2,334 research outputs found
Imaging of Infections: switch on the light:Development and evaluation of novel tracers for optical molecular fluorescence imaging
Despite major advances in medicine and patient care, infections remain a great threat to human health. This is exacerbated by increasing rates of surgical interventions and the rapid increment of antimicrobial resistance that poses challenges for effective therapeutic interventions. Current diagnostic tools for infection detection, such as molecular and culturing techniques, are time-consuming and rely on the collection of clinical samples which is not always possible. Furthermore, there is a great need for improvement of the diagnosis and treatment of infections at early stages. In this context, imaging is an attractive approach to localize sites of infection. However, traditional imaging modalities, such as radiography, are non-specific and unable to distinguish infection from sterile inflammation. To solve this specificity challenge, targeted molecular imaging, based on the use of specific tracers, has emerged. This approach enables specific, non-invasive and real-time visualization of causative pathogens. Accordingly, the aim of the research described in this PhD thesis was to develop novel tracers for targeted fluorescence imaging of infections, and to evaluate optical fluorescence imaging for the detection of infections at early stages. To achieve these objectives, the evaluation of novel fluorescent tracers was performed through in vitro, ex vivo and in vivo analyses following various clinical settings, such as fluorescence-guided arthroscopy or fluorescence-guided bronchoscopy. The results demonstrate the potential of targeted fluorescence imaging for early detection of Gram-positive bacterial and fungal infections, and highlight the importance of targeted imaging to accelerate the time-to-result between diagnosis and treatment, which is crucial for successful infection management
New In Situ-Generated Polymer-Iodine Complexes with Broad-Spectrum Antimicrobial Activity
Iodine-containing systems show broad antiseptic properties that can be an invaluable tool in controlling infections in humans and animals. Here, we describe the first proof-of-concept studies on biocidal active polyamide- and polyurethane-iodine complexes that are produced in situ directly during the fabrication and/or polymerization process at laboratory and commercially relevant scales. These polymer-iodine materials are active against a broad range of microorganisms, including bacteria and fungi. It is suggested that the ease of manufacture and subsequent commercialization make said systems especially suited for applications as base materials for medical devices to reduce infection risks and control the spread of pathogens. IMPORTANCE Infectious diseases are of mounting medical and public concern. A major contributor to this trend is the proliferation of medical implants, which are inherently vulnerable to microbial contamination and the subsequent onset of hospital-acquired infections. Moreover, implant-associated infections in humans are often difficult to diagnose and treat and are associated with substantial health care costs. Here, we present the development of biocidal active polyamide- and polyurethane-iodine complexes that are generated in situ during fabrication. We show that the excellent antiseptic properties of water-soluble povidone-iodine can be similarly realized in water-insoluble engineering plastics, specifically polyamide- and polyurethane-iodine. These complexes have inherent biocidal activity against major pathogenic bacteria and fungi
A Facile and Reproducible Synthesis of Near-Infrared Fluorescent Conjugates with Small Targeting Molecules for Microbial Infection Imaging
Optical imaging of microbial infections, based on the detection of targeted fluorescent probes, offers high sensitivity and resolution with a relatively simple and portable setup. As the absorbance of near-infrared (NIR) light by human tissues is minimal, using respective tracers, such as IRdye800CW, enables imaging deeper target sites in the body. Herein, we present a general strategy for the conjugation of IRdye800CW and IRdye700DX to small molecules (vancomycin and amphotericin B) to provide conjugates targeted toward bacterial and fungal infections for optical imaging and photodynamic therapy. In particular, we present how the use of coupling agents (such as HBTU or HATU) leads to high yields (over 50%) in the reactions of amines and IRDye-NHS esters and how precipitation can be used as a convenient purification strategy to remove excess of the targeting molecule after the reaction. The high selectivity of the synthesized model compound Vanco-800CW has been proven in vitro, and the development of analogous agents opens up new possibilities for diagnostic and theranostic purposes. In times of increasing microbial resistance, this research gives us access to a platform of new fluorescent tracers for the imaging of infections, enabling early diagnosis and respective treatment
Double trouble:Bacillus depends on a functional Tat machinery to avoid severe oxidative stress and starvation upon entry into a NaCl-depleted environment
The widely conserved twin-arginine translocases (Tat) allow the transport of fully folded cofactor-containing proteins across biological membranes. In doing so, these translocases serve different biological functions ranging from energy conversion to cell division. In the Gram-positive soil bacterium Bacillus subtilis, the Tat machinery is essential for effective growth in media lacking iron or NaCl. It was previously shown that this phenomenon relates to the Tat-dependent export of the heme-containing peroxidase EfeB, which converts Fe2+ to Fe3+ at the expense of hydrogen peroxide. However, the reasons why the majority of tat mutant bacteria perish upon dilution in NaCl-deprived medium and how, after several hours, a sub-population adapts to this condition was unknown. Here we show that, upon growth in the absence of NaCl, the bacteria face two major problems, namely severe oxidative stress at the membrane and starvation leading to death. The tat mutant cells can overcome these challenges if they are fed with arginine, which implies that severe arginine depletion is a major cause of death and resumed arginine synthesis permits their survival. Altogether, our findings show that the Tat system of B. subtilis is needed to preclude severe oxidative stress and starvation upon sudden drops in the environmental Na+ concentration as caused by flooding or rain
Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model:a feasibility study for clinical diagnosis of prosthetic joint infections
Purpose Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints. Methods Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses. Results We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW. Conclusion The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection
Comparison of two fluorescent probes in preclinical non-invasive imaging and image-guided debridement surgery of Staphylococcal biofilm implant infections
Abstract Implant-associated infections are challenging to diagnose and treat. Fluorescent probes have been heralded as a technologic advancement that can improve our ability to non-invasively identify infecting organisms, as well as guide the inexact procedure of surgical debridement. This studyâs purpose was to compare two fluorescent probes for their ability to localize Staphylococcus aureus biofilm infections on spinal implants utilizing noninvasive optical imaging, then assessing the broader applicability of the more successful probe in other infection animal models. This was followed by real-time, fluorescence image-guided surgery to facilitate debridement of infected tissue. The two probe candidates, a labelled antibiotic that targets peptidoglycan (Vanco-800CW), and the other, a labelled antibody targeting the immunodominant Staphylococcal antigen A (1D9-680), were injected into mice with spine implant infections. Mice were then imaged noninvasively with near infrared fluorescent imaging at wavelengths corresponding to the two probe candidates. Both probes localized to the infection, with the 1D9-680 probe showing greater fidelity over time. The 1D9-680 probe was then tested in mouse models of shoulder implant and allograft infection, demonstrating its broader applicability. Finally, an image-guided surgery system which superimposes fluorescent signals over analog, real-time, tissue images was employed to facilitate debridement of fluorescent-labelled bacteria
Soil organic carbon stocks in native forest of Argentina: a useful surrogate for mitigation and conservation planning under climate variability
Background The nationally determined contribution (NDC) presented by Argentina within the framework of the Paris Agreement is aligned with the decisions made in the context of the United Nations Framework Convention on Climate Change (UNFCCC) on the reduction of emissions derived from deforestation and forest degradation, as well as forest carbon conservation (REDD+). In addition, climate change constitutes one of the greatest threats to forest biodiversity and ecosystem services. However, the soil organic carbon (SOC) stocks of native forests have not been incorporated into the Forest Reference Emission Levels calculations and for conservation planning under climate variability due to a lack of information. The objectives of this study were: (i) to model SOC stocks to 30 cm of native forests at a national scale using climatic, topographic and vegetation as predictor variables, and (ii) to relate SOC stocks with spatialâtemporal remotely sensed indices to determine biodiversity conservation concerns due to threats from high interâannual climate variability. Methods We used 1040 forest soil samples (0â30 cm) to generate spatially explicit estimates of SOC native forests in Argentina at a spatial resolution of approximately 200 m. We selected 52 potential predictive environmental covariates, which represent key factors for the spatial distribution of SOC. All covariate maps were uploaded to the Google
Earth Engine cloudâbased computing platform for subsequent modelling. To determine the biodiversity threats from high interâannual climate variability, we employed the spatialâtemporal satelliteâderived indices based on Enhanced Vegetation Index (EVI) and land surface temperature (LST) images from Landsat imagery. Results SOC model (0â30 cm depth) prediction accounted for 69% of the variation of this soil property
across the whole native forest coverage in Argentina. Total mean SOC stock reached 2.81 Pg C (2.71â2.84 Pg C with a probability of 90%) for a total area of 460,790 km2, where Chaco forests represented 58.4% of total SOC stored, followed by Andean Patagonian forests (16.7%) and Espinal forests (10.0%). SOC stock model was fitted as a function of regional climate, which greatly influenced forest ecosystems, including precipitation (annual mean precipitation and precipitation of warmest quarter) and temperature (day land surface temperature, seasonality, maximum temperature of warmest month, month of maximum temperature, night land surface temperature, and monthly minimum temperature). Biodiversity was influenced by the SOC levels and the forest regions. Conclusions In the framework of the Kyoto Protocol and REDD+, information derived in the present work from the estimate of SOC in native forests can be incorporated into the annual National Inventory Report of Argentina
to assist forest management proposals. It also gives insight into how native forests can be more resilient to reduce the impact of biodiversity loss.EEA Santa CruzFil: Peri, Pablo Luis. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Gaitan, Juan JosĂ©. Universidad Nacional de LujĂĄn. Buenos Aires; Argentina.Fil: Gaitan, Juan JosĂ©. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Mastrangelo, Matias Enrique. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Mastrangelo, Matias Enrique. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Nosetto, Marcelo Daniel. Universidad Nacional de San Luis. Instituto de MatemĂĄtica Aplicada San Luis. Grupo de Estudios Ambientales; Argentina.Fil: Nosetto, Marcelo Daniel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Villagra, Pablo Eugenio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales (IANIGLA); Argentina.Fil: Villagra, Pablo Eugenio. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Balducci, Ezequiel. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Yuto; Argentina.Fil: Pinazo, MartĂn Alcides. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Montecarlo; Argentina.Fil: Eclesia, Roxana Paola. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria ParanĂĄ; Argentina.Fil: Von Wallis, Alejandra. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Montecarlo; Argentina.Fil: Villarino, SebastiĂĄn. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Villarino, SebastiĂĄn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Alaggia, Francisco Guillermo. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Alaggia, Francisco Guillermo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Gonzalez-Polo, Marina. Universidad Nacional del Comahue; Argentina.Fil: Gonzalez-Polo, Marina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. INIBIOMA; Argentina.Fil: Manrique, Silvana M. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Investigaciones en EnergĂa No Convencional. CCT SaltaâJujuy; Argentina.Fil: Meglioli, Pablo A. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales (IANIGLA); Argentina.Fil: Meglioli, Pablo A. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: RodrĂguezâSouilla, JuliĂĄn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro Austral de Investigaciones CientĂficas (CADIC); Argentina.Fil: MĂłnaco, MartĂn H. Ministerio de Ambiente y Desarrollo Sostenible. DirecciĂłn Nacional de Bosques; Argentina.Fil: Chaves, Jimena Elizabeth. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro Austral de Investigaciones CientĂficas (CADIC); Argentina.Fil: Medina, Ariel. Ministerio de Ambiente y Desarrollo Sostenible. DirecciĂłn Nacional de Bosques; Argentina.Fil: Gasparri, Ignacio. Universidad Nacional de TucumĂĄn. Instituto de EcologĂa Regional; Argentina.Fil: Gasparri, Ignacio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Alvarez Arnesi, Eugenio. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina.Fil: Alvarez Arnesi, Eugenio. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Santa Fe; Argentina.Fil: Barral, MarĂa Paula. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias. Grupo de Estudio de Agroecosistemas y Paisajes Rurales; Argentina.Fil: Barral, MarĂa Paula. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Von MĂŒller, Axel. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Esquel Argentina.Fil: Pahr, Norberto Manuel. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Montecarlo; Argentina.Fil: Uribe EchevarrĂa, Josefina. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria QuimilĂ; Argentina.Fil: Fernandez, Pedro Sebastian. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria FamaillĂĄ; Argentina.Fil: Fernandez, Pedro Sebastian. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de EcologĂa Regional; Argentina.Fil: Morsucci, Marina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales (IANIGLA); Argentina.Fil: Morsucci, Marina. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Lopez, Dardo Ruben. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Lopez, Dardo Ruben. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Cellini, Juan Manuel. Universidad Nacional de la Plata (UNLP). Facultad de Ciencias Naturales y Museo. Laboratorio de Investigaciones en Maderas; Argentina.Fil: Alvarez, Leandro M. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales (IANIGLA); Argentina.Fil: Alvarez, Leandro M. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: Barberis, Ignacio MartĂn. Universidad Nacional de Rosario. Instituto de Investigaciones en Ciencias Agrarias de Rosario; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Santa Fe; Argentina.Fil: Barberis, Ignacio MartĂn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico Santa Fe; Argentina.Fil: Colomb, HernĂĄn Pablo. Ministerio de Ambiente y Desarrollo Sostenible. DirecciĂłn Nacional de Bosques; Argentina.Fil: Colomb, HernĂĄn. AdministraciĂłn de Parques Nacionales (APN). Parque Nacional Los Alerces; Argentina.Fil: La Manna, Ludmila. Universidad Nacional de la Patagonia San Juan Bosco. Centro de Estudios Ambientales Integrados (CEAI); Argentina.Fil: La Manna, Ludmila. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Barbaro, Sebastian Ernesto. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Cerro Azul; Argentina.Fil: Blundo, Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de EcologĂa Regional; Argentina.Fil: Blundo, Cecilia. Universidad Nacional de TucumĂĄn. TucumĂĄn; Argentina.Fil: Sirimarco, Marina Ximena. Universidad Nacional de Mar del Plata. Grupo de Estudio de Agroecosistemas y Paisajes Rurales (GEAP); Argentina.Fil: Sirimarco, Marina Ximena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina.Fil: Cavallero, Laura. Instituto Nacional de TecnologĂa Agropecuaria (INTA). EstaciĂłn Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Zalazar, Gualberto. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto Argentino de NivologĂa, GlaciologĂa y Ciencias Ambientales (IANIGLA); Argentina.Fil: Zalazar, Gualberto. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias; Argentina.Fil: MartĂnez Pastur, Guillermo JosĂ©. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro Austral de Investigaciones CientĂficas (CADIC); Argentina
MĂ©todo epidemiolĂłgico
Tomado de la cubierta : "Manual de MĂ©todo EpidemiolĂłgico"El presente volumen incluye trece temas elaborados por diferentes autores, todos ellos expertos en salud pĂșblica y profesores de la Escuela Nacional de Sanidad, con la orientaciĂłn fundamental de servir de apoyo a la docencia del mĂ©todo epidemiolĂłgico. AsĂ, partiendo de la definiciĂłn de epidemiologĂa y de la descripciĂłn de sus usos potenciales, se describen los conceptos bĂĄsicos de este mĂ©todo cientĂfico, sus principales diseños de investigaciĂłn, los mĂ©todos bĂĄsicos de anĂĄlisis de datos, las tĂ©cnicas de control de sesgos y factores de confusiĂłn, las bases de la inferencia causal y los aspectos fundamentales de la epidemiologĂa clĂnica en el escenario actual
Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication
International audienceno abstrac
The Genome Sequence of the Grape Phylloxera Provides Insights into the Evolution, Adaptation, and Invasion Routes of an Iconic Pest
Background: Although native to North America, the invasion of the aphid-like grape phylloxera Daktulosphaira vitifoliae across the globe altered the course of grape cultivation. For the past 150âyears, viticulture relied on grafting-resistant North American Vitis species as rootstocks, thereby limiting genetic stocks tolerant to other stressors such as pathogens and climate change. Limited understanding of the insect genetics resulted in successive outbreaks across the globe when rootstocks failed. Here we report the 294-Mb genome of D. vitifoliae as a basic tool to understand host plant manipulation, nutritional endosymbiosis, and enhance global viticulture. Results: Using a combination of genome, RNA, and population resequencing, we found grape phylloxera showed high duplication rates since its common ancestor with aphids, but similarity in most metabolic genes, despite lacking obligate nutritional symbioses and feeding from parenchyma. Similarly, no enrichment occurred in development genes in relation to viviparity. However, phylloxera evolved >â2700 unique genes that resemble putative effectors and are active during feeding. Population sequencing revealed the global invasion began from the upper Mississippi River in North America, spread to Europe and from there to the rest of the world. Conclusions: The grape phylloxera genome reveals genetic architecture relative to the evolution of nutritional endosymbiosis, viviparity, and herbivory. The extraordinary expansion in effector genes also suggests novel adaptations to plant feeding and how insects induce complex plant phenotypes, for instance galls. Finally, our understanding of the origin of this invasive species and its genome provide genetics resources to alleviate rootstock bottlenecks restricting the advancement of viticulture
- âŠ