Plasma oxidized LDL: a predictor for acute myocardial infarction?

Objectives. Oxidized LDL has been attributed a key role in the development of atherosclerosis. Previous studies have demonstrated increased plasma levels of oxidized LDL in patients with established coronary artery disease. The aim of the present study was to investigate if plasma oxidized LDL also predicts risk for development of coronary heart disease (CHD). Design. We used a nested case-control design to study the association between plasma levels of oxidized LDL and risk for development of acute myocardial infarction (AMI) and/or death by CHD. Subjects. Oxidized LDL was analysed by ELISA in cases (n = 26), controls (n = 26) and controls with LDL cholesterol >5.0 mmol L-1 (n = 26). Results. Oxidized LDL correlated with total plasma and LDL cholesterol in both cases (r = 0.72, P < 0.01, r = 0.69, P < 0.01, respectively) and controls (r = 0.71, P < 0.01, r = 0.77, P < 0.01, respectively). The oxidized LDL/plasma cholesterol ratio was higher amongst cases (13.5, range 10.7-19.8) than in controls (12.6, range 9.5-15.8, P < 0.05) and hypercholesterolaemic controls (12.2, range 8.0-16.0, P < 0.01). Conclusions. These findings identify high plasma oxidized LDL/total cholesterol ratio as a possible indicator of increased risk for AMI

Obstacles and risks in the traffic environment for users of powered wheelchairs in Sweden

ObjectiveAccording to the European Union, fatal\ua0road accidents\ua0involving Vulnerable Road Users (VRUs) are equal in proportion to fatal car road accidents (46%). VRUs include individuals with mobility challenges such as the elderly and Powered Wheelchair (PWC) users. The aim of this interdisciplinary qualitative study was to identify obstacles and risks for PWC users by exploring their behaviour and experiences in traffic environments.MethodsVideos and in-depth interviews with 13 PWC users aged 20–66 were analysed for this study. The interviews and videos, which include real-life outdoor observations, originate from a qualitative study exploring experiences of PWC use on a daily basis in Sweden. Underlying causal factors to identified risks and obstacles were identified, based on human, vehicle (PWC) and environmental factors in accordance with the Haddon Matrix.ResultsThe results show significant potential for improvement within all three perspectives of the Haddon Matrix used in the analysis. Participants faced and dealt with various obstacles and risks in order to reach their destination. For example, this includes uneven surfaces, differences in ground levels, steep slopes, as well as interactions with other road users and the influence of weather conditions, resulting in PWC users constantly accommodating and coping with the shortcomings of the vehicle and the environment.ConclusionsThere are still major challenges with regard to preventing obstacles and risks in the traffic environment for PWC users. To discern PWC users in traffic accident and injury data bases, a start would be to register type of aid used for persons involved in an accident. Furthermore, to emphasise PWC users’ role as VRUs, it may also be advantageous to describe them as drivers rather than users when navigating the traffic environment. Given the limited sample, further research covering more data from a broader perspective would be beneficial. By incorporating emerging knowledge of PWC users’ prerequisites and needs, and including them in research and traffic planning, the society will grow safer and more inclusive, and become better prepared for meeting future demands on accessibility from an\ua0aging population

A longitudinal study of perceived health during pregnancy: antecedents and outcomes

Perceived health was studied longitudinally in a sample of 364 nulliparous women. Psychosocial, contextual, and biomedical factors were taken into account to predict medically relevant versus benign symptoms which were then used to predict perceived health over time. The results of structural equation modeling showed that pregnancy adjustment and medically relevant symptoms which were affected by social support, perceived stress, and negative affect predicted later perceived health. The outcomes of perceived health were examined during the third trimester in terms of medical care utilization and emergency room visits. Perceived health solely accounted for medical care utilization, while emergency room visits were accounted by medical care utilization and perceived stress

Rediscovery and reclassification of the dipteran taxon Nothomicrodon Wheeler, an exclusive endoparasitoid of gyne ant larvae

The myrmecophile larva of the dipteran taxon Nothomicrodon Wheeler is rediscovered, almost a century after its original description and unique report. The systematic position of this dipteran has remained enigmatic due to the absence of reared imagos to confirm indentity. We also failed to rear imagos, but we scrutinized entire nests of the Brazilian arboreal dolichoderine ant Azteca chartifex which, combined with morphological and molecular studies, enabled us to establish beyond doubt that Nothomicrodon belongs to the Phoridae (Insecta: Diptera), not the Syrphidae where it was first placed, and that the species we studied is an endoparasitoid of the larvae of A. chartifex, exclusively attacking sexual female (gyne) larvae. Northomicrodon parasitism can exert high fitness costs to a host colony. Our discovery adds one more case to the growing number of phorid taxa known to parasitize ant larvae and suggests that many others remain to be discovered. Our findings and literature review confirm that the Phoridae is the only taxon known that parasitizes both adults and the immature stages of different castes of ants, thus threatening ants on all fronts.Peer reviewe

Interprofessional education in a student-led emergency department : a realist evaluation

This paper reports a realist evaluation undertaken to identify factors that facilitated or hindered the successful implementation of interprofessional clinical training for undergraduate students in an emergency department. A realist evaluation provides a framework for understanding how the context and underlying mechanisms affect the outcome patterns of an intervention. The researchers gathered both qualitative and quantitative data from internal documents, semi-structured interviews, observations and questionnaires to study what worked, for whom and under what circumstances in this specific interprofessional setting. The study participants were medical, nursing and physiotherapy students, their supervisors and two members of the emergency department’s management staff. The data analysis indicated that the emergency ward provided an excellent environment for interprofessional education (IPE), as attested by the students, supervisors and the clinical managers. An essential prerequisite is that the students have obtained adequate skills to work independently. Exemplary conditions for IPE to work well in an emergency department demand the continuity of effective and encouraging supervision throughout the training period and supervisors who are knowledgeable about developing a team

Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses

The antibody response to SARS-CoV-2 shows biased immunoglobulin heavy chain variable (IGHV) gene usage, allowing definition of genetic signatures for some classes of neutralizing antibodies. We investigated IGHV gene usage frequencies by sorting spike-specific single memory B cells from individuals infected with SARS-CoV-2 early in the pandemic. From two study participants and 703 spike-specific B cells, the most used genes were IGHV1-69, IGHV3-30-3, and IGHV3-30. Here, we focused on the IGHV3-30 group of genes and an IGHV3-30-3-using ultrapotent neutralizing monoclonal antibody, CAB-F52, which displayed broad neutralizing activity also in its germline-reverted form. IGHV3-30-3 is encoded by a region of the IGH locus that is highly variable at both the allelic and structural levels. Using personalized IG genotyping, we found that 4 of 14 study participants lacked the IGHV3-30-3 gene on both chromosomes, raising the question if other, highly similar IGHV genes could substitute for IGHV3-30-3 in persons lacking this gene. In the context of CAB-F52, we found that none of the tested IGHV3-33 alleles, but several IGHV3-30 alleles could substitute for IGHV3-30-3, suggesting functional redundancy between the highly homologous IGHV3-30 and IGHV3-30-3 genes for this antibody

Improving GSEA for Analysis of Biologic Pathways for Differential Gene Expression across a Binary Phenotype

Gene-set analysis evaluates the expression of biological pathways, or a priori defined gene sets, rather than that of single genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the single-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS). Specifically, we illustrate, in a simulation study, that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are highly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs perfectly in the simulation study: none of the null gene sets is identified with statistical significance, while all of the truly-associated gene sets are. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the diverging results of which clearly show the advantages of SAM-GS over GSEA, both statistically and biologically

A Biological Evaluation of Six Gene Set Analysis Methods for Identification of Differentially Expressed Pathways in Microarray Data

Gene-set analysis of microarray data evaluates biological pathways, or gene sets, for their differential expression by a phenotype of interest. In contrast to the analysis of individual genes, gene-set analysis utilizes existing biological knowledge of genes and their pathways in assessing differential expression. This paper evaluates the biological performance of five gene-set analysis methods testing “self-contained null hypotheses” via subject sampling, along with the most popular gene-set analysis method, Gene Set Enrichment Analysis (GSEA). We use three real microarray analyses in which differentially expressed gene sets are predictable biologically from the phenotype. Two types of gene sets are considered for this empirical evaluation: one type contains “truly positive” sets that should be identified as differentially expressed; and the other type contains “truly negative” sets that should not be identified as differentially expressed. Our evaluation suggests advantages of SAM-GS, Global, and ANCOVA Global methods over GSEA and the other two methods

Improving gene set analysis of microarray data by SAM-GS

<p>Abstract</p> <p>Background</p> <p><it>Gene-set </it>analysis evaluates the expression of biological pathways, or <it>a priori </it>defined gene sets, rather than that of individual genes, in association with a binary phenotype, and is of great biologic interest in many DNA microarray studies. Gene Set Enrichment Analysis (GSEA) has been applied widely as a tool for gene-set analyses. We describe here some critical problems with GSEA and propose an alternative method by extending the individual-gene analysis method, Significance Analysis of Microarray (SAM), to gene-set analyses (SAM-GS).</p> <p>Results</p> <p>Using a mouse microarray dataset with simulated gene sets, we illustrate that GSEA gives statistical significance to gene sets that have no gene associated with the phenotype (null gene sets), and has very low power to detect gene sets in which half the genes are moderately or strongly associated with the phenotype (truly-associated gene sets). SAM-GS, on the other hand, performs very well. The two methods are also compared in the analyses of three real microarray datasets and relevant pathways, the diverging results of which clearly show advantages of SAM-GS over GSEA, both statistically and biologically. In a microarray study for identifying biological pathways whose gene expressions are associated with <it>p53 </it>mutation in cancer cell lines, we found biologically relevant performance differences between the two methods. Specifically, there are 31 additional pathways identified as significant by SAM-GS over GSEA, that are associated with the presence vs. absence of <it>p53</it>. Of the 31 gene sets, 11 actually involve <it>p53 </it>directly as a member. A further 6 gene sets directly involve the extrinsic and intrinsic apoptosis pathways, 3 involve the cell-cycle machinery, and 3 involve cytokines and/or JAK/STAT signaling. Each of these 12 gene sets, then, is in a direct, well-established relationship with aspects of <it>p53 </it>signaling. Of the remaining 8 gene sets, 6 have plausible, if less well established, links with <it>p53</it>.</p> <p>Conclusion</p> <p>We conclude that GSEA has important limitations as a gene-set analysis approach for microarray experiments for identifying biological pathways associated with a binary phenotype. As an alternative statistically-sound method, we propose SAM-GS. A free Excel Add-In for performing SAM-GS is available for public use.</p