Day-night variation in aggressive behavior among psychiatric inpatients

Self-directed aggressive behaviors of human beings show a 24h pattern. The aim of this study was to evaluate if violence of psychiatric inpatients against one another and hospital staff varies over the 24h. The clock time occurrence of 334 episodes of assault behaviors by 119 psychiatric inpatients (78 males and 41 females, mean age 34.8 ± 11.3 years) committed during a 5-year span in the psychiatric unit of the university-based hospital of Ferrara, Italy, was evaluated. The clock time of each event was categorized by hour during the 24h and into one of four 6h intervals for analysis of temporal variation by cosinor and χ² tests, respectively. A significant 24h variation, characterized by an early afternoon peak, was detected irrespective of gender and number (single vs. repeated) of episodes committed. Changes during the 24h in ward activity, patient contact, and endogenous circadian rhythms are likely to contribute to the observed 24h pattern, although further study is needed to confirm our findings and to define causal factors. (Chronobiology International, 18(3), 503-511, 2001)     

Modulating effects of hesperidin on circadian pattern indices of rotenone induced redox homeostasis in clock mutant (cryb) of Drosophila melanogaster

The circadian timing system controls drug metabolism and cellular processes over the 24 h period in every cell. Impaired redox homeostasis is a casual factor for a number of diseases and it is desirable to understand the orchestration of circadian clock under oxidative stress in the model organism, Drosophila melanogaster. This study evaluates the effect of hesperidin on the circadian rhythms of lipid peroxidation products and antioxidants during rotenone-induced oxidative stress in fruit fly. The characteristics of temporal rhythms (acrophase, amplitude, and mesor) of glutathione peroxides (GPx), reduced glutathione (GSH)), were markedly declined in rotenone-treated flies when compared to other groups. Treatment of hesperidin to rotenone-treated flies significantly increased the mesor and modified the amplitudes of antioxidants. Further, delays in acrophase in rotenone-induced flies were reversed by hesperidin treatment. Thus, treatment of hesperidin results in normalization of the altered rhythms of these indices plausibly by its cytoprotective and antioxidant effects. Impairment of 24 h rhythms in oxidative stress markers and antioxidants were observed during rotenone treatment and the impairment is severe in circadian clock mutant cry^b flies. A reversibility of rhythms was prominent consequent to hesperidin treatment in wild-type flies than cry^b flies. These findings revealed a role of circadian clock in redox homeostasis and the use of Drosophila model in screening putative antioxidative phytomedicines earlier to their use in mammalian systems.     

Peripheral clock system circadian abnormalities in Cushing’s disease

ABSTRACT

In Cushing’s syndrome, the cortisol rhythm is impaired and can be associated with the disruption in the rhythmic expression of clock genes. In this study, we evaluated the expression of CLOCK, BMAL1, CRY1, CRY2, PER1, PER2, PER3 genes in peripheral blood leukocytes of healthy individuals (n = 13) and Cushing’s disease (CD) patients (n = 12). Participants underwent salivary cortisol measurement at 0900 h and 2300 h. Peripheral blood samples were obtained at 0900 h, 1300 h, 1700 h, and 2300 h for assessing clock gene expression by qPCR. Gene expression circadian variations were evaluated by the Cosinor method. In healthy controls, a circadian variation in the expression of CLOCK, BMAL1, CRY1, PER2, and PER3 was observed, whereas the expression of PER1 and CRY2 followed no specific pattern. The expression of PER2 and PER3 in healthy leukocytes presented a late afternoon acrophase, similarly to CLOCK, whereas CRY1 showed night acrophase, similarly to BMAL1. In CD patients, the circadian variation in the expression of clock genes was lost, along with the abolition of cortisol circadian rhythm. However, CRY2 exhibited a circadian variation with acrophase during the dark phase in patients. In conclusion, our data suggest that Cushing’s disease, which is characterized by hypercortisolism, is associated with abnormalities in the circadian pattern of clock genes. Higher expression of CRY2 at night outlines its putative role in the cortisol circadian rhythm disruption.     

Prevalence and Risk Factors of Violence by Psychiatric Acute Inpatients: A Systematic Review and Meta-Analysis

Background

Violence in acute psychiatric wards affects the safety of other patients and the effectiveness of treatment. However, there is a wide variation in reported rates of violence in acute psychiatric wards.

Objectives

To use meta-analysis to estimate the pooled rate of violence in published studies, and examine the characteristics of the participants, and aspects of the studies themselves that might explain the variation in the reported rates of violence (moderators).

Method

Systematic meta-analysis of studies published between January 1995 and December 2014, which reported rates of violence in acute psychiatric wards of general or psychiatric hospitals in high-income countries.

Results

Of the 23,972 inpatients described in 35 studies, the pooled proportion of patients who committed at least one act of violence was 17% (95% confidence interval (CI) 14–20%). Studies with higher proportions of male patients, involuntary patients, patients with schizophrenia and patients with alcohol use disorder reported higher rates of inpatient violence.

Conclusion

The findings of this study suggest that almost 1 in 5 patients admitted to acute psychiatric units may commit an act of violence. Factors associated with levels of violence in psychiatric units are similar to factors that are associated with violence among individual patients (male gender, diagnosis of schizophrenia, substance use and lifetime history of violence).     

Accidents in children do not happen at random: Predictable time-of-day incidence of childhood trauma

In a prospective study, 15,110 childhood traumas were recorded by the Pediatric Surgery Service (CHUV, Lausanne) between January 1, 1990 and December 31, 1997. The exact clock hour when the injury occurred and other germane data were obtained. Time series thus obtained were analyzed by several statistical (ANOVA, cosinor, χ², Table Curve, etc.) methods. High statistically significant circadian patterns were detected with a trough at night—almost no traumas/hour (t/h), and a peak in the afternoon (～16:00h)—9.3±0.4 (SD) t/h. Such 24h variation was validated for the whole sample for the entire 8yr study span as well as the data of each year. Neither gender- nor age-related differences in the 24h pattern were detected between children under 5 yr of age, who have not yet attended school and children from 5 to 16 yr of age, who attend school. Small but statistically significant differences in the 24h patterns were observed when categorized by the type of activity associated with the trauma and the place of trauma occurrence. The great stability of the 24h pattern in childhood trauma over the 8yr study span suggests an endogenous origin in addition to the role presumably played by environmental factors. Periods of 12 and 8 h were also detected in the time series. The afternoon peak time of childhood traumas differs from that of adults, which is located ～04:00h in rotating shift workers and automobile drivers and 06:00–08:00h in adult day-workers. The validation of a circadian pattern in childhood traumas with an afternoon peak should be taken into account in the design of children's preventative injury programs.     

Altered Clock Gene Expression in Obese Visceral Adipose Tissue Is Associated with Metabolic Syndrome

Clock gene expression was associated with different components of metabolic syndrome (MS) in human adipose tissue. However, no study has been done to compare the expression of clock genes in visceral adipose tissue (VAT) from lean and obese subjects and its clinical implications. Therefore, we studied in lean and obese women the endogenous 24 h expression of clock genes in isolated adipocytes and its association with MS components. VAT was obtained from lean (BMI 21–25 kg/m²; n = 21) and morbidly obese women (BMI >40 kg/m²; n = 28). The 24 h pattern of clock genes was analyzed every 6 hours using RT-PCR. Correlation of clinical data was studied by Spearman analysis. The 24 h pattern of clock genes showed that obesity alters the expression of CLOCK, BMAL1, PER1, CRY2 and REV-ERB ALPHA in adipocytes with changes found in CRY2 and REV-ERB ALPHA throughout the 24 h period. The same results were confirmed in VAT and stromal cells (SC) showing an upregulation of CRY2 and REV-ERB ALPHA from obese women. A positive correlation was observed for REV-ERB ALPHA gene expression with BMI and waist circumference in the obese population. Expression of ROR ALPHA was correlated with HDL levels and CLOCK with LDL. Obese subjects with MS exhibited positive correlation in the PER2 gene with LDL cholesterol, whereas REV-ERB ALPHA was correlated with waist circumference. We identified CRY2 and REV-ERB ALPHA as the clock genes upregulated in obesity during the 24 h period and that REV-ERB ALPHA is an important gene associated with MS.     

Day‐Night Variations of Serum Interleukin‐6 in Patients with Severe Obstructive Sleep Apnea Syndrome before and after Continuous Positive Airway Pressure (CPAP)

Obstructive sleep apnea syndrome (OSAS) causes intermittent hypoxia and increases in sympathetic activity and contributes to cardiovascular disorders. Interleukin‐6 (IL‐6) is one of the important proinflammatory cytokines. We examined the levels of serum IL‐6 concentrations in nine patients with severe OSAS at four different clock times during the 24 h before and after three months of continuous positive airway pressure (CPAP) therapy. Serum IL‐6 levels were significantly reduced after CPAP therapy by 46% (6.2±1.0 vs. 3.3±0.4 pg/ml, p<0.005). No significant 24 h variation of serum IL‐6 in severe OSAS patients was found before CPAP; however, a significant 24 h variation of serum IL‐6 was found after CPAP. Intermittent hypoxia during sleep may contribute to systemic inflammation and result in an elevation of serum IL‐6 in severe OSAS patients.     

Daily rhythms of clock gene expression and feeding behavior during the larval development in gilthead seabream,Sparus aurata

Light is the main environmental time cue which synchronizes daily rhythms and the molecular clock of vertebrates. Indeed, alterations in photoperiod have profound physiological effects in fish (e.g. reproduction and early development). In order to identify the changes in clock genes expression in gilthead seabream larvae during ontogeny, three different photoperiods were tested: a regular 12L:12D cycle (LD), a continuous light 24L:0D (LL) and a two-phases photoperiod (LL?+?LD) in which the photoperiod changed from LL to LD on day 15 after hatching (dph). Larvae were sampled on 10, 18, 30 and 60 days post-hatch (dph) during a 24?h cycle. In addition to the expression of clock genes (clock, bmal1, cry1 and per3), food intake was measured. Under LD photoperiod, larvae feed intake and clock genes expression showed a rhythmic pattern with a strong light synchronization, with the acrophases occurring at the same hour in all tested ages. Under LL photoperiod, the larvae also showed a rhythmic pattern but the acrophases occurred at different times depending on the age, although at the end of the experiment (60 dph) clock genes expression and feed intake rhythms were similar to those larvae exposed to LD photoperiod. Moreover, the expression levels of bmal1 and cry1 were much lower than in LD photoperiod. Under the LL?+?LD photoperiod, the 10 dph larvae showed the same patterns as LL treatment while 18 and 30 dph larvae showed the same patterns as LD treatment. These results revealed the presence of internal factors driving rhythmic physiological responses during larvae development under constant environmental conditions. The LL?+?LD treatment demonstrates the plasticity of the clock genes expression and the strong effect of light as synchronizer in developing fish larvae.     

Diurnal feeding as a potential mechanism of osmoregulation in aphids

Diurnal variation in phloem sap composition has a strong infuence on aphid performance.The sugar-rich phloem sap serves as the sole diet for aphids and a suite of physiological mechanisms and behaviors allowv them to tolerate the high osmotic stress.Here,we tested the hypothesis that night-time feeding by aphids is a behavior that takes advantage of the low sugar diet in the night to compensate for osmotic stress incurred while feeding on high sugar diet during the day.Using the electrical penetration graph(EPG)technique.we examined the eiects of diurmal rhythm on feeding behaviors of bird cherry-oat aphid(Rhopalosiphurm padi L.)on wheat.A strong diurmal rhythm in aphids as indicated by the presence of a cyclical pattern of expression in a core clock gene did not impact aphid feeding and similar feeding behaviors were observed during day and night.The major difference observed between day and night feeding was that aphids spent significantly longer time in phloem salivation during the night compared to the day.In contrast,aphid hydration was reduced at the end of the day-time feeding compared to end of the night-time fepding.Gene expression analysis of R.padi osmoregulatory genes indicated that sugar break down and water transport into the aphid gut was reduced at night.These data suggest that while diumal variation occurs in phloem sap composition,aphids use night time feeding to overcome the high osmotic stress incurred while feeding on sugar-rich phloem sap during the day.     

Psychiatric Hospital Bed Numbers and Prison Population Sizes in 26 European Countries: A Critical Reconsideration of the Penrose Hypothesis

Background

Recently, there has been a revived interest in the validity of the Penrose hypothesis, which was originally postulated over 75 years ago. It suggests an inverse relationship between the numbers of psychiatric hospital beds and the sizes of prison population. This study aims to investigate the association between psychiatric hospital beds and prison populations in a large sample of 26 European countries between 1993 and 2011.

Methods

The association between prison population sizes and numbers of psychiatric hospital beds was assessed by means of Spearman correlations and modeled by a mixed random coefficient regression model. Socioeconomic variables were considered as covariates. Data were retrieved from Eurostat, the statistical office of the European Union.

Outcomes

Mean Spearman correlation coefficients between psychiatric beds and prison population showed a significant negative association (-0.35; p = <0.01). However, in the mixed regression model including socioeconomic covariates there were no significant fixed parameter estimates. Meanwhile, the covariance estimates for the random coefficients psychiatric beds (σ² = 0.75, p = <0.01) and year (σ² = 0.0007, p = 0.03) yielded significant results.

Interpretation

These findings do not support the general validity of the Penrose hypothesis. Notably, the results of the mixed-model show a significant variation in the magnitude and direction of the association of psychiatric hospital bed numbers and the prison population sizes between countries. In this sense, our results challenge the prevalent opinion that a reduction of psychiatric beds subsequently leads to increasing incarcerations. These findings also work against the potential stigmatization of individuals suffering from mental disorders as criminals, which could be an unintentional byproduct of the Penrose hypothesis.     

Abscisic-acid-induced turion formation in Spirodela polyrrhiza L III. Specific changes in protein synthesis and translatable RNA during turion development

Abstract The developmental process leading to the formation of the abscisic acid (ABA) induced turion of Spirodela polyrrhiza was accompanied by a repression of nucleic acid and protein synthesis. DNA synthesis in the developing lurion (induced by 10⁻⁴mol m⁻³ ABA) was inhibited within 3h of ABA addition, followed by a repression of protein synthesis after 24 h, while RNA synthesis was not inhibited until 3 d. The inhibitory effect of ABA on protein synthesis was found to be selective and the synthesis of several novel proteins appeared to be induced. These effects were specific to ABA-sensitive tissue. The relationship between the changes in the protein and mRNA profiles during the development of the turion was investigated. The rapid general inhibition of protein synthesis at early stages of lurion formation could not be accounted for by the level of translatable mRNA, indicating an effect of ABA at the translational level. The specific alteration to the pattern of in vivo labelled proteins could have resulted, however, from control of the level of specific mRNAs for those particular proteins. Only after 3 d in ABA, when the developing primordium is committed to the turion developmental pathway, is there a total inhibition in the production of mRNA leading to the shutdown of all primary processes and the onset of the irreversible events leading to the dormant state.     

24-Hour Variation in the Reactivity of Rate-Pressure-Product to Everyday Physical Activity in Patients Attending a Hypertension Clinic

The exercise-related response of the rate-pressure-product (RPP) is a prognostic marker of autonomic imbalance, cardiovascular mortality, and silent myocardial ischemia in hypertension. In view of the well-known 24 h variation in out-of-hospital sudden cardiac events, our aim was to investigate whether the reactivity of RPP to everyday physical activities varies over the 24 h. Ambulatory measurements of systolic blood pressure (BP) and heart rate were recorded every 20 min for 24 h in 440 diurnally active patients attending a hypertension clinic. Wrist activity counts were summed over the 15 min that preceded a BP measurement. An RPP reactivity index was derived for each of twelve 2 h data bins by regressing the change in RPP against the change in logged activity counts. The RPP showed 24 h variation (p?<?0.0005), with a peak of 11,004 (95% CI?=?10,757 to 11,250) beat?·?min^?1?·?mmHg occurring at 10:00 h (2 h after mean wake-time). The overall 24 h mean of RPP reactivity was 477 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?426 to 529). The largest increase in RPP reactivity occurred within the first 2 h after waking (p?<?0.0005). There were no subsequent significant differences in RPP reactivity up to 14 h after waking. The lowest RPP reactivity was found 18–20 h after waking, with a peak-to-trough variation of 593 beat?·?min^?1?·?mmHg?·?logged activity counts^?1 (95% CI?=?394 to 791, p?<?0.0005). Although this variation was not moderated by BP status, age, or sex, less variability in RPP reactivity was found for the medicated individuals during the waking hours. These data suggest that under conditions of normal living, the reactivity of RPP to a given change in physical activity increases markedly during the first 2 h after waking from nocturnal sleep, the time when out-of-hospital sudden cardiac events are also most common. Therefore, these data add weight to the notion that reactivity of RPP to physical activity could be a prognostic marker of autonomic imbalance and cardiovascular mortality, although more research is needed to assess the specific prognostic value of 24 h ambulatory measurements of RPP and physical activity.     

Seven-year survey of sleep timing in Russian children and adolescents: chronic 1-h forward transition of social clock is associated with increased social jetlag and winter pattern of mood seasonality

Previous studies indicate that solar clock (daily changes in the Earth’s surface illumination) is a main zeitgeber for human circadian system. It has been shown that human biological clock is weakly adjusted to such changes in social clock as daylight saving time (DST). There are two changes of social clock in Russian Federation: on 25 March 2011, DST has been replaced by permanent DST (DSTp), which was subsequently revoked on 26 October 2014 (non-DSTp). These manipulations with social clock may lead to prolonged disturbances of human circadian system. Our hypothesis is that during period of DSTp, the dissociation between social and biological clocks was greatest as compared with DST and non-DSTp periods. Here, we examine the effects of DSTp on the sleep timing, social jetlag (SJL), academic performance, and winter and summer seasonality of mood and behavior of 10–24-year-old inhabitants of European North of Russia. A cross-sectional retrospective analysis of questionnaire data (n = 7968) was performed using chi squared-test and analysis of covariance. Our findings indicate that SJL (F_2,7967 = 31.9; p < 0.0001; η² = 0.009), and winter pattern of mood seasonality (χ²_2,7967 = 10.5; p < 0.01) were increased in adolescents during the period of DSTp as compared with DST and non-DSTp periods. The largest increase in SJL was occurred in ages between 10 and 17-year-olds. The finding suggests that increase in SJL can be attributed to a later rise time on free days (F_2,7967 = 44.9; p < 0.0001; η² = 0.012). Similar changes were observed in three subsamples obtained in Syktyvkar, Petrozavodsk, and Vorkuta. Effect sizes of studied relationships were small or very small. The greatest effect sizes (η² ～ 0.05) were observed in Arctic city of Vorkuta indicating that in polar region, solar clock is still stronger zeitgeber for human circadian system, than the social clock. In conclusion, we have shown for the first time that there is a greatest dissociation between social and biological clocks during the period of DSTp which potentially exerts a negative influence on adolescents’ sleep habits, mood, and behavior. Our data indicate that “non-DSTp” social clock system most suitable for prevention dissociation between social and biological clocks.     

Glucocorticoids Affect 24 h Clock Genes Expression in Human Adipose Tissue Explant Cultures

Aims

to examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock genes expression.

Subjects and Methods

VAT and SAT biopsies were obtained from morbid obese women (body mass index≥40 kg/m²) (n = 6). In order to investigate rhythmic expression pattern of clock genes and the effect of DEX on CLOCK, PER2 and BMAL1 expression, control AT (without DEX) and AT explants treated with DEX (2 hours) were cultured during 24 h and gene expression was analyzed at the following times: 10:00 h, 14:00 h, 18:00 h, 22:00 h, 02:00 h and 06:00 h, using qRT-PCR.

Results

CLOCK, BMAL1 and PER2 expression exhibited circadian patterns in both VAT and SAT explants that were adjusted to a typical 24 h sinusoidal curve. PER2 expression (negative element) was in antiphase with respect to CLOCK and in phase with BMAL1 expression (both positive elements) in the SAT (situation not present in VAT). A marked effect of DEX exposure on both positive and negative clock genes expression patterns was observed. Indeed, DEX treatment modified the rhythmicity pattern towards altered patterns with a period lower than 24 hours in all genes and in both tissues.

Conclusions

24 h patterns in CLOCK and BMAL1 (positive clock elements) and PER2 (negative element) mRNA levels were observed in human adipose explants. These patterns were altered by dexamethasone exposure.     

Cognitive functioning of female nurses during the night shift: The impact of age,clock time,time awake and subjective sleepiness

ABSTRACT

Decline in cognitive functioning in the workplace is a major concern for health care systems. Understanding factors associated with nighttime functioning is imperative for instituting organizational risk management policies and developing personalized countermeasures. The present study aims to identify individual factors associated with cognitive functioning during the night shift of hospital nurses working on irregular rotating-shift schedules. Ninety-two female nurses were recruited from 17 wards in two general hospitals, using convenience sampling by clusters. Inclusion criteria were working at least 28 h a week (75% of full time) and one night shift per week. Exclusion criteria were pregnancy, diagnosed sleep disorders or medical conditions that may affect sleep and/or function. Cognitive performance was measured during the middle (03:00 h) and at the end (07:00 h) of the night shift using the Digit Symbol Substitution Task (DSST) and the Letter Cancellation Task (LCT) over two night shifts. Subjective sleepiness was assessed by the Karolinska Sleepiness Scale (KSS) at the same time points. All participants completed a sociodemographic questionnaire, the Munich ChronoType Questionnaire for Shift-Workers (MCTQShift) and the Pittsburgh Sleep Quality Index (PSQI). Sleep duration 24 h before the night shift and time awake since last sleep opportunity were monitored by actigraphy. Univariate repeated measures ANOVA found main effects for clock time (p<0.001), age (p<0.05), time awake (p<0.05) and sleepiness (p<0.01) for DSST correct responses; main effects for clock time (p<0.001) and sleepiness (p<0.001) for LCT capacity; and main effects for clock time (p<0.001) and age (p<0.01) for LCT omission errors. All factors remained significant in a mixed-model analysis for DSST. Cognitive performance among hospital nurses is low during the middle of the night shift and increases at the end of the shift; decreased functioning is associated with increased subjective sleepiness, older age and prolonged time awake. Identifying factors contributing to performance during the night shift may provide a basis for the development of risk management policies and preventative interventions.     

The cell adhesion molecule EphA4 is involved in circadian clock functions

Circadian (～24 h) rhythms of cellular network plasticity in the central circadian clock, the suprachiasmatic nucleus (SCN), have been described. The neuronal network in the SCN regulates photic resetting of the circadian clock as well as stability of the circadian system during both entrained and constant conditions. EphA4, a cell adhesion molecule regulating synaptic plasticity by controlling connections of neurons and astrocytes, is expressed in the SCN. To address whether EphA4 plays a role in circadian photoreception and influences the neuronal network of the SCN, we have analyzed circadian wheel‐running behavior of EphA4 knockout (EphA4^?/?) mice under different light conditions and upon photic resetting, as well as their light‐induced protein response in the SCN. EphA4^?/? mice exhibited reduced wheel‐running activity, longer endogenous periods under constant darkness and shorter periods under constant light conditions, suggesting an effect of EphA4 on SCN function. Moreover, EphA4^?/? mice exhibited suppressed phase delays of their wheel‐running activity following a light pulse during the beginning of the subjective night (CT15). Accordingly, light‐induced c‐FOS (FBJ murine osteosarcoma viral oncogene homolog) expression was diminished. Our results suggest a circadian role for EphA4 in the SCN neuronal network, affecting the circadian system and contributing to the circadian response to light.     

Bayesian random local clocks,or one rate to rule them all

Background  

Relaxed molecular clock models allow divergence time dating and "relaxed phylogenetic" inference, in which a time tree is estimated in the face of unequal rates across lineages. We present a new method for relaxing the assumption of a strict molecular clock using Markov chain Monte Carlo to implement Bayesian modeling averaging over random local molecular clocks. The new method approaches the problem of rate variation among lineages by proposing a series of local molecular clocks, each extending over a subregion of the full phylogeny. Each branch in a phylogeny (subtending a clade) is a possible location for a change of rate from one local clock to a new one. Thus, including both the global molecular clock and the unconstrained model results, there are a total of 2^2n-2 possible rate models available for averaging with 1, 2, ..., 2n - 2 different rate categories.     

TEMPORAL ORGANIZATION OF FEEDING IN SYRIAN HAMSTERS WITH A GENETICALLY ALTERED CIRCADIAN PERIOD

The variation in spontaneous meal patterning was studied in three genotypes (tau +/+, tau +/?and tau ?/?) of the Syrian hamster with an altered circadian period. Feeding activity was monitored continuously in 13 individuals from each genotype in constant dim light conditions. All three genotypes had on average six feeding episodes during the circadian cycle (about 20h in homozygous tau mutants and 22h in heterozygotes compared with 24h in wild-type hamsters). Thus, homozygous tau mutant hamsters had significantly more feeding episodes per 24h than wild types, and heterozygotes were intermediate. The average duration of feeding bouts (FBs) was indistinguishable (around 30 minutes) among the three genotypes, whereas the intermeal (IM) intervals were significantly shorter for homozygote tau mutant hamsters (99 minutes), intermediate for heterozygotes (116 minutes), and the longest for wild-type hamsters (148 minutes). Thus, the meal-to-meal duration was on average 25% shorter in homozygous tau mutants (16% in heterozygous) than in wild-type hamsters. The reduction of the circadian period has a pronounced effect on short-term feeding rhythms and meal frequency in hamsters carrying the tau mutation. (Chronobiology International, 18(4), 657–664, 2001)     

BIOLOGICAL RHYTHMS OF SPINAL-EPIDURAL LABOR ANALGESIA

Pain exhibits temporal variations in intensity due to multiple factors, including endogenous neuroendocrine and various external influences that vary over the 24?h. Also, medications can vary in potency and/or toxicity according to the time when they are administered. However, there is no consensus among studies regarding the 24-h pattern of analgesia during labor. Taking into account the time-of-day when labor analgesia is administered, this study aimed to answer two questions: (i) Is there diurnal variation in visual analogue scale (VAS)–rated pain relief and duration of intrathecal analgesia in patients undergoing labor analgesia? (ii) If there is, what is the influence of the duration of labor on the diurnal variation of the level of pain relief and duration of intrathecal analgesia? This prospective cohort included 41 healthy, nulliparous women in the first stage of labor undergoing spinal-epidural (CSE) analgesia using fentanyl combined with bupivacaine. Subjects had an epidural catheter fitted for additional, patient-controlled analgesia (PCA) if their pain relief was unsatisfactory. The number of VAS assessments (n?=?558) was divided into six time periods of the 24?h. The adjusted coefficient of determination (r²), the proportion of the variance explained by the association between the duration of labor and the temporal pattern of the outcomes variable, was 58% (r²?=?0.58) for pain relief and 44% (r²?=?0.44) for duration of intrathecal analgesia. The peak effect of labor analgesia occurred between 02:00 and 05:59?h. However, the duration of intrathecal analgesia showed two peaks, i.e., at ～00:00 and ～12:00?h. These results demonstrate that labor analgesia achieved by fentanyl combined with bupivacaine shows a diurnal pattern in pain relief and duration of spinal analgesia. However, part of these temporal patterns was explained by the association with duration of labor. (Author correspondence: caumo@cpovo.net)