Natriuretic Peptides and the Microcirkulation in Heart Failure Patients

The increased prevalence of chronic congestive heart failure (HF) is a tremendous challenge for society. In spite of effective medical treatment for acute HF, better pharmacological treatment for specific neurohormonal intervention and better diagnostic tools, e.g. biomarkers of natriuretic peptides, the morbidity and mortality due to this disease are still prominent. HF leads to vascular dysfunction in the general circulation but the interpretation of this is not clear. In our studies we have focussed on defining endothelial and smooth muscle dysfunction in the microvasculature of HF patients and correlating this dysfunction with the disease state. This thesis addresses studies of elderly patients with varying degrees of HF. We determined blood levels of homocysteine and the natriuretic peptide precursor, NT-proBNP which is released by the failing heart. We also investigated vasoreactive response of the cutaneous microcirculation to different stimuli using a non-invasive iontophoresis-Laser Doppler probe method. Paper I: We investigated the prognostic value of NT-proBNP for monitoring progression of HF. High blood levels (>5000) were found to indicate a poor prognosis of HF. Paper II: An open study,- in which we evaluated the function of the cutaneous peripheral circulation of patients with chronic HF. We found that vasoreactivity declines with increasing age and HF. Paper III: We evaluated vasoreactive responses in HF patients with homocysteinemi, before and 6 weeks after supplementary by B vitamin treatment. Homocysteine levels where then normalized and the cutaneous responses improved. Paper IV: A controlled study in which, we investigated the microcirculation in chronic HF patients with different degrees of HF. We saw that the degree of severity of congestive HF did not correlate with decrease in vasoreactive responses. Paper V: The effect of BNP in the microcirculation was studied in patients with severe congestive HF and compared to healthy, matched controls. The result shows that BNP has a significantly weaker vasodilation in HF patients and this is probably due to down regulation at the receptor-coupling level

Perspectives on regeneration of alveolar bone defects

Bone atrophy of the alveolar process is an important parameter in patients undergoing dental implants. There are several methods for preserving the alveolar process, with the autologous bone graft as the gold standard. Other approaches include the use of allografts, xenografts and synthetic bone grafts. In recent years, the use of stem cells has increased in importance. Th e most common type of stem cells used are mesenchymal stem cells from various sources, including bone marrow, adipose tissue and dental pulp. The discovery of induced pluripotent stem cells and the continued research on embryonic stem cells open new possibilities in this field. However, further research is needed to optimise protocols for isolation, diff erentiation and transplantation of cells with or without appropriate scaff olds, and to determine the correct clinical and therapeutic implications

Байесовские сети доверия как вероятностная графическая модель для оценки медицинских рисков

Realization of medical risks leads to occurrence of adverse effects which negatively affect patient’s health; result in irrational use of human and economic recourses, economic losses. In the framework of system risk analysis medical risks is connected with uncertainty related to crucial impact of human factor to the medical system. The problem of medical risks assessment and decision making on different stages of patients’ health care support systems’ construction comes up. In the paper I provide a state-of-art analysis of Bayesian belief networks use for medical risk assessment and decision making under uncertainty support in particular in the framework of health care organizations’ risk management and insurance risk assessment.Реализация медицинских рисков приводит к возникновению нежелательных событий, которые характеризуются нанесением вреда здоровью пациентов, неэффективным использованием человеческих и экономических ресурсов, экономическим ущербом организации здравоохранения. В рамках системного подхода к анализу риска, медицинский риск связан с неопределенностью, которая описывается значительным влиянием человеческого фактора в медицинской системе. Стоит задача оценки медицинских рисков и построения систем поддержки принятия решения на различных этапах работы с пациентом. В статье рассмотрено современное состояние применения аппарата байесовских сетей доверия для оценки медицинского риска и поддержки принятия решений в медицинской диагностике и прогностике, в частности, в контексте риск-менеджмента медицинских организации и оценке страховых рисков

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 184

This bibliography lists 139 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1978

Building expert systems: cognitive emulation.

Chapter 1 briefly introduces the concept of cognitive emulation, and outlines its current status. Chapter 2 reviews psychological research on human expert thinking. First, the study of expert thinking is placed in the context of modern cognitive psychology. Next, the principal methods and techniques employed by psychologists examining expert cognition are examined. The remainder of the chapter is given over to a review of the published literature on the nature and development of human expertise. Chapter 3 reviews the main arguments for and against cognitive emulation in expert system design. The tentative conclusion reached is that a significant degree of emulation is inevitable, but that a pure, unselective strategy of emulation is neither realistic nor desirable. Chapter 4 examines the prospects for cognitive emulation from a more pragmatic angle. Several factors are identified that represent constraints on the usefulness of a cognitive approach. However, a second set of factors is identified which should facilitate an emulation strategy - especially in the longer term. Some guidance is given on when to seriously consider adopting an emulation strategy. Chapter 5 presents a critical survey of expert system research that has already addressed the emulation issue. Six basic approaches to cognitive emulation are distinguished and evaluated. This helps draw out in more detail the implications of an emulation strategy for knowledge acquisition, knowledge representation and system architecture. The chapter concludes by discussing the issues that arise when different approaches to emulation are combined. Some guidance is offered on how this might be achieved. Chapter 6 summarizes the main themes and issues to have emerged, the design advice contained in the thesis, and the original contributions made by the thesis

Nonlinear Stochastic Dynamic Systems Approach for Personalized Prognostics of Cardiorespiratory Disorders

This research investigates an approach rooted in nonlinear stochastic dynamic systems principles for personalized prognostics of cardiorespiratory disorders in the emerging point-of-care (POC) treatment contexts. Such an approach necessitates new methods for (a) quantitative and personalized modeling of underlying cardiovascular system dynamics to serve as a virtual instrument to derive surrogate (hemodynamic) signals, (b) high-specificity diagnostics to identify and localize disorders, (c) real-time prediction to provide forecasts of impending disorder episodes, and (d) personalized prognosis of the short-term variations of the risk, necessary for effective treatment decisions, based on estimating the distribution of the times remaining till the onset of an anomaly episode. The specific contributions of the dissertation work are as follows: 1. Quantitative modeling for real-time synthesis of hemodynamic signals. Features extracted from ECG signals were used to construct atrioventricular excitation inputs to a nonlinear deterministic lumped parameter model of cardiovascular system dynamics. The model-derived hemodynamic signals, personalized to an individual's physiological and anatomical conditions, would lead to cost-effective virtual medical instruments necessary for personalized POC prognostics. 2. Random graph representation of the complex cardiac dynamics for disorder diagnostics. The quantifiers of a random walk on a network reconstructed from vectorcardiogram (VCG) were investigated for the detection and localization of cardiovascular disorders. Extensive tests with signals from PTB database of PhysioNet databank suggest that locations of myocardial infarction can be determined accurately (sensitivity of ~88% and specificity of ~92%) from tracking certain consistently estimated invariants of this random walk representation. 3. Nonparametric prediction modeling of disorder episodes. A Dirichlet process based mixture Gaussian process was utilized to track and forecast the evolution of the complex nonlinear and nonstationary cardiorespiratory dynamics underlying of the measured signal features and health states. Extensive sleep tests suggest that the method can predict an impending sleep apnea episode to accuracies (R^2) of 83% and 77% for 1 step and 3 step-ahead predictions, respectively.4. Color-coded random graph representation of the state space for personalized prognostic modeling. The prognostic model used the stochastic evolution of the transition pathways from a normal state to an anomalous state in the color-coded state space network to estimate the distribution of the remaining useful life. The prognostic model was validated using the data from ECG Apnea Database (Physionet.org). The model can predict the estimated time till a disorder (apnea episode) onset to within 15% of the observed times 1-45 min ahead of their inception.Industrial Engineering & Managemen

Isheemia reperfusiooni kahjustuse terapeutilised mehhanismid

Väitekirja elektrooniline versioon ei sisalda publikatsiooneHüpoksilis-isheemiline kahjustus avaldub, kui peaaju või südame verevarustus on häiritud, mistõttu tekib hapniku- ja toitainevaegus. Ilma nendeta surevad rakud kiiresti. Antud töö aitabki paremini mõista, millised tegurid võiksid kaitsta kude hapnikupuuduse eest, mis kaasneb erinevate südameveresoonkonna haigustega. Tegu on molekulaarsel tasemel alusuuringutega rakkudel ja hiirtel, mille käigus uurisime kolme potentsiaalset terapeutilist mehhanismi isheemia reperfusiooni kahjustuse ravis - hüpotermia, vesiniksulfiid ja lümfangiogenees. Uued ravimeetodid aitavad laiendada arusaamist hüpoksilis-isheemilisest kahjustusest ja parandada patsientide taastumisvõimalusi. Kliinilises praktikas on kehatemperatuuri langetamine kasutusel eelkõige sekundaarse ajukahjustuse vähendamiseks, samas näitavad mõningad uuringud, et hüpotermia on võimeline vähendama ka südamelihase kahjustust. Seni on hüpotermiat vaadeldud kui tegurit, mis vähendab metabolismi ja hapniku tarbimist. Meie tulemused näitavad, et lisaks sellele võimaldab hüpotermia suurendada vastupanu hapnikupuudusest tulenevale stressile läbi Nrf2 ja HIF1 signaaliradade. Vesiniksulfiidi peeti pikka aega mürgiseks gaasiks, kuid sellel põhinevad ravimimeetodid võivad saada oluliseks mitmete südame-veresoonkonna haiguste puhul. Südamekahjustus vähendab rakus mitokondrite hulka, mis varustab aga rakku eluks vajaliku energiaga. Meie tulemused näitavad, et vesiniksulfiid reguleerib rakus mitokondrite hulka läbi AMPK-PGC1α signaaliraja. Südamekahjustuse puhul aitab eksogeenne vesiniksulfiid (SG-1002) taastada vesiniksulfiidi tasemed. Selle tulemusena suureneb südame mitokondrite hulk ja paraneb südame funktsioon. Lümfangiogeneesile ehk lümfisoonte tekkele on isheemia reperfusiooni kahjustuse ravis oluliselt vähem tähepanu pööratud kui angiogeneesile ehk veresoonte tekkele, kuid isheemia reperfusiooni kahjustuse tulemusena muutub südame lümfisüsteem. Meie tulemused näitavad, et endogeense lümfangiogeneesi inhibeerimine südamekahjustuse olukorras tekitab põletikuvastust, südame talitushäiret ning ei toimunud iseloomulikku lümfisoonte tiheduse suurenemist. Selle leevendamiseks manustati hiirtele lokaalselt VEGFC-d, mis vähendas põletikku ja parandas südame talitushäiret. Seega on lümfangiogenees üks oluline uus terapeutiline lähenemine isheemia reperfusiooni kahjustuse ravis.Ischemic-hypoxic injury is caused by diminished or absent blood flow and result of oxygen deprivation (e.g. stroke, heart attack). It encompasses a complex constellation of pathophysiological and molecular injuries, if left untreated can result in death. In this dissertation we studied therapeutic mechanisms that might be protective against ischemia reperfusion injury in order to enhance both our knowledge of ischemia reperfusion injury pathophysiology and mechanisms of protection. Clinical hypothermia is considered as one of the most effective intervention for a range of hypoxic ischemic pathologies of the central nervous system, however, the mechanisms that underlie its protective effects are uncertain. Currently, it is widely accepted that therapeutic effects of hypothermia are due to reduced metabolism and oxygen consumption. Our study demonstrates for the first time that mild hypothermia activates major transcription factors Nrf2 and HIF1A, which orchestrate adaptive responses to hypoxic stress. Hydrogen sulfide (H2S) is now recognized as a novel gaseous signaling molecule along with nitric oxide and carbon monoxide, although it was considered to be a toxic gas for hundreds of years. We show here that not only does H2S regulate mitochondrial biogenesis via AMPK-PGC1α signaling pathway but also that correcting H2S levels with SG-1002 (H2S-releasing prodrug) could protect against heart failure. The lymphatic system has been suggested to play an important role in cardiovascular disease. Our results show that inhibition of cardiac lymphangiogenesis exaggerates ischemia reperfusion injury even more. Furthermore, stimulation of cardiac lymphangiogenesis with VEGF-C improves cardiac function following ischemia reperfusion injury. This dissertation provides clues to additional opportunities that could be translated into more efficient therapeutic approaches towards ischemia reperfusion injury.https://www.ester.ee/record=b5249899~S

Evaluation of efficiency of repulsion in speed-and-strength types of athletics

Efficiency of repulsion in speed-and-strength types of athletics is an integral measure of skill, since the performance of repulsive movements involves interaction of almost all organs and body systems. Dynamic repulsion lays the foundation for high sports results and the conditions of effective interaction of internal and external forces. With the special test exercises, one can determine the level of functioning of individual systems, on which the result of an exercise depends, which during training sessions provides focused opportunity to influence the stimulation of individual systems, increasing their level of activity. The article presents an electromyographic evaluation of the effectiveness of repulsion during the high jump at a run. The implementation of this method will make it possible to objectively evaluate the level of technical skills of athletes and purposefully influence the improvement of basic biomechanical characteristics of sports exercises