259594 research outputs found
Sort by
Development and validation of a clinical risk model for postoperative outcome in newly diagnosed glioblastoma: a report of the RANO resect group
No full textType-specific impacts of protein defects in pathogenic NFKB2 variants: novel clinical findings from 138 patients
No full textBackgroundThe noncanonical NF-κB2 (nuclear factor kappa B subunit 2) pathway is integral in regulating immunologic responses, supervising immune function, development, and homeostasis. NFKB2 encodes the cytoplasmic precursor p100, which undergoes processing of its inhibitory C-terminal half to generate p52. Impeding C-terminal defects are well established to cause primary immunodeficiency disorder. In contrast, the mechanism of truncating N-terminal defects remains obscure.ObjectiveWe characterized clinical phenotypes associated with 3 distinct protein-defect types: (1) early truncations: typically occurring N-terminal relative to the nuclear localization sequence and affecting the Rel homology domain, predicting p100 expression to be halved and subsequent p52 generation by processing to be diminished; (2) central truncations: mainly affecting the ARD and predicting immediate expression of p52-like proteins and a 50% reduction of p100; and (3) C-terminal phosphorylation-/ubiquitination domain defects: causing expression of nonprocessable p100 with retained IκB-like activity and subsequently reducing generation of p52.MethodsWe performed literature research on PubMed, Clinvar, and Human Gene Mutation Database collecting clinical and immunologic data on NFKB2 patients, focusing on comparing protein-defect–specific impacts.ResultsThe highest prevalence of early-onset primary immunodeficiency disorder and antibody deficiency occurred in the CTD-defect group. In addition, endocrinological abnormalities and T-cell–mediated autoimmunity were common and frequently required immunosuppression. An extensive immunologic workup revealed patients with C-terminal defects to have pan-hypogammaglobulinemia and reduced specific antibody responses and markedly impaired B-cell differentiation, but normal to elevated T-cell counts. In contrast, pathogenic NFKB2 variants causing central or early-truncating protein defects were only partially penetrant, with ameliorated symptoms and diminished T-cell–mediated autoimmunity.ConclusionsOur work defines a clear genotype-phenotype correlation for NFKB2 mutations
Frequencies and causes of ABO‐incompatible red cell transfusions in France, Germany and the United Kingdom
No full textDifferent people, equally bound by water? - the lower Don region of the 18th and 19th century as a riparian society
No full textThis paper explores the concept of riparian societies as a framework for interaction between the Don river and different neighbouring communities that emerged at the end of the 18th century, namely the Don-Cossacks, a military estate, and a growing number of Ukrainian peasants that migrated to the region since the late 17th century. While close in proximity, each community was organised by a different set of privileges and a particular socio-economic order, resembling the Russian “empire of difference” in miniature. At the turn of the 19th century, a high density of political, administrative, cultural, and economic boundaries shaped the lower Don area. The paper argues that differing from the artificial administrative imperial creation of the Don-Cossack territory and the governorate of Ekaterinoslav from above that overlapped in this region, the river liquefied social, economic, and political borders set from above, and helped to create a particular region whose diverse inhabitants formed a unique riparian society at its shores. This approach follows the trend in recent research on Eurasian empires, according to which imperial regions are not solely shaped as administrative creations “from above”, but develop from an interplay of trade, migration networks and historical geography. Behind the façade of a contradictory social and ethnic order, the lower Don territory transformed into a genuine region defined less by imperial boundaries but by a shared and often fluid set of challenges and promises of the river to its inhabitants. Thus, the paper argues for stronger attention towards the nexus between ecology and empire that not only defined agricultural production or migration, but peculiar social and ethnic orders on the peripheries of the Empire
Impact of Pseudomonas aeruginosa carriage on intensive care unit-acquired pneumonia: a European multicentre prospective cohort study
No full textObjectivesPseudomonas aeruginosa (PA) is a common causative pathogen of pneumonia acquired in the intensive care unit (ICU). The aim of this study was to determine the incidence of PA ICU pneumonia (PAIP) and to quantify its independent association with PA colonization at different body sites.MethodsAdult patients on mechanical ventilation at ICU admission were prospectively enrolled across 30 European ICUs. PA colonization in the perianal area and in the lower respiratory tract was assessed within 72 hours after ICU admission and twice weekly until ICU discharge. PAIP development was evaluated daily. Competing risk models with colonization as a time-varying exposure and ICU death and discharge as competing events were fitted and adjusted for confounders to investigate the association between PA carriage and PAIP.ResultsA total of 1971 subjects were enrolled. The colonization prevalence with PA in the first 72 hours of ICU admission was 10.4% (179 perianal and 51 respiratory), whereas the acquisition incidence during the ICU stay was 7.0% (158 perianal and 47 respiratory). Of the 43 (1.8%) patients who developed PAIP, 11 (25.6%) were PA colonized on admission and 9 (20.9%) acquired colonization before PAIP onset. Both perianal (adjusted subdistribution hazard ratio, 4.4; 95% CI, 1.7–11.6) and respiratory colonization (adjusted subdistribution hazard ratio: 4.6, 95% CI, 1.9–11.1) were independently associated with PAIP development.DiscussionPAIP incidence was higher in PA colonized vs. non-colonized patients. Colonization of both the rectum and of the respiratory tract was associated with development of PAIP. The increased risk of PA colonization for subsequent infection provides an opportunity for targeted preventive interventions
Cone beam computed tomography - frequency and exposure settings at University (Dental) hospitals in Central and Northern Europe
No full textTopographical variations in the skin barrier and their role in disease pathogenesis
No full textThe skin barrier can be divided into at least four functional units: chemical, microbial, physical and immunological barriers. The chemical and microbial barriers have previously been shown to exhibit different characteristics in topographically distinct skin regions. There is increasing evidence that the physical and immunological barriers also show marked variability in different areas of the skin. Here, we review recent data on the topographical variations of skin barrier components, the contribution of these variations to the homeostatic function of the skin and their impact on the pathogenesis of specific immune-mediated skin diseases (such as atopic dermatitis and papulopustular rosacea). Recognition of these topographical barrier differences will improve our understanding of skin homeostasis and disease pathogenesis and provide a basis for body site-specific targeted therapies
