Control mechanisms of circadian rhythms in body composition: Implications for manned spaceflight

The mechanisms underlying the internal synchronization of the circadian variations in electrolyte content in body compartments were investigated, and the significance of these oscillations for manned spaceflight were examined. The experiments were performed with a chair-acclimatized squirrel monkey system, in which the animal sits in a chair, restrained only around the waist. The following information was given: (1) experimental methodology description, (2) summary of results obtained during the first contract year, and (3) discussion of the research performed during the second contract year. This included the following topics: physiological mechanisms promoting normal circadian internal synchronization, factors precipitating internal desynchronization, pathophysiological consequences of internal desynchronization of particular relevance to spaceflight, and validation of a chair-acclimatized system

Renal response to seven days of lower body positive pressure in the squirrel monkey

As a ground-based model for weightlessness, the response of the chair-trained squirrel monkey to lower body positive pressure (LBPP) was evaluated in a length of study similar to a typical Space Shuttle mission (7 days). Results were compared to time control experiments that included chair-sitting without exposure to LBPP. Chronic exposure to LBPP results in an acute diuretic and natriuretic response independent of changes in plasma aldosterone concentrations and produces a chronic reduction in fluid volume lasting the duration in the stimulus

Innovative Fatigue Management Approach in the Trucking Industry

Driver fatigue, recognized as a major safety problem in the transportation industry, is strongly influenced by employee work and sleep schedules. The work and rest hours of truck drivers have been regulated by Hours-of-Service (HoS) rules in the U.S since 1938, but it has become increasingly apparent these rules are inconsistent with the science of sleep and fatigue. We present and assess an innovative alternative safety management system, which takes a pro-active, science-based complimentary approach. This Risk-Informed Performance-Based (RIPB) safety system for sleep and fatigue management was implemented at one major trucking company, and involved the training of managers and dispatchers on scientific aspects of work assignments and a regular feedback system that assessed the fatigue risk of the work schedules. Driver fatigue was assessed using the Circadian Alertness Simulator (CAS) software system for simulating sleep and alertness based on work-rest patterns (Moore-Ede et al., 2004). Each driver was assigned a cumulative fatigue risk score based on logbook data processed for multiple one-month periods before and after the implementation of the safety management system. The implementation of the RIPB safety management system resulted in a significant reduction of fatigue risk scores, a reduction of the rate and costs of accidents, and improvement of other operational parameters. The success of the RIPB system was sustained over an extended time period of more than three years, and thus could permit the relaxation of overly prescriptive HoS regulations

Technologies for the Monitoring and Prevention of Driver Fatigue

A series of driving simulation pilot studies on various technologies for alertness monitoring (head position sensor, eye-gaze system), fitness-for-duty testing (two pupil-based systems), and alertness promotion (in-seat vibration system) has been conducted in Circadian Technologies’ Alertness Testbed. The results indicate that, all tested technologies show promise for monitoring/testing or preventing driver fatigue, respectively. However, particularly for fatigue monitoring, no single measure alone may be sensitive and reliable enough to quantify driver fatigue. Since alertness is a complex phenomenon, a multi-parametric approach needs to be used. Such a multi-sensor approach imposes challenges for online data interpretation. We suggest using a neural-fuzzy hybrid system for the automatic assessment of complex data streams for driver fatigue. The final system output can then be used to trigger the activation of alertness countermeasures

Potential Causes of Increased Vocalisation in Elderly Cats with Cognitive Dysfunction Syndrome as assessed by their owners

The objectives of this study were to explore owner perception of the causes of increased vocalisation in cats diagnosed with cognitive dysfunction syndrome (CDS) and consider what impact this vocalisation may have on the cat’s household. Owners of cats diagnosed with CDS that presented with increased vocalisation were invited to complete an online survey. The survey consisted of 28 questions including the cat’s signalment, its medical history, and questions pertaining to the owner’s perception of what motivated their cat´s increased vocalisation. This was determined by looking at the cat’s behaviour when vocalising, where it was looking when it was vocalising, and if the vocalisation stopped when the owner interacted with it, e.g., petting or feeding it. The owners were also asked how stressful they found their cat’s vocalisation. There were 37 responses. The majority of owners reported that the main cause of their cat’s vocalisation appeared to be disorientation (40.5%) or attention seeking (40.5%). Seeking a resource such as food was reported in 16.2%, and pain was perceived to be the cause in only 2.7% of cats. However, the majority of owners (64.8%) believed there was >1 cause of their cat’s increased vocalisation. Importantly, when owners were asked how stressful they found their cat’s increased vocalisation, 40.5% scored ≥3 (where 1 = not stressful; 5 = significantly stressful). This study provides novel insight into owner perception of feline CDS, as well as potential causes for increased vocalisation; this will allow veterinarians to better advise owners on how to manage their cat with CDS

Assessing Driver Fatigue as a Factor in Road Accidents

Fatigue is one of the most pervasive yet under-investigated causes of human-error-related driving accidents, incidents, and injuries. Several studies suggest that 25-30% of driving accidents are fatigue related (Horne et al., 1995). However, government reports estimate that only 1-4% of crashes may be attributable to the driver falling asleep or being drowsy, based largely on data derived from police reports recorded at these accidents (Cummings et al., 2001). The reason for this wide disparity is that there is no simple tool or objective way for investigators to collect the (right) data needed to correlate accidents with fatigue. To bridge this gap, a diagnostic survey instrument was developed, along with a weighted risk model based on Fuzzy Scalable Monotonic Chaining (FSMC), to help investigators readily determine (by standardized criteria and with high probability) the role of fatigue as a causal factor in driving accidents

Nephron-Specific Deletion of Circadian Clock Gene Bmal1 Alters the Plasma and Renal Metabolome and Impairs Drug Disposition.

The circadian clock controls a wide variety of metabolic and homeostatic processes in a number of tissues, including the kidney. However, the role of the renal circadian clocks remains largely unknown. To address this question, we performed a combined functional, transcriptomic, and metabolomic analysis in mice with inducible conditional knockout (cKO) of BMAL1, which is critically involved in the circadian clock system, in renal tubular cells (Bmal1(lox/lox)/Pax8-rtTA/LC1 mice). Induction of cKO in adult mice did not produce obvious abnormalities in renal sodium, potassium, or water handling. Deep sequencing of the renal transcriptome revealed significant changes in the expression of genes related to metabolic pathways and organic anion transport in cKO mice compared with control littermates. Furthermore, kidneys from cKO mice exhibited a significant decrease in the NAD(+)-to-NADH ratio, which reflects the oxidative phosphorylation-to-glycolysis ratio and/or the status of mitochondrial function. Metabolome profiling showed significant changes in plasma levels of amino acids, biogenic amines, acylcarnitines, and lipids. In-depth analysis of two selected pathways revealed a significant increase in plasma urea level correlating with increased renal Arginase II activity, hyperargininemia, and increased kidney arginine content as well as a significant increase in plasma creatinine concentration and a reduced capacity of the kidney to secrete anionic drugs (furosemide) paralleled by an approximate 80% decrease in the expression level of organic anion transporter 3 (SLC22a8). Collectively, these results indicate that the renal circadian clocks control a variety of metabolic/homeostatic processes at the intrarenal and systemic levels and are involved in drug disposition

Waking up to sleepiness: Modafinil, the media and the pharmaceuticalisation of everyday/night life

This paper examines the social construction of the new wakefulness-promoting drug Modafinil (brand name Provigil) in the British press. Key themes in this newspaper coverage include the potential 'uses' and 'abuses' of this drug in relation to: (i) medical conditions; (ii) lifestyle choices; (iii) military operations; and (iv) sporting competition. The British press, we show, play a dual role in reporting on these trends and developments: on the one hand constructing this as something of a 'wonder drug' in relation to the treatment of a number of medical complaints or conditions, on the other hand articulating and amplifying a range of cultural concerns and anxieties about the non-medical 'uses' and 'abuses' of this drug, both now and in the future. These issues, it is argued, are best interpreted in terms of media concerns over the pharmaceuticalisation rather than the medicalisation of everyday/night life. The paper concludes with some further thoughts and reflections on these issues, including the potential reworking of notions of 'pharmaceutical Calvinism' and the 'elective affinity' between this 'smart' new drug and the spirit of (bio)capitalism

The Circadian Rhythm of Blood Pressure During Pregnancy

To review the literature on the circadian rhythm of blood pressure during pregnancy. Data Sources : Computerized searches on MEDLINE, CINAHL, and MIRLYN. Study Selection : Selected studies from 1969 to 1997 were evaluated. Data Extraction : Data were extracted and information was organized under the following areas: definition of and the interconnection between circadian rhythm and blood pressure; the circadian variability of blood pressure throughout the trimesters; the patterns of the circadian rhythm of blood pressure in pregnancies defined as normal and those complicated by chronic hypertension and preeclampsia; and clinical implications. Data Synthesis : The circadian rhythm of blood pressure in pregnancy is the same as in the nonpregnant state, with a nocturnal decrease, especially during sleep. In patients with chronic hypertension, the nocturnal fall in blood pressure may be steeper. Patients with mild preeclampsia may experience a less pronounced nocturnal decrease in blood pressure. Patients with severe preeclampsia may display a reversed circadian rhythm, with no decrease and/or an increase in nocturnal blood pressure. Conclusions : The patterns of the circadian rhythm of blood pressure during normal pregnancy and pregnancies complicated by chronic hypertension and preeclampsia warrant consideration when monitoring patients and implementing management plans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71412/1/j.1552-6909.2000.tb02771.x.pd

Robust Food Anticipatory Activity in BMAL1-Deficient Mice

Food availability is a potent environmental cue that directs circadian locomotor activity in rodents. Even though nocturnal rodents prefer to forage at night, daytime food anticipatory activity (FAA) is observed prior to short meals presented at a scheduled time of day. Under this restricted feeding regimen, rodents exhibit two distinct bouts of activity, a nocturnal activity rhythm that is entrained to the light-dark cycle and controlled by the master clock in the suprachiasmatic nuclei (SCN) and a daytime bout of activity that is phase-locked to mealtime. FAA also occurs during food deprivation, suggesting that a food-entrainable oscillator (FEO) keeps time in the absence of scheduled feeding. Previous studies have demonstrated that the FEO is anatomically distinct from the SCN and that FAA is observed in mice lacking some circadian genes essential for timekeeping in the SCN. In the current study, we optimized the conditions for examining FAA during restricted feeding and food deprivation in mice lacking functional BMAL1, which is critical for circadian rhythm generation in the SCN. We found that BMAL1-deficient mice displayed FAA during restricted feeding in 12hr light:12hr dark (12L:12D) and 18L:6D lighting cycles, but distinct activity during food deprivation was observed only in 18L:6D. While BMAL1-deficient mice also exhibited robust FAA during restricted feeding in constant darkness, mice were hyperactive during food deprivation so it was not clear that FAA consistently occurred at the time of previously scheduled food availability. Taken together, our findings suggest that optimization of experimental conditions such as photoperiod may be necessary to visualize FAA in genetically modified mice. Furthermore, the expression of FAA may be possible without a circadian oscillator that depends on BMAL1