The possible role of machine learning in detection of increased cardiovascular risk patients - KSC MR Study (design).

Introduction: Currently, just a few major parameters are used for cardiovascular (CV) risk quantification to identify many of the high-risk subjects; however, they leave a lot of them with an underestimated level of CV risk which does not reflect the reality. Material and methods: The submitted study design of the Kosice Selective Coronarography Multiple Risk (KSC MR) Study will use computer analysis of coronary angiography results of admitted patients along with broad patients' characteristics based on questionnaires, physical findings, laboratory and many other examinations. Results: Obtained data will undergo machine learning protocols with the aim of developing algorithms which will include all available parameters and accurately calculate the probability of coronary artery disease. Conclusions: The KSC MR study results, if positive, could establisha base for development of proper software for revealing high-risk patients, as well as patients with suggested positive coronary angiography findings, based on the principles of personalised medicine.

Human galectin­3: Molecular switch of gene expression in dermal fibroblasts in vitro and of skin collagen organization in open wounds and tensile strength in incisions in vivo.

Understanding the molecular and cellular processes in skin wound healing can pave the way for devising innovative concepts by turning the identified natural effectors into therapeutic tools. Based on the concept of broad­scale engagement of members of the family of galactoside­binding lectins (galectins) in pathophysiological processes, such as cancer or tissue repair/regeneration, the present study investigated the potential of galectins­1 (Gal­1) and ­3 (Gal­3) in wound healing. Human dermal fibroblasts, which are key cells involved in skin wound healing, responded to galectin exposure (Gal­1 at 300 or Gal­3 at 600 ng/ml) with selective changes in gene expression among a panel of 84 wound­healing­related genes, as well as remodeling of the extracellular matrix. In the case of Gal­3, positive expression of Ki67 and cell number increased when using a decellularized matrix produced by Gal­3­treated fibroblasts as substrate for culture of interfollicular keratinocytes. In vivo wounds were topically treated with 20 ng/ml Gal­1 or ­3, and collagen score was found to be elevated in excisional wound repair in rats treated with Gal­3. The tensile strength measured in incisions was significantly increased from 79.5±17.5 g/mm2 in controls to 103.1±21.4 g/mm2 after 21 days of healing. These data warrant further testing mixtures of galectins and other types of compounds, for example a combination of galectins and TGF­ß1.

Genistein Improves Skin Flap Viability in Rats: A Preliminary In Vivo and In Vitro Investigation.

Selective estrogen receptor modulators (SERMs) have been developed to achieve beneficial effects of estrogens while minimizing their side effects. In this context, we decided to evaluate the protective effect of genistein, a natural SERM, on skin flap viability in rats and in a series of in vitro experiments on endothelial cells (migration, proliferation, antioxidant properties, and gene expression profiling following genistein treatment). Our results showed that administration of genistein increased skin flap viability, but importantly, the difference is only significant when treatment is started 3 days prior the flap surgery. Based on our in vitro experiments, it may be hypothesized that the underlying mechanism may rather by mediated by increasing SOD activity and Bcl-2 expression. The gene expression profiling further revealed 9 up-regulated genes (angiogenesis/inflammation promoting: CTGF, CXCL5, IL-6, ITGB3, MMP-14, and VEGF-A; angiogenesis inhibiting: COL18A1, TIMP-2, and TIMP-3). In conclusion, we observed a protective effect of genistein on skin flap viability which could be potentially applied in plastic surgery to women undergoing a reconstructive and/or plastic intervention. Nevertheless, further research is needed to explain the exact underlying mechanism and to find the optimal treatment protocol.

Income Inequality in Non-communicable Diseases Mortality among the Regions of the Slovak Republic.

AIM: A great amount of non-communicable disease deaths poses a threat for all people and therefore represents the challenge for health policy makers, health providers and other health or social policy actors. The aim of this study is to analyse regional differences in non-communicable disease mortality in the Slovak Republic, and to quantify the relationship between mortality and economic indicators of the Slovak regions. METHODS: Standardised mortality rates adjusted for age, sex, region, and period were calculated applying direct standardisation methods with the European standard population covering the time span from 2005 to 2013. The impact of income indicators on standardised mortality rates was calculated using the panel regression models. RESULTS: The Bratislava region reaches the lowest values of standardised mortality rate for non-communicable diseases for both sexes. On the other side, the Nitra region has the highest standardised mortality rate for non-communicable diseases. Income quintile ratio has the highest effect on mortality, however, the expected positive impact is not confirmed. Gini coefficient at the 0.001 significance level and social benefits at the 0.01 significance level look like the most influencing variables on the standardised mortality rate. By addition of one percentage point of Gini coefficient, mortality rate increases by 148.19 units. When a share of population receiving social benefits increases by one percentage point, the standardised mortality rate will increase by 22.36 units. CONCLUSIONS: Non-communicable disease mortality together with income inequalities among the regions of the Slovak Republic highlight the importance of economic impact on population health.

Risk of Dying from Cancer by Socio-demographic Indicators in the Slovak Republic.

AIM: Cancer mortality distribution was investigated by detailed neoplasms groups, age, sex, marital status of deceased, and regions in the Slovak Republic, and examined how these determinants influence the odds of dying due to cancer. METHODS: A retrospective analysis of cancer mortality statistics registered in the Slovak Republic during the years 1996-2014. For this time period, data was available only on the underlying subgroups of cancer deaths, place of death, age, year, sex, and marital status. Binary logistic regression was applied for odds of dying calculation influenced by these socio-demographic factors. RESULTS: The most common are deaths from malignant neoplasms of digestive organs in males as well as females. The biggest difference among both genders is recognized in malignant neoplasms of lip, oral cavity and pharynx, where deaths among males are on average 7.9 times higher in comparison to females. As for place of death the Bratislava region reports the highest level of cancer mortality stated at 25.22% of all deaths, on the contrary the Banská Bystrica region reports only 21.40% of all deaths. Age has a negative influence on odds of dying due to neoplasms compared to all other causes of death by 1.7%. In all regions compared to the reference Bratislava region, the odds of dying from neoplasms are lower. Being female diminishes the odds of dying due to neoplasms by 25.7% compared to males. Yearly the relative ratio of dying from neoplasms increases with respect to all other causes of death. When single people are set as the reference category, the relation of the probability of death from cancer to the probability of death due to other causes of death is higher for married, divorced and widowed persons. CONCLUSIONS: The results should be taken into account when comparing risk of dying due to cancer among people with the mentioned sociodemographic characteristics. Health policy makers should consider place of death and cancer types while planning hospital care units.

Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities.

Diabetes mellitus (DM) is frequently diagnosed at a time when patients already suffer from several cardiovascular complications. Our previously published data (Molecules 201520 (11): 20538-50) on the anti-oxidative properties of Agrimonia eupatoria L. (AE) and Cynara cardunculus L. (CC) prompted us to extend the available evidence on their possible protective activities on selected DM-related parameters in a streptozotocin-induced DM rat model and in a series of in vitro experiments. Male rats were divided into four groups: control group, untreated diabetic group, AE and CC treated diabetic groups. During a five-week period, changes in blood glucose and body weight were monitored. Then, rats were sacrificed and subjected to the assessment of changes in the reactivity of aortas and measurement of butyrylcholinesterase activity. To complete the panel of experiments, α-glucosidase activity was assessed in vitro. Our results demonstrate that both tested extracts exert similar anti-diabetic activities. However, better anti-oxidant activity of the A. eupatoria extract indicates its higher clinical potential in the prevention and/or adjuvant therapy of developing cardiovascular complications related to DM and diseases associated with oxidative stress.

Effect of Ivabradine on Endothelial Function in Patients with Stable Angina Pectoris: Assessment with the Endo-PAT 2000 Device.

INTRODUCTION: Ivabradine has opened up new possibilities for treating stable angina and chronic heart failure by lowering heart rate. Ivabradine lowers heart rate by selectively inhibiting the I f current in the sinoatrial node. This study aimed to determine whether the decrease in heart rate achieved with ivabradine was accompanied by hemodynamic changes that might lead to an enhancement of endothelial function. METHODS: Thirty patients with stable angina pectoris were included in the study. Ivabradine (5 mg bid) was added to the recommended standard treatment. Endothelial function was assessed at baseline and after 3 months of ivabradine therapy, with an Endo-PAT 2000 device (Itamar Medical, Israel). This device was recently developed for the noninvasive assessment for endothelial dysfunction. We evaluated reactive hyperemia index (RHI), which reflects endothelial function, and augmentation index (AI), which provides an indication of arterial stiffness. RESULTS: The study population consisted of 25 (83.3%) men and five (16.7%) women. The mean age of the patients was 65.4 ± 6.7 years. Twenty-eight (93.3%) patients had a history of myocardial infarction (ST-segment elevation myocardial infarction or non-ST-segment elevation myocardial infarction), 23 (76.6%) had undergone revascularization (percutaneous coronary intervention or coronary artery bypass graft), 16 (53.3%) had type 2 diabetes mellitus, and 29 (96.6%) had arterial hypertension. The mean resting heart rate decreased significantly, from 77 ± 7 bpm at the start of the study to 65 ± 6 bpm after treatment (P < 0.0001). Endothelial function was found to have improved significantly after 3 months of ivabradine therapy. Mean RHI before treatment was 1.54 ± 0.30, suggesting probable endothelial dysfunction, whereas mean RHI at the end of the study was 1.83 ± 0.36 (P < 0.0001). AI also improved significantly on treatment, from 21 ± 20% to 10 ± 21% (P < 0.0001). CONCLUSION: The addition of ivabradine to the treatment regimen of patients with stable angina pectoris both lowered heart rate and improved endothelial function. However, broader, randomized, double-blind, placebo-controlled clinical trials are required to confirm these findings.