135 research outputs found

    Russell bodies in a skin biopsy: a case report

    Get PDF
    <p>Abstract</p> <p>Introduction</p> <p>The presence of eosinophilic bodies in a skin biopsy can be found in a variety of situations and this may present a challenge to the pathologist. The differential diagnosis of these eosinophilic structures include microorganisms such as histoplasmosis or cryptococcosis, fungi, Michaelis-Gutmann bodies, deposits of amyloid or immunoglobulins, colloid bodies or elastic bodies.</p> <p>Case presentation</p> <p>During a routine examination of a skin biopsy with actinic keratosis taken from the cheek of a 61-year-old man, clusters of eosinophilic bodies were seen within an inflammatory infiltrate in the dermis, both intracytoplasmic and extracellular. Using additional immunohistochemical staining, these structures were identified as polyclonal Russell bodies.</p> <p>Conclusion</p> <p>The differential diagnosis of intracytoplasmic eosinophilic structures in a skin biopsy includes Russell bodies, an uncommon finding that may be associated with chronic inflammatory conditions.</p

    State estimation for discrete-time neural networks with Markov-mode-dependent lower and upper bounds on the distributed delays

    Get PDF
    Copyright @ 2012 Springer VerlagThis paper is concerned with the state estimation problem for a new class of discrete-time neural networks with Markovian jumping parameters and mixed time-delays. The parameters of the neural networks under consideration switch over time subject to a Markov chain. The networks involve both the discrete-time-varying delay and the mode-dependent distributed time-delay characterized by the upper and lower boundaries dependent on the Markov chain. By constructing novel Lyapunov-Krasovskii functionals, sufficient conditions are firstly established to guarantee the exponential stability in mean square for the addressed discrete-time neural networks with Markovian jumping parameters and mixed time-delays. Then, the state estimation problem is coped with for the same neural network where the goal is to design a desired state estimator such that the estimation error approaches zero exponentially in mean square. The derived conditions for both the stability and the existence of desired estimators are expressed in the form of matrix inequalities that can be solved by the semi-definite programme method. A numerical simulation example is exploited to demonstrate the usefulness of the main results obtained.This work was supported in part by the Royal Society of the U.K., the National Natural Science Foundation of China under Grants 60774073 and 61074129, and the Natural Science Foundation of Jiangsu Province of China under Grant BK2010313

    Dual proteotoxic stress accelerates liver injury via activation of p62-Nrf2

    Get PDF
    Protein accumulation is the hallmark of various neuronal, muscular, and other human disorders. It is also often seen in the liver as a major protein-secretory organ. For example, aggregation of mutated alpha1-antitrypsin (AAT), referred to as PiZ, is a characteristic feature of AAT deficiency, whereas retention of hepatitis B surface protein (HBs) is found in chronic hepatitis B (CHB) infection. We investigated the interaction of both proteotoxic stresses in humans and mice. Animals overexpressing both PiZ and HBs (HBs-PiZ mice) had greater liver injury, steatosis, and fibrosis. Later they exhibited higher hepatocellular carcinoma load and a more aggressive tumor subtype. Although PiZ and HBs displayed differing solubility properties and distinct distribution patterns, HBs-PiZ animals manifested retention of AAT/HBs in the degradatory pathway and a marked accumulation of the autophagy adaptor p62. Isolation of p62-containing particles revealed retained HBs/AAT and the lipophagy adapter perilipin-2. p62 build-up led to activation of the p62–Nrf2 axis and emergence of reactive oxygen species. Our results demonstrate that the simultaneous presence of two prevalent proteotoxic stresses promotes the development of liver injury due to protein retention and activation of the p62–Nrf2 axis. In humans, the PiZ variant was over-represented in CHB patients with advanced liver fibrosis (unadjusted odds ratio = 9.92 [1.15–85.39]). Current siRNA approaches targeting HBs/AAT should be considered for these individuals. © 2021 The Authors. The Journal of Pathology published by John Wiley &amp; Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

    Gluten Induces Subtle Histological Changes in Duodenal Mu-cosa of Patients with Non-Coeliac Gluten Sensitivity: A Multi-center Study

    Get PDF
    Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in μm), crypt depth (CrD, in μm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture

    A special gift we bestow on you for being representative of us: Considering leader

    Get PDF
    Two experiments tested hypotheses, derived from social identity and self-categorization theories, regarding the attribution of charisma to leaders. In Experiment I (N = 203), in-group prototypical leaders were attributed greater levels of charisma and were perceived to be more persuasive than in-group non-prototypical leaders. In Experiment 2 (N = 220), leaders described with in-group stereotypical characteristics were attributed relatively high levels of charisma regardless of their group-oriented versus exchange rhetoric. Leaders described with out-group stereotypical characteristics, however, had to employ group-oriented rhetoric to be attributed relatively high levels of charisma. We conclude that leadership emerges from being representative of 'us'; charisma may, indeed, be a special gift, but it is one bestowed on group members by group members for being representative of, rather than distinct from, the group itself. © 2006 The British Psychological Society

    A systematic review of the effectiveness of self-management interventions in people with multiple sclerosis at improving depression, anxiety and quality of life.

    Get PDF
    BACKGROUND: Self-management interventions have become increasingly popular in the management of long-term health conditions; however, little is known about their impact on psychological well-being in people with Multiple Sclerosis (MS). PURPOSE: To examine the effectiveness of self-management interventions on improving depression, anxiety and health related quality of life in people with MS. METHOD: A structured literature search was conducted for the years 2000 to 2016. The review process followed the PRISMA guidelines, and is registered with PROSPERO (no. CRD42016033925). RESULTS: The review identified 10 RCT trials that fulfilled selection criteria and quality appraisal. Self-management interventions improved health-related quality of life in 6 out of 7 studies, with some evidence of improvement in depression and anxiety symptoms. CONCLUSION: Although the results are promising more robust evaluation is required in order to determine the effectiveness of self-management interventions on depression, anxiety and quality of life in people with MS. Evaluation of the data was impeded by a number of methodological issues including incomplete content and delivery information for the intervention and the exclusion of participants representing the disease spectrum. Recommendations are made for service development and research quality improvement

    A catalogue of Triticum monococcum genes encoding toxic and immunogenic peptides for celiac disease patients

    Get PDF
    The celiac disease (CD) is an inflammatory condition characterized by injury to the lining of the small-intestine on exposure to the gluten of wheat, barley and rye. The involvement of gluten in the CD syndrome has been studied in detail in bread wheat, where a set of “toxic” and “immunogenic” peptides has been defined. For wheat diploid species, information on CD epitopes is poor. In the present paper, we have adopted a genomic approach in order to understand the potential CD danger represented by storage proteins in diploid wheat and sequenced a sufficiently large number of cDNA clones related to storage protein genes of Triticum monococcum. Four bona fide toxic peptides and 13 immunogenic peptides were found. All the classes of storage proteins were shown to contain harmful sequences. The major conclusion is that einkorn has the full potential to induce the CD syndrome, as already evident for polyploid wheats. In addition, a complete overview of the storage protein gene arsenal in T. monococcum is provided, including a full-length HMW x-type sequence and two partial HMW y-type sequences

    Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: wheat breeding may have contributed to increased prevalence of celiac disease

    Get PDF
    Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of ‘low CD toxic’ as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD

    Physiological response to firefighting activities of various work cycles using extended duration and prototype SCBA

    Get PDF
    Firefighters’ self-contained breathing apparatus (SCBA) protects the respiratory system during firefighting but increases the physiological burden. Extended duration SCBA (>30 min) have increased air supply, potentially increasing the duration of firefighting work cycles. To examine the effects of SCBA configuration and work cycle (length and rest), 30 firefighters completed seven trials using different SCBA and one or two bouts of simulated firefighting following work cycles common in the United States. Heart rate, core temperature, oxygen consumption, work output and self-reported perceptions were recorded during all activities. Varying SCBA resulted in few differences in these parameters. However, during a second bout, work output significantly declined while heart rates and core temperatures were elevated relative to a single bout. Thirty seven per cent of the subjects were unable to complete the second bout in at least one of the two-bout conditions. These firefighters had lower fitness and higher body mass than those who completed all assigned tasks. Practitioner Summary: The effects of extended duration SCBA and work/rest cycles on physiological parameters and work output have not been examined. Cylinder size had minimal effects, but extended work cycles with no rest resulted in increased physiological strain and decreased work output. This effect was more pronounced in firefighters with lower fitness.This work was supported by the Department of Homeland Security Fire Prevention and Safety, Federal Emergency Management Agency [grant number EMW-2010-FP-01606].Ope
    corecore