Drug Provocation Tests to Betalactam Antibiotics: Experience in a Paediatric Setting

Background: Few studies have been performed in children withs uspected betalactam allergy.We aimed to assess the role of the drug provocation test(DPT)with betalactams in a paediatric setting and to study the association between allergy to betalactam antibiotics and other allergic diseases. Methods:We included all the patients under 15 years old who were consecutively referred to the Immunoallergy Department, Dona Estefânia Hospital,Portugal(January 2002 to April 2008)for a compatible history of allergic reaction to betalactam. All were submitted to a DPT.Children were proposed to performs kintests(ST)to betalactam antibiotics followed by DPT. If they decline ST,a DPT with the culprit drug was performed. Results: We studied 161 children,60%were boys,with a median age of 5years old at the time of the DPT.Thirty-three patients(20.5%)had an immediate reaction and 33(20.5%)a non-immediate reaction. These verity of there porte dreactions was low in most cases. Skin tests to betalactams were performed in 47 children and were positive in 8.DPT was positive inonlyone(3.4%)of the patients skin tested and in 11(13.4%)of those not skin tested. These verity of the DPT reaction was low.Asthma and food allergy were associated with a positive DPT in the later group. Conclusions: DPT seems a safe procedure even in the absence of ST in non-severe cases. This could be a practical optionin infants and pre-school children,where ST are painful and difficult to perform.Additional caution should be taken in children with asthma and food allergy

Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals

The aim of this study was to compare results obtained by eight different short-term assays of estrogenlike actions of chemicals conducted in 10 different laboratories in five countries. Twenty chemicals were selected to represent direct-acting estrogens, compounds with estrogenic metabolites, estrogenic antagonists, and a known cytotoxic agent. Also included in the test panel were 17β-estradiol as a positive control and ethanol as solvent control. The test compounds were coded before distribution. Test methods included direct binding to the estrogen receptor (ER), proliferation of MCF-7 cells, transient reporter gene expression in MCF-7 cells, reporter gene expression in yeast strains stably transfected with the human ER and an estrogen-responsive reporter gene, and vitellogenin production in juvenile rainbow trout. 17β-Estradiol, 17α-ethynyl estradiol, and diethylstilbestrol induced a strong estrogenic response in all test systems. Colchicine caused cytotoxicity only. Bisphenol A induced an estrogenic response in all assays. The results obtained for the remaining test compounds—tamoxifen, ICI 182.780, testosterone, bisphenol A dimethacrylate, 4-n-octylphenol, 4-n-nonylphenol, nonylphenol dodecylethoxylate, butylbenzylphthalate, dibutylphthalate, methoxychlor, o,p′-DDT, p,p′-DDE, endosulfan, chlomequat chloride, and ethanol—varied among the assays. The results demonstrate that careful standardization is necessary to obtain a reasonable degree of reproducibility. Also, similar methods vary in their sensitivity to estrogenic compounds. Thus, short-term tests are useful for screening purposes, but the methods must be further validated by additional interlaboratory and interassay comparisons to document the reliability of the methods

An Intelligent Transportation System Application for Smartphones Based on Vehicle Position Advertising and Route Sharing in Vehicular Ad-Hoc Networks

[EN] Alerting drivers about incoming emergency vehicles and their routes can greatly improve their travel times in congested cities, while reducing the risk of accidents due to distractions. This paper contributes to this goal by proposing Messiah, an Android application capable of informing regular vehicles about incoming emergency vehicles like ambulances, police cars and fire brigades. This is made possible by creating a network of vehicles capable of directly communicating between them. The user can, therefore, take driving decisions in a timely manner by considering incoming alerts. Using the support of our GRCBox hardware, the application can rely on vehicular ad-hoc network communications in the 5 GHz band, being V2V (vehicle-to-vehicle) communication provided through a combination of Android-based smartphone and our GRCBox device. The application was tested in three different scenarios with different levels of obstruction, showing that it is capable of providing alerts up to 300 meters, and notifying vehicles within less than one secondThis work was partially supported by the "Ministerio de Economia y Competividad, Programa Estatal de Investigacion, Desarollo e Innovacion Orientada a los Retos de la Sociedad, Proyectos I+D+I 2014", Spain, under Grant Nos. TEC2014-52690-R and BES-2015-075988.Hadiwardoyo, SA.; Patra, S.; Tavares De Araujo Cesariny Calafate, CM.; Cano, J.; Manzoni, P. (2018). An Intelligent Transportation System Application for Smartphones Based on Vehicle Position Advertising and Route Sharing in Vehicular Ad-Hoc Networks. Journal of Computer Science and Technology. 33(2):249-262. https://doi.org/10.1007/s11390-018-1817-4S249262332Papadimitratos P, De La Fortelle A, Evenssen K, Brignolo R, Cosenza S. Vehicular communication systems: Enabling technologies, applications, and future outlook on intelligent transportation. IEEE Communications Magazine, 2009, 47(11): 84-95.Gerla M, Kleinrock L. Vehicular networks and the future of the mobile Internet. Computer Networks, 2011, 55(2): 457-469.Vegni A M, Loscrí V. A survey on vehicular social networks. IEEE Communications Surveys & Tutorials, 2015, 17(4): 2397-2419.Eze E C, Zhang S J, Liu E J. Vehicular ad hoc networks (VANETs): Current state, challenges, potentials and way forward. In Proc. the 20th Int. Conf. Automation and Computing, September 2014, pp.176-181.Qi L. Research on intelligent transportation system technologies and applications. In Proc. Workshop on Power Electronics and Intelligent Transportation System, August 2008, pp.529-531.Gozalvez J. First Google’s Android phone launched [Mobile Radio]. IEEE Vehicular Technology Magazine, 2008, 3(4): 3-69.Haklay M,Weber P. OpenStreetMap: User-generated street maps. IEEE Pervasive Computing, 2008, 7(4): 12-18.Hadiwardoyo S A, Patra S, Calafate C T, Cano J C, Manzoni P. An Android ITS driving safety application based on vehicle-to-vehicle (V2V) communications. In Proc. the 26th Int. Conf. Computer Communication and Networks, July 31-August 3, 2017.Eriksson J, Balakrishnan H, Madden S. Cabernet: Vehicular content delivery using WiFi. In Proc. the 14th ACM Int. Conf. Mobile Computing and Networking, September 2008, pp.199-210.Gerla M, Weng J T, Giordano E, Pau G. Vehicular testbeds-validating models and protocols before large scale deployment. In Proc. Int. Conf. Computing Networking and Communications, January 30-February 2, 2012, pp.665-669.Wahlström J, Skog I, Händel P. Smartphone-based vehicle telematics: A ten-year anniversary. IEEE Trans. Intelligent Transportation Systems, 2017, 18(10): 2802-2825.Whipple J, Arensman W, Boler M S. A public safety application of GPS-enabled smartphones and the Android operating system. In Proc. IEEE Int. Conf. Systems Man and Cybernetics, October 2009, pp.2059-2061.Meseguer J E, Calafate C T, Cano J C, Manzoni P. DrivingStyles: A smartphone application to assess driver behavior. In Proc. IEEE Symp. Computers and Communications, July 2013, pp.000535-000540.You C W, Lane N D, Chen F L, Wang R, Chen Z Y, Bao T J, Montes-De-Oca M, Cheng Y T, Lin M, Torresani L, Campbell A T. CarSafe app: Alerting drowsy and distracted drivers using dual cameras on smartphones. In Proc. the 11th Annual Int. Conf. Mobile Systems Applications and Services, June 2013, pp.461-462.Patra S, Arnanz J H, Calafate C T, Cano J C, Manzoni P. EYES: A novel overtaking assistance system for vehicular networks. In Proc. the 14th Int. Conf. Ad-Hoc Networks and Wireless, June 2015, pp.375-389.Togneri M C, Deriaz M. On-board navigation system for smartphones. In Proc. Int. Conf. Indoor Positioning and Indoor Navigation, October 2013.Dancu A, Franjcic Z, Fjeld M. Smart flashlight: Map navigation using a bike-mounted projector. In Proc. the SIGCHI Conf. Human Factors in Computing Systems, April 2014, pp.3627-3630.Yamabe T, Ikegami S, Ishizaki A, Kitagami S, Kiyohara R. Car navigation user interface based on a smartphone. In Proc. the 7th Int. Conf. Mobile Computing and Ubiquitous Networking, January 2014, pp.85-86.Matsuyama S, Yamabe T, Takahashi N, Kiyohara R. Intelligent user interface of smartphones for on-vehicle information devices. Procedia Computer Science, 2014, 35: 1635-1643.Kovacevic B, Kovacevic M, Maruna T, Papp I. A java application programming interface for in-vehicle infotainment devices. IEEE Trans. Consumer Electronics, 2017, 63(1): 68-76.Liu R L, Liu H Z, Kwak D, Xiang Y, Borcea C, Nath B, Iftode L. Themis: A participatory navigation system for balanced traffic routing. In Proc. IEEE Vehicular Networking Conf., December 2014, pp.159-166.Liu R L, Liu H Z, Kwak D, Xiang Y, Borcea C, Nath B, Iftode L. Balanced traffic routing: Design, implementation, and evaluation. Ad Hoc Networks, 2016, 37: 14-28.Vochin M, Zoican S, Borcoci E. Intelligent system for vehicle navigation assistance. In Proc. World Conf. Information Systems and Technologies, April 2017, pp.142-148.Sha W J, Kwak D, Nath B, Iftode L. Social vehicle navigation: Integrating shared driving experience into vehicle navigation. In Proc. the 14th Workshop on Mobile Computing Systems and Applications, February 2013, Article No. 16.Kwak D, Liu R L, Kim D, Nath B, Iftode L. Seeing is believing: Sharing real-time visual traffic information via vehicular clouds. IEEE Access, 2016, 4: 3617-3631.Djajadi A, Putra R J. Inter-cars safety communication system based on Android smartphone. In Proc. IEEE Conf. Open Systems, October 2014, pp.12-17.Dorairaj P, Mohammed A, Grbic N. Location-Aware services using Android mobile operating platform for safety, emergency and health applications. In Mobile Health, Adibi S (ed.), Springer, 2015, pp.283-298.Dorairaj P, Ramamoorthy S, Ramalingam A K. Emergency based remote collateral tracking system using Google’s Android mobile platform. In Advances in Computer Science Engineering & Applications, Wyld D C, Zizka J, Nagamalai D (eds.), Springer, 2012, pp.391-403.Zulkafi A Z, Basri S, Jung L T, Ahmad R. Android based car alert system. In Proc. the 3rd Int. Conf. Computer and Information Sciences, August 2016, pp.501-506.Tornell S M, Calafate C T, Cano J C, Manzoni P, Fogue M, Martinez F J. Evaluating the feasibility of using smartphones for ITS safety applications. In Proc. the 77th IEEE Vehicular Technology Conf., June 2013.Tornell S M, Patra S, Calafate C T, Cano J C, Manzoni P. GRCBox: Extending smartphone connectivity in vehicular networks. International Journal of Distributed Sensor Networks, 2015, 2015: Article No. 5.Mirkovic J, Dietrich S, Dittrich D, Reiher P. Internet Denial of Service: Attack and Defense Mechanisms (Radia Perlman Computer Networking and Security). Prentice Hall PTR, 2004.Chen S, Xu J, Sezer E C, Gauriar P, Iyer R K. Non-control-data attacks are realistic threats. In Proc. the 14th Conf. USENIX Security Symp., July 31-August 5, 2005.Fung C K, Lee M C. A denial-of-service resistant public-key authentication and key establishment protocol. In Proc. the 21st IEEE Int. Performance Computing and Communications Conf., April 2002, pp.171-178.Abadi M, Budiu M, Erlingsson Ú, Ligatti J. Control-flow integrity. In Proc. the 12th ACM Conf. Computer and Communications Security, November 2005, pp.340-353

Functionalized Cyclopentenones with Low Electrophilic Character as Anticancer Agents

In this study were synthesized non-Michael acceptor cyclopentenones (CP) from biomass derivative furfural as anticancer agents. Cyclic enones, both from natural sources and synthetic analogues, have been described as cytotoxic agents. Most of these agents were unsuccessful in becoming valuable therapeutic agents due to toxicity problems derived from unselective critical biomacromolecule alkylation. This may be caused by Michael addition to the enone system. Ab initio studies revealed that 2,4-substituted CPs are less prone to Michael additions, and as such were tested three families of those derivatives. We prepare the new CPs from furfural through a tandem furan ring opening/nazarov electrocyclization and further functionalization. Experimentally the 2,4-substituted CPs exhibited no reactivity towards sulphur nucleophiles, while maintaining cytotoxicity against HT-29, MCF-7, NCI-H460, HCT-116 and MDA-MB 231 cells lines. Moreover, the selected CP are non-toxic against healthy HEK 293T cell lines and present proper calculated drug-like properties

Functional Locomotor Consequences of Uneven Forefeet for Trot Symmetry in Individual Riding Horses

ABSTRACT: Left-right symmetrical distal limb conformation can be an important prerequisite for a successful performance, and it is often hypothesized that asymmetric or uneven feet are important enhancing factors for the development of lameness. On a population level, it has been demonstrated that uneven footed horses are retiring earlier from elite level competition, but the biomechanical consequences are not yet known. The objectives of this study were to compare the functional locomotor asymmetries of horses with uneven to those with even feet. Hoof kinetics and distal limb kinematics were collected from horses (n = 34) at trot. Dorsal hoof wall angle was used to classify horses as even or uneven (1.5° difference between forefeet respectively) and individual feet as flat (55°). Functional kinetic parameters were compared between even and uneven forefeet using MANOVA followed by ANOVA. The relative influences of differences in hoof angle between the forefeet and of absolute hoof angle on functional parameters were analysed using multiple regression analysis (P<0.05). In horses with uneven feet, the side with the flatter foot showed a significantly larger maximal horizontal braking and vertical ground reaction force, a larger vertical fetlock displacement and a suppler fetlock spring. The foot with a steeper hoof angle was linearly correlated with an earlier braking-propulsion transition. The conformational differences between both forefeet were more important for loading characteristics than the individual foot conformation of each individual horse. The differences in vertical force and braking force between uneven forefeet could imply either an asymmetrical loading pattern without a pathological component or a subclinical lameness as a result of a pathological development in the steeper foot

Time to harmonize dengue nomenclature and classification

Dengue virus (DENV) is estimated to cause 390 million infections per year worldwide. A quarter of these infections manifest clinically and are associated with a morbidity and mortality that put a significant burden on the affected regions. Reports of increased frequency, intensity, and extended geographical range of outbreaks highlight the virus's ongoing global spread. Persistent transmission in endemic areas and the emergence in territories formerly devoid of transmission have shaped DENV's current genetic diversity and divergence. This genetic layout is hierarchically organized in serotypes, genotypes, and sub-genotypic clades. While serotypes are well defined, the genotype nomenclature and classification system lack consistency, which complicates a broader analysis of their clinical and epidemiological characteristics. We identify five key challenges: (1) Currently, there is no formal definition of a DENV genotype; (2) Two different nomenclature systems are used in parallel, which causes significant confusion; (3) A standardized classification procedure is lacking so far; (4) No formal definition of sub-genotypic clades is in place; (5) There is no consensus on how to report antigenic diversity. Therefore, we believe that the time is right to re-evaluate DENV genetic diversity in an essential effort to provide harmonization across DENV studies.publishersversionpublishe

Conditional embryonic lethality to improve the sterile insect technique in Ceratitis capitata (Diptera: Tephritidae)

<p>Abstract</p> <p>Background</p> <p>The sterile insect technique (SIT) is an environment-friendly method used in area-wide pest management of the Mediterranean fruit fly <it>Ceratitis capitata </it>(Wiedemann; Diptera: Tephritidae). Ionizing radiation used to generate reproductive sterility in the mass-reared populations before release leads to reduction of competitiveness.</p> <p>Results</p> <p>Here, we present a first alternative reproductive sterility system for medfly based on transgenic embryonic lethality. This system is dependent on newly isolated medfly promoter/enhancer elements of cellularization-specifically-expressed genes. These elements act differently in expression strength and their ability to drive lethal effector gene activation. Moreover, position effects strongly influence the efficiency of the system. Out of 60 combinations of driver and effector construct integrations, several lines resulted in larval and pupal lethality with one line showing complete embryonic lethality. This line was highly competitive to wildtype medfly in laboratory and field cage tests.</p> <p>Conclusion</p> <p>The high competitiveness of the transgenic lines and the achieved 100% embryonic lethality causing reproductive sterility without the need of irradiation can improve the efficacy of operational medfly SIT programs.</p

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice

Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes