Evaluating quality of life tools in North American patients with erythropoietic protoporphyria and X-linked protoporphyria.

BackgroundErythropoietic protoporphyria (EPP) and X-linked Protoporphyria (XLP) are rare photodermatoses presenting with severe phototoxicity. Although anecdotally, providers who treat EPP patients acknowledge their life-altering effects, tools that fully capture their impact on quality of life (QoL) are lacking.MethodsAdult patients with EPP/XLP were given four validated QoL tools: the Patient Reported Outcomes Measurement Information System 57 (PROMIS-57), the Hospital Anxiety and Depression Scale (HADS), the Illness Perception Questionnaire Revised (IPQR), and an EPP-Specific tool. All patients received the PROMIS-57 while the HADS, IPQR, and EPP-Specific tools were introduced at a later date. Associations between responses and clinical phenotypes were explored.ResultsTwo hundred and two patients were included; 193 completed PROMIS-57, 104 completed IPQR, 103 completed HADS, and 107 completed the EPP-Specific tool. The IPQR showed that patients strongly believed EPP/XLP had a negative impact on their lives. Mean scores in anxiety and depression domains of both HADS and PROMIS-57 were normal; however, anxiety scores from HADS were borderline/abnormal in 20% of patients. The EPP-Specific tool revealed a decreased QoL in most patients. The PROMIS-57 showed that 21.8% of patients have clinically significant pain interference. Several tool domains correlated with measures of disease severity, most being from the PROMIS-57.ConclusionsImpaired QoL is an important consequence of EPP/XLP. PROMIS-57 was most sensitive in evaluating impaired QoL in EPP/XLP. Further research is needed to compare the effectiveness of it for assessing response to treatment

Critical role for interferon regulatory factor 3 (IRF-3) and IRF-7 in type i interferon-mediated control of murine norovirus replication

Human noroviruses (HuNoV) are the major cause of epidemic, nonbacterial gastroenteritis in the world. The short course of HuNoV-induced symptoms has implicated innate immunity in control of norovirus (NoV) infection. Studies using murine norovirus (MNV) confirm the importance of innate immune responses during NoV infection. Type I alpha and beta interferons (IFN-α/β) limit HuNoV replicon function, restrict MNV replication in cultured cells, and control MNV replication in vivo. Therefore, the cell types and transcription factors involved in antiviral immune responses and IFN-α/β-mediated control of NoV infection are important to define. We used mice with floxed alleles of the IFNAR1 chain of the IFN-α/β receptor to identify cells expressing lysozyme M or CD11c as cells that respond to IFN-α/β to restrict MNV replication in vivo. Furthermore, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and overlapping antiviral responses to restrict MNV replication in vivo. IRF-3 and IRF-7 restrict MNV replication in both cultured macrophages and dendritic cells, are required for induction of IFN-α/β in macrophages but not dendritic cells, and are dispensable for the antiviral effects of IFN-α/β that block MNV replication. These studies suggest that expression of the IFN-α/β receptor on macrophages/neutrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses to NoV infection

Two Pfam protein families characterized by a crystal structure of protein lpg2210 from Legionella pneumophila.

BackgroundEvery genome contains a large number of uncharacterized proteins that may encode entirely novel biological systems. Many of these uncharacterized proteins fall into related sequence families. By applying sequence and structural analysis we hope to provide insight into novel biology.ResultsWe analyze a previously uncharacterized Pfam protein family called DUF4424 [Pfam:PF14415]. The recently solved three-dimensional structure of the protein lpg2210 from Legionella pneumophila provides the first structural information pertaining to this family. This protein additionally includes the first representative structure of another Pfam family called the YARHG domain [Pfam:PF13308]. The Pfam family DUF4424 adopts a 19-stranded beta-sandwich fold that shows similarity to the N-terminal domain of leukotriene A-4 hydrolase. The YARHG domain forms an all-helical domain at the C-terminus. Structure analysis allows us to recognize distant similarities between the DUF4424 domain and individual domains of M1 aminopeptidases and tricorn proteases, which form massive proteasome-like capsids in both archaea and bacteria.ConclusionsBased on our analyses we hypothesize that the DUF4424 domain may have a role in forming large, multi-component enzyme complexes. We suggest that the YARGH domain may play a role in binding a moiety in proximity with peptidoglycan, such as a hydrophobic outer membrane lipid or lipopolysaccharide

Polls and the political process: the use of opinion polls by political parties and mass media organizations in European post‐communist societies (1990–95)

Opinion polling occupies a significant role within the political process of most liberal-capitalist societies, where it is used by governments, parties and the mass media alike. This paper examines the extent to which polls are used for the same purposes in the post-communist countries of Central and Eastern Europe, and in particular, for bringing political elites and citizens together. It argues that these political elites are more concerned with using opinion polls for gaining competitive advantage over their rivals and for reaffirming their political power, than for devolving political power to citizens and improving the general processes of democratization

Molybdenum evidence for expansive sulfidic water masses in ~750Ma oceans

The Ediacaran appearance of large animals, including motile bilaterians, is commonly hypothesized to reflect a physiologically enabling increase in atmospheric and oceanic oxygen abundances (pO2). To date, direct evidence for low oxygen in pre-Ediacaran oceans has focused on chemical signatures in the rock record that reflect conditions in local basins, but this approach is both biased to constrain only shallower basins and statistically limited when we seek to follow the evolution of mean ocean chemical state through time. Because the abundance and isotopic composition of molybdenum (Mo) in organic-rich euxinic sediments can vary in response to changes in global redox conditions, Mo geochemistry provides independent constraints on the global evolution of well-oxygenated environments. Here, we establish a theoretical framework to access global marine Mo cycle in the past from the abundance and isotope composition of ancient seawater. Further, we investigate the ~ 750 Ma Walcott Member of the Chuar Group, Grand Canyon, which accumulated in a rift basin with open connection to the ocean. Iron speciation data from upper Walcott shales indicate that local bottom waters were anoxic and sulfidic, consistent with their high organic content (up to 20 wt.%). Similar facies in Phanerozoic successions contain high concentrations of redox-sensitive metals, but in the Walcott Member, abundances of Mo and U, as well as Mo/TOC (~ 0.5 ppm/wt.%) are low. δ98Mo values also fall well below modern equivalents (0.99 ± 0.13‰ versus ~ 2.35‰ today). These signatures are consistent with model predictions where sulfidic waters cover ~ 1–4% of the global seafloor, corresponding to a ~ 20–80 fold increase compared to the modern ocean. Therefore, our results suggest globally expansive sulfidic water masses in mid-Neoproterozoic oceans, bridging a nearly 700 million-year gap in previous Mo data. We propose that anoxic and sulfidic (euxinic) conditions governed Mo cycling in the oceans even as ferruginous subsurface waters re-appeared 800–750 Ma, and we interpret this anoxic ocean state to reflect a markedly lower atmospheric and oceanic O2 level, consistent with the hypothesis that pO2 acted as an evolutionary barrier to the emergence of large motile bilaterian animals prior to the Ediacaran Period.Organismic and Evolutionary Biolog

Evaluating the Patient-Reported Outcomes Measurement Information System scales in acute intermittent porphyria.

PurposeAcute intermittent porphyria (AIP) is a rare inborn error of heme biosynthesis characterized by life-threatening acute attacks. Few studies have assessed quality of life (QoL) in AIP and those that have had small sample sizes and used tools that may not have captured important domains.MethodsBaseline data from the Porphyrias Consortium's Longitudinal Study were obtained for 259 patients, including detailed disease and medical history data, and the following Patient-Reported Outcomes Measurement Information System (PROMIS) scales: anxiety, depression, pain interference, fatigue, sleep disturbance, physical function, and satisfaction with social roles. Relationships between PROMIS scores and clinical and biochemical AIP features were explored.ResultsPROMIS scores were significantly worse than the general population across all domains, except depression. Each domain discriminated well between asymptomatic and symptomatic patients with symptomatic patients having worse scores. Many important clinical variables like symptom frequency were significantly associated with domain scores in univariate analyses, showing responsiveness of the scales, specifically pain interference and fatigue. However, most regression models only explained ~20% of the variability observed in domain scores.ConclusionPain interference and fatigue were the most responsive scales in measuring QoL in this AIP cohort. Future studies should assess whether these scales capture longitudinal disease progression and treatment response

‘Dominant ethnicity’ and the ‘ethnic-civic’ dichotomy in the work of A. D. Smith

This article considers the way in which the work of Anthony Smith has helped to structure debates surrounding the role of ethnicity in present-day nations. Two major lines of enquiry are evident here. First, the contemporary role of dominant ethnic groups within 'their' nations and second, the interplay between ethnic and civic elements in nationalist argument. The two processes are related, but maintain elements of distinctiveness. Smith's major contribution to the dominant ethnicity debate has been to disembed ethnicity from the ideologically-charged and/or anglo-centric discourse of ethnic relations and to place it in historical context, thereby opening up space for dominant group ethnicity to be considered as a distinct phenomenon. This said, Smith's work does not adequately account for the vicissitudes of dominant ethnicity in the contemporary West. Building on the classical works of Hans Kohn and Friedrich Meinecke, Anthony Smith has also made a seminal contribution to the debate on civic and ethnic forms of national identity and nationalist ideology. As well as freeing this debate from the strong normative overtones which it has often carried, he has continued to insist that the terms civic and ethnic should be treated as an ideal-typical distinction rather than a scheme of classification