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Wanda Kwan Ulrike Tr?ger Dimitrios Davalos Austin Chou Jill Bouchard Ralph Andre Aaron Miller Andreas Weiss Flaviano Giorgini Christine Cheah Thomas M?ller Nephi Stella Katerina Akassoglou Sarah J. Tabrizi Paul J. Muchowski 《The Journal of clinical investigation》2012,122(12):4737-4747
In Huntington disease (HD), immune cells are activated before symptoms arise; however, it is unclear how the expression of mutant huntingtin (htt) compromises the normal functions of immune cells. Here we report that primary microglia from early postnatal HD mice were profoundly impaired in their migration to chemotactic stimuli, and expression of a mutant htt fragment in microglial cell lines was sufficient to reproduce these deficits. Microglia expressing mutant htt had a retarded response to a laser-induced brain injury in vivo. Leukocyte recruitment was defective upon induction of peritonitis in HD mice at early disease stages and was normalized upon genetic deletion of mutant htt in immune cells. Migration was also strongly impaired in peripheral immune cells from pre-manifest human HD patients. Defective actin remodeling in immune cells expressing mutant htt likely contributed to their migration deficit. Our results suggest that these functional changes may contribute to immune dysfunction and neurodegeneration in HD, and may have implications for other polyglutamine expansion diseases in which mutant proteins are ubiquitously expressed. 相似文献
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Nilton Di Chiacchio Débora Cadore de Farias Bianca Maria Piraccini Sergio Henrique Hirata Bertrand Richert Martin Zaiac Ralph Daniel Pier Alessandro Fanti Josette Andre Beth S Ruben Philip Fleckman Phoebe Rich Eckart Haneke Patricia Chang Judith Dominguez Cherit Richard Scher Antonella Tosti 《Anais brasileiros de dermatologia》2013,88(2):309-313
This statement, focused on melanonychia and nail plate dermoscopy, is intended to guide medical professionals working with melanonychia and to assist choosing appropriate management for melanonychia patients. The International Study Group on Melanonychia was founded in 2007 and currently has 30 members, including nail experts and dermatopathologists with special expertise in nails. The need for common definitions of nail plate dermoscopy was addressed during the Second Meeting of this Group held in February 2008. Prior to this meeting and to date (2010) there have been no evidence-based guidelines on the use of dermoscopy in the management of nail pigmentation. 相似文献
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The risk factors associated with the use of glucose-6-phosphate dehydrogenase (G6PD)–deficient blood in transfusion have not yet been well established. Therefore, the aim of this review was to evaluate whether whole blood from healthy G6PD-deficient donors is safe to use for transfusion. The study undertook a systematic review of English articles indexed in COCHRANE, MEDLINE, EMBASE, and CINHAL, with no date restriction up to March 2013, as well as those included in articles' reference lists and those included in Google Scholar. Inclusion criteria required that studies be randomized controlled trials, case controls, case reports, or prospective clinical series. Data were extracted following the Preferred Reporting Items for Systematic Reviews using a previously piloted form, which included fields for study design, population under study, sample size, study results, limitations, conclusions, and recommendations. The initial search identified 663 potentially relevant articles, of which only 13 studies met the inclusion criteria. The reported effects of G6PD-deficient transfused blood on neonates and children appear to be more deleterious than effects reported on adult patients. In most cases, the rise of total serum bilirubin was abnormal in infants transfused with G6PD-deficient blood from 6 hours up to 60 hours after transfusion. All studies on neonates and children, except one, recommended a routine screening for G6PD deficiency for this at-risk subpopulation because their immature hepatic function potentially makes them less able to handle any excess bilirubin load. It is difficult to make firm clinical conclusions and recommendations given the equivocal results, the lack of standardized evaluation methods to categorize red blood cell units as G6PD deficient (some of which are questionable), and the limited methodological quality and low quality of evidence. Notwithstanding these limitations, based on our review of the available literature, there is little to suggest that G6PD-deficient individuals should be excluded from donating red blood cells, although transfusions of such blood may potentially have negative impacts on premature neonates or patients who need repeated transfusions, and thus, for this group, screening for G6PD deficiency may be appropriate. 相似文献
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Ashley Sharp Berit Muller-Pebody Andre Charlett Bharat Patel Rebecca Gorton Jonathan Lambourne Martina Cummins Adela Alcolea-Medina Mark Wilks Robin Smith Damien Mack Susan Hopkins Andrew Dodgson Phillipa Burns Nelun Perera Felicia Lim Gopal Rao Priya Khanna Elizabeth Johnson Andrew Borman Silke Schelenz Rebecca Guy Joanna Conneely Rohini J Manuel Colin S Brown 《Euro surveillance : bulletin européen sur les maladies transmissibles = European communicable disease bulletin》2021,26(8)
Background Candida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment.AimWe aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance.MethodsBetween May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017.ResultsAll C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities.ConclusionThese findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment. 相似文献
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Priscila Rios Bomfim Chaves Alexandre Melo Karam Andre Wilson Machado 《The Angle orthodontist》2021,91(1):54
ObjectiveTo evaluate the influence of a midline diastema on dentofacial esthetic perceptions of orthodontists, restorative dental specialists or prosthodontists, and laypersons in a frontal facial evaluation performed by means of video.Materials and MethodsTwo individuals aged between 20 and 25 years, one of each gender, with presence of a midline diastema were selected. An acrylic resin mockup was made of the maxillary anterior region, simulating ideal conditions of smile esthetics. Four standardized frontal view videos of the complete face were filmed of each individual in the following situations: with the ideal smile (unchanged mockup) and with the presence of midline diastemas of 0.5, 1.0, and 1.5 mm created by the mockup. In all videos, the patient said a certain sentence and, at the end, simulated a posed smile. Dentofacial esthetic perceptions of all four videos of each individual were evaluated by 51 orthodontists, 51 restorative dental specialists or prosthodontists, and 51 laypersons by means of visual analog scales. Data were evaluated using analysis of variance and Tukey post hoc test, with the level of significance set at 5%.ResultsThe most attractive videos for all groups of examiners were those without diastema and with a diastema of 0.5 mm, for both the woman and the man. For a diastema of 1 mm or 1.5 mm, the dentofacial characteristics were considered unesthetic.ConclusionsDiastemas equal to or greater than 1 mm negatively influence dentofacial esthetics in a frontal facial evaluation performed by means of video. 相似文献
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