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1Eurofarm Centar Medical Clinic, Sarajevo, Bosnia and Herzegovina 2Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina 3General Hospital Sarajevo, Sarajevo, Bosnia and Herzegovina KeYWORdS: heart failure, statin therapy, outcome. citAtiON: Cardiol Croat. 2019;14(9-10):222. | https://doi.org/10.15836/ccar2019.222 *AddReSS fOR cORReSpONdeNce: Amina Godinjak, Fra Anđela Zvizdovića 1, 71000 Sarajevo, Bosnia and Herzegovina. / Phone: +38761187010 / Email: aminagodinjak@gmail.com ORcid: Amina Godinjak, https://orcid.org/0000-0002-3697-8006 • Miralem Dešević, https://orcid.org/0000-0001-8760-6192 Amer Iglica, https://orcid.org/0000-0002-4677-8489 • Adis Kukuljac, https://orcid.org/0000-0002-4900-5094

Neil D. Shah, Meritxell Ventura-Cots, J. Abraldes, Mohamed Alboraie, A. Alfadhli, J. Argemí, E. Badia-Aranda, E. Soler et al.

BACKGROUND & AIMS Despite recent advances in treatment of viral hepatitis, liver-related mortality is high, possibly owing to the large burden of advanced alcohol-related liver disease (ALD). We investigated whether patients with ALD are initially seen at later stages of disease development than patients with hepatitis C virus (HCV) infection or other etiologies. METHODS We performed a cross-sectional study of 3453 consecutive patients with either early or advanced liver disease (1699 patients with early and 1754 with advanced liver disease) seen at 17 tertiary care liver or gastrointestinal units worldwide, from August 2015 through March 2017. We collected anthropometric, etiology, and clinical information, as well as and model for end-stage liver disease scores. We used unconditional logistic regression to estimate the odds ratios for evaluation at late stages of the disease progression. RESULTS Of the patients analyzed, 81% had 1 etiology of liver disease and 17% had 2 etiologies of liver disease. Of patients seen at early stages for a single etiology, 31% had HCV infection, 21% had hepatitis B virus infection, and 17% had nonalcoholic fatty liver disease, whereas only 3.8% had ALD. In contrast, 29% of patients seen for advanced disease had ALD. Patients with ALD were more likely to be seen at specialized centers, with advanced-stage disease, compared with patients with HCV-associated liver disease (odds ratio, 14.1; 95% CI, 10.5-18.9; P < .001). Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. These patients had significantly more visits to health care providers, with more advanced disease, compared with patients without excess alcohol use. The mean model for end-stage liver disease score for patients with advanced ALD (score, 16) was higher than for patients with advanced liver disease not associated with excess alcohol use (score, 13) (P < .01). CONCLUSIONS In a cross-sectional analysis of patients with liver disease worldwide, we found that patients with ALD are seen with more advanced-stage disease than patients with HCV-associated liver disease. Of patients with 2 etiologies of liver disease, excess alcohol use was associated with 50% of cases. Early detection and referral programs are needed for patients with ALD worldwide.

PURPOSE To explore the experience of preoperative communication of nurse anesthetists (NAs) in brief meetings with patients in an orthopaedic setting. DESIGN Qualitative research. METHODS Three group interviews based on experiences of 18 NAs were conducted. Content data analysis was used. FINDINGS The brief communication was characterized by both difficulties and opportunities. Protecting the patient's integrity, informing worried patients, lack of routines, language difficulties, being present at the meeting, protecting the patient from disturbance, and encouraging the patient to participate were stated as the main challenges in the brief meeting with patients. The NAs also gave some suggestions for improvement. CONCLUSIONS The Preoperative meetings need to be developed and structured to improve communication. A way to assess the results of this conversation should be developed. Other recommendations include finding a way to improve patient involvement in this dialogue and development of skills of NAs to enhance the meeting for patients.

S. Mehanovic, Raifish E. Mendoza-Villarroel, Robert S Viger, J. Tremblay

Abstract The nuclear receptor chicken ovalbumin upstream promoter–transcription factor type II (COUP-TFII)/NR2F2 is expressed in adult Leydig cells, and conditional deletion of the Coup-tfii/Nr2f2 gene impedes their differentiation. Steroid production is also reduced in COUP-TFII–depleted Leydig cells, supporting an additional role in steroidogenesis for this transcription factor. COUP-TFII action in Leydig cells remains to be fully characterized. In the present work, we report that COUP-TFII is an essential regulator of the gene encoding the anti-Müllerian hormone receptor type 2 (Amhr2), which participates in Leydig cell differentiation and steroidogenesis. We found that Amhr2 mRNA levels are reduced in COUP-TFII–depleted MA-10 Leydig cells. Consistent with this, COUP-TFII directly activates a −1486 bp fragment of the mouse Amhr2 promoter in transient transfection assays. The COUP-TFII responsive region was localized between −67 and −34 bp. Chromatin immunoprecipitation assay confirmed COUP-TFII recruitment to the proximal Amhr2 promoter whereas DNA precipitation assay revealed that COUP-TFII associates with the −67/−34 bp region in vitro. Even though the −67/−34 bp region contains an imperfect nuclear receptor element, COUP-TFII–mediated activation of the Amhr2 promoter requires a GC-rich sequence at −39 bp known to bind the specificity protein (SP)1 transcription factor. COUP-TFII transcriptionally cooperates with SP1 on the Amhr2 promoter. Mutations that altered the GCGGGGCGG sequence at −39 bp abolished COUP-TFII–mediated activation, COUP-TFII/SP1 cooperation, and reduced COUP-TFII binding to the proximal Amhr2 promoter. Our data provide a better understanding of the mechanism of COUP-TFII action in Leydig cells through the identification and regulation of the Amhr2 promoter as a novel target.

J. Sehic, F. Gaši, D. Benediková, M. Blouin, P. Drogoudi, D. Giovannini, M. Höfer, G. Lācis et al.

A DNA marker-based study in European plum was performed within the project “Identification of a representative set of Prunus domestica accessions of European origin, well documented and characterized, to be included into the AEGIS system (PRUNDOC)”. A total of 46 local plum accessions from 10 European countries (Belgium, France, Germany, Greece, Italy, Latvia, Norway, Serbia, Slovakia and Sweden) were analysed using SSR loci. In addition, seven reference cultivars (Bistrica, Hanita, Mirabelle de Nancy, Reine Claude Violette, Stanley, Valor and Victoria) were analysed for standardization of allele sizes. The following nine primers were used; PacA33 is an EST-SSR developed in apricot, BPPCT039, BPPCT007, BPPCT014, BPPCT034, BPPCT040, UDP96 and UDP98 were developed from genomic peach DNA while CPSCT026 was developed from genomic DNA of Japanese plum Prunus salicina. None of the 46 investigated local plum accessions were identical, nor were any of them identical to any of the 7 reference cultivars. Genetic similarity among accessions was examined using Jaccard's similarity coefficients. The obtained dendrogram showed that the plum accessions did not group in a pattern corresponding to their country of origin.

Z. Calic, V. Rakočević-Stojanović, S. Perić, M. Vujnić, B. Bjelica, I. Božović, M. Welgampola

Elizabeth C. Corfield, D. Smajlagić, Siobhan Connoly, A. Havdahl, M. Tesli, H. Hakonarson, I. Waldman, J. Elia et al.

M. Petrovic, A. Djordjevic-Dikic, J. Stepanović, Giga, N. Bošković, Vukcevic, Cvetic, A. Mladenovič et al.

Coronary collateral circulation exerts protective effects on myocardial ischemia due to coronary artery disease (CAD) and can be promoted by exercise (E) with heparin (H) co-administration. Whether this arteriogenetic effects is accompanied by functional improvement of left ventricle (LV) during stress remains unknown. To establish the stress-induced functional effects on LV regional and global function of 2-week cycle of H+E in patients with “no-option” CAD. In a prospective, single-center, double-blind, randomized, parallel-group study we recruited 32 “no-option” patients (27 males; mean age of 61±8 years), with stable angina and CTO, refractory to OMT, not suitable for revascularization and with E-induced ischemia. All underwent 2-week cycle of E (2 E test per day, 5 days a week) and were pre-treated with i.v. 0.9% saline or unfractionated H (100 IU/kg up to maximum of 5.000IU, 10 min prior to E). Canadian Class Score (CCS) and 12-lead E-ECG for time-to-1 mm ST-segment depression were assessed at entry and after treatment. LV function was evaluated during treadmill exercise with conventional and advanced imaging indices: Wall Motion Score Index (WMSI); Ejection Fraction (EF); Force (systolic blood pressure/end-systolic volume); Global Longitudinal Strain (GLS). Post-treatment exercise-time and CCS improved in both groups. In H+E patients exercise-time improved from 369.8±107.8 sec to 475.3±114.6 sec (p=0.001) while in E patients improved from 384±152.7 sec to 464.8±134.1 sec (p=0.019). CCS score changed in H+E from 2.6±0.7 to 1.9±0.7 (p=0.000), and in E group from 2.4±0.7 to 2.1±0.9 (p=0.046). At peak exercise, H+E was different from E group for EF and GLS (see Table). Effects of H+E on SE parameters H+E p P+E p *H+E vs P+E STRESS Time 0 vs Time 1 Time 0 vs Time 1 Time 0 Time 1 WMSI 1.377 vs 1.279 0.005 1.404 vs 1.376 0.290 0.626 0.255 EF (%) 60.9 vs 64.8 0.016 61.2 vs 57.8 0.284 0.943 0.016 Force (mmHg/mL) 6.36 vs 6.5 0.158 5.82 vs 4.68 0.209 0.760 0.098 GLS (%) −16.96 vs −18.50 0.001 −15.79 vs −15.60 0.380 0.325 0.027 SE = stress echocardiography; H+E = heparin+exercise; P+E = placebo+exercise; Time 0 = before randomization; Time 1 = after 2-week therapy cycle. *p values. A 2-week, H+E cycle is associated with improvement in regional and global LV function during exercise, concordantly shown by conventional (WMSI, EF) and advanced (GLS) echocardiographic indices of LV function. This integrates and supplements the classical objective index based on ST-segment depression, unable to localize and quantify the functional consequences of therapy on myocardial ischemia.

I. Burazor, P. Seferovic, M. Ostojić, B. Ivanovic, M. Andjić, P. Otasevic, D. Constantinos, Y. Adler

Heart failure is a major cause of morbidity, mortality and re-hospitalizations and is highly prevalent in myocardial infarction survivors. Cardiac rehabilitation based on exercise training and heart failure self-care counseling have each been shown to improve clinical status and clinical outcomes. We designed our study with aim to evaluate the usefulness of exercise based in house cardiac rehabilitation/ secondary prevention program in patients with heart failure with mid-range ejection fraction (HFmrEF) after myocardial infarction. Out of 2753 patients who were admitted to our three weeks in- hospital secondary prevention program – exercised based cardiac rehabilitation, we analyze a total of 219 patients who were admitted early after coronary revascularization (percutaneus coronary interventions or coronary bypass surgery) with HFmrEF. The majority of patients were males (68%). Risk factors and co morbidities were noted. Patients were selected for exercise training after six minute walking test or exercise stress test (cardiopulmonary dominantly to evaluate unexpected exertional dyspnea). After 3 weeks in house cardiac rehabilitation the patients were re-tested. The major comorbidities in our patient population were as follows: hypertension, diabetes and dyslipidemia. Six minutes walking test was performed and the total distance walked ranged from 120 to 480 meters and the beginning of the program. Patient had 7 -days a week training program. After the 3 weeks in hospital exercise rehabilitation the improvement in the test was ∼32%. Cardiopulmonary test showed also improvement of functional capacity.We noted several rhythm disturbance complications by telemetry (VES, SVES). None had acutisation of heart failure (with peripheral edema and congestion). All patients fulfilled cardiac rehabilitation program. Supervised multidisciplinary cardiac rehabilitation program, including an individualized exercise component is effective and can improve functional status and exercise tolerance in patient with HFmrEF after myocardial infarction.

S. Obradovic, B. Džudović, Igor Sekulić, B. Subotic, J. Matijašević, U. Batranović, S. Šalinger, M. Nikolić et al.

Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. None

Marija Galić, Darija Bilandžija, Aleksandra Perčin, I. Šestak, M. Mesić, M. Blažinkov, Ž. Zgorelec

The agricultural sector is a source of greenhouse gas emissions that directly affect the global problem of climate change and contribute approximately 11% in total greenhouse gas emissions in the world and in Croatia too. Irregular and irresponsible agricultural practices, such as excessive tillage and improper fertilization often lead to soil carbon loss and increased carbon dioxide emissions to the atmosphere. This field study provides results how agricultural practices affect carbon dioxide emissions from soil, carbon sequestration and soil quality during the cultivation of winter wheat. The field experiment was conducted in a temperate continental climate on distric Stagnosol. Four investigated treatments were: organic fertilization, mineral fertilization, control treatment and black fallow. The lowest carbon dioxide emission was recorded on bare soil and the highest on organic fertilization treatment. The application of manure, mineral fertilizers and calcification rendered significant effect on some soil chemical characteristics and daily carbon dioxide flux.

In recent times, the global financial system has embraced more people from more regions of the world, but we are yet to fully understand who remains excluded and why. Globally, 2 billion adults are still unbanked (World Bank, 2015). Of those, many are poor women. Even when they gain financial access, women tend to refrain from actively using their bank accounts. India represents a potent example of this global challenge. Our study offers a quantitative analysis of the Financial Insights Inclusion and Findex datasets and finds that even when they are given the opportunity and potential benefits of financial access - many of India’s poor women opt out of actively engaging with the formal banking institutions. In examining reasons behind their account dormancy, we find that education is a significant determinant shaping decisions of India’s poor women.

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