NONINVASIVE METHODS IN CARDIOLOGY
2023
Edited by: Cornélissen G., Siegelová J., Pohanka M., Dobšák P.
MASARYK UNIVERSITY
PRESS
Brno 2023
Under the auspices of
Prof. MUDr. Martin Repko, Ph.D., Dean of Faculty of Medicine Masaryk University Brno
Reviewed by: Prof. MUDr. Kamil Javorka, DrSc.
Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Slovak Republic
© 2023 Masaryk University ISBN 978-80-280-0441-5
Contents
SARS-CoV-2 infection in HIV-positive patients with or without antiretroviral therapy in sub-Saharan
Africa: An overview of the protocol and preliminary results...............................................................5
Nandu Goswami
Chronotherapy of blood pressure: beyond comparing morning vs. evening dosing.............................9
Germaine Cornelissen, Alena Havelková, Jarmila Siegelová, Gubin D, Beaty LA, Otsuka K
Application of Mathematica Toolkit to Data from Residents in the Arctic........................................27
A. Chase Turner, Denis Gubin, Larry Beaty, Germaine Cornelissen
Prof. MUDr. Bohumil Fišer, CSc. (October 22. 1943 - March 21. 2011)...........................................37
Marie Nováková
80 years anniversary of Prof. MUDr. Bohumil Fišer, CSc. (October 22. 1943 - March 21. 2011).....39
Jarmila Siegelová
The history of the Teaching Bachelor and Magister in Physiotherapy
in the Faculty of Medicine Masaryk University.................................................................................65
Jarmila Siegelová, Leona Dunklerová, Michal Pohanka
Scientific International Cooperation
between Masaryk University Brno and University of Minnesota.......................................................75
Jarmila Siegelová
Night-to-day blood pressure ratio from seven day/24 h ambulatory blood pressure monitoring by
repeated measurements in patients with coronary heart disease........................................................79
Jarmila Siegelová, Alena Havelková, Jiri Dušek, Leona Dunklerová, Kristýna Lapciková, Michal Pohanka, Petr Dobšák, Germaine Cornelissen
From Oita, Hometown Japan to Medical Care and Welfare in the Republic of Kenya Medical, Health
and Welfare Improvement Project......................................................................................................89
Mitsuo Takei
NONINVASIVE METHODS IN CARDIOLOGY 2023
SARS-CoV-2 Infection in Hiv-Positive Patients with or without Antiretroviral Therapy in Sub-Saharan Africa: an Overview of the Protocol and Preliminary Results
Nandu Goswami, Coordinator
Medical University Graz, Austria
On behal of the EndoCOVID Team
Austria: Goswami, N., Steuber, B., Schmid-Zalaudek, K
Norway: Fredriksen, P.M., Lundin, K.E.A.,
South Africa: Motaung, S., Nkeh Chungag, B, Hyera, F.
Nigeria: Elias, S.
Prof. Nandu Goswami Prof. Francis Hyera, Prof. Knut Lundin,       Prof. Shirley Motaung
Austria South Africa Norway South Africa
Dr. Karin Schmid,      Dr. Bianca Steuber       Prof. Simiat Elias,   Prof. Peter Moten, Benedicta Zalaudek Frederiksen Nkeh Chungag
Austria Austria Nigeria Norway South Africa
Abstract Background
COVID-19 has affected almost every country in the world, especially in terms of health system capacity and economic burden. People from sub-Saharan Africa (SSA) often face
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NONINVASIVE METHODS IN CARDIOLOGY 2023
interaction between human immunodeficiency virus (HIV) infection and non-communicable diseases such as cardiovascular disease. Role of HIV infection and anti-retroviral treatment (ART) in altered cardiovascular risk is questionable and there is still need to further carry out research in this field. However, thus far it is unclear, what impact the COVID-19 co-infection in people living with HIV (PLHIV), with or without therapy will have. The ENDOCOVID project aims to investigate whether and how HIV-infection in COVID-19 patients modulates the time course of the disease, alters cardiovascular risk, and changes vascular endothelial function and coagulation parameters/ thrombosis risk.
Methods:
A total of 1026 patients will be included into this study. Cardiovascular research PLHIV with (n= 114 in each of the three recruiting centers) - or without - ART (n= 114 in each of the three recruiting centers) with COVID-19 and HIV-negative with COVID-19 (n=114 in each of the three recruiting centers) will be carried out via clinical and biochemical measurements for cardiovascular risk factors and biomarkers of cardiovascular disease (CVD). Vascular and endothelial function will be measured by brachial artery flow-mediated dilatation (FMD), carotid intima-media thickness (IMT) assessments, and retinal blood vessel analyses, along with vascular endothelial biomarkers and cogualation markers. The correlation between HIV-infection in COVID-19 PLHIV with or without ART and its role in enhancement of cardiovascular risk and endothelial dysfunction will be assessed at admission, weekly, at discharge and, 4 weeks post-discharge (if possible).
Impact of project
The ENDOCOVID project aims to evaluate in the long-term the cardiovascular risk and vascular endothelial function in PLHIV thus revealing an important transitional cardiovascular phenotype in COVID-19. The study was registered under clinicaltrials.gov (NCT04709302).
Declaration: This abstract has been presented as a protocol paper by the EndoCOVID team:
Goswami, N., Fredriksen, P.M., Lundin, K.E.A. et al. COVID-19 and its effects on endothelium in HIV-positive patients in sub-Saharan Africa: Cardiometabolic risk, thrombosis and vascular function (ENDOCOVID STUDY). BMC Infect Dis 21, 719 (2021). https://doi. org/10.1186/sl2879-021-06426-8
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NONINVASIVE METHODS IN CARDIOLOGY 2023
mm
science
& technology
Department:
Science and Technology REPUBLIC OF SOUTH AF
«51
E D C T P
Walter Sisulu University
*DUT
DURBAN UNIVERSITY OF TECHNOLOGY
INYUVESI YASETHEMNI YEZO BUCHWEPHESHE
Inland Norway University of Applied Sciences
i Met
Medical University of Graz
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NONINVASIVE METHODS IN CARDIOLOGY 2023
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NONINVASIVE METHODS IN CARDIOLOGY 2023
Chronotherapy of Blood Pressure: Beyond Comparing Morning vs. Evening Dosing
Cornelissen G1, Havelková A2, Siegelová J2, Gubin D3, Beaty LA1, Otsuka KM
'Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA; 2Masaryk University, Brno, Czech Republic;
3Laboratory for Chronobiology and Chronomedicine, Research Institute of Biomedicine and Biomedical Technologies, Medical University, Tyumen, Russia;
4Executive Medical Center, Totsuka Royal Clinic, Tokyo Women's Medical University, Tokyo, Japan
Correspondence:
Germaine Cornelissen Halberg Chronobiology Center University of Minnesota, 420 Delaware St. S.E. MMC8609
Minneapolis, MN 55455, USA Tel.: +1 612 624 6976 E-mail: corneOOl @ umn.edu
Website: https://halbergchronobiologycenter.umn.edu/halberg-chronobiology-center Support:
Halberg Chronobiology Fund (GC)
University of Minnesota Supercomputing Institute (GC)
A&D (GC
Abstract
The day-night ratio (DNR) of blood pressure (BP) is the index currently used most often by those relying on ambulatory blood pressure monitoring (ABPM) for the diagnosis and prognosis of hypertensive patients. It is also used as a gauge of the response to antihypertensive medication. Herein, we illustrate how ongoing debates regarding the relative merits of administering anti-hypertensive drugs in the morning or evening are misguided by trying to answer the wrong question. We review evidence showing that cardiovascular disease risk tends to be more strongly associated with a reverse dipping pattern of BP than with a non-
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dipping pattern. We also offer some explanation why extreme dipping may be associated with increased risk in the elderly while it is protective in younger populations. Based on abstract models, we demonstrate that reliance on the circadian amplitude and phase interpreted in the light of chronobiologic reference values qualified by gender and age constitutes a more robust and more reliable approach than the classification in terms of dipping based on the DNR. We conclude by redefining the question to be answered in future clinical trials, leading to the suggestion of chronotherapy protocols aimed at a personalized treatment of BP disorders.
Introduction
Blood pressure (BP) in clinical health and uncomplicated hypertension undergoes a large-amplitude circadian rhythm with lower values during nightly sleep and higher values during the active daytime [1]. On average, BP is lower in women than in men in the absence of antihypertensive treatment [2]. While systolic (S) BP increases at least up to 80 years of age, diastolic (D) BP reaches a maximum around 40 years of age, and starts decreasing thereafter. As a consequence, pulse pressure (PP), the difference between SBP and DBP starts increasing after 40 years of age [3]. The circadian amplitude of BP also changes as a function of age, reaching a maximum around 45 years of age [3], while the circadian acrophase tends to advance in the elderly [4]. The circadian waveform of BP undergoes further changes with age in terms of the post-prandial dip in early afternoon, which is accentuated in older persons [5].
These changes in circadian characteristics of BP as a function of age were first mapped when ABPM devices became available and were used to monitor clinically healthy populations [6]. On their basis, time-specified reference values were derived [7] as well as reference values, determined as 90% prediction limits, for the parameters of the 24-hour component of BP assessed by cosinor [8, 9]. Vascular variability disorders (VVDs) were defined as conditions such that one or the other circadian characteristic of BP (or heart rate, HR) deviated from the reference range from clinically healthy peers matched by gender and age [10].
Over the years, awareness of the large extent of day-to-day variability in all parameters of the 24-hour BP rhythm emerged [11, 12]. This realization prompted our recommendation to perform ABPM for spans longer than 24 hours [10]. Current practice, however, still limits ABPM mostly to 24 hours in special cases for which a diagnosis is difficult to make, as stipulated in the guidelines [13, 14]. Clinical trials concerned with the optimization of the time of administration of anti-hypertensive medications also often rely on ABPM carried out over spans of 24 hours. Clinicians using ABPM to monitor the BP of their patients mostly rely on an index, the day-night ratio (DNR) that is intended to approximate the circadian variation in BP. Herein, we review some of the literature showing how the DNR affects cardiovascular risk. We show how the information derived from estimates of the circadian amplitude and
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acrophase may be less biased than reliance of the DNR. Finally, we question whether current chronotherapy trials of BP ask the right question and suggest protocols for use in future studies that could resolve the current controversy regarding treatment in the morning or evening, while leading the way toward personalized chronotherapy.
Day-Night Ratio of Blood Pressure and Dipping Patterns - Association with C VD Risk
The day-night ratio (DNR) was introduced as a way to estimate the extent of predictable daily change in BP without having to use regression models [15]. The DNR is computed as DNR = (average daytime BP - average nighttime BP)/(average 24-hour BP), where daytime and nighttime have been defined somewhat differently by different investigators [15-18]. In order to include BP measurements during daytime or nighttime when they are most stable and not contaminated by measurements taken around the times of awakening or falling asleep when BP changes rapidly, we defined daytime as the daily span from 10:00 to 20:00 and nighttime as the daily span from 00:00 to 06:00 [19]. When the times of awakening and falling asleep are known, daytime starts 3 hours after the time of awakening and ends 3 hours before the time of falling asleep, while nighttime starts 1 hour after the time of falling asleep and ends 1 hour before the time of awakening.
ABPM results from clinical studies determined that patients for whom BP dropped by less than 10% during the night compared to daytime had a higher incidence of adverse cardiovascular events than patients with a day-night difference in BP larger than 10% [15-18]. They were called "non-dippers" and "dippers", respectively [15]. Dipping categories based on the DNR were later extended to include reverse dippers (RD) when DNR<0%, non-dippers (ND) when 0%<DNR<10%, dippers (DP) when 10%<DNR<20%, and extreme dippers € when DNR>20% [20]. Dipping has since also been assessed based on the night-day ratio (NDR) of BP [21], defined as NDR = (average nighttime BP)/(average daytime BP). The four dipping categories defined based on the NDR are RD when NDR>1, ND when 1>NDR>0.9, DP when 0.9>NDR>0.8, and ED when NDR<0.8. These limits apply to all adults of both genders.
As illustrated in Figure 1, which summarizes results from Verdecchia et al. [20], non-dipping and reverse dipping have been associated with a higher cardiovascular risk. This study included 3012 initially untreated patients with essential hypertension. Over a mean follow-up period of 8.44 years, 268 patients developed a major cardiovascular event and 220 died. Each patient provided a 24-hour ABPM profile with measurements at 15-minute intervals, which determined that there were 3.9% RD, 27.8% ND, 54.8% DP, and 13.6% ED. RD and ND, but not ED were found to have a higher cardiovascular risk than DP [20].
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NONINVASIVE METHODS IN CARDIOLOGY 2023
While some studies report an increased cardiovascular risk in the absence of BP dipping, reverse dippers are generally found to carry the largest risk [22-31], as illustrated in Figure 2 based on data from Fagard et al. [21]. Conditions such as diabetes [32, 33] and kidney disease [34-36] have long been known to be associated with changes in the circadian BP acrophase, and even with a reversal of the circadian BP rhythm, which can be associated with marked changes in the DNR or NDR (and corresponding dipping category).
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Figure 2. Events after follow-up of23,164 patient-years in 3,468 treated or untreated hypertensive patients from four prospective studies performed in Europe, classified by their night-day ratio as reverse dippers (RD, N=421), non-dippers (ND, N=1407), dippers (DP, N=1295), or extreme dippers (ED, N=345) based on 24-hour ABPM. Data from Fagard et al. [21]. © Halberg Chronobiology Center
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Effect of Phase Shift on the Day-Night Ratio
To illustrate this point, Figure 3 shows how the phase of the circadian rhythm in BP can affect the DNR greatly in the absence of any change in the extent of predictable daily change assessed by the fit of a single 24-hour cosine curve or of a two-component model consisting of cosine curves with periods of 24 and 12 hours that approximates more closely the circadian waveform of BP. In all models of Figure 3, the 24-hour amplitude of systolic (S) BP is 15 mmHg around a rhythm-adjusted mean (MESOR) of 120 mmHg. When the 24-hour acrophase occurs at 6 pm, the DNR is 14.3 and the NDR is 0.87, indicative of a dipper pattern. Shifting this rhythm in SBP as a 2- to 4-hour delay results in large decreases in the DNR (or increases in the NDR) that would be interpreted as representing non-dipping or even reverse dipping patterns even though the 24-hour amplitude remained the same. Phase delays such as those modeled in Figure 3 may be due to differences in chronotype, differences in lifestyle habits, or the presence of underlying conditions such as diabetes or chronic kidney disease, even when the rest-activity schedule is unchanged.
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Figure 3. Left: One- or two-component models approximate the circadian variation in SBP. The Day-Night Ratio (DNR) is between 10% and 20% and the Night-to-Day Ratio (NDR) is between 0.8 and 0.9, both corresponding to a dipper pattern. Right: As compared to the one-component model shown on the left (solid black curve), similar models delayed by 2, 3, or 4 hours (solid, dashed, and dotted gray curves, respectively) are associated with non-dipper and even reverse-dipper patterns. Similar results apply to the two-component model: after a delay of 2, 3, or 4 hours, the DNR is 2.82, -2.78, and -7.65, respectively, and the NDR is 0.97, 1.03, and 1.08, respectively.
© Halberg Chronobiology Center
Effect of Post-Prandial Dip on Day-Night Ratio
Changes in the circadian waveform of BP observed with advancing age include a more pronounced post-prandial dip in the early afternoon [5]. Response to anti-hypertensive
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NONINVASIVE METHODS IN CARDIOLOGY 2023
medication can also account for similar circadian BP patterns. Such a change in the circadian waveform of BP is not necessarily associated with a change in the amplitude of the 24-hour component, but is rather contributed by additional harmonic terms in the model. Often the second and sometimes the third harmonic terms with periods of 12 and 8 hours are sufficient to approximate the post-prandial dip in BP, as shown in Figure 4. Whereas the single-component 24-hour cosine model remains compatible with a dipper pattern based on the DNR and NDR, their computation from the multiple-component model that approximates the data more closely now indicates a non-dipper pattern. The change in dipping category, however, occurred in the absence of a change in the 24-hour amplitude.
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Figure 4. Left: The single-component 24-hour cosine model, with an amplitude of 15 mmHg around a MESOR of 120 mmHg, approximates the circadian variation in SBP of young adults. The DNR is between 10% and 20% and the NDR is between 0.8 and 0.9, both corresponding to a dipper pattern. Right: A composite model, differing mostly from the model on the left by a sharp post-prandial dip in early afternoon, approximates the circadian pattern of SBP in some older individuals. The DNR is below 10% and the NDR is between 0.9 and 1.0, both corresponding to a non-dipper pattern, while the 24-hour amplitude remained unchanged.
© Halberg Chronobiology Center
Is Extreme Dipping Associated with Cardiovascular Risk?
Controversy remains regarding cardiovascular risk associated with extreme dipping. Several Japanese studies reported an increased risk of stroke and silent cerebral disease in association with extreme dipping [37-41]. An increased risk among extreme dippers tends to affect older populations, as extreme dipping is reportedly protective in the young [42-44]. Some investigators have linked the risk associated with extreme dipping to the morning BP surge [45, 46], but others refuted this relationship [47]. As apparent from Figure 2, extreme dipping relates to an increased risk for all cardiovascular events, but not for major cardiovascular events in analyses from the same databases. Our own results based on an Asian population documented a large increase in the risk of cerebral ischemic events but not to coronary artery disease in relation to
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NONINVASIVE METHODS IN CARDIOLOGY 2023
circadian hyper-amplitude-tension (CHAT), which represents too large a 24-hour amplitude of BP [19, 48, 49], Figure 5.
Relative Risk of Systolic CHAT after 6-year Follow-up
100
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Figure 5: Relative risk (and 95% CI) of coronary artery disease (H), retinopathy (E), nephropathy (K), and cerebral ischemic events (B) associated with too large a 24-hour amplitude of systolic (left) or diastolic (right) BP in 297 normotensive or treated hypertensive patients without any morbidity at the start of study. Patients were followed-up for 6 years at 6-month intervals. © Halberg Chronobiology Center
Our results also showed that the 24-hour amplitude of BP does not have a linear relationship with cardiovascular disease risk [5, 48, 49], Figure 6. Our 7-day/24-hour monitoring of clinically healthy individuals also documented how the 24-hour amplitude of BP changes as a function of age in men and women [3, 4]. As seen in Figure 7, the 24-hour BP amplitude of a 75-year old is about half that of a 45-year old, on average. Translating these results into estimates of the DNR or NDR, the 20% or 0.8 limit delineating extreme dipping from dipping requires a larger deviation from norms for a 75-year old than for a 45-year old, thereby accounting, in part, for differences reported in the literature regarding the risk of extreme dipping in the old or the young. Modeling in Figure 8 illustrates this point.
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NONINVASIVE METHODS IN CARDIOLOGY 2023
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90% prediction limits of parameters of the 24-hour BP rhythm from clinically healthy peers matched by gender
and age. © Halberg Chronobiology Center
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NONINVASIVE METHODS IN CARDIOLOGY 2023
Figure 8. The DNR and NDR computed based on one- or two-component models of the circadian BP rhythm already assume values corresponding to extreme dipping when the 24-hour amplitude is still in the acceptable range (see model in middle corresponding to a 24h-A of 16.4 mmHg). They assume values close to 30% or 0.7for models of CHAT (last model on right), deviating markedly from the 20% or 0.8 limit delineating extreme dipping
from dipping. © Halberg Chronobiology Center
Implications for Chronotherapy Trials
Considering that a number of studies find a higher cardiovascular risk among non-dippers and among reverse dippers in particular, whereas extreme dipping tends to be protective in young populations, some investigators consider the additional benefit of achieving a nocturnal BP dip between 10% and 20% when treating hypertensive patients. Several trials compared outcomes between patients receiving anti-hypertensive treatment in the morning or evening [50]. Evening dosing is generally viewed as beneficial since it tends to decrease nocturnal BP, thereby increasing the DNR [51, 52]. Evening dosing achieved a reduction in adverse outcomes mostly in patients with diabetes and chronic kidney disease who tend to have a weakened circadian BP rhythm, some even showing a reverse circadian BP pattern [52-55]. There should be concern, however, for the risk of achieving extreme dipping in some patients with glaucoma, for whom nocturnal hypotension represents a known risk of optic neuropathy [56]. In our experience, similar concern should be extended to patients presenting with CHAT.
The issue of determining the optimal time of administration of anti-hypertensive medications is, however, much broader. Figure 9 illustrates the problem. It displays the average circadian pattern of SBP monitored around the clock for 7 days by ABPM for five different patients, where the data are stacked over an idealized 24-hour day. In one case (left), the circadian variation of SBP is blunted and it would make sense to time treatment aiming at amplifying its circadian rhythm. In another case, BP peaks during the night, when treatment efficacy should reach its maximum. Another case (middle) has an excessive circadian amplitude of SBP (CHAT), for whom caution should be taken not to decrease BP to values that are too low during the night. Maximal drug action may need to target the highest SBP values around mid-day in this case. BP is elevated across the entire day in another case, who would benefit from treatment acting
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NONINVASIVE METHODS IN CARDIOLOGY 2023
equally throughout the 24 hours. Another case (right) shows the characteristic pronounced post-prandial dip in BP in early afternoon. Highest efficacy of the treatment in this case should target two times of day, the morning peak and the evening peak. The point of these examples is that different patients present with different circadian BP profiles in the absence of treatment, suggesting that the optimal treatment time may also differ among them.
Figure 9. The circadian profile ofSBP can differ markedly among patients, suggesting that the optimal time of anti-hypertensive treatment may also differ greatly from one patient to another. © Halberg Chronobiology Center
Rather than asking the question whether evening dosing is better than morning dosing, future clinical trials could ask a more pertinent question while also leading the way toward personalized chronotherapy. One approach could consist of using N-of-6 or N-of-1 designs [57, 58] to first determine the best treatment time for individual patients, then enter patients on that regimen to be compared with matched controls treated conventionally. Another approach could be to monitor BP around the clock for several (e.g., 7) days by ABPM, to analyze the data by cosinor, and to interpret the circadian parameters in the light of chronobiologic reference values from clinically healthy peers matched by gender and age. Based on the results thus obtained, the time when medication needs to be the most effective could be estimated and treatment timing (dosing) could be determined by accounting for the pharmacokinetics of the drug(s) used. Each patient could enter the clinical trial on the regimen that was individually optimized for comparison with a matched control to be treated conventionally. The personalized optimization of treatment timing could account for all VVDs. The 7-day/24-hour ABPM could be repeated at intervals during follow-up when outcomes are recorded prospectively. Results from such clinical trials would answer the question whether a personalized chronotherapeutic approach is superior to treatment as usual.
Discussion and Conclusion
Many factors affect BP [59]. It is not surprising then that circadian characteristics of BP fluctuate greatly from one day to another [12]. These reasons underlie the recommendation to
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NONINVASIVE METHODS IN CARDIOLOGY 2023
monitor BP around the clock for longer than 24 hours [10]. Activity [60], sleep [61], age [44, 62], and medications [63] all reportedly affect the DNR, and are likely to contribute to its poor reproducibility [64, 65]. As shown herein, a different daily routine associated with a phase shift of the circadian BP rhythm, or a more pronounced post-prandial dip in BP can drastically change the DNR and the dipping category when the 24-hour amplitude of BP remains the same. Reproducibility of a diagnosis in terms of VVDs is much higher [66] when a chronobiologic approach is used to interpret cosinor-derived parameters in the light of reference values from clinically healthy peers matched by gender and age.
The limitations of the DNR or NDR need to be better understood. The merits of assessing the circadian BP rhythm in terms of its amplitude and phase should be recognized, and means should be provided for their easy determination by clinicians. The limitations of current clinical trials comparing morning versus evening dosing to draw across-the-board recommendations for treatment timing need to be better understood. Clinical trials should be implemented that aim at personalized chronotherapy by accounting for the fact that different patients present with different circadian BP patterns in the absence of treatment (chronodiagnosis).
Monitoring the circadian variation in BP for spans longer than 24 hours is critical to address the issue of the large day-to-day variability in all parameters of the 24-hour BP rhythm. Estimates of the 24-hour amplitude and phase of BP are more robust than the computation of the DNR or NDR. The interpretation of the 24-hour amplitude and phase in the light of chronobiologic reference values from clinically healthy peers matched by gender and age renders a diagnosis in terms of VVDs more reliable (more reproducible) than a diagnosis in terms of dipping based on the DNR or NDR. Determining whether personalized chronotherapy that accounts for the chronodiagnosis is superior to conventional treatment should be the question investigated in future clinical trials instead of the misguided question whether morning or evening dosing is better, since the best treatment time cannot be the same for a patient with CHAT and for patient who is a reverse dipper.
References
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7-day monitoring in healthy subjects and patients with ischemic heart disease. In: Halberg F, Kenner T, Fišer B, Siegelová J (Eds.) Proceedings, Noninvasive Methods in Cardiology, Brno, Czech Republic. 2009; 330-344.
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6. Scarpelli PT, Livi R, Scarpelli L, Croppi E, Germanö G, Cagnoni S, Halberg F. Cigarette-smoking effects on circadian rhythm parameters of blood pressure. Proc. 2nd Ann. IEEE Symp. on Computer-Based Medical Systems, Minneapolis, June 26-27, 1989. Washington DC: Computer Society Press; 1989. pp. 267-272.
7. Nelson W, Cornelissen G, Hinkley D, Bingham C, Halberg F. Construction of rhythm-specified reference intervals and regions, with emphasis on "hybrid" data, illustrated for plasma Cortisol. Chronobiologia 1983; 10: 179-193.
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10. Halberg F, Cornelissen G, Otsuka K, Siegelová J, Fišer B, Dušek J, Homolka P, Sanchez de la Pena S, Singh RB, BIOCOS project. Extended consensus on means and need to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs). World Heart J 2010; 2 (4): 279-305.
11. Halberg F, Scheving LE, Lucas E, Cornelissen G, Sothern RB, Halberg E, Halberg J, Halberg Francine, Carter J, Straub KD, Redmond DP. Chronobiology of human blood pressure in the light of static (room-restricted) automatic monitoring. Chronobiologia 1984; 11: 217-247.
12. Cornelissen G, Gierke CL, Havelkova A, Dušek J, Siegelová J. Day-to-day variability of circadian characteristics of systolic blood pressure and effect of exercise. In: Kenner T, Cornelissen G, Siegelová J, Dobsak P (Eds.) Noninvasive Methods of Cardiology. Masaryk University, Brno, Czech Republic 2014; 25-32.
13. Greenland P, Peterson E. The new 2017 ACC/AHA guidelines "up the pressure" on diagnosis and treatment of hypertension. JAMA 2017; 318 (21): 2083-2084.
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14. The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. 2018 ESC/ESH Guidelines for the management of arterial hypertension. J Hypertens 2018; 36: 1953-2041.
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22. Kim BK, Kim YM, Lee Y, Lim YH, Shin J. A reverse dipping pattern predicts cardiovascular mortality in a clinical cohort. J Korean Med Sei 2013; 28 (10): 1468-1473.
23. Tadic M, Cuspidi C, Celic V, Pencic B, Mancia G, Grassi G, Stankovic G, Ivanovic B. The prognostic effect of circadian blood pressure pattern on long-term cardiovascular outcome is independent of left ventricular remodeling. J Clin Med 2019; 8 (12): 2126.
24. Abdalla M, Caughey MC, Tanner RM, Booth JN 3rd, Diaz KM, Anstey DE, Sims M, Ravenell J, Muntner P, Viera AJ, Shimbo D. Associations of blood pressure dipping patterns with left ventricular mass and left ventricular hypertrophy in blacks: The Jackson Heart Study. J Am Heart Assoc 2017; 6 (4): e004847.
25. Fujiwara T, Hoshide S, Kanegae H, Kario K. Prognostic value of a riser pattern of nighttime blood pressure in very elderly adults of >80 years: A general practice-based prospective SEARCH study. Am J Hypertens 2020; 33 (6): 520-527.
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26. Tadic M, Cuspidi C, Celic V, Petrovic O, Pencic B, Mancia G, Grassi G, Ivanovic B. The prognostic importance of right ventricular remodeling and the circadian blood pressure pattern on the long-term cardiovascular outcome. J Hypertens 2020; 38 (8): 1525-1530.
27. Gavriilaki M, Anyfanti P, Nikolaidou B, Lazaridis A, Gavriilaki E, Douma S, Gkaliagkousi E. Nighttime dipping status and risk of cardiovascular events in patients with untreated hypertension: A systematic review and meta-analysis. J Clin Hypertens 2020; 22 (11): 1951-1959.
28. Jhee JH, Nam BY, Lee CJ, Park JT, Han SH, Kang SW, Park S, Yoo TH. Soluble urokinase-type plasminogen activator receptor, changes of 24-hour blood pressure, and progression of chronic kidney disease. J Am Heart Assoc 2021; 10 (1): e017225.
29. Tan X, Sundstrom J, Lind L, Franzon K, Kilander L, Benedict C. Reverse dipping of systolic blood pressure is associated with increased dementia risk in older men: A longitudinal study over 24 years. Hypertension 2021; 77 (4): 1383-1390.
30. Cuspidi C, Tadic M, Sala C, Carugo S, Mancia G, Grassi G. Reverse dipping and subclinical cardiac organ damage: a meta-analysis of echocardiographic studies. J Hypertens 2021; 39 (8): 1505-1512.
31. Di Raimondo D, Musiari G, Casuccio A, Colomba D, Rizzo G, Pirera E, Pinto A, Tuttolomondo A. Cardiac remodeling according to the nocturnal fall of blood pressure in hypertensive subjects: The Whole Assessment of Cardiac Abnormalities in Non-Dipper Subjects with Arterial Hypertension (Wacanda) Study. J Pers Med 2021; 11 (12): 1371.
32. Matteucci E, Consani C, Masoni MC, Giampietro O. Circadian blood pressure variability in type 1 diabetes subjects and their nondiabetic siblings - influence of erythrocyte electron transfer. Cardiovascular Diabetology 2010; 9: 61.
33. Matteucci E, Delia Bartola L, Giampietro O. Differences in circadian time structure of diastolic blood pressure between diabetes mellitus and essential hypertension. Diabetology & metabolic syndrome 2012; 4 (1): 51.
34. Nakano S, Uchida K, Kigoshi T, Azukizawa S, Iwasaki R, Kaneko M, Morimoto S. Circadian rhythm of blood pressure in normotensive NIDDM subjects. Its relationship to microvascular complications. Diabetes Care 1991; 14 (8): 707-711.
35. Nakano S, Fukuda M, Hotta F, Ito T, Ishii T, Kitazawa M, Nishizawa M, Kigoshi T, Uchida K. Reversed circadian blood pressure rhythm is associated with occurrences of both fatal and nonfatal vascular events in NIDDM subjects. Diabetes 1998; 47 (9): 1501-1506.
36. Nakano S, Ogihara M, Tamura C, Kitazawa M, Nishizawa M, Kigoshi T, Uchida K. Reversed circadian blood pressure rhythm independently predicts endstage renal failure in non-insulin-dependent diabetes mellitus subjects. Journal of Diabetes & its Complications 1999; 13 (4): 224-231.
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37. Kario K, Pickering TG, Matsuo T, Hoshide S, Schwartz JE, Shimada K. Stroke prognosis and abnormal nocturnal blood pressure falls in older hypertensives. Hypertension 2001; 38 (4): 852-857.
38. Kario K, Shimada K, Pickering TG. Abnormal nocturnal blood pressure falls in elderly hypertension: clinical significance and determinants. Journal of Cardiovascular Pharmacology 2003; 41 (Suppl 1): S61-S66.
39. Kario K, Shimada K. Risers and extreme-dippers of nocturnal blood pressure in hypertension: antihypertensive strategy for nocturnal blood pressure. Clinical & Experimental Hypertension (New York) 2004; 26 (2): 177-189.
40. Maeda K, Yasunari K, Watanabe T, Nakamura M. Oxidative stress by peripheral blood mononuclear cells is increased in hypertensives with an extreme-dipper pattern and/or morning surge in blood pressure. Hypertension Research - Clinical & Experimental 2005; 28 (9): 755-761.
41. Hamada T, Murata T, Narita K, Takahashi T, Wada Y, Kimura H, Yoshida H. The clinical significance of abnormal diurnal blood pressure variation in healthy late middle-aged and older adults. Blood Pressure 2008; 17 (3): 134-140.
42. Ishikawa J, Shimizu M, Hoshide S, Eguchi K, Pickering TG, Shimada K, Kario K. Cardiovascular risks of dipping status and chronic kidney disease in elderly Japanese hypertensive patients. Journal of Clinical Hypertension 2008; 10 (10): 787-794.
43. Palatini P, Verdecchia P, Beilin LJ, Eguchi K, Imai Y, Kario K, Ohkubo T, Pierdomenico SD, Saladini F, Schwartz JE, Wing L, Signorotti S, Reboldi G. Association of extreme nocturnal dipping with cardiovascular events strongly depends on age. Hypertension 2020; 75 (2): 324-330.
44. Cardoso CRL, Salles GF. Associations of the nocturnal blood pressure fall and morning surge with cardiovascular events and mortality in individuals with resistant hypertension. Journal of Hypertension 2021; 39 (6): 1177-1187.
45. Cohen DL, Townsend RR. Is it morning blood pressure surge or extreme nocturnal dipping that accounts for the increased stroke risk in the morning waking hours? Journal of Clinical Hypertension 2014; 16 (12): 847.
46. Gorcan A, Argan O, Avci E, Kiris T, Safak O, Yildirim ST, Yildirim E, Lutfi Kisacik H, Kadi H. A new risk factor for predicting stroke in patients with atrial fibrillation: morning blood pressure surge. Blood Pressure Monitoring 2023; 28 (2): 73-78.
47. Zhang H, Cui Y, Zhao Y, Dong Y, Wang J, Duan D, Ji T, Zhou T, Hu W, Chen Y, Sun S, Gong G, Chai Q, Liu Z. Association of circadian rhythm of blood pressure and cerebral small vessel disease in community-based elderly population. Journals of Gerontology Series A-Biological Sciences & Medical Sciences 2019; 74 (8): 1322-1330.
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48. Otsuka K, Cornelissen G, Halberg F, Oehlert G. Excessive circadian amplitude of blood pressure increases risk of ischemic stroke and nephropathy. J Medical Engineering & Technology 1997; 21: 23-30.
49. Cornelissen G, Halberg F, Otsuka K, Singh RB, Chen CH. Chronobiology predicts actual and proxy outcomes when dipping fails. Hypertension 2007; 49: 237-239.
50. Mackenzie IS, Rogers A, Poulter NR, Williams B, Brown MJ, Webb DJ, Ford I, Rorie DA, Guthrie G, Grieve JWK, Pigazzani F, Rothwell PM, Young R, McConnachie A, Struthers AD, Lang CC, MacDonald TM; TIME Study Group. Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial. The Lancet 2022; 400: 1417-1425.
51. Bowles NP, Thosar SS, Herzig MX, Shea SA. Chronotherapy for Hypertension. Curr Hypertens Rep 2018; 20 (11): 97
52. Wang C, Ye Y, Liu C, Zhou Y, Lv L, Cheng C, Li S, Lou T, Liu X. Evening versus morning dosing regimen drug therapy for chronic kidney disease patients with hypertension in blood pressure patterns: a systematic review and meta-analysis. Intern Med J 2017; 47 (8): 900-906.
53. Stranges PM, Drew AM, Rafferty P, Shuster JE, Brooks AD. Treatment of hypertension with chronotherapy: is it time of drug administration? Ann Pharmacother 2015; 49 (3): 323-334.
54. Chiriaco M, Sacchetta L, Forotti G, Leonetti S, Nesti L, Taddei S, Natali A, Solini A, Trico D. Prognostic value of 24-hour ambulatory blood pressure patterns in diabetes: A 21-year longitudinal study. Diabetes, Obesity & Metabolism 2022; 24 (11): 2127-2137
55. Wang C, Ye Z, Li Y, Zhang J, Zhang Q, Ma X, Peng H, Lou T Prognostic value of reverse dipper blood pressure pattern in chronic kidney disease patients not undergoing dialysis: Prospective cohort study. Scientific Reports 2016; 6: 34932.
56. Melgarejo JD, Lee JH, Petitto M, Yepez JB, Murati FA, Jin Z, Chavez CA, Pirela RV, Calmon GE, Lee W, Johnson MP, Mena LJ, Al-Aswad LA, Terwilliger JD, Allikmets R, Maestre GE, De Moraes CG. Glaucomatous Optic Neuropathy Associated with Nocturnal Dip in Blood Pressure: Findings from the Maracaibo Aging Study. Ophthalmology 2018; 125 (6): 807-814.
57. Prikryl P, Cornelissen G, Neubauer J, Prikryl P Jr, Karpisek Z, Watanabe Y, Otsuka K, Halberg F Chronobiologically explored effects of telmisartan. Clinical and Experimental Hypertension 2005; 2 & 3: 119-128.
58. Watanabe Y, Halberg F, Otsuka K, Cornelissen G. Toward a personalized chronotherapy of high blood pressure and a circadian overswing. Clin Exp Hypertens 2013; 35 (4): 257-266.
59. Gubin DG, Cornelissen G. Factors that must be considered while solving the problem of adequate control of blood pressure. Journal of Chronomedicine 2019; 21 (1): 14-20.
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60. Kario K, Schwartz JE, Pickering TG. Ambulatory physical activity as a determinant of diurnal blood pressure variation. Hypertension 1999; 34 (4 Pt 1): 685-691.
61. Zhao S, Fu S, Ren J, Luo L. Poor sleep is responsible for the impaired nocturnal blood pressure dipping in elderly hypertensive: A cross-sectional study of elderly. Clinical & Experimental Hypertension (New York) 2018; 40 (6): 582-588.
62. Otsuka K, Watanabe H, Cornelissen G, Shinoda M, Uezono K, Kawasaki T, Halberg F. Gender, age and circadian blood pressure variation of apparently healthy rural vs. metropolitan Japanese. Chronobiologia 1990; 17: 253-265.
63. Salles GF, Reboldi G, Fagard RH, Cardoso CR, Pierdomenico SD, Verdecchia P, Eguchi K, Kario K, Hoshide S, Polonia J, de la Sierra A, Hermida RC, Dolan E, O'Brien E, Roush GC. Prognostic effect of the nocturnal blood pressure fall in hypertensive patients: The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) Meta-Analysis. Hypertension 2016; 67 (4): 693-700.
64. Cuspidi C, Meani S, Salerno M, Valerio C, Fusi V, Severgnini B, Lonati L, Magrini F, Zanchetti A. Reproducibility of nocturnal blood pressure fall in early phases of untreated essential hypertension: a prospective observational study. Journal of Human Hypertension 2004; 18 (7): 503-509.
65. Sackett Lundeen L, Otsuka K, Havelkova A, Siegelovä J, Beaty LA, Cornelissen G. From self-surveillance in schools and monitoring in the experimental laboratory to vascular variability disorders. World Heart Journal 2021; 13 (1): 25-27.
66. Sackett Lundeen L, Havelkova A, Beaty LA, Voth M, Siegelovä J, Otsuka K, Cornelissen G. Day-to-day variation in day-night ratio of blood pressure. In: Cornelissen G, Siegelovä J, Dobsak P (Eds.) Noninvasive Methods in Cardiology 2019. Masaryk University, Brno, Czech Republic 2019; 41-49.
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Application of Mathematica Toolkit to Data from Residents in the Arctic
A. Chase Turner1, Denis Gubin2, Larry Beaty1, Germaine Cornelissen1
'Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA
2Laboratory for Chronobiology and Chronomedicine, Research Institute of Biomedicine and
Biomedical Technologies, Medical University, Tyumen, Russia
Correspondence:
Halberg Chronobiology Center University of Minnesota, 420 Delaware St. S.E. - MMC8609 Minneapolis, MN 55455, USA E-mail: turn0383@umn.edu corneOOl @ umn.edu
Website: https://halbergchronobiologycenter.umn.edu/halberg-chronobiology-center Support:
Halberg Chronobiology Fund (GC)
Introduction
The natural photoperiodic environment is a major synchronizer of circadian rhythms [1]. At higher latitudes, it varies drastically across seasons, thereby affecting health and well-being [2]. Working in the Arctic at latitudes above the Polar circle entails month-long sojourns in the Arctic alternating with month-long stays at home in cities located within one time zone of the workplace in Yamburg [3]. For a better understanding of how photoperiodic conditions in the Arctic influence the rhythmic architecture of physiologic processes, another approach can be used, namely examining circadian rhythms of residents who have lived in this region for at least 5 years. As part of a larger investigation, this study addresses a specific methodological question concerning the modelling of circadian rhythms of physiological variables and of the residents' exposure to ambient and blue light to which the circadian system is particularly sensitive [4].
The single cosinor method [5-9] is usually well suited to model the circadian variation in physiological variables. While the 24-hour component usually accounts for the largest
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proportion of the variability in the data, harmonic terms determine the shape of circadian rhythms, which can deviate markedly from a sinusoid. The question herein is whether a single 24-hour model is sufficient to describe the variables monitored in Arctic residents during the summer, or whether a multiple-component model is needed to describe the circadian variation in these variables. Cosinor methods developed in Mathematica that aim at answering this question are illustrated herein.
Subjects and Methods
The study adhered to the tenets of the Declaration of Helsinki and was approved by the Ethics Committee of Tyumen State Medical University (Protocol No. 101, September 13, 2021). Written informed consent was obtained from all participants.
The study was carried out in the nearby locations of Salekhard (66°53' N, 66°60' E), Aksarka settlement (66°33' N, 67°48' E - during March 22-April 8, 2022), and Urengoy town (65°58' N, 76°63' E). It involved 32 residents, in two cohorts, one monitored from June 18 to 24, 2022, and the other from June 18 to 24, 2023, near the summer solstice. Daylight hours were 2:55 am to 9:45 pm (local), and twilight from 9:45 pm to 2:54 am.
Each resident provided 7-day actigraphy records collected by ActTrust 2 wearable devices that measured light exposure in different spectral domains in addition to skin temperature and activity at 1-minute intervals. Analyses herein focus on ambient light and blue light as well as on skin temperature and the zero-crossing mode (ZCM) of activity.
Analyses and graphic illustrations of the results were produced with Mathematica 13.2 running on an Apple macOS 14.0 host with 32 GB of RAM. Other supported Mathematica configurations are documented on the software publisher's website [10].
The following analyses were carried out in Mathematica.
1. Chronograms [11], plots of the data as a function of time, are prepared for one of the study participants as an illustration of some of the graphics generated in Mathematica.
2. Least Squares Spectral Analysis (LSSA), a cosinor-based technique that yields the same results as a Discrete Fourier Transform (DFT) when data are equidistant with no missing value [12], was first applied to all records. LSSA consists of separately fitting (by least squares) cosine curves with frequencies in the range of 1/T (where T is the record length) to l/2At (where At is the sampling interval). In the presence of missing data or when data are not equidistant, provided the data are uniformly distributed, the LSSA still provides approximate results in the frequency range from 1/T to l/2At, where At is less well defined and lies between the average and the longest sampling interval. In a LSSA, trial frequencies
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are incremented by 1/T. Even though records spanned about a week, since the question concerned the circadian variation more specifically, a partial LSSA was performed, as a fundamental period of 24 hours instead of 7 days was considered and only the first 48 harmonic terms (shortest trial period of 0.5 hour) were computed. The LSSA was thus computed at trial periods of 24h, 24h/2=12h, 24h/3=8h, 24h/48=0.5h. Spectral lines with large amplitudes indicate the presence of rhythmic components, which can be validated statistically by the zero-amplitude (no-rhythm) test after adjustment for multiple testing. Herein, they are also considered as input to the next analytical step.
3. For each variable, at each trial period, the arithmetic mean and standard error of amplitudes across all 32 participants were calculated and plotted. Individual LSSA results were compared to the population average, using a logarithmic scale on the vertical axis.
4. The population-mean cosinor, which summarizes results from the single cosinor across all individuals that are randomly selected from a homogeneous population, was applied across all 32 participants for each variable at each trial period of the LSSA. In this approach, instead of computing the arithmetic mean of amplitudes, the average vectorial mean of (amplitude, acrophase) pairs is calculated. In other words, amplitudes are phase-weighted. A component is detected as being statistically significant when individuals in the population have similar phases as well as similar amplitudes. As long as participants are a random sample of a homogeneous population, results from the population-mean cosinor can be extended to the whole population they represent.
5. Based on results from the population-mean least squares spectra, components contributing a sizable amount to the overall variance were selected to model the circadian rhythm of each variable. Several models were considered in order to answer the original question whether a single 24-hour cosine curve fitted to a given variable was sufficient to depict its circadian rhythm.
Results
Data were received as a compressed file, the contents of which were unpacked into 32 individual files, each with 21 columns of measured variables. A Mathematica-based import function was written to import and process the contents of each file to produce 32 individual multiple-variable records from which the four variables of interest were extracted together with their associated date and time stamps. As an example, Figure 1 illustrates the chronogram of all 4 variables from one of the study participants (A002), shown as a ListLogPlot, where a logarithmic scale is used on the vertical axis.
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Subject: A002
TEMPERATURE ZCM
AMB LIGHT BLUE LIGHT
Figure 1. Chronogram of all four variables investigated for participant AO 02, shown as an example of a ListLogPlot in Mathematica (vertical scale is logarithmic).
As an example, Figure 2 shows the LSSA of activity (ZCM) for the same participant (A002), displayed as a ListLogPlot and overlaid with the phase-unweighted average LSSA across all participants (gray line).
a
N
<
100 50
10 5
1
0.5
Subject A002
LSSA ListLogPlot
10 20 30 40
Frequency (Cycles/Day)
A002
Population
Figure 2. LSSA of activity for A002 shown as a ListLogPlot (logarithmic vertical axis) compared to the phase-unweighted average spectrum for the whole population (gray line).
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In order to apply the population-mean cosinor to the LSSA results, a common time reference (tR) was needed. It was set to midnight (00:00) on Wednesday, June 15, 2022 before running the individual LSSA analyses. In addition to obtaining parameter estimates and a measure of their uncertainty as standard error (SE) and 95% confidence limits, results are also shown in a polar plot. In such plots, the 360° circle is equated to the length of the trial period (x) being considered, and 0° shown on top represents tR. The average vector, which originates from the center of the plot is a directed line that has a length and angle corresponding to the vectorial average of individual (A, ((>) pairs, where A is the amplitude and d> is the acrophase in the cosinor model
Y(t) = M + Acos(27t(t-tR)/x + <|>) + e(t).
The 95% confidence region of the average (A, ((>) vector is an ellipse around the tip of the vector. Statistical significance is determined by the non-overlap of the origin (center of the plot) by the error ellipse. In Mathematica, results from the population-mean cosinor spectra include error ellipses in relation to the origin, thereby providing an immediate visual determination of components characterizing the time structure of the variable investigated.
Figure 3 displays results for the first few components from the phase-weighted least squares spectra obtained by population-mean cosinor. Since the fundamental period was 24 hours, the first few components are expected to account for most of the variance in the data. On the left are the first four harmonic terms of the circadian rhythm of activity (ZCM), with periods of 24, 12, 8, and 6 hours. Error ellipses do not cover the origin (black dot) in the case of the 24-, 12-, and 6-hour components, indicating that they all contribute to the waveform of the circadian rhythm of activity. The 8-hour harmonic, however, is not statistically significant since the error ellipse covers the origin. The fact that the error ellipse for the 24-hour component points toward the lower left indicates that, on average, activity is highest in the afternoon (sometime between noon and 6 pm). On the right, results for the 12-hour component are shown for all four variables examined. It can be readily seen from the error ellipses that this component contributes significantly to the waveform of the circadian rhythm of skin temperature and activity but not to that of ambient or blue light.
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Variable	Plot	r
ZCM		24.00 h
ZCM	o-	12.00 h
ZCM	*	8.000 h
ZCM		6.000 h
Variable	Plot	T
TEMPERATURE	• o	12.00 h
ZCM		12.00 h
AMB LIGHT	* *	12.00 h
BLUE LIGHT	* * * t	12.00 h
Figure 3. Polar display of results for the first few components from the phase-weighted LSSA obtained by population-mean cosinor. Left: Results of first four harmonic terms of activity (ZCM). Right: Results of 12-hour component for all four variables. Dashed arrowhead lines indicate components that are not statistically significant (for which the 95% confidence ellipse includes the origin).
Based on results from the phase-unweighted and phase-weighted average least squares spectra, models were derived for the four variables examined herein. As reference, single 24-hour cosine models were generated, using the parameter estimates from the population-mean cosinor spectra. To answer the original question, the second harmonic with a period of 12 hours was added to the model, since this component usually contributes most of the residual variance for these variables. Since some other harmonic terms also reached statistical significance and contributed fairly to the overall variance in the data, additional models were generated that accounted for their contribution.
Results are illustrated for all four variables in Figure 4. In each case, the single 24-hour cosine model and the composite model consisting of cosine curves with periods of 24 and 12 hours are shown. Models incorporating some additional harmonic terms are also included. A single 24-hour cosine component may be sufficient to describe the circadian rhythm of exposure to ambient light and to blue light. This is not the case, however, for activity or skin temperature. For instance, activity is higher in the evening than the morning and values during
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the night are lower when a 2-component model is considered instead of the single 24-hour cosine curve. Likewise, skin temperature assumes higher night-time values and daytime values remain more similar when considering a 2-component model instead of the single 24-hour cosine curve.
00:00        06:00        12:00        18:00 00:00
33.5 m 33.0 Ü) 32.5 5 32.0 m 31.5 I 31.0 |ü 30.5
30.0
As		
		
{24.h,12.h,6.0h,4.8h}
{zi.n.iz.n;
tz*.n>
{24.h,12.h,8.0h,6.0h,4.8h}
\t*t- II, It. 11/
00:00   06:00   12:00   18:00 00:00
00:00 06:00 12:00 18:00 00:00
Figure 4. Single 24-hour and multiple-component models approximating the circadian variation of activity (ZCM) (upper left), skin temperature (lower left), ambient and blue light (upper and lower right).
Discussion and Conclusion
Analyses herein of variables automatically measured by a wearable device during the summer solstice by individuals living in the far north region of Siberia, above the Arctic Circle illustrate the ease with which results can be obtained in Mathematica.
For example, Mathematica's 30 years support of hybrid symbolic-number methodologies and multi-paradigm languages allows for coding using both TraditionalForm and InputForm interchangeably to maximize awareness of the code, as illustrated in Table 1.
	TraditionalForm InputForm
Variance Standard Deviation Covariance	^ £=i (S, - 3T)2                Variance [s] \Jo2s                              StandardDeviation [s] ^ S=i (Si - 5) (t, - t)      Covariance [s, t]
Table 1. Mathematica code examples for well-known statistical functions.
Results in Figure 4 also highlight some methodological issues that remain to be addressed. For instance, models generated for exposure to ambient and blue light assume negative values
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during part of the 24-hour day. Such a result could be interpreted as having no such exposure, but negative values are nonsensical. Data should have been pre-processed, for instance by log-transformation or by square-root transformation prior to analysis, since the assumption of normality of the data is not validated in this case.
Models were determined based on results from the population-mean least squares spectra. A multiple-component model could have been fitted to the individual records before proceeding to the population-mean cosinor analyses. Results herein would not differ very much, however, since most records covered exactly 7 days and there were practically no missing data.
Subject Population Mean
LSSA ListPlot
Population-Mean Cosinor
100
30
24h
0.0000       0.0001        0.0002       0.0003       0.0004 0.0005
Frequency (Hz)
06:00
J_I_I_I_L
12:0C
_!_I_I_I_L
18:00
J_I_I_I_I_L
	•	24.00 h
		
0	•	12.00 h
.0 * *		8.000 h
		6.000 h
o-		4.800 h
Breakfast, Lunch and Dinner?
Figure 5. The three peaks, perhaps related to the timing of breakfast, lunch and dinner, are accounted for by the addition to the model of harmonic terms with periods of 6 and 4.8 hours (they are not present when a 2-component model including cosine curves with periods of 24 and 12 hours is considered, as shown in Figure 4,
top left).
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Of interest is the 4-component model approximating the circadian waveform of activity (ZCM), shown in Figure 5. It includes cosine curves with periods of 24, 12, 6 and 4.8 hours, all detected with statistical significance, and omitting the non-significant 8-hour harmonic (Figure 5, top left and right). The addition of the 6- and 4.8-hour harmonics to the model brings about three daytime peaks that perhaps correspond to breakfast, lunch, and dinner (Figure 5, bottom left) since these residents follow a similar daily routine.
The HCC is creating a Mathematica-based open-source toolkit for Chronobiologists. Utilizing cosinor methods developed in Mathematica will facilitate data analysis to assess their broad time structure, to compare rhythm parameters among individuals or populations, and to model rhythms as illustrated herein for the Arctic residents.
References
1. Halberg F, Halberg E, Barnum CP, Bittner JJ. Physiologic 24-hour periodicity in human beings and mice, the lighting regimen and daily routine. In: Withrow RB (Ed.) Photoperiodism and Related Phenomena in Plants and Animals. Ed. Publ. No. 55. Washington DC: American Association for the Advancement of Science 1959; 803-878.
2. Arendt J. Biological rhythms during residence in polar regions. Chronobiol Int 2012; 29 (4): 379-394.
3. Gubin D, Vetoshkin A, Shurkevich N, Gapon L, Borisenkov M, Cornelissen G, Weinert D. Chronotype and lipid metabolism in Arctic Sojourn Workers. Chronobiol Int 2023; 40 (9): 1198-1208.
4. Tosini G, Ferguson I, Tsubota K. Effects of blue light on the circadian system and eye physiology. Mol Vis 2016; 22: 61-72.
5. Halberg F, Tong YL, Johnson EA. Circadian system phase - an aspect of temporal morphology; procedures and illustrative examples. Proc. International Congress of Anatomists. In: Mayersbach H v, ed. The Cellular Aspects of Biorhythms. Springer-Verlag, New York, 1967; pp. 20-48.
6. Bingham C, Arbogast B, Cornelissen Guillaume G, Lee JK, Halberg F Inferential statistical methods for estimating and comparing cosinor parameters. Chronobiologia 1982; 9: 397-439.
7. Refinetti R, Cornelissen G, Halberg F. Procedures for numerical analysis of circadian rhythms. Biological Rhythm Research 2007; 38 (4): 275-325.
8. Cornelissen G. Cosinor-based rhythmometry. Theoretical Biology and Medical Modelling 2014; 11: 16. 24 pp.
9. Cornelissen G. Applications of cosinor rhythmometry in pharmacology. Journal of Pharmacokinetics and Pharmacodynamics 2021; 48: 339-359.
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10. Wolfram Research, Inc., Mathematica, Version 13.2, Champaign, IL. 2022. https://www.wolfram. com/mathematica/system-requirements.html
11. Halberg F, Carandente F, Cornelissen G, Katinas GS. Glossary of chronobiology. Chronobiologia 1977; 4 (Suppl. 1), 189 pp.
12. Bloomfield P: Fourier Analysis of Time Series: An Introduction. New York: Wiley; 1976.
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Prof. MUDr. Bohumil Fišer, CSc. (October 22.1943 - March 21. 2011)
Marie Nováková
Dept. of Physiology, Faculty of Medicine, Masaryk University
It is hard to believe that prof. Fišer left our community already 12 years ago. His decease at still productive age was unexpected by all his colleagues, students, friends. We knew he was seriously ill, however could not believe that it was true. These days we commemorate birthday anniversary of prof. Fišer. This short remembrance is dedicated to his personality rather than his scientific and political achievements.
Prof. Fišer is remembered among those who were lucky to meet him and to work with him first of all as a great teacher. His lectures represented scientifically-oriented information transfer accompanied by entertaining his students. He was for instance willing to demonstrate symptoms of various disorders, thus showing his students clearly the importance of the subject lectured. Many medical students remember his lectures at Physiology as the most interesting ones among the preclinical subjects.
Prof. Fišer naturally affected also numerous doctoral students passing the Department of Physiology, regardless it was during the years when he served as a head of the department or not. I remember him suggesting some improvements of my experimental set-up, although he was neither my supervisor nor the direct collaborator. He was always willing to give advice, to support, to help.
Bohumil Fišer was each time able to find the proper way how to talk to particular person, he knew almost immediately what kind of communication will work best, he managed to solve various problems. He showed clear social awareness, which later transformed into his engagement in political issues.
The personality of prof. Fišer was extraordinary. I personally very often come across a situation or problem which he mentioned many years ago and predicted what would happen. Not only me, but all my colleagues at the Department of Physiology miss prof. Fišer with his humour and unobtrusive support.
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80 Years Anniversary of Prof. MUDr. Bohumil Fiser, CSc. (October 22.1943 - March 21. 2011)
Jarmila Siegelova
Department of Physiotherapy and Rehabilitation, Faculty of Medicine, Masaryk University, St. Anne's University Hospital in Brno, CZ
Figure 1: Prof. Bohumil Fišer
Prof. Bohumil Fišer was Head of the Department of Physiology, Faculty of Medicine, Masaryk University, Brno in the years 1995-2008, Minister of Health of the Czech Republic in 2000-2002, Member of Executive Committee of WHO in 2003-2008. He was a highly regarded scientist of worldwide renown in the field of normal and pathological physiology and
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a successful organizer in health service, as it was described in the publications by Professor Franz Halberg et al. in World Heart Journal in 2011.
Scientific achievements of Professor Bohumil Fišer CSc. are still fresh in our memory and continue to inspire all who were fortunate to know him. I started working with him in Physiological Institute of Masaryk (at that time Purkynje) University in Brno in 1965. The head of the Institute, Prof. MUDr. Vladislav Kruta, DrSc. signed the Proclamation of 200 words in the year 1968, because of this I was obliged to leave the Institute of Physiology and also Prof. Fišer could not reach higher pedagogical qualification.
After the revolution in 1989 we started a very closed cooperation and also the common international activities with Prof. Dr. Franz Halberg, Dr.h.c. multi, Prof. Germaine Cornelissen, Halberg Chronobiology Center, University of Minnesota, USA, Prof. Dr. Thomas Kenner, Dr.h.c multi, Dean of Faculty of Medicine and Rector of University in Graz, Austria, and Prof. Dr. Jean Paul Martineaud, University of Paris, Hopital Lariboisier, France.
In Brno we started scientific presentations together with the international universities mentioned above and organized in Masaryk University international workshops, meetings and congresses. They presented the results in the fields of cardiology, physiology, pathology, chronobiology, neurology, rehabilitation, internal medicine and neurology which were published as full papers in Brno, as Noninvasive Methods in Cardiology (https://www.med. muni.cz/noninvasive-methods-in-cardiology).
The editors of Noninvasive Methods in Cardiology were Prof. F. Halberg, Prof. T. Kenner, Prof. B. Fišer, Prof. J. Siegelová, later prof. Cornelissen, and Prof. Dobsak. In the year 2003 the Congress of "Noninvasive Methods of Cardiology" was dedicated to the 60 years of Prof. B. Fišer anniversary. The lectures presented at the occasion of the Congress in 2003 were published all in Noninvasive Methods in Cardiology 2003. The Congress in 2003 was organized by Prof. MUDr. Jarmila Siegelová, DrSc.
The Congress in 2003 took place under the auspices of Prof. RNDr. Jiri Zlatuska, CSc, Rector of Masaryk University Brno, Prof. MUDr. Jan Zaloudik, CSc, Dean of Faculty of Medicine Masaryk University Brno, Prof. MUDr. Helena Illnerova, DrSc, President of the Academy of Sciences of the Czech Republic, Prof. MUDr. Jaroslav Blahos, DrSc, President of the Czech Medical Society and World Medical Association, Mgr. Karla Pochyla, Director of National Centre of Nursing and Other Health Professions.
The scientific lectures were presented by Prof. Dr. Franz Halberg, University of Minnesota, USA, Prof. Dr. Germaine Cornelissen, University of Minnesota, USA, Prof. Dr. Thomas Kenner, M.D., Rector of University of Graz, Austria, Prof. Dr. Falko Škrabal, University of Graz, Austria, Prof. Dr. Falko Škrabal, Dr. H. Mayer, Dr. J. Lindenmann, University of Graz,
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Austria, Prof. Dr. Jean Paul Martineaud, University of Paris, France, from Masaryk University, Czech Republic Prof. MUDr. Jarmila Siegelová, DrSc., Prof. MUDr. Bořivoj Semrad, CSc, Prof. MUDr. Natasa Honzikova, CSc, Prof. MUDr. Miloslav Kukleta, CSc, Prof. MUDr. Zdenek Kadanka, CSc, Prof. MUDr. Hana Hrstková, CSc, Prof. MUDr. Petr Dobsak, CSc. and participants from abroad Dr. Itsuro Saito, Kyorin university, Tokio, Japan, Prof. Dr. Takashi Isoyama, Kyorin university, Tokio, Japan, Dr. Othild Schwartzkoppf, University Minnesota, USA, Prof. Dr. Franz Halberg, University of Minnesota, USA, Prof. Dr. Helena Rašková, DrSc, UK, Praha, Czech Republic.
The extensive bibliography of Prof. B. Fišer illustrates the active scientific career of Professor Fišer. The innovations he made in the field brought him to the Head the Department of Physiology Masaryk University and the Czech Republic also could not have chosen a better person to serve as Minister of Health. The responsibilities of Professor Fišer have been expanded even further when he served on the Executive Board of the World Health Organization.
We will continue the work of Professor Bohumil Fišer in medicine together with Professor Germaine Cornelissen, PhD, Director of Halberg Chronobiology Center, Professor of Integrative Biology and Physiology, University of Minnesota, USA and her scientific international team, with Professor Masairo Kohzuki, University Graduate School of Medicine, Japan, Assoc. Prof. PD Dr. med. Nandu Goswami, Dept. of Physiology, Medical University of Graz, Austria, the staff of Dept. of Physiology Masaryk University Professor Marie Novákova, Professor Petr Babula, Dr. Zuzana Novákova, and with the members from Department of Physiotherapy and Rehabilitation, members from Department of Sports Medicine and Rehabilitation, Masaryk University Professor Jarmila Siegelová, Professor Petr Dobsak and his team, Assoc. Professor Michal Pohanka, Dr. Jiri Dusek and others.
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Figure 2: Prof. Franz Halberg, M.D., Dr. h. c. multi and prof. MUDr. Bohumil Fišer, CSc. in Brno at the
symposium Noninvasive Methods in Cardiology 2003
Figure 3: Professor Halberg, Dr. Soucek, Professor Siegelovd, B. Kenner, Professor Kenner, Professor Fiser in
Brno congress
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Figure 4: Prof. Fišer, Prof. Siegelová and Prof. Jean Paul Martineaud, M.D., Paris, France (cooperation from
1976 to 2010) in Dept. of Physiology Brno.
References
1. Proceedings of the 1st Int.Fair of med Technology and Pharmacy. Brno: Eds T Kenner, J.P.Martineaud, P.Mayer, B.Semrád, J.Siegelová, B. Fišer. 1993.
2. Halberg F, Kenner T, Fišer B, Siegelová J(eds): Faculty of Medicine, Masaryk University, Brno (1996).
3. Halberg F, Kenner T, Fišer B, Siegelová J(eds): Chronobiology and non-invasive methods in cardiology. Brno IDV PZ, MU, 1999. ISBN 80-7013-279-5. Faculty of Medicine, Masaryk University, Brno (1999).
4. Halberg F, Kenner T, Fišer B (eds): The importance of chronobiology in diagnosis and therapy of internal diseases. Faculty of Medicine, Masaryk University, Brno (2002)
5. Halberg F, Kenner T, Siegelová J (eds): The importance of chronobiology in diagnosis and therapy of internal diseases. Faculty of Medicine, Masaryk University, Brno (2003)
6. Cornelissen G, Kenner T, Fišer B, Siegelová J (eds): Chronobiology in medicine. Faculty of Medicine, Masaryk University, Brno (2004)
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7. Halberg F, Kenner T, Fišer B, Siegelová J (eds): Nonivasive methods in cardiology 2006. Faculty of Medicine, Masaryk University, Brno (2006)
8. Halberg F, Kenner T, Fišer B, Siegelová J (eds): Nonivasive methods in cardiology 2007. Faculty of Medicine, Masaryk University, Brno (2007)
9. Halberg F, Kenner T, Fišer B, Siegelová J (eds): Nonivasive methods in cardiology 2008 Faculty of Medicine, Masaryk University, Brno (2008)
10. Halberg F, Kenner T, Fišer B, Siegelová J (eds): Nonivasive methods in cardiology 2009 Faculty of Medicine, Masaryk University, Brno (2009)
11. Halberg F, Kenner T, Fišer B, Siegelová J(eds): Nonivasive methods in cardiology 2010; Faculty of Medicine, Masaryk University, Brno (2010)
12. Přikryl P, Siegelová J, Cornélissen G, Dušek J, Dankova E, Fišer B, Vacha J, Ferrazzani S, Tocci A, Caruso A, Rao G, Fink H, Halberg F, International Womb-to-Tomb Chronome Initiative Group: Chronotherapeutic pilot on 6 persons may guide tests on thousands: Toward a circadian optimization of prophylactic treatment with daily low-dose aspirin. University of Minnesota/ Medtronic Chronobiology Seminar Series, #3, December 1991, 4 pp. text, 4 figures.
13. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. 24-Stunden-Baroreflex-Sensitivitätsmessung bei normotonen Personen. Hochdruck 11: 101, 1991.
14. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Baroreflex sensitivity during 24 hours. Scripta medica (Brno) 64: 186, 1991.
15. Fišer B., Siegelová J., Dušek J., Cornélissen G., Halberg F. Baroreflex heart rate sensitivity during 24 hours period evaluated by spectral analysis of blood pressure record. Scripta medica (Brno) 65: 315, 1992.
16. Fišer B., Siegelová J., Dusek J., Cornélissen G., Halberg F. Cosinor analysis of baroreceptor heart rate sensitivity during 24-hour period. Arch. int. Physiol. Biochim. Biophys. 100: A87, 1992.
17. Fišer B., Siegelová J., Dusek J., Halberg F, Cornélissen G. Circadian variation of baroreflex heart rate sensitivity in man. Abstract, IV International Symposium on Control of Heart Rhythm, Slovak Academy of Sciences, Smolenice Castle, April 6-9, 1992, #11.
18. Fišer B., Siegelová J., Dusek J., Halberg F, Cornélissen G. Is the circadian variability of baroreflex dependent upon sleep? Abstract, 6th Int. Cong. Psychophysiology, Charité, Berlin, Germany, Sept. 2-6, 1992, p. 63.
19. Siegelová J., Fišer B., Dusek J., Cornélissen G., Halberg F. Analysis of time parameters of respiratory cycle during 24 hours. Arch. int. Physiol. Biochim. Biophys. 100: A130, 1992.
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20. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Conscious state and control of breathing: power spectral density of respiratory and cardiovascular parameters. Abstract, 6th Int. Cong. Psychophysiology, Charitě, Berlin, Germany, Sept. 2-6, 1992, p. 219.
21. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F Noninvasive determination of baroreflex heart rate sensitivity in patients with mild hypertension during 24-hours. Abstracts, 14th Scientific Meeting, International Society for Hypertension, Madrid, June 14-19, 1992, p. 326.
22. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F Spectral analysis of the timing of respiratory cycle and cardiovascular parameters during 24 hours period. Abstract, 2nd High Tatras International Health Symposium: Health Management, Organization, and Planning in Changing Eastern Europe, Štrbské Pleso, Czecho-Slovakia, October 16-18, 1992, p. 38.
23. Siegelová J., Fišer B., Dušek J., Halberg F, Cornélissen G. Circadian variations of baroreflex heart rate sensitivity in man. Physiological Research 41: 15 pp., 1992.
24. Siegelová J., Fišer B., Dušek J., Halberg F, Cornélissen G. Control of respiratory cycle during 24-hours period. Abstract, 13th Martin's Days of Respiration, Martin, September 7-8, 1992, p. 16.
25. Siegelová J., Fišer B., Dušek J., Semrád B., Halberg F, Cornélissen G. 24-hodinové monitorování krevního tlaku u pacientu s esenciální hypertenzí. Abstract, XX Celostátní Internisticky Kongres s Mezinárodní Ucasti Zlin, 1992, p. 64.
26. Siegelová J., Fišer B., Dušek J., Semrád B., Mayer P., Sevela K., Halberg F, Cornélissen G. Circadian variations of blood pressure in patients with essential and nephrogen hypertension. Scripta medica (Brno) 65: 316, 1992.
27. Siegelová J., Fišer B., Sevela K., Dusek J., Mayer P., Halberg F, Cornélissen G. 24-hodinové monitorování krevního tlaku u pacientu s nefrogenné hypertenzí léčených aceprilem. Abstract, XX Celostátní Internisticky Kongres s Mezinárodní Ucasti, Zlin, 1992, p. 65.
28. Dusek J., Siegelová J., Fišer B., Al-Kubati M., Cornélissen G., Halberg F Noninvasive determination of baroreflex heart rate sensitivity in patients with essential hypertension during 24 hours. Abstract 173.38/P, IUPS Congress, Glasgow, 1993, p. 79.
29. Fišer B., Siegelová J., Dusek J., Cornélissen G., Halberg F Is the circadian variability of baroreflex dependent upon sleep? Int. J. Psychophysiol. 14: 122, 1993.
30. Fišer B., Siegelová J., Dusek J., Cornélissen G., Halberg F Determination of heart rate-baroreflex sensitivity in man by spectral analysis during 24-hour period. Scripta medica (Brno) 66: 11-14, 1993.
31. Fišer B., Siegelová J., Dusek J., Al-Kubati M., Cidl K., Semrád B., Cornélissen G., Halberg F Determination of baroreflex heart rate sensitivity in patients with essential hypertension during 24 hours using vasodilatation method. Proceedings, 1st Int. Fair of Medical Technology and Pharmacy,
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Brno, Czech Rep., November 3-6, 1993, Kenner T., Marineaud J.P., Mayer P., Semrád B., Siegelová J., Fišer B. eds., pp. 43-52.
32. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Conscious state and control of breathing power spectral density of respiratory and cardiovascular parameters. Int. J. Psychophysiol. 14: 149-150, 1993.
33. Siegelová J., Fišer B., Dušek J., Mayer P., Semrád B., Halberg F, Cornélissen G. Cirkadianni variabilita krevniho tlaku u pacientu v administrative. "Clovek a technika ocima ergonoma", Sbornik, Vysoká škola zemědělská, Brno, 1993, pp. 30-37.
34. Siegelová J, Fišer B, Dušek J, Semrád B, Cidl K, Sevela K, Halberg F, Cornélissen G. Blood pressure monitoring in patients with essential hypertension during 24-hour. In: Kenner T, Marineaud JP, Mayer P, Semrád B, Siegelová J, Fišer B, editors. Proceedings, 1st Int. Fair of Medical Technology and Pharmacy, Brno, Czech Rep.; November 3-6, 1993. p. 53-59.
35. Siegelová J., Fišer B., Dušek J., Semrád B., Cornélissen G., Halberg F. Baroreflex heart rate sensitivity measurement in patients with essential hypertension (I WHO) during 24-hour period. Proceedings, 1st Int. Fair of Medical Technology and Pharmacy, Brno, Czech Rep., November 3-6, 1993, Kenner T., Marineaud J.P., Mayer P., Semrád B., Siegelová J., Fišer B. eds., pp. 36-39.
36. Siegelová J., Fišer B., Dušek J., Mayer P., Halberg F, Cornélissen G. Circadian variation of baroreflex heart rate sensitivity using non-invasive determination in healthy subjects. Proceedings, 1st Int. Fair of Medical Technology and Pharmacy, Brno, Czech Rep., November 3-6, 1993, Kenner T., Marineaud J.P., Mayer P., Semrád B., Siegelová J., Fišer B. eds., pp. 12-19.
37. Siegelová J., Fišer B., Dušek J., Semrád B., Halberg F, Cornélissen G. 24-hodinove monitorováni krevniho tlaku u pacientu s esencialni hypertenzi. Vnitř. Lek. 39: 183-190, 1993.
38. Siegelová J, Fišer B, Dušek J, Sevela K, Halberg F, Cornélissen G. Circadian variability of blood pressure in patients with essential hypertension and nephrogenous hypertension treated with enalapril. Scripta medica (Brno) 1993; 66: 99-104.
39. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Spectral analysis of the timing of respiratory cycle and cardiovascular parameters during 24 hours period. 2nd High Tatras International Health Symposium: Health Management, Organization, and Planning in Changing Eastern Europe, Štrbské Pleso, Czecho-Slovakia, October 16-18, 1992, New York, Bratislava, 1993, pp. 71-78.
40. Cornélissen G, Bingham C, Siegelová J, Fišer B, Dušek J, Přikryl P, Sonkowsky RP, Halberg F. Cardiovascular disease risk monitoring in the light of chronobioethics. Chronobiologia 1994; 21: 321-325.
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41. Cornélissen G., Halberg F. Chronobiology of blood pressure: international cooperation with Dr. Jarmila Siegelová, Dr. Jiri Dusek and Dr. Bohumil Fišer of Masaryk University. Scripta medica (Brno) 67 (Suppl. 1): 7-8, 1994.
42. Cornélissen G, Sothern RB, Wendt HW, Tarquini B, Antunano M, Siegelová J, Fišer B, Dusek J, Přikryl P, Halberg F Statistical significance without biologic signification is not enough: illustrative example. Chronobiologia 1994; 21: 315-320.
43. Dusek J., Siegelová J., Fišer B., Cornélissen G., Halberg F. Chronobiology of blood pressure in waking man under light mental load. Proc. Workshop, Chronobiology in Health and Disease— Control of Cardiovascular and Respiratory Functions, Medical Faculty, Masaryk University, Brno, Czech Republic, July 2-4, 1994, pp. 33-37.
44. Halberg F, Bingham C, Siegelová J, Fišer B, Dusek J, Přikryl P, Sonkowsky RP, Cornélissen G. "Cancer marker chronomes" assessed in the light of chronobioethics. Chronobiologia 1994; 21: 327-330.
45. Siegelová J., Fišer B., Al-Kubati M., Dusek J., Cornélissen G., Halberg F Airway resistance and cardiovascular parameters during a 24-hour period. In: Proceedings, 3rd High Tatras International Health Symposium, Preventive and Clinical Medicine in Changing Europe, Salat D., Badalik L., Krcmery V. (eds.), Sympos, Tatranská Polianka, Slovak Republic, 1994, pp. 386-391.
46. Siegelová J., Fišer B., Dusek J., Cornélissen G., Halberg F Chronobiology of blood pressure in essential hypertension. Proc. Workshop, Chronobiology in Health and Disease—Control of Cardiovascular and Respiratory Functions, Medical Faculty, Masaryk University, Brno, Czech Republic, July 2-4, 1994, pp. 13-25.
47. Siegelová J., Fišer B., Dusek J., Cornélissen G., Halberg F. Cosinor analysis of 24-hour variations of respiratory and cardiovascular values in awake healthy man. Abstract, XIV Martin's Days of Respiration, September 6-7, 1994, Martin, Czech Rep. (?), p. 6.
48. Siegelová J., Fišer B., Dusek J., Halberg F, Cornélissen G. Cosinor analysis of blood pressure in patients with essential and nephrogenous hypertension. Proc. International Workshop, Sun, Moon and Living Matter, Mikulecky M. (ed.), Bratislava, Slovakia, June 29-July 1, 1994. Slovak Medical Society, Bratislava, 1994, pp. 116-121.
49. Siegelová J., Fišer B., Dusek J., Halberg F., Cornélissen G. Posobeni bdelehu stavu a lehke mentalni zateze na cirkadianni variabilitu krevniho tlaku a zdravých osob. Česka Ergonomická Společnost uzemni organizace Brno a katedra automobilu Vojenské akademie v Brne, Seminar: Cesty Rozvoje a Uplatňováni Ergonomie a Bezpečnosti Prače v Podminkach Denni Praxe, 25 května 1994, pp. 17-24. [In Czech.]
50. Dusek J., Siegelová J., Fišer B., Cornélissen G., Halberg F. Chronobiology of blood pressure in waking man under light mental load. Scripta medica (Brno) 68: 62-63, 1995.
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51. Dušek J., Siegelová J., Nekvasil R., Cornélissen G., Halberg F. Circaseptan rhythm in blood pessure and heart rate in newborns. Abstract, MEFA '95 Congress, Brno, Czech Republic, October 24-27, 1995, p. 10.
52. Dušek J., Siegelová J., Fišer B., Nekvasil R., Cornélissen G., Halberg F. Blood pressure variations in newborns. Abstract #64, 1st Congress, Federation of European Physiological Societies, September 9-12,1995, Maastricht, The Netherlands. Pflügers Archiv / Eur. J. Physiol. 430 (Suppl.): R24, 1995.
53. Halberg F, Cornélissen G, Johnson D, Wrbsky P, Portela A, Beystrom B, Siegelová J, Fišer B, Dušek J, Nekvasil R, Syutkina EV, Grigoriev AE, Abramian A, Mitish M, Yatsyk GV, Revilla M, Ardura J, Garcia Alonso L, Bakken E, Delmore P, Maggioni C, Tarquini B, Mainardi G, Otsuka K, Watanabe Y, Kumagai Y, Wakasugi K, Saito Yuzo, Tamura K. Chronobiologic environmental optimization starting with neonatal care: opportunities for health and device industries. Handout, The Physical and Developmental Environment of the High-Risk Infant, Orlando, Florida, January 19-21, 1995, 70 pp.
54. Halberg F, Cornélissen G, Raab F, Schaffer E, Siegelová J, Fišer B, Dušek J, Přikryl P, Otsuka K. Automatic physiologic 7-day monitoring and chronobiology. Jpn J Electrocardiol 1995; 15 (Suppl. 1): S-1-5-S-1-11.
55. Halberg F, Cornélissen G, Siegelová J, Fišer B, Dušek J, Přikryl P, Otsuka K. Automatic physiology 7-day monitoring and chronobiology. Policlinico (Chrono) 1995; 1 (2): 33-42.
56. Siegelová J, Cornélissen G, Dušek J, Přikryl P, Fišer B, Dankova E, Tocci A, Ferrazzani S, Hermida R, Bingham C, Hawkins D, Halberg F. Aspirin and the blood pressure and heart rate of healthy women. Policlinico (Chrono) 1995; 1 (2): 43-49.
57. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Cosinor analysis of 24-hour blood pressure profile in hypertensives before and after treatment with ACE-inhibitor enalapril. EuroRehab 4: 203-206, 1995.
58. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Chronobiology of blood pressure in essential hypertension. Scripta medica (Brno) 68: 60-61, 1995.
59. Cornélissen G, Halberg F, Johnson D, Gubin D, Gubin G, Otsuka K, Watanabe Y, Kumagai Y, Syutkin V, Syutkina E, Grigoriev AE, Turti T, Mitish M, Siegelová J, Fišer B, Dušek J, Garcia Alonso L. Blood pressure and heart rate chronomes, yardsticks of ontogeny and vascular disease risk. Keynote #114, 2nd World Congress of Cellular and Molecular Biology, Ottawa, Canada, September 3-7, 1996. Cell Molec Biol 1996; 42 (Suppl.): S83-S84.
60. Cornélissen G., Siegelová J., Fišer B., Dušek J., Halberg F. Current limitations and promise of ambulatory blood pressure monitoring. In: Proceedings, Cardiovascular Coordination in Health and Blood Pressure Disorders, Medical Faculty, Masaryk University, Brno, Czech Republic, May 24, 1996, Halberg F., Kenner T., Fišer B., Siegelová J. eds., 1996, pp. 11-13.
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61. Dušek J., Siegelová J., Al-Kubati M., Fišer B., Cornélissen G., Halberg F. Blood pressure variability during 24 h in patients with essential hypertension. Abstract, Aerosols in Diagnosis, Therapy, and Prophylaxis & Cardio-Respiratory Relations, International Symposium, High Tatras, Sanatorium Helios, Slovakia, May 14-17, 1996, p. 19.
62. Fišer B., Siegelová J., Turti T, Syutkina E.V., Cornélissen G., Grigoriev A.E., Mitish M.D., Abramian A.S., Dušek J., Nekvasil R., Al-Kubati M., Muchova L., Halberg F. Neonatal blood pressure and heart rate rhythm: multiseptan over circadian prominence. Abstract, International Workshop and Teaching Course: Spontaneous Motor Activity as a Diagnostic Tool, Karl-Franzens-Univ., Graz, Austria, September 11-18, 1996, p. 64.
63. Fišer B, Siegelová J, Cornélissen G, Dušek J, Al-Kubati M, Watanabe Y, Halberg F. Chronometaanalysis of blood pressure data from drug tests. Abstract, 2nd Int. Symp. of Chronobiology and Chronomedicine, Shenyang, China, Sept. 28-Oct. 2, 1996. p. 53-54.
64. Halberg F, Cornélissen G, Gubin D, Gubin G, Fišer B, Dušek J, Al-Kubati M, Siegelová J. Circadiani, circaseptani, circasemiseptanique in chronomis seclusorum, praematurorum, seniumque: in honorem Johannis Penazensis modo Mendeliano, Goedeliano, Keplerianoque. In: Halberg F, Kenner T, Fišer B, Siegelová J, editors. Proceedings, Cardiovascular Coordination in Health and Blood Pressure Disorders, Brno, Czech Republic: Medical Faculty, Masaryk University; May 24, 1996. p. 8-10.
65. Siegelová J, Dušek J, Fišer B, Nekvasil R, Muchova M, Cornélissen G, Halberg F. Circaseptan rhythm in blood pressure and heart rate in newborns. Scripta medica (Brno) 1996; 67 (Suppl. 2): 63-70.
66. Siegelová J., Fišer B., Dušek J., Al-Kubati M., Nekvasil R., Cornélissen G., Halberg F. Blood pressure and heart rate coordination in newborn: circadian and circaseptan rhythms. Abstract, International Workshop and Teaching Course: Spontaneous Motor Activity as a Diagnostic Tool, Karl-Franzens-Univ., Graz, Austria, September 11-18, 1996, p. 63.
67. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Limitace ambulantniho monitorováni krevniho tlaku. In: XII. Pracovni Konference Arterialni Hypertenze a Prevence Kardiovaskularnich Chorob, Abstrakta, Dum techniky Brno, 1996, p. 10.
68. Siegelová J., Fišer B., Kadanka Z., Moran M., Dušek J., Al-Kubati M., Cornélissen G., Halberg F. Sleep apnea syndrome and 24-h blood pressure. Electroenceph. Clin. Neurophysiol. 99: 393, 1996.
69. Siegelová J, Moran M, Fišer B, Kadanka Z, Dušek J, Al-Kubati M, Cornélissen G, Halberg F. Blood pressure monitoring in healthy subjects, in patients with sleep apnea syndrom[e] and in patients with essential hypertension. Scripta medica (Brno) 1996; 67 (Suppl 2): 59-62. [In Czech.]
70. Siegelová J, Cornélissen G, Halberg F, Fišer B, Dušek J, Al-Kubati M, Machat R, Kumagai Y, Watanabe Y, Otsuka K. Self-starting cumulative sums for the individualized assessment of
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antihypertensive response and optimization by timing. Keynote, 2nd Int. Symp. of Chronobiology and Chronomedicine, Shenyang, China, Sept. 28-Oct. 2, 1996. p. 48.
71. Siegelová J., Fišer B., Al-Kubati M., Dušek J., Cornélissen G., Halberg F. Baroreflex heart rate sensitivity in hypertensives: the role of antihypertensive therapy. In: Proceedings, Cardiovascular Coordination in Health and Blood Pressure Disorders, Medical Faculty, Masaryk University, Brno, Czech Republic, May 24, 1996, Halberg F., Kenner T., Fišer B., Siegelová J. eds., 1996, pp. 18-34. [2221]
72. Siegelová J., Morán M., Fišer B., Kadanka Z., Dušek J., Al-Kubati M., Halberg F., Cornélissen G. Circadian variations in blood pressure in patients with sleep apnea and essential hypertension. Abstract PS 103, 23rd Congress, International Society of Internal Medicine, Manila, Philippines, February 1-6, 1996, p. 159. [2218]
73. Siegelová J., Morán M., Fišer B., Kadanka Z., Dušek J., Al-Kubati M., Halberg F., Cornélissen G. Circadian variations in blood pressure in patients with sleep apnea and essential hypertension. Proceedings, 23rd Congress, International Society of Internal Medicine, Manila, Philippines, February 1-6, 1996, Aquino A.V., Piedad F.F., Sulit Y.Q.M. (eds.), Monduzzi Editore, Bologna, 1996, pp. 273-276.
74. Turti T, Syutkina EV, Cornélissen G, Grigoriev AE, Mitish MD, Abramian AS, Siegelová J, Fišer B, Dušek J, Al-Kubati M, Muchova L, Uhlir M, Halberg F Multiseptan-over-circadian prominence of neonatal blood pressure and heart rate in Moscow, Russia. Scripta medica (Brno) 1996; 67 (Suppl. 2): 85-92.
75. Baevsky RM, Petrov VM, Cornélissen G, Halberg F, Orth-Gomér K, Akerstedt T, Otsuka K, Breus T, Siegelová J, Dušek J, Fišer B. Meta-analyzed heart rate variability, exposure to geomagnetic storms, and the risk of ischemic heart disease. Scripta medica (Brno) 1997; 70: 199-204.
76. Gubin D., Cornélissen G., Halberg F, Fišer B., Dušek J., Al-Kubati M., Siegelová J., Gubin G. Aging is accompanied by increased variability and acircadian dessimination of blood pressure (BP) biorhythms. Proc. XXXIII Int. Cong. International Union of Physiological Sciences, St. Petersburg, Russia, June 30-July 5, 1997, abstract P041.42.
77. Gubin D, Cornélissen G, Halberg F, Gubin GD, Turti T, Syutkina EV, Grigoriev AE, Mitish MD, Yatsyk GV, Ikonomov O, Stoynev A, Madjirova N, Siegelová J, Fišer B, Dušek J. Half-weekly and weekly blood pressure patterns in late human ontogeny. Scripta medica (Brno) 1997; 70: 207-216.
78. Halberg F., Cornélissen G., Watanabe Y, Siegelová J., Fišer B., Dušek J., Al-Kubati M. Chronobiologic concepts: tempora mutantur et nos mutamur in illis. Scripta medica (Brno) 70: 231-237, 1997.
79. Halberg F., Cornélissen G., Wendt H, Siegelová J., Dušek J., Fišer B. New trends in cosmobiophysics and the need for a space weather report. Folia Mendeliana 31-32, Supplementum ad Acta Musei Moraviae, Scientiae naturales LXXXI-II: 13-15,1996/1997 (© 1997).
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80. Siegelová J., Cornélissen G., Dušek J., Fišer B., Watanabe Y., Otsuka K., Halberg F. Diagnosis and assessment of treatment effects: a single 24-hour blood pressure (BP) monitoring (ABPM) profile. 5th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 5-8, 1997, section 6 (Neinvazivni vyšetřováci metody v kardiologii), abstract 8.
81. Siegelová J., Fišer B., Dušek J., Cornélissen G., Halberg F. Circaseptan variability in blood pressure in newborn. Abstract #314, International Congress on Chronobiology. Chronobiology int. 14 (Suppl. 1): 158, 1997.
82. Siegelová J, Fišer B, Dušek J, Halberg F, Cornélissen G. 24-h blood pressure profile in essential hypertension after verapamil, nitrendipine and enalapril treatment. Scripta medica (Brno) 1997; 70: 373-374.
83. Siegelová J., Fišer J., Kadanka Z., Moran M., Dušek J., Cornélissen G., Halberg F. Syndrom spankove apnoe a 24-hodinove monitorováni krevniho tlaku. Abstract, XIV konference o arterialni hypertenzi & VI konference preventivni kardiologie, Plzeň, 15.-17. rijna 1997, p. 43.
84. Siegelová J., Kadanka Z., Moran M., Fišer B., Homolka P., Dobsak P., Dušek J., Cornélissen G., Halberg F. 24-hour blood pressure profile in patients with sleep apnea syndrome: the effect of therapy. 5th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 5-8, 1997, section 6 (Neinvazivni vyšetřováci metody v kardiologii), abstract 12.
85. Syutkina EV, Cornélissen G, Grigoriev AE, Mitish MD, Turti T, Yatsyk GV, Pimenov K, Breus TK, Studenikin MY, Siegelová J, Fišer B, Dusek J, Johnson D, Halberg F. Neonatal intensive care may consider associations of cardiovascular rhythms with local magnetic disturbance. Scripta medica (Brno) 1997; 70: 217-226.
86. Siegelová J, Cornélissen G, Dusek J, Fišer B, Watanabe Y, Otsuka K, Halberg F. Diagnosis and assessment of treatment effects: a single 24-hour blood pressure monitoring profile. Scripta medica (Brno) 1998; 71: 209-214.
87. Siegelová J., Fišer B., Dusek J., Cornélissen G., Halberg F. Circadian variability of rate pressure product in hypertension with enalapril therapy. Abstract, Investigator-Initiated Satellite Symposium to 17th Scientific Meeting, International Society of Hypertension: Renin-angiotensin-aldosterone system: Where to block it ?, Prague, Czech Republic, June 4, 1998, p. 6.
88. Siegelová J., Fišer B., Dusek J., Dobsak P., Cornélissen G., Halberg F. Cirkadianni kolisani kardiovaskularnich veličin. Abstract, Nove Trendy ve Funkcni Diagnostice a Rehabilitaci, Slavnosti Pracovni Schůze, 75 Let, Brno 27. února 1998, p. 12.
89. Siegelová J., Fišer B., Dusek J., Placheta Z., Cornélissen G., Halberg F. Circadian variability of rate pressure product in essential hypertension with enalapril therapy. Abstract 3, Neinvazivni metody v
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kardiovaskulárním výzkumu, 6th International Fair of Medical Technology and Pharmacy, MEFA Congress, Brno, Czech Republic, November 3-4, 1998.
90. Siegelová J., Kadanka Z., Moran M., Fišer B., Homolka P., Dobsak P., Dušek J., Cornélissen G., Halberg F 24-h blood pressure profile in patients with sleep apnea syndrom: the effect of therapy. Scripta medica (Brno) 71: 239-244, 1998.
91. Siegelová J., Fišer B., Dušek J., Kadanka Z., Moran M., Cornélissen G., Halberg F Sleep apnea syndrom[e] and circadian blood pressure variability: the effect of CPAP therapy. Abstract, XVI Martin Days of Respiration with international participation, Martin, Czech Republic, September 16-17, 1998, p. 26.
92. Halberg F, Cornélissen G, Schwartzkopff O, Syutkina EV, Grigoriev AE, Mitish MD, Yatsyk GV, Studenikin MY, Gubin D, Gubin G, Siegelová J, Fišer B, Dušek J, Homolka P, Watanabe Y, Otsuka K, Perfetto F, Tarquini R, Delmore P. Spin-offs from blood pressure and heart rate studies for health care and space research (review), in vivo 1999; 13: 67-76.
93. Fišer B, Cornélissen G, Siegelová J, Dušek J, Homolka P, Mazánkova V, Halberg F Increase in stroke deaths after 1997 in the Czech Republic. MEFA 8th International Fair of Medical Technology and Pharmacy, Brno, Czech Republic, 7-10 Nov 2000, abstract 4.
94. Halberg F, Cornélissen G, Otsuka K, Watanabe Y, Katinas GS, Burioka N, Delyukov A, Gorgo Y, Zhao ZY, Weydahl A, Sothern RB, Siegelová J, Fišer B, Dušek J, Syutkina EV, Perfetto F, Tarquini R, Singh RB, Rhees B, Lofstrom D, Lofstrom P, Johnson PWC, Schwartzkopff O, International BIOCOS Study Group. Cross-spectrally coherent -10.5- and 21-year biological and physical cycles, magnetic storms and myocardial infarctions. Neuroendocrinol Lett 2000; 21: 233-258. [Invited presentation, NATO Advanced Study Institute on Space Storms and Space Weather Hazards, Crete, Greece, June 19-29, 2000.]
95. Halberg F, Cornélissen G, Sanchez de la Pefia S, Schwartzkopff O, Wall DG, Kysylyczyn J, Sarkozy S, Delmore P, Borer K, Otsuka K, Siegelová J, Homolka P, Dušek J, Fišer B. [Why and how to implement 7-day/24-hour blood pressure monitoring.] Addendum 1, Proceedings, 4th International Symposium of Chronobiology and Chronomedicine, Yantai, China, Oct. 7-14, 2000, 37 pp. [Translated into Chinese.]
96. Halberg F, Cornélissen G, Siegelová J, Fišer B, Dušek J, Otsuka K, Delyukov AA, Gorgo Y, Gubin DG, Gubin GD, Schwartzkopff O. The Cosmos and CHAT, prompting blood pressure and heart rate monitoring for Derer's week. Bratislavské lékařské listy 2000; 101: 260-271.
97. Siegelová J, Dušek J, Fišer B, Halberg F, Cornélissen G. Biological rhythms in medicine. J Oncol Pharm Practice 2000; 6: 15-16 (www.nature.com/jopp).
98. Siegelová J, Fišer B, Dušek J, Halberg F, Cornélissen G. Circadian variability of blood pressure. Abstract, Stabilität und Oszillationen, 8. AKP-Tagung in Weiz bei Graz, 30.9.2000 - 3.10.2000,
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Tagung der Gruppe der Angewandten, Klinischen und Pathologischen Physiologen der Deutschen Physiologischen Gesellschaft gemeinsam mit der Österreichischen Physiologen Gesellschaft, 2000, p. 16.
99. Siegelová J, Fišer B, Dusek J, Placheta Z, Cornélissen G, Halberg F. Circadian variability of rate-pressure product in essential hypertension with enalapril therapy. Scripta medica (Brno) 2000; 73: 69-75.
100. Siegelová J, Fišer B, Dusek J, Placheta J, Dobsak P, Svačinová H, Jancik J, Cornélissen G, Halberg F. Baroreflex sensitivity in "essential hypertension" treated with trandolapril and diltiazem in combination. Abstract 22.11, APS Conference, Baroreceptor and Cardiopulmonary Receptor Reflexes, Iowa City, IA, August 23-27, 2000. The Physiologist 2000; 43: 283.
101. Siegelová J, Homolka P, Dusek J, Fišer B, Cornélissen G, Halberg F. Extracircadian-to-circadian variance transpositions early and vice versa late in life in the human circulation. Proceedings, 1st International Symposium, Workshop on Chronoastrobiology & Chronotherapy (Satellite Symposium, 7th Annual Meeting, Japanese Society for Chronobiology), Kudan, Chiyodaku, Tokyo, 11 Nov 2000, pp. 58-60.
102. Nintcheu-Fata S, Cornélissen G, Katinas G, Halberg F, Fišer B, Siegelová J, Masek M, Dusek J. Software for contour maps of moving least squares spectra. Abstract 15, MEFA 9th International Fair of Medical Technology and Pharmacy, Brno, November 6-11, 2001.
103. Dusek J, Fišer B, Siegelová J, Cornélissen G, Svoboda L, Homolka P, Jancik J, Svačinová H, Mazánkova V, Schwartzkopff O, Halberg F. Vzestup incidence cevni mozkové prihody po r. 1997 v Ceske Republice. Cor et Vasa 2002; 44: 18.
104. Fišer B, Cornélissen G, Siegelová J, Dusek J, Homolka P, Mazánkova V, Halberg F. Increase in stroke deaths after 1997 in the Czech Republic. Scripta medica (Brno) 2002; 75: 95-100.
105. Halberg F, Cornélissen G, Engebretson M, Fišer B, Siegelová J, Dusek J, Katinas G, Schwartzkopff O. Dedicne biosfericke analogie nesvetelnych solarnich nebo galaktických cyklu. Abstract, Clovek ve svem pozemském a kosmickém prostredi, Úpice, 21-23 May 2002, pp. 30-31.
106. Halberg F, Cornélissen G, Otsuka K, Katinas GS, Schwartzkopff O, Halpin C, Mikulecky M, Revilla M, Siegelová J, Homolka P, Dusek J, Fišer B, Singh RB. Chronomics* (*the study of time structures, chronomes) detects altered vascular variabilities constituting risks greater than hypertension: with an illustrative case report. In: Mitro P, Pella D, Rybar R, Valocik G, editors. Proceedings, 2nd Congress on Cardiovascular Diseases, Kosice, Slovakia, 25-27 April 2002. Bologna: Monduzzi Editore; 2002. p. 223-258.
107. Halberg F, Cornélissen G, Přikryl P, Katinas G, Dusek J, Homolka P, Karpisek Z, Sonkowsky RP, Schwartzkopff O, Fišer B, Siegelová J, International BIOCOS Project Team. Chronomics complement genomics in Brno. What Johann Gregor Mendel wished, Jarmilka Siegelová
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accomplished: Broadening system times and transdisciplinary time horizons. In: Halberg F, Kenner T, Fišer B, editors. Proceedings, Symposium: The Importance of Chronobiology in Diagnosing and Therapy of Internal Diseases. Faculty of Medicine, Masaryk University, Brno, Czech Republic, January 10-13, 2002. Brno: Masaryk University; 2002. p. 7-56.
108. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y, Halhuber M, Müller-Bohn T, Delmore P, Siegelová J, Homolka P, Fišer B, Dušek J, Sanchez de la Pefia S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F, Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part I. Biomedical Instrumentation & Technology 2002; 36: 89-122.
109. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y, Halhuber M, Müller-Bohn T, Delmore P, Siegelová J, Homolka P, Fišer B, Dušek J, Sanchez de la Pefia S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Carandente F, Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part II. Biomedical Instrumentation & Technology 2002; 36: 183-197.
110. Cornélissen G, Halberg F, Bakken EE, Wang ZR, Tarquini R, Perfetto F, Laffi G, Maggioni C, Kumagai Y, Přikryl P, Homolka P, Dušek J, Siegelová J, Fišer B. Can society afford not to follow a chronobiological approach to blood pressure screening, diagnosis and treatment? In: Halberg F, Kenner T, Siegelová J, editors. Proceedings, Symposium, Chronobiological Analysis in Pathophysiology of Cardiovascular System. Brno: Masaryk University; 2003. p. 75-90. [Dedicated to the 60th Anniversary of Prof. Bohumil Fišer.]
111. Cornélissen G, Halberg F, Otsuka K, Shinagawa M, Kubo Y, Ohkawa S, Fišer B, Siegelová J, Dušek J. Iatrogenic excessive blood pressure variability (CHAT): implications for chronotherapy. Scripta medica (Brno) 2003; 76: 275-278.
112. Fišer B, Cornélissen G, Siegelová J, Dušek J, Mazánkova V, Halberg F. Spektraini analýza padesatileteno zazmamu mortality pro cevni Mozkovou prihodu v Ceske Republice. Abstract, XL vyrocniho sjezdu Ceske kardiologicke společnosti, 11-14 května 2003, Brno. Cor et Vasa 2003; 4 (Suppl): 21.
113. Halberg F, Cornélissen G, Otsuka K, Maggioni C, Schwartzkopff G, Fišer B, Dusek J, Siegelová J. Chronomics: the broad scope of monitoring chronomes. A review. Scripta medica (Brno) 2003; 76: 269-273.
114. Halberg F, Cornélissen G, Stoynev A, Ikonomov O, Katinas G, Sampson M, Wang ZR, Wan CM, Singh RB, Otsuka K, Sothern RB, Sothern SB, Sothern MI, Syutkina EV, Masalov A, Perfetto F, Tarquini R, Maggioni C, Kumagai Y, Siegelová J, Fišer B, Homolka P, Dusek J, Uezono K, Watanabe Y, Wu JY, Sonkowsky R, Schwartzkopff O, Hellbrügge T, Spector NH, Baciu I, Hriscu
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M, Bakken E. Season's Appreciations 2002 and 2003. Imaging in time: The transyear (longer-than-the-calendar year) and the half-year. Neuroendocrinol Lett 2003; 24: 421-440.
115. Kelsey R, Cornélissen G, Kapfer D, Siegelová J, Masek M, Dušek J, Fišer B, Halberg F. Research in practice: inferential statistical procedures applicable to the individual patient's response to benetensive treatment. Abstract #15, MEFA, Brno, Czech Republic, 04-07 Nov 2003. p. 20.
116. Nintcheu-Fata S, Cornélissen G, Katinas G, Halberg F, Fišer B, Siegelová J, Masek M, Dušek J. Software for contour maps of moving least-squares spectra. Scripta medica (Brno) 2003; 76: 279-283.
117. Otsuka K, Cornélissen G, Halberg F, Fišer B, Siegelová J, Sosikova M, Dušek J, Jancik J. Assessment of different administration schedules of Sotalol by electrocardiography. Scripta medica (Brno) 2003; 76: 297-300.
118.Schwartzkopff O, Halberg F, Cornélissen G, Katinas G, Wang ZR, Kröz M, Hecht K, Tarquini R, Perfetto F, Maggioni C, Siegelová J, Dušek J, Fišer B, Singh RB, Bakken E. Self-experimentation: dangerous when first done by a few, now safe for everybody's health? In: Halberg F, Kenner T, Siegelová J, editors. Proceedings, Symposium, Chronobiological Analysis in Pathophysiology of Cardiovascular System. Brno: Masaryk University; 2003. p. 91-104. [Dedicated to the 60th Anniversary of Prof. Bohumil Fišer.]
119. Schwartzkopff O, Katinas G, Singh RB, Sanchez de la Pena S, Zhao ZY, Uezono K, Přikryl P, Siegelová J, Fišer B, Dušek J, Otsuka K, Cornélissen G, Halberg F. Self-surveillance and self-experimentation (SSSE) for preventing vascular diseases needed to follow established successes of anesthesia and vaccine development. Abstract #13, MEFA, Brno, Czech Republic, 04-07 Nov 2003. p. 18.
120. Siegelová J, Cornélissen G, Fišer B, Dušek J, Homolka P, Masek M, Jancik J, Svačinová H, Halberg F. Blood pressure and heart rate monitoring in humans: the circaseptan and circadian rhythms. Abstract, 3rd International Workshop on The Human Circulation: Noninvasive Haemodynamic, Autonomic and Vascular Monitoring, Graz, Austria, 9-11 May 2003. Clinical Autonomic Research 2003; 13: 60-61.
121. Siegelová J, Fišer B, Dušek J, Placheta Z, Vlček J, Svoboda L, Pazdirek J, Cornélissen G, Halberg F. Chrono therapy: rate-pressure produce in essential hypertension. In: Halberg F, Kenner T, Siegelová J, editors. Proceedings, Symposium, Chronobiological Analysis in Pathophysiology of Cardiovascular System. Brno: Masaryk University; 2003. p. 118-121. [Dedicated to the 60th Anniversary of Prof. Bohumil Fišer.]
122. Sothern RB, Cornélissen G, Engel P, Fišer B, Siegelová J, Vlček J, Dušek J, Halberg F. Chronomics: instrumentation for monitoring of peak expiratory flow. Scripta medica (Brno) 2003; 76: 313-315.
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123. Watanabe Y, Cornélissen G, Watanabe F, Siegelová J, Dušek J, Halberg F. The trans- (-1.3) year in the blood pressure of a 10-year-old boy. Abstract 17, MEFA, Brno, Czech Republic, 04-07 Nov 2003. p. 22.
124. Cornélissen G, Palermo J, Carandente F, Siegelová J, Fišer B, Dušek J, Halberg F. Chronomics: chronome of suicides in Minnesota (1968-2002). Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 8.
125. Crawford VLS, Cornélissen G, Fišer B, Dušek J, Siegelová J, Halberg F. Infrannual changes in the incidence of myocardial infarctions and strokes in Northern Ireland. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 9.
126. Dušek J, Siegelová J, Fišer B, Brázdová Z, Homolka P, Vank P, Forejt M, Hollan J, Cornélissen G, Halberg F. Alterations of circadian rhythm in blood pressure by lack of dark: 24-h ambulatory blood-pressure monitoring. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 16.
127. Fišer B, Cornélissen G, Otsuka K, Chibisov S, Dušek J, Siegelová J, Halberg F. Blood pressure and heart rate readings for solar science and health care. Abstract, 2nd International Conference, Pathophysiology and Contemporary Medicine, Moscow, Russia, 22-24 April 2004. p. 472-473; and Science without Borders, Transactions of the International Academy of Science H&E, 2003/2004; 1: 420-421.
128. Fišer B, Siegelová J, Dušek J, Moudr J, Cornélissen G, Halberg F. Assessment of high blood pressure risk for stroke chronobiological approach. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 11.
129. Halberg F, Cornélissen G, Otsuka K, Siegelová J, Homolka P, Fišer B, Dušek J, Sanchez de la Pena S, Schwartzkopff O, Singh RB. Home ambulatory blood pressure and heart rate monitoring in practice and for science: transyears and magnetoperiodism vs. photoperiodism. Abstract S8-02, 3rd Int Congress on Cardiovascular Disease, Taipei, Taiwan, 26-28 Nov 2004. Int J Cardiol 2004; 97 (Suppl 2): S12.
130. Halberg F, Cornélissen G, Panksepp J, Schwartzkopff O, Siegelová J, Fišer B, Dušek J. Near-transyears in geophysics and autism. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 7.
131. Katinas GS, Chopra RK, Singh RB, Siegelová J, Fišer B, Dušek J, Cornélissen G, Halberg F. Design for timing nutriceuticals. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 19.
132. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. Vztah mezi věkem a cirkadianni variabilitou krevniho tlaku. Cor Vasa 2004; 46 (4) (Suppl): 81.
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133. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. Rozdíly v krevním tlaku mezi dnem a noci a vik. Congress of Atherosclerosis, TIGIS, Prague 2004. Abstract, DMEV 2004, Suppl 3, p. 38.
134. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. The relationship between age and circadian blood pressure variation. J Hypertens 2004; 22 (Suppl 2): S210.
135. Siegelová J, Dusek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. Rozdíly v krevním tlaku mezi dnem a noci a vek 26. Abstract, XXI. konference Ceske společnosti pro hypertenzi, XIII. konference pracovní skupiny Preventivní kardiologie CKS, Konference pracovní skupiny Srdecni selháni CKS, Prague, 2004. p. 44.
136. Siegelová J, Dusek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. Circadian blood pressure variation analyzed from 7-day monitoring. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 12.
137. Siegelová J, Dusek J, Homolka P, Vank P, Vlcek J, Cornélissen G, Halberg F. The relationship between age and circadian blood pressure variation. In: Cornélissen G, Kenner R, Fišer B, Siegelová J, eds. Proceedings, Symposium: Chronobiology in Medicine. Dedicated to the 85th Anniversary of Professor Franz Halberg. Brno: Masaryk University; 2004. p. 110-116.
138. Siegelová J, Homolka P, Cornélissen G, Fišer B, Dusek J, Halberg F. Health watch in Brno, Czech Republic. Abstract S8-13, 3rd Int Congress on Cardiovascular Disease, Taipei, Taiwan, 26-28 Nov
2004. Int J Cardiol 2004; 97 (Suppl 2): S15-S16.
139. Siegelová J, Homolka P, Cornélissen G, Fišer B, Dusek J, Vank P, Masek M, Halberg F. Ambulatory blood pressure monitoring: Health Watch in Brno, Czech Republic. Abstract, Noninvasive methods in cardiology, 2.11.2004, Congress MEFA, Brno, Czech Republic, 2.-4.11.2004, p. 10.
140. Bhatt MLB, Singh RK, Cornélissen G, Srivastava M, Rai G, Singh R, Halberg Francine, Siegelová J, Fišer B, Dusek J, Halberg F. Chronoradiotherapy guided by circadian rhythm in tumor temperature. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14,
2005, p. 19.
141. Cornélissen G, Delcourt A, Toussaint G, Otsuka K, Watanabe Y, Siegelová J, Fišer B, Dusek J, Homolka P, Singh RB, Kumar A, Singh RK, Sanchez S, Gonzalez C, Holley D, Sundaram B, Zhao Z, Tomlinson B, Fok B, Zeman M, Dulkova K, Halberg F. Opportunity of detecting pre-hypertension: worldwide data on blood pressure overswinging. Biomedicine & Pharmacotherapy 2005; 59 (Suppl 1): S152-S157.
142. Cornélissen G, Halberg F, Schwartzkopff O, Gvozdjakova A, Siegelová J, Fišer B, Dusek J, Mifkova L, Chopra RK, Singh RB. Coenzyme-Q10 effect on blood pressure variability assessed with a chronobiological study design. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 10.
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143. Cornelissen G, Schwartzkopff O, Katinas G, Halberg F, Bakken EE, Holley D, Sundaram S, Sanchez S, Gonzalez C, Delcourt A, Toussaint G, Siegelovä J, Fiser B, Dusek J, Homolka P, Zeman M, Dulkova K, Otsuka K, Watanabe Y, Tomlinson B, Fok B, Zhao ZY, Singh RB, Singh RK, Kumar A, Chibisov SM. Diagnosing blood pressure overswinging chronomically worldwide. Abstract, III International Conference, Civilization diseases in the spirit of V.l. Vernadsky, People's Friendship University of Russia, Moscow, Oct. 10-12, 2005, p. 34-35.
144. Cornelissen G, Watson D, Mitsutake G, Fiser B, Siegelovä J, Dusek J, Vohlidalova L, Svacinova H, Halberg F Mapping of circaseptan and circadian changes in mood. Scripta medica 2005; 78: 89-98.
145. Dusek J, Siegelovä J, Homolka P, Fiser B, Masek M, Cornelissen G, Halberg F Ambulatory blood pressure monitoring lasting seven days. J Hypertens 2005; 34 (Suppl 2): S154.
146. Fiser B, Siegelovä J, Dusek J, Homolka P, Vank P, Cornelissen G, Halberg F Seven-day blood pressure monitoring and casual blood pressure measurement. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 11.
147. Fiser B, Siegelovä J, Dusek J, Moudr J, Cornelissen G, Halberg F Assessment of high blood pressure risk for stroke. J Hypertens 2005; 34 (Suppl 2): S151.
148. Gvozdjakova A, Kucharska J, Cornelissen G, Singh RB, Mikulecky M, Siegelovä J, Fiser B, Dusek J, Halberg F Coenzyme Q10 and the circadian system of cardiac oxidative phosphorylation in rats. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 24.
149. Halberg F, Cornelissen G, Otsuka K, Fiser B, Mitsutake G, Wendt HW, Johnson P, Gigolashvili M, Breus T, Sonkowsky R, Chibisov SM, Katinas G, Siegelovä J, Dusek J, Singh RB, Berri BL, Schwartzkopff O. Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears. Biomedicine & Pharmacotherapy 2005; 59 (Suppl 1): S239-S261.
150. Halberg F, Katinas G, Cornelissen G, Schwartzkopff O, Fiser B, Siegelovä J, Dusek J, Jancik J. Ambulatory blood pressure monitoring: the need of 7-day record. Scripta medica 2005; 78: 83-88.
151. Halberg F, Katinas G, Schwartzkopff O, Siegelovä J. Fiser B, Dusek J, Cornelissen G. An about-2-year component in 15-year, largely half-hourly human blood pressure but not heart rate records. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 7.
152. Katinas G, Nintcheu-Fata S, Cornelissen G, Siegelovä J, Dusek J, Vlcek J, Masek M, Halberg F Moving least-squares spectra scrutinize chronomics in and around us. Scripta medica 2005; 78: 115-120.
153. Regal P, Cornelissen G, Siegelovä J, Fiser B, Dusek J, Halberg F Chronomics, the site-specific magnetic environment and an opportunity for the World Health Organization. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 9.
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154. Schwartzkopff O, Cornélissen G, Halpin C, Katinas G, Siegelová J, Fišer B, Dusek J, Halberg F Untreated transient longer than 7-day CHAT, circadian hyper-amplitude-tension, in a 7-year perspective. Scripta medica 2005; 78: 75-82.
155. Schwartzkopff O, Schwartzkopff C, Katinas GS, Siegelová J, Fišer B, Dusek J, Cornélissen G, Halberg F Chronomes, not imaginary baselines, are needed as longitudinal reference values. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 8.
156. Singh RB, Cornélissen G, Kumar A, Bathina S, Siegelová J, Fišer B, Dusek J, Vohlidalova I, Halberg F Effect of prayer on heart rate variability in Asian Indians. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 20.
157. Sonkowsky RP, Cornélissen G, Siegelová J, Fišer B, Dusek J, Masek M, Halberg F Myriadennian cyclicities in the tradition of Archimedes and the International System of Units (SI): invitation for comment. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 21.
158. Watanabe Y, Cornélissen G, Kodera I, Shimizu J, Ohmo G, Siegelová J, Fišer B, Dusek J, Vlcek J, Halberg F Chronomics of human blood pressure and heart rate in the Antarctic. Abstract, Noninvasive Methods in Cardiology, Brno, Czech Republic, September 14, 2005, p. 22.
159. Yamanaka T, Cornélissen G, Kazuma M, Kazuma N, Murakami S, Otsuka K, Siegelová J, Dusek J, Sosikova M, Halberg F Further mapping of the natality chronome, in Toda City (Japan) Maternity Hospital. Scripta medica 2005; 78: 99-106.
160. Cornélissen G, Delcourt A, Toussaint G, Otsuka K, Watanabe Y, Siegelová J, Fišer B, Dusek J, Homolka P, Singh RB, Kumar A, Singh RK, Sanchez S, Gonzalez C, Holley D, Sundaram
B, Zhao Z, Tomlinson B, Fok B, Zeman M, Dulkova K, Halberg F Opportunity of detecting pre-hypertension: worldwide data on blood pressure overswinging. (Reprint of Biomedicine & Pharmacotherapy 2005; 59 [Suppl 1]: S152-S157. Proceedings, International Conference on the Frontiers of Biomedical Science: Chronobiology, Chengdu, China, September 24-26, 2006, p. 123-129.
161. Cornélissen G, Halberg F, Katinas G, Schwartzkopff O, Holley D, Borer K, Homolka P, Siegelová J, Fišer B, Dusek J, Otsuka K, Yano A, Delcourt A, Toussaint G, Sanchez de la Pefia S, Gonzalez
C, Zhao Z, Aslanian N, Singh RB, Kumar A, Tarquini R, Perfetto F Stroke and other vascular disease prevention by chronomics. Scripta medica (Brno) 2006; 79 (3): 141-146.
162. Cornélissen G, Halberg F, Katinas G, Watanabe Y, Sothern RB, Siegelová J, Fišer B, Dusek J, Homolka P, Přikryl P, Singh RB, Otsuka K, Schwartzkopff O, Refinetti R. Chronotheranostics of MESOR-normotension vs. circadian overswing, i.e., CHAT In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 30-32.
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163. Dušek J, Fišer B, Siegelová J, Holub J, Mazánkova V, Cornélissen G, Halberg F. Decrease of myocardial infarction mortality and seasonal mortality in the Czech Republic in the period from 1994 to 2003. J Hypertension 2006; 24 (Suppl 4): 245.
164. Dušek J, Siegelová J, Fišer B, Cornélissen G, Holub J, Mazánkova V, Halberg F. Mortality data of stroke: 50-year record in the Czech Republic. Abstract 367, 10th Annual Meeting, French Society of Pharmacology, 73rd Annual Meeting, Society of Physiology, 27th pharmacovigilance meeting, 54th APNET Seminar and 4th CHU CIC meeting (Corum Montpellier 10-12 April 2006). Fundamental and Clinical Pharmacology 2006; 201: 206.
165. Dušek J, Siegelová J, Fišer B, Holub J, Mazánkova V, Cornélissen G, Halberg F. Pokles celkové a sezonni úmrtnosti pro infarkt myokardu v Ceske Republice v letech 1994-2003. Supplementum CorVasa 2006; 48 (4): 21.
166. Fišer B, Cornélissen G, Siegelová J, Pohanka M, Tarasova M, Barlova B, Nosavcova E, Dušek J, Homolka P, Erajhi AA, Abais FH, Holub J, Mazánkova V, Halberg F. Stroke in the Czech Republic. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 55-61.
167. Fišer B, Siegelová J, Dusek J, Holub J, Mazánkova V, Cornélissen G, Halberg F. Spektralni analýza úmrtnosti na infarkt myokardu v Ceske Republice. Supplementum Cor Vasa 2006; 48 (4): 26.
168. Fišer B, Siegelová J, Dusek J, Holub J, Mazánkova V, Cornélissen G, Halberg F. Spectral analysis of the myocardial infarction mortality data in the Czech Republic. J Hypertension 2006; 24 (Suppl 4): 246.
169. Halberg F, Cornélissen G, Schwartzkopff O, Katinas G, Siegelová J, Fišer B, Dusek J, Homolka P, Vank P. Seven day blood pressure measurement: contraversion in single 24-h profiles of blood pressure and heart rate. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 10-26.
170. Halberg F, Katinas G, Cornélissen G, Otsuka K, Sothern RB, Singh RB, Schwartzkopff O, Siegelová J, Fišer B, Dusek J, Homolka P, Přikryl P, Refinetti R. Lessons about "loads" learned while detecting and greatly reducing residual MESOR-hypertension and CHAT. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 27-29.
171. Hillman D, Halberg F, Cornélissen G, Katinas G, Sothern RB, Otsuka K, Singh RB, Siegelová J, Fišer B, Dusek J, Homolka P, Přikryl P, Schwatzkopff O. Need to standardize data collection and reference values. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium,
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Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 36-38.
172. Katinas G, Halberg F, Cornélissen G, Otsuka K, Singh RB, Siegelová J, Fišer B, Dušek J, Homolka P, Přikryl P, Schwatzkopff O. Chronobiologic serial sections complement spectra to seek social vs. physical signatures in human heart rate circaseptans. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 39-41.
173. Rostagno C, Cornélissen G, Halberg F, Tarquini R, Perfetto F, Jozsa R, Siegelová J, Fišer B, Dušek J, Homolka P, Přikryl P, Bakken EE. Yet another cis-semiannual (cis-halfyear) spectral component in cardiac arrhythmia: in Italy. Proceedings, International Conference on the Frontiers of Biomedical Science: Chronobiology, Chengdu, China, September 24-26, 2006, p. 61-63.
174. Schwartzkopff O, Halberg F, Cornélissen G, Katinas G, Sothern RB, Siegelová J, Fišer B, Dušek J, Homolka P, Přikryl P, Singh RB. Occasional transient CHAT occurs in the MESOR-normotensive individual. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 33-35.
175. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Cornélissen G, Halberg F. Blood pressure variation analyzed from seven day monitoring. Abstract 366, 10th Annual Meeting, French Society of Pharmacology, 73rd Annual Meeting, Society of Physiology, 27th pharmacovigilance meeting, 54th APNET Seminar and 4th CHU CIC meeting (Corum Montpellier 10-12 April 2006). Fundamental and Clinical Pharmacology 2006; 201: 205.
176. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Kohzuki M, Cornélissen G, Halberg F. Relationship between circadian blood pressure variation and age analyzed from 7-day ambulatory monitoring. Abstract PM1-10-05, 21st Scientific Meeting, International Society of Hypertension, Fukuoka, Japan, October 15-19, 2006. J Hypertension 2006; 24 (Suppl 6): 122.
177. Watanabe Y, Katinas G, Cornélissen G, Sothern RB, Siegelová J, Fišer B, Dušek J, Homolka P, Přikryl P, Singh RB, Schwartzkopff O, Halberg F. Time course of blood pressures over 18 years analyzed separately by day and by week. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Symposium, Noninvasive Methods in Cardiology. Brno, Czech Republic: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University; 2006. p. 42-46.
178. Cornélissen G, Halberg F, Bakken EE, Wang Z, Tarquini R, Perfetto F, Laffi G, Maggioni C, Kumagai Y, Homolka P, Havelkova A, Dušek J, Svačinová H, Siegelová J, Fišer B. Chronobiology of high blood pressure. Scripta medica (Brno) 2007; 80 (4): 157-166.
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179. Dušek J, Siegelová J, Fišer B, Forejt M, Homolka P, Vank P, Hollan J, Cornélissen G, Halberg F. Blood pressure and the illumination of bedroom at night. PI.31, 17th European Meeting on Hypertension, Milan, June 15-19, 2007. J Hypertension 2007; 25 (Suppl 2): S33.
180. Fišer B, Siegelová J, Dušek J, Pohanka M, Masek M, Barak J, Moudr J, Cornélissen G, Halberg F. Analysis of baroreflex function by means of mathematical model. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Noninvasive Methods in Cardiology 2007, Brno, Czech Republic, November 11-14, 2007. Brno: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University (ISBN 978 80 7018 463 4); 2007. p. 90-93.
181. Halberg F, Cornélissen G, Katinas G, Dušek J, Homolka P, Karpíšek Z, Sonkowsky RP, Schwartzkopff O, Fišer B, Siegelová J. Chronomics and genetics. Scripta medica (Brno) 2007; 80 (4): 133-150.
182. Havelkova A, Siegelová J, Fišer B, Mifkova L, Chludilova V, Pochmonova J, Vank P, Pohanka M, Dušek J, Cornélissen G, Halberg F. Physiotherapy and circadian blood pressure variability. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Noninvasive Methods in Cardiology 2007, Brno, Czech Republic, November 11-14, 2007. Brno: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University (ISBN 978 80 7018 463 4); 2007. p. 113-120.
183. Havelkova A, Siegelová J, Fišer B, Mifkova L, Chludlikova V, Pochmonova J, Vank P, Pohanka M, Dušek J, Cornélissen G, Halberg F. Circadian blood pressure variability and exercise therapy. Scripta medica (Brno) 2007; 80 (5): 191-196.
184. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Masek M, Havelkova A, Cornélissen G, Halberg F. Circadian blood pressure variation analyzed from 7-day monitoring. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Noninvasive Methods in Cardiology 2007, Brno, Czech Republic, November 11-14, 2007. Brno: Department of Functional Diagnostics and Rehabilitation, Faculty of Medicine, Masaryk University (ISBN 978 80 7018 463 4); 2007. p. 75-89.
185. Siegelová J, Dušek J, Fišer B, Homolka P, Vank P, Masek M, Havelkova A, Cornélissen G, Halberg F. The relationship between circadian blood pressure variation and age analysed from 7-day monitoring. Scripta medica (Brno) 2007; 80 (4): 179-187.
186. Halberg F, Cornélissen G, Siegelová J, Fišer B, Dobsak P, Kenner T, Placheta Z, Dušek J, Homolka P, Al-Kubati M, Schwartzkopff O, Blagonravov MB, Chibisov SM, Agarwal RK. Blood pressure or, rather, blood pressure variability disorders, VVDs, discussed in Brno on October 6, 2008. Bulletin of People's Friendship University of Russia: Series Medicine 2008; (7): 26-30.
187. Halberg F, Cornélissen G, Otsuka K, Sanchez de la Pefia S, Schwartzkopff O, Watanabe Y, Pati AK, Wall DG, Delmore P, Borer K, Beaty LA, Nolley ES, Adams C, Siegelová J, Homolka P, Dušek J, Fišer B, Přikryl P. Why and how to implement 7-day/24-hour blood pressure monitoring? Int J Geronto-Geriatrics 2005; 8 (1): 1-31. [Dated 2005 but published in June 2008.]
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188. Halberg F, Cornélissen G, Otsuka K, Watanabe Y, Singh RB, Revilla M, Sanchez de la Pena S, Gonzalez C, Siegelová J, Homolka P, Dušek J, Zeman M, Singh RK, Johnson D, Fišer B. Home C-ABPM for preventive and curative health care and transdisciplinary science. World Heart J 2008; 1 (3): 233-261.
189. Halberg F, Cornélissen G, Siegelová J, Fišer B, Dobsak P, Kenner T, Placheta Z, Dušek J, Homolka P, Al-Kubati M, Schwartzkopff O, Blagonravov MB, Chibisov SM, Agarwal RK. Blood pressure or, rather, blood pressure variability disorders, VVDs, discussed in Brno on October 6, 2008. Bulletin of People's Friendship University of Russia: Series Medicine 2008; (7): 26-30.
190. Halberg F, Schwartzkopff O, Cornélissen G, Hardeland R, Müller-Bohn T, Katinas G, Revilla MA, Beaty L, Otsuka K, Jozsa R, Zeman M, Csernus V, Hoogerwerf WA, Nagy G, Stebelova K, Olah A, Singh RB, Singh RK, Siegelová J, Dušek J, Fišer B, Czaplicki J, Kumagai Y, Chibisov SM, Frolov VA. Vaskuläres Variabilitäts-Syndrom (WS) und andere Chronomik 2005-2007. In: Hardeland R, ed. Sonderdruck aus Abhandlungen der Leibniz-Sozietät der Wissenschaften, Band 23: Facetten der Chronobiologie. Berlin: trafo verlag; 2008. p. 89-154.
191. Siegelová J, Fišer B, Havelkova A, Dobsak P, Dusek J, Pohanka M, Cornélissen G, Halberg F. Ambulatory arterial stiffness index in patients monitored for 6 consecutive days. In: Halberg F, Kenner T, Fišer B, Siegelová J, eds. Proceedings, Noninvasive Methods in Cardiology, Brno, Czech Republic, October 4-7, 2008. p. 233-237. Proceedings volume downloadable free of charge from http://web.fnusa.cz/files/kfdr2008/sbornik_2008.pdf [3133]
192. Siegelová J, Fišer B, Havelkova A, Dobsak P, Pohanka M, Dusek J, Cornélissen G, Halberg F Seven-day ambulatory blood pressure monitoring and ambulatory arterial stiffness index. Scripta medica (Brno) 2008; 81 (3): 181-184.
193. Halberg F, Cornélissen G, Otsuka K, Siegelová J, Fišer B, Dusek J, Homolka P, Sanchez de la Pena S, Singh RB, BIOCOS project. Extended consensus on means and need to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs). Leibniz-Online Nr. 5, 2009 (http://www.leibniz-sozietaet.de/journal). 35 pp, AND World Heart J, in press.
194. Savin, E., Siegelová, J., Fišer, B., & Martineaud, J. -. (1996). Non-invasive determination of aortic compliance in man. [Determination non invasive de la compliance aortique chez l'homme] Archives of Physiology and Biochemistry, 104(3), 257-264.
195. Siegelová, J., Fišer, B., Dusek, J., & Al-Kubati, M. (1995). Baroreflex sensitivity in patients with essential hypertension: Role of enalapril. [Baroreflex-sensitivitatsmessung bei patienten mit essentieller hypertonie: einfluss von enalapril] Nieren- Und Hochdruckkrankheiten, 24(1), 20-22.
196. Dušek J., Siegelová J., Přikryl P., Fišer B., Karpíšek Z., Prášek J. (1992) Alpha2 Adrenozeptoren bei essentieller Hypertonie: Einfluss eines ACE-Inhibitors. Nieren- Und Hochdruckkrankheiten, 24(1), 658-659
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197. Savin, E., Siegelová, J., Fišer, B., & Bonnin P. (1997) Intra- and extracranial artery blood velocity during a sudden blood pressure decrease in humans. Eur J Appl Physiol 76: 289 -293.
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The History of the Teaching Bachelor and Magister in Physiotherapy in the Faculty of Medicine Masaryk University
Siegelová Jarmila, Dunklerová Leona, Pohanka Michal
Dept. of Physiotherapy and Rehabilitation, Faculty of Medicine, Masaryk University
At the beginning of the 90th in the Czech Republic started the teaching of the profession of non-medical professional workers in the health services in the universities and this trend started also in Masaryk University.
Prof. MUDr. Zdeněk Placheta, DrSc. as the Head of the Department of Functional Diagnostics and Sport medicine (1988 - 1996) at that time, which provided health service, education of medical students and science, was asked by a group of experts in rehabilitation and physical medicine MUDr. J. Svobodová, MUDr. B. Miillerová, doc. MUDr. I. Müller, CSc, MUDr. E. Drápelová, MUDr. J. Roubalová, MUDr. F. Trkan and physiotherapist J. Burianová, at that time president of UNIFY, to start the teaching of the bachelor's program in physiotherapy at the Faculty of Medicine, Masaryk University. With the support of the Dean of Faculty of Medicine at that time, prof. MUDr. J. Bilder, CSc. The teaching of the bachelor's program was started under the Dept. of Functional Diagnostics and Sport medicine in the school year 1994/1995.
In the year 1996 Prof. MUDr. Jarmila Siegelová, DrSc started to work as a Head of the Department of Functional Investigation and Sport Medicine and to educate the students in physiotherapy. In the year 1997, with the support of the rector Prof. Dr.Jiří Zlatuska, CSc, of Masaryk University, director of Teaching Hospital of St. Anna in Brno MUDr. A. Štětková CSc and Dean of Faculty of Medicine Masaryk University Prof. MUDr. J. Vorlíček, CSc, the health service of rehabilitation with 32 beds and ambulatory out patients was added to the Dept. of Functional Diagnostics and Sport Medicine and the name was changed to Department of Functional Investigation and Rehabilitation. The staff of the Dept. of Functional Diagnostics and Rehabilitation consisted at that time of 150 doctors of medicine, physiotherapists and nurses. In 2007 at the age of 65 years (as usual) Prof. MUDr. Jarmila Siegelová, DrSc finished as a Head of this Department and was replaced by professor MUDr. P. Dobšák, CSc who was a member of her staff of the Department from 1997. Prof. MUDr. Jarmila Siegelová, DrSc continued the work in the Department of Physiotherapy and Rehabilitation in the Medical Faculty of FNUSA.
From 2010 the department was named Dept. of Sport Medicine under professor Dobšák as its Head. Prof. Siegelová continued to work as the professor until 2022, when she was nominated professor emeritus of Masaryk University.
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The Dept. of Functional Diagnostics and Rehabilitation, later Dept. of Sport Medicine and Rehabilitation provides the teaching of medical students in in the subject of internal medicine and the teaching program of different topics of bachelor studies in physiotherapy.
The first students in bachelor studies finished for the first time in 1998 and two-year master studies in physiotherapy were started; the first complete masters of physiotherapy finished in the year 2000.
In the year 2005 the Faculty of Medicine decided to form a separate Department of Physiotherapy and Rehabilitation only for the teaching of the program of physiotherapy. I was the Head of this Department until 2012.
Mgr. Leona Dunklerova has been in charge of the teaching the Be. and Mgr. of physiotherapy, administration and accreditations of the program in physiotherapy and organizing the theoretical and practical education since the year 1998 until now.
In order to innovate and improve the teaching process in the bachelor and master study of physiotherapy it was necessary to renew the teaching. Prof. MUDr. Jarmila Siegelova, DrSc. directed the Operational Program "Modifying a system of education in the field of physiotherapy, in the topic of Education for Competitiveness, funded from European sources, from 2012 to 2014. The project has been successfully completed.
In order to increase the education of the teaching staff of the Dept. of Functional Diagnostics and Rehabilitation, now the Sports Medicine and Rehabilitation, and the Dept. of Physiotherapy and Rehabilitation, it was necessary to increase their qualifications by postgraduate study. Prof. Siegelova successfully as a supervisor completed 17 doctoral students and Prof. Dobsak as a supervisor successfully completed 7 doctoral students.
According to the law of university school studies in the Czech Republic both forms of study, bachelor's and master's, must end with the defense of the bachelor's and master's theses. Supervisors of Be. theses and Mgr. diploma theses are both doctors and masters of physiotherapy. For carrying out of physiotherapy diploma theses, it is an indisputable benefit if the supervisors have a scientific degree CSc. or Ph.D. or have a higher scientific in pedagogical rank (associate professor, professor. In the Dept. of Functional Diagnostics and Rehabilitation - Dept. of Sport Medicine and Rehabilitation there were two members of staff, who accomplished titles assoc. prof, and one professor.
The Department of Physiotherapy and Rehabilitation in cooperation with Dept. of Sports Medicine and Rehabilitation organized every year international and national congresses, meetings and workshops, attended by leading foreign academic experts, as well as specialists from the field of rehabilitation and physiotherapy from abroad and the entire Czech Republic.
The scientific cooperation takes place namely with the following departments: Halberg Chronobiology Center, Minneapolis, USA, Department of Internal Medicine & RHB Science,
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Tohoku University, Sendai, Japan, Physiologisches Institut, Karl-Franzens-Universitát, Graz, Austria, Centre de Cardiologie, Universitě de Bourgogne, Dijon, France, Department of Internal Medicine, Toho University, Japan, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
In the Czech program of Be. program 724 students completed their studies and these students wrote 724 Czech Be. theses, which are presented in the archive of Information System Masaryk University. The bachelor thesis includes a case study with practical work from the Be. Physiotherapist.
A total of 433 physiotherapy students completed their master's studies, which means 433 diploma theses. The diploma theses of our students of physiotherapy contain pilot studies on the therapeutic effects of physiotherapy in various medical fields, for example in internal medicine, surgery, traumatology, neurology, pediatrics, etc. In these works they also use statistical evaluation of the achieved results.
For these works, it is very important that the supervisors obtained a scientific qualification of at least Ph.D.
Dean of the Faculty of Medicine, MU Prof. MUDr. J. Mayer, CSc. commissioned in 2013 Prof. MUDr. P. Dobšák, CSc, Head of the Department of Physiotherapy and Rehabilitation of the Faculty of Medicine of the MU by accreditation and implementation of the bachelor's degree in physiotherapy in English. Prof. MUDr. P. Dobšák, CSc. together with Prof. MUDr. J. Siegelová, DrSc, Mgr. L. Dunklerová and other members of the Dept. of Physiotherapy and Rehabilitation, in cooperation with the Dept. of Sport Medicine and Rehabilitation successfully started this english course in 2014. The first graduates completed their studies in 2017 and also wrote bachelor theses with case studies in English, which are listed in the MU Information System and are cited in this thesis. The Dean of Faculty of Medicine, Masaryk University Prof. MUDr. Martin Repko, CSc decided to finish the program of teaching the Be Physiotherapy in English and the lat students fish the bachelor studies.
We completed the last year of the Bachelor of Physiotherapy in English in 2023. In references we have summarized the Be. thesis, written in English, done by our students in the years 2017 to 2023.
On the pictures there are our students on the last day of our state exams together with the members of the State Examination Commission in all these years.
This year Professor Dobšák will complete the age of 65 years and will leave the position of Head of the Dept. of Sports Medicine and Rehabilitation in Faculty of Medicine, Masaryk University, St. Anna Teaching Hospital and his successor will be Assoc. MUDr. M. Pohanka, Ph.D.
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Figure 1: State final exams of the Bachelor of Physiotherapy program in English in 2017, committee members: Prof. MUDr. Petr Dobšák, CSc, Prof. MUDr. Jarmila Siegelová, DrSc, MUDr. Eva Drápelová, Doc. MUDr.
Ivan Müller, CSc. graduates: Eli Odnopozpv, Tessa Lynn Bell
Figure 2: State final exams of the Bachelor of Physiotherapy program in English in 2018, committee members: Prof. MUDr. Jarmila Siegelová, DrSc, Prof. MUDr. Petr Dobšák, CSc, Doc. MUDr. Michal Pohanka, Ph.D.,
MUDr. Eva Drápelová, Doc. MUDr. Ivan Müller, CSc. graduates: Josh Tilrem, Roy Even Omlid
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Figure 3: State final exams of the Bachelor of Physiotherapy program in English in 2019, committee members: Prof. MUDr. Jarmila Siegelová, DrSc, Prof. MUDr. Petr Dobšák, CSc, MUDr. Eva Drápelová, MUDr. Vítězslav
Ruber, Ph.D. graduates: Lilly Warhanek, Jan Ondruš
Figure 4: State final exams of the Bachelor of Physiotherapy program in English in 2020, committee members: Doc. MUDr. Michal Pohanka, Ph.D., Mgr. Alena Sedláková, Prof. MUDr. Jarmila Siegelová, DrSc, Prof. MUDr. Petr Dobšák, CSc, Mgr. Veronika Mrkvicová, Ph.D. graduates: Irene Solomou, Louis Amin Lotfalla Mamdouh, Liron Neuman, Akoma Anomu Omamuli
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Figure 5: State final exams of the Bachelor of Physiotherapy program in English in 2021, committee members: MUDr. Eva Drápelová, Prof MUDr. Petr Dobšák, CSc, Prof MUDr. Jarmila Siegelová, DrSc, Doc. MUDr.
Michal Pohanka, Ph.D. graduates: Marios Giannakou, Shuai Jiaqi, Ada Jacqueline Zubercova
Figure 6: State final exams of the Bachelor of Physiotherapy program in English in 2022, committee members: MUDr. Eva Drápelová, Prof. MUDr. Petr Dobšák, CSc, Prof. MUDr. Jarmila Siegelová, DrSc, Mgr. Simona
Srubařová, Ph.D.
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Figure 8: State final exams of the Bachelor of Physiotherapy program in English in 2023, committee members: Doc. MUDr. Michal Pohanka, Ph.D., Mgr. Alena Havelková, Ph.D., MUDr. Eva Drápelová, Prof. MUDr. Petr
Dobšák, CSc, Prof. MUDr. Jarmila Siegelová, DrSc. graduates: Sebastiano Emeterio San Albino, Gina Francesca Evans, Isabelle Patricia Océane Giret, Giulio Massocco, Amina Muhanbetaman, Theresa Schwab, Supanut Thongprapai,
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References:
1. BELL, T. Rehabilitation plan and process in patient after stroke [online]. Brno, 2017 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/m71g4/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce P. VÍTKOVÁ.
2. ODNOPOZOV, E. Medical rehabilitation plan and process in a patient after myocardial infarction [online]. Brno, 2017 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/fmsou/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce A. HAVELKOVÁ.
3. OMLID, R.E. Rehabilitation in patients after amputation of lower limb [online]. Brno, 2018 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/d8da2/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce P. VÍTKOVÁ.
4. TILREM, J. Rehabilitation in patients after total knee arthroplasty [online]. Brno, 2018 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/neye9/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V. MRKVICOVÁ.
5. ONDRUŠ, J. Rehabilitation plan and process in a patient with acute myocardial infarction [online]. Brno, 2019 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/iupnc/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce A. HAVELKOVÁ.
6. WARHANEK, L. Rehabilitation in patients after total hip arthroplasty [online]. Brno, 2019 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/btlrj/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V. MRKVICOVÁ.
7. ANOMU, A.O. Rehabilitation after lower limb fractures [online]. Brno, 2020 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/ztkpw/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V. MRKVICOVÁ.
8. MAMDOUH LOTFALLA AMIN, L. Rehabilitation plan and process in patients after stroke [online]. Brno, 2020 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/loj2d/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce L. NAGYOVÁ.
9. NEUMAN, L. Rehabilitation plan and process after spinal trauma [online]. Brno, 2020 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/klll6/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce P. VÍTKOVÁ.
10. SOLOMOU, I. Rehabilitation plan of patients with proximal femoral fractures [online]. Brno,
2020 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/c6811/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce H. ROZMANOVÁ.
11. GIANNAKOU, M. Rehabilitation plan and process in patients after a hip fracture [online]. Brno,
2021 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/fvzhm/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ZENDULKOVÁ.
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12. SHUAI, J. Rehabilitation after lower limb amputation [online]. Brno, 2021 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/igqfh/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ŠRUBAŘOVÁ.
13. ZUBERCOVA, A.J. Rehabilitation Plan and Process of Patients after Stroke [online]. Brno,
2021 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/wl3vb/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ŠRUBAŘOVÁ.
14. ALQURAYSHAH, G. Rehabilitation Plan and Process of Patients after Stroke [online]. Brno,
2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/hl7xv/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce D. HAVELKA.
15. BRAGGIO, V Rehabilitation after knee arthroplasty [online]. Brno, 2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/k01a0/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V MRKVICOVÁ.
16. GOLIKOV, S. Rehabilitation Plan and Process in a Patient After a Myocardial Infarction [online]. Brno, 2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/lxx9d/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce A. HAVELKOVÁ.
17. ISMAIL, R.m.a. Rehabilitation plan and process of patient with heart failure [online]. Brno, 2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/dba68/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce M. ULEHLA.
18. YEVGEN, O. Kinesiotherapy in Geriatrics [online]. Brno, 2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/gabpk/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ŠRUBAŘOVÁ.
19. SADEGHI, A. Treatment rehabilitation plan and procedure in patients with algic spine syndrome [online]. Brno, 2022 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/u66dl/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ZENDULKOVÁ.
20. ALBINO SAN EMETERIO, S. Rehabilitation after knee arthroplasty [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/tsyfm/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ŠRUBAŘOVÁ.
21. EVANS, EG. Rehabilitation Plan and Process a Patient with Chronic Lower Back Pain [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/zsyfb/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V MRKVICOVÁ.
22. GIRET, O.I.P. Rehabilitation After Transfemoral Amputation [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/c3zla/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V MRKVICOVÁ.
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23. MASSOCCO, G. Rehabilitation After Reverse Shoulder Arthroplasty [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/y5ce3/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce V. MRKVICOVÁ.
24. MUHANBETAMANOVA, A. Post-operative rehabilitation at orthopedic department in patients after total knee replacement [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/ th/r8mu8/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce J. ČAJKA.
25. SCHWAB, T. Rehabilitation Plan and Process of Patients after Stroke [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/jj956/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce S. ZENDULKOVÁ.
26. THONGPRAPAI, S. Medical rehabilitation plan and procedure in a patient with respiratory disease [online]. Brno, 2023 [cit. 2023-08-07]. Dostupné z: https://is.muni.cz/th/i5b6d/. Bakalářská práce. Masarykova univerzita, Lékařská fakulta. Vedoucí práce M. ULEHLA.
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Scientific International Cooperation
between Masaryk University Brno and University of Minnesota
Prof. MUDr. Jarmila Siegelovä, DrSc.
Department of Physiotherapy and Rehabilitation, Faculty of Medicine Masaryk University
Scientific international cooperation is possible after Velvet Revolution in the Czech Republic with the cooperation between Masaryk University and University of Minnesota.
Cooperation with Professor Franz Halberg and with Professor Germaine Cornelissen, Dr. Othild Schwartzkopff, Halberg Chronobiology Center of the University of Minnesota, USA started in 1988 with Brno team - Professor Bohumil Fiser, Jiri Dusek, M.D. and Professor Jarmila Siegelovä.
The common studies of circadian variability of cardiovascular variables and baroreflex sensitivity were published in many papers as the result of this common work and our Brno team participated in international projects Womb to Tomb, later BIOCOS, under the direction of the Halberg Chronobiology Center at the University of Minnesota.
Franz Halberg, M.D., Dr. h.c. (Montpellier), Dr. h.c. (Ferrara), Dr. h.c. (Tyumen), Dr. h.c. (Brno), Dr. h.c. (L'Aquila), Dr. h.c. (People's FriendshipUniversity of Russia, Moscow), Professor of Laboratory Medicine andPathology, Physiology, Biology, Bioengineering and Oral medicine
5. 6. 1919-9. 6. 2013
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From 80th of the last century, Prof. Franz Halberg and Prof. Germaine Cornelissen became coordinators of international chronobiology project "Womb-to-Tomb Study", now BIOCOS (The BlOsphere and the COSmos). The chronobiological team from MU was part of both projects. On November 22, 1994 BIOCOS was described for the first time. The BlOsphere and the COSmos, BIOCOS, as the task of building a novel transdisciplinary spectrum was pursued, and further periods of decades, centuries, and thousands and millions of years were documented. Much of the evidence was provided very successfully by Germaine Cornelissen, PhD, Professor of Integrative Biology and Physiology at the University of Minnesota.
Professor Germaine Cornelissen, PhD director of Halberg Chronobiology Center (from 2013- until now) Professor of Integrative Biology and Physiology University of Minnesota, USA (from 2006 until now)
In the thirty years of the duration of international cooperation and every year Congresses of Noninvasive Methods in Cardiology in Masaryk University, Brno, the number of members of the Brno chronobiological team increased with Professor Petr Dobsak, Assoc. Professor Michal Pohanka, Dr. Pavel Vank, Dr. Michaela Sosikova PhD., Mgr. Alena Havelkova PhD, Mgr. Veronika Mrkvicova PhD., Mgr. Leona Dunklerova and others.
The Noninvasive Methods in Cardiology congresses and symposia in Masaryk University were visited every time by famous scientific personalities from abroad - Prof. Franz Halberg and Prof. Germaine Cornelissen from the University of Minnesota, USA, Prof. Thomas Kenner, Rector of University and Dean of Medical Faculty, University of Graz, Austria and Prof. Jean-Paul Martineaud, Medical Faculty, Hopital Lariboisiere, Paris, France, Prof. Dr. Etienne
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Savin, Hopital Lariboisiere, University Paris, France, Professeur Jean-Eric Wolf, C.H.U. du Bocage, Dr. Jean-Christophe Eicher, C.H.U. du Bocage, University Dijon, France, Professor Kou Imachi, M.D., Ph.D., T.U.B.E.R.O., Tohoku University, Sendai, Japan, Professor Masahiro Kohzuki, M.D. Ph.D., Tohoku University, Sendai, Japan, Professor Yambe Tomoyuki, M.D. Ph.D., Tohoku University, Sendai, Japan. In the last year there were also new co-workers of Prof. T. Kenner, namely Prof. Dieter Platzer, University Graz, Prof. Nandu Goswami, Prof. Maxmilián Moser, University Graz, Prof. Daniel Schneditz, University Graz, Mgr. Bianca Brix, University Graz.
Since the year 2013 Professor Germaine Cornelissen has been director of the Halberg Chronobiology Center and leads international cooperation of Halberg Chronobiology Center all over the world in the project BIOCOS very successfully and many publications also together with us. She directs the international Project BIOCOS, is a member of the Phoenix Group, which comprises members of the Twin Cities chapter of the Electrical and Electronics Engineers in Minnesota, USA. Professor Germaine Cornelissen is an active member in the International Society of Chronobiology, the American Association for the Advancement of Science, the American Physical Society, the American Statistical Association, the New York Academy of Sciences, the American Physiological Society. She was the secretary of the North American branch of the International Society for Research on Civilization Diseases and the Environment (SIRMCE) and a member of the Scientific Council of SIRMCE.
In 2008, the very important Consensus meeting at St. Anna Hospital, Faculty of Medicine, Masaryk University was held. The participants under the leadership of Prof. Franz Halberg -Prof. Germaine Cornelissen, Prof. Thomas Kenner, Prof. Bohumil Fišer, Jarmila Siegelová, Dr. Jiri Dusek and others proclaimed Vascular Variability Disorders - MESOR hypertension, circadian hyperamplitude-tension, excessive pulse pressure, deficient heart variability and deviation of circadian rhythm, biomarkers of cardiovascular disease risk derived from 7-day/24-hour ambulatory blood pressure monitoring (1-7).
In the footsteps of the late prof. Franz Halberg, in the intensive collaboration with the leading personality Prof. Germaine Cornelissen, University of Minnesota in the future we plan further intensive scientific work with the University of Minnesota, USA on the BIOCOS project and other chronobiological studies.
References
1. Halberg F, Cornelissen G, Halberg E, Halberg J, Delmore P, Shinoda M, Bakken E. Chronobiology of human blood pressure. Medtronic Continuing Medical Education Seminars, 4th ed. Minneapolis: Medtronic Inc.; 1988. 242 pp.
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2. Halberg F, Cornelissen G, Otsuka K, Siegelovä J, Fiser B, Dusek J, Homolka P, Sanchez de la Pena S, Singh RB, BIOCOS project. Extended consensus on need and means to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs). Int. J. of Geronto-Geriatrics 11 (14) 119-146, 2008.
3. Halberg F, Cornelissen G., Otsuka K., Siegelovä J., Fiser B., Dusek J., Homolka P., Sanches de la Pena S., Sing R.B. and The BIOCOS project. Extended consensus on means and need to detect vascular variability disorders and vascular variability syndrome. World Heart J 2010; 2,4:279-305.
4. Halberg F, Cornelissen G., Dusek J., Kenner B., Kenner T., Schwarzkoppf O., Siegelovä J. Bohumil Fiser (22.10.1943 - 21.3.2011): Chronobiologist, Emeritus Head of Physiology Department at Masaryk University (Brno, Czech Republic), Czech Minister of Health, and Executive Board Member of World Health Organization:His Legacies for Public and Personal Health Care. World Heart J 2011; 3,1:63 -77.
6. Otsuka K., Cornelissen G., Halberg F. Chronomics and continuous ambulatory blood pressure monitoring. Springer Japan, 2016, 870p. ISBN 978-4-43154630-6.
6. Siegelovä J., Fiser B. Day-to-day variability of 24-h mean values of SBP and DBP in patients monitored for 7 consecutive days. J Hypertens, 2011; 294: 818-819.
7. Havelkova A., Dvorak P., Siegelovä J., Dobsak P., Filipensky P., Cornelissen G. Possibilities of Interpreting the Night-to-Day Ratio Specified by 24-Hour Blood Pressure Monitoring. Internat. J. Clinical Practice. Vol. 2023, Article ID 6530295, 11 pages, https://doi.org/10.1155/2023/6530295.
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Night-to-day Blood Pressure Ratio from Seven Day/24 h Ambulatory Blood Pressure Monitoring by Repeated Measurements in Patients with Coronary Heart Disease
Siegelova J., Havelkova A., Dusek J. Dunklerova L., Lapcikova K., Pohanka M., Dobsak P., *Cornelissen G.
Dept. Physiotherapy and Rehabilitation, Dept. Sports Medicine and Rehabilitation, St. Anna Teaching Hospital, Masaryk University, Brno, ^University of Minnesota, USA
Night-to-day blood pressure ratio with a less marked decrease in night-time blood pressure led to an increase in cardiovascular outcomes and it was described in 1988 by O' Brien at al. (1). In our earlier studies we have described from seven day/24 h ambulatory blood pressure measurement large variability of circadian blood pressure profile in every subject (2-10) and also large variabiliy in night-to-day ratio (11).
The aim of the present study was to examine night-to-day blood pressure variability in two repeated seven day/24 h ambulatory blood presure monitoring in patients with coronary heart disease.
Methods
20 patients with coronary heart diseases were characterized in Tab.l and divided in two subgroups.
The 20 patients with coronary heart diseases were under pharmacological therapy with ACE inhibitors, beta blokers and statins. The ambulatory blood pressure monitoring was in every patient provided twice and every measurement, which lasted seven days/ 24 hours repeatedly with the device from A&D (Tokyo, Japan). The 20 patients were divided in subgroups 1 and 2.
Subgroup 1 was monitored before and after 3 months of our patients cardiovascular rerhabilitation 3 times a week (10 min warm-up period, 25 min aerobic training, 15 min resistant training, 10 min cool-down period.
Supgroup 2 was monitored before and after usual every day activity.
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Results
We evaluated night-to-day blood pressure ratio in every day of blood pressure profile and seven day mean value before and after cardiac RHB in SBP and DBP in subgroup 1 and subgroup 2 and the results are in every individual value presented in following figures 1,2,3,4.
Tab. 1: The characteristic of the subgroup 1 and 2 in 20 patients with coronary heart disease
PARAMETERS	WITH REHABILITATION	WITHOUT REHABILITATION
	x± SD	x ± SD
NUMBER OF PATIENTS [n]	10	10
AGE [years]	64,0±2,77	49,3±1,49
HEIGHT [m]	1,7±2,25	1,8±2,42
WEIGHT [kg]	89,3±4,71	89,4±7,33
BMI [kg.m2]	29,9±1,32	28,6±2,05
EJECTION FRACTION [%]	52±4,5	53±3,1
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Patients following cardiovascular rehabilitation SBP
	35,0
	30,0
N? ON	25,0
O	
as	20,0
>	
ro	15,0
c	
JE:	10,0
op	
a	
	5,0
	0,0
il I. Ii I.
3        4        5 6 Patient number
I
1st monitoring 2nd monitoring
10
Figure 1: Mean values of night-to-day systolic blood pressure ratio evaluated from seven day/24 h ambulatory blood pressure monitoring in subgroup of patients with coronary heart diseases and cardiovascular
rehabilitation in the ľ' and 2ni monitoring.
Patients following cardiovascular rehabilitation DBP
35,0 30,0
123456789 10 Patient number
Figure 2: Mean values of night-to-day diastolic blood pressure ratio evaluated from seven day/24 h ambulatory blood pressure monitoring in subgroup of patients with coronary heart diseases and cardiovascular
rehabilitation in the Is' and 2nd monitoring.
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g —-j -i—
>-
ro
35,0 30,0 25,0 20,0 15,0
op 10,0 c
5,0 0,0
Patients without cardiovascular rehabilitation SBP
I
4 5 6 7
Patient number
1st monitoring 2nd monitoring
10
Figure 3: Mean values of night-to-day systolic blood pressure ratio evaluated from seven day/24 h ambulatory blood pressure monitoring in subgroup 1 of patients with coronary heart diseases and with every day aktivity
between i the ľ' and 2ni monitoring
Patients without cardiovascular rehabilitation DBP
	35,0
	30,0
OX	
	25,0
O	
ro	20,0
>-	
ro	
o	15,0
sz 60	10,0
C	
	5,0
	0,0
I
11st monitoring i 2nd monitoring
5 6 7 Patient number
10
Figure 4: Mean values of night-to-day diastolic blood pressure ratio evaluated from seven day/24 h ambulatory blood pressure monitoring in subgroup of patients with coronary heart diseases and every day aktivity between
the Is' and 2nd monitoring
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The mean values of night-to-day ratio in blood pressure from seven day/24 h AMBP by repeated measurement in subgroup 1 and subgroup 2 are presented for SBP and DBP in figures 5, 6, 7, and 8.
Patients with cardiovascular rehabilitation SBP
30,0 25,0 o 20,0
to 15,0
Group of patients with cardiovascular rehabilitation
Figure 5: Mean values of night-to-day systolic blood pressure ratio evaluated from seven day/24 hour ambulatory blood pressure monitoring in the whole subgroup 1 in patients with coronary heart disease and cardiovascular rehabilitation between the Is' and 2nd monitoring.
The mean values of night-to-day systilic blood pressure ratio estimated from seven day/24hour ambulatory blood pressure monitoring in subgroup 1 is the 1st monitoring: 12.0±1.85 % , 2nd monitoring: 8.4±1.89 %, the difference is not statistically significant.
Patients with cardiovascular rehabilitation DBP
30,0 25,0 o 20,0
1st monitoring ■ 2nd monitoring
Group of patients with cardiovascular rehabilitation
Figure 6: Mean values of night-to-day diastolic blood pressure ratio evaluated from seven day/24 hour ambulatory blood preasure measurement in the whole subgroup 1 in patients with coronary heart disease and cardiovascular rehabilitation between the Is' and 2nd monitoring.
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The mean values of night-to-day diastolic blood pressure ratio evaluated from seven day/24 hour ambulastory blood pressure monitoring in subroup 1: 1st monitoring: 13.7±1.54 % ; 2nd monitoring: 11.4±1.34 %, the difference is not statistically significant.
Patients without cardiovascular rehabilitation SBP
25,0
o 20,0
1st monitoring I 2nd monitoring
Group of patients without cardiovascular rehabilitation
Figure 7: Mean values of night to day systolic blood pressure ratio evaluated from seven deay/ 24 h ambulatory blood pressure monitoring in the whole subgroup 2 in patients with coronary heart disease and every day activity
beween the ľ' and 2ni measurement.
The mean value of night to day systolic blood pressure ratio evaluated from seven day/24 hour ambulatory blood pressure monitoring in subgroup 2: 1st monitoring: 17.3±2.23 % ; 2nd monitoring: 18.8±1.16 %
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Patients without cardiovascular rehabilitation DBP
30,0
Group of patients without cardiovascular rehabilitation
Figure 8: Mean values of night to day ratio diastolic blood pressure ratio evaluated from seven day/ 24 hour ambulastory blood pressure monitoring in patients with coronary heart disease and every day aktivity between
třhe nlswt and 2ni measurement.
The mean values of night to day diastolic blood pressure ratio evaluated from seven day /24 hour abulatory blood pressure monitoring in subgroup 2: 1st monitoring: 19.6±2.66 % ; 2nd monitoring: 20.7±1.33 %, the difference is not statistically significant.
Discussion
Our finding of large night-to-day ratio variability in individual patients with coronary heart diseases corresponds to the results of other studies in healthy subjects. The night-today blood pressure ratio is subject to regression-to-the mean. Dipping status has also a low reproducibility, with up to 40 % of individuals from Europe and Asia changing status between repeat recordings. In our former study we demonstrated that the relation between night-today ratio and risk of cardiovascular events is not linear as it is in the case of mean 24-hour systolic and diastolic pressure ( 2-10 ). We observed at low circadian double amplitude which roughly corresponds to the difference between night and day blood pressure (5 mmHg of systolic and 4 mmHg of diastolic pressure) about 30 % higher incidence of cardiovascular events than at circadian double amplitude of 15 to 35 mmHg systolic and of 12 to 20 mmHg diastolic pressure but at double amplitude higher than 35 mmHg in systolic and 28 mmHg in diastolic pressure the incidence was double. This indicates the existence of overswinging or circadian Hyper-Amplitude-Tension (CHAT) syndrome which is associated with a large
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increase in cardiovascular disease risk. The incidence of ultra-dipping is more frequent that the incidence of CHAT but existence of CHAT alone can lead to misdiagnosis of risk based on night-today blood pressure ratio. In conclusion, despite the low night-to-day ratio of blood pressure predicted increased risk for cardiovascular events in large studies, the determination of this value is useless for management of arterial hypertension in individual patients.
Conclusion
Night-to-day blood pressure ratio from seven day/24 h ABPM varied in one ambulatory blood pressure 24h profile and also in mean values from seven day/24 h ABPM in 1st and 2nd measurement.
We have not found significant difference between the subgroup 1 before and after cardiac rehabilitation. We have not found significant difference in repeated measurement in subgroup 2 with usual activities between repeated measurements.
References
1. O'Brien E., Sheridan J., O'Malley K. Dippers and non-dippers, Lancet 1988, Vol. 332, p.397
2. Halberg F, Cornélissen G, Halberg E, Halberg J, Delmore P, Shinoda M, Bakken E. Chronobiology of human blood pressure. Medtronic Continuing Medical Education Seminars, 4th ed. Minneapolis: Medtronic Inc.; 1988. 242 pp.
3. Halberg F, Cornélissen G, Otsuka K, Siegelová J, Fišer B, Dušek J, Homolka P, Sanchez de la Pena S, Singh RB, BIOCOS project. Extended consensus on need and means to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs). Int. J. of Geronto-Geriatrics 11 (14) 119-146, 2008.
4. Halberg F, Cornélissen G, Wall D, Otsuka K, Halberg J, Katinas G, Watanabe Y, Halhuber M, Miiller-Bohn T, Delmore P, Siegelová J, Homolka P, Fišer B, Dušek J, Sanchez de laPena S, Maggioni C, Delyukov A, Gorgo Y, Gubin D, Caradente F, Schaffer E, Rhodus N, Borer K, Sonkowsky RP, Schwartzkopff O. Engineering and gowernmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part II. Biomedical Instrumentation & Technology 2002; 36: 183-197.
5. Siegelová J., Dušek J., Fišer B., Homolka P., Vank P., Kohzuki M., Cornellisen G., Halberg F. Relationship between circadian blood pressure variation and age analyzed from 7-day ambulatory monitoring. J Hypertension, 2006, vol. 24, Suppl.6, p. 122.
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6. Siegelová J., Fišer B. Day-to-day variability of 24-h mean values of SBP and DBP in patients monitored for 7 consecutive days. J Hypertens, 2011; 294: 818-819.
7. Halberg F, Cornelissen G., Otsuka K., Siegelová J., Fišer B., Dušek J., Homolka P., Sanches de la Pena S., Sing R.B. and The BIOCOS project. Extended consensus on means and need to detect vascular variability disorders and vascular variability syndrome. World Heart J 2010; 2,4:279-305.
8. Halberg F., Cornelissen G., Dušek J., Kenner B., Kenner T, Schwarzkoppf O., Siegelová J. Bohumil Fišer (22.10.1943 - 21.3.2011): Chronobiologist, Emeritus Head of Physiology Department at Masaryk University (Brno, Czech Republic), Czech Minister of Health, and Executive Board Member of World Health Organization:His Legacies for Public and Personal Health Care. World Heart J 2011; 3,1:63 -77.
9. Otsuka K., Cornelissen G., Halberg F. Chronomics and continuous ambulatory blood pressure monitoring. Springer Japan, 2016, 870p. ISBN 978-4-43154630-6.
10. Siegelová J., Havelkova A., Dobsak P. Seven day/24-h ambulatory blood pressure monitoring: night time and dipping status. J Hypertension 2016, vol 34, Suppl.4, p. 807.
11. Havelkova A., Dvorak P., Siegelová J., Filipensky P., Cornelissen G. Possibilities of interpreting night-to-day ratio specified by 24-h blood pressure monitoring. International journal of Clinical practice , 2023, p.1-11.
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From Oita, Hometown Japan to Medical Care and Welfare in the Republic of Kenya Medical, Health and Welfare Improvement Project
Mitsuo Takei
CEO and Founder of Medical Corporation KOSHINKAI in JAPAN. CEO and Founder of GRAND FOREST JAPAN HOSPITAL in KENYA. Chairman of (NGO) DREAM WORLD HEALTHCARE PROGRAMME in KENYA
Practicing Japanese-style meticulous medical care in Africa
In March 2013, the Limited Company "Grand Forest Japan Hospital" was registered with the Government of the Republic of Kenya. We opened a medical center in Nairobi City in order to provide the people of Kenya with meticulous medical services based on Japanese
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scientific evidence. With the motto of "prompt and accurate diagnosis and treatment," we have steadily taken root in the local community and expanded our business by establishing a new rehabilitation center. While making use of our local experience and know-how, we continue to provide high quality medical services and expand and expand our business with the aim of perpetuating our activities in the future. Apart from medical services, we also established a local NGO, Dream World Healthcare Programme, in January 2013. In collaboration with Nakuru and Kaziad County, the program provides monthly mobile healthcare services to maintain and improve health and quality of life, mainly in residential areas with high poverty rates.
Introduction of Japanese medical equipment
Equipped with X-ray, CT scan, Ultrasound, gastro-camera, colonic camera, blood, urine and stool testing equipment. As much as possible, we have installed Japanese-made medical equipment that is precise and has few failures. We provide Kenyan medical professionals who visit our facility with an opportunity to learn about Japanese medical equipment, which leads to purchases.
Providing quality medical care and staff education thoughtful Japanese--style
Forest Japan Medical Center also conducts health checks, which are rare in Kenya. In addition, the level of medical care in Japan is trusted, and after the MOU was concluded, we began to receive requests for tests from local medical facilities. In the future, it is expected that needs from various fields will increase, and we are contributing to improving the quality of medical care in Kenya. In November 2020, Forest Japan Rehabilitation Centre opened in Karen District, Nairobi Province. We offer Japanese-style rehabilitation in accordance with scientific evidence. Although it was opened in the Corona Vortex, there are repeat patients. The center differentiates itself from rehabilitation centers in Kenya, where physical therapy is the mainstay of rehabilitation, and offers a wide range of rehabilitation services to help patients return to their daily lives. Our activities are in line with the policies of the Kenyan government and we have signed MOUs with provincial governments and educational institutions. We believe that by providing Japanese medical care and traveling clinic services, we can contribute to the health maintenance of Kenyan citizens, labor force improvement, and ultimately economic development. Furthermore, since 2016, we have been conducting local training programs and building relationships of trust through the development of medical professionals. Through these activities, we also introduce Japanese culture, medical conditions, and equipment.
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Figure 1: MACHAKOS Level 5 Hospital
Present situation
Now, our organization implement a free medical camp (outreach activity) in slam area to improve a healthcare services, medical treatment and social welfare services once a month (it started from May 2013 in collaboration with Ministry of Health in Nakuru-county Republic of Kenya). Now increased to twice a month to every week. Totally, we have treated over 70.000 citizens from new born, maternity woman to aged. Nowadays obesity is a big problem not only in high-end people but also in BOP (base of pyramid) people in slam area. Because it depends on life style, cultural background and everyday food habits. They don't have an enough knowledge and not well educated about health care. So, NCD's (like a diabetes, hypertension, hyperlipidemia and obesity) will become a serious problem. Near future (2025), number of patients who are suffering from NCD's will be exceeding Communicable Disease (infectious disease). Death rate of newborn and maternity woman is also a serious problem, it is a hundred times a lot compared to Japan. At the same time, it is very important to have an educational activity to Kenyan medical staff. We have already started to educate in Nairobi-University, some technical school and some Hospitals.
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Figure 2: Meeting with vice President Ruto
Contents of our free medical camp (list of services provided)
Height, body weight, BMI calculation, body temperature, oximetry, blood pressure, blood sugar, general urinalysis, HIV test, malaria test, parasite inspection, fungus and tuberculosis infection test, sexually transmitted disease (STD) inspection, family planning and HIV counselling, education for a prevention of infectious disease, education for prevention of a lifestyle disease, data acquisition to grasp the actual state of NCD's in the slum area, prevention education about an infection and lifestyle disease, and so on.
Another activities
A medical staff from Japan has a class, which gives a lesson about various kinds of medics regularly. We have a MOU with Nairobi University, which regulate rules between Nairobi University and Medical Corporation KOSHINKAI in Japan from 2017.
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Memorandum of Understanding (MOU)
An education program for interchange of the student, research program, participation to a meeting and seminar and other cooperation.
Conclusion
With economic growth in Kenya, the disease structure is changing and becoming more Westernized, especially in Nairobi City. As a result, lifestyle-related diseases are on the rise and the number of people with disabilities is increasing, as in Japan. In addition, there are few policies for children with disabilities. We are building a medical support system that considers these factors. We are also focusing on human resource development. Good medical care, welfare, and healthcare require good human resources. Exchange between Japan and Kenya is mutually beneficial. There are many challenges ahead, but we intend to move forward slowly, one at a time. I would be very happy if our activities can help Kenyans maintain and improve their health and become a cornerstone of the country's prosperity.
With the aim of protecting the precious lives of our patients, we strive every day to provide high-quality medical services to patients who visit our center. The smiles of our patients bring us joy, and by interacting with many patients, we gain valuable experience every day.
Note
The above text provides an overview of the content of the lecture, which was held on September 19, 2023 at the Faculty of Medicine, Masaryk University in Brno.
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Edited by: Cornélissen G., Siegelová J., Pohanka M., Dobšák P.
Published by Masaryk University Press, Žerotínovo nám. 617/9, 601 77 Brno, CZ
First edition, 2023 Print run: 60 copies
Printed by Tiskárna Knopp s.r.o., U Lípy 926, 549 01 Nové Město nad Metují ISBN 978-80-280-0441-5