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Background--Timely follow-up after hospitalization for heart failure (HF) is recommended. However, follow-up is suboptimal, especially in lower socioeconomic groups. Patient-centered solutions for facilitating follow-up post-HF hospitalization have not been extensively evaluated. Methods and Results--Face-to-face surveys were conducted between 2015 and 2016 among 83 racially diverse adult patients (61% African American, 34% Caucasian, and 5% Other) hospitalized for HF at a university hospital centered in a low-income area of Columbus, Ohio. Patient perceptions of methods to facilitate follow-up post-HF hospitalization and likelihood of using interventions were investigated using a Likert scale: 1=very much to 5=not at all. Results were analyzed by Wilcoxon signed-rank test with Bonferroni correction. The response rate was 82%. The annual household income was <$35 000 for 49% of patients. An appointment near the patient's home was the most desired intervention (77%), followed by reminder message (73%), transportation to appointment (63%), and elimination of copayment (59%). Interventions most likely to be used if provided were similarly ranked: reminder message (48%), appointment near home (46%), elimination of copay (46%), and transportation to appointment (39%). There were significant differences (P=0.001) in high-ranking interventions related to location (appointment near home, transportation, home appointment) and reminder for visit compared with low-ranking interventions related to time (weekend appointment, appointment after 5 PM) and telemedicine. Conclusions--Among this cohort of racially diverse low-income patients hospitalized with HF, an appointment near the patient's home and a reminder message were the most desired interventions to facilitate follow-up. Further study of similar populations nationwide is warranted. [ABSTRACT FROM AUTHOR]

Regulatory single-nucleotide polymorphisms (rSNPs) alter gene expression. Common approaches for identifying rSNPs focus on sequence variants in conserved regions; however, it is unknown what fraction of rSNPs is undetectable using this approach. We present a systematic analysis of gene expression variation at the single-nucleotide level in the Saccharomyces cerevisiae GAL1-10 regulatory region. We exhaustively mutated nearly every base and measured the expression of each variant with a sensitive dual reporter assay. We observed an expression change for 7% (43/582) of the bases in this region, most of which (35/43, 81%) reside in conserved positions. The most dramatic changes were caused by variants that produced AUGs upstream of the translation start (uAUGs), and we sought to understand the consequences and molecular mechanisms underlying this class of mutations. A genome-wide analysis showed that genes with uAUGs display significantly lower mRNA and protein levels than genes without uAUGs. To determine the generality of this mechanism, we introduced uAUGs into S. cerevisiae genes and observed significantly reduced expression in 17/21 instances (p < 0.01), suggesting that uAUGs are functional in a wide variety of sequence contexts. Quantification of mRNA and protein levels for uAUG mutants showed that uAUGs affect both transcription and translation. Expression of uAUG mutants under the upf1Δ strain demonstrated that uAUGs stimulate the nonsense-mediated decay pathway. Our results suggest that uAUGs are potent and widespread regulators of gene expression that act by attenuating both protein and RNA levels. [ABSTRACT FROM AUTHOR]

Background: The renin-angiotensin-aldosterone system (RAAS) and adiposity measures are independently associated with the development of diabetes in African American (AA) adults. However, studies have not examined the combined interaction between RAAS and adiposity measures in relation to diabetes risk in AA adults., Objective: We examined the longitudinal association of combined RAAS and adiposity measures with incident diabetes among AAs in the Jackson Heart Study., Methods: AA adults were assessed at baseline (2000-2004) and over 12 years of follow-up. RAAS, anthropometric (waist circumference [WC], body mass index [BMI]) and adipokine (adiponectin, leptin, leptin: adiponectin ratio [LAR]) measures were collected at baseline. Aldosterone, WC, and LAR were chosen as the best predictor variables. The final model, adjusting for age, sex, education, occupation, systolic blood pressure, smoking, physical activity and RAAS altering medications, incorporated these variables and their interactions (WC*Aldosterone + LAR*Aldosterone) to explore their impact on incident diabetes., Results: Among 3,220 participants without diabetes at baseline, there were 554 incident cases over a median follow-up of 7.5 years. Aldosterone, WC, and LAR were positively associated with incident diabetes (all p < 0.05). A significant interaction was found between WC and aldosterone with a greater association among individuals with lower WC. This interaction was significant in participants with prediabetes but not in those with normoglycemia. No significant interaction was found between log-LAR and aldosterone with risk of incident diabetes., Conclusion: Higher aldosterone in participants is associated with greater risk of diabetes, particularly among individuals with prediabetes and lower WC., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Autophagy, a form of lysosomal degradation capable of eliminating dysfunctional proteins and organelles, is a cellular process associated with homeostasis. Autophagy functions in cell survival by breaking down proteins and organelles and recycling them to meet metabolic demands. However, aberrant up regulation of autophagy can function as an alternative to apoptosis. The duality of autophagy, and its regulation over cell survival/death, intimately links it with human disease. Non-coding RNAs regulate mRNA levels and elicit diverse effects on mammalian protein expression. The most studied non-coding RNAs to-date are microRNAs (miRNA). MicroRNAs function in post-transcriptional regulation, causing profound changes in protein levels, and affect many biological processes and diseases. The role and regulation of autophagy, whether it is beneficial or harmful, is a controversial topic in cardiovascular disease. A number of recent studies have identified miRNAs that target autophagy-related proteins and influence the development, progression, or treatment of cardiovascular disease. Understanding the mechanisms by which these miRNAs work can provide promising insight and potential progress towards the development of therapeutic treatments in cardiovascular disease.

Background: Peripheral artery disease (PAD) is a major health burden in the world. Stem cell-based therapy has emerged as an attractive treatment option in regenerative medicine. In this study, we sought to test the hypothesis that stem cell-based therapy can ameliorate ischemia induced limb injury., Methods: We isolated mesenchymal stem cells derived from human placentas (PMSCs) and intramuscularly transplanted them into injured hind limbs. Treatment with PMSCs reduced acute muscle fibers apoptosis induced by ischemia., Results: PMSC treatment significantly enhanced regeneration of the injured hind limb by reducing fibrosis and enhancing running capacity when the animals were subjected to treadmill training. Mechanistically, injected PMSCs can modulate acute inflammatory responses by reducing neutrophil and macrophage infiltration following limb ischemia. ELISA assays further confirmed that PMSC treatment can also reduce pro-inflammatory cytokines, TNF-α and IL-6, and enhance anti-inflammatory cytokine, IL-10 at the injury sites., Conclusion: Taken together, our results demonstrated that PMSCs can be a potential effective therapy for treatment of PAD via immunomodulation.

Regulatory single-nucleotide polymorphisms (rSNPs) alter gene expression. Common approaches for identifying rSNPs focus on sequence variants in conserved regions; however, it is unknown what fraction of rSNPs is undetectable using this approach. We present a systematic analysis of gene expression variation at the single-nucleotide level in the Saccharomyces cerevisiae GAL1-10 regulatory region. We exhaustively mutated nearly every base and measured the expression of each variant with a sensitive dual reporter assay. We observed an expression change for 7% (43/582) of the bases in this region, most of which (35/43, 81%) reside in conserved positions. The most dramatic changes were caused by variants that produced AUGs upstream of the translation start (uAUGs), and we sought to understand the consequences and molecular mechanisms underlying this class of mutations. A genome-wide analysis showed that genes with uAUGs display significantly lower mRNA and protein levels than genes without uAUGs. To determine the generality of this mechanism, we introduced uAUGs into S. cerevisiae genes and observed significantly reduced expression in 17/21 instances (p < 0.01), suggesting that uAUGs are functional in a wide variety of sequence contexts. Quantification of mRNA and protein levels for uAUG mutants showed that uAUGs affect both transcription and translation. Expression of uAUG mutants under the upf1Δ strain demonstrated that uAUGs stimulate the nonsense-mediated decay pathway. Our results suggest that uAUGs are potent and widespread regulators of gene expression that act by attenuating both protein and RNA levels.