Effect of Artificial Lung Fiber Bundle Geometric Design on Micro- and Macro-scale Clot Formation.

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm). Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. These results can be used to create less thrombogenic, more efficient artificial lung designs. Translational Impact Sentence: Fiber bundle parameters, such as decreased packing density, increased blood flow velocity, and a longer path length, can be used to design a less thrombogenic, more efficient artificial lung to extend functionality.

C-type natriuretic peptide induces inotropic and lusitropic effects in human 3D-engineered cardiac tissue: Implications for the regulation of cardiac function in humans.

The role of C-type natriuretic peptide (CNP) in the regulation of cardiac function in humans remains to be established as previous investigations have been confined to animal model systems. Here, we used well-characterized engineered cardiac tissues (ECTs) generated from human stem cell-derived cardiomyocytes and fibroblasts to study the acute effects of CNP on contractility. Application of CNP elicited a positive inotropic response as evidenced by increases in maximum twitch amplitude, maximum contraction slope and maximum calcium amplitude. This inotropic response was accompanied by a positive lusitropic response as demonstrated by reductions in time from peak contraction to 90% of relaxation and time from peak calcium transient to 90% of decay that paralleled increases in maximum contraction decay slope and maximum calcium decay slope. To establish translatability, CNP-induced changes in contractility were also assessed in rat ex vivo (isolated heart) and in vivo models. Here, the effects on force kinetics observed in ECTs mirrored those observed in both the ex vivo and in vivo model systems, whereas the increase in maximal force generation with CNP application was only detected in ECTs. In conclusion, CNP induces a positive inotropic and lusitropic response in ECTs, thus supporting an important role for CNP in the regulation of human cardiac function. The high degree of translatability between ECTs, ex vivo and in vivo models further supports a regulatory role for CNP and expands the current understanding of the translational value of human ECTs. NEW FINDINGS: What is the central question of this study? What are the acute responses to C-type natriuretic peptide (CNP) in human-engineered cardiac tissues (ECTs) on cardiac function and how well do they translate to matched concentrations in animal ex vivo and in vivo models? What is the main finding and its importance? Acute stimulation of ECTs with CNP induced positive lusitropic and inotropic effects on cardiac contractility, which closely reflected the changes observed in rat ex vivo and in vivo cardiac models. These findings support an important role for CNP in the regulation of human cardiac function and highlight the translational value of ECTs.

Examining the impact of social distancing and methamphetamine use on sexual risk and intimate partner violence in sexual and gender minority young adults during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic in 2020, concerns were raised about the potential impact of pandemic-related social distancing measures on existing health disparities among sexual and gender minority (SGM) young adults, including HIV transmission risk and intimate partner violence (IPV). Another concern was the potential for increased methamphetamine use during the pandemic, which is a known risk factor for HIV transmission and IPV. METHODS: The present analysis examines the impact of COVID-19 social distancing (social distancing and quarantining) and methamphetamine use on HIV risk and IPV in a combined dataset from 3 cohort studies of SGM young adults (two in Los Angeles and one in Chicago) from May 2020 to April 2021 (n = 1142). Bivariate analyses and multivariable logistic regressions were estimated. RESULTS: The median age was 26. All participants were assigned male at birth and most participants were men (93.8%). The largest racial groups were Hispanic/Latinx (44.6%) and Black (29.0%). In adjusted models methamphetamine use was consistently associated with having a new sex partner, higher numbers of sex partners, and experience of IPV, during the pandemic. Reporting no social distancing and reporting one social distancing behavior, were associated with experience of IPV relative to reporting 2 social distancing behaviors. Social distancing was not associated with sexual risk behavior or Pre-exposure Prophylaxis use. CONCLUSIONS: SGM young adults live at the intersection of multiple vulnerabilities during the COVID-19 pandemic. Addiction services, HIV prevention services, and violence support services should be prepared to support young adult SGM needs, particularly those who use methamphetamine.