105 research outputs found

    Short-Term Starvation of Immune Deficient Drosophila Improves Survival to Gram-Negative Bacterial Infections

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    Background: Primary immunodeficiencies are inborn errors of immunity that lead to life threatening conditions. These predispositions describe human immunity in natura and highlight the important function of components of the Toll-IL-1receptor-nuclear factor kappa B (TIR-NF-kB) pathway. Since the TIR-NF-kB circuit is a conserved component of the host defence in higher animals, genetically tractable models may contribute ideas for clinical interventions. Methodology/Principal Findings: We used immunodeficient fruit flies (Drosophila melanogaster) to address questions pertaining to survival following bacterial infection. We describe here that flies lacking the NF-kB protein Relish, indispensable for countering Gram-negative bacteria, had a greatly improved survival to such infections when subject to dietary short-term starvation (STS) prior to immune challenge. STS induced the release of Nitric Oxide (NO), a potent molecule against pathogens in flies, mice and humans. Administering the NO Synthase-inhibitory arginine analog N-Nitro-L-Arginine-Methyl-Ester (L-NAME) but not its inactive enantiomer D-NAME increased once again sensitivity to infection to levels expected for relish mutants. Surprisingly, NO signalling required the NF-kB protein Dif, usually needed for responses against Gram-positive bacteria. Conclusions/Significance: Our results show that NO release through STS may reflect an evolutionary conserved process. Moreover, STS could be explored to address immune phenotypes related to infection and may offer ways to boost natura

    Applications of multi-walled carbon nanotube in electronic packaging

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    Thermal management of integrated circuit chip is an increasing important challenge faced today. Heat dissipation of the chip is generally achieved through the die attach material and solders. With the temperature gradients in these materials, high thermo-mechanical stress will be developed in them, and thus they must also be mechanically strong so as to provide a good mechanical support to the chip. The use of multi-walled carbon nanotube to enhance the thermal conductivity, and the mechanical strength of die attach epoxy and Pb-free solder is demonstrated in this work

    More stories on Th17 cells

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    For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. the Th1/Th2 paradigm implied the existence of two different, mutually regulated, CD4(+) T helper subsets: Th1 cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particularly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4(+) T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells. the Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Th1, Th2 and Th17 effector cells but there is also a dichotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-beta or TGF-beta plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.Crohn's and Colitis Foundation of AmericaNIHLa Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilNIH: RO1 AI050265-06Web of Scienc

    Molecular imaging of hypoxia with radiolabelled agents

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    Tissue hypoxia results from an inadequate supply of oxygen (O2) that compromises biological functions. Structural and functional abnormalities of the tumour vasculature together with altered diffusion conditions inside the tumour seem to be the main causes of tumour hypoxia. Evidence from experimental and clinical studies points to a role for tumour hypoxia in tumour propagation, resistance to therapy and malignant progression. This has led to the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments. A variety of invasive and non-invasive approaches have been developed to measure tumour oxygenation including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), autoradiography and immunohistochemistry. This review aims to give a detailed overview of non-invasive molecular imaging modalities with radiolabelled PET and SPECT tracers that are available to measure tumour hypoxia

    Breast MRI: guidelines from the European Society of Breast Imaging

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    The aim of breast MRI is to obtain a reliable evaluation of any lesion within the breast. It is currently always used as an adjunct to the standard diagnostic procedures of the breast, i.e., clinical examination, mammography and ultrasound. Whereas the sensitivity of breast MRI is usually very high, specificity—as in all breast imaging modalities—depends on many factors such as reader expertise, use of adequate techniques and composition of the patient cohorts. Since breast MRI will always yield MR-only visible questionable lesions that require an MR-guided intervention for clarification, MRI should only be offered by institutions that can also offer a MRI-guided breast biopsy or that are in close contact with a site that can perform this type of biopsy for them. Radiologists involved in breast imaging should ensure that they have a thorough knowledge of the MRI techniques that are necessary for breast imaging, that they know how to evaluate a breast MRI using the ACR BI-RADS MRI lexicon, and most important, when to perform breast MRI. This manuscript provides guidelines on the current best practice for the use of breast MRI, and the methods to be used, from the European Society of Breast Imaging (EUSOBI)

    Quality of life in preoperative patients with sacroiliac joint dysfunction is at least as depressed as in other lumbar spinal conditions

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    Daniel Joseph Cher, W Carlton RecklingSI-BONE, Inc., San Jose, CA, USABackground: Pain from the sacroiliac joint (SIJ) is an under-recognized cause of low back pain. The degree to which SIJ pain decreases quality of life has not been directly compared to other more familiar conditions of the lumbar spine.Methods: Multivariate regression analysis of individual patient data from two prospective multicenter clinical trials of SIJ fusion and three prospective multicenter clinical trials of surgical treatments for degenerative lumbar spine conditions.Results: Controlling for baseline demographic parameters as well as a validated disability score, quality of life scores (EuroQOL 5-D and SF-36) were, in most cases, lower in the SIJ cohorts compared to the three other spine surgery cohorts.Conclusion: Patients with SIJ dysfunction considering surgery have decrements in quality of life as or more severe compared to patients with degenerative spondylolisthesis, spinal stenosis, and intervertebral disc herniation.Keywords: spine surgery, disability, low back pain, sacroiliac joint pain, lumbar stenosis, intervertebral disc herniation, degenerative spondylolisthesis, sacroiliac joint fusio

    Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction

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    Josh D Saavoss,1 Lane Koenig,1 Daniel J Cher2 1KNG Health Consulting, LLC, Rockville, MD, 2SI-BONE, Inc., San Jose, CA, USA Introduction: Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Methods: Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Results: Patients who receive SIJ fusion using iFuse Implant System® have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%–21%) relative to nonsurgical patients. The expected change in earnings across groups was US 3,128(notstatisticallysignificant).Combiningthetwometrics,theannualincreaseinworkerproductivitygivensurgicalvsnonsurgicalcarewas3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was 6,924 (95% CI 1,890–11,945). Conclusion: For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment. Keywords: sacroiliac joint fusion, low back pain, sacroiliac joint pain, clinical trial, health care costs, indirect cost
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