Continuous BP monitoring is essential to intraoperative care, as hypotensive events can significantly increase the risk of AKI, MI, and mortality post-op1,2 . The Hypotension Prediction Index (HPI) is a novel algorithm derived from machine learning that gives anesthesiologists the ability to predictive hypotensive events. The HPI derived from intra-arterial catheter monitoring has been shown to predict hypotensive events with sensitivity and specificity >80%3 . However, the utility and accuracy of the HPI when derived from non-invasive monitoring techniques, such the ClearSight finger cuff, have yet to be examined. This study seeks to compare the intraarterial catheter-derived HPI vs the ClearSight finger cuff-derived HPI, to see if it is viable tool for anesthesiologists to use when non-invasive monitoring is not indicated.

Stimulant-use disorders can present with long-term cognitive and mental health deficits. Little is known about the underlying molecular mechanisms perpetuating sex differences in cognitive and behavioral deficits in preclinical models of addiction to stimulants such as methamphetamine (MA). The current study investigated the neurochemical shifts underlying sex disparities in MA-induced working memory deficits and an addictive phenotype following abstinence from chronic MA abuse. We used our previously reported mouse model of voluntary oral methamphetamine administration (VOMA) consisting of an acquisition phase (days 1-14) characterized by escalating doses of MA and a binge phase (days 14-28) characterized by static doses. Female VOMA mice exhibited sustained MA consumption during the binge phase, demonstrating sex-specific vulnerabilities to the maintenance of MA addiction. The 8-arm radial maze was used to test spatial working memory performance following abstinence from VOMA. Results indicate working memory deficits correlated to higher MA consumption in females only. Hippocampal and accumbal tissue were collected and analyzed by immunoblotting. Female VOMA mice had decreased GluA1, but not GluA2, in the hippocampus, which may perpetuate synaptic destabilization and working memory deficits. Female-specific increases in GluA1 and p-GSK3β expression in accumbal tissue suggest vulnerability toward abstinence-induced drug craving and heightened downstream neurotoxicity. Our study reveals female-specific neurochemical shifts in hippocampal and accumbal AMPA receptor signaling following abstinence from chronic MA consumption that may perpetuate female susceptibility to MA-induced cognitive deficits. These data demonstrate a novel molecular pathway that would exacerbate memory deficits and perpetuate an addictive phenotype in female populations following MA abuse.

Rationale

Quantifying cellular proteins in ventricular myocytes (MCs) is challenging due to tissue heterogeneity and the variety of cell sizes in the heart. In post-weaning cardiac ontogeny, rod-shaped MCs make up the majority of the cardiac mass while remaining a minority of cardiac cells in number. Current biochemical analyses of cardiac proteins do not correlate well the content of MC-specific proteins to cell type or size in normally developing tissue.

Objective

To develop a new large-particle fluorescent-activated cell sorting (LP-FACS) strategy for the purification of adult rod-shaped MCs. This approach is developed to enable growth-scaled measurements per-cell of the MC proteome and sarcomeric proteins (i.e. myosin heavy chain (MyHC) and alpha-actin (α-actin)) content.

Methods and results

Individual cardiac cells were isolated from 21 to 94days old mice. An LP-FACS jet-in-air system with a 200-μm nozzle was defined for the first time to purify adult MCs. Cell-type specific immunophenotyping and sorting yielded ≥95% purity of adult MCs independently of cell morphology and size. This approach excluded other cell types and tissue contaminants from further analysis. MC proteome, MyHC and α-actin proteins were measured in linear biochemical assays normalized to cell numbers. Using the allometric coefficient α, we scaled the MC-specific rate of protein accumulation to growth post-weaning. MC-specific volumes (α=1.02) and global protein accumulation (α=0.94) were proportional (i.e. isometric) to body mass. In contrast, MyHC and α-actin accumulated at a much greater rate (i.e. hyperallometric) than body mass (α=1.79 and 2.19 respectively) and MC volumes (α=1.76 and 1.45 respectively).

Conclusion

Changes in MC proteome and cell volumes measured in LP-FACS purified MCs are proportional to body mass post-weaning. Oppositely, MyHC and α-actin are concentrated more rapidly than what would be expected from MC proteome accumulation, cell enlargement, or animal growth alone. LP-FACS provides a new standard for adult MC purification and an approach to scale the biochemical content of specific proteins or group of proteins per cell in enlarging MCs.

Introduction

Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care.

Methods

We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculum's impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes.

Results

Three core themes emerged from analysis of participants' comments. First, participants valued the curriculum's focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions.

Discussion

This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health.

Enhancing health research capacity in developing countries is a global health priority. Understanding the orthopedic burden of disease in Latin America will require close partnership between more-developed and less-developed countries. To this end, the Osteosynthesis and Trauma Care Foundation assembled a research consortium of Latin-American orthopedic leaders. Prior to the meeting, we surveyed attendees on perceived barriers to conducting research at their institutions. During the event, working groups discussed these barriers, developed strategies for addressing them, and planned future steps for collaboration. The participants established the need for global relationships that allow colleagues from Latin America to access to training and established investigational infrastructure of North American centers to address research questions relevant to their communities. As a result of the discussion, the International Orthopaedic Multicenter Study (INORMUS) in Fracture Care was initiated. Since then, an expanded international working group, Associación de Cirujanos Traumatológicos en las Americas (ACTUAR), has been created with the purpose of promoting increased global partnership for research capacity development.

INTRODUCTION: Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care. METHODS: We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculums impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes. RESULTS: Three core themes emerged from analysis of participants comments. First, participants valued the curriculums focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions. DISCUSSION: This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health.