Effects of 12‐Hour Rotating Shifts on Menstrual Cycles of Photoelectronic Workers in Taiwan

12 h rotating shifts are common in high‐tech industries in Taiwan. The aim of this longitudinal study was to evaluate the effect of the disruption of circadian rhythms by the shift schedule on menstrual cycle length (MCL) and regularity of female workers at an optoelectronic company in Taiwan. We recruited females who worked rotating shifts in a clean room environment as the shift‐work group and female office workers who worked normal business hours as the comparison group. Every participant recorded their MCL for each menstruation cycle up to eight consecutive months prospectively and provided demographic characteristics, reproductive history, and menstrual characteristics. We collected data on 1,135 and 117 menstruation cycles in the shift‐work (n=280) and comparison groups (n=49). Whereas the two groups had similar group means for MCL and number of menstrual bleeding days, the prevalence of menstrual cycle irregularity (cycles<25 or>35 days) was higher in the shift‐work group (p=0.04). Univariate and multivariate logistic regression analyses demonstrated that rotating shift work was an independent predictor of menstrual cycle irregularity (odds ratio=1.71, 95% confidence interval: 1.03–2.88) after adjusting for shift‐work history, employment duration, coffee consumption, and pre‐employment menstrual cycle irregularity. Although further study is required to confirm our findings plus to explore prevention and control measures, our data indicate rotating shift work can increase the risk of MCL irregularity.     

Regularity of Daily Activities in Stroke

Various studies have been performed using the Social Rhythm Metric (SRM), though none has been developed with stroke patients. Stroke is a pathology that provokes a strong physical and social impact caused by an abnormality in cerebral circulation. Consequently, we performed two studies to validate the SRM and translate it into Portuguese, and to evaluate the regularity of the daily activities of stroke patients. Both healthy individuals and patients with unilateral cerebral lesions were evaluated. Subjects were of both sexes and between 45 and 65 yrs of age. Participants underwent clinical evaluation and recorded the time of 17 daily activities on the SRM for two weeks. Data were analyzed by the Pearson correlation and Fisher tests. After conceptual translation into Portuguese, corrections were made to arrive at the final version. Normative SRM scores varied from 3.2 to 7.0, suggesting that the activities presented in SRM adequately represented the daily routines of the patients. A correlation was found in SRM between the weeks (r=0.84; p=0.0001), indicating instrument reliability. The mean (±SD) score of the stoke patients was 4.8 (±1.0), and the correlation between the SRM and level of neurological damage showed that patients with lower SRM values were more physically compromised (r=?0.29; p=0.04), suggesting that SRM may be a clinical predictor. Activities related to eating and the sleep‐wake cycle were rated by most patients. In all, 71% of the patients did not work, while 84% of healthy individuals did (p=0.001). Only 64% of patients left home compared to 90% of the healthy subjects (p=0.001), and 59% of patients recorded the activity of going home compared to 82% of healthy individuals (p=0.001). According to the results, there is evidence of the validity and reliability of the SRM, enabling it to be reliably used in chronobiological studies of stroke patients. Given that a less regular lifestyle may be associated with neurological compromise and a decrease in social activities, we suggest new studies with the repeated application of this instrument over the clinical evolution of the disease to better define improvement or worsening of the patient's condition in terms of their social and health aspects.     

Survival of Rats Undergoing Continuous Bile Drainage Depends on Maintenance of Circadian Rhythm of Bile Secretion

It is very difficult to collect bile secretions from animals for extended periods of time. We compared the use of saline or water as drinking fluids to sustain the animals, which were being continuously drained of bile. Complete bile drainage was performed in 16 male Wistar rats by surgical intervention. After surgery, 8 rats were given tap water, and the other 8 were given normal saline for water. The rats that received water rapidly lost weight after bile drainage, and all died within 8 days after the operation. In contrast, all rats that drank saline maintained their body weight and survived 14 days or longer after surgery. Serum biochemistry of the rats with water intake on the third day after bile drainage revealed hyponatremia, hypochloremia, and acute renal failure resulting in hyperkalemia. In contrast, electrolyte balance and renal function were normal in the rats with saline intake, and bile was secreted continuously with a circadian rhythm. These results clearly demonstrate that saline as drinking water is essential to the replacement of lost fluids and loss of electrolytes due to bile drainage. Further, saline proved efficacious for sustaining experimental animals undergoing continuous bile collection.     

Circadian Variations in Exsorptive Transport: In Situ Intestinal Perfusion Data and In Vivo Relevance

The circadian timing system (CTS) governs the 24-h rhythm of the organism and, hence, also main pathways responsible for drug pharmacokinetics. P-glycoprotein (P-gp) is a drug transporter that plays a pivotal role in drug absorption, distribution, and elimination, and temporal changes in its activity may affect input, output, activity, and toxicity profile of drugs. In the current study, the influence of different circadian stages on the overall intestinal permeability (P_eff) of the P-gp substrates talinolol and losartan was evaluated in in situ intestinal perfusion studies in rats. Additionally, in vivo studies in rats were performed by employing the P-gp probe talinolol during the day (nonactive) and night (active) period in rats. Effective intestinal permeabilities of talinolol and losartan were smaller in studies performed during the night (p?<?.05), indicating that P-gp–dependent intestinal secretion is greater during the nighttime activity span than daytime rest span of the animals. P-gp modulators vinblastine and PSC833 led to a significant decrease of talinolol and losartan exsorption in the intestinal segments as compared with control groups. Strikingly, the permeability-enhancing effect of vinblastine and PSC833 was higher with night perfusions, for both talinolol and losartan. In vivo studies performed with talinolol revealed—consistent with the in situ studies (P_eff day?>?night)—a day vs. night difference in the oral availability of talinolol in the group of male rats in terms of the area under the curve (AUC) data (AUC_day?>?AUC_night). The P-gp modulator vinblastine significantly increased talinolol AUC_day (p?<?.05), whereas only a weak vinblastine effect was seen in night. According to the in situ data, the functional activity of P-gp was regulated by the CTS in jejunum and ileum, which are major intestinal segments for energy-dependent efflux. In conclusion, circadian rhythms may affect carrier-mediated active efflux and play a role in the absorption process. In addition to daily rhythms in P-gp activity in rat intestine, the in vivo studies indicate that absorption-, distribution-, metabolism-, and elimination-relevant rhythms may be involved in the circadian kinetics of the drug, besides transporter-dependent efflux, such well-known aspects as metabolic or renal clearance or motility. Since this also holds true for a potentially interacting second compound (modulator), modulator effects should be evaluated carefully in transporter related drug-drug interactions. (Author correspondence: aokyar@istanbul.edu.tr)     

The Dual-Oscillator System of Drosophila melanogaster Under Natural-Like Temperature Cycles

Dual-oscillator systems that control morning and evening activities can be found in a wide range of animals. The two coupled oscillators track dawn and dusk and flexibly adapt their phase relationship to seasonal changes. This is also true for the fruit fly Drosophila melanogaster that serves as model organism to understand the molecular and anatomical bases of the dual-oscillator system. In the present study, the authors investigated which temperature parameters are crucial for timing morning and evening activity peaks by applying natural-like temperature cycles with different daylengths. The authors found that the morning peak synchronizes to the temperature increase in the morning and the evening peak to the temperature decrease in the afternoon. The two peaks did not occur at fixed absolute temperatures, but responded flexibly to daylength and overall temperature level. Especially, the phase of the evening peak clearly depended on the absolute temperature level: it was delayed at high temperatures, whereas the phase of the M peak was less influenced. This suggests that the two oscillators have different temperature sensitivities. The bimodal activity rhythm was absent in the circadian clock mutants Clk^Jrk and cyc⁰¹ and reduced in per⁰¹ and tim⁰¹ mutants. Whereas the activity of Clk^Jrk mutants just followed the temperature cycles, that of per⁰¹ and tim⁰¹ mutants did not, suggesting that these mutants are not completely clockless. This study revealed new characteristics of the dual-oscillator system in Drosophila that were not detected under different photoperiods. (Author correspondence: yoshii@cc.okayama-u.ac.jp)     

Rest-activity rhythms characteristics and seasonal changes in seasonal affective disorder

ABSTRACT

Identifying objectively measurable seasonal changes in 24-h activity patterns (rest-activity rhythms or RARs) that occur in seasonal affective disorder (SAD) could help guide research and practice towards new monitoring tools or prevention targets. We quantified RARs from actigraphy data using non-parametric and extended cosine based approaches, then compared RARs between people with SAD and healthy controls in the summer (n = 70) and winter seasons (n = 84). We also characterized the within-person seasonal RAR changes that occurred in the SAD (n = 19) and control (n = 26) participants who contributed repeated measures. Only controls had significant winter increases in RAR fragmentation (intra-daily variability; in controls mean winter-summer changes (log scale) = 0.05, 0.21 standard deviation, p = 0.03). In SAD participants only, estimated evening settling times (down-mesor) were an average of 30 min earlier in the winter compared with the summer (1-h standard deviation, p = 0.045). These RAR characteristics correlated with greater fatigue (Spearman r = 0.36) but not depression symptom severity. Additional research is needed to ascertain why healthy controls, but not people with SAD, appear to have increased RAR fragmentation in the winter. People with SAD lacked this increase in RAR fragmentation, and instead had earlier evening setting in the winter. Prospective and intervention studies with greater temporal resolution are warranted to ascertain how these seasonal behavioral differences relate to fatigue pathophysiology in SAD. Future research is needed to determine whether extending the winter active period, even in relatively fragmented bouts, could help reduce the fatigue symptoms common in SAD.     

Hospitalization-induced exacerbation of the ill effects of chemotherapy on rest-activity rhythm and quality of life of breast cancer patients: a prospective and comparative cross-sectional follow-up study

ABSTRACT

Chemotherapy administration may result in the disruption of circadian rhythms and impairment of quality of life (QoL) of cancer patients. Nevertheless, we have little knowledge on the long-term consequences of chemotherapy and the effects of hospitalization. In the present study, we employed the two-factor repeated-measure cross-sectional design to determine the effects of chemotherapy and hospitalization on rest-activity (RA) rhythm and QoL of breast cancer patients. Initially, we randomly selected 39 inpatients and 42 outpatients, scheduled to receive six cycles of chemotherapy, from the Regional Cancer Center (RCC), Raipur, India. Finally, 30 patients in each group were included in the current study. We monitored circadian RA rhythm and QoL using wrist actigraphy and QLQ-C30 and QLQ-BR23, respectively, during the 1st (C1), 3rd (C3) and 6th (C6) chemotherapy cycles. Results revealed that with the progression of chemotherapy cycles (from C1 to C6), all rhythm parameters, namely mesor, amplitude, acrophase, rhythm quotient (RQ), circadian quotient (CQ), peak activity (PA), dichotomy index and autocorrelation coefficient, significantly decreased in both cancer in- and outpatients. In both groups of patients and during C1–C6, all functional and global QoL measures of QLQ-C30 and QLQ-BR23 significantly decreased and the symptoms significantly increased, except constipation, body image, sexual functioning and future perspectives in outpatients. The hospitalization exacerbated the problems associated with the RA rhythm and the QoL of the patients. In conclusion, the current study highlighted the negative consequences of hospitalization among inpatients, irrespective of the stage of cancer. We, therefore, recommend that cancer patients should be administered with chemotherapy as outpatients. The proposed protocol might have a covert bearing on the expression of better physiological state leading to satisfactory treatment outcomes.     

INTERNAL TEMPORAL ORDER IN THE CIRCADIAN SYSTEM OF A DUAL-PHASING RODENT,THE OCTODON DEGUS

Daily rhythms in different biochemical and hematological variables have been widely described in either diurnal or nocturnal species, but so far no studies in the rhythms of these variables have been conducted in a dual-phasing species such as the degus. The Octodon degus is a rodent that has the ability to switch from diurnal to nocturnal activity under laboratory conditions in response to wheel-running availability. This species may help us discover whether a complete temporal order inversion occurs parallel to the inversion that has been observed in this rodent's activity pattern. The aim of the present study is to determine the phase relationships among 26 variables, including behavioral, physiological, biochemical, and hematological variables, during the day and at night, in diurnal and nocturnal degus chronotypes induced under controlled laboratory conditions through the availability of wheel running. A total of 39 male degus were individually housed under a 12:12 light-dark (LD) cycle, with free wheel-running access. Wheel-running activity (WRA) and body temperature (Tb) rhythms were recorded throughout the experiment. Melatonin, hematological, and biochemical variables were determined by means of blood samples obtained every 6?h (ZT1, ZT7, ZT13, and ZT19). In spite of great differences in WRA and Tb rhythms between nocturnal and diurnal degus, no such differences were observed in the temporal patterns of most of the biological variables analyzed for the two chronotypes. Variation was only found in plasma urea level and lymphocyte number. A slight delay in the phase of the melatonin rhythm was also observed. This study shows the internal temporal order of a dual-phasing mammal does not show a complete inversion in accordance with its activity and body temperature pattern; it would appear that the switching mechanism involved in the degu's nocturnalism is located downstream from the pacemaker. (Author correspondence: angerol@um.es).     

Role of SCN in Daily Rhythms of Plasma Glucose,FFA, Insulin and Glucagon

The daily changes in plasma glucose, FFA, insulin and glucagon concentrations in rats under 12 hr-12 hr light-dark conditions, and the role of the suprachiasmatic nucleus (SCN) of the hypothalamus in these changes were examined. In sham-operated rats, the four parameters showed significant daily rhythms. However, after bilateral lesions of the SCN, daily rhythms could not be detected in these parameters under the present experimental conditions. Furthermore, after the SCN lesions the plasma glucose concentration remained at the minimum level of that in sham-operated rats, while the plasma insulin and glucagon concentrations reduced to approximately the mean level and about half the minimum level of sham-operated rats, respectively, and the FFA concentration lowered to somewhat below the minimum level. Gradual increase in the plasma insulin concentration at the end of the light period was observed in intact rats even after starvation for 24 hr. These findings suggest that the SCN is essential for generation of the daily changes in the plasma glucose, FFA, insulin and glucagon concentrations and also that it plays critical roles in regulation of the secretion of pancreatic hormones. The gradual increase in the plasma insulin level observed at the end of the light period is discussed in connection with initiation of spontaneous feeding behaviour.