Detection of the European epidemic strain of Trichomonas gallinae in finches, but not other non-columbiformes, in the absence of macroscopic disease

Finch trichomonosis is an emerging infectious disease affecting European passerines caused by a clonal strain of Trichomonas gallinae. Migrating chaffinches (Fringilla coelebs) were proposed as the likely vector of parasite spread from Great Britain to Fennoscandia. To test for such parasite carriage, we screened samples of oesophagus/crop from 275 Apodiform, Passeriform and Piciform birds (40 species) which had no macroscopic evidence of trichomonosis (i.e. necrotic ingluvitis). These birds were found dead following the emergence of trichomonosis in Great Britain, 2009-2012, and were examined post-mortem. Polymerase chain reactions were used to detect (ITS1/5.8S rRNA/ITS2 region and single subunit rRNA gene) and to subtype (Fe-hydrogenase gene) T. gallinae. Trichomonas gallinae was detected in six finches (three chaffinches, two greenfinches (Chloris chloris) and a bullfinch (Pyrrhula pyrrhula)). Sequence data had 100% identity to the European finch epidemic A1 strain for each species. While these results are consistent with finches being vectors of T. gallinae, alternative explanations include the presence of incubating or resolved T. gallinae infections. The inclusion of histopathological examination would help elucidate the significance of T. gallinae infection in the absence of macroscopic lesions

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Restricted by borders: trade-offs in transboundary conservation planning for large river systems

Effective conservation of freshwater biodiversity requires accounting for connectivity and the propagation of threats along river networks. With this in mind, the selection of areas to conserve freshwater biodiversity is challenging when rivers cross multiple jurisdictional boundaries. We used systematic conservation planning to identify priority conservation areas for freshwater fish conservation in Hungary (Central Europe). We evaluated the importance of transboundary rivers to achieve conservation goals by systematically deleting some rivers from the prioritization procedure in Marxan and assessing the trade-offs between complexity of conservation recommendations (e.g., conservation areas located exclusively within Hungary vs. transboundary) and cost (area required). We found that including the segments of the largest transboundary rivers (i.e. Danube, Tisza) in the area selection procedure yielded smaller total area compared with the scenarios which considered only smaller national and transboundary rivers. However, analyses which did not consider these large river segments still showed that fish diversity in Hungary can be effectively protected within the country’s borders in a relatively small total area (less than 20 % of the country’s size). Since the protection of large river segments is an unfeasible task, we suggest that transboundary cooperation should focus on the protection of highland riverine habitats (especially Dráva and Ipoly Rivers) and their valuable fish fauna, in addition to the protection of smaller national rivers and streams. Our approach highlights the necessity of examining different options for selecting priority areas for conservation in countries where transboundary river systems form the major part of water resources.Full Tex

Investigation of Exomic Variants Associated with Overall Survival in Ovarian Cancer

BACKGROUND: While numerous susceptibility loci for epithelial ovarian cancer (EOC) have been identified, few associations have been reported with overall survival. In the absence of common prognostic genetic markers, we hypothesize that rare coding variants may be associated with overall EOC survival and assessed their contribution in two exome-based genotyping projects of the Ovarian Cancer Association Consortium (OCAC). METHODS: The primary patient set (Set 1) included 14 independent EOC studies (4,293 patients) and 227,892 variants, and a secondary patient set (Set 2) included six additional EOC studies (1,744 patients) and 114,620 variants. Because power to detect rare variants individually is reduced, gene-level tests were conducted. Sets were analyzed separately at individual variants and by gene, and then combined with meta-analyses (73,203 variants and 13,163 genes overlapped). RESULTS: No individual variant reached genome-wide statistical significance. A SNP previously implicated to be associated with EOC risk and, to a lesser extent, survival, rs8170, showed the strongest evidence of association with survival and similar effect size estimates across sets (Pmeta = 1.1E-6, HRSet1 = 1.17, HRSet2 = 1.14). Rare variants in ATG2B, an autophagy gene important for apoptosis, were significantly associated with survival after multiple testing correction (Pmeta = 1.1E-6; Pcorrected = 0.01). CONCLUSIONS: Common variant rs8170 and rare variants in ATG2B may be associated with EOC overall survival, although further study is needed. IMPACT: This study represents the first exome-wide association study of EOC survival to include rare variant analyses, and suggests that complementary single variant and gene-level analyses in large studies are needed to identify rare variants that warrant follow-up study

Wide-scale continuous quality improvement: A study of stakeholders' use of quality of care reports at various system levels, and factors mediating use

© 2019 Laycock, Bailie, Percival, Matthews, Cunningham, Harvey, Copley, Patel and Bailie. Introduction: Increasing the use of evidence in healthcare policy and practice requires greater understanding of how stakeholders use evidence to inform policy, refine systems and change practice. Drawing on implementation theory, we have used system-focused participatory research to engage diverse stakeholders in using aggregated continuous quality improvement (CQI) data from Australian Indigenous primary health care settings to identify priority evidence-practice gaps, barriers/enablers and strategies for improvement. This article reports stakeholders' use or intended use of evidence at various levels of the system, and factors mediating use. Material and Methods: Interviews were undertaken with a purposeful sample of 30 healthcare stakeholders in different roles, organization types and settings in one Australian jurisdiction and with national participants, as part of the project's developmental evaluation. Qualitative data were analyzed to identify themes and categories relating to use of evidence. Results: Context-specific aggregated CQI data that were relatable to the diverse professional roles and practices provided an effective starting point for sharing perspectives, generating practice-based evidence and mobilizing evidence-use. Interviewees perceived the co-produced findings as applicable at different levels and useful for planning, policy development, supporting best practice and reflection, capacity strengthening and developing new research. Factors mediating use were commitment to best practice; the credibility of the evidence and its perceived relevance to work roles, contexts and decision needs; report format and language; facilitation and communication; competing work pressures and the organizational environment for change. Conclusions: This study found that primary health care stakeholders used evidence on quality of care for a variety of purposes. This could be linked to the interactive research processes used to engage stakeholders in different roles and settings in interpreting data, sharing and generating knowledge. Findings indicate that system-based participatory research using CQI data and iterative, interactive and systematic CQI-based methods can be applied at scale to support concurrent action for healthcare improvement at different system levels. Factors known to influence implementation should be addressed within the research design to optimize evidence use. Further research is needed to explore the utility of interactive dissemination for engaging healthcare stakeholders in informing policy and system change