Abstract Buško Blato Reservoir, the third largest hydro accumulation in Europe, is situated in the south-eastern part of the karstic Livanjsko Polje Valley. This aquatic ecosystem is distinguished by a very rich ichthyofauna and the presence of four endemic fish species. Numerous studies focus on ichthyological researches of Buško Blato Reservoir. Its ichthyofauna has been exposed to changes in ecological factors, which in turn reflected on the structure and composition of fish populations. The main objective of this paper was to assess the current state and predict future trends in the ichthyofauna structure and dynamics based on the field data and comprehensive analyses of literature data. The results of the research indicated the presence of 11 fish species from four families, which is the largest number of fish species ever recorded in this ecosystem. Sander lucioperca, Lepomis gibbosus, Pseudorasbora parva and Tinca tinca were recorded for the first time in this ecosystem, while some previously recorded species were not found. The results of the analyses clearly indicate the presence of natural interspecific competition and significant level of threats to the endemic fish species caused by human activities.

In this paper, the Incremental Conductance maximum power point tracking (MPPT) algorithm is evaluated using an experimental setup consisting of two 75W photovoltaic (PV) panels connected in series. Humusoft MF 634 board is used to obtain and produce signals. The model was tested under changing solar irradiance conditions, and the acquired results show that it is able to respond to these changes appropriately.

Introduction: Optical coherence tomography angiography (OCT-A) is a useful diagnostic tool for assessing eyes’ health in patients with chronic diseases, such as diabetes, hypertension, Parkinson’s disease and chronic kidney disease (CKD). Aim: To detect changes in macular structure and retinal vascular meshwork in the macular area and peripapillary in patients with chronic kidney disease (CKD). Methods: This cross-sectional study included 80 eyes of patients with CKD in stages 2, 3 or 4, who were followed-up in the Nephrology Clinic of University Clinical Center Sarajevo. All patients were categorized according to the stage of CKD. All patients were scanned by a high-speed 840-nm-wavelength spectral-domain optical coherence tomography instrument (RTVue XR Avanti; Optovue, Inc, Fremont, California, USA). Blood flow was detected using a split-spectrum amplitude-decorrelation angiography algorithm. A fully automated microstructural analysis of the foveal avascular zone (FAZ), FAZ perimeter, foveal vessel density in a 300-μm area around the FAZ (FD), nonflow area, flow index in superficial and deep vascular plexus, choriocapillary flow, vascular density, radial peripapillary capillary density was performed. Results: When comparing patients with CKD stage 2 and stage 3 there were no statistically significant changes in microvascular parameters on OCT angiography, as well as when comparing patients with CKD stage 3 and stage 4. But in the comparison between patients with less developed CKD (stage 2) and terminal CKD (stage 4) there was a significant difference between some microvascular parameters such as FAZ area, FAZ perimeter, choriocapillary flow. Conclusion: Many studies demonstrated that evaluation of the microvascular changes in different retinal layers using SS-OCTA may be considered as a key to assessing the systemic perfusion status. Evaluation of retinal microvasculature may ease the management and approach of patients with CKD, having in mind that the retinal and the kidney vascular network are, concerning structure, development and the function, very similar.

Women represent an increasing proportion of the overall rheumatology workforce, but are underrepresented in academic rheumatology, especially in leadership roles [1].The EULAR Task Force on Gender Equity in Academic Rheumatology has been convened to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and EMEUNET.To investigate gender equity in academic rheumatology, an anonymous web-based survey was targeted at the membership of EULAR and Emerging EULAR Network (EMEUNET) and their wider networks. The survey was developed based on a narrative literature review [1], best practice from The Association of Women in Rheumatology, a survey of task force members and face-to-face task force discussions. Personal experiences were explored and 24 potential interventions to aid career advancement were ranked. Statistics were descriptive with significance testing for male/female responses compared using chi-squared/t-tests. The level of significance was set at p<0.001.A total of 301 respondents from 24 countries fully completed the survey. By profession, 290 (86.4%) were rheumatologists, 19 (6.3%) health professionals, and 22 (7.3%) non-clinical scientists. By gender, 217 (72.1%) were women, 83 (27.6%) men, and 1 (0.3%) third gender. By age, 203 (67.5%) were 40 or under. By ethnicity, 30 (10.0%) identified themselves as ethnic minority. A high proportion of respondents reported having experienced gender discrimination (47.2% total: 58.1% for women and 18.1% for men) and sexual harassment (26.2%: 31.8% and 10.8% respectively) (Figure 1). Chi-squared tests on the numbers on which these proportions were based showed statistically significant differences between women and men in having experienced gender discrimination (Χ2=36.959 (df=1), p <0.001) and sexual harassment (Χ2=12.633 (df=1), p <0.001). The highest-ranked interventions for career advancement regardless of respondents’ gender included: leadership skills training; speaking/presentation/communication skills training; information on training/career pathways; effective career planning training; support on grant writing applications; and high-impact scientific writing master-classes (Figure 2). Only 8 of 24 proposed interventions showed a significantly higher ranking (p<0.001) by female respondents and these typically related to promotion of female role models and gender-balance in committees, editorial boards and research funding (Figure 2).Figure 1.Perceived gender discrimination and sexual harassment, 301 responsesFigure 2.Mean perceived utility of potential interventions for career advancement by gender and statistically significant gender differences (p<.001), 300 responsesThe results of the survey will inform the development of task force policy proposals for interventions to support career advancement among EULAR and EMEUNET members. The identified interventions have potential to support career advancement of all rheumatologists, health professionals and non-clinical scientists regardless of gender.[1]Andreoli L, Ovseiko PV, Hassan N, Kiltz U, van Mens L, Gossec L, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint, Bone, Spine: Revue du Rhumatisme. 2019;86(6):669-672.We gratefully acknowledge the rheumatologists, health professionals and non-clinical scientists who responded to the survey.Pavel V Ovseiko: None declared, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Laura Andreoli: None declared, Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Leonieke van Mens: None declared, Neelam Hassan: None declared, Marike van der Leeden: None declared, Heidi J Siddle: None declared, Alessia Alunno: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Florence Apparailly: None declared, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Elena Nikiphorou: None declared, Katie Druce Speakers bureau: Pfizer and Lilly, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen, Alexandre Sepriano: None declared, Tadej Avcin: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Anne Maree Keenan: None declared, Laura C Coates: None declared

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world. From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

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.

To meet the demand for new functional foods in line with the trend of sustainable development, a novel probiotic yogurt fortified with 1%, 3%, and 5% apple pomace flour (APF) added immediately after inoculation with Lactobacillus acidophilus, Streptococcus thermophilus, and Bifidobacterium bifidum was developed. Upon fermentation in the presence of APF, a number of probiotic strains remained within the required range, while the syneresis of enriched yogurts was reduced up to 1.8 times in comparison to the control. Supernatants (i.e., extracted whey) obtained from yogurts with 1%, 3%, and 5% APF respectively had 1.4-, 1.8-, and 2.3-fold higher total phenolic content (TPC) than the control, 3.3-, 4.7-, and 8.0-fold higher radical scavenging (DPPH), and 1.3-, 1.6-, and 1.7-fold higher reducing activity (FRAP). Also, probiotic yogurt supernatants (3% and 5%) inhibited colon cancer cells’ viability (HCT 116, 12% and 17%; SW-620, 13% and 19%, respectively). The highest firmness, cohesiveness, and viscosity index values, and the highest scores for color and taste, were obtained for yogurt with 3% APF, indicating that this is the optimal APF amount for the production of novel yogurt with functional properties.

Abstract Acute kidney damage associated with pregnancy occurs in 1/20.000 pregnancies. In developing countries, the main cause of the development of acute kidney damage is septic abortion, and preeclampsia in the developed countries of the world. Preeclampsia is defined as newly developed hypertension, proteinuria and swelling in pregnant women after the 20th week of gestation. It occurs due to disorders in the development of placenta and systemic disorders of the function of the endothelium of the mother. It is treated with methyldopa, magnesium sulfate and timely delivery. Urgent delivery is indicated if the age of gestation is ≥ 34 weeks. HELLP syndrome is a difficult form of preeclampsia. Its main characteristics are decreased platelet count, microangiopathic hemolysis anemia, increased concentration of aminotransferase in the serum and acute kidney damage. Severe HELLP syndrome is treated with emergency delivery, antihypertensives, magnesium sulfate, and in some cases plasmapheresis and hemodialysis. Acute fatty liver in pregnancy occurs because of decreased activity of the LCHAD enzyme of the fetus. Due to the reduced beta oxidation of fatty acids in the hepatocytes of the fetus, long chain fatty acids that cause damage to the mother’s hepatocytes are released. Swansea criteria are used for diagnosis, and the difficult form of the disease is treated with plasmapheresis and extracorporeal liver support. Atypical HUS is due to a reduced protein activity that regulates the activity of the alternative pathway of the complement system. Its main features are thrombocytopenia, microangiopathic hemolytic anemia and acute kidney damage. It is treated with plasmapheresis, and in case of resistance with eculizumab. Thrombotic thrombocytopenic purpura is due to decreased activity of the ADAMTS13 enzyme. It is characterized by thrombocytopenia, microangiopathic hemolytic anemia, high temperature, nervous system disorders and acute kidney damage. It is treated with plasmapheresis, and severe form of disease with corticosteroids and azathioprine. Early detection and timely treatment of acute kidney damage provides a good outcome for the mother and fetus.

Introduction: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease, with more frequent occurrence in the female gender, it primarily affects the lining of the synovial joints, and is associated with lower quality of life, inability to work, progressive disability, and all of these patients are more likely to develop other comorbidities. Aim: To display the role of anti-cyclic citrullinated peptide antibody (anti-CCP) in evaluating RA complications during a one-year follow-up, and compare its values with values of rheumatoid factor (RF). Methods: The study included 40 patients with RA, out of which 6 were excluded during the 1-year follow-up. All patients were treated with anti-rheumatics, methothrexate 15-25mg, occasionally corticosteroids at the same doses. Results: Anti-CCP values were also significantly higher during the second examination and were 5.0 ± 1.9 (range 0.5-7.6) compared to the first examination when they were 4.2 ± 1.3 (range 0.4-6.2) indicating a higher sensitivity of Anti-CCP in detecting of disease progression (t = -2.064; p = 0.043). Anti-CCP values were statistically significant in patients with complications compared to those without during the first examination and at follow-up after one year (t = 5,382; p = 0.0001). Conclusion: The positivity of anti-CCP antibodies is a useful marker in terms of predicting the course and prognosis of the RA. A higher titer of anti-CCP antibodies represents a poorer prognosis for the disease. Determination of the presence of anti-CCP antibodies should be performed as a routine examination in all patients with suspected rheumatoid arthritis.

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.

One of the main problems during in the treatment of anal cancer with chemotherapy and radiation is the occurrence of Hematologic Toxicity (HT). In particular, during radiotherapy it is crucial to spare Bone Marrow (BM), since the radiation dose received by BM in pelvic bones predicts the onset of HT. In this direction, the most popular strategies are based on the identification of the hematopoietically active BM (actBM), that is the part of BM in charge of blood cells generation, using MRI, SPECT or PET, but no approached have been proposed based on CT. In this study we compare four different classifiers in recognizing actBM from CT images using 36 radiomic features. We used Genetic Algorithms (GAs) to simultaneously optimize the feature subsets and the classifier parameters, separately for three pelvic subregions: iliac bone marrow (IBM), lower pelvis bone marrow (LPBM), and lumbosacral bone marrow (LSBM). The obtained classifiers were applied to CT sequences of a cohort of 25 patients affected by carcinoma of the anal canal. Classifiers results were compared with the actBM identified from 18FDG-PET (reference standard, RS). It emerged that the performances of the 4 classifiers are similar and they are satisfactory for IBM and LSBM subregions (Dice > 0.7) whereas they are poor for LPBM (Dice < 0.5).

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.