key secondary objectives are to compare the effect of cognitive behavioural therapy for insomnia relative to usual care on changes in sleep onset latency, wake after sleep onset, total sleep time, insomnia, sleep quality, fatigue, impact of rheumatoid arthritis and depressive symptoms from baseline to week 26 in patients with rheumatoid arthritis. METHODS: The Sleep-RA trial is a randomised controlled trial with a two-group parallel design. Sixty patients with rheumatoid arthritis, insomnia and low-to-moderate disease activity will be allocated 1:1 to treatment with cognitive behavioural therapy for insomnia or usual care. Patients in the intervention group will receive nurse-led, group-based cognitive behavioural therapy for insomnia once a week for 6 weeks. Outcome assessments will be carried out at baseline, after treatment (week 7) and at follow-up (week 26). DISCUSSION: Data on treatment of insomnia in patients with rheumatoid arthritis are sparse. The Sleep-RA trial is the first randomised controlled trial to investigate the efficacy of cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis. Because symptoms of rheumatoid arthritis and insomnia have many similarities, we also find it relevant to investigate the secondary effects of cognitive behavioural therapy for insomnia on fatigue, impact of rheumatoid arthritis, depressive symptoms, pain, functional status, health-related quality of life and disease activity. If we find cognitive behavioural therapy for insomnia to be effective in patients with rheumatoid arthritis this will add weight to the argument that evidence-based non-pharmacological treatment for insomnia in rheumatological outpatient clinics is eligible in accordance with the existing international guidelines on sleep. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03766100. Registered on 30 November 2018.

Simultaneous spectrophotometric flow injection determination of phosphate and silicate.

A method for the simultaneous determination of phosphate and silicate based on spectrophotometric measurement at 385 nm of a single peak using a flow injection system with two component calibration is described. In the system, a stream of sample containing both analytes is merged with a stream of ammonium molybdate to form (at 1