Background and Objectives: In the development of type 2 diabetes mellitus (T2DM) and its complications, genetic and environmental factors play important roles. Diabetic nephropathy (DN), one of the major microangiopathic chronic diabetic complications, is associated with an increased risk of major cardiovascular events and all-cause mortality. The present study was designed to investigate the possible modifying effect of glutathione transferase polymorphisms (GSTM1, GSTT1, GSTP1 rs1138272/rs1695, GSTO1 rs4925 and GSTO2 rs156697) in the susceptibility to T2DM and diabetic nephropathy. Materials and Methods: GSTM1 and GSTT1 deletion polymorphisms were determined by multiplex PCR, whereas GSTO1, GSTO2, and GSTP1 polymorphisms were determined by the real-time PCR in 160 T2DM patients and 248 age- and gender-matched controls. Advanced glycation end products (AGEs) were measured by ELISA. Results: Among six investigated GST polymorphisms, a significant association between the GST genotypes and susceptibility for development of diabetes mellitus was found for the GSTM1, GSTT1, GSTP1 (rs1138272) and GSTO1 polymorphisms. When the GST genotypes’ distribution in diabetes patients was assessed in the subgroups with and without diabetic nephropathy, a significant association was found only for the GSTO2 rs156697 polymorphism. Diabetic patients, carriers of the GSTM1 null, GSTT1 null and variant GSTO1*AA genotypes, had significantly increased levels of AGEs in comparison with carriers of the GSTM1 active, GSTT1 active and referent GSTO1*CC genotypes (p < 0.001, p < 0.001, p = 0.004, respectively). Conclusions: The present study supports the hypothesis that GST polymorphisms modulate the risk of diabetes and diabetic nephropathy and influence the AGEs concentration, suggesting the potential regulatory role of these enzymes in redox homeostasis disturbances.

Speech is a way of communication formed by rhythmic units of syllables, words and sentences, and as such is inherent in man, the only being whose organs and psyche are trained for this process. Delayed speech is defined as a phenomenon in which a child does not start speaking on time, or there are errors in the speech pattern that are not appropriate in relation to a given age. It is known that significant risk factors for the development of delayed speech in preschool children are physical, and most often social and emotional in nature. For the normal development of speech, it is necessary that the child is in a human environment, and therefore the circle of people with whom children come into contact should always be expanded. The aim of this study is to review the existing literature on studies examining the impact of social isolation during the COVID-19 pandemic on preschool children, as well as the speech and language development in preschool children. The recent pandemic of corona virus infection (COVID-19) has led to a state of emergency, quarantine, closure of public institutions, and preschools, kindergartens and schools in 172 countries. These epidemiological measures have led to social isolation and the need for children to learn from home, which has manifested itself in the emergence of difficulties in the development of speech and language. Research has shown that during the pandemic, children spent significantly more time watching television and computer screens than before pandemic, and less in play and physical activity.

Introduction. Cardiac magnetic resonance imaging (CMR) is considered the reference diagnostic method for quantifying right ventricular size and function, and pulmonary regurgitation in patients with tetralogy of Fallot surgery. The aim of this paper is to confirm the importance of magnetic resonance continuous postoperative monitoring of right and left heart function parameters as a diagnostic method that provides the most precise and accurate assessment. Methods. The prospective observational study included subjects with TOF surgery who were diagnosed with residual morphological and/or functional disorders on control postoperative echocardiographic examinations. All subjects underwent magnetic resonance imaging of the heart on a 1.5 T scanner with dedicated coils for the heart surface according to the standard protocol for a period of one year from the beginning of the study. Criteria for exclusion from the study were: significant residual pulmonary stenosis, condition after pulmonary valve replacement, existence of residual shunt lesions, contraindications for cardiac magnetic resonance imaging (pacemaker, ICD, claustrophobia). Depending on the time elapsed since the tetralogy of Fallot surgery, the subjects were divided into groups: more than 15 years, 11-15 years, 6-10 years, less than 5 years. Results. The study included 131 subjects with an average age of 24.18 ± 11.57 years with complete correction of TOF. Intergroup differences in values of right ventricular end-diastolic volume, right ventricular ejection fraction, and left ventricular ejection fraction were demonstrated, but there was no statistically significant intergroup difference in values of pulmonary regurgitation fraction. The negative interaction of the right and left ventricles intensifies during the years of follow-up of patients after TOF surgery, which is especially true fifteen years after surgery. Conclusion. CMR has the most significant role in research efforts aimed at improving the outcomes of operated patients with tetralogy of Fallot.

Cancer-related cognitive dysfunction is an important clinical problem that can interfere with the daily functioning, work productivity, childcare, and other responsibilities of women with a history of breast cancer. Risks of cancer-related cognitive impairment include cancer and cancer treatment, as well as patient-related vulnerabilities. There is no established standard of neuroprotective care or treatment for breast cancer-related cognitive impairment.

Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (DM2) and its complications. Diabetic nephropathy (DN) is one of the most common microangiopathic chronic complications of diabetes. Oxidative stress occurs under condition of increased production of free radicals and/or decreased activity of antioxidant defense mechanisms and it is an important link in the complex mechanism of diabetic vascular changes. Glutathione transferases (GST) are enzymes involved in xenobiotic metabolism and they are part of complex antioxidant defense mechanisms. Numerous studies have found an association of GST gene polymorphism to a predisposition to various diseases, including diabetes and diabetic nephropathy. Our and other authors' results suggest that genetic variations in enzymes involved in free radical metabolism are associated with the development of end-stage kidney disease in patients with diabetes, which could become the basis for the development of preventive and early therapeutic strategies in high risk people.

Introduction. Art reception and experiencing is a complex process, containing creative components. The experience of a work of art involves reproduction, in the viewer's consciousness, of the experiences and excitement that the artist himself or herself have undergone in the process of creating the same works of art. When viewing visual images, our perception is directed towards the identification of objects, and when viewing visual images as works of art, we also tend to experience them - we subjectively react to elements, such as stylistic and structural characteristics. The aim of the research is to examine the effectiveness of the experimental program named the Impact of Verbal, Auditory and Visual Incentives, designed to foster students' visual perception and visual reception during art education. Methods. The experimental method with parallel groups was used. The research included the sample consisting of 98 students, out of which 45 belonged to experimental group while 53 were control students from Trebinje region. Test LV1, examining visual creativity, as well as visual perception and visual reception (art appreciation), was used. Results. The results indicated that the experimental program influenced the development of the visual perceptive (F = 3.76; p = 0.05) and visual receptive (F = 8.01; p = 0.00) abilities among students during art education because the experimental group students achieved significantly better results than the control group students. The experimental program was aligned with the curriculum and designed to influence the development of students' visual-perceptual and visual-receptive abilities. Conclusion. The obtained results indicate that it is possible to influence the development of students' visual-perceptual and visual-receptive abilities by using a specially designed program, aimed at stimulating verbal, auditory and visual aspects of visual expression.

ABSTRACT Background: Risk of cardiovascular disease (CVD) has been associated with stress from serving in a war, but it has not been established whether children who experience war-related stress are at increased CVD risk. Objective: This study aimed to compare CVD risk factors in young adults according to whether they experienced traumatic events as children during the 1990–1995 war in Bosnia and Herzegovina, and whether those exposed to trauma have evidence of subclinical atherosclerosis. Method: We examined 372 first-year medical students who were preschool children during the war (1990–1995) (average age 19.5 ± 1.7 years, 67% female) in 2007–2010. They completed the Semi-Structured Interview for Survivors of War. CVD risk factors and carotid intima–media thickness (CIMT) measurements were obtained and compared in individuals with and without trauma. We also examined whether increased CIMT was independently associated with trauma after adjustment for other risk factors. Results: From multiple logistic regression, only elevated triglycerides (> 1.7 mmol/l) were associated with a 5.2 greater odds of having experienced trauma. The mean CIMT of subjects with trauma was greater than that of non-trauma-exposed subjects (0.53 mm vs 0.50 mm, p = 0.07). Moreover, trauma was independently associated with higher CIMT (difference = 0.036 mm, p = 0.024) after adjustment for CVD risk factors. Conclusions: We show that most CVD risk factors are associated with post-war trauma in young adults, and, if present, such trauma is associated with higher triglycerides and higher levels of CIMT in multivariable analysis. HIGHLIGHTS • Our investigation was to examine whether there are differences in cardiovascular risk factors and subclinical atherosclerosis in persons previously exposed compared to not exposed to trauma during the war in Bosnia and Herzegovina.• We demonstrated that while traditional risk factors are not strongly related to the presence of post-war trauma in young adults, those with greater CIMT appear to have been more likely to have had been prevoiusly exposed to trauma.

Introduction/Objective. During the past 20 years, there have been numerous attempts to design and apply a simple, affordable blood analysis tool for diagnostic and prognostic purposes in psychiatry. In this article we demonstrate that some mathematical parameters of chromatin organization and distribution in blood neutrophil granulocytes are related to stress levels in patients diagnosed with recurrent depressive disorder (RDD). Methods. The study was performed on 50 RDD participants who were asked to complete Depression, Anxiety and Stress Scales (DASS-21). Peripheral blood samples were obtained from all the participants, smeared on glass slides and stained using a modification of Giemsa method. A total of 500 representative chromatin structures (10 per patient) of neutrophil granulocytes were evaluated using textural analysis with the application of gray level co-occurrence matrix (GLCM) method. Parameters such as angular second moment (indicator of textural uniformity), inverse difference moment (textural homogeneity), and textural sum variance were calculated. Results. The results indicate that there is a statistically highly significant correlation (p < 0.01) between certain chromatin GLCM parameters such as inverse difference moment, and DASS-21 stress score. There was also a significant difference (p < 0.05) in some chromatin GLCM parameters in patients diagnosed with RDD with psychotic features, when compared to the ones without psychosis. Conclusion. These findings suggest that in the future, chromatin GLCM features might have a certain predictive value for some clinical features of recurrent depressive disorder.

Tendency of modern diagnostic visualization development in biomedicine is focused on the integration of detection and quantification of molecular, functional and morphological events in the biological systems. The increasing number of patients with chronic kidney disease stimulated the development of new diagnostic methods. The development of magnetic resonance technology encouraged the use of functional magnetic resonance imaging of kidneys in both scientific research and clinical practice. The paper presents the basic characteristics of the functional magnetic resonance imagining and the possibilities for its use in the examination of kidney functions.

Aims: The aim of this study was to compare the risk factors and prevalence of vascular calcification (VC) in pre-dialysis and hemodialysis (HD) patients with Balkan endemic nephropathy (BEN) or other kidney diseases (non-BEN). Materials and Methods: The study involved 115 patients, 32 pre-dialysis and 83 HD patients, separated into groups of BEN and non-BEN patients. In addition to interviews, objective examinations and laboratory analyses, VC was assessed using Adragao score. Results: Patients with BEN were significantly older in both groups, while pre-dialysis BEN patients had significantly lower systolic blood pressure, serum cholesterol and phosphorus levels, but higher urinary excretion of phosphorus than non-BEN patients. These differences were lost in HD groups. In pre-dialysis patients, prevalence of VC was lower in BEN than in non-BEN group and mean VC score differed significantly between them (2.8 (1.7) vs. 4.6 (1.8); p = 0.009). No significant difference in VC score was found between BEN and non-BEN patients on HD. Multivariate analysis showed that in pre-dialysis patients VC score >4 was associated with lower iPTH and higher serum cholesterol level, but in the HD group with higher serum triglyceride level and longer HD vintage. Conclusions: Lower prevalence of risk factors for VC in the BEN than non-BEN patients was found in pre-dialysis but not in HD group and this was reflected in the prevalence and severity of VC in the groups. Prevalence of VC and mean VC score were significantly lower in pre-dialysis BEN than in non-BEN patients but not for those on HD.

Đorđe Božović1, Nedeljka Ivković1, Maja Račić2, Siniša Ristić3 1University of East Sarajevo, Faculty of Medicine, Department of Oral Rehabilitation, Foča, Republic of Srpska, Bosnia and Herzegovina; 2University of East Sarajevo, Faculty of Medicine, Department for Primary Care and Public Health, Foča, Republic of Srpska, Bosnia and Herzegovina; 3University of East Sarajevo, Faculty of Medicine, Department of Basic Medical Sciences – Physiology, Foča, Republic of Srpska, Bosnia and Herzegovina

Introduction Vascular calcifications (VC) are common in patients with chronic kidney disease and present one of manifestations of mineral and bone disorders in these patients. Objective The aim of this pilot study was to examine the prevalence and risk factors of VC in pre-dialysis patients with Balkan endemic nephropathy (BEN) and other kidney diseases. Methods The study involved 32 pre-dialysis patients, 15 with BEN and 17 with other kidney diseases. All the patients underwent an interview, objective examination, routine laboratory analyses and measurement of serum concentration of intact parathyroid hormone (iPTH), 25-hydroxyvitamin D3 [25(OH)D3] and osteopontin. VCs in iliac, femoral, radial, and digital arteries were evaluated and Adragao VC score was calculated. The samples of radial artery were collected during the first creation of an arteriovenous fistula, and expression of osteocalcin, bone morphogenic protein-2 osteopontin, and matrix Gla-protein in arterial wall were examined. Results Patients with BEN were significantly older (71.1 ± 6.1 vs. 54.7 ± 11.1 years), but they had significantly lower systolic and mean blood pressure (95.7 ± 13.2 mmHg vs. 104.3 ± 7.4 mmHg) and lower serum concentration of phosphorus (1.32 ± 0.36 mmol/l vs. 1.65 ± 0.35 mmol/l) and cholesterol (4.3 ± 1.1 mmol/l vs. 5.2 ± 0.8 mmol/l) than patients with other kidney diseases. Mean VC score was significantly lower in patients with BEN than in those with other kidney diseases (2.8 ± 1.7 vs. 4.6 ± 1.8; p = 0.009), but expression of four examined proteins in arterial wall differed insignificantly between the two groups. VC score correlated significantly with serum concentrations of cholesterol, triglycerides (positively), and iPTH (negatively). Conclusion Pre-dialysis BEN patients had a significantly lower mean score of VC than patients with other kidney diseases.

BACKGROUND Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. AIM To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. PATIENTS AND METHODS Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. RESULTS In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. CONCLUSIONS Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.

Background: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. Aim: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. Patients and methods: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. Results: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. Conclusions: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.