24-hour pattern of work-related injury risk of French firemen: nocturnal peak time

The first aim of the study was to assess clock-time patterning of work-related injuries (WRIs) of firemen (FM) of Sa?ne et Loire-71 (France) during the 4-yr span of 1 January 2004 to 31 December 2007. FM of this service are legally required to log every WRI and seek its evaluation by the medical service, whether the WRI was the result of worksite duties or exercise/sport activities at the station. WRI was defined specifically as a (nonexercise, nonsport, and nonemotional/stress) work-associated trauma, verified both by log book and medical records. For the corresponding years, the 24-h pattern of emergency calls (Calls) plus road traffic (Traffic) on the main roads of the service area was also assessed. Relative risk (R) of WRI was calculated as the quantity of WRIs/h divided by the quantity of Call responses/h?×?1000, which takes into account the number of at-risk FM/unit time, since each dispatched emergency vehicle is staffed with 4 FM. Comparably trained regular (RFM) and volunteer (VFM) FM experienced a total of 187 WRIs. The 24-h WRI curve patterns of RFM and VFM were correlated (r?=?0.4, p??.05). Analysis of variance (ANOVA) validated comparable clock-time patterns in WRIs of RFM and VFM each year and each season (all p??.0006; Cosinor analysis, p?相似文献   

24-hour Pattern in Lag Time of Response by Firemen to Calls for Urgent Medical Aid

The aim of the study was to assess the group 24-h pattern of lag time (LT) in response by regular and volunteer firemen (RFM and VFM) to calls for medical help (CFMH), specifically calls for out-of-hospital cardiac arrest (OHCA). LT, duration in min between a CFMH and departure of service vehicle equipped with a semiautomated defibrillator and generally staffed with four well-trained and ready-to-go FM, represents the integrated duration of several processes, each with separate reaction and decision-making times. The exact time of each CFHM (in min, h, day, month, yr) was recorded electronically, and the exact departure time from the station of the responding FM vehicle was recorded by an on-duty FM. Overall, CFMH made up 53?±?9% (SEM) of all emergencies calls for aid. To standardize the study methods, the reported findings are based on 568 CFMH specifically regarding OHCA that occurred during the 4-yr study span (January 2005 to December 2008). CFMH exhibited a 24-h pattern with a major peak at 10:00?h (mean?±?SEM: n?=?9.5?±?1.6) and major trough at 01:00?h (n?=?1.3?±?0.3; t test, p?<?.001). From year to year and season to season, a 24-h pattern was detected in the total of CFMH/h with two peaks (～10:00 and ～17:00h) and two troughs (～01:00 and ～15:00?h) (analysis of variance [ANOVA], p?<?.01; Cosinor, p?<?.05 to?<?.003), with neither season- nor year-related differences (χ², p?>?.05). In CFMH/h pooled time series, ANOVA-detected differences between the hourly means (p?<?.01), and Cosinor analysis validated a 24-h rhythm (p?<?.002). In raw data, the longest LT, indicative of poorest performance, occurred at 05:00?h (8.8?±?0.7?min) and the trough of LT, indicative of best performance, at 16:00?h (4.3?±?0.8?min (t test, p?<?.02). 24-h patterning in LT was validated both by ANOVA of hourly means (p?<?.0006) and Cosinor analysis (p?<?.05), with longest LT ～05:00?h and shortest LT ～16.00?h for data of the individual yearly time-series data. The 24-h LT rhythm was also validated in the pooled time series by Cosinor (p?<?.0001), with the 24-h mean?±?SEM?=?6?±?0.17?min and acrophase (peak) of 03:00?h?±?88?min (SD). Curve patterns of CFMH/h and LT/h differed widely. As a group phenomenon, the LT 24-h rhythm mimics the 24-h pattern of performance, as demonstrated by many laboratory and field investigations. The stability of the LT rhythm between years and seasons and its weak relationship with the CFMH 24-h pattern favors the hypothesis of an endogenous component or origin. The nighttime trough of performance is presumably linked to the elevated risk of work accidents in the same population of FM.     

24-hour pattern in lag time of response by firemen to calls for urgent medical aid

The aim of the study was to assess the group 24-h pattern of lag time (LT) in response by regular and volunteer firemen (RFM and VFM) to calls for medical help (CFMH), specifically calls for out-of-hospital cardiac arrest (OHCA). LT, duration in min between a CFMH and departure of service vehicle equipped with a semiautomated defibrillator and generally staffed with four well-trained and ready-to-go FM, represents the integrated duration of several processes, each with separate reaction and decision-making times. The exact time of each CFHM (in min, h, day, month, yr) was recorded electronically, and the exact departure time from the station of the responding FM vehicle was recorded by an on-duty FM. Overall, CFMH made up 53 ± 9% (SEM) of all emergencies calls for aid. To standardize the study methods, the reported findings are based on 568 CFMH specifically regarding OHCA that occurred during the 4-yr study span (January 2005 to December 2008). CFMH exhibited a 24-h pattern with a major peak at 10:00 h (mean ± SEM: n = 9.5 ± 1.6) and major trough at 01:00 h (n = 1.3 ± 0.3; t test, p??.05). In CFMH/h pooled time series, ANOVA-detected differences between the hourly means (p?相似文献   

Light Exposure Among Adolescents With Delayed Sleep Phase Disorder: A Prospective Cohort Study

The objective of this study was to compare light exposure and sleep parameters between adolescents with delayed sleep phase disorder (DSPD; n?=?16, 15.3?±?1.8 yrs) and unaffected controls (n?=?22, 13.7?±?2.4 yrs) using a prospective cohort design. Participants wore wrist actigraphs with photosensors for 14 days. Mean hourly lux levels from 20:00 to 05:00?h and 05:00 to 14:00?h were examined, in addition to the 9-h intervals prior to sleep onset and after sleep offset. Sleep parameters were compared separately, and were also included as covariates within models that analyzed associations with specified light intervals. Additional covariates included group and school night status. Adolescent delayed sleep phase subjects received more evening (p?<?.02, 22:00–02:00?h) and less morning (p?<?.05, 08:00–09:00?h and 10:00–12:00?h) light than controls, but had less pre-sleep exposure with adjustments for the time of sleep onset (p?<?.03, 5–7?h prior to onset hour). No differences were identified with respect to the sleep offset interval. Increased total sleep time and later sleep offset times were associated with decreased evening (p?<?.001 and p?=?.02, respectively) and morning (p?=?.01 and p?<?.001, respectively) light exposure, and later sleep onset times were associated with increased evening exposure (p?<?.001). Increased total sleep time also correlated with increased exposure during the 9?h before sleep onset (p?=?.01), and a later sleep onset time corresponded with decreased light exposure during the same interval (p?<?.001). Outcomes persisted regardless of school night status. In conclusion, light exposure interpretation requires adjustments for sleep timing among adolescents with DSPD. Pre- and post-sleep light exposures do not appear to contribute directly to phase delays. Sensitivity to morning light may be reduced among adolescents with DSPD. (Author correspondence: auger.raymond1@mayo.edu)     

Adipokine Levels Are Altered by Shiftwork: A Preliminary Study

Shiftwork is often associated with metabolic diseases, and in the past few years, several cytokines have been postulated to contribute to various diseases, including insulin resistance. The aim of this study was to compare the concentrations of adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in samples of young adult men exposed to a fixed (i) night shift (n?=?9), working from 22:00 to 06:00?h; (ii) early morning shift (n?=?6), working from 06:00 to 14:00?h; and (iii) day shift (n?=?7), working from 08:00 to 17:00?h. The fixed night-shift and early-morning-shift samples were considered collectively as a shiftworker group given their work times. Blood samples were collected during the regular working day at 4-h intervals over the course of 24?h, thus totaling six samples. Morphological and physical activity parameters did not differ between the three groups. Total energy intake was lowest on the early morning shifts (p?<?.03). Both shiftworker groups ingested a significantly higher percentage of fat (p?<?.003) and a lower percentage of carbohydrate (p?<?.0005) than the day group. The early morning group had a lower mean 24-h level of adiponectin than the other two groups (p?=?.016), and both the early morning and night groups exhibited higher mean 24-h levels of TNF-α than the day group (p?=?.0001). The 24-h mean levels of IL-6 did not differ significantly between the groups (p?=?.147). None of the groups exhibited a significant circadian effect on adiponectin (p?=?.829), TNF-α (p?=?.779), or IL-6 (p?=?.979) levels. These results indicate that individuals who are enrolled in shiftwork are susceptible to alterations in the secretion of cytokines that are involved in insulin resistance and cardiovascular disease, both of which are known to affect this population. (Author correspondence: tmello@demello.net.br)     

Acute and delayed responses of C-reactive protein,malondialdehyde and antioxidant markers after resistance training session in elite weightlifters: Effect of time of day

The aim of this study was to investigate the effect of an Olympic-Weightlifting-session followed by 48-h recovery period on the oxidative and antioxidant parameters’ diurnal variation. Nine weightlifters (21?±?0.5 years) performed, in randomized order, three Olympic-Weightlifting-sessions at 08?h:00, 14?h:00 and 18?h:00. Blood samples were collected: at rest and 3?min and 48?h after each session. C-reactive protein (CRP), rate of lipid peroxidation and antioxidant activities were assessed. At rest, analysis of variance showed a significant time of day (TOD) effect (p?<?0.05) for uric acid, catalase and glutathione peroxidase with higher values at 14?h:00 and 18?h:00 compared with 08?h:00. However, no significant TOD effect for malondialdehyde, total bilirubin and CRP was observed. Given the profound changes (p?<?0.001) in the post-training session values, these diurnal variations have been altered immediately and even 48?h after the training sessions. Despite the significant decreases in the post-training values after the 48-h recovery period (p?<?0.05), levels of lipid peroxidation and enzymatic defense remained elevated (p?<?0.05) 48?h after the morning training session. However, after the afternoon and evening sessions, the same period was sufficient to return values to the baseline levels. In conclusion, the morning session seems to generate the most important acute and delayed lipid peroxidation responses. Therefore, weightlifting coaches should avoid scheduling their training sessions in the morning-hours.     

Diurnal Variations of Plasma Homocysteine,Total Antioxidant Status,and Biological Markers of Muscle Injury During Repeated Sprint: Effect on Performance and Muscle Fatigue—A Pilot Study

The aim of this study was (i) to evaluate whether homocysteine (Hcy), total antioxidant status (TAS), and biological markers of muscle injury would be affected by time of day (TOD) in football players and (ii) to establish a relationship between diurnal variation of these biomarkers and the daytime rhythm of power and muscle fatigue during repeated sprint ability (RSA) exercise. In counterbalanced order, 12 football (soccer) players performed an RSA test (5?×?[6 s of maximal cycling sprint?+?24 s of rest]) on two different occasions: 07:00–08:30?h and 17:00–18:30?h. Fasting blood samples were collected from a forearm vein before and 3–5?min after each RSA test. Core temperature, rating of perceived exertion, and performances (i.e., Sprint 1, Sprint 2, and power decrease) during the RSA test were significantly higher at 17:00 than 07:00?h (p?<?.001, p?<?.05, and p?<?.05, respectively). The results also showed significant diurnal variation of resting Hcy levels and all biological markers of muscle injury with acrophases (peak times) observed at 17:00?h. These fluctuations persisted after the RSA test. However, biomarkers of antioxidant status' resting levels (i.e., total antioxidant status, uric acid, and total bilirubin) were higher in the morning. This TOD effect was suppressed after exercise for TAS and uric acid. In conclusion, the present study confirms diurnal variation of Hcy, selected biological markers of cellular damage, and antioxidant status in young football players. Also, the higher performances and muscle fatigue showed in the evening during RSA exercise might be due to higher levels of biological markers of muscle injury and lower antioxidant status at this TOD. (Author correspondence: n_souissi@yahoo.fr)     

Ring the Bell for Matins: Circadian Adaptation to Split Sleep by Cloistered Monks and Nuns

Cloistered monks and nuns adhere to a 10-century-old strict schedule with a common zeitgeber of a night split by a 2- to 3-h-long Office (Matins). The authors evaluated how the circadian core body temperature rhythm and sleep adapt in cloistered monks and nuns in two monasteries. Five monks and five nuns following the split-sleep night schedule for 5 to 46 yrs without interruption and 10 controls underwent interviews, sleep scales, and physical examination and produced a week-long sleep diary and actigraphy, plus 48-h recordings of core body temperature. The circadian rhythm of temperature was described by partial Fourier time-series analysis (with 12- and 24-h harmonics). The temperature peak and trough values and clock times did not differ between groups. However, the temperature rhythm was biphasic in monks and nuns, with an early decrease at 19:39?±?4:30?h (median?±?95% interval), plateau or rise of temperature at 22:35?±?00:23?h (while asleep) lasting 296?±?39?min, followed by a second decrease after the Matins Office, and a classical morning rise. Although they required alarm clocks to wake-up for Matins at midnight, the body temperature rise anticipated the nocturnal awakening by 85?±?15?min. Compared to the controls, the monks and nuns had an earlier sleep onset (20:05?±?00:59?h vs. 00:00?±?00:54?h, median?±?95% confidence interval, p?=?.0001) and offset (06:27?±?0:22?h, vs. 07:37?±?0:33?h, p?=?.0001), as well as a shorter sleep time (6.5?±?0.6 vs. 7.6?±?0.7?h, p?=?.05). They reported difficulties with sleep latency, sleep duration, and daytime function, and more frequent hypnagogic hallucinations. In contrast to their daytime silence, they experienced conversations (and occasionally prayers) in dreams. The biphasic temperature profile in monks and nuns suggests the human clock adapts to and even anticipates nocturnal awakenings. It resembles the biphasic sleep and rhythm of healthy volunteers transferred to a short (10-h) photoperiod and provides a living glance into the sleep pattern of medieval time. (Author correspondence: isabelle.arnulf@psl.aphp.fr)     

Circadian Phase,Sleepiness, and Light Exposure Assessment in Night Workers With and Without Shift Work Disorder

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean?±?SD] age: 39.2?±?12.5 yrs; mean yrs on shift?=?9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6?±?8.6 yrs; mean years on shift?=?8.4) participated. All participants were admitted to the sleep center at 16:00?h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00?h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42?±?3.25?h, whereas in the SWD group it was 20:42?±?2.21?h (z = 2.4; p?<?.05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00–09:00?h) was significantly shorter (3.6?±?.90?min: [M?±?SEM]) in the SWD group compared with that in ANW group (6.8?±?.93?min). DLMO was significantly correlated with insomnia severity (r = ?.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00?h) as than ANW ones (798 vs. 180 lux [M?±?SD], respectively z?=??1.7; p?<?.05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule. (Author correspondence: vgumeny1@hfhs.org)     

Stability and Fragmentation of the Activity Rhythm Across the Sleep-Wake Cycle: The Importance of Age,Lifestyle, and Mental Health

The rhythms of activity across the 24-h sleep-wake cycle, determined in part by the circadian clock, change with aging. Few large-scale studies measured the activity rhythm objectively in the general population. The present population-based study in middle-aged and elderly persons evaluated how activity rhythms change with age, and additionally investigated sociodemographics, mental health, lifestyle, and sleep characteristics as determinants of rhythms of activity. Activity rhythms were measured objectively with actigraphy. Recordings of at least 96?h (138?±?14?h, mean?±?SD) were collected from 1734 people (age: 62?±?9.4?yrs) participating in the Rotterdam Study. Activity rhythms were quantified by calculating interdaily stability, i.e., the stability of the rhythm over days, and intradaily variability, i.e., the fragmentation of the rhythm relative to its 24-h amplitude. We assessed age, gender, presence of a partner, employment, cognitive functioning, depressive symptoms, body mass index (BMI), coffee use, alcohol use, and smoking as determinants. The results indicate that older age is associated with a more stable 24-h activity profile (β?=?0.07, p?=?0.02), but also with a more fragmented distribution of periods of activity and inactivity (β?=?0.20, p?<?0.001). Having more depressive symptoms was related to less stable (β?=??0.07, p?=?0.005) and more fragmented (β?=?0.10, p?<?0.001) rhythms. A high BMI and smoking were also associated with less stable rhythms (BMI: β?=??0.11, p?<?0.001; smoking: β?=??0.11, p?<?0.001) and more fragmented rhythms (BMI: β?=?0.09, p?<?0.001; smoking: β?=?0.11, p?<?0.001). We conclude that with older age the 24-h activity rhythm becomes more rigid, whereas the ability to maintain either an active or inactive state for a longer period of time is compromised. Both characteristics appear to be important for major health issues in old age.     

Timing Light Treatment for Eastward and Westward Travel Preparation

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9±8.2 yrs (mean±SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6±6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0±7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p?<?.028) and B (p?<?0.004). Experiment 2 showed significant phase advances in conditions A (p?<?0.018) and B (p?<?0.003) but not C (p?<?0.23), relative to condition D. In Experiment 3, only condition B (p?<?0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R²?=?0.94) provided a partial phase-response curve with maximum advance at approximately 9–11 h and maximum delay at approximately 5–6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).     

Influence of acoustic stimulation on the circadian and ultradian rhythm of premature infants

The aim of the present study was to evaluate the development of the circadian rhythm of the salivary cortisol in premature infants and its correlation with the onset of the sleep–activity behavior pattern during the first 3 weeks of life under controlled light:dark conditions. Furthermore, we investigated the influence of acoustic stimulation by audiotaped lullabies or the maternal voice on the cortisol values and long-term sleep–activity patterns. The study was a block-randomized, prospective clinical trial with a study population of 62 preterm neonates (30?<?37 gestational age). We compared two study groups who listened either to music or to the maternal voice (music: N?=?20; maternal voice: N?=?20) with a matched control group (N?=?22). The acoustic stimulation took place every evening between 20:00 and 21:00?h for 30?min over a period of 2 weeks. The cortisol values and activity–rest behavior of the neonates were determined during the first 3 weeks of life on the 1st, 7th and 14th day. Actigraphic monitoring was used to record the activity pattern continuously over 24?h and a validated algorithm for neonates was used to estimate sleep and wakefulness. The saliva samples were obtained 10?min before and 10?min after the acoustic interventions for the study groups. Additionally, saliva samples were obtained from the control group seven times over a 24-h period (20:00, 21:00, 01:00, 05:00, 08:00, 13:00 and 17:00?h). The cortisol data were analyzed by fast Fourier transformation to assess periodic characteristics and frequencies. Hierarchical linear modeling was further performed for the statistical analysis. Results: The cortisol rhythm analysis indicated a circadian rhythm pattern for only one premature infant, all others of the neonates showed no circadian or ultradian rhythm in cortisol. Cortisol level of the premature neonates was significantly higher during the first day of the study period at night-time (median: 17.1?nmol/L, IQR?=?9.7–24.4?nmol/L) than on days 7 (median: 9.6?nmol/L, IQR?=?4.7–14.6?nmol/L; Tukey-HSD, z?=?4.12, p?<?0.001) and 14 (IQR?=?5.8–13.7?nmol/L; Tukey-HSD, z?=?2.89, p?<?0.05). No significant effect of acoustic stimulation was observed on the cortisol concentration and sleep–wake behavior. The activity–sleep rhythm of preterm neonates was dominated by ultradian rhythm patterns with a prominent period length of 4?h (30.5%). Activity frequencies of neonates were also significantly higher overnight on the first study day (mean: 329?±?185.1?U) than of night seven (mean: 260.2?±?132.4?U; Tukey-HSD, z?=?2.50, p?<?0.05). Quiet-activity patterns increased, whereas high-activity patterns decreased during the observation period. Average sleep time increased significantly during the study time from day 1 to day 7 (Tukey-HSD, z?=?2.51, p?<?0.05). In conclusion, premature infants showed higher cortisol levels – without a circadian rhythmicity – and higher activity frequencies in the first days after birth which may reflect an adaptation process of neonates after birth. Cortisol concentrations and the activity patterns were not influenced by music interventions.     

Clock Genes Display Rhythmic Expression in Human Hearts

Thus far, clock genes in the heart have been described only in rodents, and alterations of these genes have been associated with various myocardial malfunctions. In this study, we analyzed the expression of clock genes in human hearts. Left papillary muscles of 16 patients with coronary heart disease, 39 subjects with cardiomyopathy, and 9 healthy donors (52 males and 12 females, mean age 55.7±11.2; 16–70 yrs) were obtained during orthotopic heart transplantation. We assessed the mRNA levels of PER1, PER2, BMAL1, and CRY1 by real time PCR and analyzed their rhythmic expression by sliding means and Cosinor functions. Furthermore, we sought for differences between the three groups (by ANOVAs) for both the total 24 h period and separate time bins. All four clock genes were expressed in human hearts. The acrophases (circadian rhythm peak time) of the PER mRNAs occurred in the morning (PER1: 07:44 h [peak level 187% higher than trough, p?=?.008]; PER2: 09:42 h [peak 254% higher than trough, p?<?.0001], and BMAL1 mRNA in the evening at 21:44 h [peak 438% higher than trough; p?<?.0001]. No differences were found in the rhythmic patterns between the three groups. No circadian rhythm was detected in CRY1 mRNA in any group. PER1, PER2, and BMAL1 mRNAs revealed clear circadian rhythms in the human heart, with their staging being in antiphase to those in rodents. The circadian amplitudes of the mRNA clock gene levels in heart tissue are more distinct than in any other human tissue so far investigated. The acrophase of the myocardial PER mRNAs and the trough of the myocardial BMAL1 coincide to the time of day of most frequent myocardial incidents.     

Influence of feeding schedules on the chronobiology of renin activity,urinary electrolytes and blood pressure in dogs

The contribution of the renin–angiotensin–aldosterone system (RAAS) to the development of congestive heart failure (CHF) and hypertension (HT) has long been recognized. Medications that are commonly used in the course of CHF and HT are most often given with morning food for the sake of convenience and therapeutic compliance. However, biological rhythms and their responsiveness to environmental clues such as food intake may noticeably impact the effectiveness of drugs used in the management of cardiovascular disorders. Only sparse information about the effect of feeding schedules on the biology of the RAAS and blood pressure (BP) is presently available. Two studies were designed to explore the chronobiology of renin activity (RA), BP, renal sodium (U_Na,fe) and potassium (U_K,fe) handling in relation to meal timing in dogs. In a first experiment (Study a), blood and urinary samples for measurement of RA, U_Na,fe and U_K,fe were drawn from 18 healthy beagle dogs fed a normal-sodium diet at either 07:00, 13:00 or 19:00?h. In a second experiment (Study b), BP was recorded continuously from six healthy, telemetered beagle dogs fed a similar diet at 07:00, or 19:00?h. Data were collected throughout 24-h time periods, and analyzed by means of nonlinear mixed-effects models. Differences between the geometric means of early versus late time after feeding observations were further compared using parametric statistics. In agreement with our previous investigations, the results indicate that RA, U_Na,fe, U_K,fe, systolic, and diastolic BP oscillate with a circadian periodicity in dogs fed a regular diet at 07:00?h. A cosine model with a fixed 24-h period was found to fit the variations of RA, U_K,fe and BP well, whereas cyclic changes in U_Na,fe were best characterized by means of a combined cosine and surge model, reflecting a postprandial sodium excretion followed by a monotonous decay. Our data show that feeding time has a marked influence on the chronobiology of the renin cascade, urinary electrolytes, and BP. Introducing a 6- or 12-h delay in the dogs’ feeding schedule caused a shift of similar magnitude (05:06 and 12:32?h for Studies a and b, respectively) in the rhythm of these biomarkers. In all study groups, RA and BP exhibited a marked fall just after food intake. The drop in RA is consistent with sodium and water-induced body fluid expansion, while the reduction of BP could be related to the decreased activity of renin and the secretion of vasodilatory gut peptides. An approximately 1.5-fold (1.2–1.6-fold) change between the average early and late time after feeding observations was found for RA (p?<?0.0001), U_Na,fe (p?<?0.01) and U_K,fe (p?<?0.05). Postprandial variations in BP, albeit small (ca. 10?mmHg), were statistically significant (p?<?0.01) and supported by the model-based analysis.

In conclusion, the timing of food intake appears to be pivotal to the circadian organization of the renin cascade and BP. This synchronizing effect could be mediated by feeding-related signals, such as dietary sodium, capable of entraining circadian oscillators downstream of the master, light–dark-adjusted pacemaker in the suprachiasmatic nucleus.     

INCREASED SENSITIVITY TO LIGHT-INDUCED MELATONIN SUPPRESSION IN PREMENSTRUAL DYSPHORIC DISORDER

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00?h where nurses inserted an intravenous catheter at 17:00?h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00?h, including between 00:00 and 01:00?h for baseline values, between 01:30 and 03:00?h during the 200 lux light exposure administered from 01:00 to 03:00?h, and at 03:30 and 04:00?h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (?0.2%) women (p?=?.040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (?0.15%) phase (p?=?.047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p ?=? .007) in PMDD patients, but not in NC subjects (p?>?.05). (Author correspondence: bparry@ucsd.edu)     

CHRONIC SLEEP DEFICIT AND PERFORMANCE OF A SUSTAINED ATTENTION TASK—AN ELECTROOCULOGRAPHY STUDY

Electrooculography (EOG) was used to explore performance differences in a sustained attention task during rested wakefulness (RW) and after 7 days of partial sleep deprivation (SD). The RW condition was based on obtaining regular sleep, and the SD condition involved sleep restriction of 3?h/night for a week resulting in a total sleep debt of 21?h. The study used a counterbalanced design with a 2-wk gap between the conditions. Participants performed a sustained attention task for 45?min on four occasions: 10:00–11:00, 14:00–15:00, 18:00–19:00, and 22:00–23:00?h. The task required moving gaze and attention as fast as possible from a fixation point to a target. In each session, 120 congruent and 34 incongruent stimuli were presented, totaling 1232 observations/participant. Correct responses plus errors of omission (lapses) and commission (false responses) were recorded, and the effect of time-of-day on sustained attention following SD was investigated. The analysis of variance (ANOVA) model showed that SD affected performance on a sustained attention task and manifested itself in a higher number of omission errors: congruent stimuli (F_(1,64)?=?13.3, p?<?.001) and incongruent stimuli (F_(1,64)?=?14.0, p?<?.001). Reaction times for saccadic eye movements did not differ significantly between experimental conditions or by time-of-day. Commission errors, however, exhibited a decreasing trend during the day. The visible prevalence of omissions in SD versus RW was observed during the mid-afternoon hours (the so-called post-lunch dip) for both congruent and incongruent stimuli (F_(1,16)?=?5.3, p?=?.04 and F_(1,16)?=?5.6, p?=?.03, respectively), and at 18:00?h for incongruent stimuli (F_(1,13)?=?5.7, p?=?.03). (Author correspondence: magda.fafrowicz@uj.edu.pl)     

Circadian Variation in Patient Characteristics and Outcomes in ST-Segment Elevation Myocardial Infarction

A morning peak in ST-segment elevation myocardial infarction (STEMI) has been described. The authors explored the relationship between variation of symptom onset, patient characteristics, and outcomes in two worldwide fibrinolytic trials. A total of 35 492 patients with STEMI were grouped into 8-h intervals by time of symptom onset: early (06:00 to 13:59?h), late-day (14:00 to 21:59?h), overnight (22:00 to 05:59?h). The authors correlated timing with patient characteristics and outcomes (adjusted for thrombolysis in myocardial infarction [TIMI] risk score) first in InTIME II-TIMI 17 trial (N?=?15 031), and confirmed in the ExTRACT-TIMI 25 trial (N?=?20 461). Timing was similar in the derivation (early 49%, late-day 30%, and overnight 21%; p?<?.001) and validation set (48%, 31%, and 21%, respectively; p?<?.001). Some patient characteristics consistently varied with time of symptom onset. Patients in the early cohort were older with poorer renal function. The late-day group had more smokers with higher initial heart rate and systolic blood pressure. Those with overnight symptom onset had higher rates of obesity, prior myocardial infarction, and treatment delays. Prior use of aspirin and beta-blockers was also highest in the overnight group. Relative to the early cohort, adjusted mortality was higher with late-day onset (derivation odds ratio [OR]: 1.19, p?=?.04; validation OR: 1.18, p?=?.01), but there was no excess in mortality overnight compared with early (derivation OR: .97, p?=?.72; validation OR: 1.01, p?=?.90). Composite endpoints followed similar patterns. This study indicates that circadian patterns in onset of STEMI continue to exist with patient characteristics differing by time of day. Despite a potential physiologic resistance to morning thrombolysis, outcomes were best in the early cohort, intermediate overnight, and worst with late-day symptom onset. Efforts to reduce smoking and improve control of blood pressure could reduce the number of patients with late-day onset of STEMI who experience the worst outcomes. (Author correspondence: owen@mogabgab.com)     

HYPOCRETIN DEFICIENCY IN NARCOLEPSY WITH CATAPLEXY IS ASSOCIATED WITH A NORMAL BODY CORE TEMPERATURE MODULATION

Narcolepsy with cataplexy (NC) is a sleep disorder caused by the loss of the hypothalamic neurons producing hypocretin. The clinical hallmarks of the disease are excessive daytime sleepiness, cataplexy, other rapid eye movement (REM) sleep phenomena, and a fragmented wake-sleep cycle. Experimental data suggest that the hypocretin system is involved primarily in the circadian timing of sleep and wakefulness but also in the control of other biological functions such as thermoregulation. The object of this study was to determine the effects of the hypocretin deficit and of the wake-sleep cycle fragmentation on body core temperature (BcT) modulation in a sample of drug-free NC patients under controlled conditions. Ten adult NC patients with low cerebrospinal fluid (CSF) hypocretin levels (9 men; age: 38?±?12 yrs) were compared with 10 healthy control subjects (7 men; age: 44.9?±?12 yrs). BcT and sleep-wake cycle were continuously monitored for 44?h from 12:00?h. During the study, subjects were allowed to sleep ad libitum, living in a temperature- and humidity-controlled room, lying in bed except when eating, in a light-dark schedule (dark [D] period: 23:00–07:00?h). Sleep structure was analyzed over the 24-h period, the light (L) and the D periods. The wake-sleep cycle fragmentation was determined by calculating the frame-shift index (number of 30-s sleep stage shifts occurring every 15?min) throughout the 44-h study. The analysis of BcT circadian rhythmicity was performed according to the single cosinor method. The time-course changes in BcT and in frame-shift index were compared between narcoleptics and controls by testing the time?×?group (controls versus NC subjects) interaction effect. The state-dependent analysis of BcT during D was performed by fitting a mixed model where the factors were wake-sleep phases (wake, NREM stages 1 and 2, slow-wave sleep, and REM sleep) and group. The results showed that NC patients slept significantly more than controls during the 24?h due to a higher representation of any sleep stage (p?<?.001) during L, whereas the total amount of night sleep and its architecture were comparable in the two groups. Wake-sleep fragmentation was higher (p?<?.001) in NC subjects especially during L. Despite these differences, mesor (24-h mean), amplitude, and acrophase (peak time) of BcT circadian rhythm were comparable in narcoleptics and controls, and no between-group differences were detected in the time-course changes and in the state-dependent modulation at night of BcT. These data indicate that the hypocretin deficit in drug-free NC patients and their altered wake-sleep cycle couple with an intact modulation of BcT. (Author correspondence: daniela.grimaldi@unibo.it)     

Comparison of Ambulatory Blood Pressure Parameters of Hypertensive Patients With and Without Chronic Kidney Disease

There is strong association between chronic kidney disease (CKD) and increased prevalence of hypertension, risk of end-organ damage, and cardiovascular disease (CVD). Non-dipping, as determined by ambulatory blood pressure (BP) monitoring (ABPM), is frequent in CKD and has also been consistently associated with increased CVD risk. The reported prevalence of non-dipping in CKD is highly variable, probably due to relatively small sample sizes, reliance only on a single, low-reproducibility, 24-h ABPM evaluation per participant, and definition of daytime and nighttime periods by arbitrary fixed clock-hour spans. Accordingly, we assessed the circadian BP pattern of patients with and without CKD by 48-h ABPM to increase reproducibility of the results. This cross-sectional study involved 10 271 hypertensive patients (5506 men/4765 women), 58.0?±?14.2 (mean?±?SD) yrs of age, enrolled in the Hygia Project. Among the participants, 3227 (1925 men/1302 women) had CKD. At the time of recruitment, 568/2234 patients with/without CKD were untreated for hypertension. Patients with than without CKD were more likely to be men and of older age, have diagnoses of obstructive sleep apnea, metabolic syndrome, diabetes, and/or obesity, plus have higher glucose, creatinine, uric acid, and triglyceride, but lower cholesterol, concentrations. In patients with CKD, ambulatory systolic BP (SBP) was significantly elevated (p?<?.001), mainly during the hours of nighttime sleep, independent of presence/absence of BP-lowering treatment. In patients without CKD, ambulatory diastolic BP (DBP), however, was significantly higher (p?<?.001), mainly during the daytime. Differing trends for SBP and DBP between groups resulted in large differences in ambulatory pulse pressure (PP), it being significantly greater (p?<?.001) for the entire 24?h in patients with CKD. Prevalence of non-dipping was significantly higher in patients with than without CKD (60.6% vs. 43.2%; p?<?.001). The largest difference between groups was in the prevalence of the riser BP pattern, i.e., asleep SBP mean?>?awake SBP mean (17.6% vs. 7.1% in patients with and without CKD, respectively; p?<?.001). The riser BP pattern significantly and progressively increased from 8.1% among those with stage 1 CKD to a very high 34.9% of those with stage 5 CKD. Elevated asleep SBP mean was the major basis for the diagnosis of hypertension and/or inadequate BP control among patients with CKD; thus, among the uncontrolled hypertensive patients with CKD, 90.7% had nocturnal hypertension. Our findings document significantly elevated prevalence of a blunted nocturnal BP decline in hypertensive patients with CKD. Most important, prevalence of the riser BP pattern, associated with highest CVD risk among all possible BP patterns, was 2.5-fold more prevalent in CKD, and up to 5-fold more prevalent in end-stage renal disease. Patients with CKD also presented significantly elevated ambulatory PP, reflecting increased arterial stiffness and enhanced CVD risk. Collectively, these findings indicate that CKD should be included among the clinical conditions for which ABPM is mandatory for proper diagnosis and CVD risk assessment, as well as a means to establish the best therapeutic scheme to increase CVD event-free survival. (Author correspondence: rhermida@uvigo.es)