7,060 research outputs found

    Discussion of Christ\u27s First Word on the Cross.

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    Towards understanding the gliotoxin detoxification mechanism: in vivo thiomethylation protects yeast from gliotoxin cytotoxicity

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    Gliotoxin (GT) is a mycotoxin produced by some species of ascomycete fungi including the opportunistic human pathogen Aspergillus fumigatus . In order to produce GT the host organism needs to have evolved a selfprotection mechanism. GT contains a redox-cycling disulfide bridge that is important in mediating toxicity. Recently is has been demonstrated that A. fumigatus possesses a novel thiomethyltransferase protein called GtmA that has the ability to thiomethylate GT in vivo , which aids the organism in regulating GT biosynthesis. It has been suggested that thiomethylation of GT and similar sulfur-containing toxins may play a role in providing self-protection in host organisms. In this work we have engineered Saccharomyces cerevisiae , a GT-naïve organism, to express A. fumigatus GtmA. We demonstrate that GtmA can readily thiomethylate GT in yeast, which results in protection of the organism from exogenous GT. Our work has implications for understanding the evolution of GT self-protection mechanisms in organisms that are GT producers and non-producers

    Haiti: The South African perspective

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    Background and problem statement. The South African response to the Haitian earthquake consisted of two independent nongovernment organisations (NGOs) working separately with minimal contact. Both teams experienced problems during the deployment, mainly owing to not following the International Search and Rescue Advisory Group (INSARAG) guidelines. Critical areas identified. To improve future South African disaster responses, three functional deployment categories were identified: urban search and rescue, triage and initial stabilisation, and definitive care. To best achieve this, four critical components need to be taken into account: rapid deployment, intelligence from the site, government facilitation, and working under the auspices of recognised organisations such as the United Nations and the World Health Organization. Conclusion. The proposed way forward for South African medical teams responding to disasters is to be unified under a leading academic body, to have an up-to-date volunteer database, and for volunteers to be current with the international search and rescue course currently being developed by the Medical Working Group of INSARAG. An additional consideration is that South African rescue and relief personnel have a primary responsibility to the citizens of South Africa, then the Southern African Development Community region, then the rest of the African continent and finally further afield. The commitment of government, private and military health services as well as NGOs is paramount for a unified response

    Patient-maintained sedation for oral surgery using a target-controlled infusion of propofol - a pilot study

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    OBJECTIVE: To assess the safety and efficacy of a new patient-maintained propofol system for conscious sedation in dentistry. DESIGN: Prospective clinical trial SETTING: Department of Sedation, Glasgow Dental Hospital and School, 2001 SUBJECTS AND METHODS: Patients scheduled for oral surgery with conscious sedation. Exclusions included ASA IV -V, inability to use the handset, opioid use and severe respiratory disease. INTERVENTIONS: Patients were given intravenous propofol to a level of 1.0 microg/ml (reducing from 1.5 microg/ml) using a target controlled infusion system, they then controlled their sedation level by double-clicking a handset which on each activation increased the propofol concentration by 0.2 microg/ml. MAIN OUTCOME MEASURES: Oxygen saturation, patient satisfaction, and surgeon satisfaction. RESULTS: Twenty patients were recruited, 16 female and four male. Nineteen patients completed sedation and treatment successfully. Mean lowest oxygen saturation was 94%. No patients were over-sedated. All patients successfully used the system to maintain a level of sedation adequate for their comfort. Patient and surgeon satisfaction were consistently high. CONCLUSIONS: Initial experience with this novel system has confirmed safety, patient satisfaction and surgeon satisfaction

    Trichloroethylene Exposure during Cardiac Valvuloseptal Morphogenesis Alters Cushion Formation and Cardiac Hemodynamics in the Avian Embryo

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    It is controversial whether trichloroethylene (TCE) is a cardiac teratogen. We exposed chick embryos to 0, 0.4, 8, or 400 ppb TCE/egg during the period of cardiac valvuloseptal morphogenesis (2–3.3 days’ incubation). Embryo survival, valvuloseptal cellularity, and cardiac hemodynamics were evaluated at times thereafter. TCE at 8 and 400 ppb/egg reduced embryo survival to day 6.25 incubation by 40–50%. At day 4.25, increased proliferation and hypercellularity were observed within the atrioventricular and outflow tract primordia after 8 and 400 ppb TCE. Doppler ultrasound revealed that the dorsal aortic and atrioventricular blood flows were reduced by 23% and 30%, respectively, after exposure to 8 ppb TCE. Equimolar trichloroacetic acid (TCA) was more potent than TCE with respect to increasing mortality and causing valvuloseptal hypercellularity. These results independently confirm that TCE disrupts cardiac development of the chick embryo and identifies valvuloseptal development as a period of sensitivity. The hypercellular valvuloseptal profile is consistent with valvuloseptal heart defects associated with TCE exposure. This is the first report that TCA is a cardioteratogen for the chick and the first report that TCE exposure depresses cardiac function. Valvuloseptal hypercellularity may narrow the cardiac orifices, which reduces blood flow through the heart, thereby compromising cardiac output and contributing to increased mortality. The altered valvuloseptal formation and reduced hemodynamics seen here are consistent with such an outcome. Notably, these effects were observed at a TCE exposure (8 ppb) that is only slightly higher than the U.S. Environmental Protection Agency maximum containment level for drinking water (5 ppb)

    Motion-Based Technical Skills Assessment in Transoesophageal Echocardiography

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    This paper presents a novel approach for evaluating technical skills in Transoesophageal Echocardiography (TEE). Our core assumption is that operational competency can be objectively expressed by specific motion-based measures. TEE experiments were carried out with an augmented reality simulation platform involving both novice trainees and expert radiologists. Probe motion data were collected and used to formulate various kinematic parameters. Subsequent analysis showed that statistically significant differences exist among the two groups for the majority of the metrics investigated. Experts exhibited lower completion times and higher average velocity and acceleration, attributed to their refined ability for efficient and economical probe manipulation. In addition, their navigation pattern is characterised by increased smoothness and fluidity, evaluated through the measures of dimensionless jerk and spectral arc length. Utilised as inputs to well-known clustering algorithms, the derived metrics are capable of discriminating experience levels with high accuracy (>84 %)

    Osteogenic sarcoma of the breast arising in a cystosarcoma phyllodes: a case report and review of the literature

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    <p>Abstract</p> <p>Introduction</p> <p>Primary tumors of the breast containing bone and cartilage are extremely rare, and an osteogenic sarcoma arising from a cystosarcoma phyllodes is exceptional.</p> <p>Case presentation</p> <p>A 40-year-old Indian woman presented with a breast mass which was diagnosed as osteosarcoma of the breast on biopsy. Our patient was treated with a simple mastectomy after excluding the presence of skeletal primary and extra-mammary metastases. Final pathology showed a cystosarcoma phyllodes with signs of osteogenic sarcoma.</p> <p>Conclusion</p> <p>Although osteogenic sarcomas of the breast are rare, they need to be distinguished from carcinosarcomas and metaplastic carcinomas as the management of the two differ.</p

    Icing: Large-scale inference of immunoglobulin clonotypes

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    Immunoglobulin (IG) clonotype identification is a fundamental open question in modern immunology. An accurate description of the IG repertoire is crucial to understand the variety within the immune system of an individual, potentially shedding light on the pathogenetic process. Intrinsic IG heterogeneity makes clonotype inference an extremely challenging task, both from a computational and a biological point of view. Here we present icing, a framework that allows to reconstruct clonal families also in case of highly mutated sequences. icing has a modular structure, and it is designed to be used with large next generation sequencing (NGS) datasets, a technology which allows the characterisation of large-scale IG repertoires. We extensively validated the framework with clustering performance metrics on the results in a simulated case. icing is implemented in Python, and it is publicly available under FreeBSD licence at https://github.com/slipguru/icing
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