The Canadian Medical Student Ultrasound Curriculum: A Statement From the Canadian Ultrasound Consensus for Undergraduate Medical Education Group.

OBJECTIVES: This study sought to establish by expert review a consensus-based, focused ultrasound curriculum, consisting of a foundational set of focused ultrasound skills that all Canadian medical students would be expected to attain at the end of the medical school program. METHODS: An expert panel of 21 point-of-care ultrasound and educational leaders representing 15 of 17 (88%) Canadian medical schools was formed and participated in a modified Delphi consensus method. Experts anonymously rated 195 curricular elements on their appropriateness to include in a medical school curriculum using a 5-point Likert scale. The group defined consensus as 70% or more experts agreeing to include or exclude an element. We determined a priori that no more than 3 rounds of voting would be performed. RESULTS: Of the 195 curricular elements considered in the first round of voting, the group reached consensus to include 78 and exclude 24. In the second round, consensus was reached to include 4 and exclude 63 elements. In our final round, with 1 additional item added to the survey, the group reached consensus to include an additional 3 and exclude 8 elements. A total of 85 curricular elements reached consensus to be included, with 95 to be excluded. Sixteen elements did not reach consensus to be included or excluded. CONCLUSIONS: By expert opinion-based consensus, the Canadian Ultrasound Consensus for Undergraduate Medical Education Group recommends that 85 curricular elements be considered for inclusion for teaching in the Canadian medical school focused ultrasound curricula.

POCUS literature primer: key papers on POCUS in cardiac arrest and shock.

OBJECTIVE: The objective of this study is to identify the top five most influential papers published on the use of point-of-care ultrasound (POCUS) in cardiac arrest and the top five most influential papers on the use of POCUS in shock in adult patients. METHODS: An expert panel of 14 members was recruited from the Canadian Association of Emergency Physicians (CAEP) Emergency Ultrasound Committee and the Canadian Ultrasound Fellowship Collaborative. The members of the panel are ultrasound fellowship trained or equivalent, are engaged in POCUS research, and are leaders in POCUS locally and nationally in Canada. A modified Delphi process was used, consisting of three rounds of sequential surveys and discussion to achieve consensus on the top five most influential papers for the use of POCUS in cardiac arrest and shock. RESULTS: The panel identified 39 relevant papers on POCUS in cardiac arrest and 42 relevant papers on POCUS in shock. All panel members participated in all three rounds of the modified Delphi process, and we ultimately identified the top five most influential papers on POCUS in cardiac arrest and also on POCUS in shock. Studies include descriptions and analysis of safe POCUS protocols that add value from a diagnostic and prognostic perspective in both populations during resuscitation. CONCLUSION: We have developed a reading list of the top five influential papers on the use of POCUS in cardiac arrest and shock to better inform residents, fellows, clinicians, and researchers on integrating and studying POCUS in a more evidence-based manner.

RéSUMé: OBJECTIF: L'objectif de cette étude est d'identifier les cinq articles les plus influents publiés sur l'utilisation de l'échographie au point de soin (POCUS) dans l'arrêt cardiaque et les cinq articles les plus influents sur l'utilisation de POCUS dans le choc chez les patients adultes. MéTHODES: Un comité d'experts composé de 14 membres a été recruté par le Comité d'échographie d'urgence de l'Association canadienne des médecins d'urgence (ACMU) et le Canadian Ultrasound Fellowship Collaborative. Les membres du comité sont formés en échographie ou l'équivalent, participent à la recherche sur le POCUS et sont des chefs de file du POCUS à l'échelle locale et nationale au Canada. Un processus Delphi modifié a été utilisé, consistant en trois séries de sondages séquentiels et de discussions pour parvenir à un consensus sur les cinq articles les plus influents pour l'utilisation de POCUS dans les arrêts cardiaques et les chocs. RéSULTATS: Le panel a identifié 39 articles pertinents sur le POCUS en arrêt cardiaque et 42 articles pertinents sur le POCUS en état de choc. Tous les membres du panel ont participé aux trois cycles du processus Delphi modifié, et nous avons finalement identifié les cinq articles les plus influents sur le POCUS en arrêt cardiaque et aussi sur le POCUS en état de choc. Les études comprennent des descriptions et des analyses de protocoles POCUS sûrs qui ajoutent de la valeur d'un point de vue diagnostique et pronostique dans les deux populations pendant la réanimation. CONCLUSION: Nous avons dressé une liste de lecture des cinq principaux articles influents sur l'utilisation du POCUS en cas d'arrêt cardiaque et de choc afin de mieux informer les résidents, les boursiers, les cliniciens et les chercheurs sur l'intégration et l'étude du POCUS d'une manière plus factuelle.

Point-of-Care Ultrasound (POCUS) Literature Primer: Key Papers on Renal and Biliary POCUS.

Objective The objective of this study is to identify the top five influential papers published on renal point-of-care ultrasound (POCUS) and the top five influential papers on biliary POCUS in adult patients. Methods A 14-member expert panel was recruited from the Canadian Association of Emergency Physicians (CAEP) Emergency Ultrasound Committee and the Canadian Ultrasound Fellowship Collaborative. All panel members have had ultrasound fellowship training or equivalent, are actively engaged in POCUS scholarship, and are involved with POCUS at their local site and nationally in Canada. We used a modified Delphi process consisting of three rounds of sequential surveys and discussion to achieve consensus on the top five influential papers for renal POCUS and biliary POCUS. Results The panel identified 27 relevant papers on renal POCUS and 30 relevant papers on biliary POCUS. All panel members participated in all three rounds of the modified Delphi process, and after completing this process, we identified the five most influential papers on renal POCUS and the five most influential papers on biliary POCUS. Conclusion We have developed a list, based on expert opinion, of the top five influential papers on renal and biliary POCUS to better inform all trainees and clinicians on how to use these applications in a more evidence-based manner. This list will also be of interest to clinicians and researchers who strive to further advance the field of POCUS.

Combined polymorphisms in oxidative stress genes predict coronary artery disease and oxidative stress in coronary angiography patients.

Oxidative stress has been implicated in all stages of atherosclerosis, but how inherited variations in oxidative stress genes influence the severity of cardiovascular disease is not known. We tested associations between polymorphisms in candidate oxidative stress genes, plasma oxidative stress biomarkers, and cardiovascular mortality in an angiography cohort. Single nucleotide polymorphisms (SNPs) across 15 genes were selected by linkage disequilibrium tagging. Genotyping was performed using customized arrayed primer extension micro-arrays, with automated genotype calling methods. Effects of SNPs and haplotypes on plasma oxidative stress and coronary artery disease (CAD) were estimated using a stochastic estimation maximization algorithm. Proportionate hazards analyses were used to determine effects of single and combined genetic markers on cardiovascular mortality risk, and on the following oxidative stress biomarkers: myeloperoxidase (MPO), nitrotyrosine, oxidized low-density lipoprotein, and antioxidant capacity. Oxidative stress gene SNPs associated with CAD were combined into an oxidative stress risk allele score, which predicted disease presence (1.5-fold risk increase per allele, P < 0.001). Combined risk alleles were also associated with elevated plasma MPO (P < 0.003), an oxidative stress biomarker that predicts cardiovascular mortality. Genetic markers that represent lifetime oxidative stress burden may implicate specific oxidative stress pathways in the pathogenesis of atherosclerosis, and offer therapeutic opportunities.

Bilateral Retinal Detachments Caused by Severe Preeclampsia Diagnosed with Point-of-Care Ultrasound.

Bilateral retinal detachments are a rare complication of preeclampsia. We present a case report of a patient with an unknown pregnancy who presented with acute bilateral vision loss and elevated blood pressure. Point-of-care ocular ultrasound revealed bilateral retinal detachments. She was diagnosed with severe preeclampsia and taken for an urgent caesarean section with the delivery of a 26-week-old infant.

Myeloperoxidase and C-reactive protein have combined utility for long-term prediction of cardiovascular mortality after coronary angiography.

OBJECTIVES: We evaluated the relative and combined value of oxidative stress biomarkers for predicting cardiovascular mortality in patients undergoing selective coronary angiography. BACKGROUND: Oxidative stress participates in all stages of cardiovascular disease, from lipoprotein modification to plaque rupture, and biomarkers of oxidative stress predict development of coronary artery disease (CAD). Oxidative stress biomarkers merit investigation for the value they may offer for long-term cardiovascular risk prediction. METHODS: Myeloperoxidase (MPO), nitrotyrosine, oxidized low-density lipoprotein, and antioxidant capacity were measured in a prospective cohort of 885 selective coronary angiography patients followed up for >13 years for cardiovascular mortality. RESULTS: MPO independently predicted CAD, and top tertile MPO levels predicted a 2.4-fold risk of cardiovascular mortality (95% confidence interval [CI]: 1.47 to 2.98), compared with patients with lowest tertile MPO levels. MPO also improved risk model discrimination and patient risk category classification. Elevations in multiple oxidative stress biomarkers predicted increased mortality risk; however, the strongest risk prediction was achieved by assessing MPO and C-reactive protein (CRP) together. Patients with either MPO or CRP elevated had 5.3-fold higher cardiovascular mortality risk (95% CI: 1.86 to 14.9), and patients with high levels of both MPO and CRP had a 4.3-fold risk compared with patients with only elevated marker (95% CI: 2.26 to 8.31). These results remained significant with adjustment for cardiovascular risk factors and baseline disease burden. CONCLUSIONS: MPO accurately predicted cardiovascular mortality risk in coronary angiography patients. Considering MPO and CRP together may improve long-term risk assessment and CAD patient outcomes.

Neighbourhood socioeconomics status predicts non-cardiovascular mortality in cardiac patients with access to universal health care.

BACKGROUND: Although the Canadian health care system provides essential services to all residents, evidence suggests that socioeconomic gradients in disease outcomes still persist. The main objective of our study was to investigate whether mortality, from cardiovascular disease or other causes, varies by neighbourhood socioeconomic gradients in patients accessing the healthcare system for cardiovascular disease management. METHODS AND FINDINGS: A cohort of 485 patients with angiographic evidence of coronary artery disease (CAD) and neighbourhood socioeconomic status information was followed for 13.3 years. Survival analyses were completed with adjustment for potentially confounding risk factors. There were 64 cases of cardiovascular mortality and 66 deaths from non-cardiovascular chronic diseases. No socioeconomic differentials in cardiovascular mortality were observed. However, lower neighbourhood employment, education, and median family income did predict an increased risk of mortality from non-cardiovascular chronic diseases. For each quintile decrease in neighbourhood socioeconomic status, non-cardiovascular mortality risk rose by 21-30%. Covariate-adjusted hazard ratios (95% confidence interval) for non-cardiovascular mortality were 1.21 (1.02-1.42), 1.21 (1.01-1.46), and 1.30 (1.06-1.60), for each quintile decrease in neighbourhood education, employment, and income, respectively. These patterns were primarily attributable to mortality from cancer. Estimated risks for mortality from cancer rose by 42% and 62% for each one quintile decrease in neighbourhood median income and employment rate, respectively. Although only baseline clinical information was collected and patient-level socioeconomic data were not available, our results suggest that environmental socioeconomic factors have a significant impact on CAD patient survival. CONCLUSIONS: Despite public health care access, CAD patients who reside in lower-socioeconomic neighbourhoods show increased vulnerability to non-cardiovascular chronic disease mortality, particularly in the domain of cancer. These findings prompt further research exploring mechanisms of neighbourhood effects on health, and ways they may be ameliorated.

Selective up-regulation of LXR-regulated genes ABCA1, ABCG1, and APOE in macrophages through increased endogenous synthesis of 24(S),25-epoxycholesterol.

Liver X receptor (LXR) activation represents a mechanism to prevent macrophage foam cell formation. Previously, we demonstrated that partial inhibition of oxidosqualene:lanosterol cyclase (OSC) stimulated synthesis of the LXR agonist 24(S),25-epoxycholesterol (24(S),25-epoxy) and enhanced ABCA1-mediated cholesterol efflux. In contrast to a synthetic, nonsteroidal LXR activator, TO-901317, triglyceride accumulation was not observed. In the present study, we determined whether endogenous 24(S),25-epoxy synthesis selectively enhanced expression of macrophage LXR-regulated cholesterol efflux genes but not genes that regulate fatty acid metabolism. THP-1 human macrophages incubated with the OSC inhibitor (OSCi) RO0714565 (15 nM) significantly reduced cholesterol synthesis and maximized synthesis of 24(S),25-epoxy. Endogenous 24(S),25-epoxy increased ABCA1, ABCG1, and APOE mRNA abundance and consequently increased cholesterol efflux to apoAI. In contrast, OSCi had no effect on LXR-regulated genes LPL (lipoprotein lipase) and FAS (fatty acid synthase). TO-901317 (>or=10 nM) significantly enhanced expression of all genes examined. OSCi and TO-901317 increased the mRNA and precursor form of SREBP-1c, a major regulator of fatty acid and triglyceride synthesis. However, conversion of the precursor to the active form (nSREBP-1c) was blocked by OSCi-induced 24(S),25-epoxy but not by TO-901317 (>or=10 nm), which instead markedly increased nSREBP-1c. Disruption of nSREBP-1c formation by 24(S),25-epoxy accounted for diminished FAS and LPL expression. In summary, endogenous synthesis of 24(S),25-epoxy selectively up-regulates expression of macrophage LXR-regulated cholesterol efflux genes without stimulating genes linked to fatty acid and triglyceride synthesis.

Hydrophobic helical hairpins: design and packing interactions in membrane environments.

Helix-helix interactions within membranes are dominated by van der Waals packing motifs and side chain-side chain hydrogen bond formation, which act in tandem to determine the residues that comprise the interface between two given helices. To explore in a systematic manner the tertiary contacts between transmembrane helices, we have designed and expressed in Escherichia coli highly hydrophobic helix-loop-helix constructs of prototypic sequence K(1)KKKKKKFAIAIAIIAWAX(19)AIIAIAIAIKSPGSKIAIAIAIIAZ(44)AWAIIAIAIAFKKKKKKK(62), where "small" (Ala) and "large" (Ile) residues were used to maximize the tertiary contact area. Evidence that the two transmembrane (TM) segments in the AI construct contain an interface conducive for folding into a hairpin structure was obtained from the results that (i) the single TM AI(pep) peptide derived from the AI hairpin forms SDS-resistant dimers on PAGE gels and (ii) the corresponding sequence forms a strong dimer when examined in vivo in TOXCAT assays. Site-directed mutagenesis of AI hairpins was carried out to incorporate each of the 20 commonly occurring amino acids at X positions. Analysis on Western blots using an oligomerization assay in 12% NuPage-sodium dodecyl sulfate (SDS) indicated that mutants with X = E, D, Q, R, N, H, and K largely formed SDS-resistant dimers-which likely correspond to H-bonded four-helix bundles-while all the others (e.g., X = F, W, L, I, M, V, C, Y, A, T, S, G, and P) remained monomeric. Systematic studies of X/Z double mutants indicated that formation of hairpin dimers is the result of the disruption of stabilizing interactions between the antiparallel helices within the AI construct. The overall results suggest that, in situations where hydrophobic van der Waals packing energy between helices is sufficient to prevent significant rotation about the major axes of interacting helices, intrahairpin side chain-side chain H-bond formation will occur mainly when pairs of polar residues are interfacially located and proximal. Knowledge of the relative contributions of these forces should be of value, for example, in clarifying the context--and the structural consequences--of disease-related mutations.