Midline Estimating Statistic Of Rhythm Research Articles

Renal tubular SGK1 is required to achieve blood pressure surge and circadian rhythm.

Blood pressure (BP) follows a circadian pattern that rises during the active phase of the day (morning surge) and decreases during the inactive (night dipping) phase of the day. The morning surge coincides with increased circulating glucocorticoids and aldosterone, ligands for glucocorticoid receptors and mineralocorticoid receptors, respectively. Serum- and glucocorticoid-induced kinase 1 (SGK1), a clock-controlled and glucocorticoid receptor- and mineralocorticoid receptor-induced gene, plays a role in BP regulation in human and animal models. However, the role of SGK1 in BP circadian regulation has not yet been demonstrated. Using telemetry, we analyzed BP in the inducible renal tubule-specific Sgk1Pax8/LC1 model under basal K+ diet (1% K+) and high-K+ diet (HKD; 5% K+). Our data revealed that, under basal conditions, renal SGK1 plays a minor role in BP regulation; however, after 1 wk of HKD, Sgk1Pax8/LC1 mice exhibited significant defects in diastolic BP (DBP), including a blunted surge, a decreased amplitude, and reduced day/night differences. After prolonged HKD (7 wk), Sgk1Pax8/LC1 mice had lower BP than control mice and exhibited reduced DBP amplitude, together with decreased DBP day/night differences and midline estimating statistic of rhythm (MESOR). Interestingly, renal SGK1 deletion increased pulse pressure, likely secondary to an increase in circulating aldosterone. Taken together, our data suggest that 1) the kidney plays a significant role in setting the BP circadian rhythm; 2) renal tubule SGK1 mediates the BP surge and, thus, the day/night BP difference; 3) long-term renal SGK1 deletion results in lower BP in mutant compared with control mice; and 4) renal SGK1 indirectly regulates pulse pressure due to compensatory alterations in aldosterone levels.NEW & NOTEWORTHY Dysregulation of blood pressure (BP) circadian rhythm is associated with metabolic, cardiovascular, and kidney diseases. Our study provides experimental evidence demonstrating, for the first time, that renal tubule serum- and glucocorticoid-induced kinase 1 (SGK1) plays an essential role in inducing the BP surge. Inhibitors and activators of SGK1 signaling are parts of several therapeutic strategies. Our findings highlight the importance of the drug intake timing to be in phase with SGK1 function to avoid dysregulation of BP circadian rhythm.

Preliminary study on the relationship between biological rhythm changes and pregnancy complications during pregnancy

To study the characteristics of heart rate rhythm in pregnant women at different trimester of pregnancy, and to explore the relationship between the basic rhythm of heart rate and pregnancy complications. Thirteen pregnant women who were diagnosed with normal early pregnancy in the Reproductive Center of the Second Affiliated Hospital of Soochow University from June 2018 to December 2019 were prospectively selected. Personal files were created and the heart rate data of pregnancy women was collected 24 hours a day by wearable devices until delivery. Prenatal examination and pregnancy outcomes were surveyed at follow-up. The cosine analysis method and the designed statistical module were used to analyze the long-term rhythm of pregnant women's heart rate. The heart rate of pregnant women showed a significant rhythm at different gestational weeks. Compared with the gestational week of 12, the midline-estimating statistic of rhythm(MESOR) increased significantly at the gestational week of 28 and 32 (t=-2.751,P=0.013;t=-2.314,P=0.032).The phase of rhythm shifted from 14∶00 pm in the first trimester of pregnancy (12 weeks) to 16∶00 pm in the second trimester (24 weeks) (t=2.613,P=0.018) and returned to 14∶00 pm at the third trimester (32 weeks) (t=-2.176,P=0.046). Season had no significant effect on the changes of MESOR, amplitude and phase of maternal heart rate in the first trimester (t=-0.356,P=0.729;t=-0.777,P=0.464;t=-0.434,P=0.673), while season had no significant effect on the changes of MESOR, amplitude and phase in the third trimester (t=-0.663,P=0.532;t=-0.209,P=0.841;t=0.625,P=0.592). The heart rate of one pregnant woman with natural delivery had rhythm disorder from the start of labor to delivery. The heart rate of one pregnant woman with premature rupture of membranes showed rhythm disorder before and after the rupture of membranes, and smaller amplitude. Rhythm disturbance may play a suggestive role in preterm delivery and labor initiation. In conclusion, pregnancy may cause changes in the internal heart rate rhythm. Maternal internal rhythm disturbance may occur when delivery or premature rupture of membranes occurs. The heart rate rhythm of pregnant women may be related to some common complications of pregnancy such as premature rupture of membranes.

Association of intra-shift nap duration with heart rate variability in medical night shift workers.

Napping during night shifts effectively reduces disease risk and improves work performance, but few studies have investigated the association between napping and physiological changes, particularly in off-duty daily lives. Changes in the autonomic nervous system precede diseases like cardiovascular disease, diabetes, and obesity. Heart rate variability is a good indicator of autonomic nervous system. This study aimed to investigate the link between night shift nap durations and heart rate variability indices in the daily lives of medical workers. As indicators of chronic and long-term alterations, the circadian patterns of heart rate variability indices were evaluated. We recruited 146 medical workers with regular night shifts and divided them into four groups based on their self-reported nap durations. Heart rate variability circadian parameters (midline-estimating statistic of rhythm, amplitude, and acrophase) were obtained by obtaining 24-h electrocardiogram on a day without night shifts, plotting the data of the heart rate variability indices as a function of time, and fitting them into periodic cosine curves. Using clinical scales, depression, anxiety, stress, fatigue, and sleepiness were assessed. Linear regression analysis revealed a positive relationship between 61-120-min naps and 24-h, daytime, and night-time heart rate variability indices, and the parasympathetic activity oscillation amplitude (indexed by high-frequency power, the square root of the mean of the sum of squares of differences between adjacent normal intervals, standard deviation of short-term R-R-interval variability) within one circadian cycle. This study indicated that napping for 61-120 min during night shifts could benefit medical workers' health, providing physiological evidence to promote nap management.

Abstract 096: Adrenal-specific KO Of The Circadian Clock Protein Bmal1 Alters Blood Pressure Rhythm

BMAL1 is a core circadian clock protein that regulates most physiological functions, including blood pressure (BP). Global BMAL1 knockout (KO) male mice exhibit reduced, non-dipping BP and loss of diurnal rhythm of renal sodium (Na) excretion. Although, BP and renal Na excretion rhythm remained intact in kidney-specific BMAL1 KO male mice. The adrenal gland synthesizes hormones which influence BP rhythm and renal electrolyte handling. The role of adrenal BMAL1 in the regulation of BP and renal function remains unknown. The goal was to test the hypothesis that adrenal BMAL1 is required for normal circadian rhythms of BP and renal Na excretion. Adrenal-specific aldosterone synthase Cre positive (AS)-BMAL1 KO male mice ( n =5) and littermate Cre negative, floxed control (CNTL) male mice ( n =6) underwent a telemetry study to measure BP. Cosinor analysis was performed to assess BP rhythms. During telemetry recordings, mice were placed in metabolic cages for 5 days on a normal salt diet. The latter 3 days, 12 h urine samples were collected before each light-dark Zeitgeber (6AM and 6PM/ Zeitgeber Time (ZT)0 and ZT12) to measure night/day patterns in renal Na excretion. Kidneys were collected from a separate cohort of mice ( n =7-8/genotype) at ZT0 and ZT12 for gene expression analysis of key Na transporters. No BMAL1-dependent changes in the 24 h averages for BP were observed. Cosinor analysis revealed significant differences in BP rhythm, however. The period (time taken for a full circadian cycle, ~24 h) was significantly shortened for BP in AS-BMAL1 KO mice vs. CNTL (23 h 31 vs 24 h 16, p =0.01). Acrophase (the time at which BP peaks) was shifted ~2 hours later in KO mice (KO ZT17 h 38 vs CNTL ZT15 h 45, p =0.002). The MESOR (midline estimating statistic of rhythm) of BP remained similar between groups (KO 133.5 mmHg vs CNTL 132.7 mmHg, p =0.904). Day/night Na excretion was not different in AS-BMAL1 KO mice vs. CNTL (ANOVA interaction p =0.168). This was consistent with a lack of genotype effects on gene expression for NCC, α, β, or γ ENaC. Significant time of day effects were observed for all 4 genes (all with p <0.001). In conclusion, BMAL1 KO in the adrenal gland altered BP rhythm, with no changes in renal Na excretion. This work is the first to investigate the role of adrenal BMAL1 on BP regulation.

Association between circadian activity rhythms and mood episode relapse in bipolar disorder: a 12-month prospective cohort study

A significant proportion of patients with bipolar disorder experience mood episode relapses. We examined whether circadian activity rhythms were associated with mood episode relapses in patients with bipolar disorder. This prospective cohort study included outpatients with bipolar disorder who participated in a study titled “Association between the Pathology of Bipolar Disorder and Light Exposure in Daily Life (APPLE) cohort study.” The participants’ physical activity was objectively assessed using a wrist-worn accelerometer over 7 consecutive days for the baseline assessment and then at the 12-month follow-up for mood episode relapses. The levels and timing of the circadian activity rhythms were estimated using a cosinor analysis and a nonparametric circadian rhythm analysis. Of the 189 participants, 88 (46%) experienced mood episodes during follow-up. The Cox proportional hazards model adjusting for potential confounders showed that a robust circadian activity rhythm, including midline-estimating statistic of rhythm (MESOR) and amplitude by cosinor analysis and 10 consecutive hours with the highest amplitude values (M10) by the nonparametric circadian rhythm analysis, was significantly associated with a decrease in mood episode relapses (per counts/min, hazard ratio [95% confidence interval]: MESOR, 0.993 [0.988–0.997]; amplitude, 0.994 [0.988–0.999]; and M10, 0.996 [0.993–0.999]). A later timing of the circadian activity rhythm (M10 onset time) was significantly associated with an increase in the depressive episode relapses (per hour; 1.109 [1.001–1.215]). We observed significant associations between circadian activity rhythms and mood episode relapses in bipolar disorder.

Sex Differences in Rest-Activity Circadian Rhythm in Patients With Metabolic Syndrome.

Rest-Activity circadian Rhythm (RAR) can be used as a marker of the circadian timing system. Recent studies investigated the relationship between irregular circadian rhythms and cardiovascular risk factors such as hypertension, obesity, and dyslipidemia. These factors are related to the Metabolic Syndrome (MS), a clustering of metabolic risk factors that increases the risk of several cardiovascular and metabolic diseases. This cross-sectional analysis aimed to explore the RAR characteristics by actigraphy in subjects with MS, particularly in relation to sex and MS parameters, using parametric and non-parametric analyses. Distinguishing the characteristics of RAR based on sex could prove useful as a tool to improve the daily level of activity and set up customized activity programs based on each person’s circadian activity profile. This study showed that female participants exhibited higher values than male participants in the Midline Estimating Statistic of Rhythm (MESOR) (243.3 ± 20.0 vs 197.6 ± 17.9 activity count), Amplitude (184.5 ± 18.5 vs 144.2 ± 17.2 activity count), which measures half of the extent of the rhythmic variation in a cycle, and the most active 10-h period (M10) (379.08 ± 16.43 vs 295.13 ± 12.88 activity count). All these parameters are indicative of a higher daily activity level in women. Female participants also had lower Intradaily Variability (IV) than male participants (0.75 ± 0.03 vs 0.85 ± 0.03 activity count), which indicates a more stable and less fragmented RAR. These preliminary data provide the first experimental evidence of a difference in RAR parameters between male and female people with MS.

The onset of pediatric refractory status epilepticus is not distributed uniformly during the day

PurposeTo evaluate whether the onset of pediatric refractory status epilepticus (rSE) is related to time of day. MethodWe analyzed the time of day for the onset of rSE in this prospective observational study performed from June 2011 to May 2019 in pediatric patients (1 month to 21 years of age). We evaluated the temporal distribution of pediatric rSE utilizing a cosinor analysis. We calculated the midline estimating statistic of rhythm (MESOR) and amplitude. MESOR is the estimated mean number of rSE episodes per hour if they were evenly distributed. Amplitude is the difference between MESOR and maximum rSE episodes/hour, or between MESOR and minimum rSE episodes/hour. We also evaluated the temporal distribution of time to treatment. ResultsWe analyzed 368 patients (58% males) with a median (p25 – p75) age of 4.2 (1.3–9.7) years. The MESOR was 15.3 (95% CI: 13.9–16.8) and the amplitude was 3.2 (95% CI: 1.1–5.3), p = 0.0024, demonstrating that the distribution is not uniform, but better described as varying throughout the day with a peak in the morning (11am–12 pm) and trough at night (11 pm–12 am). The duration from rSE onset to application of the first non-benzodiazepine antiseizure medication peaked during the early morning (2am–3 am) with a minimum during the afternoon (2 pm–3 pm) (p = 0.0179). ConclusionsThe distribution of rSE onset is not uniform during the day. rSE onset shows a 24-h distribution with a peak in the mid-morning (11am–12 pm) and a trough at night (11 pm-12am).

Rest-activity circadian rhythm in breast cancer survivors at 5 years after the primary diagnosis

ABSTRACTRest-activity circadian rhythm (RAR) is a marker of the circadian timing system. Particular attention has been given to RAR characteristics in cancer diseases. Specifically, alterations of RAR parameters have been found, at different stages of clinical pathway, in breast cancer (BC) patients. No studies to date have analyzed RAR alterations in breast cancer survivors several years after the diagnosis. The aim of this study was to determine RAR by actigraphy in a population of BC survivors at 5 years after the primary diagnosis, and to compare their RAR characteristics with healthy controls. The study sample was 28 women: 15 BC survivors at 5 years from the primary diagnosis (BC-group) and 13 healthy controls (Ctrl-group), matched for age and body mass index. All participants have been monitored for 7 days by actigraphy to evaluate RAR. A statistically significant circadian rhythm (T = 24) was found in all 28 subjects (p < .001). The group analysis revealed a significant RAR both in BC- and Ctrl-group (p < .001). The acrophase was not different between the BC- and Ctrl-group (15:09 vs. 15:01 hr:min in BC- and Ctrl-group, respectively). In contrast, the MESOR (Midline Estimating Statistic of Rhythm) and the amplitude were lower in the BC-group with respect to the Ctrl-group. Indeed, the MESOR was 192.0 vs. 276.4 activity counts in BC- and Ctrl-group, respectively (p < .001), while the amplitude was 167.0 vs. 222.6 activity counts in BC- and Ctrl-group, respectively (p < .001). These results provide the first experimental evidence of alterations in RAR parameters in BC survivors at 5 years after the primary diagnosis. Larger studies with a prospective design are needed to assess the role of RAR in the quality of life and prognosis in BC survivors.

Circadian variations in electric current responses at ryodoraku points across the waking stage: A prospective observational study.

Human body undergoes the 24-hour daily rhythm in response primarily to light and darkness. The circadian rhythms of biomarkers reflect bodily conditions including the prognosis of some pathologies. As a sensitive index of sympathetic nervous response (SNR), electrodermal activity (EDA) is a recent research topic in healthcare industry as a noninvasive and easy-access biosignal. The EDA response at Ryodoraku points (RPs) is of potential clinical usage in relation to SNR and meridian theory, but still remains in its primitive development stage.In this study, the 24-hour variations of EDA for 14 hospitalized participants were monitored over 3 days using a Ryodoraku device, and a circadian model of EDA was constructed using a cosinor analysis based on the linear mixed effect model.As a result, EDA at every RP showed a circadian cycle with its value the lowest in the morning and increased gradually until the late afternoon, and monotonically decreased again until the next morning. Circadian variations were observed in EDAs of all 12 RPs. However, Ryodoraku-specific features were not detected. Midline estimating statistic of rhythm (MESOR) values in men and young group were higher than in women and old group, and cosinor analysis showed significant circadian rhythms, especially for men and young groups. Especially, circadian variation in EDA in the young group went above 35% of the MESOR value.It implies that the circadian rhythm should be considered for the Ryodoraku analysis to examine bodily conditions or the prognosis of some pathologies.

Seasonal differences in rhythmicity of salivary cortisol in healthy adults.

The existence of seasonal changes in secretion of stress hormones and inflammatory mediators by humans is not certain. Here, we aimed to determine whether concentrations of cortisol and IL-6 displayed seasonal rhythmicity. The study was performed in Poznań, Poland (52°N, 16°E) in 7 healthy female volunteers (age 22.6 ± 0.8 yr). Samples of whole mixed unstimulated saliva were collected in winter (February) and summer (June) at 2-h intervals over a 24-h period and analyzed for cortisol and IL-6 by immunoassays. During each season, the subjects answered questionnaires related to their sleeping habits, food intake, physical activity, and perceived seasonality. It turned out that salivary concentrations of cortisol followed a daily rhythm both in winter and summer, as determined by a cosine analysis. However, compared with the winter season, a midline-estimating statistic of rhythm in the summer was significantly higher. Moreover, the rhythm acrophase occurred ~4 h later in the summer than in the winter, whereas the amplitudes did not differ. These fluctuations did not correspond to sleeping habits, food and fluid intake, physical exercise, and the self-assessed chronotype. However, the individuals with higher scores on the seasonal affective disorder scale showed a tendency toward lower relative cortisol amplitude in the summer. In contrast to cortisol, salivary IL-6 concentration did not display daily rhythmicity, and its concentrations did not differ significantly between the seasons. In conclusion, in the summer, cortisol level in saliva is elevated, and its circadian pattern of secretion is shifted. The causes for these alterations do not seem to be related to lifestyle and thus remain to be established.

Circadian periodicity and effect of gender, age, diet and smoking on circulating plasma lipid peroxides and antioxidant enzymes in healthy Indians of different age groups

ABSTRACT This study aims at assessing circadian rhythm characteristics of oxidants and antioxidants, testing for any effect of gender, age, diet and smoking status. Blood samples from clinically healthy Indians (103 males and 59 females, 7–75 years of age) were collected at 6-hour intervals for 24 hours for determination of MDA, SOD, CAT, GPx and GR. Data were analyzed by the single and population-mean cosinor to estimate circadian rhythm characteristics. The latter were further analyzed by multi-factor analysis of variance. A marked circadian rhythm was documented for all variables. Its parameters were found to undergo marked changes as a function of age. Males differed from females in terms of the rhythm-adjusted mean (MESOR) of CAT and GPx and of the 24-hour amplitude of GR. The MESOR of GPx differed between vegetarians and omnivores. Smoking status affected the MESOR of MDA and CAT and the 24-hour amplitude of CAT. As oxidative stress is being reported for most diseases, the mapping of circadian rhythms in oxidant and antioxidant enzymes in health may help refine reference values, thereby allowing the early detection of pathophysiological conditions, prompting the early institution of treatment. Abbreviations CAT: Catalase; FRAP: Ferric Reducing Antioxidant Power; GPx: Glutathione Peroxidase; GR: Glutathione Reductase; GSH: Glutathione; MDA: Malondialdehyde; MESOR: Midline Estimating Statistic Of Rhythm; ROS: Reactive Oxygen Species; SCN: Suprachiasmatic Nuclei; SOD: Superoxide Dismutase; TBARs: Thiobarbituric acid reactive substances; XPA: Xeroderma Pigmentosum, Complementation Group A (DNA Damage Recognition And Repair Factor)

Effect of gender, age, diet and smoking status on chronomics of circulating plasma lipid components in healthy Indians

BackgroundCirculating lipid components were studied under near-normal tropical conditions (around Lucknow) in 162 healthy volunteers — mostly medical students, staff members and members of their families (103 males and 59 females; 7 to 75y), subdivided into 4 age groups: A (7–20y; N=42), B (21–40y; N=60), C (41–60y; N=35) and D (61–75y; N=25). MethodsBlood samples were collected from each subject every 6h for 24h (4 samples). Plasma was separated and total cholesterol, high-density-lipoprotein (HDL) cholesterol, phospholipids and total lipids were measured spectrophotometrically. Data from each subject were analyzed by cosinor. We examined by multiple-analysis of variance how the MESOR (Midline Estimating Statistic Of Rhythm, a rhythm-adjusted mean) and the circadian amplitude of these variables is affected by gender, age, diet (vegetarian vs. omnivore), and smoking status. ResultsIn addition to effects of gender and age, diet and smoking were found to affect the MESOR of circulating plasma lipid components in healthy Indians residing in northern India. Age also affected the circadian amplitude of these variables. ConclusionThese results indicate the possibility of using non-pharmacological interventions to improve a patient's metabolic profile before prescribing medication under near normal tropical conditions. They also add information that may help refine cut-off values in the light of factors shown here to affect blood lipids.

Chronobiological assessment of habitual physical activity in humans in Western Siberia

The concept of typological variability of physiological individuality was a methodological basis for chrono-physiological assessment of habitual physical activity (HPA) and heart rate (HR) in individuals with different functional types of constitution (FTC) (low HPA (FTC-1), medium HPA (FTC-2), and high HPA (FTC-3)) living at different latitudes of West Siberia (Tyumen, 57°09’N; Khanty–Mansi Autonomous Okrug (KhMAO)–Yugra, 61°00’N; and Yamal–Nenets Autonomous Okrug (YaNAO), 63°12’N). The typical chronostructure of the circadian rhythm of HPA and HR was established for each FTC under the conditions of both mid-latitude (Tyumen) and northern regions. The regional differences were determined too. Compared to the mid-latitude parameters, the chrono-physiological assessment of typological variability of HPA and HR in FTC-1, FTC-2 and FTC-3 subjects living under the climatic and geographical conditions of KhMAO–Yugra and YaNAO in each respective group demonstrated a decrease in the midline-estimating statistic of rhythm (MESOR) and energy intensity of the circadian rhythm, an increase in the proportion of ultradian rhythms, differences in the time of HPA and HR acrophases, a decrease in synchronization and coherence indices, as well as a higher coefficient of the number of heart beats per locomotion and a lower circadian index. All of the above parameters of northerners with each FTC, with regard for the general principles of modern approaches, are not pathologies but rather regional characteristics that should be taken into consideration in the assessment of general state of health and prenosological diagnostics; they were the basis for using chronoprevention and time correction of reduced physical activity.

Circadian rhythm disruption was observed in hand, foot, and mouth disease patients.

Hand, foot, and mouth disease (HFMD) with central nerve system complications may rapidly progress to fulminated cardiorespiratory failure, with higher mortality and worse prognosis. It has been reported that circadian rhythms of heart rate (HR) and respiratory rate are useful in predicting prognosis of severe cardiovascular and neurological diseases. The present study aims to investigate the characteristics of the circadian rhythms of HR, respiratory rate, and temperature in HFMD patients with neurological complications.Hospitalized HFMD patients including 33 common cases (common group), 61 severe cases (severe group), and 9 critical cases (critical group) were contrasted retrospectively. Their HR, respiratory rate, and temperatures were measured every 4 hours during the first 48-hour in the hospital. Data were analyzed with the least-squares fit of a 24-hour cosine function by the single cosinor and population-mean cosinor method.Results of population-mean cosinor analysis demonstrated that the circadian rhythm of HR, respiratory rate, and temperature was present in the common and severe group, but absent in the critical group. The midline-estimating statistic of rhythm (MESOR) (P = 0.016) and acrophase (P < 0.01) of temperature and respiratory rate were significantly different among 3 groups. But no statistical difference of amplitude in temperature and respiratory rate was observed among the 3 groups (P = 0.14). MESOR value of HR (P < 0.001) was significantly different in 3 groups. However, amplitude and acrophase revealed no statistical difference in circadian characteristics of HR among 3 groups. Compared with the common group, the MESOR of temperature and respiratory rate was significantly higher, and acrophase of temperature and respiratory rate was 2 hours ahead in the severe group, critical HFMD patients lost their population-circadian rhythm of temperature, HR, and respiratory rate. The high values of temperature and respiratory rate for the common group were concentrated between 3 and 9 pm, whereas those for the severe group were more dispersive. And the high values for the critical group were equally distributed in 24 hours of the day.Circadian rhythm of patients’ temperature in the common group was the same as the normal rhythm of human body temperature. Circadian rhythm of patients’ temperature, HR and respiratory rate in 3 groups were significantly different.

Adolescent and Adult Circadian Rhythm Activity Modulated Differently Following Chronic Methylphenidate Administration

Methylphenidate is one of the most common pharmaceutical treatments for Attention Deficit Hyperactive Disorder (ADHD). It is also gaining popularity as a cognitive enhancement and recreational substance. The current study assesses the long-term effects of methylphenidate (MPD) on the circadian rhythm activity pattern of adolescent and adult male Sprague-Dawley (SD) rats. The experiment lasted for 11 days of non-stop recording, the evaluation was divided into 4 phases: acute, induction, washout, and expression phases. Circadian rhythm changes in each phase were compared between the adolescent and adult rats using the following parameters MESOR (midline estimating statistic of rhythm) or average activity, amplitude (distance from MESOR to the peak activity), and acrophase (time at which peak amplitude occurs). Overall, more significant changes in circadian rhythm pattern among adult rats were observed as compared to adolescent rats. As the circadian rhythm governs the diurnal locomotor activity pattern, changes in the locomotor pattern induced by chronic treatment MPD indicate that the drug exerts a long-term effect on the circadian rhythm.

Ambulatory Blood Pressure Monitoring and Circadian Rhythm of Blood Pressure in Diabetes Mellitus

Systolic and diastolic blood pressures display a circadian rhythmicity that can be assessed by 24-hour ambulatory blood pressure monitoring and analysed using the cosinor procedure. Altered characteristics to the circadian rhythm of blood pressure, which may result in adverse health outcomes, have been observed in both prediabetes and diabetes. We have investigated the circadian variability of blood pressure in patients with type 1 and type 2 diabetes. Chronobiologically interpreted ambulatory blood pressure monitoring uncovered not only midline estimating statistic of rhythm (MESOR)-hypertension and circadian hyper-amplitude-tension, but also circadian ecphasia (an odd timing of the daily blood pressure swing). Diastolic blood pressure acrophases were found to be phase shifted to earlier along the time axis only in patients with diabetes, but not in those with essential hypertension. Several mechanisms, from changes in nutrient-dependent signalling pathways to diabetic autonomic neuropathy, can contribute to alterations of circadian time structures in diabetic people. The chronology of blood pressure changes in animal models of diabetes and hypertension suggests that a chronobiological approach to the diagnosis of blood pressure disorders could offer advantages, but longitudinal studies in humans are needed to determine its potential relevance in hypertension associated with diabetes.

24‐hour intraocular pressure rhythm in young healthy subjects evaluated with continuous monitoring using contact lens sensor

AbstractPurpose To evaluate 24‐h intraocular pressure (IOP) rhythm reproducibility during repeated continuous 24‐h IOP monitoring with non‐contact tonometry (NCT) and a contact lens sensor (CLS) in healthy subjects.Methods Twelve young healthy subjects were housed in a sleep laboratory and underwent four 24‐h sessions of IOP measurements over a 6‐month period. After randomized attribution, the IOP of the first eye was continuously monitored using the CLS Sensimed TriggerFish® and the IOP of the fellow eye was measured hourly using the Pulsair Intellipuff® non‐contact tonometer. A nonlinear least‐squares dual harmonic regression analysis was used to model the 24‐h IOP rhythm. Comparison of acrophase, bathyphase, amplitude, the midline estimating statistic of rhythm (MESOR), IOP values, IOP changes and agreement were evaluated in the two tonometry methods.Results A significant nyctohemeral IOP rhythm was found in 31 out of 36 sessions (86%) using NCT and in all sessions (100%) using CLS. Hourly awakening during NCT IOP measurements did not significantly change the mean phases of the 24‐h IOP pattern evaluated using CLS in the contralateral eye. Throughout the sessions, intraclass correlation coefficients (ICCs) of the CLS acrophase (0.6 [0–0.9]; p=0.03), CLS bathyphase (0.7 [0.1–0.9]; p=0.01), NCT amplitude (0.7 [0.1–0.9]; p=0.01) and NCT MESOR (0.9 [0.9–1]; p&lt;0.01) were significant.Conclusion The CLS is an accurate and reproducible method to characterize the nyctohemeral IOP rhythm in healthy subjects but does not allow to estimate the IOP value in millimeters of mercury corresponding to the relative variation of the electrical signal measured.

Three-time feeding does not influence insulin daily rhythm in horses

The aim of the present study was to investigate the influence of three-time feeding on insulin daily rhythm in horses. At this purpose, five clinically healthy Italian saddle horses were housed under natural photoperiod (L/D) followed by constant darkness (D/D). Horses were fed three times a day (6:00; 12:00; 18:00) with hay and a mix of cereals. Blood samples were collected every 3 h over 48-h period (24 h during L/D and 24 h during D/D). On each serum sample insulin concentration was assessed. Two-way for repeated measures analysis of variance (ANOVA) was applied to investigate statistically differences due to time of day and experimental conditions. Cosinor rhythmometry was applied to investigate daily rhythmicity in the two experimental periods. Our results showed a significant effect of time of day and experimental conditions on serum insulin concentrations. Daily rhythmicity of insulin serum concentrations was observed during L/D and D/D. Statistically differences in MESOR (Midline-Estimating Statistic of Rhythm), amplitude and acrophases were observed between L/D and D/D. MESOR and amplitude statistically decreased in D/D respect to L/D, and acrophase was postponed in L/D respect to D/D. Robustness of rhythm did not change between the two experimental period. In conclusion, we can hypothesised that the daily rhythm of insulin in horses is endogenously generated; and that during the routine management of the stabled horses providing feed three times a day favourite the physiological secretion of insulin in this species.

Clock Gene Expression in the Liver of Streptozotocin-induced and Spontaneous Type 1 Diabetic Rats

Several investigations have shown a relation between diabetes and alterations of the liver circadian clock. We investigated the diurnal expression of clock genes and clock-controlled genes (CCGs) in 3-hour intervals for a 24-h period in the livers of male streptozotocin (STZ)-treated rats, male spontaneous type 1 diabetic LEW.1AR1-iddm (Iddm) rats, and Iddm rats treated for 10 days with insulin. Hepatic mRNA was extracted, and the relative expression of clock genes (Per1, Per2, Bmal1, Clock, Cry1), as well as CCGs (Dbp, E4bp4, RevErbα, Rorα, Pparγ), was analyzed by reverse transcription followed by real-time polymerase chain reaction. Diabetic STZ and Iddm rats, as well as insulin-substituted Iddm rats, exhibited a significant diurnal expression pattern of clock genes as determined by Cosinor analysis; however, the MESOR (midline estimating statistic of rhythm) of Bmal1, Per2, and Clock transcript expression was altered in Iddm and insulin-substituted Iddm rats. The hepatic expression of the CCGs Dbp and RevErbα revealed a diurnal rhythm in all investigated groups. Insulin administration to Iddm rats normalized the enhanced MESOR in the expression of Dbp, RevErbα, and E4bp4 to the levels of normoglycemic controls. Cosinor analysis indicated no diurnal rhythm of Pparγ expression in the livers of diabetic STZ or Iddm rats or in those of insulin-substituted Iddm rats. Also, insulin substitution could not reverse the decreased MESOR of Pparγ expression in Iddm rats. In consequence of the diabetic disease, changes in the expression of clock genes and CCGs suggest alterations in the hepatic peripheral clock mechanism.

24-Hour Intraocular Pressure of Young Healthy Humans in Supine Position: Rhythm and Reproducibility

We evaluated the supine 24-hour IOP rhythm reproducibility over 6 weeks in healthy humans. Six healthy young male subjects underwent six 24-hour sessions of IOP measurements over a 6-week period. Subjects were housed in a sleep laboratory in a constant controlled supine position and in a strictly controlled environment. IOP was measured hourly using a pneumatonometer. A nonlinear least-squares dual harmonic regression analysis was used to model the 24-hour IOP rhythm. The intra- and intersubject variability of acrophase, bathyphase, amplitude, and IOP values were evaluated. A significant nyctohemeral IOP rhythm was noted in 30 of 36 (83%) sessions. Mean nocturnal IOP was significantly higher than diurnal IOP (20.1 0.2 MM HG [SD] VS. 18.8 0.1 MM HG, P 0.001) in all subjects. Amplitudes were not statistically different among subjects (P = 0.52). IN contrast, acrophase and bathyphase were statistically different (P 0.05). Intrasubject homogeneity of distribution over time of the acrophase and bathyphase was significant in 3 of 6 and 4 of 6 subjects, respectively. Intraclass correlation coefficients of midline estimating statistic of rhythm (MESOR) and IOP values AT 2: 00, 3:00, 4:00, 10:00, and 11:00 AM, and 2:00 PM showed fair to good agreement among sessions. In a constant supine position, all subjects exhibited a nyctohemeral IOP rhythm present at an average rate of 80% of all sessions. With the currently available methods of tonometry, intrasubject reproducibility of rhythmic parameters and IOP values is limited. IOP values in the morning and IOP MESOR were the most reproducible parameters among the six visits.