Affinity tagging & purification of the fucose binding LecB protein

The fucose binding LecB protein is one of two identified lectins produced by the opportunistic pathogen Pseudomonas aeruginosa (PA01) and is implicated in contributing to its virulence. A large number of homologous proteins have been identified in other bacterial species that exhibit extremely high sequence identity and similarity to LecB. However, key amino acid residues known to participate in fucose binding in LecB are altered in many of these proteins. Some of these proteins have been shown to exhibit altered sugar specificities while others are as yet uncharacterised. The existence of such homologues suggests the sugar binding specificity of the LecB protein could potentially be further diversified through mutagenesis to generate novel biomolecular recognition molecules for glycoprotein characterisation and purification applications

The range of peripapillary retinal nerve fibre layer and optic disc parameters in children aged up to but not including 18 years of age, as measured by optical coherence tomography:protocol for a systematic review

BACKGROUND: The parameters of the optic disc and peripapillary retinal nerve fibre layer (pRNFL) in children may vary with disease processes that contribute to visual impairment and blindness and so could be useful as an objective measure in at-risk children. There is no standardised reference for the normal parameters of the optic disc and pRNFL in children; however, there are a large number of small individual studies that have been undertaken to look at these measures. METHODS: A systematic review of current literature on the range of pRNFL and optic disc parameters in children aged less than 18 years will be performed. Studies will be considered for review if they report numerical data on optic disc and pRNFL parameters, measured using optical coherence tomography. Outcome measures will include mean pRNFL thickness and cup-disc ratio. The bibliographic databases Medline, CINAHL, EMBASE, Scopus and Web of Science will be systematically searched from 1991. Screening of search results will be conducted by two authors working independently, as will extraction of primary and secondary outcome data. Ten per cent of all other data extraction will be checked by a second author. Results will be compiled and presented in evidence tables. Where possible and appropriate, study-specific estimates will be combined to obtain an overall summary estimate of pRNFL thickness and cup-disc ratio across studies and results will be presented by age of population. Subgroup analyses will be undertaken for children of different ethnicities. DISCUSSION: This review aims to provide an overview of the parameters of the optic disc and pRNFL in children of different ages in order to identify gaps in knowledge and to improve understanding of what might be considered within/outside the range of normality. The findings will be presented in peer-reviewed journals and will be presented at conferences. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033068 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13643-016-0247-z) contains supplementary material, which is available to authorized users

Montreal Cognitive Assessment for the detection of dementia

Background: Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource‐limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. Objectives: To determine the accuracy of the Montreal Cognitive Assessment (MoCA) for the detection of dementia. Search methods: We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta‐analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C‐EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence‐based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed ‘related articles’ feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. // Selection criteria: Cross‐sectional designs where all participants were recruited from the same sample were sought; case‐control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson’s disease or specific settings such as nursing homes. // Data collection and analysis: We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS‐2 criteria. Methodological variation in selected studies precluded quantitative meta‐analysis, therefore results from individual studies were presented with a narrative synthesis. // Main results: Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population‐derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic‐based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. // Authors' conclusions: The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case‐control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies

Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients.

BACKGROUND: Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood. METHODS: A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression. RESULTS: Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain. CONCLUSIONS: Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed

Montreal Cognitive Assessment for the diagnosis of Alzheimer's disease and other dementias.

BACKGROUND: Dementia is a progressive syndrome of global cognitive impairment with significant health and social care costs. Global prevalence is projected to increase, particularly in resource-limited settings. Recent policy changes in Western countries to increase detection mandates a careful examination of the diagnostic accuracy of neuropsychological tests for dementia. OBJECTIVES: To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) at various thresholds for dementia and its subtypes. SEARCH METHODS: We searched MEDLINE, EMBASE, BIOSIS Previews, Science Citation Index, PsycINFO and LILACS databases to August 2012. In addition, we searched specialised sources containing diagnostic studies and reviews, including MEDION (Meta-analyses van Diagnostisch Onderzoek), DARE (Database of Abstracts of Reviews of Effects), HTA (Health Technology Assessment Database), ARIF (Aggressive Research Intelligence Facility) and C-EBLM (International Federation of Clinical Chemistry and Laboratory Medicine Committee for Evidence-based Laboratory Medicine) databases. We also searched ALOIS (Cochrane Dementia and Cognitive Improvement Group specialized register of diagnostic and intervention studies). We identified further relevant studies from the PubMed 'related articles' feature and by tracking key studies in Science Citation Index and Scopus. We also searched for relevant grey literature from the Web of Science Core Collection, including Science Citation Index and Conference Proceedings Citation Index (Thomson Reuters Web of Science), PhD theses and contacted researchers with potential relevant data. SELECTION CRITERIA: Cross-sectional designs where all participants were recruited from the same sample were sought; case-control studies were excluded due to high chance of bias. We searched for studies from memory clinics, hospital clinics, primary care and community populations. We excluded studies of early onset dementia, dementia from a secondary cause, or studies where participants were selected on the basis of a specific disease type such as Parkinson's disease or specific settings such as nursing homes. DATA COLLECTION AND ANALYSIS: We extracted dementia study prevalence and dichotomised test positive/test negative results with thresholds used to diagnose dementia. This allowed calculation of sensitivity and specificity if not already reported in the study. Study authors were contacted where there was insufficient information to complete the 2x2 tables. We performed quality assessment according to the QUADAS-2 criteria.Methodological variation in selected studies precluded quantitative meta-analysis, therefore results from individual studies were presented with a narrative synthesis. MAIN RESULTS: Seven studies were selected: three in memory clinics, two in hospital clinics, none in primary care and two in population-derived samples. There were 9422 participants in total, but most of studies recruited only small samples, with only one having more than 350 participants. The prevalence of dementia was 22% to 54% in the clinic-based studies, and 5% to 10% in population samples. In the four studies that used the recommended threshold score of 26 or over indicating normal cognition, the MoCA had high sensitivity of 0.94 or more but low specificity of 0.60 or less. AUTHORS' CONCLUSIONS: The overall quality and quantity of information is insufficient to make recommendations on the clinical utility of MoCA for detecting dementia in different settings. Further studies that do not recruit participants based on diagnoses already present (case-control design) but apply diagnostic tests and reference standards prospectively are required. Methodological clarity could be improved in subsequent DTA studies of MoCA by reporting findings using recommended guidelines (e.g. STARDdem). Thresholds lower than 26 are likely to be more useful for optimal diagnostic accuracy of MoCA in dementia, but this requires confirmation in further studies.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/14651858.CD010775.pub