Predicting the timing and duration of sleep in an operational setting using social factors

In recent years, there has been increasing interest in the use of bio-mathematical models to predict alertness, performance, and/or fatigue in operational settings. Current models use only biological factors to make their estimations, which can be limited in operational settings where social and geo-physical factors also dictate when sleep occurs. The interaction between social and biological factors that help determine the timing and duration of sleep during layover periods have been investigated in order to create and initially validate a mathematical model that may better predict sleep in the field. Participants were 32 male transmeridian airline pilots (17 captains, 10 first officers, and 5 second officers) flying the Sydney-Bangkok-London-Singapore-Sydney (SYD-LHR) pattern. Participants continued their regular schedule while wearing activity monitors and completing sleep and work diaries. The theoretical sleep timing model underpinning this analysis consists of separate formulations for short (<32 h) and long (>32 h) break periods. Longer break periods are split into three distinct phases-recovery (break start until first local night), personal (first local night until last local night), and preparation phases (last local night until break end)-in order to exploit potential differences specific to each. Furthermore, an iterative procedure combining prediction and retrodiction (i.e., using future duty timing information to predict current sleep timing) was developed to optimize predictive ability. Analysis found an interaction between the social and circadian sleep pressures that changed over the break period. Correlation analysis indicated a strong relationship between the actual sleep and new model's predictions (r = 0.7-0.9), a significant improvement when compared to existing models (r = 0.1-0.4). Social and circadian pressures play important roles in regulating sleep for international flight crews. An initial model has been developed in order to regulate sleep in these crews. The initial results have shown promise when applied to small sets of data; however, more rigorous validation must be carried out.     

CCR5 in T cell-mediated liver diseases: what's going on?

The chemokine receptor CCR5 came into worldwide prominence a decade ago when it was identified as one of the major coreceptors for HIV infectivity. However, subsequent studies suggested an important modulatory role for CCR5 in the inflammatory response. Specifically, CCR5 has been reported to directly regulate T cell function in autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and type 1 diabetes. Moreover, T cell-mediated immune responses are proposed to be critical in the pathogenesis of autoimmune and viral liver diseases, and recent clinical and experimental studies have also implicated CCR5 in the pathogenesis of autoimmune and viral liver diseases. Therefore, in this brief review, we highlight the evidence that supports an important role of CCR5 in the pathophysiology of T cell-mediated liver diseases with specific emphasis on autoimmune and viral liver diseases.     

Population genomics in natural microbial communities

Little is known about the evolutionary processes that structure and maintain microbial diversity because, until recently, it was difficult to explore individual-level patterns of variation at the microbial scale. Now, community-genomic sequence data enable such variation to be assessed across large segments of microbial genomes. Here, we discuss how population-genomic analysis of these data can be used to determine how selection and genetic exchange shape the evolution of new microbial lineages. We show that once independent lineages have been identified, such analyses enable the identification of genome changes that drive niche differentiation and promote the coexistence of closely related lineages within the same environment. We suggest that understanding the evolutionary ecology of natural microbial populations through population-genomic analyses will enhance our understanding of genome evolution across all domains of life.     

A role for cyclic nucleotide monophosphates in synaptic modulation by a crayfish neuropeptide

DF2 (DRNFLRFamide), a FMRFamide-like peptide, has been shown to increase the amount of transmitter released at crayfish neuromuscular junctions. Here, we examined a possible role for the cyclic nucleotide monophosphates, cAMP and cGMP, in DF2's effects on synaptic transmission. The effects of DF2 on synaptic transmission were monitored by recording excitatory postsynaptic potentials (EPSPs) in the deep abdominal extensor muscles of the crayfish, Procambarus clarkii. A number of activators and inhibitors were used to determine whether or not cAMP, cGMP, protein kinase A (PKA) and protein kinase G (PKG) mediate the effect of this neuropeptide. Phosphodiesterase inhibitors, known to inhibit the breakdown of cAMP (IBMX) and/or cGMP (mdBAMQ), potentiate the effect of DF2 on synaptic transmission. Activators of PKA (Sp-cAMPS) and PKG (8-pCPT-cGMP) increase EPSP amplitude, mimicking the effects of DF2. Inhibitors of PKA (Rp-cAMPS) and PKG (Rp-8-pCPT-cGMPS) each block a portion of the response to the peptide, and when applied together these two inhibitors completely block the response. Taken together, these results indicate that cyclic nucleotides and cyclic nucleotide-dependent protein kinases are necessary components of the pathway underlying modulation by this neuropeptide.     

ACE2: A novel therapeutic target for cardiovascular diseases

Hypertension afflicts over 65 million Americans and poses an increased risk for cardiovascular morbidity such as stroke, myocardial infarction and end-stage renal disease resulting in significant mortality. Overactivity of the renin-angiotensin system (RAS) has been identified as an important determinant that is implicated in the etiology of these diseases and therefore represents a major target for therapy. In spite of the successes of drugs inhibiting various elements of the RAS, the incidence of hypertension and cardiovascular diseases remain steadily on the rise. This has lead many investigators to seek novel and innovative approaches, taking advantage of new pathways and technologies, for the control and possibly the cure of hypertension and related pathologies. The main objective of this review is to forward the concept that gene therapy and the genetic targeting of the RAS is the future avenue for the successful control and treatment of hypertension and cardiovascular diseases. We will present argument that genetic targeting of angiotensin-converting enzyme 2 (ACE2), a newly discovered member of the RAS, is ideally poised for this purpose. This will be accomplished by discussion of the following: (i) summary of our current understanding of the RAS with a focus on the systemic versus tissue counterparts as they relate to hypertension and other cardiovascular pathologies; (ii) the newly discovered ACE2 enzyme with its physiological and pathophysiological implications; (iii) summary of the current antihypertensive pharmacotherapy and its limitations; (iv) the discovery and design of ACE inhibitors; (v) the emerging concepts for ACE2 drug design; (vi) the current status of genetic targeting of the RAS; (vii) the potential of ACE2 as a therapeutic target for hypertension and cardiovascular disease treatment; and (viii) future perspectives for the treatment of cardiovascular diseases.     

Alcohol consumption patterns of shiftworkers compared with dayworkers

The detrimental effects of excessive alcohol consumption are well documented. There is some evidence that shiftworkers consume more alcohol than dayworkers as a sleep aid to compensate for sleep difficulties associated with work schedules. This study investigated drinking patterns between shiftworkers and dayworkers using the 2006 and 2007 waves from the Household Income and Labour Dynamics Survey. A subset of workers who were not in full-time study and had a single job were selected; participants who did not drink alcohol (n = 2090) were excluded. Using the 2001 Australian Government alcohol guidelines, alcohol consumption for risk of short-term harm (7+ standard drinks for men, 5+ for women) was investigated. The number of workers who drank alcohol "nearly every day" or "every day" was also examined. Some 13% of shiftworkers and 10% of those on standard schedules reported consuming alcohol at levels risky for short-term harm. Having a child less than 17 yrs (odds ratio [OR]?=?.39, 95% confidence interval [CI]?=?.22-.69), higher job demands (OR =?.71, 95% CI =?.58-.86), being female (OR =?.45, 95% CI=. 26-.79), and being older (OR =?.89, 95% CI =?.87-.92) significantly reduced, whereas being a shiftworker (OR = 2.10, 95% CI = 1.08-4.12) significantly increased, the odds of drinking alcohol in short-term risky levels. Nearly 10% of shiftworkers and 8% of those on standard schedules reported consuming alcohol in short-term risky levels at least weekly. Having a child less than 17 yrs (OR =?.40, 95% CI =?.22-.74), higher job demands (OR =?.69, 95% CI =?.56-.86), being female (OR =?.28, 95% CI =?.15-.53), and being older (OR =?.92, 95% CI =?.89-.94) were associated with a significant reduction in the odds of consuming alcohol at risky levels at least weekly. Being a shiftworker was not associated with a significant increase in the odds of consuming alcohol at such risky levels at least weekly, but a trend was evident (OR = 1.47, 95% CI =?.73-3.00). Some 13.5% of shiftworkers and 21% of those on standard schedules reported consuming alcohol in any amount "near daily" or "daily." Working more hours than preferred (OR = 1.80, 95% CI = 1.12-2.89) and being older (OR = 1.10, 95% CI = 1.07-1.13) were associated with a significant increase, and being female (OR =?.18, 95% CI =?.10-.33), and being a shiftworker (OR =?.20, 95% CI =?.09-.45) were associated with a significant decrease in the odds of consuming alcohol "daily" or "near daily." Overall, the results suggest that shiftworkers may be more likely to consume alcohol at levels considered to be risky for health in the short term. In contrast, they appear less likely to drink alcohol daily. This pattern is suggestive of "binge drinking" behavior.