Natural Radioactivity and the Evaluation of Related Radiological Risks in Concrete Used in Prizren District, Kosovo

This study aims to investigate the natural radioactivity levels in concrete made of Portland cement and used in Prizren district, Republic of Kosovo. The activity concentrations of 40K, 226Ra and 232Th were determined by gamma-ray spectroscopy technique with High Purity Germanium (HPGe) detector. The activity concentrations of 40K, 226Ra, and 232Th were found to be 15.4-28.4 Bq kg-1, 4.3-5.9 Bq kg-1 and 2.0-4.1 Bq kg-1, respectively. These results were used to calculate the activity concentration index as recommended by the Basic Safety Standard of Council Directive 2013/59/EURATOM for the safe use of building material. Kosovo must comply with this recommendation in the framework of legislative harmonization with the European Union. The activity concentration index was found to be lower than the reference level of unity (I=0.05), corresponding to an annual effective dose rate of AED=0.05 mSv y-1. The concentration of radionuclides and radiological hazard parameters for concrete investigated in this study were compared with respective results found in literature from different countries. These results show very low activity concentrations, indicating that concrete used in Prizren, Kosovo, does not pose any significant risk due to its use as building material

A novel EGFR inhibitor acts as potent tool for hypoxia-activated prodrug systems and exerts strong synergistic activity with VEGFR inhibition in vitro and in vivo

Small-molecule EGFR inhibitors have distinctly improved the overall survival especially in EGFR-mutated lung cancer. However, their use is often limited by severe adverse effects and rapid resistance development. To overcome these limitations, a hypoxia-activatable Co(III)-based prodrug (KP2334) was recently synthesized releasing the new EGFR inhibitor KP2187 in a highly tumor-specific manner only in hypoxic areas of the tumor. However, the chemical modifications in KP2187 necessary for cobalt chelation could potentially interfere with its EGFR-binding ability. Consequently, in this study, the biological activity and EGFR inhibition potential of KP2187 was compared to clinically approved EGFR inhibitors. In general, the activity as well as EGFR binding (shown in docking studies) was very similar to erlotinib and gefitinib (while other EGFR-inhibitory drugs behaved different) indicating no interference of the chelating moiety with the EGFR binding. Moreover, KP2187 significantly inhibited cancer cell proliferation as well as EGFR pathway activation in vitro and in vivo. Finally, KP2187 proved to be highly synergistic with VEGFR inhibitors such as sunitinib. This indicates that KP2187releasing hypoxia-activated prodrug systems are promising candidates to overcome the clinically observed enhanced toxicity of EGFR-VEGFR inhibitor combination therapies

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and typically severe intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorders including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioral abnormalities including delayed habituation and alterations in the 2-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggests an important role of SLC4A10 in the production of the cerebrospinal fluid. However, it is notable that despite diverse roles of the cerebrospinal fluid in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel characteristic neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties

Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.This work was supported by European Union FP7 Grant No. 278568 “PRIMES” and Science Foundation Ireland Investigator Program Grant 14/IA/2395 to W.K. B.K. is supported by SmartNanoTox (Grant no. 686098), NanoCommons (Grant no. 731032), O.R. by MSCA-IF-2016 SAMNets (Grant no. 750688). D.M. is supported by Science Foundation Ireland Career Development award 15-CDA-3495. I.J. is supported by the Canada Research Chair Program (CRC #225404), Krembil Foundation, Ontario Research Fund (GL2-01-030 and #34876), Natural Sciences Research Council (NSERC #203475), Canada Foundation for Innovation (CFI #225404, #30865), and IBM. O.S. is supported by ERC investigator Award ColonCan 311301 and CRUK. I.S. is supported by the Canadian Cancer Society Research Institute (#703889), Genome Canada via Ontario Genomics (#9427 & #9428), Ontario Research fund (ORF/ DIG-501411 & RE08-009), Consortium Québécois sur la Découverte du Médicament (CQDM Quantum Leap) & Brain Canada (Quantum Leap), and CQDM Explore and OCE (#23929). T.C. was supported by a Teagasc Walsh Fellowshi

Prizren as A City-State Under Roman-Byzantine Administration

The rule of the Roman Empire left its mark on ancient Dardania as well. At the time of the division of the empire into Roman and Byzantine, Prizren fell under the Byzantine rule. Theranda, as Prizren was called in Roman times, developed as a very important place in many spheres of life, first in trade then in administration and culture. As we know, Rome, at the time of the occupation of the new lands, compulsorily introduced both law and management and administration. The initial cartographic data for Prizren come from the Roman period, when the city with its ancient name, Theranda, is shown on Peutinger's table. Regarding the functioning of Prizren as a city-state or provincial state, according to the Kanun of Prizren of 1570, part of the Sanjak of Prizren were six kazas (districts): Prizren, Hoça, Sesrit (Neubicare), Bihor (important fortification) and Trgovishte (Rozhaje). According to Haxhi Kalfi, in the middle of the XVII century, this sanjak had Perser (Prizren) Suhareka, Havas Prizren (Gora and Opoja), Firqne (Hoqa), Bihor and Trgovishte as kadiluks. The paper treats Prizren since ancient Roman Byzantine times, Prizren as a city-state, Theranda as an important cultural trade centre and as the first administrative centre, a province of the Roman Empire

Changing the Manner of Electing the President of the Republic of Kosovo

The Constitution of the Republic of Kosovo in its basic provisions has constituted the principle of separation and control of the balance between state powers as a fundamental principle of democracy, by designating representative bodies belonging to state powers such as Parliament, Government, and Judiciary. In addition, the Constitution sanctions other state bodies that have a constitutional character and together create the form of governance in the Republic of Kosovo. Among them also the President functions as a constitutional body exercising the executive duty and having ceremonial competencies. The President in Kosovo is a neutral authority because he/she is a representative of the people's unity. The authorities in Kosovo create a "check and balance" among themselves for the normal functioning of the state. Kosovo is considered a parliamentary Republic, not sanctioned by the constitution but implied based on the decision of the Parliament of the Republic of Kosovo.In addition to electing the Government, the Parliament also elects the President of the Republic, so in this study, we will address the function of the President, the exercise of his duties, his competencies, and his relationship with other state bodies. We will also analyze the system of governance and the principle of separation and balance of powers, with special emphasis on the constitutional position of the President in the Republic of Kosovo. Among other things, we will address in particular the complexity of the procedures for the election of the President of the Republic of Kosovo. Considering the ongoing problems that have accompanied the presidential elections in the Republic of Kosovo and that continue to be so, it is necessary to clarify whether “the constitutional reform initiative for the President of the Republic of Kosovo to be voted by the people is considered the most current and best way of overcoming the present parliamentary stalemate in the election of the candidate for the President of the Republic, as well as whether the implementation of this reform is conditioned by the will of the political parties and the people”. In general, from the stated scientific elaboration of the topic, we can conclude that the intention of this paper consists in determining the constitutional regulation of the institution of the President of the Republic of Kosovo applied in the parliamentary system, empirical elaboration of problems that accompanied the election of presidents in the Republic of Kosovo as well as the immediate need to change the manner of electing the President of the Republic of Kosovo

Pharmacy students’ knowledge and attitudes about antibiotics in Kosovo

Objective: The main objective of this study was to assess the knowledge and attitude among Pharmacy students of the University of Prishtina in regards to the antibiotics. Methods: 144 pharmacy students at the University of Prishtina were recruited in this study to complete a self-administered questionnaire. The total number of questions in this questionnaire was eight (8), covering two (2) major themes: self-report of the current and past antibiotic use and behavior; and anticipated prescription behavior of antibiotics upon graduation. The data was statistically analyzed through using SPSS for Windows. Descriptive analysis was employed, and the results were expressed in frequency and percentages. Results: The results showcased a good knowledge of antibiotic among students. The most common answer of students' knowledge about antibiotics was good or moderate (82 %), while 63.2% of the subjects used antibiotics by self-decision, most of them (45 %) for sore throat. Upon graduation, 56.9 % of the students will not sell antibiotics without prescription and 85.4% think that module for rational use of antibiotics is very necessary to be inside the pharmacy syllabus. Conclusion: The study showed good and moderate knowledge of pharmacy students regarding the antibiotics. Half of them use antibiotics by self-decision but the majority of them stated that they will not serve the antibiotics without medical prescription. Specific modules and training for proper antibiotic use should be implemented within the Pharmacy program in The Faculty of Medicine

Macromolecular Bioscience / Macromolecular Pt(IV) Prodrugs from Poly(organo)phosphazenes

The preparation of novel macromolecular prodrugs via the conjugation of two platinum(IV) complexes to suitably functionalized poly(organo)phosphazenes is presented. The inorganic/organic polymers provide carriers with controlled dimensions due to the use of living cationic polymerization and allow the preparation of conjugates with excellent aqueous solubility but long-term hydrolytic degradability. The macromolecular Pt(IV) prodrugs are designed to undergo intracellular reduction and simultaneous release from the macromolecular carrier to present the active Pt(II) drug derivatives. In vitro investigations show a significantly enhanced intracellular uptake of Pt for the macromolecular prodrugs when compared to small molecule Pt complexes, which is also reflected in an increase in cytotoxicity. Interestingly, drug-resistant sublines also show a significantly smaller resistance against the conjugates compared to clinically established platinum drugs, indicating that an alternative uptake route of the Pt(IV) conjugates might also be able to overcome acquired resistance against Pt(II) drugs. In vivo studies of a selected conjugate show improved tumor shrinkage compared to the respective Pt(IV) complex.P 24659-N28(VLID)308360

A campaign of discrete radon concentration measurements in soil of Niska Banja town, Serbia

The first radon soil gas survey in Serbia, using passive detectors (SSNTD, CR-39), was carried out in June 2005 at field sites in Niska Banja town. The aim of the survey was to identify risk zones characterised by high levels of this radioactive gas. Radon measurements were made at the depth of 50cm, in the ground according to a systematic grid pattern. Furthermore, at all 48 measurement points, the surface gamma dose rates in the air was also measured at the same locations and soil samples were collected for gamma spectrometric analysis for the radionuclides Ra-226, Th-228 and K-40. Radon concentrations were found to range from 1270 to 155000 Bq m(-3) with an average of 33765 Bq m(-3) and a median value of 12626 Bq m(-3). The geometrical mean value and geometrical standard deviation were calculated as 16160 Bq m(-3) and 3.5 Bq m(-3), respectively. Gamma dose rate varies from 92 to 316 nGy h(-1), with an average of 132 nGy h(-1). The radium content in collected soil samples ranges from 24 to 1810 Bq kg(-1) with an average of 187 Bq kg(-1). High correlations (r(2) GT 0.8) between soil gas radon concentration, gamma dose rate and Ra-226 content in soil were found for each pair. The distribution of radon concentrations in soil gas shows bimodal shape. (C) 2007 Elsevier Ltd. All rights reserved