CRISPR delivery with extracellular vesicles: Promises and challenges.

The CRISPR gene editing tool holds great potential for curing genetic disorders. However, the safe, efficient, and specific delivery of the CRISPR/Cas9 components into cells and tissues remains a challenge. While many currently available delivery methods achieve high levels of gene editing effects in vivo, they often result in genotoxicity and immunogenicity.

ALM/BMI: A Clinically Superior Index for Identifying Skeletal Muscle Dysfunction in Patients With Heart Failure.

Background: Skeletal muscle wasting is critical in patients with heart failure (HF). Whereas prior studies have employed appendicular lean mass (ALM) normalized by height squared to identify low skeletal muscle mass, the potential of ALM normalized to body mass index (ALM/BMI) remains unexplored in patients with HF. In this study, we compared the use of 2 skeletal muscle mass indices in patients with HF to examine their sex-specific correlations with measures of physical capacity, quality of life, and daily physical activity.

Short-Chain Fatty Acid Butyrate Is an Inotropic Agent With Vasorelaxant and Cardioprotective Properties.

Background: The heart can metabolize the microbiota-derived short-chain fatty acid butyrate. Butyrate may have beneficial effects in heart failure, but the underlying mechanisms are unknown. We tested the hypothesis that butyrate elevates cardiac output by mechanisms involving direct stimulation of cardiac contractility and vasorelaxation in rats.

Enantiomer-Specific Cardiovascular Effects of the Ketone Body 3-Hydroxybutyrate.

Background: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined.

Methods And Results: Three groups of 8 pigs each underwent a randomized, crossover study.

Urinary Prostaglandin E2 Excretion and the Risk of Cardiovascular and Kidney Disease.

Background: Inhibition of prostaglandin synthesis by nonsteroidal anti-inflammatory drugs is associated with cardiovascular mortality and kidney disease. This study hypothesizes that urinary prostaglandin E2 (PGE2) and PGE2 metabolite (PGEM) excretions are markers of cardiovascular and kidney health, because they reflect both systemic and kidney-derived PGE2 production.

Methods And Results: PGE2 and PGEM were measured in spot urine samples from 2291 participants (≥55 years old) of the population-based Rotterdam Study.

Transitory Activation and Improved Transition from Erosion to Formation within Intracortical Bone Remodeling in Hypoparathyroid Patients Treated with rhPTH(1-84).

In hypoparathyroidism, lack of parathyroid hormone (PTH) leads to low calcium levels and decreased bone remodeling. Treatment with recombinant human PTH (rhPTH) may normalize bone turnover. This study aimed to investigate whether rhPTH(1-84) continued to activate intracortical bone remodeling after 30 months and promoted the transition from erosion to formation and whether this effect was transitory when rhPTH(1-84) was discontinued.

External Validation of Proposed American Heart Association Algorithm for Cardiovascular Screening Before Kidney Transplantation.

Background: Screening for cardiovascular disease is currently recommended before kidney transplantation. The present study aimed to validate the proposed algorithm by the American Heart Association (AHA-2022) considering cardiovascular findings and outcomes in kidney transplant candidates, and to compare AHA-2022 with the previous recommendation (AHA-2012).

Methods And Results: We applied the 2 screening algorithms to an observational cohort of kidney transplant candidates (n=529) who were already extensively screened for coronary heart disease by referral to cardiac computed tomography between 2014 and 2019.

Attention-deficit/hyperactivity disorder is associated with increased risk of cardiovascular diseases: A systematic review and meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with other psychiatric and physical diseases. However, available evidence on associations between ADHD and cardiovascular diseases (CVDs) is mixed. To systematically review, quantitatively synthesize, and appraise available evidence on the link between ADHD with CVDs, we searched relevant articles in PubMed, Embase, PsycINFO, and Web of Science from inception to May 1, 2022.

Neurovascular Uncoupling Is Linked to Microcirculatory Dysfunction in Regions Outside the Ischemic Core Following Ischemic Stroke.

Background Normal brain function depends on the ability of the vasculature to increase blood flow to regions with high metabolic demands. Impaired neurovascular coupling, such as the local hyperemic response to neuronal activity, may contribute to poor neurological outcome after stroke despite successful recanalization, that is, futile recanalization. Methods and Results Mice implanted with chronic cranial windows were trained for awake head-fixation before experiments.

The proteomic landscape of small urinary extracellular vesicles during kidney transplantation.

Kidney transplantation is the preferred renal replacement therapy available. Yet, long-term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) - as a non-invasive source of information - were collected from 22 living donors and recipients.

Northern European (L.) populations are genetically divergent across geographical regions and environmental gradients.

The salmonid fish Brown trout is iconic as a model for the application of conservation genetics to understand and manage local interspecific variation. However, there is still scant information about relationships between local and large-scale population structure, and to what extent geographical and environmental variables are associated with barriers to gene flow. We used information from 3,782 mapped SNPs developed for the present study and conducted outlier tests and gene-environment association (GEA) analyses in order to examine drivers of population structure.