Distinguishing Dystrophic Calcification from Calciphylaxis

Introduction Calcinosis cutis, a disorder in which calcium salts deposit in skin and subcutis, is categorized into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis. Dystrophic calcification, the most common subtype, typically results from local tissue damage1,2 and is proposed to be caused by the release of phosphate binding proteins by necrotic cells in response to tissue damage, inflammation, or hypoxia.2 The condition often presents with nontender nodules of the skin or subcutis and normal serum calcium. Calciphylaxis is believed to be caused by impaired inhibition of calcification in the microvasculature.3 A deficiency in carboxylated matrix Gla protein, a vitamin K dependent inhibitor of vascular calcification, has been associated with calciphylaxis.3 Conditions resulting in vitamin K deficiency, including Warfarin usage and end stage renal disease, have been implicated.3 Several causes of nonuremic calciphylaxis have been reported, notably in association with alcoholic cirrhosis.1,4,5 Additional risk factors include hypercalcemia, hyperphosphatemia, and hyperparathyroidism.3 Intramural vascular calcification of small to medium-sized vessels, typically of the dermis and subcutaneous fat, is a key pathologic diagnostic criterion of calciphylaxis.1 Following medial calcification, subintimal fibroplasia and thrombosis result in vascular occlusion, ischemia, inflammation, and necrosis of surrounding tissue.3 Consequently, calciphylaxis is associated with severely painful lesions.3 Diagnosis requires clinicopathologic correlation as diagnostic histopathological findings of intramural calcification of small vessels and vasculopathy can be subtle. The following case underscores how variations in the clinicopathologic presentation of dystrophic calcification and calciphylaxis can create diagnostic challenges

Induction of Multiple Immune Regulatory Pathways with Differential Impact in HCV/HIV Coinfection

Persistent viral infections including HCV, HBV, and HIV are associated with increased immune regulatory pathways including the extrinsic FoxP3+CD4+ regulatory T cells (Tregs) and intrinsic inhibitory pathways such as programed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) with potentially reversible suppression of antiviral effector T cells (1–12). Immunological consequences of viral coinfections relative to these immune regulatory pathways and their interplay are not well-defined. In this study, we examined the frequency, phenotype, and effector function of circulating T cell subsets in patients with chronic HCV and/or HIV infection, hypothesizing that HCV/HIV coinfection will result in greater immune dysregulation with pathogenetic consequences (13, 14). We show that multiple T cell inhibitory pathways are induced in HCV/HIV coinfection including FoxP3+ Tregs, PD-1, and CTLA-4 in inverse association with overall CD4 T cell frequency but not with liver function or HCV RNA titers. The inverse association between CD4 T cell frequency and their FoxP3, PD-1, or CTLA-4 expression remained significant in all subjects combined regardless of HCV and/or HIV infection, suggesting a global homeostatic mechanism to maintain immune regulation relative to CD4 T cell frequency. PD-1 blockade rescued T cell responses to HIV but not HCV without significant impact by CTLA-4 blockade in vitro. Collectively, these findings highlight complex immune interactions in viral coinfections and differential regulatory pathways influencing virus-specific T cells that are relevant in immunotherapeutic development

Synergistic Reversal of Intrahepatic HCV-Specific CD8 T Cell Exhaustion by Combined PD-1/CTLA-4 Blockade

Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1+ T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4+FoxP3+ Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity

Characteristics of Adults in the Hepatitis B Research Network in North America Reflect Their Country of Origin and Hepatitis B Virus Genotype

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the US and Canada might be disproportionately affected. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network

Selection of low voltage contactors for hazardous environment

Import 26/06/2013Tato práce se zabývá vhodným výběrem stykačů do prostorů s rizikem výbuchu. Obsahuje rozbor problematiky klasifikace vnějších vlivů v prostorách, kde jsou instalována elektrická zařízení. Dále jsou zde uvedeny informace týkající se problematiky výbuchu: podmínek vzniku výbuchu, fyzikálních vlastností látek a důležité pojmy. V následující části jsou uvedeny požadavky na elektrická zařízení instalovaná v prostorách s nebezpečím výbuchu včetně jejich označování. Druhá část obsahuje rozbor stykače, a to především možnosti konstrukčního provedení a problematiky spínání. Zvláštní pozornost je věnována vakuovým stykačům, s ohledem na problematiku elektrického oblouku ve vakuu a výběru vhodných materiálů pro elektrické kontakty. Poslední část zahrnuje samotný výběr vhodných stykačů, včetně několika různých výrobců v rámci EU.My bachelor thesis deals with suitable choice of contactors to environment with risk of explosion. The thesis also includes the analysis of classification of external influences in areas where electric equipments are installed. You can also find here some information about explosions: sources, physical properties of substances and other important concepts. In the following part, there are requirements for electric equipments installed in environment that is in danger of explosion, furthermore there is also described their labelling. The second part of my thesis deals with analysis of contactor and above all with possibility of structural design and the issue of switching. A great deal of the thesis is also focused on vacuum contactors regard to the issues of electric arc in vacuum and it is also focused on choice of suitable materials for electric contacts. The last part includes the choice of suitable contactors including comparison of several producers in EU.410 - Katedra elektroenergetikyvýborn

Optimization study of HV and MV distribution systems in industrial plant

Import 22/07/2015Tato práce se zabývá optimalizací rozvodů elektrické energie v průmyslovém závodu na napěťových hladinách VVN a VN. Úvodní kapitola definuje požadavky kladené na rozvody v průmyslu, roztříděné podle různých kritérií. Samotná práce se skládá ze čtyř hlavních částí. Nejprve je provedena analýza stávajícího stavu rozvodů a jeho zhodnocení, na tuto kapitolu přímo navazuje kapitola zabývající se návrhem nového konceptu napájení. Další, neméně důležitou součástí, je ekonomické zhodnocení návratnosti investic do nové konfigurace sítě. Poslední část tvoří projektová dokumentace, provedená na úrovni studie stavby.This thesis deals with electric distribution optimization in industrial plant, including high voltage and medium voltage levels. Very first chapter defines distribution systems' requirements, classified according to various criterions. The practical part of thesis consists of four main parts. First, analysis of present distribution system is performed. Following chapter contains new concept of power distribution. As next chapter, economic evaluation of suggested concept is quantified. Very last part comprises project documentation drawings, at the level of construction study.410 - Katedra elektroenergetikyvýborn

The New Leadership Challenge: Creating the Future of Nursing. 4th edition

Whatever your role, practice or educational environment, here are the tools and techniques you can use to realize your leadership potential, advance your career, and contribute to the future of nursing. This 2009 AJN Book of the Year Winner, by two noted educators in the field of leadership development, guides you through the process. An easy-to-read, interactive approach helps you identify the characteristics of leaders and followers and illustrates not only how, but also when to use the qualities associated with each to achieve professional and personal success.https://digitalcommons.fairfield.edu/nursing-books/1043/thumbnail.jp