Motivation: CYP2D6 is highly polymorphic gene which encodes the (CYP2D6) enzyme, involved in the metabolism of 20–25% of all clinically prescribed drugs and other xenobiotics in the human body. CYP2D6 genotyping is recommended prior to treatment decisions involving one or more of the numerous drugs sensitive to CYP2D6 allelic composition. In this context, high-throughput sequencing (HTS) technologies provide a promising time-efficient and cost-effective alternative to currently used genotyping techniques. To achieve accurate interpretation of HTS data, however, one needs to overcome several obstacles such as high sequence similarity and genetic recombinations between CYP2D6 and evolutionarily related pseudogenes CYP2D7 and CYP2D8, high copy number variation among individuals and short read lengths generated by HTS technologies. Results: In this work, we present the first algorithm to computationally infer CYP2D6 genotype at basepair resolution from HTS data. Our algorithm is able to resolve complex genotypes, including alleles that are the products of duplication, deletion and fusion events involving CYP2D6 and its evolutionarily related cousin CYP2D7. Through extensive experiments using simulated and real datasets, we show that our algorithm accurately solves this important problem with potential clinical implications. Availability and implementation: Cypiripi is available at http://sfu-compbio.github.io/cypiripi. Contact: cenk@sfu.ca.

OBJECTIVES Matrix metalloproteinases (MMPs) has been implicated in the pathogenesis of infective, cancer and autoimmune diseases. In this study, we investigated the serum level of MMPs and its clinical importance in human brucellosis. PATIENTS AND METHODS This study included 60 brucellosis patients treated at the Clinic for Infectious Diseases, Clinical Centre, University of Sarajevo. Matrix metalloproteinases serum levels were quantified by ELISA. RESULTS The investigation involved three groups: 30 patients with complications, 30 patients without complications of brucellosis and 30 healthy control examinees. The complications of human brucellosis varied but osteoarticular involvement dominated (n=21/30; 70%). Matrix metalloproteinases serum levels in the patients with complications were highest. The serum level of MMP-1 in patients with complications was the highest at 9.45; in patients without complications it was 3.78 and in the control examinees it was lowest at 3.62 (p=0.001). The serum level of MMP-9 in patients with complications was the highest at 105.66; in patients without complications 64.67, and in the control examinees it was lowest at 37.32 (p=0.001). The serum level of MMP-13 in patients with complications was highest at 138.86; in patients without complications at 64.85; and in the control examinees it was the lowest at 29.55 (p=0.001). Pearson's coefficient showed a statistically significant positive correlation between levels of tested matrix metalloproteinases and development complications in human brucellosis (p=0.001). CONCLUSION This study showed the diagnostic value and importance of detection of matrix metalloproteinases in human brucellosis. MMPs are a useful serum biomarker for assessment of disease activity.

UNLABELLED The Postgraduate studies (PS) at the Medical Faculty (MF) of the University of Tuzla (UT) were founded with the aim of training future staff of the MF in scientific research work. The course lasted four semesters. Up to 1986, classes were attended by five generations or 141 postgraduate students, and 57 of them received their Master's degree (MSc's). Classes were held every week on Fridays and Saturdays. One part of the classes was taught at the MF in Szeged (Hungary). Besides teachers from the UT, classes were also taught by teachers from other universities from the former Yugoslavia and abroad. The most important textbooks were: Cell and Molecular Biology by de Robertisa, Mathematics and statistics for use in pharmacy, biology, and chemistry by Saunders & Fleming, and Kako se pišu saopštenja o medicinskim istraživanjima (How to write reports of medical research) by Rajko Igić. Searching the index base Pub Med at the end of 2014, by the surnames and initials of the names of the 57 masters, we found that they had published 14 articles before completing their MSc's and 821 articles after completing their Master of Science. Later, 35 masters received PhDs and were appointed assistant professors, and later they were also appointed to higher ranks. CONCLUSION Looking at the results of the PS, MF of the UT in the above mentioned period, it can be said that the PS was the place where the formation began of the future scientific and teaching staff of the MF in Tuzla.

Some of the most important nanoporous materials that are used for industrial applications are formed as intergrowths between structurally related phases. Further, the specific properties and functions are often strongly related to the nature of these intergrowths. By their nature such structures are notoriously difficult to characterize in detail and thereby formulate a structure/property relationship. We approach the problem of the industrially relevant CHA/AEI intergrowth system by getting insight into not only the structure of the materials but also the crystal-growth mechanism and show that the former is crucially dependent upon the latter. Through a detailed X-ray diffraction analysis with optimization of the CHA/AEI layer stacking sequence, it is shown that up to three distinct components are present. These consist of the two end member structures intimately cocrystallizing with an intergrowth structure. The intergrowth composition is further corroborated by nuclear magnetic resonance and unit cell ...

OBJECTIVE To provide anatomical information on the position, morphological variations and incidence of mental foramen (MF) and accessory mental foramen (AMF) as they are important for dental surgeons, anesthetists in nerve block and surgical procedures, to avoid injury to the neurovascular bundle in the mental foramen area. METHODS Our study was conducted on 150 adult dry human mandibles from the osteological collection of the Department of Anatomy of the Faculty of Medicine, University of Sarajevo. The location and shape of the MF and the presence of the AMF were studied by visual examination. The size and position of the MF were measured using a digital vernier caliper. SPSS, version 17 software was used for the statistical analysis. RESULTS Bilateral mental foramina were presented in all 150 mandibles. In the majority of mandibles, the MF was located between the first and second premolar (20.3%) or on the level of the root of the second premolar (60.3%), midway between the inferior margin and the alveolar margin of the mandible. Most of the mental foramina were oval in shape (83.3%). An AMF was present in four mandibles (2.7%) on the right side. CONCLUSION This study may be a very useful new supplement to data on variations in the incidence, position, shape and size of mental and accessory mental foramina, which may help surgeons, anaesthetists, neurosurgeons and dentists in carrying out surgical procedures successfully.

UNLABELLED In this article we describe Cochrane and its products: Cochrane systematic reviews (CSRs) and other Cochrane evidence. Cochrane is a unique, international, non-profit organisation that offers health care providers, health care consumers and other decision makers unbiased and highly reliable information on health, which is pivotal for conscientious and responsible decision making in overall healthcare. Cochrane offers the highest ranked evidence in Evidence Based Medicine (EBM)--systematic reviews. Currently, CSRs are freely available in BH, and therefore, they ought to be widely used, and understood. We will present the new Cochrane Strategy to 2020, which was the main topic of the 6th Croatian Cochrane Symposium (CroCoS), as well as explore prospects for spreading Cochrane activities to Bosnia and Herzegovina (BH), through collaboration with Cochrane Croatia. BH has no officially organized Cochrane activity, as yet. We hope that this article will raise awareness about Cochrane in BH, help promote its activities, and deepen the existing collaboration with Cochrane Croatia. There are already some changes being introduced concerning Cochrane--at least, in one half, the Federation of BH (FBH). Two documents symbolising official recognition of policy changes towards Cochrane have recently been published in the Official Gazette of FBH. CONCLUSION Since founding a BH Cochrane Branch would be costly and difficult to achieve in a complicated environment, such as the one we have, BH could use the good will, experience, knowledge, and translated educational, training and web materials of Cochrane Croatia, particularly given the language similarities, to promote evidence based medicine in BH.

The histiocytoses are rare tumors characterized by the primary accumulation and tissue infiltration of histiocytes and dendritic cells. Identification of the activating BRAFV600E mutation in Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) cases provided the basis for the treatment with BRAF and/or MEK inhibitors, but additional treatment options are needed. Twenty-four cases of neoplastic histiocytic diseases [11 extrapulmonary LCH, 4 ECD, 4 extranodal Rosai-Dorfman disease (RDD), 3 follicular dendritic cell sarcoma (FDCS), 1 histiocytic sarcoma (HS) and 1 blastic plasmacytoid dendritic cell neoplasm (BPDCN)] were analyzed using immunohistochemical and mutational analysis in search of biomarkers for targeted therapy. BRAF V600E mutations were detected in 4/11 LCH and 4/4 ECD cases. A pathogenic PTEN gene mutation and loss of PTEN protein expression were identified in the case of HS. Increased expression of PD-L1 (≥2+/≥5%) was seen in 3/4 ECD, 7/8 LCH, 3/3 FDCS and 1/1 HS, with overall 81% concordance between 2 antibodies used in the study (SP142 vs. MAB1561 clone). These results show for the first time significant expression of the PD-L1 immune checkpoint protein in these disorders, which may provide rationale for addition of immune check-point inhibitors in treatment of disseminated and/or refractory histiocytoses.

A bstractIn view of recent experimental indications of violations of Lepton Flavor Universality (LFU) in B decays, we analyze constraints and implications of LFU interactions, both using an effective theory approach, and an explicit dynamical model. We show that a simple dynamical model based on a SU(2)L triplet of massive vector bosons, coupled predominantly to third generation fermions (both quarks and leptons), can significantly improve the description of present data. In particular, the model decreases the tension between data and SM predictions concerning: i) the breaking of τ-μ universality in B→D(*)ℓν decays; ii) the breaking of μ-e universality in B → Kℓ+ℓ− decays. Indirectly, the model might also decrease the discrepancy between exclusive and inclusive determinations of |Vcb| and |Vub|. The minimal version of the model is in tension with ATLAS and CMS direct searches for the new massive vectors (decaying into τ+τ− pairs), but this tension can be decreased with additional non-standard degrees of freedom. Further pre-dictions of the model both at low- and high-energies, in view of future high-statistics data, are discussed.