Faculty of Medical Sciences, Kragujevac
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Item 10th World IHEA and ECHE joint congress: Health economics in the age of longevity(2014) Jakovljevic, Mihajlo; GETZEN T.; Torbica A.; Anegawa T.© 2014 Informa UK Ltd. The 10th consecutive World Health Economics conference was organized jointly by International Health Economics Association and European Conference on Health Economics Association and took place at The Trinity College, Dublin, Ireland in July 2014. It has attracted broad participation from the global professional community devoted to health economics teaching, research and policy applications. It has provided a forum for lively discussion on hot contemporary issues such as health expenditure projections, reimbursement regulations, health technology assessment, universal insurance coverage, demand and supply of hospital services, prosperity diseases, population aging and many others. The high-profile debate fostered by this meeting is likely to inspire further methodological advances worldwide and spreading of evidence-based policy practice from OECD towards emerging markets.Item A Case of Erythema Dyschromicum Perstans(2022) Nikolić A.; Milicic, Vesna; Jovovic-Dagovic B.; Mitrović, AleksandarItem A case of uterine torsion in term pregnancy associated with placental abruption and intrauterine fetal demise(2018) Protrka, Zoran; Arsenijevic P.; Jović N.; Zivanovic, Suzana; Djuric, Janko; Dimitrijevic, Aleksandra© 2018. All rights reserved. Uterine torsion is defined as rotation of the uterus of more than 45° on its long axis. It is an unusual complication of pregnancy and probably represents a once-in-a-lifetime diagnosis. Fetal mortality up to 12 % and occasional maternal mortality are reported. The authors report a case of 180 degrees dextrogyre torsion at 38 weeks of gestation complicated by placental abruption with resultant maternal hypovolemic shock and intrauterine fetal demise. Emergency cesarean section was performed. After exteriorization of the uterus the authors observed the anterior crossing over of the proper ovarian ligaments, and at that time they realised that the uterus was axially rotated by 180 degrees. They performed a counterclockwise detorsion of the uterus and confirmed a low transverse incision of the posterior wall of the organ. Intraoperative plication of the uterosacral ligaments should be performed for prevention of recurrent torsion.Item A case report of female patient with laryngeal granuloma(2017) Simović A.; Vulović S.; Stojanovic, Jasmina; Živanovic M.; Koravovic M.© 2017, University of Kragujevac, Faculty of Science. All rights reserved. The aim of this case report is to present the laryngeal granuloma in 23 year old female patient. Case outline: The 23 year old female was admitted for examination, because of long lasting, progressive hoarseness. In anamnesis, we found that she has undergone general anesthesia for 8 times, in the early childhood. We performing direct laryngoscopy with complete otorhinolaryngologic examination, rigid endovideostroboscopy and the large granuloma of the larynx was found. Conclusions: Laryngeal granuloma of vocal cords affected mainly men, except for cases associated with laryngeal intubation. We should keep in mind that postintubation laryngeal granuloma might develop after tracheal intubation, so care must be taken to avoid the potential complication.Item A Comparative FE Analysis of a Flat Foot with and without a Custom-made Orthotic Insole(2019) Savić Z.; Lukic N.; Prodanovic, Nikola; Devedzic G.© 2019 IEEE. In the present study a stress analysis on a deformed footprint was performed in the case when an anatomical customized insole is used and in the case when an anatomical customized insole is not used. For specific deformities of the foot, an anatomical insole is made by using EasyCAD software. Solid models of the foot and insole, which are necessary for creating finite element models, were obtained by scanning the physical objects of the footprint and insole, and by their reconstruction and optimization in Geomagic software. Stress analysis was performed in Catia V5 R21 software for the case of a neutral standing position on the ground. Results show maximum values of the pressures in the medial region of the foot and toe region in the case when an anatomical customized insole is not used. With the use of the customized insole, pressures are significantly reduced, both by size and region.Item A comparative study of aerobic capacity among elite basketball players according to five different positions in the team(2022) Stojmenović, Dragutin; Trunic N.; Stojmenović T.The subject of this paper is the comparison of the obtained values of maximum oxygen consumption for senior basketball players in relation to their different positions and roles in the team. Sixty senior basketball players from four Serbian basketball clubs (BC Red Star n=14, BC FMP n=16, BC Mega n=15, and BC Borac n=15) participated in the study. The basic sports medical examination was performed in the Vita Maxima sports medicine clinic in Belgrade, which provided insight into their health conditions, and an assessment of their health capacity for participation in the study – i.e., for the implementation of maximum CPET (Cardiopulmonary Exercise Testing) – was carried out. The basic sports medical examination included: determination of body height, assessment of complete body composition (body weight, height-to-weight ratio (BMI), percentage of body fat (FAT%), 12-channel electrocardiogram (ECG) at rest with determination of heart rate, as well as measurement of arterial blood pressure on both arms and auscultation of the heart and lungs. After the introductory part of the test, which served as a warm-up, the speed of the conveyor belt increased to 9 km/h, and did not change during the test, while the elevation of the belt was raised by 2º every one minute in order to achieve the maximum load. The results of the study showed that maximal oxygen consumption as a measure of aerobic capacity is higher among players playing the positions of point guard and shooting guard compared to centers, but that it differs neither between point guards, shooting guards, and small forwards, nor between small forwards, power forwards, and centers. Furthermore, no difference in maximal oxygen consumption was observed between teams competing in different league ranks.Item A comparative study of complex formation in the reactions of gold(III) with Gly-Gly, Gly-l-Ala and Gly-l-His dipeptides(2010) Glišić, Biljana; Rajković, Snežana; Zivkovic, Marija; Djuran, MilošProton NMR spectroscopy was applied to study the reactions of the dipeptides glycyl-glycine (Gly-Gly) and glycyl-l-alanine (Gly-l-Ala) with hydrogen tetrachloridoaurate(III) (H[AuCl4]). All reactions were performed at pH 2.0 and 3.0 and at 40 °C. The final products in these reactions were [Au(Gly-Gly-κ3NG1,N G2,OG2)Cl] and [Au(Gly-l-Ala- κ3NG,NA,OA)Cl] complexes. Tridentate coordination of the corresponding dipeptides and square-planar geometry of these Au(III) complexes was confirmed by NMR (1H and 13C) spectroscopy. This study showed that at pH < 3.0 the Au(III) ion was able to deprotonate the amide nitrogen atom. However this displacement reaction was very slow and the total concentration of the corresponding Au(III)-peptide complex formed after 5 days was less than 60% for the Gly-l-Ala or 70% for the Gly-Gly dipeptide. The kinetic data of the reactions between the Gly-Gly and Gly-l-Ala dipeptides and [AuCl4]- were compared with those for the histidine-containing Gly-l-His dipeptide. The differences in the reactivity of these three dipeptides with the Au(III) ion are discussed. © 2010 Elsevier Inc.Item A comparison of bone mass and body composition according to playing positions and playing roles in male adolescent basketball players(2021) Stojanović E.; Jakovljevic, Vladimir; Jančíková, Vendula; Marek, Pavel; Radovanovic, DraganBACKGROUND: Limited research has quantified bone mass and body composition relative to playing position and playing role in male adolescent basketball players. The aim of this study was to determine whether bone mass and body composition differ according to playing position and playing role in male adolescent basketball players. METHODS: A between-subject, cross-sectional design was adopted. Thirty-four male, adolescent basketball players (age: 13-15 years) were grouped according to playing position (backcourt [guards] vs. frontcourt [forwards/centers]) and playing role (starters vs. bench). Bone mass (of the calcaneus and forearm) was measured using a peripheral dual energy X-ray absorptiometry scanner, while body composition was determined using a multifrequency bioelectrical impedance analyzer. RESULTS: Body height (ηp2 =0.23, large), total mass (ηp2=0.24, large), lean body mass (ηp2 =0.22, large), and absolute muscle mass (ηp2 =0.23, large) were significantly (P=0.01) higher in frontcourt players compared to backcourt players. Bone mineral density (BMD) and bone mineral content (BMC) of the left calcaneus (BMD: P=0.04, ηp2 =0.13, moderate; BMC: P=0.04, ηp2 =0.14, moderate) and right calcaneus (BMD: P=0.03, ηp2 =0.16, large; BMC: P=0.03, ηp2 =0.16, large) were significantly higher in starting players compared to bench players. Relative muscle mass (P=0.01, ηp2 =0.21, large) was significantly higher in starting than bench players, while body fat percentage (P=0.02, ηp2 =0.18, large) was significantly higher in bench players compared to starting players. CONCLUSIONS: Frontcourt players possessed higher body height, total mass, lean mass, and absolute muscle mass compared to backcourt players. Starters possessed superior bone mass of the calcaneus, relative muscle mass and lower body fat proportion compared to bench players.Item A comparison of the effects of cumene hydroperoxide and hydrogen peroxide on retzius nerve cells of the leech Haemopis sanguisuga(2013) Jovanovic, Zorica; Jovanovic, SvetlanaOxidative stress and the production of reactive oxygen species are known to play a major role in neuronal cell damage, but the exact mechanisms responsible for neuronal injury and death remain uncertain. In the present study, we examined the effects of oxidative stress on spontaneous spike activity and depolarizing outward potassium current by exposing the Retzius neurons of the leech to cumene hydroperoxide (CHP) and hydrogen peroxide (H2O2), the oxidants commonly used to examine oxidative mechanisms mediating cell death. We observed that relatively low concentrations of CHP (0.25, 1, and 1.5 mM) led to a marked prolongation of spontaneous repetitive activity. The prolonged action potentials showed an initial, spike-like depolarization followed by a plateau phase. In contrast, H2O2 at the same and much higher concentrations (0.25 to 5 mM) did not significantly change the duration of spontaneous spike potentials of leech Retzius nerve cells (LRNCs). In the voltage clamp experiments, calcium-activated outward potassium currents, needed for the repolarization of the action potential, were suppressed with CHP, but not with H2O2. The present findings indicate that CHP is a more potent oxidant and neurotoxin than H2O2 and that the effect of CHP on the electrophysiological properties of LRNCs may be due to the inhibition of the potassium channels. © 2013 Japanese Association for Laboratory Animal Science.Item A Correlation Study of the Colorectal Cancer Statistics and Economic Indicators in Selected Balkan Countries(2020) Vekic, Berislav; Dragojević Simić V.; Jakovljevic, Mihajlo; Kalezic M.; Zagorac Z.; Dragovic S.; Zivić R.; Pilipovic F.; Simic R.; Jovanovic D.; Milovanovic J.; Rancic, Nemanja© Copyright © 2020 Vekic, Dragojevic-Simic, Jakovljevic, Kalezic, Zagorac, Dragovic, Zivic, Pilipovic, Simic, Jovanovic, Milovanovic and Rancic. Colorectal cancer (CRC) is one of the most commonly diagnosed malignant neoplasms. The aim of the study was to evaluate and correlate most important epidemiological and economic indicators of CRC in 11 selected Balkan countries. The number of new CRC cases was 56,960, and the highest 5-year CRC prevalence was in Slovenia, Croatia, and Greece. Age-standardized CRC incidence rates were highest in Slovenia, Serbia, and Croatia, and age-standardized mortality rates were highest in Croatia, Serbia, and Bulgaria. Current Health Expenditure as % of Gross Domestic Product was the highest in Bosnia and Herzegovina and Serbia. The GDP per capita levels have shown positive correlation with the CRC incidence rate and prevalence. Absolute numbers of new and death-related CRC cases and 5-year prevalence in absolute numbers have shown strong positive correlation with GDP in million current US$. It has been shown that various economic indicators can be linked to the rate of incidence and prevalence of the CRC patients in the selected Balkan countries. Therefore, economic factors can influence the epidemiology of CRC, and heavy CRC burden in the Balkan region may be one of the indexes of the economic development.Item A country pandemic risk exposure measurement model(2020) Grima, Simon; Kizilkaya M.; Rupeika-Apoga, Ramona; Romānova, Inna; Gonzi R.; Jakovljevic, Mihajlo© 2020 Grima et al. Purpose: The purpose of this study is to develop a Pandemic Risk Exposure Measurement (PREM) model to determine the factors that affect a country’s prospective vulnerability to a pandemic risk exposure also considering the current COVID-19 pandemic. Methods: To develop the model, drew up an inventory of possible factor variables that might expose a country’s vulnerability to a pandemic such as COVID-19. This model was based on the analysis of existing literature and consultations with some experts and associa-tions. To support the inventory of selected possible factor variables, we have conducted a survey with participants sampled from people working in a risk management environment carrying out a risk management function. The data were subjected to statistical analysis, specifically exploratory factor analysis and Cronbach Alpha to determine and group these factor variables and determine their reliability, respectively. This enabled the development of the PREM model. To eliminate possible bias, hierarchical regression analysis was carried out to examine the effect of the “Level of Experienced Hazard of the Participant (LEH)” considering also the “Level of Expertise and Knowledge about Risk and Risk Management (LEK)”. Results: Exploratory factor analysis loaded best on four factors from 19 variables: Demographic Features, Country’s Activity Features, Economic Exposure and Societal Vulnerability (i.e. the PREM Model). This model explains 65.5% of the variance in the level of experienced hazard (LEH). Additionally, we determined that LEK explains only about 2% of the variance in LEH. Conclusion: The developed PREM model shows that monitoring of Demographic Features, Country’s Activity Features, Economic Exposure and Societal Vulnerability can help a country to identify the possible impact of pandemic risk exposure and develop policies, strategies, regulations, etc., to help a country strengthen its capacity to meet the economic, social and in turn healthcare demands due to pandemic hazards such as COVID-19.Item A Critique of Pharmacokinetic Calculators for Drug Dosing Individualization(2020) Jankovic, Slobodan© 2019, Springer Nature Switzerland AG. The ‘one-dose-fits-all’ approach where drug dosing regimen is prescribed according to recommendations from a summary of product characteristics is not appropriate for many patients whose clinical characteristics significantly differ from the most frequent ones in a population, as it cannot guarantee optimal exposure of target tissues to the drug. Our aim here is to provide a concise review of pharmacokinetic calculators currently available for clinical use and, at the same time, to suggest the minimum standards that they should satisfy to be routinely used in clinical practice. A systematic search of Medline, Ebsco, Scopus, Scindeks, Cochrane Library and Google Scholar was performed to find publications about available pharmacokinetic calculators for drug dose individualization. Theoretically well-founded and mathematically correct calculators for many drugs are available, but only a few calculators for specific drugs have been validated in clinical practice or through clinical trials, and the results published in peer-reviewed journals. The majority of available pharmacokinetic calculators for drug dosing individualization remain unvalidated, i.e., there is no evidence of their efficacy and safety in real-life clinical settings. Pharmacokinetic calculators for drug dose individualization are irreplaceable tools for achieving precision medicine, where dosing regimens are tailored to the needs and personal characteristics of each patient, maximizing efficacy and minimizing toxicity.Item A Deep Learning Model for Automatic Detection and Classification of Disc Herniation in Magnetic Resonance Images(2022) Sustersic, Tijana; Rankovic, Vesna; Milovanović, Vladimir; Kovacevic, Vojin; Rasulić L.; Filipovic, NenadLocalization of lumbar discs in magnetic resonance imaging (MRI) is a challenging task, due to a vast range of shape, size, number, and appearance of discs and vertebrae. Based on a review of the cutting-edge methods, the majority of applied techniques are either semi-automatic, extremely sensitive to change in parameters, or involve further modification of the results. All of the above represents a motivation for implementing deep learning-based approaches for automatic segmentation and classification of disc herniation in MR images. This paper proposes a complete automated process based on deep learning to diagnose disc herniation. The methodology includes several steps starting from segmentation of region of interest (ROI), in this case disc area, bounding box cropping and enhancement of ROI, after which the image is classified based on convolutional neural network (CNN) into adequate classes (healthy, bulge, central, right or left herniation for axial view and healthy, L4/L5, L5/S1 level of herniation in sagittal view). The results show high accuracy of segmentation for both axial view (dice = 0.961, IOU = 0.925) and sagittal view (dice = 0.897, IOU = 0.813) images. After cropping and enhancing the region of interest, accuracy of classification was 0.87 for axial view images and 0.91 for sagittal view images. Comparison with the literature shows that proposed methodology outperforms state-of-the-art results when it comes to multiclassification problems. A fully automated decision support system for disc hernia diagnosis can assist in generating diagnostic findings in a timely manner, while human mistakes caused by cognitive overload and procedure-related errors can be reduced.Item A Discrepancy: Calcium Channel Blockers Are Effective for the Treatment of Hypertensive Left Ventricular Hypertrophy but Not as Effective for Prevention of Heart Failure(2022) Koracévić G.; Perišić, Zoran; Stanojkovic M.; Stojanovic, Maja; Zdravkovic M.; Tomasevic, Miloje; Djordjevic, Dragan; Mladenovic, Katarina; Koracévic M.; Trkulja J.Arterial hypertension (HTN) is important due to its high prevalence, morbidity, and mortality rates. Calcium channel blockers (CCBs) are the first-line antihypertensive drugs. HTN can lead to heart failure (HF) by causing hypertensive left ventricular hypertrophy (HTN LVH). CCBs are recommended for the treatment of HTN LVH. The aim of this study was to analyze the status of CCBs regarding (1) HTN LVH treatment and (2) capability to prevent HTN-induced HF in the guidelines. For this narrative review, the following databases were searched: Medline, Scopus, Science Direct, Springer, SAGE, Wiley, Oxford Journals, Cambridge, and Google Scholar. CCBs are effective antihypertensive drugs and a very good therapeutic option for HTN LVH as they can cause reverse LVH remodeling. Consequently, we may expect that CCBs would prevent HF. However, evidence suggests that CCBs confer less protection from HF than other first-line antihypertensive drugs. A negative inotropic action of nondihydropyridine CCBs may contribute to suboptimal protection against HF. This discrepancy is clinically relevant because CCBs are in one of the two recommended (single pill) combinations for the initial treatment of HTN. LVH is a strong risk factor for HF in HTN patients. When LVH arises, the risk of HF increases dramatically. CCBs are inferior to renin-angiotensin-aldosterone system blockers but still very effective in bringing about regression of HTN LVH; consequently, CCBs are expected to protect from HF. On the contrary, CCBs protect from HF less effectively than other first-line antihypertensive drugs. This discrepancy needs to be investigated further to improve clinical practice.Item A family of antimicrobial and immunomodulatory peptides related to the frenatins from skin secretions of the Orinoco lime frog Sphaenorhynchus lacteus (Hylidae)(2014) Conlon, John Michael; Mechkarska, Milena; Radosavljevic, Gordana; Attoub S.; King J.; Lukic, Miodrag; McClean, StephenPeptidomic analysis of norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus (Hylidae, Hylinae) revealed the presence of three structurally related host-defense peptides with limited sequence similarity to frenatin 2 from Litoria infrafrenata (Hylidae, Pelodryadinae) and frenatin 2D from Discoglossus sardus (Alytidae). Frenatin 2.1S (GLVGTLLGHIGKAILG.NH and frenatin 2.2S (GLVGTLLGHIGKAILS.NH are C-terminally α-amidated but frenatin 2.3S (GLVGTLLGHIGKAILG) is not. Frenatin 2.1S and 2.2S show potent bactericidal activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MIC &16 μM) but are less active against a range of Gram-negative bacteria. Frenatin 2.1S (LC;bsubesub& = 80 ;plusmn& 6 μM) and 2.2S (LC;bsubesub& = 75 ;plusmn& 5 μM) are cytotoxic against non-small cell lung adenocarcinoma A549 cells but are less hemolytic against human erythrocytes (LC;bsubesub& = 167 ;plusmn& 8 μM for frenatin 2.1S and 169 ;plusmn& 7 μM for 2.2S). Weak antimicrobial and cytotoxic potencies of frenatin 2.3S demonstrate the importance of C-terminal α-amidation for activity. Frenatin 2.1S and 2.2S significantly (P ;lt& 0.05) increased production of proinflammatory cytokines IL-1β and IL-23 by lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages and frenatin 2.1S also enhanced production of TNF-α. Effects on IL-6 production were not significant. Frenatin 2.2S significantly downregulated production of the anti-inflammatory cytokine IL-10 by LPS-stimulated cells. The data support speculation that frenatins act on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms. They may represent a template for the design of peptides with therapeutic applications as immunostimulatory agents. © 2014 Elsevier Inc.Item A five-compartment biokinetic model for 90Y-DOTATOC therapy(2018) Jeremic M.; Matovic, Milovan; Krstic, Dragana; Pantović M.; Nikezic, Dragoslav© 2018 American Association of Physicists in Medicine Purpose: Neuroendocrine tumors (NETs) are now routinely treated by radiopeptide targeted therapy using somatostatin receptor-binding peptides such as 90Y- and 177Lu-DOTATOC. The objective of this work was to develop a biokinetics model of 90Y labelled DOTATOC, which is applied in the therapy of NETs to estimate doses in kidney and tumor. Methods: A multi-compartment model described by two sets of differential equations, one set for the actual 30-min infusion and the other set for the post-infusion period was developed and activities were measured by liquid scintillation counting in blood (compartment 1) and the urine (compartment 3). The inter-compartment transfer coefficients, λij, were varied to yield the best fit of the calculated to the measured time-activity data and the 90Y-DOTATOC time-activity data in the five-compartments comprising the human body were thus determined. The resulting time-activity curves were integrated over the interval from 0 to 72 h post administration to obtain the number of radioactive decays in each compartment and, in case of the kidneys and tumor, then multiplied by the self-dose 90Y beta particle absorbed fraction, determined by Monte Carlo (MC) simulation, the kidney and tumor absorbed doses. Results: Transfer coefficients λij, were determined for five-compartments for all patients. Time- activity curves of 90Y-DOTATOC in 14 patients were determined, and two typical ones are shown graphically. Absorbed doses in the tumor and kidneys, obtained by the developed method, were determined. The mean absorbed dose in a kidney per unit of administered activity is 1.43 mGy/MBq (range 0.73–2.42 mGy/MBq). The tumor dose was determined as 30.94 mGy/MBq (range 20.05–42.31 mGy/MBq). Conclusion: Analytical solution of a biokinetic model for 90Y-DOTATOC therapy enabled determination of the transfer coefficients and derivation of time-activity curves and kidney and tumor absorbed doses for 14 treated patients. The model can be applied to other radionuclides where elimination is predominantly through urine, which is often the case in radiopharmaceuticals.Item A framework for technology enhanced education in orthopaedics: Knee surgery case study(2017) Devedzic G.; Petrovic Savic, Suzana; Matic, Aleksandar; Ristic, Branko; Devedzic, Vladan; Asgharpour Z.; Cukovic, Sasa© Springer Nature Singapore Pte Ltd. 2018. The paper presents a framework for technology enhanced education (TEE) in orthopaedics aimed at employment of ubiquitous information and communication technology (ICT) and digital technologies in order to compensate for an unaffordable learning environment. On the other side, the concept involves both (bio)engineers, ICT specialists, and orthopaedic surgeons in an interprofessional collaboration, leveraging multidisciplinary approaches to improve the quality of clinical-oriented education. Preliminary results indicate increased motivation and satisfaction of both the learners and educators.Item A giant exulcerated phyllodes breast tumor a case report(2020) Spasic, Marko; Milosevic, Bojan; Mitrović, Slobodanka; Markovic, Nenad; Pavlovic, Mladen; Jevdjic, Jasna; Milisavljevic, Slobodan; Zornic, Nenad; Nedovic, Nikola; Jevtic, Milica; Kozomara, Zoran; Marković, Ivan; Ninkovic, Srdjan© 2020, University of Kragujevac, Faculty of Science. All rights reserved. Phyllodes tumors of the breast can be benign, malignant, or borderline. Benign and borderline tumors are rare tumor types that have a positive outlook and high survival rate, while the risk of recurrence is typical for malignant breast tumors. Giant phyllodes tumors are larger than 10 cm in diameter and demand a serious diagnostic and treatment approach. In this study we present a case of a female patient treated for an exulcerated breast carcinoma-a giant borderline phyllodes tumor of the breast. The patient presented to the department for the right breast lump with ulcerated skin and nipple abnormalities. The core biopsy was performed and the patient was diagnosed with a benign tumor. Simple mastectomy was performed and final histopathological report revealed a borderline phyllodes tumor. Diagnosis and treatment of a giant phyllodes tumor remain a great challenge for the surgeons. Establishing the preoperative diagnosis based on histopathological findings is imperative to disease management. Surgery is the mainstay of treatment and mastectomy has been the traditional procedure; in cases where suspicious findings in the axilla are revealed, radical mastectomy is performed and the axilla is to be dissected.Item A Global Assessment of Sustainable Development: Integrating Socioeconomic, Resource and Environmental Dimensions(2022) Sun J.; Jin H.; Tsai F.; Jakovljevic, MihajloSustainable development and its assessment have increasingly played a key background role in government policymaking across the world. Generally, sustainable development is defined as the coordination of economic, environmental, and social development in order to balance intra-generational welfare and maximize inter-generational overall welfare. Therefore, the purpose of our research is to assess national sustainable development from the perspective of integrating economic, environmental, and social dimensions, and then to better monitor the status of sustainable development. We first adopt and modify the National Sustainable Development Index, which has been proposed as a way to amend the Human Development Index, including 12 indicators (weighted by the Entropy Method) in economic, environmental, and social dimensions. After that, we assess the sustainable development status of 179 countries from 2010 to 2016. The result shows that there is no obvious trend of narrowing the gap in sustainable development levels among countries, or even an expanding trend in this period. We also make a comparison between the original NSDI and our modified NSDI and find that the modified NSDI not only retains the merits but also makes up for the shortcomings of the original one in acceptability, reliability, and continuity.Item A human iPSC model of Ligase IV deficiency reveals an important role for NHEJ-mediated-DSB repair in the survival and genomic stability of induced pluripotent stem cells and emerging haematopoietic progenitors(2013) Tilgner K.; Neganova I.; Moreno-gimeno I.; Al-Aama J.; Burks D.; Yung S.; Singhapol C.; Saretzki G.; Evans J.; Gorbunova V.; Gennery, Andrew; Przyborski S.; Stojkovic, Miodrag; armstrong, lyle; Jeggo P.; lako, majlindaDNA double strand breaks (DSBs) are the most common form of DNA damage and are repaired by non-homologous-end-joining (NHEJ) or homologous recombination (HR). Several protein components function in NHEJ, and of these, DNA Ligase IV is essential for performing the final 'end-joining' step. Mutations in DNA Ligase IV result in LIG4 syndrome, which is characterised by growth defects, microcephaly, reduced number of blood cells, increased predisposition to leukaemia and variable degrees of immunodeficiency. In this manuscript, we report the creation of a human induced pluripotent stem cell (iPSC) model of LIG4 deficiency, which accurately replicates the DSB repair phenotype of LIG4 patients. Our findings demonstrate that impairment of NHEJ-mediated-DSB repair in human iPSC results in accumulation of DSBs and enhanced apoptosis, thus providing new insights into likely mechanisms used by pluripotent stem cells to maintain their genomic integrity. Defects in NHEJ-mediated-DSB repair also led to a significant decrease in reprogramming efficiency of human cells and accumulation of chromosomal abnormalities, suggesting a key role for NHEJ in somatic cell reprogramming and providing insights for future cell based therapies for applications of LIG4-iPSCs. Although haematopoietic specification of LIG4-iPSC is not affected per se, the emerging haematopoietic progenitors show a high accumulation of DSBs and enhanced apoptosis, resulting in reduced numbers of mature haematopoietic cells. Together our findings provide new insights into the role of NHEJ-mediated-DSB repair in the survival and differentiation of progenitor cells, which likely underlies the developmental abnormalities observed in many DNA damage disorders. In addition, our findings are important for understanding how genomic instability arises in pluripotent stem cells and for defining appropriate culture conditions that restrict DNA damage and result in ex vivo expansion of stem cells with intact genomes. © 2013 Macmillan Publishers Limited All rights reserved.