Web-Based Chronobiological Analysis

In this paper we describe a computer application that allows users from all over the world to perform chronobiological analyses with popular Internet browsers. Our application is based on the client-server philosophy, and it has been designed so as to minimize the network resources and connections to be used. Presently, our application includes several well-known data analysis techniques, mainly, that known as the cosinor method and those related. All the problems concerning security restrictions are solved, so that the user can have a real interactive chronobiological application.     

Features of the circadian rhythm of temperature of the skin at children of 8-9 years and young men and girls

Problem of the present work was studying age features circadian rhythm of temperature of a skin with application of a method "Termochron iButton". Day-night rhythm of a skin temperature at two age-grades was investigated: boys and girls of 8-9 years and young men and girls of 20-22 years. For this purpose monitoring temperature during 48 hours with an interval of registration 10 minutes has been lead. Are revealed authentic chronobiological differences: mesor temperatures above at girls, than at boys, and at young men, above, than at girls. Amplitude of a circadian rhythm is above at boys and at girls. Researches chronobiological parameters in the different terms of day have shown, that an average level of temperature at night below at all examinees. The amplitude at adult people in the different terms of day does not differ, while at children it above in the night term.     

The Maximization of Mean Vector Length for the Identification of Unknown Periods in Biological Rhythms: An Extension to Continuous Variables

In a recent paper Rocchi and Ghiandoni proposed the maximization of mean vector length as a circular statistics tool for the preliminary identification of unknown and unforeseeable periods in biological rhythms, but its application was limited to unitless data. In this paper an extension of the method to the case of continuous variables collected at equidistant time intervals is proposed. The extended method is proposed as an exploratory tool in the analysis of chronobiological data. Two different examples of the application of this method (to edible white truffle harvesting data and to TSH level data) are also included and compared with the Fourier spectral analysis.     

The Maximization of Mean Vector Length for the Identification of Unknown Periods in Biological Rhythms: An Extension to Continuous Variables

In a recent paper Rocchi and Ghiandoni proposed the maximization of mean vector length as a circular statistics tool for the preliminary identification of unknown and unforeseeable periods in biological rhythms, but its application was limited to unitless data. In this paper an extension of the method to the case of continuous variables collected at equidistant time intervals is proposed. The extended method is proposed as an exploratory tool in the analysis of chronobiological data. Two different examples of the application of this method (to edible white truffle harvesting data and to TSH level data) are also included and compared with the Fourier spectral analysis.     

A Circular Statistics Tool for the Preliminary Identification of Unknown Periods in Biological Rhythms: An Application

A tool for the preliminary identification of unknown and unforeseeable periods in biological rhythms is presented. This method, called 'maximization of mean vector length', is based on circular statistics assumptions. It can be used effectively as an exploratory tool in the analysis of chronobiological data, while it carries a high risk of type I statistical error when used as a confirmative method. However, a correction term is provided in order to reduce this risk. An example of the application of this method to a set of spontaneous delivery data is also included.     

Pharmfit-a Nonlinear Fitting Program for Pharmacology

A new program is presented for nonlinear fitting of data from pharmacological and chronobiological investigations. It contains functions for calculating data from ligand-binding studies and competition experiments, for the analysis of dose-response curves, for pharmacokinetic calculations, and for cosine analysis of harmonic and overlapping rhythms. In addition, it is possible to implement general equations by the user. The program allows data exchange with most spreadsheet, database, and graphics presentation programs, and accepts data from two widely used ambulatory 24-h blood-pressure monitoring systems. The fitting procedure uses the Marquardt-Levenberg algorithm. It calculates the weighted or the unweighted fit together with a great variety of statistics for estimation of goodness of fit. A graphics module permits graphical presentation of the fitted curve. Moreover, fitting of data to different models can be compared for the most likely fit and model discrimination statistics for improvement of further experiments are provided. To demonstrate the chronobiological application of the fitting program PHARMFIT, the analysis of telemetric heart rate data from rats is presented.     

PHARMFIT—a Nonlinear Fitting Program for Pharmacology

A new program is presented for nonlinear fitting of data from pharmacological and chronobiological investigations. It contains functions for calculating data from ligand-binding studies and competition experiments, for the analysis of dose-response curves, for pharmacokinetic calculations, and for cosine analysis of harmonic and overlapping rhythms. In addition, it is possible to implement general equations by the user. The program allows data exchange with most spreadsheet, database, and graphics presentation programs, and accepts data from two widely used ambulatory 24-h blood-pressure monitoring systems. The fitting procedure uses the Marquardt–Levenberg algorithm. It calculates the weighted or the unweighted fit together with a great variety of statistics for estimation of goodness of fit. A graphics module permits graphical presentation of the fitted curve. Moreover, fitting of data to different models can be compared for the most likely fit and model discrimination statistics for improvement of further experiments are provided. To demonstrate the chronobiological application of the fitting program PHARMFIT, the analysis of telemetric heart rate data from rats is presented.     

A chronobiological study on the relation between heart rate and QT interval duration in newborn infants

The relation between heart rate and QT interval is the result of the autonomic nervous system control on cardiac function in healthy adults; accordingly, chronobiological studies have shown that adult subjects have circadian rhythms of heart rate (expressed as R-R interval) and QT interval in phase. We have employed chronobiological methods to study heart rate and QT interval relation in 10 newborn infants, who are known to have an immature cardiac control. Findings from this study indicate that not all the newborns show circadian rhythms of heart rate and QT interval and that when both rhythms are present they do not correlate like in the adults. Likely, this lack of relationship between heart rate and QT interval in newborns is due to different maturational stages of the newborns studied. As a practical implication, in newborn infants, mathematical correction of QT interval by heart rate is not a reliable method.     

Chronobiological analysis of superimposed period data sets using bivariate cosine series models

The non-linear cosine fit (so-called cosinor method) of chronobiological sets is suited to one-dimensional effect versus time data. Extending the method to multiple components allows one to look for subharmonics or superimposed underlying periods. In more complex two-dimensional chronobiological time series, alternative models may be advantageous to visualise the time structure. Bivariate cosine series and the corresponding numerical surface discussion including first and second partial derivatives may be a suited method to characterise individual maxima or minima. Moreover, the method permits one to define a mean over two periods (bivariate MESOR) of a two-dimensional data set.     

Chronobiological effects on exercise performance and selected physiological responses

Previous studies investigating the impact of circadian rhythms on physiological variables during exercise have yielded conflicting results. The purpose of the present investigation was to examine maximal aerobic exercise performance, as well as the physiological and psychophysiological responses to exercise, at four different intervals (0800 hours, 1200 hours, 1600 hours, and 2000 hours) within the segment of the 24-h day in which strenuous physical activity is typically performed. Ten physically fit, but untrained, male university students served as subjects. The results revealed that exercise performance was unaffected by chronobiological effects. Similarly, oxygen uptake, minute ventilation and heart rate showed no time of day influences under pre-, submaximal, and maximal exercise conditions. Ratings of perceived exertion were unaffected by time of day effects during submaximal and maximal exercise. In contrast, rectal temperature exhibited a significant chronobiological rhythm under all three conditions. Under pre- and submaximal exercise conditions, significant time of day effects were noted for respiratory exchange ratio, while a significant rhythmicity of blood pressure was evident during maximal exercise. However, none of these physiological variables exhibited significant differential responses (percent change from pre-exercise values) to the exercise stimulus at any of the four time points selected for study. Conversely, resting plasma lactate levels and lactate responses to maximal exercise were found to be significantly sensitive to chronobiological influences. Absolute post-exercise plasma norepinephrine values, and norepinephrine responses to exercise (percent change from pre-exercise values), also fluctuated significantly among the time points studied. In summary, these data suggest that aerobic exercise performance does not vary during the time frame within which exercise is normally conducted, despite the fact that some important physiological responses to exercise do fluctuate within that time period. Accepted: 18 August 1997     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

From a static to a dynamic concept of risk: the circadian epidemiology of cardiovascular events

A growing body of evidence substantiates that the occurrence of cardiovascular events in unevenly distributed in time, especially during the 24 h. These temporal patterns are indicative of temporal variation in the (1) pathophysiological mechanisms that trigger cardiovascular events and (2) physiological status of the cardiovascular system, which combine to give rise to 24 h and other periodicities in the susceptibility to disease. The classic assumption of epidemiologic studies is constancy (or homeostasis) in one's risk to disease during the 24 h, as well as other, time domains. However, we propose a new concept, that of chronorisk since it takes into account the temporal variability in the pathophysiological mechanisms and their reciprocal temporal interactions that lead to day-night and other time-dependent patterns in cardiovascular events. This chronobiological approach, which is expected to contribute new insight into the prognostic and therapeutic assessment of cardiovascular events, is worthy of broader application in cardiovascular and other fields of medicine and warrants further investigation.     

The Circadian Rhythm of Plasma Thyrotropin in Depression and Recovery

The 24-hr patterns of plasma thyrotropin have been observed in 12 endogenous depressed patients in both depressed and recovered states and in 13 normal subjects. A clear circadian rhythm was detected in controls with high values at night. In depression, the circadian rhythm was altered with amplitude reduction and blunted nocturnal secretion, abnormalities particularly relevant in bipolar patients. This flattened profile could be linked to the blunted response of TSH to TRH administration reported in depressed patients. Normal nyctohemeral patterns have been restored after recovery. These chronobiological abnormalities as well as their normalization under antidepressant drugs seem to be similar to those reported for various parameters (e.g. temperature, Cortisol, etc) in depression which could support the chronobiological hypothesis for affective disorders.     

Modelling and model-free mathematical description of biological relationships

The features of the modelling and the model free approaches for handling measured data of functional connections in respect to their advantages as well as to their troubles will be discussed theoretically and by means of morphometrical, histokinetical, and chronobiological examples.     

HOW TO SHOW THAT UNICORN MILK IS A CHRONOBIOTIC: THE REGRESSION-TO-THEMEAN STATISTICAL ARTIFACT

Few chronobiologists may be aware of the regression-to-the-mean (RTM) statistical artifact, even though it may have far-reaching influences on chronobiological data. With the aid of simulated measurements of the circadian rhythm phase of body temperature and a completely bogus stimulus (unicorn milk), we explain what RTM is and provide examples relevant to chronobiology. We show how RTM may lead to erroneous conclusions regarding individual differences in phase responses to rhythm disturbances and how it may appear as though unicorn milk has phase-shifting effects and can successfully treat some circadian rhythm disorders. Guidelines are provided to ensure RTM effects are minimized in chronobiological investigations. (Chronobiology International, 18(6), 1041-1053, 2001)     

Twenty-four-Hour Rhythmic Variations of Histamine in Human Female Blood

We have previously observed that blood histamine levels undergo rhythmic 24 hour variations in male normal subjects. In the present study we examined whether similar 24 hour modifications were also present in female subjects. To this purpose, 60 healthy cycling women were enrolled for a chronobiological transverse study. To achieve experimental conditions as homogeneous as possible, the study was carried out on the first day of the menstrual flow. Histamine was determined in whole venous blood by a spectrophotofluorimetric method. The blood histamine levels showed significant rhythmic changes depending on the time of blood sampling, with 1 maximum and 1 minimum within a period of 24 h, with percentage rhythm 15.1, MESOR 0.15 μg/ml, amplitude 0.02 μg/ml and acrophase at 01:20 h. These results reveal the presence of 24 h cyclic variations of histamine levels in the female, as it occurred in male. However, the differences observed in the chronobiological rhythms of histamine between the two sexes may represent a peculiar feature of the first day of the menstrual cycle.     

Small shifts in diurnal rhythms are associated with an increase in suicide: The effect of daylight saving

Sleep and Biological Rhythms - Large disruptions of chronobiological rhythms are documented as destabilizing individuals with bipolar disorder; however, the impact of small phase altering events is...     

Heart rate circadian rhythm as a biological marker of desynchronization in major depression: a methodological and preliminary report

Heart rate (HR) was continuously monitored during successive 24-hr periods in 19 healthy subjects and 26 major depressed patients (DSM III-R). Recordings were performed after a 2-week wash-out period and the morningness or eveningness typology of each subject was determined. The chronobiological parameters and rhythm percentage (RP) were calculated by the single cosinor method from the smoothed HR curves of each subject. In normal subjects, HR follows a circadian rhythm (RP greater than 65%) with the lowest values at night. Morning type subjects have an earlier peak time (13:30) than evening type subjects (17:30). Major depressive patients were split into two groups; in the first one HR circadian rhythm was still present (RP greater than 63%) with a decrease in amplitude (24%) while in the second group, no circadian rhythm of HR could be detected (RP less than 25%, decrease in amplitude greater than 70%). In the group of patients with a persisting HR circadian rhythm, no veritable phase advance was observed. Our results suggest that circadian HR rhythm, which can be easily studied with non-invasive methods, might represent a chronobiological marker of some depressions. Given the lag that exists between the rhythms of morning type and evening type subjects, our study also stresses the importance of taking into account this behavioural trait in chronobiological studies.     

Twenty-four-Hour Rhythmic Variations of Histamine in Human Female Blood

We have previously observed that blood histamine levels undergo rhythmic 24 hour variations in male normal subjects. In the present study we examined whether similar 24 hour modifications were also present in female subjects. To this purpose, 60 healthy cycling women were enrolled for a chronobiological transverse study. To achieve experimental conditions as homogeneous as possible, the study was carried out on the first day of the menstrual flow. Histamine was determined in whole venous blood by a spectrophotofluorimetric method. The blood histamine levels showed significant rhythmic changes depending on the time of blood sampling, with 1 maximum and 1 minimum within a period of 24 h, with percentage rhythm 15.1, MESOR 0.15 μg/ml, amplitude 0.02 μg/ml and acrophase at 01:20 h. These results reveal the presence of 24 h cyclic variations of histamine levels in the female, as it occurred in male. However, the differences observed in the chronobiological rhythms of histamine between the two sexes may represent a peculiar feature of the first day of the menstrual cycle.     

Chronobiological Dimensions of an Olfactory Bulbectomized Rodent Animal Model for Agitated Depression

Olfactory bulbectomized (OBX) rodents mimic some behavioral and biochemical features of chronic agitated hyposerotonergic depression. These effects of OBX include increased activity levels, altered serotonin metabolism, changes in sexual behavior, and elevated corticosteroid levels. Here we summarize published research demonstrating chronobiological changes in OBX rodents, and present new data addressing effects of OBX on additional elements of biological clock function. The chronobiological consequences of OBX make this model useful for testing hypotheses about possible causal relationships between variation in biological clock function and variation in behavioral and biochemical traits associated with clinical depression.