Chronotype and anxiety are associated in patients with chronic primary insomnia

Objective: To assess the interaction of chronotype with anxiety in patients with chronic primary insomnia. Methods: Sixty-four patients (50 women) with mean age 43.9±8.1 years were investigated with the Horne and Östberg Morningness-Eveningness Questionnaire (MEQ) and State-Trait Anxiety Inventory (STAI). Results: Significant negative correlations of chronotype-MEQ score with STAI state-anxiety (r = -0.40, p < 0.05), STAI trait-anxiety (r = -0.40, p < 0.05), and STAI pre-sleep state anxiety (r = -0.30, p < 0.05) were observed. Eveningness preference was associated with higher trait, state, and pre-sleep state anxiety. Conclusions: These results suggest that chronotype may be an important parameter to identifying the origin and significance of a vicious anxiety-insomnia-depression cycle in patients with chronic primary insomnia

Effects of resistance exercise training and stretching on chronic insomnia

Objective: The aim of this study was to assess the effects of resistance exercise and stretching on sleep, mood, and quality of life in chronic insomnia patients. Methods: Three 4-month treatments included: resistance exercise (n=10), stretching (n=10), and control (n=8). Sleep was evaluated with polysomnography, actigraphy, and questionnaires. Mood and quality of life were assessed with the Profile of Mood States (POMS) and the Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36), respectively. Results: There were no significant treatment differences between resistance exercise and stretching. However, compared with the control treatment, resistance exercise and stretching led to significantly greater improvements in Insomnia Severity Index scores (-10.5±2.3, -8.1±2.0 vs. 2.3±1.8, respectively), and actigraphic measures of sleep latency (-7.1±4.6, -5.2±1.9 vs. 2.2±2.1 min), wake after sleep onset (-9.3±2.8, -7.1±3.0 vs. 3.6±4.2 min), and sleep efficiency (4.4±1.8, 5.0±0.8 vs. -2.3±2%). Pittsburgh Sleep Quality Index (PSQI) global scores (-5.3±0.8, -3.9±1.5 vs. -0.1±0.8) and sleep duration (1.2±0.3, 1.6±0.6 vs. -0.1±0.2 h) also improved following both experimental treatments compared with control. PSQI-Sleep efficiency increased after resistance exercise compared with control (19.5±3.9 vs. 2.1±4.3%). No significant differences were observed in polysomnography or quality of life measures. Tension-anxiety was lower in the stretching group than the control group. Conclusion: Moderate-intensity resistance exercise and stretching led to similar improvements in objective and subjective sleep in patients with chronic insomnia. Clinical trial registration: NCT0157111

Toxicological Evaluation of Anti-Scrapie Trimethoxychalcones and Oxadiazoles

An altered form of the cellular prion protein, the PrPScor PrPRes, is implicated in the occurrence of the still untreatable transmissible spongiform encephalopathies. We have previously synthesized and characterized aromatic compounds that inhibit protease-resistant prion protein (PrPRes) accumulation in scrapie-infected cells. These compounds belong to different chemical classes, including acylhydrazones, chalcones and oxadiazoles. Some of the active compounds were non-toxic to neuroblastoma cells in culture and seem to possess drugable properties, since they are in agreement with the Lipinski´s rule of 5 and present desirable pharmacokinetic profiles as predicted in silico. Before the evaluation of the in vivo efficacy of the aromatic compounds in scrapie-infected mice, safety assessment in healthy mice is needed. Here we used Swiss mice to evaluate the acute toxicity profile of the six most promising anti-prionic compounds, the 2,4,5-trimethoxychalcones (J1, J8, J20 and J35) and the 1,3,4-oxadiazoles (Y13 and Y17). One single oral administration (300 mg/kg) of J1, J8, J20, J35, Y13 and Y17 or repeated intraperitoneal administration (10 mg/kg, 3 times a week, for 4 weeks) of J1, J8 and J35, did not elicit toxicity in mice. We strongly believe that the investigated trimethoxychalcones and oxadiazoles are interesting compounds to be further analyzed in vivo against prion diseases