Psoriasis is not determined by a genotype consistent with high production of Th1 cytokines or low production of Th2 cytokines. Thus, the Th1 cytokine profile found in psoriatic plaques is most likely a consequence of local factors.
Background: Assessing circadian rhythmicity from infrequently sampled data is challenging, however this type of data is often encountered when measuring circadian transcripts in hospitalised patients.
Methods:We present ClinCirc. This method combines two existing mathematical methods (Lomb-Scargle periodogram and cosinor) sequentially, and is designed to measure circadian oscillations from infrequently sampled clinical data. The accuracy of this method was compared against 9 other methods using simulated and frequently sampled biological data.ClinCirc was then evaluated in 13 ICU patients as well as in a separate cohort of 29 kidney transplant recipients. Finally, the consequences of circadian alterations were investigated in a retrospective cohort of 726 kidney transplant recipients.Results: ClinCirc had comparable performance to existing methods for analysing simulated data or clock transcript expression of healthy volunteers. It had improved accuracy compared to the cosinor method in evaluating circadian parameters in PER2::luc cell lines. In ICU patients, it was the only method investigated to suggest that loss of circadian oscillations in the peripheral oscillator was associated with inflammation, a feature widely reported in animal models. Additionally, ClinCirc was able to detect other circadian alterations, including a phase shift following kidney transplantation that was associated with the administration of glucocorticoids. This phase shift could explain why a significant complication of kidney transplantation (delayed graft dysfunction) oscillates according to the time-of-day kidney transplantation is performed.
Adsorption chromatography on columns of silica gel and partition between immiscible liquids have separated 8 resin Into several non-crystalline fractions, all having the predominating chemical reactivity associated with unsaturated, enolic/ phenolic substances containing a carbonyl group. In addition, some of these frac tions contain calcium, magnesium and potassium and possess a carboxylic acid function. The overall similarity in chemical behaviour of the fractions creates difficulties of working, for there is no simple basis on which to assess either the purity of a fraction or the efficiency of a fractionation procedure. A second factor which adds to the difficulties of using conventional fractionation techniques depends on the peculiar solubility characteristics exhibited; thus, composite fractions containing grossly differing materials behave physically like homogeneous single substances.
Background Sleep disturbance is common following hospitalisation both for COVID-19 and other causes. The clinical associations are poorly understood, despite it altering pathophysiology in other scenarios. We, therefore, investigated whether sleep disturbance is associated with dyspnoea along with relevant mediation pathways. Methods Sleep parameters were assessed in a prospective cohort of patients (n=2,468) hospitalised for COVID-19 in the United Kingdom in 39 centres using both subjective and device-based measures. Results were compared to a matched UK biobank cohort and associations were evaluated using multivariable linear regression. Findings 64% (456/714) of participants reported poor sleep quality; 56% felt their sleep quality had deteriorated for at least 1-year following hospitalisation. Compared to the matched cohort, both sleep regularity (44.5 vs 59.2, p<0.001) and sleep efficiency (85.4% vs 88.5%, p<0.001) were lower whilst sleep period duration was longer (8.25h vs 7.32h, p<0.001). Overall sleep quality (effect estimate 4.2 (3.0-5.5)), deterioration in sleep quality following hospitalisation (effect estimate 3.2 (2.0-4.5)), and sleep regularity (effect estimate 5.9 (3.7-8.1)) were associated with both dyspnoea and impaired lung function (FEV1 and FVC). Depending on the sleep metric, anxiety mediated 13-42% of the effect of sleep disturbance on dyspnoea and muscle weakness mediated 29-43% of this effect. Interpretation Sleep disturbance is associated with dyspnoea, anxiety and muscle weakness following COVID-19 hospitalisation. It could have similar effects for other causes of hospitalisation where sleep disturbance is prevalent.
Circadian regulation causes the activity of biological processes to vary over a 24-h cycle. The pathological effects of this variation are predominantly studied using two different approaches: pre-clinical models or observational clinical studies. Both these approaches have provided useful insights into how underlying circadian mechanisms operate and specifically which are regulated by the molecular oscillator, a key time-keeping mechanism in the body. This review compares and contrasts findings from these two approaches in the context of four common respiratory diseases (asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and respiratory infection). Potential methods used to identify and measure human circadian oscillations are also discussed as these will be useful outcome measures in future interventional human trials that target circadian mechanisms.
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