Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide with the incidence of about 1,8 million newly diagnosed cases in 2018. According to the World Cancer Report 2014, in Bosnia and Herzegovina 6700 people died of cancer in 2014, and CRC was the cause of mortality in 724 patients (10%). Prevention programs including screening, state-of-the-art diagnostic modalities and therapeutic approaches to CRC are being constantly improved. Aim: Our study was designed to address the diagnostic accuracy of 18F-FDG PET/CT in the follow-up of CRC in patients with normal or elevated CEA. Methods: We retrospectively analyzed 50 patients previously diagnosed with CRC who were initially surgically treated. All patients were suspicious of recurrence and were referred to as 18F-FDG PET/CT for restaging between February 2014 and February 2019. Possible recurrence was indicated by rising CEA, equivocal radiological findings or clinical findings. Results: Out of a total of 50 patients for whom the follow-up of at least six months was available, 27 had CRC confirmed with the gold standard, and all 27 patients had 18F-FDG PET/CT positive for recurrence, giving a sensitivity of 18F-FDG PET/CT in detecting the recurrence of CRC of 100.0% (0.0% of false-negative – FN results). Out of 23 patients with no signs of CRC recurrence on the gold standard, 19 were also 18F-FDG PET/CT negative, giving a specificity of 18F-FDG PET/CT in detecting the recurrence of CRC of 82.6%, and 17.4% of false-positive – FP results. Out of 31 patients who were 18F-FDG PET/CT positive, 27 had it confirmed pathophysiologically or clinically, giving positive predictive value (PPV) of 18F-FDG PET/CT in detecting CRC recurrence of 87.1%; negative predictive value (NPV) was 100.0%, meaning all 19 patients showing no signs of CRC recurrence when imaged with 18F-FDG PET/CT were gold standard negative as well. Conclusion: 18F-FDG PET/CT proves to be a valid diagnostic tool in detecting recurrence in patients with CRC.

Cocoa shell is a by-product of the chocolate industry that is rich in dietary fiber and bioactive components. In this research, the influence of high voltage electric discharge (HVED) treatment on chemical and physical characteristics of the cocoa shell, i.e., the effects of applied time and frequencies on grinding ability, water binding capacity (WBC), dietary fibers and tannin content was investigated. HVED had a significant influence on the chemical and physical properties of cocoa shell, all of which could be linked to changes in fiber properties. Along with the fiber content, grinding ability and water binding capacity were increased. These properties have already been linked to fiber content and soluble/insoluble fiber ratio. However, this research implies that change in fiber properties could be linked to tannin formation via complexation of other polyphenolic components. Additional research is needed to verify this effect and to establish mechanisms of tannin formation induced by HVED and its influence on fiber quantification.

Introduction: Health education is a process of acquiring knowledge and skills in order to improve the health of the individual and the community. It is considered the most effective, most economical and most rational aspect of health care and health culture. Aim To provide data on the effectiveness of printed health-educational materials. Methods This is a quantitative, applied, descriptive-analytical study. According to the type of research, it presents a public health evaluation manipulative study with triple testing. The research was conducted in elementary schools in the Zenica-Doboj Canton. The total number of students participating in the research is divided into groups: examined, control group. The research consisted of four phases. The research tool is a modified questionnaire The Health Behavior in School-aged Children (HBSC) with 38 questions, 8 modules. Results The total number of respondents was 120. The method of distribution of health-educational posters shows a lower but still present statistical significance (p<0.05) in relation to the acquired knowledge and a change in attitudes between the conducted surveys at different time points. There is no statistically significant change (p>0.05) in the level of knowledge and attitudes using leaflets between conducted surveys at three different times. In the control group without education, there was a low statistical significance (p<0.05) in terms of changing the level of knowledge and attitudes. Conclusion The distribution of health-educational posters is recommended in situations where it is necessary to reach a wide audience for a long period of time, if the site of the poster is protected. According to this study, there is no evidence that the leaflet distribution method should be used when it comes to the promotion of healthy lifestyles among healthy children. Alternative methods and ways of health education need to be identified.

Non‐invasive axon diameter distribution (ADD) mapping using diffusion MRI is an ill‐posed problem. Current ADD mapping methods require knowledge of axon orientation before performing the acquisition. Instead, ActiveAx uses a 3D sampling scheme to estimate the orientation from the signal, providing orientationally invariant estimates. The mean diameter is estimated instead of the distribution for the solution to be tractable. Here, we propose an extension (ActiveAxADD) that provides non‐parametric and orientationally invariant estimates of the whole distribution.

Introduction: Psoriasis is a common chronic skin disorder characterized by inflammation and abnormal epidermal proliferation. Its severity ranges from a chronic plaque psoriasis (CPP) to generalized psoriatic erythroderma (PE). The cause of psoriasis is unknown although most evidence supports the hypothesis that psoriasis is an immunologically mediated disease. The T-helper (Th) 1 and Th17 cells are responsible for the inflammation of psoriasis. Immunoglobulin E (IgE) is a class of immunoglobulin essential for the allergic response. There is some evidence that IgE may take a part in the pathogenesis of psoriasis. Aim: The aim of the study was to compare serum levels of total IgE between patients with psoriasis and healthy subjects, and to assess the difference between localized form (CPP) and extensive form of disease (PE). Methods: Seventy-five patients with psoriasis and 30 healthy subjects were enrolled in this study. Data on age, gender, personal and family history, clinical type and duration of disease were collected and analyzed. Serum levels of IgE were measured using nephelometric method. Results: Serum levels of total IgE were significantly higher in patients than in controls (46.7% vs.. 10%; p<0.05). Statistical difference of IgE concentration was also observed between CPP and PE. Comparison between patients and controls with regard to the median of the serum level of total IgE levels showed a statistically highly significant elevation in patients (425 IU/ml) compared with controls (54.5 IU/ml) (p<0,05). A higher total IgE concentration was observed in the group of patients with a longer period of skin changes. No relation was found between the serum level of IgE and family history of psoriasis, age or sex (p>0.05). Conclusions: This study supports the evidence that elevation of total serum IgE is associated with psoriasis. The exact role of serum IgE in psoriasis should be additionally investigated in future studies.

Objectives The development of third molars can be helpful in dental age estimation of adolescents and in early adult period. We tested the repeatability and accuracy of the three dental age radiographic methods (Olze, Demirjian and Solari and Abramovitch) and evaluated which method is more useful. We also aimed at testing to find the correlation of estimated dental and chronological age by these three methods. Material and methods The orthopantomographs (OPGs) of 1007 individuals (8 - 25 years) were divided into two groups (cca 500 OPGs) - one group of OPGs has been presented with all four third molars, while another one was registered with third molar/s hypodontia. And all of OPGs were assessed, to verify the three methods (Olze, Demirjian and Solari and Abramovitch) for age estimation based on third molar development. Results There was a high Spearman's correlation coefficient between stages of development of wisdom tooth and chronological age of subjects by all these three methods. Conclusion We may recommend using third molars for assessing the dental age by Olze, Demirjian and Solari and Abramovitch dental method as well, on Bosnian and Herzegovinian population.

Introduction: Peritoneal dialysis (PD) is an established treatment for patients with end-srage kidney disease. The method was developed as an alternative to hemodialysis (HD) presenting a patient survival rate equivalent to HD and better preservation of residual renal function. Peritoneal dialysis (PD) patients have different peritoneal membrane permeability (transport) characteristics. High peritoneal membrane permeability is associated with increased mortality risk in the patient population. Aim: The aim of this study was to analyze the importance of the peritoneal membrane transport status in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Methods: The study included 60 adult continuous ambulatory peritoneal dialysis (CAPD) patients, 29 male and 31 female, mean age 56.63±15.06 years. All patients treated with conventional glucose- based PD fluids. For the short term (within 3 month after start of PD) and long term (more than 12 months) peritoneal dialysis analysis of peritoneal transport characteristics has been used peritoneal functional test (PFT). With the test, categorisation of patients was possible into high (H), high-average (HA), low average (LA), and low (L) transporters. Results: Dialysate–to plasma ratio (D/P) of creatinine showed significantly increased over time (0.654±0.141 vs... 0.705±0.13, p<0.001). In multivariate analysis age, gender, time on dialysis, comorbid diseases, diabetes mellitus (DM), serum albumin, were considered as independent factors influencing the PFT. The high transporter group had higher D/Pcreat (H 0.84±0.03 vs... LA 0.57±0.05, p<0.001), higher proportion of man (H 100% vs... LA 39.5%, p<0.05), higher proportion of patients with comorbid diseases (H 60% vs... LA 20.9%, p<0.05), lower serum albumin concentration (H 29±6.0 vs... LA 37±5.2, p<0.001), lower D4/D0 glucose ( H 0.23±0.07 vs... LA 0.42±0.14, p<0.001), and lower drained volume (H 600±173 vs... LA 1016±355, p<0.001). Conclusion: The PFT was en easy, inexpensive, reliable test to assess peritoneal transport type and it also provided information about peritoneal clearance of solutes and ultrafiltration. Peritoneal transport type classification was recognized not only as aid for prescription, but also as a prognostic index.

Introduction: Idiopathic Idiopathic membranous nephropathy (iMN) is an immune-complex mediated renal disease which is usually associated with the nephrotic syndrome (NS). The course of the disease is variable. Some patients maintain normal kidney function with or without a spontaneous remission of proteinuria, while others progress to end-stage renal failure or die from complications related to the nephrotic syndrome. Whether or not to treat a patient with idiopathic membranous nephropathy is still controversial. The controversy is mainly related to the toxicity of the therapy and the variable natural course of the disease-spontaneous remission occurs in 40–50% of patients. Aim: The aim of this study was to describe our experience of treatment of an idiopathic membranous nephropathy (iMN), efficacy and complications rate. Case report: Our patient was older, mail gender, in high-risk group with persistent proteinuria 10,68 g/day and stable renal function. We have taken these factors into consideration, along with age and other comorbidities, that may significantly elevate the risk of treatment. We chose to start with early treatment, following the Ponticelli’s group protocol based on high dose corticosteroids (odd months) alternating with clorambucil (even months) for six months. This treatment was accompanied by the steroid side effects, including hyperglycaemia dependance on insulin therapy and pulmonary thromboembolism despite administered prophylactically low molecular weight heparin. The six-month treatment was successfully completed with the reduction of proteinuria to nephritic values 2,86 g/day, despite many complications. Complete remission of the disease with non-significant proteinuria and with stable renal function was achieved in 14 months which has been maintained for 2 years. Conclusion: We suggest that decisions on the timing of start of therapy, whom to treat, best sequence of the use of the various immunosuppressive drugs must be based on an individualized assessment of risks and benefits.

SUMMARY The role of T regulatory lymphocytes (Treg) particularly in cancer is well known. The goal of the present study was to determine the contribution of these lymphocytes in the regulation of anti-tumor immunity of CBA/HZgr mice against MC-2 fibrosarcoma (4th generation of methylcholanthrene induced tumor). The levels of T lymphocytes (CD4+, CD8+ and CD4+CD25+) were determined 8 and 20 days after tumor transplantation. Further, the role of CD4+CD25+ (Tregs) in tumor-host interaction was evaluated in vitro and in vivo by using specific monoclonal antibodies. We found that splenocytes of both control and Treg depleted tumor bearing mice strongly but differently inhibited growth of tumor cells in vitro. While splenocytes of untreated mice exhibited significant decrease of this activity (from 74.4% to 62.6% and 32.95%), the splenocytes of Treg depleted mice showed increase of this activity (from 79.5% to 84.3% and 86.2%) from day 6 to day 13 and day 21 after tumor grafting, respectively. Further, upon i.v. injecting specific monoclonal anti-Treg antibody tumor immediately prior to tumor cell intracutaneous transplantation, the tumor was rejected after initial growth. In treated mice, the incidence of Treg cells was very low initially, reaching normal values two weeks later. These animals were shown to be resistant to tumor transplantation four months later.

Introduction: It is an undeniable fact that antidepressants can cause side effects. Antidepressants generally have a similar effect but they differ in their application safety, as well as their side effects. Aim: To determine differences in the frequency and intensity of antidepressant induced side effects in patients treated in primary care. Methods: The research was designed as a prospective, cross-sectional study, conducted on a voluntary and anonymous basis, and it included depression patients treated with antidepressant medications during 2013-2015 in Zenica-Doboj Canton using the Hamilton Depression Rating Scale and Toronto Side Effects Scale. Results: The total sample included 508 subjects. As a significant problem, abdominal pain was felt by 14% of subjects, indigestion by 19% of subjects, nausea by 15% of subjects, diarrhea by 9% of subjects, and constipation by 11% of subjects. 29% of subjects suffered from sweating, 20% suffered from a sudden heat stroke, 10% suffered from swelling, and 23% of them reported suffering from dry mouth as a significant problem. The prevalence of side effects in relation to how do they affect life and daily activities of subjects is statistically significant (P <0.000). Statistically significant side effects of SSRI antidepressants correlate with the duration of our subject’s treatment: perception of increased sleep (0.039) as well as decreased sleep (P = 0.009), sweating (P <0.001), sudden heat stroke (P <0.001), being without orgasm (P = 0.004), decreased libido (P <0.001), weight loss (P = 0.045). Conclusion: It is necessary to educate the patients about the nature and features of the depressive disorder, and to notify the patients of the expected course of recovery, as well as the need to adhere to the recommended therapy and the possible side effects of the medication.

Introduction: To show the importance of optical coherence tomography (OCT) angiography imaging of superficial and deep capillary network in patients with non-proliferative diabetic retinopathy (NPDR), and to show the correlation between blood glucose level and changes in the foveal microvasculature. Methods: A cross-sectional study was performed on eyes with NPDR and healthy subjects using a highspeed 840-nm-wavelength spectral-domain optical coherence tomography instrument (RTVue XR Avanti; Optovue, Inc, Fremont, California, USA). Blood flow was detected using the split-spectrum amplitude-decorrelation angiography algorithm. A fully automated microstructural analysis of the foveal avascular zone (FAZ) and avascular surfaces was performed. Quantitative values from diabetic patients were compared with those of healthy subjects. Data about blood status in diabetic patients and healthy subjects were taken from patients’ medical history. Results: Size of both, FAZ and vascular dropout are significantly different between healthy patients and patients with NPDR. OCT angiography detected enlargement and distortion of the foveal avascular zone, retinal capillary dropout, and a higher number of vascular loops and microaneurysms. Sizes of FAZ and vascular dropout increase with the duration of disease. Central macular thickness (CMT) is not significantly different between healthy patients and patients with NPDR. A study has proven a positive correlation between the size of FAZ and the size of vascular dropout in superficial vascular plexus in patients that have DM over 10 years. Conclusion: A qualitative and quantitative OCT angiography approach to retinal vascular status can offer objective data on monitoring patients with non-proliferative diabetic retinopathy as well as indicate the progression of the disease.

Kefir is a well-known health-promoting beverage that can be produced by using kefir grains (traditional method) or by using natural starter cultures from kefir (backslopping method). The aim of this study was to elucidate the microbial dynamics and volatilome profile occurring during kefir production through traditional and backslopping methods by using five kefir grains that were collected in Bosnia and Herzegovina. The results from conventional pour plating techniques and amplicon-based sequencing were combined. The kefir drinks have also been characterized in terms of their physico-chemical and colorimetric parameters. A bacterial shift from Lactobacillus kefiranofaciens to Acetobacter syzygii, Lactococcus lactis and Leuconostoc pseudomesenteroides from kefir grains in traditional kefir to backslopped kefir was generally observed. Despite some differences within samples, the dominant mycobiota of backslopped kefir samples remained quite similar to that of the kefir grain samples. However, unlike the lactic acid and acetic acid bacteria, the yeast counts decreased progressively from the grains to the backslopped kefir. The backslopped kefir samples showed higher protein, lactose and ash content and lower ethanol content compared to traditional kefir samples, coupled with optimal pH values that contribute to a pleasant sensory profile. Concerning the volatilome, backslopped kefir samples were correlated with cheesy, buttery, floral and fermented odors, whereas the traditional kefir samples were correlated with alcoholic, fruity, fatty and acid odors. Overall, the data obtained in the present study provided evidence that different kefir production methods (traditional vs backslopping) affect the quality characteristics of the final product. Hence, the functional traits of backslopped kefir should be further investigated in order to verify the suitability of a potential scale-up methodology for backslopping.

The occurance of mid- and longterm uremic complications is related to the low clearance rate of middle and large molecule uremic toxins when hemodialysis (HD) alone is adopted. As the uremic toxins and their corresponding biological effects become increasingly clear, blood purification treatment that aims to remove these toxins, has developed from a stage of life-sustaining to improving the quality of life. The objective of this study was to evaluated demographic, clinical and laboratory data in patients who underwent the combination of maintenance hemodialysis with hemoperfusion (HP) and in those who recieved HD alone and to investigate whether this combination could improve the clearance rate of middle and large molecule uremic toxins. A total of 26 patients, who underwent routine hemodialysis, were assessed in this study. Those patients were randomly divided into three groups: Group 1 (7 patients) received combined treatment of HD with HP biweekly (HD 2 times a week with HD+HP once a week), whereas Group 2 (10 patients) was given HD with high flux dialyzer and Group 3 (9 patients) was given HD with low flux dialyzer 3 times a week. This study was followed for 4 months. Before and after the observational period demographic and clinical data were taken from the medical history and blood samples were taken for hemoglobin (Hb), iron (Fe), total iron binding capacity (TIBC), albumin (Alb), calcium (Ca), phosphorus (P04) and parathyroid hormone (PTH). This study included 13 female and 13 male patients with a mean age of 41, 62 + 11.12 and a mean dialysis duration of 62, 78+53, 33 months. When it comes to baseline characteristics, patients of the group 3 were significantly older than patients in other groups (p=0.001). At the end of the four months observation period, the same difference according to age was noticed (p=0.01). Also, HD+HP group had significantly higher values of TIBC (p=0.006) and significantly lower serum levels of P04 (p=0.001). EPO doses were very similar in group 1 and 2, but in group 3 there were noticeably lower than in those two groups but without a significant difference. The serum levels of albumin were higher in group 3 compared to the other two groups but also without statistical difference. No statistical difference between groups after the follow up period was observed in terms of Hb, Fe, PTH, Ca, BMI, duration of dialysis treatment and vascular access. When groups are viewed individually, in the HD+HP group serum P04 levels were significantly lower after the 4 months off the follow up period than it was at the beginning (p=0.031) and also TIBC was significantly higher (p=0.018). In group 2 the values of TIBC were significantly lower after the follow up period than it was at the beginning (p=0.025). No significant difference was noticed in group 3 but serum PTH levels tends to decrease after 4 months compared to baseline measurement. This combination treatment of HD with HP was superior to HD in reducing levels of phosphorus. These findings suggests a potential role of reducing the risk of cardiovascular events in this population especially when it is known that hyperphosphatemia has been pointed out as the primary culprit in the process of cardiovascular calcification. Also, patients who underwent the combined treatment showed higher values of TIBC but unfortunately no difference was noticed between Hb levels and EPO doses. These results eventually demonstrates their role in the improvement of renal disease anemia, which opens up the possibility of further research on a larger sample and over a longer period of time.

Introduction: Calciphylaxis is a rare, but serious, kidney complication. Calciphylaxia is a vasculopathy of small blood vessels characterized by the deposition of calcium deposits in intimal arterioles with the consequent proliferation of intima, fibrosis and thrombosis. Aim: The aim was to show the significance of recognition of calciphylaxis relies on heightened clinical awareness of the presence of atypical skin nodules or ulcers that occur in patients with hemodialysis dependence and to characterize features of calciphylaxis or components of treatment that may lead to improved outcome. Case report: We present the case of 84-year-old woman with chronic kidney disease and diabetes mellitus as well as severely painful, firm, indurated plaques on the lower extremities. The plaques progressed to involve larger areas with associated local ulceration and necrosis. Laboratory testing revealed hyperparathyroidism and incisional skin biopsy confirmed calciphylaxis. Wound microbiology confirmed Staphylococcus aureus. Conclusion: The diagnosis can be based on clinical grounds, supported by histological analysis if possible. The laboratory workout must cover all the possible implications of chronic kidney disease with special attention to Ca+ and P+ values and evidence of skin or systemic infection. Calciphylaxis must be known by dermatologist as early diagnosis and proper management can be decisive for better prognosis.

Predicting response to neo-adjuvant chemotherapy of liver metastases (mts) using CT images is of key importance to provide personalized treatments. However, manual segmentation of mts should be avoid to develop methods that could be integrated into the clinical practice. The aim of this study is to evaluate if and how much automatic segmentation can affect a radiomics-based method to predict response to neoadjuvant chemotherapy of individual liver mts. To this scope, we developed an automatic deep learning method to segment liver mts, based on the U-net architecture, and we compared the classification results of a classifier fed with manual and automatic masks. In the validation set composed of 39 liver mts, the automatic deeplearning algorithm was able to detect 82% of mts, with a median precision of 67%. Using manual and automatic masks, we obtained the same classification in 19/32 mts. In case of mts with largest diameter > 20 mm, the precision of the segmentation does not impact the classification results and we obtained the same classification with both masks. Conversely, with smaller mts, we showed that a Dice coefficient of at least 0.5 should be obtained to extract the same information from the two segmentations. This are very important results in the perspective of using radiomics-based approach to predict response to therapy into clinical practice. Indeed, either precisely manually segment all lesions or refine them after automatic segmentation is a time-consuming task that cannot be performed on a daily basis.