397 research outputs found

    Inter- and intra-observer reliability of the Baumann angle of the humerus in children with supracondylar humeral fractures

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    The Baumann angle of the humerus has been commonly used as an outcome measure for supracondylar fractures in children. However, there is limited or no information about the reliability of this measurement. The purpose of this study was to determine the inter-observer reliability (IEOR) and intra-observer reliability (IAOR) of the Baumann angle of the humerus. The Baumann angle of the humerus was measured by five observers on the anteroposterior radiographs of 35 children’s elbows, all of which had sustained a nondisplaced supracondylar humeral fracture. The values of IEOR and IAOR were calculated using a Pearson coefficient of correlation. Ranges of differences in the measurement of the Baumann angle of the humerus were established, and the percentage of agreement between observers was then calculated using those ranges. The Baumann angle of the humerus is a simple, repeatable and reliable measurement that can be used for the determination of the outcome of supracondylar humeral fractures in the paediatric population. An excellent IEOR was found for the measurement of the Baumann angle (r = 0.78, p = 0.0001). When the difference between observers in the reported measurement of the Baumann’s angle was calculated to be within seven degrees of each other, at least four of the five observers agreed 100% of the time. Similarly, excellent values of IAOR were found for the measurement of the Baumann’s angle (r = 0.80, p = 0.0001). Level of evidence for this study was III

    Cytokine Production but Lack of Proliferation in Peripheral Blood Mononuclear Cells from Chronic Chagas' Disease Cardiomyopathy Patients in Response to T. cruzi Ribosomal P Proteins

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    Background:Trypanosoma cruzi ribosomal P proteins, P2β and P0, induce high levels of antibodies in patients with chronic Chagas' disease Cardiomyopathy (CCC). It is well known that these antibodies alter the beating rate of cardiomyocytes and provoke apoptosis by their interaction with β1-adrenergic and M2-muscarinic cardiac receptors. Based on these findings, we decided to study the cellular immune response to these proteins in CCC patients compared to non-infected individuals.Methodology/Principal findings:We evaluated proliferation, presence of surface activation markers and cytokine production in peripheral blood mononuclear cells (PBMC) stimulated with P2β, the C-terminal portion of P0 (CP0) proteins and T. cruzi lysate from CCC patients predominantly infected with TcVI lineage. PBMC from CCC patients cultured with P2β or CP0 proteins, failed to proliferate and express CD25 and HLA-DR on T cell populations. However, multiplex cytokine assays showed that these antigens triggered higher secretion of IL-10, TNF-α and GM-CSF by PBMC as well as both CD4+ and CD8+ T cells subsets of CCC subjects. Upon T. cruzi lysate stimulation, PBMC from CCC patients not only proliferated but also became activated within the context of Th1 response. Interestingly, T. cruzi lysate was also able to induce the secretion of GM-CSF by CD4+ or CD8+ T cells.Conclusions/Significance:Our results showed that although the lack of PBMC proliferation in CCC patients in response to ribosomal P proteins, the detection of IL-10, TNF-α and GM-CSF suggests that specific T cells could have both immunoregulatory and pro-inflammatory potential, which might modulate the immune response in Chagas' disease. Furthermore, it was possible to demonstrate for the first time that GM-CSF was produced by PBMC of CCC patients in response not only to recombinant ribosomal P proteins but also to parasite lysate, suggesting the value of this cytokine to evaluate T cells responses in T. cruzi infection.Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Atienza, Augusto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Perez Prados, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Buying, Alcinette. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Balouz, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Buscaglia, Carlos Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Santos, Radleigh. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Bonato, Ricardo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Chiale, Pablo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Pinilla, Clemencia. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Judkowski, Valeria A.. Torrey Pines Institute for Molecular Studies; Estados UnidosFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

    What Should Vaccine Developers Ask? Simulation of the Effectiveness of Malaria Vaccines

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    A number of different malaria vaccine candidates are currently in pre-clinical or clinical development. Even though they vary greatly in their characteristics, it is unlikely that any of them will provide long-lasting sterilizing immunity against the malaria parasite. There is great uncertainty about what the minimal vaccine profile should be before registration is worthwhile; how to allocate resources between different candidates with different profiles; which candidates to consider combining; and what deployment strategies to consider.We use previously published stochastic simulation models, calibrated against extensive epidemiological data, to make quantitative predictions of the population effects of malaria vaccines on malaria transmission, morbidity and mortality. The models are fitted and simulations obtained via volunteer computing. We consider a range of endemic malaria settings with deployment of vaccines via the Expanded program on immunization (EPI), with and without additional booster doses, and also via 5-yearly mass campaigns for a range of coverages. The simulation scenarios account for the dynamic effects of natural and vaccine induced immunity, for treatment of clinical episodes, and for births, ageing and deaths in the cohort. Simulated pre-erythrocytic vaccines have greatest benefits in low endemic settings (<EIR of 10.5) where between 12% and 14% of all deaths are averted when initial efficacy is 50%. In some high transmission scenarios (>EIR of 84) PEV may lead to increased incidence of severe disease in the long term, if efficacy is moderate to low (<70%). Blood stage vaccines (BSV) are most useful in high transmission settings, and are comparable to PEV for low transmission settings. Combinations of PEV and BSV generally perform little better than the best of the contributing components. A minimum half-life of protection of 2–3 years appears to be a precondition for substantial epidemiological effects. Herd immunity effects can be achieved with even moderately effective (>20%) malaria vaccines (either PEV or BSV) when deployed through mass campaigns targeting all age-groups as well as EPI, and especially if combined with highly efficacious transmission-blocking components.We present for the first time a stochastic simulation approach to compare likely effects on morbidity, mortality and transmission of a range of malaria vaccines and vaccine combinations in realistic epidemiological and health systems settings. The results raise several issues for vaccine clinical development, in particular appropriateness of vaccine types for different transmission settings; the need to assess transmission to the vector and duration of protection; and the importance of deployment additional to the EPI, which again may make the issue of number of doses required more critical. To test the validity and robustness of our conclusions there is a need for further modeling (and, of course, field research) using alternative formulations for both natural and vaccine induced immunity. Evaluation of alternative deployment strategies outside EPI needs to consider the operational implications of different approaches to mass vaccination

    Comparative Microsatellite Typing of New World Leishmania infantum Reveals Low Heterogeneity among Populations and Its Recent Old World Origin

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    Leishmania infantum (syn. L. chagasi) is the causative agent of visceral leishmaniasis (VL) in the New World (NW) with endemic regions extending from southern USA to northern Argentina. The two hypotheses about the origin of VL in the NW suggest (1) recent importation of L. infantum from the Old World (OW), or (2) an indigenous origin and a distinct taxonomic rank for the NW parasite. Multilocus microsatellite typing was applied in a survey of 98 L. infantum isolates from different NW foci. The microsatellite profiles obtained were compared to those of 308 L. infantum and 20 L. donovani strains from OW countries previously assigned to well-defined populations. Two main populations were identified for both NW and OW L. infantum. Most of the NW strains belonged to population 1, which corresponded to the OW MON-1 population. However, the NW population was much more homogeneous. A second, more heterogeneous, population comprised most Caribbean strains and corresponded to the OW non-MON-1 population. All Brazilian L. infantum strains belonged to population 1, although they represented 61% of the sample and originated from 9 states. Population analysis including the OW L. infantum populations indicated that the NW strains were more similar to MON-1 and non-MON-1 sub-populations of L. infantum from southwest Europe, than to any other OW sub-population. Moreover, similarity between NW and Southwest European L. infantum was higher than between OW L. infantum from distinct parts of the Mediterranean region, Middle East and Central Asia. No correlation was found between NW L. infantum genotypes and clinical picture or host background. This study represents the first continent-wide analysis of NW L. infantum population structure. It confirmed that the agent of VL in the NW is L. infantum and that the parasite has been recently imported multiple times to the NW from southwest Europe

    The prevalence of exposure to domestic violence and the factors associated with co-occurrence of psychological and physical violence exposure: a sample from primary care patients

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    <p>Abstract</p> <p>Background</p> <p>Since many health problems are associated with abuse and neglect at all ages, domestic violence victims may be considered as a group of primary care patients in need of special attention.</p> <p>Methods</p> <p>The aim of this multi-centre study was to assess the prevalence of domestic violence in primary care patients, and to identify those factors which influence the co-occurrence of psychological and physical violence exposure and their consequences (physical, sexual and reproductive and psychological) as obtained from medical records.</p> <p>A study was carried out in 28 family practices in Slovenia in 2009. Twenty-eight family physicians approached every fifth family practice attendee, regardless of gender, to be interviewed about their exposure to domestic violence and asked to specify the perpetrator and the frequency. Out of 840 patients asked, 829 individuals, 61.0% women (n = 506) and 39.0% men (n = 323) were assessed (98.7% response rate). They represented a randomised sample of general practice attendees, aged 18 years and above, who had visited their physician for health problems and who were given a physical examination. Visits for administrative purposes were excluded.</p> <p>Multivariate binary logistic regression analysis was used to determine the factors associated with exposure to both psychological and physical violence.</p> <p>Results</p> <p>Of 829 patients, 15.3% reported some type of domestic violence experienced during the previous five years; 5.9% reported physical and 9.4% psychological violence; of these 19.2% of men and 80.8% of women had been exposed to psychological violence, while 22.4% of men and 77.6% of women had been exposed to physical violence. The domestic violence victims were mostly women (p < 0.001) aged up to 35 years (p = 0.001). Exposure to psychological violence was more prevalent than exposure to physical violence. Of the women, 20.0% were exposed to either type of violence, compared to 8.0% of male participants, who reported they were rarely exposed to physical violence, while women reported often or constant exposure to physical violence. Their partners were mostly the perpetrators of domestic violence towards women, while amongst men the perpetrators were mostly other family members.</p> <p>In univariate analysis female gender was shown to be a risk factor for domestic violence exposure. Regression modelling, explaining 40% of the variance, extracted two factors associated with psychological and physical violence exposure: the abuse of alcohol in the patient (OR 4.7; 95% CI 1.54-14.45) and their unemployment (OR 13.3; 95% CI 1.53-116.45).</p> <p>Conclusions</p> <p>As far as the study design permits, the identified factors associated with both psychological and physical violence exposure could serve as determinants to raise family physicians' awareness when exploring the prevalence of domestic violence. The results of previous research, showing at least 15% prevalence of exposure to domestic violence among primary care patients in Slovenia, and the female gender as a risk factor, were confirmed.</p

    Visualisation of Leishmania donovani Fluorescent Hybrids during Early Stage Development in the Sand Fly Vector

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    hybrids were produced by co-infecting sand flies with two strains carrying different drug resistance markers. However, the location and timing of hybridisation events in sand flies has not been described. strains carrying hygromycin or neomycin resistance genes and red or green fluorescent markers. Fed females were dissected at different times post bloodmeal (PBM) and examined by fluorescent microscopy or fluorescent activated cell sorting (FACS) followed by confocal microscopy. In mixed infections strains LEM3804 and Gebre-1 reached the cardia and stomodeal valves more rapidly than strains LEM4265 and LV9. Hybrids unequivocally expressing both red and green fluorescence were seen in single flies of both vectors tested, co-infected with LEM4265 and Gebre-1. The hybrids were present as short (procyclic) promastigotes 2 days PBM in the semi-digested blood in the endoperitrophic space. Recovery of a clearly co-expressing hybrid was also achieved by FACS. However, hybrids could not sustain growth in vitro. has profound epidemiological significance, because it facilitates the emergence and spread of new phenotypic traits

    Markov dynamics as a zooming lens for multiscale community detection: non clique-like communities and the field-of-view limit

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    In recent years, there has been a surge of interest in community detection algorithms for complex networks. A variety of computational heuristics, some with a long history, have been proposed for the identification of communities or, alternatively, of good graph partitions. In most cases, the algorithms maximize a particular objective function, thereby finding the `right' split into communities. Although a thorough comparison of algorithms is still lacking, there has been an effort to design benchmarks, i.e., random graph models with known community structure against which algorithms can be evaluated. However, popular community detection methods and benchmarks normally assume an implicit notion of community based on clique-like subgraphs, a form of community structure that is not always characteristic of real networks. Specifically, networks that emerge from geometric constraints can have natural non clique-like substructures with large effective diameters, which can be interpreted as long-range communities. In this work, we show that long-range communities escape detection by popular methods, which are blinded by a restricted `field-of-view' limit, an intrinsic upper scale on the communities they can detect. The field-of-view limit means that long-range communities tend to be overpartitioned. We show how by adopting a dynamical perspective towards community detection (Delvenne et al. (2010) PNAS:107: 12755-12760; Lambiotte et al. (2008) arXiv:0812.1770), in which the evolution of a Markov process on the graph is used as a zooming lens over the structure of the network at all scales, one can detect both clique- or non clique-like communities without imposing an upper scale to the detection. Consequently, the performance of algorithms on inherently low-diameter, clique-like benchmarks may not always be indicative of equally good results in real networks with local, sparser connectivity.Comment: 20 pages, 6 figure

    The Influence of Radiographic Phenotype and Smoking Status on Peripheral Blood Biomarker Patterns in Chronic Obstructive Pulmonary Disease

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    Background: Chronic obstructive pulmonary disease (COPD) is characterized by both airway remodeling and parenchymal destruction. The identification of unique biomarker patterns associated with airway dominant versus parenchymal dominant patterns would support the existence of unique phenotypes representing independent biologic processes. A cross-sectional study was performed to examine the association of serum biomarkers with radiographic airway and parenchymal phenotypes of COPD. Methodology/Principal Findings: Serum from 234 subjects enrolled in a CT screening cohort was analyzed for 33 cytokines and growth factors using a multiplex protein array. The association of serum markers with forced expiratory volume in one second percent predicted (FEV1%) and quantitative CT measurements of airway thickening and emphysema was assessed with and without stratification for current smoking status. Significant associations were found with several serum inflammatory proteins and measurements of FEV1%, airway thickening, and parenchymal emphysema independent of smoking status. The association of select analytes with airway thickening and emphysema was independent of FEV1%. Furthermore, the relationship between other inflammatory markers and measurements of physiologic obstruction or airway thickening was dependent on current smoking status. Conclusions/Significance: Airway and parenchymal phenotypes of COPD are associated with unique systemic serum biomarker profiles. Serum biomarker patterns may provide a more precise classification of the COPD syndrome, provide insights into disease pathogenesis and identify targets for novel patient-specific biological therapies. © 2009 Bon et al
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