Community-based participatory research to engage disadvantaged communities: Levels of engagement reached and how to increase it. A systematic review.

Community-based participatory research (CBPR) is one of the most used community engagement frameworks to promote health changes in vulnerable populations. The more a community is engaged, the more a program can impact the social determinants of health. The present study aims to measure the level of engagement reached in randomized controlled trials (RCTs) using CBPR in disadvantaged populations, and to find out the CBPR components that better correlate with a higher level of engagement. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Embase, Web of Science, MEDLINE, Cochrane and Scopus databases were queried. Engagement level was assessed using the revised version of IAP2 spectrum, ranging from "inform" to "shared leadership" . Fifty-one RCTs were included, belonging to 36 engagement programs. Fourteen CBPR reached the highest level of engagement. According to the multivariate logistic regression, a pre-existing community intervention was associated with a higher engagement level (OR = 10.08; p<0.05). The variable "institutional funding" was perfectly correlated with a higher level of engagement. No correlation was found with income status or type of preventive programs. A history of collaboration seems to influence the effectiveness in involving communities burdened with social inequities, so starting new partnerships remains a public health priority to invest on. A strong potentiality of CBPR was described in engaging disadvantaged communities, addressing social determinants of health. The key findings described above should be taken into account when planning a community engagement intervention, to build up an effective collaborative field between researchers and population.

The Multi-Faceted Nature of Renalase for Mitochondrial Dysfunction Improvement in Cardiac Disease.

The cellular mechanisms and signaling network that guide the cardiac disease pathophysiology are inextricably intertwined, which explains the current scarcity of effective therapy and to date remains the greatest challenge in state-of-the-art cardiovascular medicine. Accordingly, a novel concept has emerged in which cardiomyocytes are the centerpiece of therapeutic targeting, with dysregulated mitochondria as a critical point of intervention. Mitochondrial dysfunction pluralism seeks a multi-faceted molecule, such as renalase, to simultaneously combat the pathophysiologic heterogeneity of mitochondria-induced cardiomyocyte injury. This review provides some original perspectives and, for the first time, discusses the functionality spectrum of renalase for mitochondrial dysfunction improvement within cardiac disease, including its ability to preserve mitochondrial integrity and dynamics by suppressing mitochondrial ΔΨm collapse; overall ATP content amelioration; a rise of mtDNA copy numbers; upregulation of mitochondrial genes involved in oxidative phosphorylation and cellular vitality promotion; mitochondrial fission inhibition; NAD+ supplementation; sirtuin upregulation; and anti-oxidant, anti-apoptotic, and anti-inflammatory traits. If verified that renalase, due to its multi-faceted nature, behaves like the "guardian of mitochondria" by thwarting pernicious mitochondrial dysfunction effects and exerting therapeutic potential to target mitochondrial abnormalities in failing hearts, it may provide large-scale benefits for cardiac disease patients, regardless of the underlying causes.

Unintentional Fall-Related Mortality among the Elderly in Serbia: Importance of Death Reporting Quality.

Background: Falls have been one of the leading causes of injury-related deaths among the elderly, having an increasing trend in many countries. We investigated trends of fall-related mortality among people aged ≥65 yr in Serbia. Methods: Based on official data, we calculated unintentional fall-related mortality rate (MR) from 1998 to 2017, using join point regression analysis to determine annual percentage changes (APC). Starting from 2005, doctors from Serbian Public Health Institute have been controlling the quality of death certificates. Results: In the 1998-2004 period, MR decreased in men and women aged 65-74 and men aged ≥85 (by -12.4; -13.0; and -15.1% yearly) followed by an upward trend in men and women aged 65-74 (by 76.3 vs.40.2%yearly) from 2004 to 2007 and men aged ≥85 (by 13.7% yearly) from 2004 to 2017. MR decreased among women aged ≥85 (by -9.8% yearly) from 1998 to 2008 and then increased (by 9.0% yearly) from 2008 to 2017. In men and women aged 75-84, an increase of MR (by 7.4 vs.3.1%) was observed during the entire study period. In all age groups, except women aged ≥85, significant negative correlation was found between fall-related deaths and ill-defined and unknown causes of deaths. Conclusion: Control of death certificates by physicians from the Institute of Public Health led to the better reporting of the increasing trend of fall-related mortality among the elderly. Policy makers must investigate risk factors for fall and then adopt national guidelines for prevention and treatment of fall-related injury.

Renalase Challenges the Oxidative Stress and Fibroproliferative Response in COVID-19.

The hallmark of the coronavirus disease 2019 (COVID-19) pathophysiology was reported to be an inappropriate and uncontrolled immune response, evidenced by activated macrophages, and a robust surge of proinflammatory cytokines, followed by the release of reactive oxygen species, that synergistically result in acute respiratory distress syndrome, fibroproliferative lung response, and possibly even death. For these reasons, all identified risk factors and pathophysiological processes of COVID-19, which are feasible for the prevention and treatment, should be addressed in a timely manner. Accordingly, the evolving anti-inflammatory and antifibrotic therapy for severe COVID-19 and hindering post-COVID-19 fibrosis development should be comprehensively investigated. Experimental evidence indicates that renalase, a novel amino-oxidase, derived from the kidneys, exhibits remarkable organ protection, robustly addressing the most powerful pathways of cell trauma: inflammation and oxidative stress, necrosis, and apoptosis. As demonstrated, systemic renalase administration also significantly alleviates experimentally induced organ fibrosis and prevents adverse remodeling. The recognition that renalase exerts cytoprotection via sirtuins activation, by raising their NAD+ levels, provides a "proof of principle" for renalase being a biologically impressive molecule that favors cell protection and survival and maybe involved in the pathogenesis of COVID-19. This premise supports the rationale that renalase's timely supplementation may prove valuable for pathologic conditions, such as cytokine storm and related acute respiratory distress syndrome. Therefore, the aim for this review is to acknowledge the scientific rationale for renalase employment in the experimental model of COVID-19, targeting the acute phase mechanisms and halting fibrosis progression, based on its proposed molecular pathways. Novel therapies for COVID-19 seek to exploit renalase's multiple and distinctive cytoprotective mechanisms; therefore, this review should be acknowledged as the thorough groundwork for subsequent research of renalase's employment in the experimental models of COVID-19.

The Scientific Rationale for the Introduction of Renalase in the Concept of Cardiac Fibrosis.

Cardiac fibrosis represents a redundant accumulation of extracellular matrix proteins, resulting from a cascade of pathophysiological events involved in an ineffective healing response, that eventually leads to heart failure. The pathophysiology of cardiac fibrosis involves various cellular effectors (neutrophils, macrophages, cardiomyocytes, fibroblasts), up-regulation of profibrotic mediators (cytokines, chemokines, and growth factors), and processes where epithelial and endothelial cells undergo mesenchymal transition. Activated fibroblasts and myofibroblasts are the central cellular effectors in cardiac fibrosis, serving as the main source of matrix proteins. The most effective anti-fibrotic strategy will have to incorporate the specific targeting of the diverse cells, pathways, and their cross-talk in the pathogenesis of cardiac fibroproliferation. Additionally, renalase, a novel protein secreted by the kidneys, is identified. Evidence demonstrates its cytoprotective properties, establishing it as a survival element in various organ injuries (heart, kidney, liver, intestines), and as a significant anti-fibrotic factor, owing to its, in vitro and in vivo demonstrated pleiotropy to alleviate inflammation, oxidative stress, apoptosis, necrosis, and fibrotic responses. Effective anti-fibrotic therapy may seek to exploit renalase's compound effects such as: lessening of the inflammatory cell infiltrate (neutrophils and macrophages), and macrophage polarization (M1 to M2), a decrease in the proinflammatory cytokines/chemokines/reactive species/growth factor release (TNF-α, IL-6, MCP-1, MIP-2, ROS, TGF-ß1), an increase in anti-apoptotic factors (Bcl2), and prevention of caspase activation, inflammasome silencing, sirtuins (1 and 3) activation, and mitochondrial protection, suppression of epithelial to mesenchymal transition, a decrease in the pro-fibrotic markers expression ('α-SMA, collagen I, and III, TIMP-1, and fibronectin), and interference with MAPKs signaling network, most likely as a coordinator of pro-fibrotic signals. This review provides the scientific rationale for renalase's scrutiny regarding cardiac fibrosis, and there is great anticipation that these newly identified pathways are set to progress one step further. Although substantial progress has been made, indicating renalase's therapeutic promise, more profound experimental work is required to resolve the accurate underlying mechanisms of renalase, concerning cardiac fibrosis, before any potential translation to clinical investigation.

Temporal Changes in Incidence Rates of the Most Common Gynecological Cancers in the Female Population in Central Serbia.

Background and Objectives: There were 1,335,503 newly diagnosed cases of the most common gynecological cancers in women (cervical, uterine and ovarian cancer) worldwide in 2020. The main objective of this paper was to assess temporal changes in incidence rates of the most common gynecological cancers and to determine the age group with the greatest increase in incidence in the Serbian female population in the period 2003-2018. Material and Methods: Trends and annual percentage change (APC) of the incidence rate with corresponding 95% confidence intervals (CI) were calculated by Joinpoint regression analysis. The trend was considered to be significantly increasing (positive change) or decreasing (negative change) when the p-value was below 0.05 (p < 0.05). Results: The total number of newly registered cancer cases from 2003 to 2018 was 35,799. There was a significant increase of age standardized rate (ASR) for all cancer incidences in women from 2012 to 2018 with APC 6.9% (95% CI from 0.9 to 13.3, p = 0.028) and for uterine cancer during the 2014-2018 period with APC of 16.8% (95% CI: from 4.0 to 31.1, p = 0.014), as well as for ovarian cancer incidence in the 2012-2018 period with APC of 12.1% (95% CI: from 6.7 to 17.8, p < 0.001). A non-significant decrease of ASRs of incidence for cervical cancer was determined from 2003 to 2015 with APC of -0.22% (95% CI: from -3.4 to 3.1, p = 0.887) and a non-significant increase of ASRs incidence from 2015 to 2018 with APC of 14.21% (95% CI: from -13.3 to 50.5, p = 0.311). The most common gynecological cancers were present in all age groups and only ovarian cancer was registered in the youngest age group (0-4 years). Cervical cancer showed a typical increase after the age of 30, with peak incidence in women aged 40-44 and 65-69 years. The increased incidence trend regarding age for cervical cancer (y = 1.3966x + 0.3765, R2 = 0.3395), uterine cancer (y = 1.7963x - 5.4688, R2 = 0.5063) and ovarian cancer (y = 1.0791x - 0.8245, R2 = 0.5317) is statistically significant. Conclusion: Based on our presented results, a significant increase of incidence trend for the most common gynecological cancers in the Serbian female population from 2012 to 2018 was determined. There has been a significant increase in the incidence of uterine cancer from 2014 up to 2018, as well as for ovarian cancer from 2012 up to 2018, while cervical cancer showed a non-significant decrease of incidence trend from 2003 until 2015 and then a non-significant increase. In women below 20 years of age, ovarian cancer was significantly more prevalent, while cervical cancer was significantly more prevalent in the age groups 20-39 and 40-59 years. In the age group of 60-79, uterine cancer had a significantly higher incidence than the other two cancers. Measures of primary prevention, such as vaccination of children against Human Papilloma Virus and screening measures of secondary prevention, for the female population aged 25 to 64 years of age are needed, as well as educating females about healthy lifestyles via media and social networks to help prevent the most common gynecological cancers.

Cancer of unknown primary - incidence, mortality trend, and mortality-to-incidence ratio is associated with human development index in Central Serbia, 1999-2018: Evidence from the national cancer registry.

OBJECTIVES: The aim was to estimate the trend of incidence, mortality and mortality-to-incidence ratio (MIR) in Central Serbia in 1999-2018 and its possible association with the human development index (HDI). METHODS: In this study, cancer of unknown primary (CUP) was included as C77-C80 codes. Trend analysis was performed in the Joinpoint Regression Programme version 4.8.0.1. HDI combines life expectancy, educational attainment and gross national income. HDI values for Serbia are extracted from the global bank site. RESULTS: Joinpoint regression analysis of the age-standardised incidence rate of CUP showed a significantly increasing trend with annual percent change (APC) of 8.5% (95% confidence interval [CI] 3.0-14.3%) in males and 7.8% (95%CI 2.7-13.2) in females. The age-standardised mortality rate of CUP showed a significantly decreasing trend with APC of -1.7% (95%CI -2.8 to -0.5%) in males and -1.4% (95%CI -2.7 to -0.1%) in females. MIR showed a significantly decreasing trend with APC of -9.3% (95%CI -14.6 - -3.6%) in males and -7.1% (95%CI -10.5% to -4.2%) in females. The linear regression showed significant inverse association among HDI and the MIR of CUP in males (r2 = 0.464, p = 0.002) and in females (r2 = 0.612, p < 0.001). CONCLUSIONS: Decline of MIR was associated with HDI, suggesting that CUP prognosis follows socio-economic status.

The Discriminatory Ability of Renalase and Biomarkers of Cardiac Remodeling for the Prediction of Ischemia in Chronic Heart Failure Patients With the Regard to the Ejection Fraction.

Background: Renalase has been implicated in chronic heart failure (CHF); however, nothing is known about renalase discriminatory ability and prognostic evaluation. The aims of the study were to assess whether plasma renalase may be validated as a predictor of ischemia in CHF patients stratified to the left ventricular ejection fraction (LVEF) and to determine its discriminatory ability coupled with biomarkers representing a range of heart failure (HF) pathophysiology: brain natriuretic peptide (BNP), soluble suppressor of tumorigenicity (sST2), galectin-3, growth differentiation factor 15 (GDF-15), syndecan-1, and cystatin C. Methods: A total of 77 CHF patients were stratified according to the LVEF and were subjected to exercise stress testing. Receiver operating characteristic curves were constructed, and the areas under curves (AUC) were determined, whereas the calibration was evaluated using the Hosmer-Lemeshow statistic. A DeLong test was performed to compare the AUCs of biomarkers. Results: Independent predictors for ischemia in the total HF cohort were increased plasma concentrations: BNP (p = 0.008), renalase (p = 0.012), sST2 (p = 0.020), galectin-3 (p = 0.018), GDF-15 (p = 0.034), and syndecan-1 (p = 0.024), whereas after adjustments, only BNP (p = 0.010) demonstrated predictive power. In patients with LVEF <45% (HFrEF), independent predictors of ischemia were BNP (p = 0.001), renalase (p < 0.001), sST2 (p = 0.004), galectin-3 (p = 0.003), GDF-15 (p = 0.001), and syndecan-1 (p < 0.001). The AUC of BNP (0.837) was statistically higher compared to those of sST2 (DeLong test: p = 0.042), syndecan-1 (DeLong: p = 0.022), and cystatin C (DeLong: p = 0.022). The AUCs of renalase (0.753), galectin-3 (0.726), and GDF-15 (0.735) were similar and were non-inferior compared to BNP, regarding ischemia prediction. In HFrEF patients, the AUC of BNP (0.980) was statistically higher compared to those of renalase (DeLong: p < 0.001), sST2 (DeLong: p < 0.004), galectin-3 (DeLong: p < 0.001), GDF-15 (DeLong: p = 0.001), syndecan-1 (DeLong: p = 0.009), and cystatin C (DeLong: p = 0.001). The AUC of renalase (0.814) was statistically higher compared to those of galectin-3 (DeLong: p = 0.014) and GDF-15 (DeLong: p = 0.046) and similar to that of sST2. No significant results were obtained in the patients with LVEF >45%. Conclusion: Plasma renalase concentration provided significant discrimination for the prediction of ischemia in patients with CHF and appeared to have similar discriminatory potential to that of BNP. Although further confirmatory studies are warranted, renalase seems to be a relevant biomarker for ischemia prediction, implying its potential contribution to ischemia-risk stratification.

Trends of Stomach Cancer in Central Serbia.

Somach cancer is the third most common cause of cancer-related deaths worldwide. The objective of the paper was to analyze the incidence and mortality trends of stomach cancer in Central Serbia in the period between 1999-2017. Materials and Methods: trends and annual percentage change (APC) of the incidence and mortality rate with corresponding 95% confidence intervals (CI) were calculated by joinpoint regression analyses. The optimal number of Joinpoints was identified using the Monte Carlo permutation method. The trend was considered to be significantly increasing (positive change) or decreasing (negative change) when the p-value was below 0.05 (p < 0.05). Results: the total number of new cases was 16,914 (10,873 males and 6041 females) and the total number of mortality cases was 14,790 (9348 in and 5442 in females). Almost one third (30.8%) of new cases were registered in the 60-69-year age group, and new cases were significantly more frequent in males than in females (30.8% vs. 29.02%, p < 0.001). Joinpoint regression analysis showed a significant decrease of incidence trend in females during the 2000-2015 period with APC of -2.13% (95% CI: -3.8 to -0.5, p < 0.001). An insignificant decrease in incidence trend was in males with APC of -0.72% (95% CI: -2.3 to 0.9, p = 0.30). According to the joinpoint analysis, a significant decrease of mortality trends both in males during 2000-2015 with APC of -2.21% (95% CI: -1.6 to -7.5, p ≤ 0.001 and in females, during the same period, with APC of -1.75% (95% CI: -2.9 to -0.6, p < 0.001) was registered. From 2015 to 2017, a significant increase of mortality was registered with APC of 44.5% (95% CI: from 24.2 to -68.1, p ≤ 0.001) in females and in males with APC of 53.15% (95% CI: 13.5 to -106.6, p ≤ 0.001). Conclusion: a significant decrease of stomach cancer incidence trend in females and insignificant decrease of incidence trend in males were determined in Central Serbia. Based on presented results, the mortality trend decreased significantly both in males and in females during 2000-2015, and from 2015 to 2017 we recorded a significant increase in mortality in both sexes. We found significantly more new cases in women than in men in the age group of 40-49, and the mortality of stomach cancer was significantly more frequent among females compared to males in the age groups 30-39, as well as in the 50-59 age group. There is a need for improving recording and registration of new cases of stomach cancer, especially in females. Urgent primary and secondary preventive measures are needed-introducing stomach cancer screening and early detection of premalignant changes. Urgent primary and secondary preventive measures are needed.

Violent deaths among adolescents in Serbia: past, present and future.

OBJECTIVES: The aim of the study was to determine the trend and methods of violent deaths (suicide and homicide) in adolescents aged 15-19 years in Serbia. METHODS: Mortality database was drawn from the Statistical Office of Serbia from the 1997-2019 period. To calculate the annual percentage change (APC) of mortality rate (MR) with corresponding 95% confidence interval we used join point regression analysis. Statistical analyses were also performed using the chi-square test and Spearman's rho correlation. RESULTS: The average suicide rate was 3.65 per 100,000 and homicide rate was 1.36 per 100,000 adolescents. The boys to girls ratio was 4.2 for suicides and 2.7 for homicides. Among girls, suicide rate significantly decreased (APC -20.7%; 95% CI -32.5 to -6.8) and homicide rate insignificantly decreased (APC -19.3%; 95% CI -37.8 to 5.1). Among boys, suicide rate significantly decreased (APC -4.6%; 95% CI -7.0 to -2.0) as well as homicide rate (APC -7.7%; 95% CI -11.5 to -4.3). The most common method of suicide was hanging (195, 44.3%) and nearly one third (198, 32.6%) of violent deaths were caused by firearms. Significantly negative correlation was observed between the Human Development Index (HDI), gross domestic product (GDP) per capita and MR due to suicides and homicides among both genders (p < 0.05). CONCLUSIONS: Increase of GDP and HDI, national preventive intervention and strict application of the provisions of the law regarding the possession and storage of weapons must be implemented in order to continue reducing violent deaths among adolescents.

Cardiac Remodeling Biomarkers as Potential Circulating Markers of Left Ventricular Hypertrophy in Heart Failure with Preserved Ejection Fraction.

Soluble suppressor of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor (GDF)-15 and syndecan-1 represent biomarkers of cardiac remodeling, involved in heart failure (HF) progression. We hypothesize that their plasma concentrations, together with brain natriuretic peptide (BNP), are different in HF stratified by ejection fraction (EF), demonstrating correlations with echocardiographic parameters that indicate left ventricular (LV) hypertrophy; LV mass index (LVMI) and posterior wall and septum diameters. HF patients (n = 77) were classified according to EF: reduced EF < 40% (HFrEF), mid-range EF = 40-49% (HFmrEF), preserved EF > 50% (HFpEF). We found that plasma concentrations of four cardiac remodeling biomarkers were highest in HFrEF and lowest in HFpEF, p < 0.001. In HFpEF, remodeling biomarkers independently correlated with LVMI: sST2 (p = 0. 002), galectin-3 (p < 0.001), GDF-15 (p = 0.011), and syndecan-1 (p = 0.006), whereas galectin-3 correlated after multivariable adjustments (p = 0.001). Independent correlates of septum and posterior wall diameters, in HFpEF, were sST2 (p = 0.019; p = 0.026), galectin-3 (p = 0.011; p = 0.009), GDF-15 (p = 0.007; p = 0.001), and syndecan-1 (p = 0.005; p = 0.002). In HFrEF, only sST2, adjusted, correlated with LVMI (p = 0.010), whereas BNP correlated with LVMI (p = 0.002) and EF (p = 0.001). GDF-15 correlated with diastolic dysfunction in HFpEF (p = 0.046) and HFrEF (p = 0.024). Cardiac remodeling biomarkers are potential circulating indicators of LV hypertrophy in HFpEF, which may ensure timely recognition of disease progression among high-risk patients.

The partnership between renalase and ejection fraction as a risk factor for increased cardiac remodeling biomarkers in chronic heart failure patients.

Objective: Heart failure (HF) represents a huge socio-economic burden. It has been demonstrated, experimentally, that renalase, a newly discovered protein, prevents cardiac hypertrophy and adverse remodeling, which is seen in HF. We postulated the following aims: to investigate associations of renalase with biomarkers of cardiac remodeling: galectin-3, soluble suppression of tumorigenicity, (sST2), growth differentiation factor 15 (GDF-15) and syndecan-1, myocardial stretch (BNP) and cardio-renal axis (cystatin C) in HF patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) to determine whether renalase, in combination with left ventricular ejection fraction (LVEF), represents a risk factor for plasma elevation in biomarkers.Methods: We classified HF patients (n = 76) according to LVEF (preserved/reduced), applied a median plasma renalase (113 ng/mL) as a cut-off value (low/high) and created four subgroups of HF patients: HFpEF/low renalase (n = 19), HFrEF/low renalase (n = 19), HFrEF/high renalase (n = 32) and HFpEF/high renalase (n = 6). A control group (n = 35) consisted of healthy volunteers.Results: Plasma concentrations of evaluated biomarkers were determined using an ELISA technique and were highest in HF patients with reduced EF (p < .001, respectively), and renalase's positive correlations were obtained relating to all biomarkers: galectin-3 (r = 0.913; p < .001), sST2 (r = 0.965; p < .001), GDF-15 (r = 0.887; p < .001), syndecan-1 (r = 0.922; p < .001), BNP (r = 0.527; p < .001) and cystatin C (r = 0.844; p < .001) and strong and negative correlation with LVEF (r = -0.456, p < .001). Increased renalase, regardless of the EF (preserved/reduced), was shown to be an independent risk factor for an increase in all evaluated cardiac remodeling biomarkers, p < .001, respectively. However, increased renalase and reduced EF was the only independent risk factor for BNP and cystatin C elevation, p < .001, respectively. Results after multivariable adjustments (age/gender) were identical.Conclusion: When elevated plasma renalase and HF are present, regardless of EF being reduced or preserved, that represents a significant risk factor for increase in cardiac remodeling biomarker plasma concentrations. However, only elevated renalase and reduced EF demonstrated significance as a risk factor for BNP and cystatin C plasma elevation. Renalase may be considered a promising molecule for the improved predictive abilities of conventional biomarkers and is worthy of further investigation.

Association of Plasma Renalase and Left Ventricle Mass Index in Heart Failure Patients Stratified to the Category of the Ejection Fraction: A Pilot Study.

Heart failure represents a growing health problem, with increasing morbidity and mortality globally. According to the mechanisms involved in the pathogenesis of heart failure, many biomarkers have been proposed for the timely diagnosis and prognostication of patients with heart failure, but other than natriuretic peptides, none of them has gained enough clinical significance. Renalase, a new protein derived from kidneys was demonstrated to metabolize catecholamines and to have a cardioprotective role. The aim of the study was to determine whether renalase and brain natriuretic peptide (BNP) concentration could be used to differentiate heart failure patients stratified to the category of the ejection fraction and whether plasma renalase could be used as a biomarker for left ventricle hypertrophy in all subgroups of heart failure patients. We included patients diagnosed with heart failure and stratified them to the three subgroups according to the ejection fraction. Regarding echocardiographic parameters, HFmrEF had an intermediate profile in between HFrEF and HFpEF, with statistical significance in most evaluated parameters. BNP concentration was significantly different in all three subgroups (p < 0.001), and renalase was statistically higher in HFrEF (p = 0.007) compared to the HFmrEF and HFpEF, where its results were similar, without statistical significance. Renalase plasma concentration was demonstrated to be highly and positively associated with left ventricle mass index in HFrEF (p = 0.029), as well as increased plasma concentration of BNP (p = 0.006). In the HFmrEF group of patients, body mass index was positively associated with LVMI (p = 0.05), while in the patients with HFpEF, diabetes mellitus was demonstrated to have a positive association with LVMI (p = 0.043). These findings suggest that renalase concentration may be measured in order to differentiate patients with reduced ejection fraction. Plasma renalase concentrations positively correlated with left ventricle hypertrophy in patients with reduced ejection fraction, being strongly associated with increased left ventricular mass index.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience.

BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niska Banja", Nis, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience

ABSTRACT BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niška Banja", Niš, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

Impact of socio-demographic characteristics and long-term complications on quality of life in patients with diabetes mellitus.

OBJECTIVE: Diabetes mellitus (DM) has been one of the leading chronic diseases worldwide over past decades. The objective of the study was to identify predictors associated with health-related quality of life (HRQOL) in diabetic patients. METHODS: A cross-sectional questionnaire-based study was conducted at the General Hospital of the city of Leskovac, between June and November 2015. The Short Form-36 (SF-36) questionnaire, EuroQol-5D (EQ-5D) and EuroQol-VAS (EQ-VAS) questionnaires were used. Univariate and multivariate linear regression analyses were performed. RESULTS: The total number of patients was 285, 112 men (39.3%) and 173 women (60.7%), average age 63.92 ± 1.07 years. The results of multiple linear regression of socio-demographic characteristics in relation to dimensions of the quality of life measured by SF-36 and EQ-VAS showed that age, country (rural) life, low level of education, retirement, and poor economic status are predictors of lower quality of life. Our results showed that employment has a significant association with higher Physical Component Score (PCS), Mental Component Score (MCS) and EQ-VAS score, which can be explained with higher incomes, improved economic status and less possibility for the occurrence of depressive mood. Patients without formal education have lower QOL. Univariate multiple regression analysis of the presence of micro- and macrovascular complications of DM showed that angina pectoris, heart failure, diabetic retinopathy, and diabetic nephropathy are the most important factors affecting the quality of life in our population. After including the multivariate model, all tested complications remained statistically significant. CONCLUSION: Our results showed that both socioeconomic and chronic complications are relevant factors of HRQOL in type 1 and 2 diabetes mellitus patients. Age, rural lifestyle, retirement, lower level of education and low socioeconomic status, as well as DM complications (angina pectoris, hearth failure, diabetes nephropathy, and diabetes retinopathy) were found to be independent risk factors for the component scores of SF-36 and EQ-VAS score. Taking into consideration the results obtained, health practitioners should be aware not only of the clinical parameters of patients with DM, but also of their educational level and working status.

Relationship between the Manner of Mobile Phone Use and Depression, Anxiety, and Stress in University Students.

Objectives: There is insufficient evidence regarding the potential risk of mobile phone use on mental health. Therefore, the aim of this research was to examine the relationship between mobile phone use and mental health by measuring the levels of depression, anxiety, and stress among university students in Serbia and Italy. Methods: This cross-sectional study was carried out at two distinguished universities in Serbia and Italy from March to May of the 2015/2016 academic year and included 785 students of both genders. The questionnaire was compiled and developed from different published sources regarding the manner and intensity of mobile phone use, along with the Depression Anxiety Stress Scale (DASS 42) for measuring psychological health. The statistical analysis of the data included the application of binary logistic regression and correlation tests. Results: Statistical analysis indicates that anxiety symptoms are somewhat more present in younger students (odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.76-0.96), in those who send more text messages SMSs (OR = 1.15, 95% CI: 1.11-1.31), and in those who browse the internet less frequently (OR = 0.84, 95% CI: 0.73-0.95). Stress is more common in students who make fewer calls a day (OR = 0.79, 95% CI: 0.64-0.97), as well in those who spend more time talking on the mobile phone per day (OR = 1.28, 95% CI: 1.12-1.56). The strongest predictor of high stress levels was keeping the mobile phone less than 1 m away during sleeping (OR = 1.48, 95% CI: 1.12-2.08). Conclusions: The results indicated that the intensity and modality of mobile phone use could be a factor that can influence causal pathways leading to mental health problems in the university student population.

Factors affecting the survival of patients with glioblastoma multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is the most aggressive malignant tumor in the brain and no therapy can achieve full recovery/cure. The aim of this study was to identify which factors could improve the survival of operated patients, and to determine which kind of therapy was most successful. METHODS: The study was conducted at the Clinic for Neurosurgery in Nis, Clinical Centre Nis and the Oncology Institute, Clinical Center Nis. A cohort of patients who underwent surgery between January 2013 and December 2015 was studied and continuous monitoring of survival lasted until June 2017. RESULTS: Patients who underwent only biopsy have 3.82- fold greater chance of death than patients with complete tumor resection (HR 3,825; p=0.001). Karnofsky performance status score significantly affected survival (preoperatively and postoperatively; p<0.001). Apart from radiotherapy, three types of chemotherapy were applied: carmustine (BCNU) - 32.80% of the patients, procarbazine/lomustine/ vincristine (PCV) - 38.80% and temozolomide - 28.40%. Kaplan-Meier overall survival showed that patients treated with temozolomide had the longest survival compared to patients treated with BCNU and/or PCV chemotherapy. CONCLUSION: The best prognosis was seen in those patients who had complete tumor resection. Patients treated with temozolomide had the best survival compared with those treated with BCNU and PCV chemotherapy.

Progress of statistical analysis in biomedical research through the historical review of the development of the Framingham score.

BACKGROUND: The interest in developing risk models in medicine not only is appealing, but also associated with many obstacles in different aspects of predictive model development. Initially, the association of biomarkers or the association of more markers with the specific outcome was proven by statistical significance, but novel and demanding questions required the development of new and more complex statistical techniques. METHODS: Progress of statistical analysis in biomedical research can be observed the best through the history of the Framingham study and development of the Framingham score. RESULTS: Evaluation of predictive models comes from a combination of the facts which are results of several metrics. Using logistic regression and Cox proportional hazards regression analysis, the calibration test, and the ROC curve analysis should be mandatory and eliminatory, and the central place should be taken by some new statistical techniques. In order to obtain complete information related to the new marker in the model, recently, there is a recommendation to use the reclassification tables by calculating the net reclassification index and the integrated discrimination improvement. Decision curve analysis is a novel method for evaluating the clinical usefulness of a predictive model. It may be noted that customizing and fine-tuning of the Framingham risk score initiated the development of statistical analysis. CONCLUSION: Clinically applicable predictive model should be a trade-off between all abovementioned statistical metrics, a trade-off between calibration and discrimination, accuracy and decision-making, costs and benefits, and quality and quantity of patient's life.

Renalase Assessment With Regard to Kidney Function, Lipid Disturbances, and Endothelial Dysfunction Parameters in Stable Renal Transplant Recipients.

BACKGROUND: Renal transplant dysfunction has been shown to be independent predictor for premature cardiovascular disease and mortality. Renalase, a flavoprotein secreted by several tissues, including the kidney, has been found to regulate sympathetic tone and blood pressure. The purpose of this secondary analysis was to explore relationships among parameters of endothelial dysfunction, lipids, glomerular filtration rate, and renalase in 2 groups: renal transplant patients with controlled hypertension and healthy volunteers. METHODS: In the parent study, 73 renal transplant recipients and 32 age- and gender-matched controls were enrolled. A fasting sample for endothelial, lipid, and renalase values, along with other clinical parameters, was obtained. RESULTS: We found statistically significant inverse correlation between renalase and estimated glomerular filtration rate ( r = -0.552, P < .001), positive correlation between renalase and creatinine ( r = 0.364, P = .003), total cholesterol ( r = 0.578, P < .001), low-density lipoprotein cholesterol ( r = 0.261, P = .046), and non-high-density lipoprotein cholesterol ( r = 0.327, P = .01). Renalase inversely correlated with hemoglobin ( r = -0.232, P = .032) and positively with white blood cells ( r = 0.233, P = .032). There was a significant difference in plasma renalase with regard to chronic kidney disease stages ( F = 13.346, P < .001) but did not correlate with C-reactive protein. Renalase did not correlate with any of parameters of endothelial dysfunction, C-reactive protein, neither with some demographic data (gender, age, time or type of transplantation, risk factors). There were no differences in renalase concentration with regard to antihypertensive therapy. CONCLUSION: Renalase strongly and inversely correlated with kidney function, positively with creatinine and lipid disturbances. Due to that it is very likely that renalase levels are determined mostly by renal function.