Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27–74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10–40 μg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967–1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001–0.534; p = 0.019; OR: 1.147; 95% CI: 1.042–1.263; p = 0.005; respectively). Conclusions: Noninvasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB.

EDITORS, We read with interest the study by Khan et al regarding the incidence and impact of IBD medications on risk of pneumonia and pneumoniarelated hospitalisation.1 We compliment the authors for their effort to address the paucity of data on infections such as pneumonia in the IBD population. Using the nationwide Veterans Affairs database, they found incidence rates of 6.47 and 2.52 per 1000 personyears (PY) for pneumonia and pneumoniarelated hospitalisations, respectively. The strict definition for pneumonia events in their study has ensured the inclusion of clinically relevant cases ( i.e., more severe cases) of pneumonia, but may have led to underreporting of milder infectious events. The choice to include a positive chest Xray in their definition might also have led to variable sensitivity rates.2 Although mildtomoderate lower respiratory tract infections (LRTIs) are generally associated with low morbidity and mortality rates, they can have negative effects on patients' quality of life and perceived health, lead to increased healthcare costs and decreased societal participation. Reporting differences in all infections is important when addressing the real burden of treatment options in IBD. To add further insight on the prevalence of these infections, we share our realworld multicentre experience with the IBD population in South Limburg based on data collected using myIBDcoach, an established telemedicine platform for IBD management, which contains several patientreported outcome measures and remote monitoring tools, including periodic assessment of infectious events.3 In 600 IBD patients (mean age at cohort entry 49.7 [SD 14.9]; n = 342 Crohn’s disease [59.9% female]; n = 258 ulcerative colitis [47.7% female]), included between 1 January 2020 and 1 January 2021, we observed 43 LRTIs during followup (including pneumonia, excluding COVID19). Of these, 16 were mild (i.e., either requiring no treatment or analgesics), 25 moderate (i.e., requiring oral antibiotics) and two severe ( i.e., hospitalisation or intravenous antibiotics), corresponding to incidence rates of 2.5, 4.0 and 0.3 per 100 PY, respectively (Table 1). All events were crosschecked with GP and pharmacy data, and no LRTIrelated deaths were observed. Representativeness of this subset of patients for the realworld situation was established by comparing demographics (age, sex, smoking) and clinical characteristics (Montreal classification) to the total IBD population in SouthLimburg.4 We acknowledge the smaller sample size when compared to the study of Khan et al and understand that their study design did not allow for capturing milder infections. However, the rates observed in our study, especially for moderate infections (requiring antibiotics), are substantially higher than those observed by Khan et al, which cannot only be explained by potential other causes of LRTIs in our cohort. Data on mild and moderate infections in medically treated IBD patients remain scarce and the most plausible explanation is that events treated by general practitioners are not systematically captured in surveillance registries. Our data particularly underscore that, in a realworld population of IBD patients, a substantial proportion of LRTIs follow a mildtomoderate course. Remote monitoring tools designed to periodically assess infectious events could overcome the paucity of data regarding mild and moderate infections.

Social media has opened the gates for collecting big data that can be used to monitor epidemic trends in real time. We evaluate whether Watson NLP service can be used to reliably predict infectious disease such as influenza-like illness (ILI) outbreaks using Twitter data during the period of the main influenza season. Watson’s performance is evaluated by computing Pearson correlation between the number of tweets classified by Watson as ILI and the number of ILI occurrences recovered from traditional epidemic surveillance system of the Centers for Disease Control and Prevention (CDC). Achieved correlation was 0.55. Furthermore, a 12 week discrepancy was found between peak occurrences of ILI predicted by Watson and CDC reported data. Additionally, we developed a scoring method for ILI prediction from Twitter posts using a simple formula with the ability to predict ILI two weeks ahead of CDC reported ILI data. The method uses Watson’s sentiment and emotion scores together with identified ILI features to analyze influenza-related posts in real time. Due to Watson's high computational costs of sentiment and emotion analysis, we tested if machine learning approach can be used to predict influenza using only identified ILI keywords as influenza predictors. All three evaluated methods (Random Forest, Logistic Regression, K-NN), achieved overall accuracy of ~68.2% and 97.5% respectively, when Watson and the developed formula are used as medical experts. The obtained results suggest that data found within social media can be used to supplement the traditional surveillance of influenza outbreaks with the help of intelligent computations.

Wearable technologies have great potential in health monitoring and disease diagnostics. As a consequence, interest in the study of wearable sensors has dramatically increased over recent years. Successful translation of this technology from research prototypes to commercial products requires addressing some of the major challenges faced by wearable sensors such as loss of, and damage in, the biological recognition layer of the skin-interfaced sensors. In this work, we propose a solution to this challenge by integrating micropillar array (MPA) surfaces as part of the sensing layer with the aim to protect and prevent the loss of the enzyme layer from mechanical stress while the sensor is worn. The proposed wearable sensing patch is composed of reference, counter, and working electrodes, all made of MPAs and is designed for measuring glucose in sweat. MPA sensing patch has a wide linear range of 50 μM to 1.4 mM, a sensitivity of 4.7 ± 0.8 μA mM-1, and a limit of detection of 26 ± 5 μM. The glucose sensing patch was tested using human sweat where glucose-level changes were successfully measured before and after meal consumption. The developed patch provides an alternative solution to the problem of the damage to the sensor microenvironment upon wear. But in addition, it also offers a user-friendly, cost-effective, and reliable sweat analysis platform with significant potential in health monitoring applications.

Entrepreneurship and small and medium enterprises are very important from a social and economic point of view. Education, and in particular higher education, creates human resources for future economic and social development. There are numerous EU and national strategic documents underlining that entrepreneurship should be promoted and encouraged in educational institutions and curricula. The primary aim of this research is to determine the entrepreneurial intentions of the student population and the differences in the entrepreneurial intentions of students with regard to the field of study. The research has been conducted at the University of Mostar from April to June 2020. For the research purpose, a questionnaire was used and delivered online to students of several faculties from different areas and fields of science and education, including the first and second educational cycle. The data were analysed in IBM SPSS Statistics 25.0. The results were expressed as number and percentage and mean and standard deviation. The results of the research showed the entrepreneurial intentions of students, their entrepreneurial education and perception of entrepreneurship, their connection, and that there are certain differences with regard to the field of study.

Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015–2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries’ vaccine coverage from 2015 to 2019. EV isolation, identification, and typing were performed by each country according to WHO protocols. Overall, a general AFP underreporting was observed. Non-Polio Enterovirus (NPEV) typing showed a high heterogeneity: over the years, several genotypes of coxsackievirus and echovirus have been identified. The polio vaccine coverage, for the data available, differs among countries. This evaluation allows for the collection, for the first time, of data from the countries of the Balkan area regarding AFP surveillance and polio vaccine coverage. The need, for some countries, to enhance the surveillance systems and to promote the polio vaccine uptake, in order to maintain the polio-free status, is evident.

Leydig cells produce androgens that are essential for male sex differentiation and reproductive function. Leydig cell function is regulated by several hormones and signaling molecules, including growth hormone (GH). Although GH is known to upregulate Star gene expression in Leydig cells, its molecular mechanism of action remains unknown. The STAT5B transcription factor is a downstream effector of GH signaling in other systems. While STAT5B is present in both primary and Leydig cell lines, its function in these cells has yet to be ascertained. Here we report that treatment of MA-10 Leydig cells with GH or overexpression of STAT5B induces Star mRNA levels and increases steroid hormone output. The mouse Star promoter contains a consensus STAT5B element (TTCnnnGAA) at -756 bp to which STAT5B binds in vitro (EMSA and supershift) and in vivo (ChIP) in a GH-induced manner. In functional promoter assays, STAT5B was found to activate a -980 bp mouse Star reporter. Mutating the -756 bp element prevented STAT5B binding but did not abrogate STAT5B-responsiveness. STAT5B was found to functionally cooperate with DNA-bound cJUN. The STAT5B/cJUN cooperation was only observed in Leydig cells and not in Sertoli or fibroblast cells, indicating that additional Leydig cell-enriched transcription factors are required. The STAT5B/cJUN cooperation was lost only when both STAT5B and cJUN elements were mutated. In addition to identifying the Star gene as a novel target for STAT5B in Leydig cells, our data provide important new insights into the mechanism of GH and STAT5B action in the regulation of Leydig cell function.

Introduction: The objective of this study is to assess the long-term effectiveness of a treat-and-extend (T&E) anti-vascular endothelial growth factor regimen in patients with neovascular age-related macular degeneration who remain on T&E and those switched from once-monthly (OM) dosing to T&E (OM-T&E). Methods: In this 12-month extension of the 2-year CANTREAT study, patients received intravitreal ranibizumab 0.5 mg in a T&E regimen. Main outcome measures included mean change in best-corrected visual acuity (BCVA) from baseline and from month 24 to month 36; percentages of patients who gained ≥5, ≥10, or ≥15 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters or lost ≥5, ≥10, or ≥15 letters from baseline and from month 24 to month 36; and number of injections administered from baseline and from month 24 to month 36 for both groups. Results: Of the 139 patients (73 T&E, 66 OM-T&E) in the extension, 121 (68 T&E, 53 OM-T&E) completed 36 months. Mean (standard deviation [SD]) BCVA changes from baseline to the extension last visit (month 33–36) were +6.6 (11.4) letters in the T&E group and +4.8 (14.3) letters in the OM-T&E group, representing maintenance of 24-month gains. The mean (SD) numbers of injections during the extension were 7.3 (2.7) for T&E and 7.1 (2.8) for OM-T&E. Discussion/Conclusion: These findings suggest that after 36 months of treatment, the mean BCVA improvement achieved at 24 months is maintained for both the patients exclusively treated with the T&E regimen and those that switched to T&E after 24 months in the OM regimen.

This paper presents the development and implementation of integrated intelligent CAD (computer aided design) system for design, analysis and prototyping of the compression and torsion springs. The article shows a structure of the developed system named Springs IICAD (integrated intelligent computer aided design). The system bounds synthesis and analysis design phases by means of the utilization of parametric 3D (three-dimensional) modeling, FEM (finite element method) analysis and prototyping. The development of the module for spring calculation and system integration was performed in the C# (C Sharp) programming language. Three-dimensional geometric modeling and structural analysis were performed in the CATIA (computer aided three-dimensional interactive application) software, while prototyping is performed with the Ultimaker 3.0 3D printer with support of Cura software. The developed Springs IICAD system interlinks computation module with the basic parametric models in such a way that spring calculation, shaping, FEM analysis and prototype preparation are performed instantly.

Hoverflies (Syrphidae) are a large Dipteran family, distributed almost worldwide. They play very important ecological roles such as plant pollination, nutrient recycling and predation of plant pests. The members of the genus Epistrophe Walker, 1852 are medium-sized hoverflies of which about 75 species have been described in the World, and 12 of them occur in Europe. During a survey, conducted from 16th June to 4th July 2021 at Blidinje Nature Park (Bosnia and Herzegovina), a new species, of the fauna of Bosnia and Herzegovina, was recorded – Epistrophe diaphana (Zetterstedt, 1843) and new records for species Epistrophe leiophthalma (Schiner & Egger, 1853) were observed. Specimens were collected from inflorescences of Common Hogweed (Heracleum sphondylium L.). Information about the records, species habitats, distribution and status in the country and the region is presented and discussed in this research work.

Though SARS-CoV-2 infections are yet to be completely characterised in a host-pathogen interaction context, some of the mechanisms governing the interaction between the novel betacoronavirus and the human host, have been brought to light in satisfactory detail. Among the emerging evidence, postulates regarding potential benefits of innate immune memory and heterologous immunity have been put under discussion. Innate immune memory entails epigenetic reprogramming of innate immune cells caused by vaccination or infections, whereas heterologous immunity denotes cross-reactivity of T cells with unrelated epitopes and bystander CD8+ activation. Familiarization of the host immune system with a certain pathogen, educates monocytes, macrophages and other innate cells into phenotypes competent for combating unrelated pathogens. Indeed, the resolution at which non-specific innate immune memory occurs, is predominant at the level of enhanced cytokine secretion as a result of epigenetic alterations. One vaccine whose non-specific effects have been documented and harnessed in treating infections, cancer and autoimmunity, is the Bacillus Calmette–Guérin (BCG) vaccine currently used for immunization against pulmonary tuberculosis (TB). The BCG vaccine induces a diverse cytokine secretion profile in immunized subjects, which in turn may stimulate epigenetic changes mediated by immunoreceptor signalling. Herein, we provide a concise summarization of previous findings regarding the effects of the BCG vaccine on innate immune memory and heterologous immunity, supplemented with clinical evidence of the non-specific effects of this vaccine on non-mycobacterial infections, cancer and autoimmunity. This interpretative synthesis aims at providing a plausible immunological and immunogenetic model by which BCG vaccination may, in fact, be beneficial for the current efforts in combating COVID-19.

Aims: Nutrient artery is the principal source of nutrition to the long bones. The topography of nutrient foramina on long bones is well known, but it has not yet been established whether the number of nutritive foramina (NF) is related to total bone length. The objective of the present study was to study the correlation of total number of nutrient foramina and long bone length of upper and lower limb to provide detailed data on such features. Study Design: A cross-sectional, descriptive study Place and Duration of Study: Department of anatomy, Medical Faculty University of Sarajevo. Study duration was 3 months. Methodology: In the present study, 300 adult human long bones of the upper (50 humeri, 50 radii, 50 ulnae) and lower (50 femora, 50 tibiae, 50 fibulae) limbs were investigated to determine the number of their nutrient foramina. The nutrient foramina were identified analysed macroscopically and total number of nutrient foramina for each bone was recorded. Total length of each bone within a group was recorded. Statistical analysis was performed to determine correlation between total bone length and number of nutrient foramina, by using SPSS version 17.0 for Windows. Results: A statistically significant negative correlations between the left humerus length and the number of NF was found. A positive correlations between the length of the right radius and the number of NF, the left ulna length and the number of NF, the right ulna length and the number of NF were found. A negative correlations between the length of the left radius and the number of NF and between right humerus length and number of NF were found. A positive correlation between the length of the right and left femur and the number of NF were found. A negative correlation between the length of left tibia and the number of NF was found, as well as negative correlation between the length of right and left fibula and number of NF. Conclusion: Total bone length is not related to the number of nutrient foramina. The number of nutrient foramina does not depend on the total length of the bone, which is important when assessing the success of grafts for transplantation on long bones in taller people.

Atherosclerosis is the underlying cause of cardiovascular diseases (CVDs) such as myocardial infarction and ischemic stroke. It is a lipid-triggered chronic inflammatory condition of the arterial vascular wall that is driven by various inflammatory pathways including atherogenic cytokines and chemokines. D-dopachrome tautomerase (D-DT), also known as macrophage migration inhibitory factor-2 (MIF-2), belongs to the MIF protein family, which is best known for its pathogenic role in a variety of inflammatory and immune conditions including CVDs. While MIF is well known as a promoter of atherogenic processes, MIF-2 has not been studied in atherosclerosis. Here, we investigated atherosclerosis in hyperlipidemic Mif-2−/−Apoe−/− mice and studied the role of MIF-2 in various atherogenic assays in vitro. We found that global Mif-2 deficiency as well as its pharmacological blockade by 4-CPPC protected against atherosclerotic lesion formation and vascular inflammation in models of early and advanced atherogenesis. On cellular level, MIF-2 promoted monocyte migration in 2D and 3D and monocyte arrest on aortic endothelial monolayers, promoted B-cell chemotaxis in vitro and B-cell homing in vivo, and increased macrophage foam cell formation. Dose curves and direct comparison in a 3D migration set-up suggest that MIF-2 may be a more potent chemokine than MIF for monocytes and B cells. We identify CXCR4 as a novel receptor for MIF-2. The evidence relies on a CXCR4 inhibitor, CXCR4 internalization experiments, MIF-2/CXCR4 binding studies by yeast-CXCR4 transformants, and fluorescence spectroscopic titrations with a soluble CXCR4 surrogate. Of note, Mif-2−/−Apoe−/− mice exhibited decreased plasma cholesterol and triglyceride levels, lower body weights, smaller livers, and profoundly reduced hepatic lipid accumulation compared to Apoe−/− mice. Mechanistic experiments in Huh-7 hepatocytes suggest that MIF-2 regulates the expression and activation of sterol-regulatory element binding protein-1 and −2 (SREBP-1, SREBP-2) to induce lipogenic downstream genes such as FASN and LDLR, while it attenuated the activation of the SREBP inhibiting AMPK pathway. Studies using receptor Inhibitors showed that SREBP activation and hepatic lipoprotein uptake by MIF-2 is mediated by both CXCR4 and CD74. Lastly and in line with a combined role of MIF-2 in vascular inflammation and hepatic lipid accumulation, MIF-2 was found to be profoundly upregulated in unstable human carotid plaques, underscoring a critical role for MIF-2 in advanced stages of atherosclerosis. Together, these data identify MIF-2 as a novel atherogenic chemokine and CXCR4 ligand that not only promotes lesion formation and vascular inflammation but also strongly affects hepatic lipogenesis in an SREBP-mediated manner, possibly linking atherosclerosis and hepatic steatosis.

Deskriptori ZOONOZE – epidemiologija, prijenos; SALMONELOZE – epidemiologija; BRUCELOZA – epidemiologija; LEPTOSPIROZA – epidemiologija; Q GROZNICA – epidemiologija; HEMORAGIJSKA GROZNICA S BUBREŽNIM SINDROMOM – epidemiologija; BOSNA I HERCEGOVINA – epidemiologija SAŽETAK. Cilj istraživanja. Ciljevi istraživanja bili su: ukazati na značaj zoonoza u ljudi te istražiti koje se zoonoze u ljudi najčešće javljaju u Zeničko-dobojskoj županiji (ZDŽ) i Federaciji Bosne i Hercegovine (FBiH), tijekom desetogodišnjeg razdoblja (2010. – 2019. godine). Materijal i metode. U svrhu istraživanja korišteni su podatci o osam najučestalih zoonoza (salmoneloze, bruceloza, leptospiroza, Q-groznica, hemoragijska groznica s renalnim sindromom, borelioza, ehinokokoza, listerioza), temeljem prijava Instituta za zdravlje i sigurnost hrane Zenica i Federalnog zavoda za javno zdravstvo. Dijagnoze su postavljene klinički, mikrobiološki i/ili epidemiološki. Rezultati. Tijekom desetogodišnjeg razdoblja u ZDŽ prijavljena je 871 zoonoza. Najviše (191/871; 21,9%) prijavljenih bilo je 2019. godine. Najučestalija zoonoza bila je salmoneloza (343/871; 39,4%; 95,3/100.000 stanovnika), a zatim slijedi bruceloza (323/871; 37,1%; 87,7/100.000). Najčešća zoonoza u FBiH je salmoneloza (2.764/5.219; 53%; 125,6/100.000). Na drugom mjestu je bruceloza (1.505/5.219; 28,8%; 68,4/100.000). Leptospiroza (386/5.219; 7,4%; 17,5/100.000), Q-groznica (203/5.219; 3,9%; 9,2/100.000) i hemoragijska groznica s renalnim sindromom (164/5.219; 3,1%; 7,5/100.000) javljaju se povremeno, u vidu manjih ili većih epidemija. Ostale zoonoze javljaju se sporadično. Zaključak. Zoonoze su od posebnoga javnozdravstvenog značaja i zahtijevaju blisku interdisciplinarnu suradnju različitih profila stručnjaka (iz područja medicine, veterine, šumarstva, biologije, zoologije, ekologije), poduzimanje učinkovitih mjera u nadzoru i suzbijanju te proučavanju i znanstvenom istraživanju tih bolesti.