System dynamics, and specifically qualitative participatory applications of system dynamics, have potential to benefit public health research, scholarship, and practice. A systematic review was conducted to examine the existing applications of participatory system dynamics (PSD) to public health research. Three databases were searched using unique search terms related to PSD and methodological applications in public health research. A total of 57 unique articles met inclusion criteria and were included for review. The studies included for review were conducted globally and represent a wide breadth of public health issues. The review identified several advantages to adopting PSD methods in public health scholarship and practice. The PSD methods provide innovative frameworks for conceptualizing complex and nuanced public health problems. The participatory nature of PSD allows for increased community engagement and empowerment to address public health problems, as well as to mitigate existing power dynamics between research institutions and marginalized communities that are disproportionately impacted by social and health inequities. Finally, causal loop diagrams developed using PSD methods have unique potential to convey complex concepts to policy makers and interventionists. This systematic review reports evidence for PSD's potential to advance equity in public health research and practice.

Trauma is the number one cause of death among Americans between the ages of 1 and 46 years, costing more than $670 billion a year. Following death related to central nervous system injury, hemorrhage accounts for the majority of remaining traumatic fatalities. Among those with severe trauma that reach the hospital alive, many may survive if the hemorrhage and traumatic injuries are diagnosed and adequately treated in a timely fashion. This article aims to review the recent advances in pathophysiology management following a traumatic hemorrhage as well as the role of diagnostic imaging in identifying the source of hemorrhage. The principles of damage control resuscitation and damage control surgery are also discussed. The chain of survival for severe hemorrhage begins with primary prevention; however, once trauma has occurred, prehospital interventions and hospital care with early injury recognition, resuscitation, definitive hemostasis, and achieving endpoints of resuscitation become paramount. An algorithm is proposed for achieving these goals in a timely fashion as the median time from onset of hemorrhagic shock and death is 2 h.

Adipose-derived stromal vascular fraction (SVF) has emerged as a potential regenerative therapy, but few studies utilize SVF in a setting of advanced age. Additionally, the specific cell population in SVF providing therapeutic benefit is unknown. We hypothesized that aging would alter the composition of cell populations present in SVF and its ability to promote angiogenesis following injury, a mechanism that is T cell-mediated. SVF isolated from young and old Fischer 344 rats was examined with flow cytometry for cell composition. Mesenteric windows from old rats were isolated following exteriorization-induced (EI) hypoxic injury and intravenous injection of one of four cell therapies: (1) SVF from young or (2) old donors, (3) SVF from old donors depleted of or (4) enriched for T cells. Advancing age increased the SVF T-cell population but reduced revascularization following injury. Both young and aged SVF incorporated throughout the host mesenteric microvessels, but only young SVF significantly increased vascular area following EI. This study highlights the effect of donor age on SVF angiogenic efficacy and demonstrates how the ex vivo mesenteric-window model can be used in conjunction with SVF therapy to investigate its contribution to angiogenesis.

Aims: The objective of this study is to identify mechanisms for adipose stromal vascular fraction's (SVF) restorative effects on vasodilation in aging-induced coronary microvascular disease (CMD). We hypothesize that reactive oxygen species (ROS) diminish β1-adrenergic receptor (β1ADR)- and flow-mediated dilation (FMD) in coronary arterioles, reversible by SVF and adipose-derived stem cells (ADSCs). Results: SVF attenuates aging-induced chronic accumulation of ROS and pro-oxidant gene and protein expression with enhancement of antioxidant gene and protein expression and glutathione, but not nitric oxide. ADSCs attenuate hydrogen peroxide while restoring nitric oxide and glutathione. Mass spectrometry of SVF- and ADSC-conditioned media reveals abundant antioxidant proteins suggesting a paracrine mechanism. FMD and β1ADR-mediated dilation diminished with aging, restored with SVF and ADSCs. FMD was restored by a switch in the acute signaling mediator from hydrogen peroxide in aging to peroxynitrite with SVF and ADSCs. Vasorelaxation to β1ADR-agonism was mechanistically linked with hydrogen peroxide, nitric oxide, and glutathione. Exogenous ROS eliminates isoproterenol-mediated dilation in youth that is blocked by inhibition of pro-desensitization and internalization proteins while nitric oxide enhances isoproterenol-mediated dilation in aging. Innovation: We introduce a novel mechanism by which ROS impacts β1ADR trafficking: the ROS/RNS-β1ADR desensitization and internalization axis. Aging-induced ROS shunts β1ADR from the plasma membrane into endosomes. SVF reduces oxidative burden, restoring functional β1ADR. Conclusions: SVF (and ADSCs to a lesser extent) reduce oxidative stress, and restore flow- and β1ADR-mediated vasodilation in aging. SVF represents a promising therapeutic strategy for CMD by addressing root cause of pathology; that is, oxidative stress-mediated hyperconstriction. Antioxid. Redox Signal. 38, 261-281.

PurposeNrf2 is a nuclear transcription factor and plays an important role in the regulation of oxidative stress and inflammation. We recently demonstrated that sulforaphane (SFN) protected mice from developing pulmonary arterial hypertension (PAH) and right ventricular (RV) dysfunction by elevating cardiac Nrf2 expression and function. Here we further investigate Nrf2 dependence for SFN-mediated prevention of PAH and RV dysfunction in an Nrf2 knockout mouse model.MethodsWe used male global Nrf2-knockout mice and male C57/6 J wild type mice in the following groups: Control group received room air and vehicle control; SuHx group received SU5416 and 10% hypoxia for 4 weeks to induce PAH; SuHx+SFN group received both SuHx and sulforaphane, a Nrf2 activator, for 4 weeks. Transthoracic echocardiography was performed to quantify RV function and estimate pulmonary vascular resistance over 4 weeks. PAH was confirmed using invasive RV systolic pressure measurement at 4 weeks.ResultsAll Nrf2 knockout mice survived the 4-week SuHx induction of PAH. SuHx caused progressive RV diastolic/systolic dysfunction and increased RV systolic pressure. The development of RV diastolic dysfunction occurred earlier in the Nrf2 knockout PAH mice when compared with the wide type PAH mice. SFN partially or completely reversed SuHx-induced RV diastolic/systolic dysfunction and increased RV systolic pressure in wild-type mice, but not in Nrf2 knockout mice.ConclusionOur findings demonstrated the essential role of Nrf2 in SFN-mediated prevention of RV dysfunction and PAH, and increasing Nrf2 activity in patients with PAH may have therapeutic potential.

Objective tracking of asthma medication use and exposure in real-time and space has not been feasible previously. Exposure assessments have typically been tied to residential locations, which ignore exposure within patterns of daily activities. We investigated the associations of exposure to multiple air pollutants, derived from nearest air quality monitors, with space-time asthma rescue inhaler use captured by digital sensors, in Jefferson County, Kentucky. A generalized linear mixed model, capable of accounting for repeated measures, over-dispersion and excessive zeros, was used in our analysis. A secondary analysis was done through the random forest machine learning technique. The 1039 participants enrolled were 63.4% female, 77.3% adult (>18) and 46.8% White. Digital sensors monitored the time and location of over 286980 asthma rescue medication uses and associated air pollution exposures over 193697 patient-days, creating a rich spatiotemporal dataset of over 10905240 data elements. In the generalized linear mixed model, an interquartile range (IQR) increase in pollutant exposure was associated with a mean rescue medication use increase per person per day of 0.201 [95% confidence interval (CI): 0.189-0.214], 0.153 (95% CI: 0.136-0.171), 0.131 (95% CI: 0.115-0.147) and 0.113 (95% CI: 0.097-0.129), for sulphur dioxide (SO2), nitrogen dioxide (NO2), fine particulate matter (PM2.5) and ozone (O3), respectively. Similar effect sizes were identified with the random forest model. Time-lagged exposure effects of 0-3 days were observed. Daily exposure to multiple pollutants was associated with increases in daily asthma rescue medication use for same day and lagged exposures up to 3 days. Associations were consistent when evaluated with the random forest modelling approach.

Our past study showed that coronary arterioles isolated from adipose-derived stromal vascular fraction (SVF)-treated rats showed amelioration of the age-related decrease in vasodilation to beta-adrenergic receptor (β-AR) agonist and improved β-AR-dependent coronary flow and microvascular function in a model of advanced age. We hypothesized that intravenously (i.v.) injected SVF improves coronary microvascular function in aged rats by re-establishing the equilibrium of the negative regulators of the internal adrenergic signaling cascade, G-protein receptor kinase 2 (GRK2) and G-alpha inhibitory (Gαi) proteins, back to youthful levels. Female Fischer-344 rats aged young (3 months, n = 24), old (24 months, n = 26), and old animals that received 1 × 107 green fluorescent protein (GFP+) SVF cells (O + SVF, n = 11) 4 weeks prior to sacrifice were utilized. Overnight urine was collected prior to sacrifice for catecholamine measurements. Cardiac samples were used for western blotting while coronary arterioles were isolated for pressure myography studies, immunofluorescence staining, and RNA sequencing. Coronary microvascular levels of the β1 adrenergic receptor are decreased with advancing age, but this decreased expression was rescued by SVF treatment. Aging led to a decrease in phosphorylated GRK2 in cardiomyocytes vs. young control with restoration of phosphorylation status by SVF. In vessels, there was no change in genetic transcription (RNAseq) or protein expression (immunofluorescence); however, inhibition of GRK2 (paroxetine) led to improved vasodilation to norepinephrine in the old control (OC) and O + SVF, indicating greater GRK2 functional inhibition of β1-AR in aging. SVF works to improve adrenergic-mediated vasodilation by restoring the β1-AR population and mitigating signal cascade inhibitors to improve vasodilation.

Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5L/min), and pressures (0 to ~420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. The pediatric VAD produced flows as high as 4.27L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.

O'Brien, IT, Kozerski, AE, Gray, WD, Chen, L, Vargas, LJ, McEnroe, CB, Vanhoover, AC, King, KM, Pantalos, GM, and Caruso, JF. Use of gloves to examine intermittent palm cooling's impact on rowing ergometry. J Strength Cond Res 35(4): 931-940, 2021-The aim of this study was to examine the use of gloves on intermittent palm cooling's impact on rowing ergometry workouts. Our methods had subjects (n = 34) complete 3 rowing ergometer workouts of up to 8 2-minute stages separated by 45- or 60-second rests. They were randomized to one of the following treatments per workout: no palm cooling (NoPC), intermittent palm cooling as they rowed (PCex), or intermittent palm cooling as they rowed and post-exercise (PCex&post). Palm cooling entailed intermittent cold (initial temperature: 8.1° C) application and totaled 10 (PCex) and 20 (PCex&post) minutes, respectively. Workouts began with 8 minutes of rest after which pre-exercise data were obtained, followed by a ten-minute warm-up and the workout, and 20 minutes of post-exercise recovery. Numerous physiological and performance variables were collected before, during, and after workouts, and each was analyzed with either a two- or three-way analysis of variance. Our results include, with a 0.05 alpha and a simple effects post hoc, the distance rowed analysis produced a significant workout effect with PCex, PCex&post > NoPC. There were also significant interworkout differences for heart rate (HR) (NoPC > PCex) and blood lactate concentration (NoPC > PCex, PCex&post). We conclude that lower HRs and blood lactate concentrations from intermittent cooling caused subjects to experience less fatigue during those workouts and enabled more work to be performed. Continued research should identify optimal cooling characteristics to expedite body heat removal. Practical applications suggest that intermittent palm cooling administered with gloves enhance performance by abating physiological markers of fatigue.

[This corrects the article DOI: 10.1007/s40200-020-00519-y.].