Heart Failure with Reduced Ejection Fraction and COVID-19, when the Sick Get Sicker: Unmasking Racial and Ethnic Inequities During a Pandemic.

Minoritized racial and ethnic groups have the highest incidence, prevalence, and hospitalization rate for heart failure. Despite improvement in medical therapies and overall survival, the morbidity and mortality of these groups remain elevated. The reasons for this disparity are multifactorial, including social determinant of health (SDOH) such as access to care, bias, and structural racism. These same factors contributed to higher rates of COVID-19 infection among minoritized racial and ethnic groups. In this review, we aim to explore the lessons learned from the COVID-19 pandemic and its interconnection between heart failure and SDOH. The pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.

Heart Failure with Reduced Ejection Fraction and COVID-19, when the Sick Get Sicker: Unmasking Racial and Ethnic Inequities During a Pandemic.

Minoritized racial and ethnic groups have the highest incidence, prevalence, and hospitalization rate for heart failure. Despite improvement in medical therapies and overall survival, the morbidity and mortality of these groups remain elevated. The reasons for this disparity are multifactorial, including social determinant of health (SDOH) such as access to care, bias, and structural racism. These same factors contributed to higher rates of COVID-19 infection among minoritized racial and ethnic groups. In this review, we aim to explore the lessons learned from the COVID-19 pandemic and its interconnection between heart failure and SDOH. The pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.

Racial, Ethnic, and Gender Disparities in Valvular Heart Failure Management.

Racial, ethnic, and gender disparities are present in the diagnosis and management of valvular heart disease. The prevalence of valvular heart disease varies by race, ethnicity, and gender, but diagnostic evaluations are not equitable across the groups, which makes the true prevalence less clear. The delivery of evidence-based treatments for valvular heart disease is not equitable. This article focuses on the epidemiology of valvular heart diseases associated with heart failure and the related disparities in treatment, with a focus on how to improve delivery of nonpharmacological and pharmacological treatments.

Development of Synthetic mRNAs Encoding Split Cytotoxic Proteins for Selective Cell Elimination Based on Specific Protein Detection.

For the selective elimination of deleterious cells (e.g., cancer cells and virus-infected cells), the use of a cytotoxic gene is a promising approach. DNA-based systems have achieved selective cell elimination but risk insertional mutagenesis. Here, we developed a synthetic mRNA-based system to selectively eliminate cells expressing a specific target protein. The synthetic mRNAs used in the system are designed to express an engineered protein pair that are based on a cytotoxic protein, Barnase. Each engineered protein is composed of an N- or C-terminal fragment of Barnase, a target protein binding domain, and an intein that aids in reconstituting full-length Barnase from the two fragments. When the mRNAs are transfected to cells expressing the target protein, both N- and C-terminal Barnase fragments bind to the target protein, causing the intein to excise itself and reconstitute cytotoxic full-length Barnase. In contrast, when the target protein is not present, the reconstitution of full-length Barnase is not induced. Four candidate constructs containing split Barnase were evaluated for the ability to selectively eliminate target protein-expressing cells. One of the candidate sets demonstrated highly selective cell death. This system will be a useful therapeutic tool to selectively eliminate deleterious cells.

Unequitable Heart Failure Therapy for Black, Hispanic and American-Indian Patients.

Despite the high prevalence of heart failure among Black and Hispanic populations, patients of colour are frequently under-prescribed guideline-directed medical therapy (GDMT) and American-Indian populations are not well characterised. Clinical inertia, financial toxicity, underrepresentation in trials, non-trustworthy medical systems, bias and structural racism are contributing factors. There is an urgent need to develop evidence-based strategies to increase the uptake of GDMT for heart failure in patients of colour. Postulated strategies include prescribing all GDMT upon first encounter, aggressive outpatient uptitration of GDMT, intervening upon social determinants of health, addressing bias and racism through changing processes or policies that unfairly disadvantage patients of colour, engagement of stakeholders and implementation of national quality improvement programmes.

3D-printed oxygen-releasing scaffolds improve bone regeneration in mice.

Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (µtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable µtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-µtank scaffolds. PCL-µtank scaffolds were loaded with pure O2 at 300-500 psi. When placed at atmospheric pressures, the scaffolds released O2 over a period of up to 8 h. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that µtank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O2-loaded, hASC-seeded, PCL-µtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-µtank scaffolds may enhance hASC-mediated bone tissue regeneration.