Branislav Milovanovic

Anxiety, personality traits and quality of life in functional dyspepsia‐suffering patients

BACKGROUND Psychosocial stressors either acute or more sustained frequently precede the onset and exacerbation of the symptoms of the functional dyspepsia (FD). Depressive mood and quality of life have been already reported for interference in functional dyspepsia suffering patients. METHODS The examination were performed on 60 FD patients (30 females and 30 males), aged 20-79 years, 60 peptic ulcer subjects and 60 healthy volunteers in which we have investigate levels of anxiety and depression, personality traits and quality of life. RESULT According to the Hamilton Depression and Anxiety Rating Scales, the population with FD had the average score which classified them into the group of patients with the moderate depression (20.57 ± 4.45). Personality traits estimation based on data obtained by the Eysenck personality questionnaire revealed higher neuroticism scores in the group with functional dyspepsia. Both parameters, level of the neuroticism and anxiety level, expressed highly significant level of mutual concordance. Patients with functional dyspepsia reported a greater adverse impact of symptoms of emotional distress and food and drink problems. CONCLUSION Results are indicating that the depression and anxiety level is the highest in patients with functional dyspepsia and that anxiety level corroborates with the neuroticism level from the Eysenck scale. Psychological disturbances are influencing the quality of life mostly in patients with dyspepsia in the form of emotional distress and the problem with the food and beverage intake.

Effect of Brain Derived Neurotrophic Factor, In Relation to Diet and Lifestyle Factors, for Prevention of Neuropsychiatric and Vascular Diseases and Diabetes

Background: Brain-derived neurotrophic factor (BDNF) is a major neurotrophin which may have promise to be a nutraceutical of this decade. It has a documented role in neurogenesis, angiogenesis, and neuronal survival. BDNF can have beneficial effects on several cardio-metabolic and neuro-psychiatric disorders, indicating that it is important in brain- body interactions. Diet and lifestyle factors may also have an influence on BDNF levels. In this review, we examine the beneficial role of BDNF on risk factors of vascular diseases, type 2 diabetes mellitus and anxiety disorders. Methods: In- ternet search and discussion with peer colleagues. Results: Majority of the BDNF (70-80%) is derived from dendrite of neurons but it is also present in other body tissues. BDNF controls the food intake and appetite as well as lipid and glu- cose metabolism. Sedentary behavior and tobacco intake may be associated with BDNF deficiency. Lower serum concen- tration of BDNF and higher vascular endothelial growth factor (VEGF) concentrations were associated with increased risk of incident stroke/TIA. BDNF may serve as an intermediate biomarker for subclinical vascular disease and may also have biological potential to serve as a therapeutic target for primary and secondary prevention of vascular diseases, as well as clinical and subclinical vascular brain disease. BDNF deficiency has been observed in association with anxiety, depres- sion, insomnia, dementia, insulin resistance, type 2 diabetes and vascular diseases. The phenotypes associated with insulin resistance are at increased risk for developing cognitive decline and neuro-degeneration resulting in vascular dementia, and depression as well as diabetes mellitus and metabolic syndrome, which are risk factors for CVDs. BDNF may be ad- ministered as nutraceutical due to its protective influence on BDNF concentrations, insulin receptors and hypothalamic dysfunction leading to beneficial effects on cardiovascular risk and neuropsychological dysfunction. It is proposed that omega-3 fatty acids and moderate physical activity may enhance BDNF release. Conclusions: It is possible that circulat- ing BDNF deficiency is a risk factor for obesity, CVDs and diabetes as well as risk factor for neuropsychiatric diseases. BDNF administration may modify the risk of clinical and subclinical stroke, depression, and dementia as well as of obe- sity and type 2 diabetes.

New Insight into Uracil Stacking in Water from Ab Initio Molecular Dynamics

Nucleobases spontaneously aggregate in water by forming stacked dimers and multimers. It is assumed that the main contributions to the aggregation stem from hydrophobic and base-base dispersion interactions. By studying the uracil monomer and dimer in bulk water with the first principle molecular dynamics, we discuss dimer structure and provide evidence that stacking increases the uracil-water hydrogen bonding strength and alters the hydration structure of uracil. These changes have a significant influence on the intensity and shift of the carbonyl stretching band as revealed by simulated infrared absorption spectra of the monomer and dimer and available experimental spectra. The contributions of dipole-dipole, dispersion, and water mediated forces to the stacking are discussed. The reported findings are valuable for understanding the microscopic mechanism of heteroaromatic association in water which is relevant to a large range of chemical and biological systems.

Follow-Up and Risk Assessment in Patients with Myocardial Infarction Using Artificial Neural Networks

Artificial neural networks (ANNs) are machine learning technique, inspired by the principles found in biological neurons. This technique has been used for prediction and classification problems in many areas of medical signal processing. The aim of this paper was to identify individuals with high risk of death after acute myocardial infarction using ANN. A training dataset for ANN was 1705 consecutive patients who underwent 24-hour ECG monitoring, short ECG analysis, noninvasive beat-to-beat heart-rate variability, and baroreflex sensitivity that were followed for 3 years. The proposed neural network classifier showed good performance for survival prediction: 88% accuracy, 81% sensitivity, 93% specificity, 0.85 -measure, and area under the curve value of 0.77. These findings support the theory that patients with high sympathetic activity (reduced baroreflex sensitivity) have an increased risk of mortality independent of other risk factors and that artificial neural networks can indicate the individuals with a higher risk.

Binarized cross-approximate entropy in crowdsensing environment

OBJECTIVES Personalised monitoring in health applications has been recognised as part of the mobile crowdsensing concept, where subjects equipped with sensors extract information and share them for personal or common benefit. Limited transmission resources impose the use of local analyses methodology, but this approach is incompatible with analytical tools that require stationary and artefact-free data. This paper proposes a computationally efficient binarised cross-approximate entropy, referred to as (X)BinEn, for unsupervised cardiovascular signal processing in environments where energy and processor resources are limited. METHODS The proposed method is a descendant of the cross-approximate entropy ((X)ApEn). It operates on binary, differentially encoded data series split into m-sized vectors. The Hamming distance is used as a distance measure, while a search for similarities is performed on the vector sets. The procedure is tested on rats under shaker and restraint stress, and compared to the existing (X)ApEn results. RESULTS The number of processing operations is reduced. (X)BinEn captures entropy changes in a similar manner to (X)ApEn. The coding coarseness yields an adverse effect of reduced sensitivity, but it attenuates parameter inconsistency and binary bias. A special case of (X)BinEn is equivalent to Shannons entropy. A binary conditional entropy for m =1 vectors is embedded into the (X)BinEn procedure. CONCLUSION (X)BinEn can be applied to a single time series as an auto-entropy method, or to a pair of time series, as a cross-entropy method. Its low processing requirements makes it suitable for mobile, battery operated, self-attached sensing devices, with limited power and processor resources.

Artifacts in Dependency Structures of Portapres® Signals

Portapres® is a unique device that reliably accomplishes a challenging task of continuous and non-invasive recording of blood pressure (BP) waveforms in moving subjects. The complex procedure of Portapres® signal acquisition includes periodic changes of cuffed fingers to avoid pain and stress, as well as the blood pressure correction due to the increasing and decreasing elevation of arm posture. Due to these procedures, the recorded waveforms are corrupted. The aim of this paper is to analyze the influence of inevitable artifacts on parameters obtained from the blood pressure waveforms. The analyzed waveforms are obtained from healthy volunteers at Bezanija Kosa Hospital, Belgrade. The parameters include systolic blood pressure (SBP) and pulse interval (PI) extracted by Beatscope® software. The interrelationship of SBP and PI signals forms a major cardiovascular feedback – baroreflex. It can be analyzed using the sequence method for spontaneous baroreflex sensitivity, but the the tools that reveal more profound dependency structures include cross-approximate and cross-sample entropy, as well as the copula structures. The influence of artifacts, inevitable in Portapres® signals, is the main goal of this study. The analyses revealed that automatic artifact correction induced no significant changes considering the statistical moments and the baroreflex sensitivity; the same applies to the copula density and rank tests. The entropy analysis, however, turned out to be extremely sensitive so its implementation in Portapres® signal analysis is not recommended.

Vasovagal syncope and infection: A new target approach in diagnostic and treatment

I have read with great interest a paper by Radovanović et al. [1] published in your esteemed journal. A few years ago at a meeting in Targu Mures, Romania, the most famous experts from the field of syncope discussed that even after 20 years of clinical practice its cause is still unknown. It was the first time that I, as one of the experts, opened a question of target approach based on cause. The most common and most provocative question about syncope is pacemaker implantation and its time. According to guidelines of the European Society of Cardiology (ESC) and other scientific institutions, the best responder group for this indication is the one with cardioinhibitory syncope, with a history of injuries and multiple faints during one year [2]. During an interactive ESC session on syncope in 2016 in Rome, a case with interesting audience voting results regarding pacemaker implantation was presented. The result of the voting was pointing to a major problem regarding making a good selection of those indications for pacemaker implantation. Misdiagnosed pacemaker implantation results with no symptom reduction and leads to lower satisfaction, poor health care, and a potential lawsuit. In most of the cases, pacemaker implantation has a psychological effect and provides a feeling of safety more than it reduces the syncope event number. The question is what triggers vagal activation, hypotension, and bradycardia with asystole presentation. It is in fact an autonomic dysfunction, which is present in many cases with parasympathetic predomination, as well in cases with sympathetic predomination, for example in postural tachycardia syndrome. In order to make the right diagnosis of neurocardiogenic syncope, it is necessary to provide the right equipment with continuous beat-tobeat monitoring and a head-up tilt table [3]. This equipment is highly sophisticated and requires a trained professional who has to be educated in the autonomic nervous system testing. Syncope units are made according to the need for autonomic nervous system testing [4]. However, if you try to count the number of syncope units in Europe, a disappointing number is reached, which is true even at a global level. Syncope units are usually added to cardiology, neurology or endocrinology departments. Cardiologist mostly performs head-up tilt test and pacemaker implantation without the neurological part of autonomic nervous system testing, using a protocol with nitroglycerin application. Neurologists use neurological diagnostics methods using Westminster’s protocol without stimulation. Endocrinologists are mostly performing tests for diabetic autonomic neuropathy. The main lack is an absence of cooperation between several scientific disciplines, particularly in the treatment phase. When all requirements are satisfied, we are back to the begging of the story – what causes the autonomic dysfunction? Is it necessary to involve another scientific discipline for cause detection and target therapy? The potential answer is an infection disease expert involvement to complete the evaluation of this very specific problem. Neurocardiological laboratory at the Clinical Hospital Center is a unique laboratory in the world, which applies a multidisciplinary approach in evaluation, treatment, and virological testing, with more than 1,000 patients examined each year. The result is the detection of acute or chronic infection in these patients. The most frequently detected microorganisms so far are coxsackievirus, cytomegalovirus, Epstein–Barr virus, Chlamydia pneumoniae, Mycoplasma pneumoniae, Toxoplasma gondii, and lately Borrelia burgdorferi (Lyme disease). Causal diagnostics provides target treatment using antioxidant therapy during a course of several months, antibiotics, and a sympathomimetic. Surprisingly good results have been achieved using the programmed placebo effect, a method developed in cooperation with physicists. The second important answer and a new approach in treatment is the fact that syncope or orthostatic hypotension has almost always been in the clinical picture of chronic fatigue syndrome or autoimmune diseases [5]. In many cases there was comorbidity of psoriasis, urticaria, anxiety, phobia, inflammatory bowel disease, or even cancer. The main question that remains unanswered is whether syncope is a disease or a symptom of an underlying disease.

On Consistency of Cross-Approximate Entropy in Cardiovascular and Artificial Environments

Cross-approximate entropy (XApEn) quantifies the mutual orderliness of simultaneously recorded time series. Despite being derived from the firmly established solitary entropies, it has never reached their reputation and deployment. The aim of this study is to identify the problems that preclude wider XApEn implementation and to develop a set of solutions. Exact expressions for XApEn and its constitutive parts are derived and compared to values estimated from artificial data. This comparison revealed vast regions within the parameter space that do not guarantee reliable probability estimation, making XApEn estimates inconsistent. A simple correction to one of the XApEn procedural steps is proposed. Three sets of formulae for joint parameter selection are derived. The first one is intended to maximize threshold profile. The remaining ones minimize XApEn instability according to the strong and weak criteria. The derived expressions are verified using cardiovascular signals recorded from rats (long signals) and healthy volunteers (short clinical signals), proposing a change of traditional parameter guidelines.