Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study.

OBJECTIVE: To evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: Prospective study of infants with mild (n = 18), moderate (n = 17), and severe HIE (n = 14) and controls (n = 17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36 hours and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5-5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH. RESULTS: Increased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5-5 years (P < .05). Infants with severe HIE showed increased BG and Th perfusion (P < .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥0.237 cm/second (Area under the curve of 0.824) correctly classified 80% of infants with severe MRI scores. CONCLUSIONS: Early dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments.

Landscape of Métis health and wellness: protocol for a scoping review.

INTRODUCTION: In Canada, Métis people are one of three distinct Indigenous peoples whose rights are recognised and affirmed in Section 35 of the federal Constitution Act, 1982. In line with Métis people having a unique culture, history, language and way of life, a distinctions-based approach is critical to understand the current landscape of Métis-specific health. In this paper, we present a scoping review protocol to describe this research landscape in Canada led by the Métis Nation of Ontario (MNO). METHODS AND ANALYSIS: This scoping review protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews reporting guidelines and follows Arksey and O'Malley's scoping review methodology. We will search electronic databases (Scopus, MEDLINE, Embase, Web of Science, CINAHL, APA PsycINFO, Anthropology Plus, Bibliography of Indigenous Peoples of North America, Canadian Business and Current Affairs, Indigenous Studies Portal, Informit Indigenous Collection, Collaborative Indigenous Garden, PubMed, ProQuest), grey literature sources and reference lists from selected papers. Two reviewers (HMB and SK) will double-blind screen all titles/abstracts and full-text studies for inclusion. Any health-related study or health report that includes a Métis-specific health, well-being or Métis social determinant of health outcome will be included. Relevant variables will be extracted following an iterative process whereby the data charting will be reviewed and updated. ETHICS AND DISSEMINATION: Findings from this scoping review will be shared back through the MNO's existing community-based communication channels. Traditional academic dissemination will also be pursued. Research ethics board approval is not required, since data are from peer-reviewed publications or publicly shared health reports and knowledge translation products.

The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake.

The erythrocyte and plasma fatty acid compositions of children with autism were compared in a case-control study with typically developing (TD) children and with children showing developmental delay (DD). Forty-five autism subjects were age-matched with TD controls and thirty-eight with DD controls. Fatty acid data were compared using paired t tests. In addition, blood fatty acids from treatment-naive autism subjects were compared with autism subjects who had consumed fish oil supplements by two-sample t tests. Relatively few differences were seen between erythrocyte fatty acids in autism and TD subjects although the former had an increased arachidonic acid (ARA):EPA ratio. This ratio was also increased in plasma samples from the same children. No changes in n-3 fatty acids or ARA:EPA ratio were seen when comparing autism with DD subjects but some SFA and MUFA were decreased in the DD subjects, most notably 24 : 0 and 24 : 1, which are essential components of axonal myelin sheaths. However, if multiple comparisons are taken into account, and a stricter level of significance applied, most of these values would not be significant. Autism subjects consuming fish oil showed reduced erythrocyte ARA, 22 : 4n-6, 22 : 5n-6 and total n-6 fatty acids and increased EPA, 22 : 5n-3, 22 : 6n-3 and total n-3 fatty acids along with reduced n-6:n-3 and ARA:EPA ratios. Collectively, the autism subjects did not have an underlying phospholipid disorder, based on erythrocyte fatty acid compositions, although the increased ARA:EPA ratio observed suggested that an imbalance of essential highly unsaturated fatty acids may be present in a cohort of autism subjects.

The development of an ELISA for group IVA phospholipase A2 in human red blood cells.

An immunoassay for IVA phospholipase A2 in human red blood cells is described. The assay is a non-competitive sandwich assay in which increasing amounts of the measured protein produce increased luminescence. The antibodies used in the assay are directed against two unique epitopes of the molecule, which sequentially trap and detect the protein. The standard curve covers the range 0.7ng to 23ng/mL (0.07 to 2.3ng/well). The intra-assay and inter-assay coefficients of variation were 9% and 12%, respectively. Evidence is presented that the assay is specific for the alpha paralog of IV PLA2. The assay allows simple and rapid quantification of IVAPLA2 in red blood cell lysates and other biological fluids.

The investigation of cytosolic phospholipase A2 using ELISA.

Two studies of the behaviour of cytosolic phospholipase A(2) (cPLA(2)) in the red blood cell (RBC), as measured by ELISA, are described. In the first study we show a significant increase in cPLA(2) in patients with schizophrenia compared to controls and suggest that this measure, if corroborated, could be used as a diagnostic marker. In a second study we found that washing the RBC introduced an unknown confounding variable which led us to reject this study. A subsequent investigation of washing red cells showed that the washing effect may be due to a plasma factor likely to be more than 5kDa MW which can be removed from red cells by washing with buffers. When the cells are washed, the concentration of cPLA(2) in the red cell, as measured by ELISA, significantly increases. We advise against washing the red cell in any study that involves measuring cPLA(2) by ELISA.

Differential effects of eicosapentaenoic and docosahexaenoic acids upon oxidant-stimulated release and uptake of arachidonic acid in human lymphoma U937 cells.

The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary supplements, as anti-inflammatory agents is supported by a variety of biochemical and physiological data. Recent studies investigating the therapeutic potential of long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion, however, that not all n-3 fatty acid types are equally efficacious. In particular eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be due to a differential ability to antagonize arachidonic acid (AA)-dependent cell signalling. In this study, we examine the effect of EPA and DHA supplementation upon uptake and release of arachidonic acid stimulated by tert-butyl hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids for 18 days, with the order of effect magnitude being EPA > DHA = AA. Supplementation of cells for 1 day gave qualitatively similar results, although the effect magnitude was smaller. To determine whether enhanced release was due to decreased reuptake of AA, cells were cultured in the presence of 10 microM fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of uptake and release of AA from phospholipids in an exposure time-dependent manner, whereas DHA has no or little effect. Our results predict that EPA will have a more pronounced effect upon AA-dependent processes compared to DHA, and suggests that the relative amounts of EPA and DHA in fish oil supplements may modify their biochemical, and potentially, behavioural effects.

Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry.

A crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information.

Cytosolic phospholipase A2 type IVA is present in human red cells.

Phospholipase A(2) type IVA (IVAPLA(2)) is a cytosolic enzyme that on activation selectively releases arachidonic acid (AA) from cell membrane phospholipids. Both AA and lysophospholipid, products of the enzymic reaction, can function as signal transducers in cellular interactions. The enzyme is present in most cells, including polymorphs, eosinophils, and platelets. This study used affinity purification to extract IVAPLA(2) from red cell lysate prepared from leukocyte- and platelet-depleted human blood to overcome the masking effect of hemoglobin on Western blot detection. We show that IVAPLA(2) is present in red cells as a 90-kDa protein.