Evaluation of Risk Factors for the Occurrence of Limb Fractures in Children Due to Unintentional Injury in Podgorica, Montenegro, Mediterranean.

Background and Objectives: Limb injuries in childhood are very common, with most of them being unintentional and often accompanied by soft tissue injuries. The aim of our study was to determine the risk factors that contribute to the occurrence of limb fractures as the most common type of accidental injury to children in our conditions. Materials and Methods: This study was designed as a prospective clinical analysis of predictive factors with a "nested" case-control study. It included all patients under the age of 18 who were diagnosed with unintentional limb injury and limb fracture due to accidental injury, at the Clinical Center of Montenegro, Podgorica, in the period of 7 January 2020-30 June 2021. Results: The gender of the child and the occurrence of the fracture are not related, and a statistically significant relationship was found between the occurrence of the fracture and the place of residence, the child's age, body mass index (BMI), the affected limb, the method of injury, and the mental state of the parents of the injured child, as well as their economic status. It was proved that the older the child was, the lower the chance of injury, while multivariate analysis proved that BMI could be a predictor of accidental fracture. The most common method of accidental limb fractures in children was a fall from a height. Conclusions: The analysis of factors that influence the occurrence of children's injuries is of great importance for public health. Such and similar research can enable a better understanding of the factors that influence accidental injuries, and therefore influence the prevention of these injuries by organizing various educational materials at the primary healthcare level or at the school level, for both children and parents.

Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease.

BACKGROUND: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events. OBJECTIVES: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF). METHODS: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay. RESULTS: In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03-2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = -0.394), glomerular filtration fraction (GFR; ϱ = -0.615), and peak VO2 (ϱ = -0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age. CONCLUSIONS: This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.

The Risk Model of Developing Schizophrenia Based on Temperament and Character.

INTRODUCTION: Cloninger's psychological model of temperament and character confirms that the personality development is influenced by biological and psychological processes. The aim of this study is to examine personality dimensions and to determine which variable separates the healthy from the ill in the best way and could be a possible psychological marker for the presence of the illness. METHODS: This research included 152 subjects, 76 patients with schizophrenia and 76 healthy controls, selected on the basis of medical interviews, random population sampling model from a wider social community using the independent T-Tests. The Temperament and Character Inventory (TCI), which compared personality traits of the patients with schizophrenia and the healthy control group, was used. Dependence of variables in these categories was assessed using the Chi-square and Fisher's tests, and the impact of variables on schizophrenia was tested using univariate and multivariate binary logistic regression. The same method was used for making the mathematical model. RESULTS: Unlike the control group, patients with schizophrenia exhibited higher Harm avoidance (HA) and Self - transcendence (ST) scores as well as lower Self - directedness (SD) and Cooperativeness (C) scores. Multivariate binary logistic regression showed that Responsibility, Purposefulness, Resourcefulness, Cooperativeness and Compassion dimensions were significantly more present in the patients with schizophrenia. The new variable Model (area=0.896, p<0.0005) is composed of five TCI parameters. It proved to be a reliable marker for separation the healthy from the ill ones (area=0.896, p<0.0005). It has a good sensitivity (80%) and specificity (84%). CONCLUSIONS: Research has emphasized variables in the temperament and character inventory, which are the best markers for distinguishing between the healthy and the ill, thus making the mathematical model.

Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation.

BACKGROUND: The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. METHODS: Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention. In another 115 patients with diastolic or systolic CHF, we investigated a possible relationship between zonulin and CHF severity. RESULTS: In the AICD cohort, zonulin associated inversely with serum creatinine (p = 0.013), carboxymethyl-lysine calprotectin (p < 0.001), and kynurenine (p = 0.009) and positively with homoarginine (p < 0.001). In the subgroup with type-2 diabetes (T2D) (n = 51), zonulin increased significantly with high-sensitivity CRP (p = 0.014). In the CHF cohort, we found a highly significant rise of NT-proBNP, but not of zonulin with NYHA functional classes I-IV or other parameters of CHF severity. CONCLUSIONS: The inverse associations of zonulin with creatinine and markers of cardio-vascular risk (high CMLcalprotectin and kynurenine, low homoarginine) are novel findings that need further experimental and clinical clarification. Our study indicates zonulin involvement in metabolic inflammation in T2D, but no association with disease status in CHF.

Analysis of risk factors for perifocal oedema after endovascular embolization of unruptured intracranial arterial aneurysms.

BACKGROUND: Endovascular embolization is a treatment of choice for the management of unruptured intracranial aneurysms, but sometimes is complicated with perianeurysmal oedema. The aim of our study was to establish incidence and outcomes of perianeurysmal oedema after endovascular coiling of unruptured intracranial aneurysms, and to reveal possible risk factors for development of this potentially serious complication. METHODS: In total 119 adult patients with endovascular embolization of unruptured intracranial aneurysm (performed at Department for Interventional Neuroradiology, Clinical Center, Kragujevac, Serbia) were included in our study. The embolizations were made by electrolite-detachable platinum coils: pure platinum, hydrophilic and combination of platinum and hydrophilic coils. Primary outcome variable was perianeurysmal oedema visualized by magnetic resonance imaging (MRI) 7, 30 and 90 days after the embolization. RESULTS: The perianurysmal oedema appeared in 47.6% of patients treated with hydrophilic coils, in 21.6% of patients treated with platinum coils, and in 53.8% of those treated with mixed type of the coils. The multivariate logistic regression showed that variables associated with occurrence of perianeurysmal oedema are volume of the aneurysm, hypertension, diabetes and smoking habit. Hypertension is the most important independent predictor of the perianeurysmal oedema, followed by smoking and diabetes. CONCLUSIONS: The results of our study suggest that older patients with larger unruptured intracranial aneurysms, who suffer from diabetes mellitus and hypertension, and have the smoking habit, are under much higher risk of having perianeurysmal oedema after endovascular coiling.

Clinical performance of the EuroSCORE II compared with the previous EuroSCORE iterations.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II has been recently introduced as an update to the previous versions. We sought to evaluate the predictive performance of the EuroSCORE II model against the original additive and logistic EuroSCORE models. PATIENTS AND METHODS: The study included 1,247 consecutive patients who underwent cardiac surgery procedures during a 14-month period starting from the beginning of 2012. The original additive and logistic EuroSCORE models were compared with the EuroSCORE II focusing on the accuracy of predicting hospital mortality. RESULTS: The overall hospital mortality rate was 3.45%. The discriminative power of the EuroSCORE II was modest and similar to other algorithms (C-statistics 0.754 for additive EuroSCORE; 0.759 for logistic EuroSCORE; and 0.743 for EuroSCORE II). The EuroSCORE II significantly underestimated the all-patient hospital mortality (3.45% observed vs. 2.12% predicted), as well as in the valvular (3.74% observed vs. 2% predicted), and combined surgery cohorts (6.87% observed vs. 3.64% predicted). The predicted EuroSCORE mortality significantly differed from the observed mortality in the third and the fourth quartile of patients stratified according to the EuroSCORE II mortality risk (p < 0.05). The calibration of the EuroSCORE II was generally good for the entire patient population (Hosmer-Lemeshow [HL] p = 0.139), for the valvular surgery subset (HL p = 0.485), and for the combined surgery subset (HL p = 0.639). CONCLUSION: The EuroSCORE II might be considered a solid predictive tool for hospital mortality. Although, the EuroSCORE II employs more sophisticated calculation methods regarding the number and definition of risk factors included, it does not seem to significantly improve the performance of previous iterations.

Incremental value of high-sensitive troponin T in addition to the revised cardiac index for peri-operative risk stratification in non-cardiac surgery.

AIMS: We aimed to evaluate the incremental value of high-sensitive troponin T (hsTnT) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index. METHODS AND RESULTS: In this prospective, international multicentre observational study, 979 patients prior to non-cardiac surgery were enrolled. The endpoints were in-hospital mortality, the combination of death, acute myocardial infarction, cardiac arrest, cardio-pulmonary resuscitation, and acute decompensated heart failure. Twenty-five patients (2.6%) deceased and 36 (3.7%) of the patients experienced the combined endpoint. Cardiac markers were elevated in those patients who died when compared with survivors (hsTnT: 21 ng/L vs. 7 ng/L; P < 0.001; NT-proBNP: 576 pg/mL vs. 166 pg/mL; P < 0.001). Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL, those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2% (P < 0.001) and with elevated NT-proBNP 4.8 vs. 1.4% (P = 0.002). The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809. In a multivariate Cox regression analyses, hsTnT was the strongest independent predictor for the combined endpoint [HR 2.6 (95% CI: 1.3-5.3); P = 0.01]. CONCLUSION: High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac index.

Homozygous-Recessive Characteristics as a Biomarker of Predisposition for COVID-19.

Coronavirus disease (COVID-19), a new form of severe acute respiratory syndrome, has caused a global pandemic. The aim of this study was to analyze homozygous-recessive characteristics (HRC) in the group of COVID-19 patients, considering their gender, forms of the disease (mild and severe symptoms), risk factors: hypertension, diabetes mellitus type 2, hyperlipidemia, smoking habits, and the distribution of ABO blood group. Using the HRC test, we analyzed 20 HRCs in a sample of 321 individuals: 205 patients and 116 controls. The average HRC in patients was significantly higher than controls, as well as in patients with severe symptoms compared to patients with mild symptoms. The patients with higher HRC (cut-off ≤5.5) experienced a significantly increased risk of disease of 2.3 times (OR = 2.315, p < .0005). Our results indicate that the HRC test could be used as a screening in recognizing predisposition for COVID-19.

Mortality of Malignant Melanoma in Central Serbia, in the Period 1999-2015.

INTRODUCTION: Malignant melanoma is one of the rarest forms of skin cancer but it is the most deadly. OBJECTIVE: The objective of this paper was to analyze the epidemiological characteristics and trends of mortality from malignant melanoma in the population of Central Serbia in the period 1999-2015. METHODS: The study was designed as a retrospective descriptive epidemiological study. Standardized mortality rates were used in statistical data processing. A linear trend model and regression analysis were used to examine trends in malignant melanoma mortality. RESULTS: In Serbia, malignant melanoma mortality shows an increasing trend. The overall age-adjusted melanoma death rate was 2.6 per 100,000 with a higher death rate among men (3.03 per 100,000) than among women (2.1 per 100,000). Malignant melanoma mortality rates increase with age in both sexes and are highest in the age group of 75 and older. The highest increase in mortality in men is recorded in the 65-69 age group, with an average percentage increase of 21.33 (95% CI, 8.40 - 51.05), while in women the largest increase in mortality was recorded in the 35-39 age group, with an average percentage increase of 31.4 and in the 70-74 age group, 12.9. CONCLUSIONS: The trend of increasing mortality from malignant melanoma in Serbia is similar to those in most developed countries. Education and improvement of awareness in the general population and among health professionals are vital to reducing melanoma mortality in the future.

Antiproliferative and proapoptotic activities of methanolic extracts from Ligustrum vulgare L. as an individual treatment and in combination with palladium complex.

The aim of this study is to examine the growth inhibitory effects of methanolic leaf and fruit extracts of L. vulgare on HCT-116 cells over different time periods and their synergistic effect with a Pd(apox) complex. The antiproliferative activity of plant extracts alone or in combination with the Pd(apox) complex was determined using MTT cell viability assay, where the IC(50) value was used as a parameter of cytotoxicity. Results show that antiproliferative effects of L. vulgare extracts increase with extension of exposure time, with decreasing IC(50) values, except for 72 h where the IC(50) values for methanolic leaf extract were lower than for the fruit extract. The Pd(apox) complex alone had a weak antiproliferative effect, but combination with L. vulgare extracts caused stronger effects with lower IC(50) values than with L. vulgare extracts alone. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. Treatments with plant extracts caused typical apoptotic morphological changes in HCT-116 cells and co-treatments with Pd(apox) complex caused higher levels of apoptotic cells than treatment with plant extracts alone. The results indicate that L. vulgare is a considerable source of natural bioactive substances with antiproliferative activity on HCT-116 cells and which have a substantial synergistic effect with the Pd(apox) complex.

Importance of quick test for screening of former drug users.

INTRODUCTION: Most frequent mode of transmission of HCV today is with intravenous drug use. Former intravenous (IV) drug users present population group more exposed to HCV infection. Longer period of substance abuse, common syringe, more sexual partners (drug users) represent independent, statistically significant risk factors in this population. Diagnosis of HCV infection is based on history, epidemiological data, and clinical presentation, blood tests, histopathological and virology investigation. Hepagnost C is fast immunochromatography test for qualitative detection of HCV antibodies in blood, serum or plasma. Sensitivity of this test compared to EIA is >99% and relative specificity 98,6%. MATERIAL AND METHODS: At Clinic for Infectious diseases (Hepatology Department) voluntary testing with Hepagnost C test was done for 22 former drug users. Results of this cross-sectional study are processed with SPSS program for Windows. RESULTS: Most of the subjects were male (95,5%), average age of 33 +/- 3,5 years with average length of drug usage of 10 (7-12,5) years. All positive (9/22) were tested with EIA test and HCV infection was confirmed (9/9), therefore positive predictive value for Hepagnost C is 100%. We investigated relative risk (RR) with IV drug usage. Higher risk for infection (1,7 times) was among IV. drug users. Odds ratio was 2,4 (chance for HCV in iv. drug users group is 2,4 times higher). Common syringes increase relative risk for 4,5 times, and Odds ratio for infection 9 times. CONCLUSIONS: Hepagnost C test of high sensitivity and specificity showed 100% prediction. It is simple, inexpensive and comfortable test with results within 15 minutes. Demographic characteristics of tested persons as well as statistical results do not deviate significantly from results in available literature.

Neuroendocrine differentiation as an indicator of chemosensitivity and prognosis in nonsmall cell lung cancer.

CONTEXT: Nonsmall cell lung cancers with neuroendocrine differentiation (NSCLC-ND) may demonstrate biologic behavior intermediate between NSCLC and small cell lung cancer (SCLC) with impact on prognosis. METHODS: We analyzed 116 consecutive patients with Stage III and IV NSCLC who were diagnosed and treated between 2001 and 2006. Using immuno-histochemical staining for neuron-specific enolase (NSE), chromogranin A (ChrA), and synaptophysin (Syn), 29 (25%) NSCLC-ND were identified. RESULTS: Expression of NSE was present in 22.4%, ChrA in 15.5% and Syn in 14.8% of patients with NSCLC. Therapeutic response was significantly better in the NSCLC-ND group and specimens with > 30% neuroendocrine (NE)-differentiated tumor cells showed favourable therapeutic response (P < 0.05). Multivariate binary logistic regression showed that percentage of NE positive tumor cells was a significant independent prognostic factor associated with a favourable outcome. Receiver operating characteristic (ROC) curves and areas under ROC curves confirmed that percentage of NE-differentiated tumor cells could be useful prediction factor of therapeutic response. Moreover, according to percentage of NE-differentiated tumor cells, optimal cutoffs and related sensitivities and specificities were determined for each markers. CONCLUSION: Advanced-stage NSCLC with NE tumor cells are clinically less aggressive tumors. Percentage of NE-differentiated tumor cells identifies patients with favourable therapy response to paclitaxel-cisplatin.

Cervical precancerous lesions--chromosomal instability in peripheral blood lymphocytes in relation to lesion stage, age and smoking habits.

OBJECTIVE: To evaluate chromosomal damage in peripheral blood lymphocytes (PBL) of patients newly diagnosed with cervical precancerous lesions with respect to age, smoking habits, miscarriages, abortions and lesion stage. DESIGN: Clinical study. SETTING: Clinic of Gynecology and Obstetrics in Kragujevac, Serbia, during 2009-2010. POPULATION: The analyzed samples included 41 untreated patients aged 24-65 years with a diagnosed low-grade squamous intraepithelial lesion (LSIL; 19 patients) or a high-grade squamous intraepithelial lesion (HSIL; 22 patients). Control samples were obtained from 40 healthy women aged 24-53 years. METHODS: The frequency of micronuclei (MN) was estimated in circulating lymphocytes by using the cytokinesis-block micronucleus assay. MAIN OUTCOME MEASURE: The frequency of MN in PBL. RESULTS: The mean MN frequencies of both LSIL and HSIL patients were significantly higher than the MN frequency of healthy control women. There was no significant difference in MN frequency between LSIL and HSIL patients, between smokers and nonsmokers in both patient and control samples, or between miscarriage groups and abortion groups of patients. Considering confounder factors, age and health status influenced MN frequency. CONCLUSIONS: The results suggest that MN frequency in PBL of patients with cervical precancerous lesions corresponds to an increase of chromosomal damage, irrespective of smoking habits, miscarriages, abortions and lesion stages.

Correction: Chronic Hepatitis C: Conspectus of immunological events in the course of fibrosis evolution.

[This corrects the article DOI: 10.1371/journal.pone.0219508.].

Chronic Hepatitis C: Conspectus of immunological events in the course of fibrosis evolution.

In chronically infected HCV patients emergence and evolution of fibrosis, as a consequence of virus persistence, can be considered as an indicator of disease advancement. Therefore the aim of this study was to correlate alterations of immune response in chronic HCV patients with liver histopathology. Sera cytokine levels and frequency of circulating and liver infiltrating cells were evaluated using 13plex Kit Flow Cytomix, flow cytometry and immunohistochemistry. We found that the number of circulating T lymphocytes (including CD4+, CD8+ and Treg) and B lymphocytes, as well as DCs, was higher in patients with no fibrosis than in healthy subjects. In patients with fibrosis frequency of these cells decreased, and contrarily, in the liver, number of T and B lymphocytes gradually increased with fibrosis. Importantly, in patients with advanced fibrosis, liver infiltrating regulatory T cells and DC-SIGN+ mononuclear cells with immunosuppressive and wound-healing effector functions were abundantly present. Cytokine profiling showed predominance of proinflammatory cytokines in patients with no fibrosis and a tendency of decline in level of all cytokines with severity of liver injury. Lower but sustained IL-4 production refers to Th2 predominance in higher stages of fibrosis. Altogether, our results reveal graduall alterations of immunological parameters during fibrosis evolution and illustrate the course of immunological events through disease progression.

Clinical trial/experimental study (consort compliant): Optimal time period to achieve the effects on synbiotic-controlled wheezing and respiratory infections in young children.

INTRODUCTION: Urban life is often followed by immune dysfunction and loss of immune tolerance in the youngest children. OBJECTIVE: The study aimed to determine optimal time efficiency of a synbiotic (5 x 109 Lactobacillus acidophilus Rosell-52, Bifidobacterium infantis Rosell-33, Bifidobacterium bifidum Rosell-71) in controlling respiratory infections and wheezing disease. METHODS: We randomly selected a group of children younger than five years, hospitalized earlier, and classified them into three groups. RESULTS: The incidence of respiratory infection before the study was once a month, while after a three-month supplementation with the synbiotic children rarely suffered from respiratory infections, and the state was maintained after six-month and nine-month supplementations with the synbiotic. The decreased incidence of respiratory infections was followed by a falling incidence of concomitant wheezing. A significant increase in tIgA serum was observed in all groups for only three months, the increase being the highest in children with recurrent respiratory infections accompanied by wheezing. After a nine-month administration of the synbiotic, total IgE serum was lower in all groups of patients. CONCLUSION: The optimal duration of administration of the synbiotic containing three probiotic cultures to provide effective control of the frequency of respiratory infections was three months, and six months were required to establish control of the frequency of wheezing. This synbiotic is useful for immunomodulation in children and is well-tolerated in young children.

The prevalence and socioeconomic correlates of depressive and anxiety symptoms in a group of 1,940 Serbian university students.

UNLABELLED: BACKGROUND/AIM. Mental health of university students is under increasing concern worldwide, because they face challenges which predisposes them to depression and anxiety. The aim of this study was to identify demographic and socioeconomic variables associated with depressive and anxiety symptoms among university students. METHODS: This cross-sectional study on 1,940 university students was performed using a questionnaire including demographic and socioeconomic variables, Beck Depression Inventory and Beck Anxiety Inventory. RESULTS: The prevalence of depressive symptoms in students was 23.6%, while the prevalence of anxiety symptoms was 33.5%. The depressive symptoms were significantly related to the study year (p = 0.002), type of faculty (p = 0.014), satisfaction with college major choice (p < 0.001), satisfaction with grade point average (p < 0.001). Female students (odds ratio--OR = 1.791, 95% confidence interval--CI = 1.351-2.374), older students (OR = 1.110, 95% CI = 1.051-1.172), students who reported low family economic situation (OR = 2.091, 95% CI = 1.383-3.162), not owning the room (OR = 1.512, 95%CI = 1.103-2.074), dissatisfaction with graduate education (OR = 1.537, 95% CI = 1.165-2.027) were more likely toshow depressive symptoms. The anxiety symptoms were significantly related to study year (p = 0.034), type of faculty(p < 0.001), family economic situation (p = 0.011), college residence (p = 0.001) satisfaction with the college major choice (p = 0.001), and satisfaction with graduate education(p < 0.001). Female students (OR = 1.901, 95% CI =1.490-2.425), and students who reported parents high expectations of academic success (OR = 1.290, 95% CI =1.022-1.630) were more likely to show anxiety symptoms. CONCLUSION: This is one of the largest study examining mental disorders in a sample of university students in Serbia. These findings underscore the importance of early detections of mental problems and prevention interventions in university students.

Diagnostic utility of new immunoassays for the cardiac markers cTnI, myoglobin and CK-MB mass.

OBJECTIVES: We investigated the diagnostic value of a new system, the Innotrac Aio! immunoassays for troponin, myoglobin and CK-MB, in 270 samples from patients with ACS, after bypass surgery (CABG) or with stable heart failure in comparison to the respective Roche assays. RESULTS: The values of the cardiac markers assessed by the respective assays correlated (cTnT/cTnI Rho = 0.94, myoglobin Rho = 0.87, CK-MB Rho = 0.84). If values were dichotomised, we found a high concordance of test positive and negative classified patients by troponins with the respective assays. CONCLUSION: There is strong evidence that the Innotrac Aio! system for cTnI measurement can be used reliably.