Salivary levels of alpha-amylase are associated with neurobehavioral alertness during extended wakefulness, but not simulated night-shift work.

Sleep loss is one of the most common causes of accidents and errors in operational environments. Currently, no single method satisfies all of the requisite criteria of an effective system for assessing the risk of injury prior to safety being compromised. Research has concentrated towards the development of a biomarker for individualized assessment of sleepiness-related deficits in neurobehavioral alertness, with salivary alpha-amylase (sAA) recently reported as a potential biomarker during acute total sleep deprivation. The present study extends on previous research by investigating the association between sAA and neurobehavioral alertness during simulated night-shift work, during individuals are required to work at night when biological processes are strongly promoting sleep and sleep during the day when endogenous processes are promoting wakefulness. In a laboratory-controlled environment, 10 healthy non-shift working males aged 24.7 ±â€¯5.3 years (mean ±â€¯SD) underwent four consecutive nights of simulated night-shift work. Between 17:30-04:30 h participants provided saliva samples and completed a 3 min psychomotor vigilance test (PVT-B), 40 min simulated driving task, and 3 min digit symbol substitution test (DSST). Higher sAA levels were associated with faster response speed on the PVT-B, reduced lane variability on the simulated driving task, and improved information processing speed on the DSST during the first night-shift. There were no associations between sAA levels and performance outcomes during subsequent night-shifts. Findings indicate that the usability of sAA to assess the risk of neurobehavioral deficits during shift-work operations is limited. However, the robust circadian rhythm exhibited by sAA during the protocol of circadian misalignment suggests that sAA could serve as a potential circadian marker.

Long-term day-and-night rotating shift work poses a barrier to the normalization of alanine transaminase.

To evaluate the impact of day-and-night rotating shift work (RSW) on liver health, we performed a retrospective analysis of the association between long-term RSW exposure and the normalization of plasma alanine transaminase (ALT) levels over a five-year period. The data from physical examinations, blood tests, abdominal sonographic examinations, personal histories, and occupational records were collected from a cohort of workers in a semiconductor manufacturing company. The sample population was divided into three subgroups for analysis, according to self-reported shift work status over the five-year interval: persistent daytime workers, workers exposed intermittently to RSW (i-RSW), and workers exposed persistently to RSW (p-RSW). Records were analyzed for 1196 male workers with an initial mean age of 32.5 years (SD 6.0 years), of whom 821 (68.7%) were identified as rotating shift workers, including 374 i-RSW (31.3%) and 447 p-RSW workers (37.4%). At the beginning of the follow-up, 275 were found to have elevated ALT (e-ALT): 25.1% daytime workers, 23.0% i-RSW workers, and 21.3% p-RSW workers (p = 0.098). Of those with e-ALT at the beginning, 101 workers showed normalized serum ALT levels at the end of five-year follow-up: 40 (10.7%) of 375 daytime workers, 32 (8.6%) of 374 i-RSW workers, and 29 (6.5%) of 447 p-RSW workers (p = 0.016). Compared with the workers having persistent e-ALT at the end of follow-up, the workers normalized serum ALT levels had significantly lesser exposures to RSW during follow-up. By performing multivariate logistic regression analyses, and comparing with the persistent daytime co-workers, after controlling for confounding variables (age, occupational factors, educational levels, lifestyle factors, metabolic syndrome, hepatovirus infection, and fatty liver), analysis indicated that the workers exposed to p-RSW were 46% less likely (OR, 0.54; 95% CI, 0.30-0.95; p = 0.03) to attain normal ALT levels within a five-year interval. These observations demonstrate that persistent day-and-night RSW pose a vigorous obstacle to the normalization of e-ALT among workers with preexisting abnormal liver function. We suggest that workers and managers approach with caution the consideration of assigning or accepting long-term day-and-night RSW when an employee health screening shows evidence of abnormal liver function.

Sleep and rhythm consequences of a genetically induced loss of serotonin.

BACKGROUND: A genetic deficiency in sepiapterin reductase leads to a combined deficit of serotonin and dopamine. The motor phenotype is characterized by a dopa-responsive fluctuating generalized dystonia-parkinsonism. The non-motor symptoms are poorly recognized. In particular, the effects of brain serotonin deficiency on sleep have not been thoroughly studied. OBJECTIVE: We examine the sleep, sleep-wake rhythms, CSF neurotransmitters, and melatonin profile in a patient with sepiapterin reductase deficiency. PATIENT: The patient was a 28-year-old man with fluctuating generalized dystonia-parkinsonism caused by sepiapterin reductase deficiency. METHODS: A sleep interview, wrist actigraphy, sleep log over 14 days, 48-h continuous sleep and core temperature monitoring, and measurement of CSF neurotransmitters and circadian serum melatonin and cortisol levels before and after treatment with 5-hydroxytryptophan (the precursor of serotonin) and levodopa were performed. RESULTS: Before treatment, the patient had mild hypersomnia with long sleep time (704 min), ultradian sleep-wake rhythm (sleep occurred every 11.8 +/- 5.3 h), organic hyperphagia, attentionlexecutive dysfunction, and no depression. The serotonin metabolism in the CSF was reduced, and the serum melatonin profile was flat, while cortisol and core temperature profiles were normal. Supplementation with 5-hydroxytryptophan, but not with levodopa, normalized serotonin metabolism in the CSF, reduced sleep time to 540 min, normalized the eating disorder and the melatonin profile, restored a circadian sleep-wake rhythm (sleep occurred every 24 +/- 1.7 h, P < 0.0001), and improved cognition. CONCLUSION: In this unique genetic paradigm, the melatonin deficiency (caused by a lack of its substrate, serotonin) may cause the ultradian sleep-wake rhythm.

Casein kinase I epsilon (CKIvarepsilon) N408 allele is very rare in the Brazilian population and is not involved in susceptibility to circadian rhythm sleep disorders.

Circadian rhythms are regulated by clock proteins through post-translational modifications. Indeed, Casein kinase I epsilon (CKIvarepsilon) promotes reversible phosphorylation of PER proteins, and a deficiency in this phosphorylation has been implicated in human sleep disorders. Here, we investigated the CKIvarepsilon S408N polymorphism in a Brazilian population sample. The N408 allele was previously described to be much less frequent in individuals with Delayed Sleep-Phase Syndrome (DSPS), than in the general Japanese population, suggesting a protective function for the allele against the disease. We found that this polymorphism is very rare in the Brazilian population (1.37%), indicating that it has no influence on susceptibility to circadian rhythm sleep disorders. Therefore, it is necessary to account for adaptative influences in genetic background, analyzing different groups with different photoperiods, to validate the effects of this and other polymorphisms on sleep and circadian disorders.

Sex differences in susceptibility to oxidative injury and sleepiness from intermittent hypoxia.

STUDY OBJECTIVES: Adult male mice exposed to long-term intermittent hypoxia (LTIH), modeling sleep apnea oxygenation patterns, develop nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent residual hypersomnolence and oxidative injury in select brain regions, including wake-active regions. Premenopausal females are less susceptible to selective oxidative brain injuries. We sought to determine whether female mice exposed to LTIH would confer resistance to LTIH-induced wake impairments and oxidative injuries. SUBJECTS AND SETTING: Young adult male and female C57BI/6J mice were studied in a university laboratory. INTERVENTIONS: Mice were randomly assigned to either LTIH or sham LTIH for 8 weeks. Total (24-h) wake time and mean sleep latency were measured under 2 conditions: rested and following 6 hours of enforced wakefulness. NADPH oxidase activation, carbonylation, and lipid peroxidation assays were also performed to assess sex differences in oxidative responses to LTIH. RESULTS: In contrast with the significant LTIH-induced wake impairments observed in male mice, females following LTIH showed normal wake times and sleep latencies. Female mice revealed less baseline carbonylation and less carbonylation following LTIH but showed robust NADPH oxidase activation and lipid peroxidation. In contrast with the female relative resistance to LTIH sleepiness, female mice showed more-pronounced sleepiness and delta response after enforced wakefulness. CONCLUSIONS: Despite a robust oxidative response to LTIH, age-matched female mice may be protected, at least temporarily, from LTIH wake impairments by lower basal carbonylation. In contrast, females show greater wake impairments after sleep deprivation. We hypothesize sex differences in polysomnographic predictors of sleepiness and residual sleepiness in humans with sleep apnea.