Pattern Of Circadian Variation Research Articles

Circadian variation pattern of sudden cardiac arrest occurred in Chinese community

BackgroundThe circadian variation pattern of sudden cardiac arrest (SCA) occurred in Chinese community including both community healthcare centres and primary hospitals remains unknown. This study analysed the circadian variation of...

Effects of Soybean Phosphate Transporter Gene GmPHT2 on Pi Transport and Plant Growth under Limited Pi Supply Condition

Phosphorus is an essential macronutrient for plant growth and development, but phosphate resources are limited and rapidly depleting due to massive global agricultural demand. This study identified two genes in the phosphate transporter 2 (PHT2) family of soybean by bioinformatics. The expression patterns of two genes by qRT-PCR at leaves and all were induced by low-phosphate stress. After low-phosphate stress, GmPHT2;2 expression was significantly higher than GmPHT2;1, and the same trend was observed throughout the reproductive period. The result of heterologous expression of GmPHT2 in Arabidopsis knockout mutants of atpht2;1 shows that chloroplasts and whole-plant phosphorus content were significantly higher in plants complementation of GmPHT2;2 than in plants complementation of GmPHT2;1. This suggests that GmPHT2;2 may play a more important role in plant phosphorus metabolic homeostasis during low-phosphate stress than GmPHT2;1. In the yeast backfill assay, both genes were able to backfill the ability of the defective yeast to utilize phosphorus. GmPHT2 expression was up-regulated by a low-temperature treatment at 4 °C, implying that GmPHT2;1 may play a role in soybean response to low-temperature stress, in addition to being involved in phosphorus transport processes. GmPHT2;1 and GmPHT2;2 exhibit a cyclic pattern of circadian variation in response to light, with the same pattern of gene expression changes under red, blue, and white light conditions. GmPHT2 protein was found in the chloroplast, according to subcellular localization analysis. We conclude that GmPHT2 is a typical phosphate transporter gene that can improve plant acquisition efficiency.

ASSOCIATION BETWEEN NOCTURNAL VARIATION IN BLOOD PRESSURE AND RISK OF ACUTE ISCHEMIC STROKE: A SYSTEMATIC REVIEW

Objective: Blood pressure (BP) is a dynamic parameter characterized by fluctuations during the 24-hour period. Variability of BP has been associated with cardiovascular risk and the occurrence of acute ischemic stroke (AIS). Circadian variation in BP during the night shows some basic patterns. The purpose of this study is to to correlate deviations from baseline patterns of circadian BP variation with the risk of AIS to select the optimal therapeutic intervention. Design and method: To complete our study, we systematically reviewed the literature from 1990-2022 through electronic medical databases (MEDLINE, Scopus and Cochrane). Results: During the nighttime hours, BP drops 10 - 20% in normotensive and untreated hypertensive patients - a dipping phenomenon, followed by a rapid and gradual increase during waking hours. In the studies being reviewed, patients were classified according to the rate of fall in systolic BP during 24-hour recording into four categories: the extreme-dippers drop >20%, dippers drop >10% and <20%, non-dippers drop <10% and >0%, and reverse-dippers or risers drop <0%. Deviating from standard dipping patterns is associated with an increased risk of AIS and highlights the value of chronotherapy, whereas no significant difference is observed in stroke prognosis. The extreme-dipping phenomenon is associated with the occurrence of ischemic stroke (IS), either due to under-treatment or due to subsequent morning hypertensive spike, whereas aggressive antihypertensive treatment seems to be significantly responsible. Interestingly, the occurrence of microbleeds in IS territory has been strongly associated with the reverse-dipping pattern. Conclusions: Overnight BP variation is an independent and robust predictor of cardiovascular risk, including AIS. Nocturnal BP may constitute a therapeutic target for the prevention of AIS. However, the available data on the effect of antihypertensive drugs and the implementation of chronotherapy with pre-sleep medication are conflicting in terms of improving cardiovascular risk. Therefore, at present, current guidelines for the treatment of BP do not recommend the aforementioned therapeutic approach as the best treatment in day-to-day clinical practice. More extensive and targeted studies are needed in the future to confirm the potential benefits of the application of chronotherapy in the prevention of AIS.

Ambulatory Local Field Potential Recordings from the Thalamus in Epilepsy: A Feasibility Study

Introduction: Stimulation of the thalamus is gaining favor in the treatment of medically refractory multifocal and generalized epilepsy. Implanted brain stimulators capable of recording ambulatory local field potentials (LFPs) have recently been introduced, but there is little information to guide their use in thalamic stimulation for epilepsy. This study sought to assess the feasibility of chronically recording ambulatory interictal LFP from the thalamus in patients with epilepsy. Methods: In this pilot study, ambulatory LFP was recorded from patients who underwent sensing-enabled deep brain stimulation (DBS, 2 participants) or responsive neurostimulation (RNS, 3 participants) targeting the anterior nucleus of the thalamus (ANT, 2 electrodes), centromedian nucleus (CM, 7 electrodes), or medial pulvinar (PuM, 1 electrode) for multifocal or generalized epilepsy. Time-domain and frequency-domain LFP was investigated for epileptiform discharges, spectral peaks, circadian variation, and peri-ictal patterns. Results: Thalamic interictal discharges were visible on ambulatory recordings from both DBS and RNS. At-home interictal frequency-domain data could be extracted from both devices. Spectral peaks were noted at 10–15 Hz in CM, 6–11 Hz in ANT, and 19–24 Hz in PuM but varied in prominence and were not visible in all electrodes. In CM, 10–15 Hz power exhibited circadian variation and was attenuated by eye opening. Conclusion: Chronic ambulatory recording of thalamic LFP is feasible. Common spectral peaks can be observed but vary between electrodes and across neural states. DBS and RNS devices provide a wealth of complementary data that have the potential to better inform thalamic stimulation for epilepsy.

Circadian blood pressure variations in normotensive and hypertensive Indian adults: An exploratory study

Background and Objectives: Though 24hours BP monitoring is a useful tool that provide insights in masked and white coat hypertension as well as can be used as a marker of allostatic load (by monitoring circadian variations) and applicable in chronotherapy, is still sparingly used clinically. Hence, the objective of present study is to explore the pattern of circadian variation of blood pressure in normotensive and hypertensive Indians to pave the way for future chronobiological research and predictive medicine. Materials and Methods: In this cross-sectional study, total 125 volunteers, referred from the medicine OPD/IPD, enrolled. All the volunteers underwent 24 hour ambulatory blood pressure monitoring. BP recording of 100 participants (37 female and 63 male, mean age = 43.15±14.47 years) was used for final analysis. On the basis of guidelines provided for diagnosis of hypertension by European Society of Heart, individuals were grouped as i) normotensives (n=37) and ii) hypertensives (n=63). For descriptive analysis, different blood pressure parameters from three segments viz. overall, awake period and asleep period were used. Between groups comparison was done using Mann-Whitney and ANNOVA test. P-value < 0.05 had been considered as significant.Observation and Results: A significance difference in circadian systolic, diastolic and mean arterial BP was observed between groups. Although a higher percentage of non-dippers (65%) was observed in hypertensives but 38% of normotensives have also shown non- dipping status that indicates altered circadian rhythm or allostatic load. Conclusion: We observed altered circadian blood pressure pattern in both groups though higher percentage of non -dipping status in hypertensive patients. In normotensives it could subserve as an early marker of disease process, in hypertensives, it may be useful for application of Chrono-pharmacology.

INFLAMMATION MARKERS IN SUBJECTS WITH DIPPER AND NON-DIPPER BLOOD PRESSURE PATTERNS

Objective: Elevated inflammation markers play important role in vessels damage and remodeling in patients with hypertension. However, the data are limited concerning the association between blood pressure circadian rhythm and inflammation status, especially in early changes of a pattern of blood pressure circadian rhythm in normotensive subjects. The aim of the work was to study the connection between dipper and non-dipper patterns of blood pressure circadian variation and inflammatory markers in normotensive and hypertensive subjects. Design and method: The cross-sectional study included 125 hypertensive patients (54 men) with an age median of 56,5 [45.0 ÷ 63.7] years old and 41 normotensive subjects 52,1 [41.5 ÷ 61.2] years old. All hypertensive patients had been on stable antihypertensive therapy during the last three months and had target blood pressure at the moment of inclusion to the study. Ambulatory blood pressure monitoring was done to all patients with Heaco ABPM50 monitoring. Fasting glucose, blood lipids, creatinine, uric acid, high sensitive C-reactive protein (hCRP), and interleukin 1 beta (IL-1B) were measured. Physical activity was assessed using the International Physical Activity Questionnaire. Data were analyzed with SPSS IBM 19.0. Results: Parameters of ambulatory blood pressure monitoring are presented in the table1 1. Normotensive subjects had lower BMI than hypertensive patients (26,1 [23,5–28,4] vs 35,3 [31,0–37,9]), p = 0.03, Mann-Whitney). It was found out that hCRP was significantly higher in a non-dipper subgroup of hypertensive patients (7.43[3.26–11.45] vs 9.50[7.70–15.87], p = 0.01, Mann-Whitney) as well as in the non-dipper subgroup of normotensive patients (2.37[0.97–4.75] vs 2.87[1.84–523], p = 0,03, Mann-Whitney). There was no significant difference in interleukin-1b level in dipper and non-dipper normotensive patients (2.10 [1.63–2.65] vs 1.8 [1.55–2.10], p = 4.13, Mann-Whitney). However, in hypertensive patients with non-dipper patterns, interleukin-1b was significantly higher, than in dipper patients (2.21 [1.62–2.77] vs 2.26 [2.0–3.11], p = 0.03, Mann-Whitney). Conclusions: Non-dipper pattern of blood pressure circadian rhythm is associated with increased inflammatory markers in hypertensive patients as well as in normotensive subjects.

Patterns of Circadian Variation in 24-Hour Ambulatory Blood Pressure, Heart Rate, and Sympathetic Tone Correlate with Cardiovascular Disease Risk: A Cluster Analysis.

To investigate whether specific time series patterns for blood pressure (BP), heart rate (HR), and sympathetic tone are associated with metabolic factors and the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). A total of 989 patients who underwent simultaneous 24-hour ambulatory BP and Holter electrocardiogram monitoring were enrolled. The patients were categorized into sixteen groups according to their circadian patterns using the consensus clustering analysis method. Metabolic factors, including cholesterol profiles and apolipoprotein, were compared. The 10-year ASCVD risk was estimated based on the Framingham risk model. Overall, 16 significant associations were found between the clinical variables and cluster groups. Age was commonly associated with all clusters in systolic BP (SBP), diastolic BP (DBP), HR, and sympathetic tone. Metabolic indicators, including diabetes, body mass index, total cholesterol, high-density lipoprotein, and apolipoprotein, were associated with the four sympathetic tone clusters. In the crude analysis, the ASCVD risk increased incrementally from clusters 1 to 4 across SBP, DBP, HR, and sympathetic tone. After adjustment for multiple variables, however, only sympathetic tone clusters 3 and 4 showed a significantly high proportion of patients at high risk (≥7.5%) of 10-year ASCVD (odds ratio (OR) = 5.90, 95% confidential interval (CI) = 1.27–27.46, and P value = 0.024 and OR = 15.28, 95% CI = 3.59–65.11, and P value < 0.001, respectively). Time series patterns of BP, HR, and sympathetic tone can serve as an indicator of aging. Circadian variations in sympathetic tone can provide prognostic information about patient metabolic profiles and indicate future ASCVD risk.

The influence of circadian variation in ischemic stroke onset on the evolution of cognitive status

Introduction. It is already known and accepted that cerebrovascular disease onset has a temporal variation pattern, the best documented being the circadian variation pattern, with a frequency peak in the morning and a second lower peak during afternoon. The impact of this circadian variation on post-stroke cognitive status has been little studied. Materials and method. The study included a cohort of 63 patients with ischemic stroke, admitted to the Neurology Departments I and II of the Rehabilitation Hospital in Cluj-Napoca between 1 June 2008 and 1 June 2009, who were evaluated for their cognitive status over 2 years, during 5 successive visits. The onset time of ischemic stroke was assigned to one of the six-hour intervals: 00.01-06.00 (night), 06.01-12.00 (morning), 12.01-18.00 (afternoon), and 18.01-24.00 (evening). Statistical analysis was performed using Excel Microsoft, descriptive and ANOVA test. Results and conclusions. The circadian variation pattern of stroke onset is confirming in our study the known incidence pattern of ischemic stroke, with the morning peak. There are differences in the evolution during dynamics of the MMSE score depending on the time of the day when stroke occurs. Patients with stroke onset during the night have seems to have a less favorable cognitive evolution in the second year after ischemic stroke compared to patients with stroke onset during the other intervals of the day.

Ccrn4l as a pre-dose marker for prediction of cisplatin-induced hepatotoxicity susceptibility

Clinical cisplatin use is often limited by its drug-induced liver injury (DILI). Particularly, individual differences in susceptibility to DILI can cause life-threatening medical conditions. This study aimed to uncover the inherent genetic factors determining individual variations in hepatotoxicity susceptibility. Rats were subjected to liver biopsy and a 3-week postoperative recovery period before cisplatin administration. At 2 days post-treatment with cisplatin, the rats exhibited histopathological and serum biochemical alterations in the liver, and changes in hydrogen peroxide and cytochrome P450-2E1 levels. Based on these results of liver-related biochemical markers, 32 rats were grouped into the susceptible (top five) and resistant (bottom five) groups. Using RNA-sequencing, we compared gene expressions in the liver pre-biopsied from these two groups before cisplatin treatment and found 161 differently expressed genes between the Susceptible and Resistant groups. Among them, the clock-controlled Ccrn4l responsible for ‘rhythmic process’ was identified as a common gene downregulated inherently prior to drug exposure in both cisplatin- and acetaminophen-sensitive animals. Additionally, low Ccrn4l levels before cisplatin treatment in the Susceptible group were maintained even after treatment, with decreased antioxidants, increased nitration, and apoptosis. The relationship of Ccrn4l with catalase and mitochondrial RNAs in the liver was confirmed by correlation of their hepatic levels among individuals and similar patterns of circadian variation in their mRNA expression. Remarkably, Ccrn4l knockdown promoted cisplatin-induced mitochondrial dysfunction in WB-F344 cells with antioxidant catalase and apoptosis-related Bax changes. Inherent individual hepatic Ccrn4l level might be a novel factor affecting cisplatin-induced hepatotoxicity susceptibility, possibly through regulation of mitochondrial and antioxidant functions.

PER3 variable number tandem repeat (VNTR) polymorphism modulates the circadian variation of the descending pain modulatory system in healthy subjects

We evaluated the circadian pattern of variation of the descending pain modulatory system (DPMS) using a conditioned pain modulation (CPM) paradigm according to the variable-number tandem-repeat (VNTR) of the clock gene PER3 polymorphism. We assessed the relationship between the genotypes PER34/4 and PER35/5 and the temporal pattern of variation across the day using the following measures: the heat pain threshold (HPT), the cold pressure test (CPT), and the serum levels of BDNF and S100-B protein. The ∆-values (from afternoon to morning) of these measures were used for the analysis. The circadian phenotype was according to the mid-point sleep time established by the Munich ChronoType Questionnaire (MCTQ). We included 18 healthy volunteers (15 women) ages 18 to 30. A Generalized Linear Model (GLM) revealed a significant difference in the ∆-CPM-task between Per34/4 and Per35/5 genotypes, with means (SDs) of −0.41 (0.78) vs. 0.67 (0.90) (χ2 = 7.256; df = 1′ P = 0.007), respectively. Both sleep deprivation of at least 2 h/day (B = −0.96, 95% confidence interval (CI) = −1.86 to −0.11)) and the ∆-S100-B protein (−0.03, 95% CI = −0.06 to −0.02) were negatively correlated with the ∆-CPM-task, while the ∆-BDNF was positively correlated with the ∆-CPM-task (0.015, 95% CI = 0.01 to 0.03). We observed a difference in the ∆-CPT between PER34/4 and PER35/5 (0.11 (4.51) vs. 4.00 (2.60), respectively) (χ2 = 22.251; df = 1 P = 0.001). These findings suggest that the polymorphism of PER35/5 is associated with a decrease in the inhibitory function of the DPMS over the course of the day. However, sleep deprivation is an independent factor that also reduces the inhibitory function of the DPMS, regardless of the PER3 VNTR polymorphism.

1729-P: Circadian Patterns of Autoimmune Components in the Blood of Persons with Type 1 Diabetes: Implications for the Timing of Blood Sampling

Purpose: Immune populations and cytokines are known to exhibit distinct circadian ("daily") variations. We sought to characterize circadian-related immune variation in persons with type 1 diabetes (T1D) to ascertain whether sampling of peripheral immune biomarkers should be timed with circadian patterns Methods: We enrolled 10 adults (6 female) volunteers between 18 and 40 years of age, with T1D diagnosed for at least 12 months and free of other diseases. Subjects were admitted to the Research Center and had blood collections performed every 4 hours over a 24-hour period. Samples were processed and aliquoted after each draw. Flow cytometric analyses of central memory, regulatory, naïve T- and B-cells, monocytes and NK cell frequencies were performed in 200μl. Circadian variation patterns were characterized with fitted cosine curves using COSINOR analysis. Results: Significant circadian patterns were identified for CD4 and CD8 T cells, T regulatory cells (T regs), Natural killer T cells (NKT), Dendritic Cells (DC) and B cells in T1D subjects. All populations except of NKT cells peaked during the night with peak levels estimated to occur respectively at (24:00 hour [95% CI]); CD4 0030 [2396,0040]; CD8 0106 [2358,0014]; T regs 2349 [2395,0005]; NKT 1527 [1217,1819]; DC 0070 [2392,0008]; B cells 0111 [2382,0014]. Conclusion: Clinical studies of immune interventions meant to influence immune populations should sample these populations at consistent times of day, and likely at peaks, or nadirs, in order to have the greatest range for therapeutic effect to be demonstrated. For B-cell reduction interventions (such as Rituximab), our study indicates the best time for PBMC sampling would be around midnight. For therapies targeting immune cell expansion, e.g., Treg expansion, the sampling may be better at nadir, where the increase will be the greatest- i.e., approximately noon. Disclosure E. Beli: None. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research &amp; Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. S. Woerner: None. C. Evans-Molina: None. K.M. McGrail: None. C. Wasserfall: None. M.A. Atkinson: None. C. Beam: None. Funding JDRF International (3-SRA-2015-7-M-RJDRF, 3-APF-2017-396-A-N)

Circadian blood pressure profile and comparison with clinic blood pressure in patients with essential hypertension on treatment; experience from a Teaching Hospital in Sri Lanka

Background and Objectives: Ambulatory blood pressure monitoring (ABPM) is more reflective of an individual’s Blood Pressure (BP) profile and its control, eliminating several confounding and contributory factors. The present study was intended to look at the circadian pattern of BP variation, the prognostication of patients with nocturnal BP fluctuations and to compare the clinic BP measurements over ambulatory readings in patients with essential hypertension, who are on treatment. Methods: A Prospective study was conducted at Teaching Hospital Kandy from August 2015 to October 2015 with recruitment of 100 patients who met the inclusion criteria. It included patients who were above 18 years with stage I to III hypertension with normal renal functions and having no previous history of coronary or cerebro-vascular events. All patients underwent electrocardiograms, 2D echocardiography assessment, manual BP as well as 24-hour ABPM. Results: There were 100 subjects with female preponderance and mean age of 61 ± 9 years. One third had uncontrolled BP according to office BP readings whereas 60% had uncontrolled BP according to ABPM. The agreement between the office BP and ABPM in diagnosing control or uncontrolled BP was low (58%, Kappa = 0.23). Significant statistical difference (p Conclusion: ABPM is more reflective of an individual’s naive BP pattern and its response to treatment. It captures the different types of diurnal variation of BP thus guiding the physician to treat the patient optimally. Moreover, its non-invasive and portable nature allows it to be used with ease and will gather more widespread recognition and acceptance as a more reliable diagnostic and prognostic tool in the future.

An in vivo biosensing, biomimetic electrochemical transistor with applications in plant science and precision farming

The in vivo monitoring of key plant physiology parameters will be a key enabler of precision farming. Here, a biomimetic textile-based biosensor, which can be inserted directly into plant tissue is presented: the device is able to monitor, in vivo and in real time, variations in the solute content of the plant sap. The biosensor has no detectable effect on the plant’s morphology even after six weeks of continuous operation. The continuous monitoring of the sap electrolyte concentration in a growing tomato plant revealed a circadian pattern of variation. The biosensor has the potential to detect the signs of abiotic stress, and therefore might be exploited as a powerful tool to study plant physiology and to increase tomato growth sustainability. Also, it can continuously communicate the plant health status, thus potentially driving the whole farm management in the frame of smart agriculture.

Behavioral depression is associated with increased vagally mediated heart rate variability in adult female cynomolgus monkeys (Macaca fascicularis)

IntroductionDepressive symptoms (DS) in humans are associated with decreased resting state vagal activity, but sex seems to moderate this association. Recently, in human females DS have been associated with greater or similar cardiac vagal activity compared to men in both, clinical and non-clinical samples. A previously validated animal model of behavioral depression was used in the present study to investigate the association of DS and cardiac vagal activity in non-human primates. MethodsThe root mean square of successive differences between adjacent heart beats (RMSSD) was used as an indicator of vagally-mediated heart rate variability in 24h heart rate recordings collected via telemetry in 42 adult female cynomolgus monkeys (Macaca fascicularis). Hierarchical regression models were used to estimate differences in RMSSD comparing monkeys with and without DS. To capture circadian variation patterns of RMSSD, additional quadratic, cubic and quartic terms of hour were added. ResultsMonkeys showing behavioral DS had higher overall 24-h RMSSD. The interaction term of daytime with DS and polynomials of hour contributed significantly to the variance across models. ConclusionsThis is the first study investigating the association of DS and 24h cardiac vagal control in female non-human primates. Results replicate existing human studies showing higher cardiac vagal control in behavioral depressed vs. non-depressed female monkeys.

Same Pattern of Circadian Variation According to the Season in the Timing of Ischemic Stroke Onset: Preliminary Report

Background and ObjectiveaaStroke occurrence shows a chronobiological variation, which is considered to be related with waking in the morning. We hypothesized that its seasonal difference would also exist because individual life activity including sleep-wake pattern can be influenced by interseasonal variability. The objective of this study was to investigate the seasonal difference of circadian variation in the timing of onset in patients with acute ischemic stroke. MethodsaaWe studied 1486 patients with acute ischemic stroke. Stroke onset time was defined as the earliest time the patient or a wit ness noted definite neurological symptoms. The patients with clear onset stroke were enrolled. Frequency of onset was analyzed for four 6-hour and twelve 2-hour intervals from 0 to 24 hour per day. ResultsaaThe clear onset time was known in 968 patients (65.1%). Mean age of the patients was 67.63 ± 12.65 years and 589 patients (60.9%) were male. Stroke occurred in spring (26.5%), summer (27.2%), fall (24.1%), and winter (22.3%). In all cases, ischemic stroke showed a significant circadian variation in time of onset (p < 0.001). High peak period was between 6:01 AM to 12:00 PM (37%) with the same pattern in each season. ConclusionsaaSeasonal difference was not significant despite circadian variation in time of onset of ischemic stroke. Thus, exogenous factors such as environmental factors and life styles may have less influence on inter-seasonal variability of circadian rhythms, which are related with chronobiological factors of stroke onset in this regional population.

Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study.

BackgroundBoth albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.MethodsThis was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).ResultsUAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m2) in its association with the changes of both night-time systolic BP (SBP) and night–day SBP ratio. After stratification, UAER strongly predicted night–day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.ConclusionsUAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.

Development of hypertension &amp;ndash; clinical impact of dysregulation of circadian rhythms and implications for treatment

Development of hypertension &ndash; clinical impact of dysregulation of circadian rhythms and implications for treatment Kristen Solocinski,1,2 Michelle L Gumz1,2 1Department of Medicine, 2Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, USA Abstract: Blood pressure, like most physiological processes, exhibits a circadian pattern of variation. Disruption of the normal circadian rhythm of blood pressure is associated with end organ damage and increased risk of adverse cardiovascular outcomes. In this review, we discuss the role of the renin angiotensin aldosterone system and the molecular clock in maintaining circadian blood pressure patterns. We also consider disrupted circadian blood pressure rhythms and hypertension in distinct populations and the role of chronotherapy in the treatment of hypertension. Keywords: clock, kidney, adrenal, aldosterone, chronotherapy, sleep

Tick Tock

A variety of physiologic functions related to the kidney, including BP, GFR, renal blood flow, and urinary sodium excretion, exhibit a circadian pattern of variation (reviewed by Stow and Gumz[1][1]). Whereas these clinical observations are well established, the underlying molecular mechanisms are

Circadian Variation of Stroke Onset: A Hospital-Based Study.

Aims and background.The circadian pattern of stroke occurrence variation has been recognized with certain differences between authors and stroke types. The underlying reason may be related to exogenous factors (cyclic physical activity, including sleep–awake cycles and assuming the up-right posture) and endogenous factors, with their diurnal variation (blood pressure, hemostatic balance, autonomic system activity). The aims of the present study are to investigate the existence of a circadian variation of stroke and the possible differences between stroke subtypes in the Cluj Napoca area.Materials and method.The stroke event data were acquired from the Patient Records of a consecutive series of 1083 patients admitted through the Emergency Room at Neurology Departments I and II of the District Hospital of Cluj Napoca, between 1 January 2012 and 31 December 2012. The classifiable onset time was assigned to one of four six-hour intervals: 00.01–06.00 (night), 06.01–12.00 (morning), 12.01–18.00 (afternoon) and 18.01–24.00 (evening). Demographic data and vascular risk factors were recorded.Results.All three stroke types (ischemic stroke, hemorrhagic stroke and subarachnoid hemorrhage) have shown a circadian variation regarding their occurrence, with the peak of incidence in the morning and the nadir during nighttime. This circadian pattern is independent by demographic factors and vascular risk factors.Conclusion.Our study confirmed the circadian variation of onset occurrence for all stroke subtypes. Some triggering factors promote ischemic stroke and prevent hemorrhagic stroke. The diurnal pattern of variation with the higher incidence in the morning and the lower in the night may lead to chrono-therapeutic and preventive approach (chrono-therapy of the risk factors), which targets the period of the highest vulnerability after awaking.

The biological clock and the molecular basis of lysosomal storage diseases.

The lysosomal storage disorders encompass nearly fifty diseases provoked by lack or deficiency of enzymes essential for the breakdown of complex molecules and hallmarked by accumulation in the lysosomes of metabolic residues. Histochemistry and cytochemistry studies evidenced patterns of circadian variation of the lysosomal marker enzymes, suggesting that lysosomal function oscillates rhythmically during the 24-h day. The circadian rhythmicity of cellular processes is driven by the biological clock ticking through transcriptional/translational feedback loops hardwired by circadian genes and proteins. Malfunction of the molecular clockwork may provoke severe deregulation of downstream gene expression regulating a complex array of cellular functions leading to anatomical and functional changes. In this review we highlight that all the genes mutated in lysosomal storage disorders encode circadian transcripts suggesting a direct participation of the biological clock in the pathophysiological mechanisms underlying cellular and tissue derangements hallmarking these hereditary diseases. The 24-h periodicity of oscillation of gene transcription and translation could lead in physiological conditions to circadian rhythmicity of fluctuation of enzyme levels and activity, so that gene transfer could be envisaged to reproduce 24-h periodicity of variation of enzymatic dynamics and circadian rhythmicity could have an impact on the schedule of enzyme replacement therapy.