2,059 research outputs found

    Treatment of Buruli Ulcer

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    BU has long been treated by surgical resection. During the last two decades, it has become increasingly clear that antimicrobial treatment, first, using a combination of streptomycin 15 mg/kg i.m. and rifampin 10 mg/kg p.o. for 8 weeks, results in relapse-free cure in lesions &lt;10 cm cross-sectional diameter. Recently, a large clinical trial from Ghana and Benin showed that fully oral treatment—rifampin 10 mg/kg combined with clarithromycin—extended release, 15 mg/kg, also for 8 weeks, was equally effective but less toxic; none of the close to 300 study participants needed surgical resection, and only four had split skin grafts; sequelae were negligible. The use of other antimicrobials including fluoroquinolones has been shown to be effective in cohort studies from Australia. The role of resection surgery was studied in Benin in patients with larger lesions. Compared to patients that were operated on at week 8, a delayed decision on surgery at week 14 appeared beneficial; delay resulted in significantly less patients being operated, with reduced in-hospital treatment, and no difference in healing rate or sequelae. Sequelae such as contractures due to scar formation around joints may need specialized care in dedicated centers. General medical care with adequate nutrition and proper wound care are critical; wound saline rinsing and cleaning, dressings with non-adhesive cover, and absorptive material with short-stretch compression are all important for speedy healing. Other topical treatments (nitric oxide crùme; traditional herbal remedies; clay; phenytoin) have been little studied; heat treatment might be an option for those that cannot tolerate antimicrobial treatment, such as during pregnancy. Active, early case finding has been shown to be highly efficacious.</p

    Treatment of Buruli Ulcer

    Get PDF
    BU has long been treated by surgical resection. During the last two decades, it has become increasingly clear that antimicrobial treatment, first, using a combination of streptomycin 15 mg/kg i.m. and rifampin 10 mg/kg p.o. for 8 weeks, results in relapse-free cure in lesions &lt;10 cm cross-sectional diameter. Recently, a large clinical trial from Ghana and Benin showed that fully oral treatment—rifampin 10 mg/kg combined with clarithromycin—extended release, 15 mg/kg, also for 8 weeks, was equally effective but less toxic; none of the close to 300 study participants needed surgical resection, and only four had split skin grafts; sequelae were negligible. The use of other antimicrobials including fluoroquinolones has been shown to be effective in cohort studies from Australia. The role of resection surgery was studied in Benin in patients with larger lesions. Compared to patients that were operated on at week 8, a delayed decision on surgery at week 14 appeared beneficial; delay resulted in significantly less patients being operated, with reduced in-hospital treatment, and no difference in healing rate or sequelae. Sequelae such as contractures due to scar formation around joints may need specialized care in dedicated centers. General medical care with adequate nutrition and proper wound care are critical; wound saline rinsing and cleaning, dressings with non-adhesive cover, and absorptive material with short-stretch compression are all important for speedy healing. Other topical treatments (nitric oxide crùme; traditional herbal remedies; clay; phenytoin) have been little studied; heat treatment might be an option for those that cannot tolerate antimicrobial treatment, such as during pregnancy. Active, early case finding has been shown to be highly efficacious.</p

    Histopathological Changes and Clinical Responses of Buruli Ulcer Plaque Lesions during Chemotherapy: A Role for Surgical Removal of Necrotic Tissue?

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    The tropical necrotizing skin disease Buruli ulcer (BU) caused by Mycobacterium ulcerans is associated with extensive tissue destruction and local immunosuppression caused by the macrolide exotoxin mycolactone. Chemotherapy with a combination of rifampicin and streptomycin for 8 weeks is the currently recommended treatment for all types of BU lesions, including both ulcerative and non-ulcerative stages (plaques, nodules and edema). Our histopathological analysis of twelve BU plaque lesions revealed extensive destruction of sub-cutaneous tissue. This frequently led to ulceration during antibiotic treatment. This should not be mistaken as a failure of the antimycobacterial chemotherapy, since we found no evidence for the persistence of active infection foci. Large necrotic areas were found to persist even after completion of antibiotic treatment. These may disturb wound healing and the role of wound debridement should therefore be formally tested in a clinical trial setting

    Family Relationship, Water Contact and Occurrence of Buruli Ulcer in Benin

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    Mycobacterium ulcerans disease (Buruli ulcer) is the most widespread mycobacterial disease in the world after leprosy and tuberculosis. How M. ulcerans is introduced into the skin of humans remains unclear, but it appears that individuals living in the same environment may have different susceptibilities. This case control study aims to determine whether frequent contacts with natural water sources, family relationship or the practice of consanguineous marriages are associated with the occurrence of Buruli ulcer (BU). The study involved 416 participants, of which 104 BU-confirmed cases and 312 age, gender and village of residence matched controls (persons who had no signs or symptoms of active or inactive BU). The results confirmed that contact with natural water sources is a risk factor. Furthermore, it suggests that a combination of genetic factors may constitute risk factors for the development of BU, possibly by influencing the type of immune response in the individual, and, consequently, the development of BU infection per se and its different clinical forms. These findings may be of major therapeutic interest

    Near-Real-Time Acoustic Monitoring of Beaked Whales and Other Cetaceans Using a Seagliderℱ

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    In most areas, estimating the presence and distribution of cryptic marine mammal species, such as beaked whales, is extremely difficult using traditional observational techniques such as ship-based visual line transect surveys. Because acoustic methods permit detection of animals underwater, at night, and in poor weather conditions, passive acoustic observation has been used increasingly often over the last decade to study marine mammal distribution, abundance, and movements, as well as for mitigation of potentially harmful anthropogenic effects. However, there is demand for new, cost-effective tools that allow scientists to monitor areas of interest autonomously with high temporal and spatial resolution in near-real time. Here we describe an autonomous underwater vehicle – a glider – equipped with an acoustic sensor and onboard data processing capabilities to passively scan an area for marine mammals in near-real time. The glider was tested extensively off the west coast of the Island of Hawai'i, USA. The instrument covered approximately 390 km during three weeks at sea and collected a total of 194 h of acoustic data. Detections of beaked whales were successfully reported to shore in near-real time. Manual analysis of the recorded data revealed a high number of vocalizations of delphinids and sperm whales. Furthermore, the glider collected vocalizations of unknown origin very similar to those made by known species of beaked whales. The instrument developed here can be used to cost-effectively screen areas of interest for marine mammals for several months at a time. The near-real-time detection and reporting capabilities of the glider can help to protect marine mammals during potentially harmful anthropogenic activities such as seismic exploration for sub-sea fossil fuels or naval sonar exercises. Furthermore, the glider is capable of under-ice operation, allowing investigation of otherwise inaccessible polar environments that are critical habitats for many endangered marine mammal species

    High content live cell imaging for the discovery of new antimalarial marine natural products

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    <p>Abstract</p> <p>Background</p> <p>The human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, <it>Plasmodium falciparum</it>.</p> <p>Methods</p> <p>A high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown <it>in vitro </it>in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope.</p> <p>Results</p> <p>Image analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts.</p> <p>Conclusion</p> <p>Collectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.</p

    Acoustic sequences in non-human animals: a tutorial review and prospectus.

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    Animal acoustic communication often takes the form of complex sequences, made up of multiple distinct acoustic units. Apart from the well-known example of birdsong, other animals such as insects, amphibians, and mammals (including bats, rodents, primates, and cetaceans) also generate complex acoustic sequences. Occasionally, such as with birdsong, the adaptive role of these sequences seems clear (e.g. mate attraction and territorial defence). More often however, researchers have only begun to characterise - let alone understand - the significance and meaning of acoustic sequences. Hypotheses abound, but there is little agreement as to how sequences should be defined and analysed. Our review aims to outline suitable methods for testing these hypotheses, and to describe the major limitations to our current and near-future knowledge on questions of acoustic sequences. This review and prospectus is the result of a collaborative effort between 43 scientists from the fields of animal behaviour, ecology and evolution, signal processing, machine learning, quantitative linguistics, and information theory, who gathered for a 2013 workshop entitled, 'Analysing vocal sequences in animals'. Our goal is to present not just a review of the state of the art, but to propose a methodological framework that summarises what we suggest are the best practices for research in this field, across taxa and across disciplines. We also provide a tutorial-style introduction to some of the most promising algorithmic approaches for analysing sequences. We divide our review into three sections: identifying the distinct units of an acoustic sequence, describing the different ways that information can be contained within a sequence, and analysing the structure of that sequence. Each of these sections is further subdivided to address the key questions and approaches in that area. We propose a uniform, systematic, and comprehensive approach to studying sequences, with the goal of clarifying research terms used in different fields, and facilitating collaboration and comparative studies. Allowing greater interdisciplinary collaboration will facilitate the investigation of many important questions in the evolution of communication and sociality.This review was developed at an investigative workshop, “Analyzing Animal Vocal Communication Sequences” that took place on October 21–23 2013 in Knoxville, Tennessee, sponsored by the National Institute for Mathematical and Biological Synthesis (NIMBioS). NIMBioS is an Institute sponsored by the National Science Foundation, the U.S. Department of Homeland Security, and the U.S. Department of Agriculture through NSF Awards #EF-0832858 and #DBI-1300426, with additional support from The University of Tennessee, Knoxville. In addition to the authors, Vincent Janik participated in the workshop. D.T.B.’s research is currently supported by NSF DEB-1119660. M.A.B.’s research is currently supported by NSF IOS-0842759 and NIH R01DC009582. M.A.R.’s research is supported by ONR N0001411IP20086 and NOPP (ONR/BOEM) N00014-11-1-0697. S.L.DeR.’s research is supported by the U.S. Office of Naval Research. R.F.-i-C.’s research was supported by the grant BASMATI (TIN2011-27479-C04-03) from the Spanish Ministry of Science and Innovation. E.C.G.’s research is currently supported by a National Research Council postdoctoral fellowship. E.E.V.’s research is supported by CONACYT, Mexico, award number I010/214/2012.This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1111/brv.1216
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