High-sensitive cardiac Troponin T (hsTnT) is the most frequently used biomarker for the detection of cardiomyocyte injury. Severe aortic stenosis (AS) leads to an increased left ventricular load, with the potential of myocardial injury reflected by increased TnT levels. However, there is a lack of studies showing the prevalence and prognostic role of elevated hsTnT in patients with asymptomatic AS. To examine the association between the hsTnT levels and AS severity in asymptomatic AS patients. We hypothesized that patients with more severe AS will have elevated hsTnT levels and that hsTnT levels are associated with a higher risk for aortic valve events (AVE) and all-cause mortality (ACM). We performed a post-hoc analysis in 1739 asymptomatic patients with mild to moderate-severe AS, enrolled in the randomized, double-blinded SEAS-study (Simvastatin and Ezetimibe in Aortic Stenosis). All patients had available hsTnT blood samples measured at baseline (Year 0) and Year 1. We defined moderate to severe (mod-severe) AS as a transaortic maximal outflow velocity (Vmax)>3.5 m/s combined with aortic valve area (AVA)<1.0 cm2, otherwise non-severe AS. An hsTnT>14 ng/L was high according to assay (Roche, Elecsys Troponin T hs on cobas e 601). Linear multivariable regression model examined the association of hsTnT levels to clinical and echocardiographic variables. Cox multivariable regression model evaluated competing risks and hazard ratios (HR) of outcomes while adjusting for relevant variables, including a Framingham 10-years risk score of cardiovascular diseases. The competing risks were either ACM or AVE, i.e. the first of AVR, cardiovascular death and heart failure due to AS progression. At baseline, hsTnT was high in 26% (453/1739) patients; 25% (380/1529) in non-severe and 35% (73/210) in mod-severe AS. Relative TnT change over one year was 17% (mean 1.17, SD 1.01); 15% in non-severe vs. 32% in mod-severe AS, and neither associated to AS severity, hsTnT at baseline or lipid-lowering treatment. In multivariable linear regression analysis, there were significant correlations between hsTnT at baseline and age, male gender, creatinine, left ventricular mass index and BMI (all p<0.001, R-square=0.42), but not with AS severity. In multivariable Cox regression analyses, a high hsTnT at baseline was associated with AVE 1.61 [95% CI 1.29–1.99]. In contrast, hsTnT at baseline was not associated to all-cause mortality (see figure). In asymptomatic AS patients without severe AS, high-sensitive Troponin T is not associated with AS severity in cross-sectional analyses, and its levels do not change substantially during one year of follow-up. However, patients with hsTnT >14 ng/l had a sixty percent higher independent risk of subsequent aortic valve events. Multivariable Cox regression Type of funding source: Private company. Main funding source(s): Acknowledgements: Main sponsor (SEAS): MSD Singapore Company, LLC, partnership between Merck & Co. Inc. and Schering-Plough Corporation. Blood analysis sponsor: Roche

Background and Study Aim. Hammer throwing is the most complex athletic throwing discipline with rotational trajectory and strong effect of several different forces that try to disable the projected throwing trajectory. Kinematic parameters are an important segment in the analysis of athletic disciplines, including hammer throw. They are an indicator of influence and often a difference between competitors of different or the same rank of the competition. The aim of the study was to determine the spatial and temporal differences of kinematic parameters between male and female elite hammers. Material and Methods. The study was conducted on sample of 16 Daegu World Championship finalists in 2011, to analyse differences in kinematic parameters between male and female throwers hammer. To obtain the required results, t-test for small independent samples was applied. Results. The data obtained in the study were given as Mean and Standard deviation. Statistically significant differences between male and female finalists were confirmed in the rate of ejection (t=3.684; p<0.004) and the speed of the fourth turn (t=4.396; p<0.002). The male finalists achieved an average ejection velocity of 27.91m/s and the female finalists 27.17m/s, with an average turn speed of 4.67m/s (male) and 4.03m/s (female). Conclusions. The research has shown that significant differences were made between male and female finalists in Daegu in 2011. The causes of differences can be found in length of training, different training process, technical mastery, competitor experience, morphological profile, motor and anatomical structures, movement technique and biomechanical parameters, which were not taken into the research.

Exponentially-growing next-generation sequencing data requires high-performance tools and algorithms. Nevertheless, the implementation of high-performance computational genomics software is inaccessible to many scientists because it requires extensive knowledge of low-level software optimization techniques, forcing scientists to resort to high-level software alternatives that are less efficient. Here, we introduce Seq—a Python-based optimization framework that combines the power and usability of high-level languages like Python with the performance of low-level languages like C or C++. Seq allows for shorter, simpler code, is readily usable by a novice programmer, and obtains significant performance improvements over existing languages and frameworks. We showcase and evaluate Seq by implementing seven standard, widely-used applications from all stages of the genomics analysis pipeline, including genome index construction, finding maximal exact matches, long-read alignment and haplotype phasing, and demonstrate its implementations are up to an order of magnitude faster than existing hand-optimized implementations, with just a fraction of the code. By enabling researchers of all backgrounds to easily implement high-performance analysis tools, Seq further opens the door to the democratization and scalability of computational genomics.

Overweight and obesity are major public health issues worldwide. There is increased risk of obesity‐related morbidity due to accumulation of abdominal fat. Regulation of body weight depends on physical activity and diet. Young adulthood is very critical period due to a tendency to gain weight and adopt poor dietary and exercise habits. This study aimed to investigate the relationships of the anthropometrical parameters with physical activity domains in everyday life and sedentary behavior among students of sixth year of the Faculty of Medicine of Sarajevo University. A cross-sectional study was conducted during May 2020. The survey covered 56 students, aged 24, who responded online to questionnaire. A self-administered questionnaire composed of two blocks of questions. In the first block of the questionnaire, questions were related to sex, and anthropometric measures. The second block referred to the practice of physical activity (vigorous, moderate, and walking), and sitting during seven days. The data collected were processed by the descriptive statistical procedure. Overweight and obesity was found at 11(19.65%). In sample 46.43% performed vigorous intensity activities that meet with WHO criteria, 58.93 performed moderate intensity activities that meet with WHO criteria, and 39.29% performed walking activities that meet with WHO criteria. There were positive, statistically significant difference between indicators of abdominal obesity and the average time spent during 7 days in vigorous physical activity. Health and physical educators can utilize these findings to better understand that physical activity, trying to balance diet and activities.

This research aims at examining how the use of DICT is part of school curriculum and teacher education by analysing and comparing the following documents: “BNCC de lingua portuguesa do Ensino Medio” (BRASIL, 2018) and “DCN para formacao inicial” (BRASIL, 2015). Besides considering the prescribed curriculum for primary and secondary education, teacher training cannot overlook the documents which change the organisation of education cycles, such as “Reforma do Ensino Medio” (BRASIL, 2017). This analysis has shown that BNCC aims at approaching DICT in its pedagogical proposal when suggesting multimodal discursive genres (ROJO, 2017), observing the new forms of sociability (SALOMAO, 2018). We intended to encourage discussions about the importance of considering teacher education through a new perspective, as well as about the need to articulate this to investments in public education, taking into account that BNCC implementation is something that teachers will have to be prepared for.

Objetivo: Descrever o papel do enfermeiro na garantia da saude do idoso no programa Hiperdia. Metodos: Trata-se de uma revisao integrativa, em que foram consultadas junto a Biblioteca Virtual de Saude (BVS) acessando as bases de dados: Literatura Latino-Americana e do Caribe em Ciencias da Saude (LILACS) e Scientific Eletronic Library Online (SciELO). Resultados: No total foram encontrados 13 artigos de atenderam aos criterios de inclusao deste trabalho. Desta forma, entende-se que os enfermeiros que atuam na Estrategia Saude da Familia (ESF) necessitam programar e implementar atividades de investigacao e acompanhamento dos idosos. De acordo com os dados coletados na pesquisa, pode notar que a hipertensao arterial sistemica e o diabetes mellitus e a primeira causa de hospitalizacoes no sistema publico de saude e sao os principais fatores de risco para as doencas cardiovasculares, dos quais cerca de 60 a 80% dos casos podem ser tratados na rede publica basica Consideracoes finais: Percebe-se que o enfermeiro tem exercido um papel muito importante priorizando o desenvolvimento das acoes basicas de saude, no acompanhamento dos idosos hipertensos e diabeticos.

MicroRNAs (miRNAs) represent endogenous small RNAs that post-transcriptionally regulate gene expression and, thus they are involved in the onset and progression of various diseases and conditions (Bader et al., 2010) such as for overweight and obesity. Antiadipogenic miRNA-27a is a negative regulator in fat metabolism, which inhibits adipocyte differentiation through downregulation of adipogenic marker genes (e.g. PPARγ) (Kim et al., 2010). Reduced miRNA-27a levels are often associated with the development of obesity and, therefore, this miRNA might represent a promising candidate for miRNA mimic replacement therapy (Lin et al., 2009). However, the application of naked RNAs has shown low membrane permeability, cellular uptake, and rapid degradation in the circulation. The present study aimed to develop a cationic, lipid-based nanoparticle system for targeting adipose tissue and delivering miRNA-27a. These systems are composed of positively charged nanostructured lipid carriers (cNLCs) and negatively charged miRNAs, which results in complex formation based on electrostatic interactions between these components. Materials and methods

Omeprazole is a proton pump inhibitor commonly used in pediatric patients (Wensel, 2009). Pediatric patients are usually unable to swallow solid dosage forms and they need dose adjustment. Therefore, the dosage form of choice for this population is compounded liquid preparation. Since pharmacies don't usually dispose of pure active substances, compounded liquid preparations are most commonly prepared from commercially available solid dosage forms, in a way that tablets are simply pulverized or capsule contents emptied, adding water or one of the commercially available vehicles (Haywood and Glass, 2013). Considering the risks associated with the preparation and use of compounded preparations, the Chapter <795> of the US Pharmacopoeia states that the beyond-use date is 14 days for non-preserved aqueous oral formulations, if stored in the refrigerator. Preserved aqueous preparations can be stored for 35 days at controlled room temperature or in the refrigerator (USP, 2015).

Approximately 70-90% of the new active pharmaceutical ingredients/drugs are poorly soluble in water/biological fluids. Improvement of solubility, dissolution rate, bioavailability are the main characteristics of drug nanocrystals that are important for oral drug administration. High bioadhesive activity, depending on the type of stabilizer, is considered to be an essential feature of drug nanocrystals for oral, dermal, ocular dosage forms (Chang et al., 2015; Sheokand et al., 2018; Tuomela et al., 2016). Drug nanocrystals are solid nanosized particles of pharmacologically active substances, mainly BCS class IIa and IIb, 200 to 600 nm in diameter, homogeneously coated with 10-50% stabilizer/surfactants and/or polymers, forming ultrafine dispersion (Malamatari et al., 2018). Drug nanocrystals are usually in the crystalline state, but depending on the manufacturing method and process parameters, they may be in the amorphous state (Shete et al., 2014). Drug nanocrystals can be obtained by increasing their particle size by controlled precipitation/agglomeration from solution or by reducing drug particle size by milling to the desirable size. The two basic methods for obtaining drug nanocrystals are bottom up (e.g., precipitation) and top down (e.g., milling) methods, or drug nanocrystals can be made by a combination of these processes. By combining these two methods the desired particle size of drugs can be achieved and disadvantages of the individual methods are overcomed. These methods are intended for the preparation of liquid pharmaceutical nanosuspensions whose internal phase consists of drug nanocrystals particles, which can be converted into solid drug nanocrystals by post-production processes (spray drying, freeze drying or other process) in order to improve chemical, physical stability of drug during storage, when the selected stabilizer of drug nanocrystal could not provide long-term stability of the liquid nanosuspension (Sheokand et al., 2018).

Plant peptide protease inhibitors are important molecules in seed storage metabolism and to fight insect pests. Commonly they contain multiple disulfide bonds and are exceptionally stable molecules. In this study, a novel peptide protease inhibitor from beetroot (Beta vulgaris) termed bevuTI-I was isolated, and its primary structure was determined via mass spectrometry-based amino acid sequencing. By sequence homology analysis a few peptides with high similarity to bevuTI-I, also known as the Mirabilis jalapa trypsin inhibitor subfamily of knottin-type protease inhibitors, were discovered. Hence, we assessed bevuTI-I for inhibitory activity toward trypsin (IC50 = 471 nM) and human prolyl oligopeptidase (IC50 = 11 μM), which is an emerging drug target for neurodegenerative and inflammatory disorders. Interestingly, using a customized bioinformatics approach, bevuTI-I was found to be the missing link to annotate 243 novel sequences of M. jalapa trypsin inhibitor-like peptides. According to their phylogenetic distribution they appear to be common in several plant families. Therefore, the presented approach and our results may help to discover and classify other plant-derived cystine knot peptides, a class of plant molecules that play important functions in plant physiology and are currently being explored as lead molecules and scaffolds in drug development.

Cancer and heart diseases are the leading causes of morbidity and mortality in many countries worldwide. Using chemotherapy and targeted therapies has led to an improvement in cancer survival rates and, unfortunately, higher cardiac adverse side effects – cardiotoxicity (Leong et al., 2019). Antineoplastic medicines have improved overall survival and progression-free survival to the oncological patients (Jemal et al., 2011; Varricchi et al., 2019). Mentioned medicines can be associated with several side effects, including cardiovascular toxicity. The National Cancer Institute defines cardiotoxicity in very general terms as “toxicity that affects the heart” (www.cancer.gov/dictionary/). Cardiotoxicity can develop in a subacute, acute, or chronic manner (Albini et al., 2018). Mitochondria are central targets for antineoplastic medicineinduced cardiovascular toxicity (Varricchi et al., 2019). Antineoplastic-related cardiovascular toxicities have been presented in many countries especially North American and European (Leong et al., 2019). Reported results from western countries are showed that the incidence rate of cancer treatment-induced cardiotoxicity is related with several chemotherapy and targeted therapies: anthracycline (0.9%–57%), cyclophosphamide (2%–28%), trastuzumab (0%– 28%) and bevacizumab (1.7%–10.9%) (Leong et al., 2019). The Agency for medicines and medical devices of Bosnia and Herzegovina (ALMBIH) was established by the Law on Drugs and Medical Devices ("Official Gazette of B&H, No. 58/08") as an authorized body for medicines and medical devices produced and used in B&H. In 2019. ALMBIH has become full member of Uppsala Monitoring Centre – World Health Organization. The aim of this work was to investigate the cardiovascular toxicity of antineoplastic medicines in Bosnia and Herzegovina.

Aflatoksin M1 ve M2, aflatoksin B1 ve B2'nin hidroksile metabolitleri olup, sut ve sut urunlerinde bulunabilir. Bu calismanin amaci, Bosna-Hersek'in farkli bolgelerinden farkli donemlere ait test sonuclarini kullanarak cig sutteki bu toksine maruz kalma ve saglik riski degerlendirmesi yapmaktir. AFM1 alim degerlendirmesi icin, Bosna-Hersek'te Tarim ve Kirsal Kalkinmaya Yonelik Katilim Oncesi Yardim Sektor Analizleri raporundaki veriler kullanilmistir. Aflatoksin M1'in cig sutteki konsantrasyonu icin, Saraybosna Eczacilik Universitesi Toksikolojik Kimya Fakultesi Laboratuvari'ndan alinan onceki calismalarin verileri ile yayinlanmamis veriler kullanilmistir. Dort maruziyet senaryosu icin yillik hepatoseluler karsinom riski (HCC) insidansi hesaplanarak risk karakterizasyonu yapilmistir. Sonuclar, ortalama tahmini gunluk aflatoksin M1 aliminin gunde 0.049 ng/kg vucut agirligi oldugunu gostermistir. Hepatoseluler karsinom riski (vaka/yil/100.000 kisi), HBsAg prevalansina bagli olarak nispeten dusuk bulunmustur (ortalama 0.000064-0.000074 vaka/yil/100.000). Son yillarda, aflatoksin M1'in kanserojen riskinin dusuk oldugu ve Bosna Hersek'te kritik olmadigi sonucuna varilmistir.