Conventionally, circadian phase of the SCN is assessed through long-term collection of biomarkers in the field or in the clinic. Knowledge of the circadian phase of the SCN is also informative for the diagnosis of CRSWDs, assessment of adaptation to new time zones, adaptation to shift work ( Mullington et al., 2016) and identification of circadian rhythm disturbances in psychiatric conditions. Optimal treatment requires that the circadian phase of the SCN is known and is thereby one example of chronotherapy, an increasingly important field in drug development and medicine ( Dallmann et al., 2016). Treatment of these circadian disorders by melatonin or light exploits the circadian phase-dependent response of the SCN to these stimuli ( Auger et al., 2015). Examples of CRSWDs are delayed sleep-wake phase disorder, which is prevalent in adolescents ( Micic et al., 2016), and non-24-hr sleep-wake disorder, such as occurs in blind individuals ( Sack et al., 1992 Sack and Lewy, 2001). Synchronization of the SCN to the L-D cycle and synchronization of the sleep-wake cycle to the SCN are disrupted during shift work and jet lag and in circadian rhythm sleep-wake disorders (CRSWDs). Exogenous melatonin can phase-shift and entrain the SCN, but its effects depend on the circadian phase of melatonin administration ( Lewy et al., 2005). The SCN is also sensitive to feedback from the pineal melatonin rhythm which impinges on the SCN through its melatonin receptors ( Pevet and Challet, 2011). The effects of light on the SCN depend on the timing, that is, the circadian phase of the SCN, at which light is administered ( St Hilaire et al., 2012). Under normal conditions, the SCN is synchronized to the 24 hr light-dark (L-D) cycle by a light-input pathway ( Lucas et al., 2014). The master circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus drives 24 hr rhythmicity in endocrine and neural factors such as cortisol, melatonin and the autonomic nervous system ( Brancaccio et al., 2014 Kalsbeek and Fliers, 2013). Many physiological and molecular variables exhibit 24 hr rhythmicity generated by central and peripheral circadian oscillators, as well as environmental and behavioral influences ( Morris et al., 2012 Mohawk et al., 2012). This blood transcriptome-based model enables assessment of circadian phase from a few samples. When given one sample as input, the R 2 of predicted vs observed phase was 0.74, whereas for two samples taken 12 hr apart, R 2 was 0.90. Validation showed that PLSR-based predictors outperform published blood-derived circadian phase predictors.
Partial least square regression (PLSR), applied to the transcriptome, identified a set of 100 biomarkers primarily related to glucocorticoid signaling and immune function. Transcriptome data were collected under normal, sleep-deprivation and abnormal sleep-timing conditions to assess robustness of the predictor. We developed and validated a multivariate whole-blood mRNA-based predictor of melatonin phase which requires few samples.
#Kimball organ r80 series
The gold-standard univariate method is based on collection of a 24-hr time series of plasma melatonin, a suprachiasmatic nucleus-driven pineal hormone. Dedicated to the company's Guiding Principles, its values and integrity are evidenced by public recognition as a highly trusted company and an employer of choice.Diagnosis and treatment of circadian rhythm sleep-wake disorders both require assessment of circadian phase of the brain’s circadian pacemaker. Kimball International now creates design driven, innovative furnishings sold through the family of brands: Kimball Office, National Office Furniture, and Kimball Hospitality. The diverse portfolio offers solutions for the workplace, learning, healing, and hospitality environments. Kimball International transformed again into a focused furniture company and continued as a publicly-traded company on the NASDAQ Exchange under the ticker symbol KBAL. On November 1, 2014, Kimball International spun-off its Kimball Electronics business segment to an independent publicly-traded company.
These brands are serving the funishing needs of the commercial office, learning, healing and hospitality markets. Since 2014, Kimball International has focused on profitable growth of its three brands, Kimball, National and Kimball Hospitality.
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