Chronotype and lipid metabolism in Arctic Sojourn Workers.

This study relates answers to the Munich Chronotype Questionnaire (MCTQ) and Pittsburgh Sleep Quality Index (PSQI) from Arctic Sojourn Workers (ASW) of Yamburg Settlement, 68° Latitude North, 75° Longitude East (n = 180; mean age ± SD; range: 49.2 ± 7.8; 25-66 y; 45% women) to Arctic Sojourn Work Experience (ASWE), age and health status. Chronotype, Mid Sleep on Free Days sleep corrected (MSFsc) and sleep characteristics of ASW were compared to those of age-matched Tyumen Residents (TR, n = 270; mean age ± SD; range: 48.4 ± 8.4; 25-69 y; 48% women), 57° Latitude North, 65° Longitude East. ASW have earlier MSFsc than TR (70 min in men, p < 0.0001, and 45 min in women, p < 0.0001). Unlike TR, their MSFsc was not associated with age (r = 0.037; p = 0.627) and was linked to a larger Social Jet Lag (+21 min in men; p = 0.003, and +18 min in women; p = 0.003). These differences were not due to outdoor light exposure (OLE): OLE on work (OLEw) or free (OLEf) days was not significantly different between ASW and TR in men and was significantly less in ASW than in TR women (OLEw: -31 min; p < 0.001; OLEf: -24 min; p = 0.036). ASWE, but not age, was associated with compromised lipid metabolism in men. After accounting for multiple testing, when corrected for age and sex, higher triglycerides to high-density lipoprotein ratio, TG/HDL correlated with ASWE (r = 0.271, p < 0.05). In men, greater SJL was associated with lower HDL (r = -0.204; p = 0.043). Worse proxies of metabolic health were related to unfavorable components of the Pittsburgh Sleep Quality Index in ASW. Higher OLE on free days was associated with lower systolic (b = -0.210; p < 0.05) and diastolic (b = -0.240; p < 0.05) blood pressure.

Methods for assessing change in brain plasticity at night and psychological resilience during daytime between repeated long-duration space missions.

This study was designed to examine the feasibility of analyzing heart rate variability (HRV) data from repeat-flier astronauts at matching days on two separate missions to assess any effect of repeated missions on brain plasticity and psychological resilience, as conjectured by Demertzi. As an example, on the second mission of a healthy astronaut studied about 20 days after launch, sleep duration lengthened, sleep quality improved, and spectral power (ms2) co-varying with activity of the salience network (SN) increased at night. HF-component (0.15-0.50 Hz) increased by 61.55%, and HF-band (0.30-0.40 Hz) by 92.60%. Spectral power of HRV indices during daytime, which correlate negatively with psychological resilience, decreased, HF-component by 22.18% and HF-band by 37.26%. LF-component and LF-band, reflecting activity of the default mode network, did not change significantly. During the second mission, 24-h acrophases of HRV endpoints did not change but the 12-h acrophase of TF-HRV did (P < 0.0001), perhaps consolidating the circadian system to help adapt to space by taking advantage of brain plasticity at night and psychological resilience during daytime. While this N-of-1 study prevents drawing definitive conclusions, the methodology used herein to monitor markers of brain plasticity could pave the way for further studies that could add to the present results.

Appropriate Circadian-Circasemidian Coupling Protects Blood Pressure from Morning Surge and Promotes Human Resilience and Wellbeing.

Background: Blood pressure (BP) variability is involved in the appraisal of threat and safety, and can serve as a potential marker of psychological resilience against stress. The relationship between biological rhythms of BP and resilience was cross-sectionally assessed by 7-day/24-hour chronobiologic screening in a rural Japanese community (Tosa), with focus on the 12-hour component and the "circadian-circasemidian coupling" of systolic (S) BP. Subjects and Methods: Tosa residents (N = 239, 147 women, 23-74 years), free of anti-hypertensive medication, completed 7-day/24-hour ambulatory BP monitoring. The circadian-circasemidian coupling was determined individually by computing the difference between the circadian phase and the circasemidian morning-phase of SBP. Participants were classified into three groups: those with a short coupling interval of about 4.5 hours (Group A), those with an intermediate coupling interval of about 6.0 hours (Group B), and those with a long coupling interval of about 8.0 hours (Group C). Results: Residents of Group B who showed optimal circadian-circasemidian coordination had less pronounced morning and evening SBP surges, as compared to residents of Group A (10.82 vs 14.29 mmHg, P < 0.0001) and Group C (11.86 vs 15.21 mmHg, P < 0.0001), respectively. The incidence of morning or evening SBP surge was less in Group B than in Group A (P < 0.0001) or Group C (P < 0.0001). Group B residents showed highest measures of wellbeing and psychological resilience, assessed by good relation with friends (P < 0.05), life satisfaction (P < 0.05), and subjective happiness (P < 0.05). A disturbed circadian-circasemidian coupling was associated with elevated BP, dyslipidemia, arteriosclerosis and a depressive mood. Conclusion: The circadian-circasemidian coupling of SBP could serve as a new biomarker in clinical practice to guide precision medicine interventions aimed at achieving properly timed rhythms, and thereby resilience and wellbeing.

Depression scores are associated with retinal ganglion cells loss.

BACKGROUND: Light is a known factor affecting mood and the circadian system. Light deficit is linked to deteriorated transduction of photic information to the brain, and reduced amplitude of the perceived circadian light signaling. Retinal ganglion cells (RGCs) loss due to advanced glaucoma can be a factor compromising light perception, with consequences for circadian rhythms, sleep and mood. This study aimed to estimate associations of RGCs loss with a depression score by multiple regression, accounting for other features of glaucoma. METHODS: One hundred and fifteen patients diagnosed with primary open-angle glaucoma completed the Beck Depression Inventory II questionnaire. The damage to their RGCs was assessed by high-definition optical coherence tomography (HD-OCT) and their function by pattern electroretinogram (PERG). On fifteen of these patients, 24-h salivary melatonin patterns were determined under light-controlled laboratory conditions, and analysis of eight clock related gene polymorphisms was performed. RESULTS: Backward stepwise multiple regression revealed that the BDI score was the strongest factor that was most closely associated with the HD-OCT-based percentage of global RGCs loss (standardized coefficient, b* = 0.784, p < 0.001), surpassing other related factors, including age, intraocular pressure, visual field loss, and PERG amplitude. A high BDI score was associated with the GNß3 825C > T polymorphism (dbSNP rs5443). LIMITATIONS: This study did not specifically address damage to intrinsically photoreceptive RGCs. The gene study is based on a limited number of volunteers. CONCLUSIONS: Depression scores are strongly associated with RGCs loss, increasing abruptly above a threshold of 15 %, supporting the hypothesis that RGCs loss in advanced glaucoma may affect non-visual photic transduction and lead to mood disturbances.

Possibilities of Interpreting the Night-to-Day Ratio Specified by 24-Hour Blood Pressure Monitoring.

Aim: Specify the risk rate of incorrect patient classification based on the night-to-day ratio specification from singular 24-h ABPM in comparison to the results of 7-day ABPM monitoring. Materials and Methods: 1197 24 h cycles were enrolled in 171 subjects in the study and divided into 4 groups: group 1 (40 healthy men and women without exercise), group 2 (40 healthy exercise-training men and women), group 3 (40 patients with ischemic coronary artery disease without exercise), and group 4 (51 patients with ischemic coronary artery disease following cardiovascular rehabilitation). The subject of the evaluation was the percentage rate of incorrect subject classification (dipper, nondipper, extreme dipper, and riser) based on the mean blood pressure values for 7 days and from seven independent 24-hour cycles (the mean value mode). Results: In the case of the individuals included in the monitored groups, the mean night-to-day ratio-based (mode for the 7 days versus the individual days of 24-hour monitoring) classification accordance ranged between 59% and 62%. Only in singular cases did the accordance reach 0% or 100%. The accordance size was not dependent on the health or cardiovascular disease (p < 0.594; 56% vs. 54%) or physical activity (p < 0.833; 55% vs. 54%) of the monitored individuals. Conclusion: The specification of the night-to-day ratio of each individual for each day of the 7-day ABPM monitoring would be the most convenient option. In many patients, diagnosing could thus be based on the most frequently occurring values (mode specification).

Blue Light and Temperature Actigraphy Measures Predicting Metabolic Health Are Linked to Melatonin Receptor Polymorphism.

This study explores the relationship between the light features of the Arctic spring equinox and circadian rhythms, sleep and metabolic health. Residents (N = 62) provided week-long actigraphy measures, including light exposure, which were related to body mass index (BMI), leptin and cortisol. Lower wrist temperature (wT) and higher evening blue light exposure (BLE), expressed as a novel index, the nocturnal excess index (NEIbl), were the most sensitive actigraphy measures associated with BMI. A higher BMI was linked to nocturnal BLE within distinct time windows. These associations were present specifically in carriers of the MTNR1B rs10830963 G-allele. A larger wake-after-sleep onset (WASO), smaller 24 h amplitude and earlier phase of the activity rhythm were associated with higher leptin. Higher cortisol was associated with an earlier M10 onset of BLE and with our other novel index, the Daylight Deficit Index of blue light, DDIbl. We also found sex-, age- and population-dependent differences in the parametric and non-parametric indices of BLE, wT and physical activity, while there were no differences in any sleep characteristics. Overall, this study determined sensitive actigraphy markers of light exposure and wT predictive of metabolic health and showed that these markers are linked to melatonin receptor polymorphism.

Unconscious mind activates central cardiovascular network and promotes adaptation to microgravity possibly anti-aging during 1-year-long spaceflight.

The intrinsic cardiovascular regulatory system (ß, 0.00013-0.02 Hz) did not adapt to microgravity after a 6-month spaceflight. The infraslow oscillation (ISO, 0.01-0.10 Hz) coordinating brain dynamics via thalamic astrocytes plays a key role in the adaptation to novel environments. We investigate the adaptive process of a healthy astronaut during a 12-month-long spaceflight by analyzing heart rate variability (HRV) in the LF (0.01-0.05 Hz) and MF1 (0.05-0.10 Hz) bands for two consecutive days on four occasions: before launch, at 1-month (ISS01) and 11-month (ISS02) in space, and after return to Earth. Alteration of ß during ISS01 improved during ISS02 (P = 0.0167). During ISS01, LF and MF1 bands, reflecting default mode network (DMN) activity, started to increase at night (by 43.1% and 32.0%, respectively), when suprachiasmatic astrocytes are most active, followed by a 25.9% increase in MF1-band throughout the entire day during ISS02, larger at night (47.4%) than during daytime. Magnetic declination correlated positively with ß during ISS01 (r = 0.6706, P < 0.0001) and ISS02 (r = 0.3958, P = 0.0095). Magnetic fluctuations may affect suprachiasmatic astrocytes, and the DMN involving ISOs and thalamic astrocytes may then be activated, first at night, then during the entire day, a mechanism that could perhaps promote an anti-aging effect noted in other investigations.

Pre-heart failure at 2D- and 3D-speckle tracking echocardiography: A comprehensive review.

Chronic heart failure (CHF) has different stages and includes pre-HF (PHF), a state of high risk of developing myocardial dysfunction and advanced CHF. Some major behavioral risk factors of PHF might predispose to biological risk factors such as obesity, diabetes mellitus, dyslipidemia, hypertension, myocardial infarction, and cardiomyopathy. These risk factors damage the myocytes leading to fibrosis, apoptosis, cardiac hypertrophy, along with alterations in cardiomyocyte' size and shape. A condition of physiological subcellular remodeling resulting into a pathological state might be developed, conducting to PHF. Both PHF and heart failure (HF) are associated with the activation of phospholipases and protease, mitochondrial dysfunction, oxidative stress and development of intra-cellular free Ca2+  [Ca2+ ]i overloading to an elevation in diastolic [Ca2+ ]i . Simultaneously, cardiac gene expression is activated leading to further molecular, structural and biochemical changes of the myocardium. The sub-cellular remodeling may be intimately involved in the transition of cardiac hypertrophy to heart failure. 2D- and 3D-speckle tracking echocardiography (STE) have been used to quantify regional alterations of longitudinal strain and area strain, through their polar projection, which permits a further assessment of both sites and degrees of myocardial damage. The examination of strain can identify sub-clinical cardiac dysfunction or cardiomyocyte remodeling. During remodeling of the myocardium cardiac strain is attenuated, therefore it is an indicator of disease assessment.

Astronauts well-being and possibly anti-aging improved during long-duration spaceflight.

This study assesses how circadian rhythms of heart rate (HR), HR variability (HRV) and activity change during long-term missions in space and how they relate to sleep quality. Ambulatory 48-h ECG and 96-h actigraphy were performed four times on ten healthy astronauts (44.7 ± 6.9 years; 9 men): 120.4 ± 43.7 days (Before) launch; 21.1 ± 2.5 days (ISS01) and 143.0 ± 27.1 days (ISS02) after launch; and 86.6 ± 40.6 days (After) return to Earth. Sleep quality was determined by sleep-related changes in activity, RR-intervals, HRV HF- and VLF-components and LF-band. The circadian amplitude of HR (HR-A) was larger in space (ISS01: 12.54, P = 0.0099; ISS02: 12.77, P = 0.0364) than on Earth (Before: 10.90; After: 10.55 bpm). Sleep duration in space (ISS01/ISS02) increased in 3 (Group A, from 370.7 to 388.0/413.0 min) and decreased in 7 (Group B, from 454.0 to 408.9/381.6 min) astronauts. Sleep quality improved in Group B from 7.07 to 8.36 (ISS01) and 9.36 (ISS02, P = 0.0001). Sleep-related parasympathetic activity increased from 55.2% to 74.8% (pNN50, P = 0.0010) (ISS02). HR-A correlated with the 24-h (r = 0.8110, P = 0.0044), 12-h (r = 0.6963, P = 0.0253), and 48-h (r = 0.6921, P = 0.0266) amplitudes of the magnetic declination index. These findings suggest associations of mission duration with increased well-being and anti-aging benefitting from magnetic fluctuations.

Applications of cosinor rhythmometry in pharmacology.

Study design and data analysis are two important aspects relevant to chronopharmacometrics. Blunders can be avoided by recognizing that most physiological variables are circadian periodic. Both ill health and treatment can affect the amplitude, phase, and/or period of circadian (and other) rhythms, in addition to their mean. The involvement of clock genes in molecular pathways related to important physiological systems underlies the bidirectional relationship often seen between circadian rhythm disruption and disease risk. Circadian rhythm characteristics of marker rhythms interpreted in the light of chronobiologic reference values represent important diagnostic tools. A set of cosinor-related programs is presented. They include the least squares fit of multiple-frequency cosine functions to model the time structure of individual records; a cosinor-based spectral analysis to detect periodic signals; the population-mean cosinor to generalize inferences; the chronobiologic serial section to follow the time course of changing rhythm parameters over time; and parameter tests to assess differences among populations. Relative merits of other available cosinor and non-parametric algorithms are reviewed. Parameter tests to compare individual records and a self-starting cumulative sum (CUSUM) make personalized chronotherapy possible, where the treatment of each patient relies on an N-of-1 design. Methods are illustrated in a few examples relevant to endocrinology, cancer and cardiology. New sensing technology yielding large personal data sets is likely to change the healthcare system. Chronobiologic concepts and methods should become an integral part of these evolving systems.

Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma.

Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma-associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long-term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open-angle glaucoma. In a laboratory study in 15 of them, 24-hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time-dependently decreased IOP and IOP standard deviation (SD). IOP 24-hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24-hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G-allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

Chronobiologic assessment of the effect of the DASH diet on blood pressure.

This study compares the effect of three diets on the circadian rhythm of blood pressure (BP). Hypertension and abnormal BP variability (BPV) are major risk factors leading to morbidity and mortality from cardiovascular disease. When detected early, a dietary approach may be preferred to medication. Data stemming from ambulatory BP monitoring (ABPM) from the Dietary Approaches to Stop Hypertension (DASH) study were re-analyzed from a chronobiologic perspective. Compared to the control diet (N = 112) that had no effect on BP (from 131.2/83.5 to 131.0/83.6 mmHg), both the Fruit and Vegetable (FV; N = 113) diet and the DASH (N = 113) diet were associated with a decrease in BP (FV: from 132.6/84.4 to 129.0/82.1 mmHg; DASH: from 131.9/83.6 to 127.2/80.9 mmHg). The decrease in BP was found to be circadian stage-dependent, and to differ between men and women. Nighttime BP was decreased to a larger extent with the DASH than with the FV diet, a difference observed in women but not in men. Study participants who had a higher BP during the reference stage were more likely to decrease their BP to a larger extent after the 8-week dietary intervention. The FV and DASH diets had different effects on BPV. In view of the relatively large day-to-day variability in BP in both normotensive and hypertensive people, it is recommended to monitor BP around the clock for longer than 24 h, and to individualize the optimization of dietary or other intervention.

Falls Risk, Circadian Rhythms and Melatonin: Current Perspectives.

Aging is associated with weakening of the circadian system. The circadian amplitude of most physiological variables is reduced, while the circadian phase becomes more labile and tends to occur earlier with advancing age. As the incidence of falls in older persons could follow circadian variations, a better understanding of conditions in which falls occur can lead to the implementation of countermeasures (such as adjusting the scheduling of hospital staff, or changing the timing of anti-hypertensive medication if falls are related to undesirable circadian patterns of blood pressure and/or heart rate). This includes knowing the times of the day, days of the week, and times of the year when falls are more likely to occur at home or in the hospital. Additionally, the links between aging processes and factors associated with an increased risk of developing autonomic dysfunction are well established. A strong association between heart rate variability indexes and aging has been shown. Circadian rhythms of autonomous nervous system activity may play important role for maintenance of orthostatic tolerance. Whether one is concerned with disease prediction and prevention or maintenance of healthy aging, the study of circadian rhythms and the broader time structure underlying physiopathology is helpful in terms of screening, early diagnosis and prognosis, as well as the timely institution of prophylactic and/or palliative/curative treatment. Timing the administration of such treatment as a function of circadian (and other) rhythms also could lead to reduction of falls in older persons. Finally, a prominent circadian rhythm characterizes melatonin, which peaks during the night. The circadian amplitude of melatonin decreases as a function of age, raising the questions whether such a decrease in the circadian amplitude of melatonin relates to a higher risk of falls and, if so, whether melatonin supplementation may be an effective countermeasure. This narrative review assesses the relationships between fall risk and the potential role circadian rhythms and melatonin play in mitigating this risk. We aim to provide healthcare workers adequate information about fall risk in older persons, including the potential role of the circadian rhythms and/or melatonin, as well as to lay foundations for future fall prevention interventional studies.

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of "marker" circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

Effects of circadian restricted feeding on parameters of metabolic syndrome among healthy subjects.

Experimental studies indicate that energy homeostasis to the circadian clock at the behavioral, physiological, and molecular levels, emphasize that timing of food intake may play a significant role in the development of obesity and central obesity. Therefore, resetting the circadian clock by circadian energy restriction via food intake in the morning or evening, may be used as a new approach for prevention of obesity, metabolic syndrome and related diseases. After ethical clearance and written, informed consent, free living subjects were included if they volunteered to take most of the total daily meals (approximately 2000 Kcal./day) in the evening (4 weeks) or morning (4 weeks). Of 22 adults, half were randomly selected by computer generated numbers to eat in the morning and the other half in the evening, after 8.00 PM. The eating pattern was changed after 4 weeks of intervention and a 4-week washout period, those who ate in the morning were advised to eat in the evening and vice versa. Validated questionnaires were used to assess food intakes, physical activity, and intake of alcohol and tobacco. Physical examination included measurement of body weight, height, and blood pressure (BP) by sphygmomanometer. Data were regularly recorded blindly, in all subjects at start of study and during follow-up. Blood samples were collected after an overnight fast for analysis of blood glucose and Hb1c. Feeding in the evening was associated with significant increase in body weight by 0.80 kg (P < .001), body mass index (BMI) by 0.30 kg/m2 (P < .001) and waist circumference by 1.13 cm (P < .05). Feeding the same amount of energy in the morning was not associated with any significant change in weight, BMI or waist circumference (P > .500). Lesser increases in all three variables were associated with AM versus PM feeding (P < .05). Systolic BP slightly increased on PM and decreased on AM feeding, with a difference between the two responses of 1.55 mmHg (P < .05). Fasting blood glucose was lower on AM than on PM feeding (74.86 vs. 77.95 mg/dl, paired t = 4.220, P < .001). Hb1C increased on PM feeding by 0.28 (from 4.45 to 4.73; t = 9.176, P < .001), but decreased on AM feeding by 0.077 (from 4.53 to 4.45; t = -6.859, P < .001). The difference in Hb1C response between AM and PM feeding is also statistically significant (t = -11.599, P < .001). Eating in the evening can predispose to obesity, central obesity and increases in fasting blood glucose and Hb1c that are indicators of the metabolic syndrome. By contrast, eating in the morning can decrease Hb1c and systolic BP, indicating that it may be protective against the metabolic syndrome.

Anti-aging effects of long-term space missions, estimated by heart rate variability.

Reports that aging slows down in space prompted this investigation of anti-aging effects in humans by analyzing astronauts' heart rate variability (HRV). Ambulatory 48-hour electrocardiograms from 7 astronauts (42.1 ± 6.8 years; 6 men) 20.6 ± 2.7 days (ISS01) and 138.6 ± 21.8 days (ISS02) after launch were divided into 24-hour spans of relative lower or higher magnetic disturbance, based on geomagnetic measures in Tromso, Norway. Magnetic disturbances were significantly higher on disturbed than on quiet days (ISS01: 72.01 ± 33.82 versus 33.96 ± 17.90 nT, P = 0.0307; ISS02: 71.06 ± 51.52 versus 32.53 ± 27.27 nT, P = 0.0308). SDNNIDX was increased on disturbed days (by 5.5% during ISS01, P = 0.0110), as were other HRV indices during ISS02 (SDANN, 12.5%, P = 0.0243; Triangular Index, 8.4%, P = 0.0469; and TF-component, 17.2%, P = 0.0054), suggesting the action of an anti-aging or longevity effect. The effect on TF was stronger during light (12:00-17:00) than during darkness (0:00-05:00) (P = 0.0268). The brain default mode network (DMN) was activated, gauged by increases in the LF-band (9.7%, P = 0.0730) and MF1-band (9.9%, P = 0.0281). Magnetic changes in the magnetosphere can affect and enhance HRV indices in space, involving an anti-aging or longevity effect, probably in association with the brain DMN, in a light-dependent manner and/or with help from the circadian clock.

Effect of Gender, Age, Diet and Smoking Status on the Circadian Rhythm of Serum Uric Acid of Healthy Indians of Different Age Groups.

The circadian rhythm of uric acid concentration was studied under near-normal tropical conditions in 162 healthy volunteers (103 males and 59 females; 7 to 75 year). They were mostly medical students, staff members and members of their families. They were classified into 4 age groups: A (7-20 y; N = 42), B (21-40 y; N = 60), C (41-60 y; N = 35) and D (61-75 y; N = 25). They followed a diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Blood samples were collected from each subject every 6 for 24 h (4 samples). Serum uric acid was measured spectrophotometrically. Data from each subject were analyzed by cosinor rhythmometry. Effects of gender, age, diet (vegetarian vs. omnivore), and smoking status on the rhythm-adjusted mean (MESOR) and circadian amplitude were examined by multiple-analysis of variance. A marked circadian variation was found in uric acid concentration in healthy Indians of all age groups. Furthermore, both the MESOR and circadian amplitude underwent changes with advancing age. In addition to effects of gender and age, diet and smoking were also found to affect the MESOR of circulating uric acid concentration in healthy Indians residing in northern India. The present observations confirmed a definite rhythm in uric acid concentrations with significant effect of gender, age, diet, and smoking status on uric acid concentration in clinical health. Mapping the circadian rhythm of serum uric acid is needed to explore their role in different pathophysiological conditions.

Chronomics of Circulating Plasma Lipid Peroxides and Antioxidant Enzymes in Renal Stone Formers.

The chronome of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of time qualified preventive therapeutic and dietary interventions. One hundred renal stone patients, 20-60 years of age, and 50 clinically healthy volunteers, 21-45 years, were synchronized for 1 week with diurnal activity from 06:00 to 22:00 and nocturnal rest. All subjects took their usual meals three times daily (breakfast around 08:30, lunch around 13:00, and dinner around 20:30) with usual fluid intake. Drugs known to affect free radical system were not taken. Blood samples were collected at 6-h intervals for 24-h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in terms of malondialdehyde (MDA) and blood superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. A marked circadian variation was demonstrated for each studied variable by population-mean cosinor in renal stone patients and healthy participants (p < 0.001). By comparison to healthy subjects, parameter tests indicate that the stone formers had a higher MESOR of MDA, but a lower MESOR of SOD, GPx, GR and CAT. Furthermore, the patients also differed from the healthy controls in terms of their circadian amplitude and acrophase (tested jointly) of all variables (p < 0.001). Mapping the broader time structure with multifrequency circadian characteristics of oxidants and anti-oxidants is needed for exploring their role as marker in the treatment and management of urolithiasis.

The fetal circadian rhythm in pregnancies complicated by pregestational diabetes is altered by maternal glycemic control and the morning cortisol concentration.

Circadian rhythmicity is fundamental to human physiology, and is present even during fetal life in normal pregnancies. The impact of maternal endocrine disease on the fetal circadian rhythm is not well understood. The present study aimed to determine the fetal circadian rhythm in pregnancies complicated by pregestational diabetes mellitus (PGDM), compare it with a low-risk reference population, and identify the effects of maternal glycemic control and morning cortisol concentrations. Long-term fetal electrocardiogram recordings were made in 40 women with PGDM at 28 and 36 weeks of gestation. Two recordings were made in 18 of the women (45.0%) and one recording was made in 22 (55.0%). The mean fetal heart rate (fHR) and the fHR variation (root mean square of squared differences) were extracted in 1-min epochs, and circadian rhythmicity was detected by cosinor analysis. The study cohort was divided based on HbA1c levels and morning cortisol concentrations. Statistically, significant circadian rhythms in the fHR and the fHR variation were found in 45 (100%) and 44 (95.7%) of the 45 acceptable PGDM recordings, respectively. The rhythms were similar to those of the reference population. However, there was no statistically significant population-mean rhythm in the fHR among PGDM pregnancies at 36 weeks, indicating an increased interindividual variation. The group with higher HbA1c levels (>6.0%) had no significant population-mean fHR rhythm at 28 or 36 weeks, and no significant fHR-variation rhythm at 36 weeks. Similarly, the group with a lower morning cortisol concentration (≤8.8 µg/dl) had no significant population-mean fHR-variation rhythm at 28 and 36 weeks. These findings indicate that individual fetal rhythmicity is present in pregnancies complicated by PGDM. However, suboptimal maternal glycemic control and a lower maternal morning cortisol concentration are associated with a less-well-synchronized circadian system of the fetus.

Chronic heart failure: a disease of the brain.

The underlying mechanism for clinical and biochemical manifestations of chronic heart failure (HF) may be due in part to neurohumoral adaptations, such as activation of the renin-angiotensin-aldosterone and sympathetic nervous systems in the periphery and the brain. Internet search and discussion with colleagues are the methods for this study. Since chronic HF is associated with autonomic imbalance with increased sympathetic nerve activity and a withdrawal of parasympathetic activity, it may be considered a brain disease. This phenomenon may be the result of an increased systemic and cerebral angiotensin II signaling because plasma angiotensin II is increased in humans and animals with chronic HF. The increase in angiotensin II signaling enhances sympathetic nerve activity through actions on both central and peripheral sites during chronic HF. Activation of angiotensin II signaling in different brain sites such as the paraventricular nucleus (PVN), rostral ventrolateral medulla (RVLM), and area postrema (AP) may increase the release of norepinephrine, oxidative stress, and inflammation leading to increased cardiac contractility. It is possible that blocking angiotensin II type 1 receptors decreases sympathetic nerve activity and cardiac sympathetic afferent reflex when therapy is administered to the PVN. The administration of an angiotensin receptor blocker by injection into the AP activates the sympatho-inhibitory baroreflex indicating that receptor blockers act by increasing parasympathetic activity. In chronic HF, in peripheral regions, angiotensin II elevates both norepinephrine release and synthesis and inhibits norepinephrine uptake at nerve endings, which may contribute to the increase in sympathetic nerve activity. Increased circulating angiotensin II during chronic HF may enhance the sympatho-excitatory chemoreflex and inhibit the sympatho-inhibitory baroreflex resulting in worsening of HF. Increased circulating angiotensin II signaling can directly act on the central nervous system via the subfornical organ and the AP to increase sympathetic outflow resulting in to neurohumoral dysfunction, resulting in to heart failure.