Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance.

Cortisol and inflammatory proteins are released into the blood in response to stressors and chronic elevations of blood cortisol and inflammatory proteins may contribute to ongoing disease processes and could be useful biomarkers of disease. How chronic circadian misalignment influences cortisol and inflammatory proteins, however, is largely unknown and this was the focus of the current study. Specifically, we examined the influence of weeks of chronic circadian misalignment on cortisol, stress ratings, and pro- and anti-inflammatory proteins in humans. We also compared the effects of acute total sleep deprivation and chronic circadian misalignment on cortisol levels. Healthy, drug free females and males (N=17) aged 20-41 participated. After 3weeks of maintaining consistent sleep-wake schedules at home, six laboratory baseline days and nights, a 40-h constant routine (CR, total sleep deprivation) to examine circadian rhythms for melatonin and cortisol, participants were scheduled to a 25-day laboratory entrainment protocol that resulted in sleep and circadian disruption for eight of the participants. A second constant routine was conducted to reassess melatonin and cortisol rhythms on days 34-35. Plasma cortisol levels were also measured during sampling windows every week and trapezoidal area under the curve (AUC) was used to estimate 24-h cortisol levels. Inflammatory proteins were assessed at baseline and near the end of the entrainment protocol. Acute total sleep deprivation significantly increased cortisol levels (p<0.0001), whereas chronic circadian misalignment significantly reduced cortisol levels (p<0.05). Participants who exhibited normal circadian phase relationships with the wakefulness-sleep schedule showed little change in cortisol levels. Stress ratings increased during acute sleep deprivation (p<0.0001), whereas stress ratings remained low across weeks of study for both the misaligned and synchronized control group. Circadian misalignment significantly increased plasma tumor necrosis factor-alpha (TNF-α), interleukin 10 (IL-10) and C-reactive protein (CRP) (p<0.05). Little change was observed for the TNF-α/IL-10 ratio during circadian misalignment, whereas the TNF-α/IL-10 ratio and CRP levels decreased in the synchronized control group across weeks of circadian entrainment. The current findings demonstrate that total sleep deprivation and chronic circadian misalignment modulate cortisol levels and that chronic circadian misalignment increases plasma concentrations of pro- and anti-inflammatory proteins.

Statins, fibrates, and melanoma risk: a systematic review and meta-analysis.

BACKGROUND: Large randomized, controlled clinical trials of lovastatin and gemfibrozil for heart disease prevention have reported statistically significantly lower melanoma incidences in persons receiving these medications. Results of in vitro animal model and human case-control studies also suggest that statins and fibrates may reduce the risk of melanoma. METHODS: We performed a systematic review of trials that randomly assigned participants to receive statins or fibrates versus an alternative therapy for a minimum of 6 months. Trials were identified by searching five electronic databases and the reference lists of eligible publications. Unpublished data were solicited from trial investigators and pharmaceutical companies. A meta-analysis was performed using a fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate pooled treatment effects. All statistical tests were two-sided. RESULTS: We obtained data on incident melanomas from 20 of 36 qualifying randomized controlled trials (12 statin trials and eight fibrate trials), with a total of 70,820 participants. A total of 127 melanomas occurred among the 39,426 participants in the statin trials (59 among the 19,872 statin group participants and 68 among the 19,554 control group participants). A total of 27 melanomas occurred among the 31,394 participants enrolled in the fibrate trials (seven among the 12,324 fibrate group participants and 20 among the 19,070 control group participants). Overall, incidence of melanoma was not statistically significantly associated with the use of either statins (OR = 0.87, 95% CI = 0.61 to 1.23) or fibrates (OR = 0.45, 95% CI = 0.20 to 1.01). In a subgroup analysis by drug, only lovastatin use (in one trial) was statistically significantly associated with lower incidence of melanoma (OR = 0.52, 95% CI = 0.27 to 0.99). CONCLUSIONS: These findings do not validate the possibility that statins or fibrates prevent melanoma.

Compliance with youth access regulations for indoor UV tanning.

OBJECTIVES: To describe youth access to indoor UV tanning and youth discount pricing incentives in 4 states with different age restrictions: Colorado (no age restrictions), Texas (age 13 years), Illinois (age 14 years), and Wisconsin (age 16 years). DESIGN: Cross-sectional telephone survey conducted in October 2003 using a standardized script to assess the practices of randomly selected UV tanning operators. PARTICIPANTS: Randomly selected licensed indoor UV tanning facility operators in Colorado, Texas, Illinois, and Wisconsin. MAIN OUTCOME MEASURES: Number of facilities (1) complying with indoor UV tanning minimum age regulations for a 12-year-old potential patron and a 15-year-old potential patron and (2) offering youth discounts. RESULTS: For a 12-year-old potential patron, 62% of facilities in states with minimum age restrictions prohibiting 12-year-olds had an operator report that they would not permit indoor tanning (Texas, 23%; Illinois, 74%; and Wisconsin, 89%) compared with 18% in Colorado, a state without youth access regulations. For a 15-year-old patron, most facilities in Wisconsin, the only state with a minimum age restriction for 15-year-olds, prohibited access (77%). Overall, 15% of operators offered youth discounts: Texas, 23%; Illinois, 14%; Wisconsin, 11%; and Colorado, 11%. CONCLUSIONS: Tanning facilities in 4 states offered price incentives directed at youths. State youth access regulations were associated with decreased youth access to indoor tanning. High compliance levels in states with long-standing youth access regulations (Illinois and Wisconsin) demonstrate the potential for successful tanning industry youth access regulation.

A case for informed consent? Indoor UV tanning facility operator's provision of health risks information (United States).

OBJECTIVE: Indoor UV tanning is associated with skin cancer. This study describes consumer health risks information provided by indoor UV tanning facility operators in four states (Colorado, Illinois, Texas, and Wisconsin) with varying operator training, regulations, enforcement and penalties. METHODS: Using a cross-sectional survey study design, 100 randomly selected licensed indoor UV tanning facilities from each state were surveyed anonymously by telephone. Facility operators were questioned regarding the provision of information on potential adverse effects of indoor UV exposure. RESULTS: Of 628 licensed indoor UV tanning facilities contacted, 400 facilities were surveyed. Most (87%) advised patrons of the potential risk of sunburn from indoor tanning. Less than half of facility operators in Colorado, Texas and Wisconsin informed patrons about the risk of skin cancer (42, 43 and 48%, respectively) compared with 81% of Illinois operators. Likewise, more operators in Illinois reported the risk of premature aging (79%) compared with other states (41% Colorado, 43% Texas and 51% Wisconsin). CONCLUSIONS: Tanning facility operators frequently misinformed patrons of indoor UV exposure risks. The provision of informed consent by indoor tanning facility operators needs improved adaptation by the tanning industry as a standard for customer service.

Information science. Going, going, gone: lost Internet references.

The use of Internet references in academic literature is common, and Internet references are frequently inaccessible. The extent of Internet referencing and Internet reference activity in medical or scientific publications was systematically examined in more than 1000 articles published between 2000 and 2003 in the New England Journal of Medicine, The Journal of the American Medical Association, and Science. Internet references accounted for 2.6% of all references (672/25548) and in articles 27 months old, 13% of Internet references were inactive. Publishers, librarians, and readers need to reassess policies, archiving systems, and other resources for addressing Internet reference attrition to prevent further information loss.