A surveillance system to assess the need for updating systematic reviews.

BackgroundSystematic reviews (SRs) can become outdated as new evidence emerges over time. Organizations that produce SRs need a surveillance method to determine when reviews are likely to require updating. This report describes the development and initial results of a surveillance system to assess SRs produced by the Agency for Healthcare Research and Quality (AHRQ) Evidence-based Practice Center (EPC) Program.MethodsTwenty-four SRs were assessed using existing methods that incorporate limited literature searches, expert opinion, and quantitative methods for the presence of signals triggering the need for updating. The system was designed to begin surveillance six months after the release of the original review, and then ceforth every six months for any review not classified as being a high priority for updating. The outcome of each round of surveillance was a classification of the SR as being low, medium or high priority for updating.ResultsTwenty-four SRs underwent surveillance at least once, and ten underwent surveillance a second time during the 18 months of the program. Two SRs were classified as high, five as medium, and 17 as low priority for updating. The time lapse between the searches conducted for the original reports and the updated searches (search time lapse - STL) ranged from 11 months to 62 months: The STL for the high priority reports were 29 months and 54 months; those for medium priority reports ranged from 19 to 62 months; and those for low priority reports ranged from 11 to 33 months. Neither the STL nor the number of new relevant articles was perfectly associated with a signal for updating. Challenges of implementing the surveillance system included determining what constituted the actual conclusions of an SR that required assessing; and sometimes poor response rates of experts.ConclusionIn this system of regular surveillance of 24 systematic reviews on a variety of clinical interventions produced by a leading organization, about 70% of reviews were determined to have a low priority for updating. Evidence suggests that the time period for surveillance is yearly rather than the six months used in this project

Evolutionarily distant I domains can functionally replace the essential ligand-binding domain of Plasmodium TRAP

Inserted (I) domains function as ligand-binding domains in adhesins that support cell adhesion and migration in many eukaryotic phyla. These adhesins include integrin alpha beta heterodimers in metazoans and single subunit transmembrane proteins in apicomplexans such as TRAP in Plasmodium and MIC2 in Toxoplasma. Here we show that the I domain of TRAP is essential for sporozoite gliding motility, mosquito salivary gland invasion and mouse infection. Its replacement with the I domain from Toxoplasma MIC2 fully restores tissue invasion and parasite transmission, while replacement with the aXI domain from human integrins still partially restores liver infection. Mutations around the ligand binding site allowed salivary gland invasion but led to inefficient transmission to the rodent host. These results suggest that apicomplexan parasites appropriated polyspecific I domains in part for their ability to engage with multiple ligands and to provide traction for emigration into diverse organs in distant phyla

Diagnostic accuracy, risk assessment, and cost-effectiveness of component-resolved diagnostics for food allergy: a systematic review

Component-resolved diagnostics (CRD) are promising tools for diagnosing food allergy, offering the potential to determine specific phenotypes and to develop patient-tailored risk profiles. Nevertheless, the diagnostic accuracy of these tests varies across studies; thus, their clinical utility remains unclear. Therefore, we synthesized the evidence from studies investigating the diagnostic accuracy, risk assessment ability, and cost-effectiveness of CRD for food allergy.We systematically searched 10 electronic databases and four clinical trial registries for studies published January 2000-February 2017. The quality of included studies was assessed using QUADAS-2. Due to heterogeneity, we narratively synthesized the evidence.Eleven studies met inclusion criteria, altogether recruiting 1,098 participants. The food allergies investigated were cow's milk, hen's egg, peanut, hazelnut, and shrimp. The components with the highest diagnostic accuracy for each allergen, along with their sensitivity-specificity pairs, were: Bos d 4 for cow's milk (62.0% and 87.5%), Gal d 1 for hen's egg (84.2% and 89.8% for heated egg, and 60.6% and 97.1% for raw egg), Ara h 2 for peanut (80.3% and 95.1%), Cor a 14 for hazelnut (100% and 93.8%), and Lit v 1 for shrimp (82.8% and 56.3%) allergy.Selected components of cow's milk, hen's egg, peanut, hazelnut, and shrimp allergen showed high specificity, but lower sensitivity. However, few studies exist for each component, and studies vary widely regarding the cut-off values used, making it challenging to synthesize findings across studies. Further research is needed to determine clinically appropriate cut-off values, risk assessment abilities, and cost-effectiveness of CRD approaches. This article is protected by copyright. All rights reserved

Structural basis of malaria transmission blockade by a monoclonal antibody to gamete fusogen HAP2.

Funder: Isaac Newton Trust; FundRef: http://dx.doi.org/10.13039/501100004815Funder: Alborada Trust; FundRef: http://dx.doi.org/10.13039/100008288Funder: Wellcome Trust; FundRef: http://dx.doi.org/10.13039/100004440Funder: University of Cambridge; FundRef: http://dx.doi.org/10.13039/501100000735Funder: Global Health Innovative Technology Fund; FundRef: http://dx.doi.org/10.13039/501100013996Funder: Rosetrees Trust; FundRef: http://dx.doi.org/10.13039/501100000833Funder: Royal Society; FundRef: http://dx.doi.org/10.13039/501100000288HAP2 is a transmembrane gamete fusogen found in multiple eukaryotic kingdoms and is structurally homologous to viral class II fusogens. Studies in Plasmodium have suggested that HAP2 is an attractive target for vaccines that block transmission of malaria. HAP2 has three extracellular domains, arranged in the order D2, D1, and D3. Here, we report monoclonal antibodies against the D3 fragment of Plasmodium berghei HAP2 and crystal structures of D3 in complex with Fab fragments of two of these antibodies, one of which blocks fertilization of Plasmodium berghei in vitro and transmission of malaria in mosquitoes. We also show how this Fab binds the complete HAP2 ectodomain with electron microscopy. The two antibodies cross-react with HAP2 among multiple plasmodial species. Our characterization of the Plasmodium D3 structure, HAP2 ectodomain architecture, and mechanism of inhibition provide insights for the development of a vaccine to block malaria transmission

'Gut health': a new objective in medicine?

'Gut health' is a term increasingly used in the medical literature and by the food industry. It covers multiple positive aspects of the gastrointestinal (GI) tract, such as the effective digestion and absorption of food, the absence of GI illness, normal and stable intestinal microbiota, effective immune status and a state of well-being. From a scientific point of view, however, it is still extremely unclear exactly what gut health is, how it can be defined and how it can be measured. The GI barrier adjacent to the GI microbiota appears to be the key to understanding the complex mechanisms that maintain gut health. Any impairment of the GI barrier can increase the risk of developing infectious, inflammatory and functional GI diseases, as well as extraintestinal diseases such as immune-mediated and metabolic disorders. Less clear, however, is whether GI discomfort in general can also be related to GI barrier functions. In any case, methods of assessing, improving and maintaining gut health-related GI functions are of major interest in preventive medicine

Detection of the peanut allergen Ara h 6 in foodstuffs using a voltammetric biosensing approach

A voltammetric biosensor for Ara h 6 (a peanut allergen) detection in food samples was developed. Gold nanoparticle-modified screen-printed carbon electrodes were used to develop a sandwich-type immunoassay using two-monoclonal antibodies. The antibody-antigen interaction was detected through the electrochemical detection of enzymatically deposited silver. The immunosensor presented a linear range between 1 and 100 ng/ml, as well as high precision (inter-day RSD ≤9.8 %) and accuracy (recoveries ≥96.7 %). The detection and quantification limits were 0.27 and 0.88 ng/ml, respectively. It was possible to detect small levels of Ara h 6 in complex food matrices

Use of a basophil activation test as a complementary diagnostic tool in the diagnosis of severe peanut allergy in adults

BACKGROUND: Diagnosis of severe peanut allergy is difficult and delays in making an accurate diagnosis may place the patient at risk. Adults with a history of anaphylaxis must strictly avoid any contact with peanuts or products that may contain traces of peanuts. For these persons, conventional evaluations with skin prick testing (SPT) and IgE tests may not be sufficient to assess the risk of anaphylaxis. Therefore, we investigated whether the basophil activation test (BAT) could be used for the diagnosis of severe peanut allergy in adults. We compared the non-invasive BAT with conventional laboratory diagnostic tests, including SPT and specific IgE to allergen extracts and components, for the diagnosis of severe peanut allergy. METHODS: Forty-seven persons with severe allergy to peanuts and a clinical diagnosis of anaphylaxis (PA-group), 22 subjects with peanut sensitization (PS-group) and 22 control (C-group) subjects, all in the age range of 18–60 years, were recruited retrospectively and prospectively into the study. Thirty-four patients with peanut allergy and 11 peanut-sensitized patients were sensitized to soy, while 36 patients in the PA-group and 20 patients in the PS-group were sensitized to birch pollen. All the patients and control subjects were investigated with BAT and SPT for responses to peanut, soy and birch extracts and their serum samples were assayed for the presence of specific IgE to peanut, soy and birch extracts, as well as IgE to allergen components (ISAC). RESULTS: In a multivariate factor analysis, severe peanut allergy (PA) was positively associated with SPT to peanut, IgE to peanut, BAT to peanut and IgE to rAra h 1, 2, 3 and 6 peanut components, as well as to soy components (nGly m 5 and nGly m 6). In contrast, peanut sensitization was positively associated with increased levels of IgE to rAra h 8, birch and birch-related components. BAT-detected reactivity to peanut was significantly higher in patients who had a history of severe allergy to peanuts, as compared with patients who were sensitized to peanuts (p < 0.001), and the receiver operating curve (ROC) analysis showed that BAT had high sensitivity and specificity for predicting severe peanut allergy, with a ROC area under the curve of 0.862. However, in the PA-group, the BAT results for peanut correlated only weakly with the levels of IgE to rAra h 1, 2 and 3 and nAra h 6. Study limitations: oral provocation in the patients with a history of severe peanut allergy could not be performed to compare clinical reactivity with the BAT result due to ethical constraints. Neither was it possible to perform BAT with peanut recombinant allergens which were not available at the time the study commenced CONCLUSIONS: BAT is useful in determining the severity of peanut allergy and may be used as a complementary diagnostic tool to ensure accurate diagnosis of severe peanut allergy in adults. Thus, it may reduce the need to subject these patients to further tests, including an open challenge with peanuts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13601-015-0064-9) contains supplementary material, which is available to authorized users