Theory of Inpatient Circadian Care (TICC): A Proposal for a Middle-Range Theory.

The circadian system controls the daily rhythms of a variety of physiological processes. Most organisms show physiological, metabolic and behavioral rhythms that are coupled to environmental signals. In humans, the main synchronizer is the light/dark cycle, although non-photic cues such as food availability, noise, and work schedules are also involved. In a continuously operating hospital, the lack of rhythmicity in these elements can alter the patient's biological rhythms and resilience. This paper presents a Theory of Inpatient Circadian Care (TICC) grounded in circadian principles. We conducted a literature search on biological rhythms, chronobiology, nursing care, and middle-range theories in the databases PubMed, SciELO Public Health, and Google Scholar. The search was performed considering a period of 6 decades from 1950 to 2013. Information was analyzed to look for links between chronobiology concepts and characteristics of inpatient care. TICC aims to integrate multidisciplinary knowledge of biomedical sciences and apply it to clinical practice in a formal way. The conceptual points of this theory are supported by abundant literature related to disease and altered biological rhythms. Our theory will be able to enrich current and future professional practice.

Study of a Functional Polymorphism in the PER3 Gene and Diurnal Preference in a Colombian Sample.

Polymorphisms in human clock genes have been evaluated as potential factors influencing circadian phenotypes in several populations. There are conflicting results for the association of a VNTR in the PER3 gene and diurnal preference in different studies. The objective of this study was to investigate the association between diurnal preference and daytime somnolence with the PER3 VNTR polymorphism (rs57875989) in healthy subjects from Colombia, a Latin American population.A total of 294 undergraduate university students from Bogotá, Colombia participated in this study. Two validated self-report questionnaires, the Composite Scale of Morningness (CSM) and the Epworth Sleep Scale (ESS) were used to assess diurnal preference and daytime somnolence, respectively. Individuals were genotyped for the PER3 VNTR using conventional PCR. Statistical comparisons were carried out with PLINK and SNPStats programs. The PER3 VNTR polymorphism was not associated with either diurnal preference or daytime somnolence in this population. No significant differences in mean scores for those scales were found between PER3 VNTR genotypes. In addition, there were no differences in allelic or genotypic frequencies between chronotype categories. This is consistent with several negative findings in other populations, indicating that the proposed influence of this polymorphism in diurnal preference, and related endophenotypes of neuropsychiatric importance, needs further clarification. This is the first report of molecular genetics of human circadian phenotypes in a Spanish-speaking population.

Common functional polymorphisms in SLC6A4 and COMT genes are associated with circadian phenotypes in a South American sample.

The molecular study of circadian rhythms in humans could be an excellent approach to understand the relation between genes and behavior. It is possible that variations in genes involved in neurotransmission and/or synaptic plasticity, such as catechol-O-methyltransferase (COMT) and serotonin transporter (SLC6A4) could be of particular interest in understanding human circadian phenotypes. The aim of this study is to analyze the possible and novel associations of the functional polymorphisms in COMT and SLC6A4 genes (Val158Met and 5-HTTLPR) and circadian phenotypes in healthy Colombian subjects. 191 university students were genotyped for two functional polymorphisms in COMT and SLC6A4 genes (rs4680 and rs4795541). We applied two scales to measure phenotypic patterns of human circadian rhythms: Composite Scale of Morningness (CSM) and Epworth Sleepiness Scale (ESS). We found a significant association between 5-HTTLPR polymorphism and morning preference score (CSM) (p = 0.027) using an overdominant genotypic model and association of COMT Val158Met with daytime sleepiness (ESS scores) (p = 0.038) in a genotypic recessive model. These results were supported by differences in genotype frequencies between circadian typologies for SLC6A4 gene (p = 0.007) and categories of diurnal sleepiness for COMT gene (p = 0.032). Our results suggest, for the first time, a significant relationship between functional SLC6A4 and COMT polymorphisms with specific human circadian phenotypes: morning preference and diurnal sleepiness. These results need to be replicated in other populations. Further study of functional polymorphisms in other synaptic genes could be of relevance for the identification of novel candidate genes for circadian phenotypes, and related endophenotypes of neuropsychiatric importance, in healthy humans.

A functional polymorphism in the promoter region of MAOA gene is associated with daytime sleepiness in healthy subjects.

Excessive daytime sleepiness (EDS) is one of the main causes of car and industrial accidents and it is associated with increased morbidity and alterations in quality of life. Prevalence of EDS in the general population around the world ranges from 6.2 to 32.4%, with a heritability of 38-40%. However, few studies have explored the role of candidate genes in EDS. Monoamine oxidase A (MAOA) gene has an important role in the regulation of neurotransmitter levels and a large number of human behaviors. We hypothesized that a functional VNTR in the promoter region of the MAOA gene might be associated with daytime sleepiness in healthy individuals. The Epworth sleepiness scale (ESS) was applied to 210 Colombian healthy subjects (university students), which were genotyped for MAOA-uVNTR. MAOA-uVNTR showed a significant association with ESS scores (p = 0.01): 3/3 genotype carriers had the lowest scores. These results were supported by differences in MAOA-uVNTR frequencies between diurnal somnolence categories (p = 0.03). Our finding provides evidence for the first time that MAOA-uVNTR has a significant association with EDS in healthy subjects. Finally, these data suggest that functional variations in MAOA gene could have a role in other phenotypes of neuropsychiatric relevance.

A novel association of two non-synonymous polymorphisms in PER2 and PER3 genes with specific diurnal preference subscales.

The circadian system is responsible for the generation and maintenance of physiological and behavioral rhythms in mammals and allows synchronization with the environment. Different polymorphisms in clock genes have been studied in healthy humans, providing inconsistent results in different populations. In this study, we evaluated the possibility that two non-synonymous polymorphisms in PER2 (p.Gly1244Glu, rs934945) and PER3 (p.Met1028Thr, rs2640909) genes might be associated with diurnal preference in healthy Colombian subjects. A total of 209 Colombian university students were genotyped for two functional polymorphisms in PER2 and PER3 genes (rs934945 and rs2640909). We applied the composite scale of morningness (CSM) to measure phenotypic patterns of human diurnal preference. Additionally, we extracted from the CSM three subscale scores ("morningness", "activity planning" and "morning alertness"). We used a false discovery rate approach (q values) for correction of multiple testing. PER2 (rs934945) showed a significant association with two CSM subscale scores: "activity planning" and "morning alertness". For PER3 (rs2640909), we observed an association with the "morningness" CSM subscale scores. We found a significant association between novel and functional polymorphisms in PER2 and PER3 genes with specific CSM subscales for diurnal preference. We showed for the first time the association of rs934945 with "morning alertness" and rs2640909 with "morningness". We suggest that these results should be replicated in order to confirm the association in other populations. Finally, the study of additional novel functional polymorphisms in other clock genes could be of relevance for a deep understanding of circadian phenotypes and neuropsychiatric disorders.