J.P. Morgan

Simulation operations specialists (SOSs) play a critical yet ill-defined role in healthcare simulation. Despite their critical involvement in operations, orientation, and support of simulation-based education, no validated needs assessment tool existed to guide professional development. This study aimed to design and validate the Simulation Operations Needs Assessment Tool (SONAT) to identify knowledge and skills gaps, guide onboarding, and inform SOS professional development. The SONAT was developed using best practice, community, and peer-reviewed documents, including the Certified Healthcare Simulation Operations Specialist Blueprint, SimGHOSTS Capability Framework, and the Healthcare Simulation Standards of Best Practice. Messick's Unified Validity Theory guided the validation process using Lawshe's method to assess survey items. Following expert feedback and item revision, the tool was disseminated for psychometric analysis. Internal consistency was assessed using Cronbach's alpha for each section of the tool. Content validity indices (CVIs) for the final SONAT exceeded the .70 acceptability threshold (CVI = .738). A sample of 256 SOSs completed the SONAT. Internal consistency was strong across 4 domains (α = .730-.912). Respondents reported high proficiency in manikin-based and task trainer simulation but less in emerging modalities (eg, Augmented Reality/Virtual Reality). Awareness of professional standards was strong, although gaps were noted in knowledge of ethics and leadership opportunities, particularly among noncertified individuals. SONAT collects valid and reliable data when assessing SOS developmental needs across diverse roles and backgrounds. It has the potential to standardize orientation, support tailored professional development, and strengthen skillsets of the evolving SOS profession.

(Abstracted from Am J Obstet Gynecol 2024;231:338.e1–338.e18) Estimated fetal weight (EFW) percentiles, derived from ultrasound biometric measurements, help obstetricians identify fetuses that are small (SGA) or large (LGA) for gestational age. Fetuses in the upper or lower 10th percentiles are at higher risk for adverse outcomes.

A modified computed tomography angiography (CTA)-based Carotid Plaque Reporting and Data System (Plaque-RADS) classification was applied to a cohort of patients with embolic stroke of undetermined source to test whether high-risk Plaque-RADS subtypes are more prevalent on the ipsilateral side of stroke. With the widespread use of CTA for stroke evaluation, a CTA-based Plaque-RADS would be valuable for generalizability. A retrospective observational cross-sectional study was conducted at a single integrated health system comprised of 3 hospitals with a comprehensive stroke center between October 1, 2015, and April 1, 2017. Patients with unilateral anterior circulation stroke and <50% carotid stenosis on CTA were retrospectively identified. Maximum plaque thickness and ulceration were assessed by a neuroradiologist blinded to the stroke side. A semiautomated segmentation software measured intraplaque hemorrhage volumes. Modified CTA-based Plaque-RADS classification was defined as (1) no plaque, (2) plaque thickness <3 mm, (3) plaque thickness ≥3 mm or ulcerated, and (4) plaque with intraplaque hemorrhage >50 mm3 irrespective of plaque thickness. High-risk plaque subtypes (Plaque-RADS 3 and 4) were compared with low-risk subtypes (Plaque-RADS 1 and 2). Ninety-four patients (55% women; median age, 66 years) were included. CTA-based Plaque-RADS categories for plaques ipsilateral to the stroke side were as follows: (1) 14.9%, (2) 42.6%, (3) 41.5%, and (4) 1.1%. Carotid plaques contralateral to stroke side were Plaque-RADS: (1) 21.3%, (2) 46.8%, (3) 31.9%, and (4) 0%. When compared with the contralateral side, plaques ipsilateral to the stroke side were significantly associated with high-risk Plaque-RADS subtypes in a mixed-effects logistic model adjusting for age and sex (adjusted odds ratio, 2.10 [95% CI, 1.20-3.71]; P=0.01). Carotid plaque ipsilateral to the stroke side was significantly associated with CTA-based high-risk Plaque-RADS subtypes in an embolic stroke of undetermined source cohort. A CTA-based Plaque-RADS classification may be useful for identifying potentially causative carotid plaque phenotypes in patients with embolic stroke of undetermined source.

Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. Apart from Parkin, little is known about additional Ub (ubiquitin) ligases that mediate mitochondrial ubiquitination and turnover, particularly in highly metabolically active organs such as the heart. In this study, we have combined in silico analysis and biochemical assay to identify CRL (cullin-RING ligase) 5 as a mitochondrial Ub ligase. We generated cardiomyocytes and mice lacking RBX2 (RING-box protein 2; also known as SAG [sensitive to apoptosis gene]), a catalytic subunit of CRL5, to understand the effects of RBX2 depletion on mitochondrial ubiquitination, mitophagy, and cardiac function. We also performed proteomics analysis and RNA-sequencing analysis to define the impact of loss of RBX2 on the proteome and transcriptome. RBX2 and CUL (cullin) 5, 2 core components of CRL5, localize to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, increased cardiomyocyte cell death, and has a global impact on the mitochondrial proteome. In vivo, deletion of the Rbx2 gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to the rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. The action of RBX2 in mitochondria is not dependent on Parkin, and Parkin gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 (PTEN-induced kinase 1) in mitochondria. These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that regulates mitophagy and cardiac homeostasis in a Parkin-independent, PINK1-dependent manner.

(Abstracted from BJOG 2023;130:881–890) The fetal heart rate is a powerful indicator of overall fetal well-being. In recent years, there has been the development of evaluation approaches of the fetal heart rate tracing such as deceleration area (DA) and capacity (DC).

Purpose: This project consisted of a technical study of the location of a wind microgeneration system and the collection of data that impact on said system at the La Bella farm in a rural area of the municipality of Acevedo (Huila, Colombia). Theoretical framework: The Weibull distribution was used to statistical analysis of the data, which is the most widely used system for calculating wind potential. Method/design/approach: The study was divided into two phases "previous study" and "intensive study", 95,760 data were collected in total and were statistically analysed using Weibull frequency distribution and WAsP software. Results and conclusion: The average annual speed of 5.7 and 6.5 m/s, these being higher than the speed necessary to obtain an electric potential. Research implications: It is concluded that the wind potential is 135.2 W/m2 and 186.2 W/m2 respectively. Originality/value: The anemometer data acquisition device is an original design assembled for this study. The statistical analysis of the wind using the Weibull distribution was programming like mathematical model in Microsoft Excel and compared with the results obtained by the WAsP Climate Analyst software.

Following the neutral results of the dal-OUTCOMES trial, a genome-wide study identified the rs1967309 variant in the adenylate cyclase type 9 (ADCY9) gene on chromosome 16 as being associated with the risk of future cardiovascular events only in subjects taking dalcetrapib, a CETP (cholesterol ester transfer protein) modulator. Homozygotes for the minor A allele (AA) were protected from recurrent cardiovascular events when treated with dalcetrapib, while homozygotes for the major G allele (GG) had increased risk. Here, we present the current state of knowledge regarding the impact of rs1967309 in ADCY9 on clinical observations and biomarkers in dalcetrapib trials and the effects of mouse ADCY9 gene inactivation on cardiovascular physiology. Finally, we present our current model of the interaction between dalcetrapib and ADCY9 gene variants in the arterial wall macrophage, based on the intracellular role of CETP in the transfer of complex lipids from endoplasmic reticulum membranes to lipid droplets. Briefly, the concept is that dalcetrapib would inhibit CETP-mediated transfer of cholesteryl esters, resulting in a progressive inhibition of cholesteryl ester synthesis and free cholesterol accumulation in the endoplasmic reticulum. Reduced ADCY9 activity, by paradoxically leading to higher cyclic AMP levels and in turn increased cellular cholesterol efflux, could impart cardiovascular protection in rs1967309 AA patients. The ongoing dal-GenE trial recruited 6145 patients with the protective AA genotype and will provide a definitive answer to whether dalcetrapib will be protective in this population.

Little is known about the prevalence of continued opioid use following aneurysmal subarachnoid hemorrhage (aSAH) despite guidelines recommending their use during the acute phase of disease. We sought to determine prevalence of opioid use following aSAH and test the hypothesis that acute pain and higher inpatient opioid dose increased outpatient opioid use. We reviewed consecutively admitted patients with aSAH from November 2015 through September 2019. We retrospectively collected pain scores and daily doses of analgesics. Pain burden was calculated as area under the pain-time curve. Univariate and multivariable regression models determined risk factors for continued opioid use at discharge and outpatient follow-up. We identified 234 patients with aSAH with outpatient follow-up. Continued opioid use was common at discharge (55% of patients) and follow-up (47% of patients, median 63 [interquartile range 49-96] days from admission). Pain burden, craniotomy, and racial or ethnic minority status were associated with discharge opioid prescription in multivariable analysis. At outpatient follow-up, pain burden (odds ratio [OR] 1.88, 95% confidence interval [CI] 1.5-2.4), depression (OR 3.1, 95% CI 1.1-8.8), and racial or ethnic minority status (OR 2.1, 95% CI 1.1-4.0) were independently associated with continued opioid use; inpatient opioid dose was not. Continued opioid use following aSAH is prevalent and related to refractory pain during acute illness, but not inpatient opioid dose. More efficacious analgesic strategies are needed to reduce continued opioid use in patients following aSAH. This study provides Class II evidence that continued opioid use following aSAH is associated with refractory pain during acute illness but not hospital opioid exposure.

Abstract The coronavirus SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Most SARS-CoV-2 infections are mild or even asymptomatic. However, a small fraction of infected individuals develops severe, life-threatening disease, which is caused by an uncontrolled immune response resulting in hyperinflammation. Antiviral interventions are only effective prior to the onset of hyperinflammation. Hence, biomarkers are needed for the early identification and treatment of high-risk patients. Here, we show in a range of model systems and data from post mortem samples that SARS-CoV-2 infection results in increased levels of CD47, which is known to mediate immune escape in cancer and virus-infected cells. Systematic literature searches also indicated that known risk factors such as older age and diabetes are associated with increased CD47 levels. High CD47 levels contribute to vascular disease, vasoconstriction, and hypertension, conditions which may predispose SARS-CoV-2-infected individuals to COVID-19-related complications such as pulmonary hypertension, lung fibrosis, myocardial injury, stroke, and acute kidney injury. Hence, CD47 is a candidate biomarker for severe COVID-19. Further research will have to show whether CD47 is a reliable diagnostic marker for the early identification of COVID-19 patients requiring antiviral therapy.