Pathophysiology of Hidradenitis suppurativa

Only limited data are available about the precise mechanism leading to tissue inflammation and damage in patients with hidradenits suppurativa (HS). The central pathogenetic event in HS is the occlusion of the upper parts of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. In early lesions, neutrophilic abscess formation and influx of mainly macrophages, monocytes and dendritic cells predominate. In chronic disease, the infiltrate expand with increased frequencies of B cells and plasma cells. In the inflammatory infiltrates toll like receptor 2 (TLR2) was highly expressed by infiltrating macrophages and dendritic cells indicating that stimulation of inflammatory cells by TLR2 activating microbial products may be important trigger factors in the chronic inflammatory process. Furthermore, the pro inflammatory cytokines IL-12 and IL-23 are abundantly expressed by macrophages infiltrating papillary and reticular dermis of HS skin. Both of these cytokines are believed to be important mediators in autoimmune tissue destruction and its blocking by biologics has been shown to be effective in the treatment of psoriasis. Especially IL-23 has been shown to be involved in the induction of a T helper cell subset producing IL-17, therefore, named Th17, which is distinct from the classical Th1/Th2 subsets. In chronic HS lesions IL-17-producing T helper cells were found to infiltrate the dermis. An overexpression of various other cytokines like IL-1beta, CYCL9 (MIG), IL-10 , IL-11 and BLC has been described in HS lesion whereas IL-20 and IL-22 have been shown to be down regulated. Similar to psoriasis also in HS the antimicrobial peptides beta defensin 2 and psoriasin are highly upregulated. This may at least in part explain the clinical finding that HS patients suffer only rarely from skin infections. Taken together the inflammatory reaction leading to HS are only poorly understood, but they show many similarity with other inflammatory reactions as e.g. in psoriasis.

German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) - presentation of design and reliability of the data as well as first results

INTRODUCTION Even though arthroplasty of the ankle joint is considered to be an established procedure, only about 1,300 endoprostheses are implanted in Germany annually. Arthrodeses of the ankle joint are performed almost three times more often. This may be due to the availability of the procedure - more than twice as many providers perform arthrodesis - as well as the postulated high frequency of revision procedures of arthroplasties in the literature. In those publications, however, there is often no clear differentiation between revision surgery with exchange of components, subsequent interventions due to complications and subsequent surgery not associated with complications. The German Orthopaedic Foot and Ankle Association's (D. A. F.) registry for total ankle replacement collects data pertaining to perioperative complications as well as cause, nature and extent of the subsequent interventions, and postoperative patient satisfaction. MATERIAL AND METHODS The D. A. F.'s total ankle replacement register is a nation-wide, voluntary registry. After giving written informed consent, the patients can be added to the database by participating providers. Data are collected during hospital stay for surgical treatment, during routine follow-up inspections and in the context of revision surgery. The information can be submitted in paper-based or online formats. The survey instruments are available as minimum data sets or scientific questionnaires which include patient-reported outcome measures (PROMs). The pseudonymous clinical data are collected and evaluated at the Institute for Evaluative Research in Medicine, University of Bern/Switzerland (IEFM). The patient-related data remain on the register's module server in North Rhine-Westphalia, Germany. The registry's methodology as well as the results of the revisions and patient satisfaction for 115 patients with a two year follow-up period are presented. Statistical analyses are performed with SAS™ (Version 9.4, SAS Institute, Inc., Cary, NC, USA). RESULTS About 2½ years after the register was launched there are 621 datasets on primary implantations, 1,427 on follow-ups and 121 records on re-operation available. 49 % of the patients received their implants due to post-traumatic osteoarthritis, 27 % because of a primary osteoarthritis and 15 % of patients suffered from a rheumatic disease. More than 90 % of the primary interventions proceeded without complications. Subsequent interventions were recorded for 84 patients, which corresponds to a rate of 13.5 % with respect to the primary implantations. It should be noted that these secondary procedures also include two-stage procedures not due to a complication. "True revisions" are interventions with exchange of components due to mechanical complications and/or infection and were present in 7.6 % of patients. 415 of the patients commented on their satisfaction with the operative result during the last follow-up: 89.9 % of patients evaluate their outcome as excellent or good, 9.4 % as moderate and only 0.7 % (3 patients) as poor. In these three cases a component loosening or symptomatic USG osteoarthritis was present. Two-year follow-up data using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Scale (AOFAS-AHS) are already available for 115 patients. The median AOFAS-AHS score increased from 33 points preoperatively to more than 80 points three to six months postoperatively. This increase remained nearly constant over the entire two-year follow-up period. CONCLUSION Covering less than 10 % of the approximately 240 providers in Germany and approximately 12 % of the annually implanted total ankle-replacements, the D. A. F.-register is still far from being seen as a national registry. Nevertheless, geographical coverage and inclusion of "high-" (more than 100 total ankle replacements a year) and "low-volume surgeons" (less than 5 total ankle replacements a year) make the register representative for Germany. The registry data show that the number of subsequent interventions and in particular the "true revision" procedures are markedly lower than the 20 % often postulated in the literature. In addition, a high level of patient satisfaction over the short and medium term is recorded. From the perspective of the authors, these results indicate that total ankle arthroplasty - given a correct indication and appropriate selection of patients - is not inferior to an ankle arthrodesis concerning patients' satisfaction and function. First valid survival rates can be expected about 10 years after the register's start.

Catching Reality or Bowing Disciplines: How to Move the Study of Citizenship

In his contribution, Joppke justifies his selection of foundational scholars by linking each to what he sees as the three key facets of citizenship: status, rights and identity. Maarten Vink explicitly links his research agenda to the first, status, and outlines why it is so important. In identifying three facets of citizenship, Joppke acknowledges that some academics would include political participation, but he ultimately decides against it. But here we can, and should, broaden citizenship studies by bringing in insights from the behavioral politics tradition in domestic politics - when and why people engage in political acts - and from the social movements literature in sociology. I believe that the American debate on immigration reform, admittedly stalled, would not have advanced as far as it has without the social movement activism of DREAMers - unauthorized young people pushing for a path to citizenship - and the belief that Barack Obama won re-election in part because of the Latino vote. Importantly, one type of political activism demands formal citizenship, the other does not. As many contributors note, the “national models” approach has had a significant impact on citizenship studies. Whether one views such models through a cultural, institutional or historical lens, this tends to be a top-down, macro-level framework. What about immigrants’ agency? In Canada, although the ruling Conservative government is shifting citizenship discourse to a more traditional language - as Winter points out - it has not reduced immigration, ended dual citizenship, or eliminated multiculturalism, all goals of the Reform Party that the current prime minister once helped build. “Lock-in” effects (or policy feedback loops) based on high immigrant naturalization and the coming of age of a second-generation with citizenship also d emands study, in North America and elsewhere. Much of the research thus far suggests that political decisions over citizenship status and rights do not seem linked to immigrants’ political activism. State-centered decision-making may have characterized policy in the early post-World War II period in Europe (and East Asia?), but does it continue to hold today? Majority publics and immigrant-origin residents are increasingly politicized around citizenship and immigration. Does immigrant agency extend citizenship status, rights and identity to those born outside the polity? Is electoral power key, or is protest necessary? How is citizenship practiced, and contested, irrespective of formal status? These are important and understudied empirical questions, ones that demand theoretical creativity - across sub-fields and disciplines - in conceptualizing and understanding citizenship in contemporary times.

Discarge compilation from The Global River Discharge (RivDIS) Project

The Global River Discharge (RivDIS) data set contains monthly discharge measurements for 1018 stations located throughout the world. The period of record varies widely from station to station, with a mean of 21.5 years. These data were digitized from published UNESCO archives by Charles Voromarty, Balaze Fekete, and B.A. Tucker of the Complex Systems Research Center (CSRC) at the University of New Hampshire. River discharge is typically measured through the use of a rating curve that relates local water level height to discharge. This rating curve is used to estimate discharge from the observed water level. The rating curves are periodically rechecked and recalibrated through on-site measurement of discharge and river stage.

Pragmatica Real sobre cosas tocantes al assiento general del Reyno de Valencia por razon de la expulsion de los moriscos y reduccion de los Censales

Hay un ejemplar encuadernado con: Descripcion del muelle que la... ciudad de Valencia ha mandado fabricar en su playa... (XVII/40).

Real Pragmatica feta per la magestat del Rey ... ab la qual mana reduhir tots los censals de les ciutats, Viles Reals, Vniuersitats, y particulars del present Regne, a raho de vint mil lo millar, que es a sou per lliura

Texto en castellano

Real Pragmatica sobre lo reparo dels danys que resulten de les nullitats ques dihuen de les sentencies ab vots del Supremo Consell y reuisions de les prouisions interlocutories ques demanem cum toto Regio Consilio

Hay un ejemplar encuadernado con: Real Pragmática ab la qual la magestat del Rey Don Felip ... prohibix tot genero de pedrenyals de qualseuol llargaria que sien, y los arcabuços de mecha menors de tres palms y mig de alna de Valencia. (XVI/461).

Real Pragmatica sobre la bona administracio del Almodi de la Ciutat de Valencia y ... bon auituallament de aquella ... manada publicar per ... don Francisco de Moncada marques de Aytona ... y Capita general en lo present Regne de Valencia

Hecha pública en Valencia el 8 de octubre de 1594

Pragmática

Hay un ejemplar encuadernado con: Real Pragmática ab la qual la magestat del Rey Don Felip ... prohibix tot genero de pedrenyals de qualseuol llargaria que sien, y los arcabuços de mecha menors de tres palms y mig de alna de Valencia. (XVI/461).

Role of B cells in antigen presentation of the hepatitis B core

The hepatitis B virus (HBV) nucleocapsid or core antigen (HBcAg) is extremely immunogenic during infection and after immunization. For example, during many chronic infections, HBcAg is the only antigen capable of eliciting an immune response, and nanogram amounts of HBcAg elicit antibody production in mice. Recent structural analysis has revealed a number of characteristics that may help explain this potent immunogenicity. Our analysis of how the HBcAg is presented to the immune system revealed that the HBcAg binds to specific membrane Ig (mIg) antigen receptors on a high frequency of resting, murine B cells sufficiently to induce B7.1 and B7.2 costimulatory molecules. This enables HBcAg-specific B cells from unprimed mice to take up, process, and present HBcAg to naive Th cells in vivo and to T cell hybridomas in vitro approximately 105 times more efficiently than classical macrophage or dendritic antigen-presenting cells (APC). These results reveal a structure–function relation for the HBcAg, confirm that B cells can function as primary APC, explain the enhanced immunogenicity of HBcAg, and may have relevance for the induction and/or maintenance of chronic HBV infection.

Evidence for a preformed transducer complex organized by the B cell antigen receptor.

The B cell antigen receptor (BCR) consists of the membrane-bound immunoglobulin (mIg) molecule and the Ig-alpha/Ig-beta heterodimer, which functions as signaling subunit of the receptor. Stimulation of the BCR activates protein tyrosine kinases (PTKs) that phosphorylate a number of substrate proteins, including the Ig-alpha/Ig-beta heterodimer of the BCR itself. How the PTKs become activated after BCR engagement is not known at present. Here, we show that BCR-negative J558L cells treated with the protein tyrosine phosphatase inhibitor pervanadate/H2O2 display only a weak substrate phosphorylation. However, in BCR-positive transfectants of J558L, treatment with pervanadate/H2O2 induces a strong phosphorylation of several substrate proteins. Treatment with pervanadate/H2O2 does not result in receptor crosslinking, yet the pattern of protein phosphorylation is similar to that observed after BCR stimulation by antigen. The response requires cellular integrity because tyrosine phosphorylation of most substrates is not visible in cell lysates. Cells that express a BCR containing an Ig-alpha subunit with a mutated immunoreceptor tyrosine-based activation motif display a delayed response. The data suggest that, once expressed on the surface, the BCR organizes protein tyrosine phosphatases, PTKs, and their substrates into a transducer complex that can be activated by pervanadate/H202 in the absence of BCR crosslinking. Assembly of this preformed complex seems to be a prerequisite for BCR-mediated signal transduction.