Many biomedical engineering degree programs lack substantial immersive clinical experiences for undergraduate students, creating a need for clinical immersion programs that contribute to training obje Show more
Many biomedical engineering degree programs lack substantial immersive clinical experiences for undergraduate students, creating a need for clinical immersion programs that contribute to training objectives that emphasize current clinical needs (Becker in Eur J Eng Educ 31:261-272, 2006; Davis et al. in J Eng Educ 91:211-221, 2002; Dym et al. in J Eng Educ 94:103-120, 2005). Immersive clinical experiences have the potential to bridge the gap between clinical and non-clinical learning objectives in biomedical engineering curriculum. In collaboration with Indiana University Health Methodist Hospital, we have created, executed, and evaluated a two-week cardiovascular clinical immersion program for biomedical engineering undergraduate students at Purdue University. As of August 2022, this program has run 11 times since 2014 with 60 participants to date, exposing students to intensive and non-intensive care environments, facilitating interactions with medical professionals, and encouraging exploration of innovative technologies shaping the training of clinicians with direct patient interaction. The variety of cardiovascular topics discussed and clinical settings observed has provided students with a unique, highly beneficial learning opportunity. Keys to the continued success and growth of similar programs include: recruiting a diverse team, support from administrative staff/clinicians, a funded student intern position, and careful consideration of liability/risk management. Areas of future consideration include, streamlining the order of scheduled events, determining if offering course credit would be beneficial to students, and tracking career trajectories after participations. Show less
Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in heart failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alteratio Show more
Limited knowledge exists of the extent of epigenetic alterations, such as DNA methylation, in heart failure (HF). We conducted targeted DNA methylation sequencing to identify DNA methylation alterations in coding and noncoding RNA (ncRNA) across different etiological subtypes of HF. A targeted bisulfite sequence capture sequencing platform was applied to DNA extracted from cardiac interventricular septal tissue of 30 male HF patients encompassing causes including hypertrophic obstructive cardiomyopathy, ischemic cardiomyopathy, dilated cardiomyopathy, and 9 control patients with nonfailing hearts. We detected 62 678 differentially methylated regions in the studied HF cohort. By comparing each HF subgroup to the nonfailing control group, we identified 195 unique differentially methylated regions: 5 in hypertrophic obstructive cardiomyopathy, 151 in dilated cardiomyopathy, and 55 in ischemic cardiomyopathy. These translated to 4 genes/1 ncRNA in hypertrophic obstructive cardiomyopathy, 131 genes/17 ncRNA in dilated cardiomyopathy, and 51 genes/5 ncRNA in ischemic cardiomyopathy. Subsequent gene/ncRNA expression analysis was assessed using quantitative reverse transcription polymerase chain reaction and revealed 6 genes: 4 hypermethylated ( HEY2, MSR1, MYOM3, and COX17), 2 hypomethylated ( CTGF and MMP2); and 2 microRNA: 1 hypermethylated (miR-24-1), 1 hypomethylated (miR-155) with significantly upregulated or downregulated expression levels consistent with the direction of methylation in the particular HF subgroup. For the first time DNA methylation alterations and associated gene expression changes were identified in etiologically variant pathological HF tissue. The methylation-sensitive and disease-associated genes/ncRNA identified from this study represent a unique cohort of loci that demonstrate a plausible potential as a novel diagnostic and therapeutic target in HF and warrant further investigation. Show less
cAMP-dependent protein kinase (PKA) regulates a broad range of cellular responses in the cardiac myocyte. Downstream regulation of the PKA pathway is mediated by a class of scaffolding proteins called Show more
cAMP-dependent protein kinase (PKA) regulates a broad range of cellular responses in the cardiac myocyte. Downstream regulation of the PKA pathway is mediated by a class of scaffolding proteins called A-kinase anchoring proteins (AKAPs), which sequester PKA to specific subcellular locations through binding to its regulatory subunit (R). However, the effect of RII autophosphorylation on AKAP binding and the degree of RII autophosphorylation in failing and nonfailing human hearts remains unknown. We investigated AKAP-RII binding by overlay analysis and surface plasmon resonance spectroscopy and measured RII autophosphorylation in human hearts by backphosphorylation. Binding of Ht31 peptide (representing the RII-binding region of AKAPs) to cardiac RII was increased approximately 145% (P<0.01) for autophosphorylated RII relative to unphosphorylated control. By surface plasmon resonance, RII autophosphorylation significantly increased binding affinity to Ht31 by approximately 200% (P<0.01). Baseline PKA-dependent phosphorylation of RII was significantly decreased approximately 30% (P<0.05) in human hearts with dilated cardiomyopathy compared with nonfailing controls. These results suggest that AKAP binding of PKA in the heart is regulated by RII autophosphorylation. Therefore AKAP targeting of PKA may be reduced in patients with end-stage heart failure. This mechanism may be responsible for the decreased cAMP-dependent phosphorylation of proteins in dilated cardiomyopathy that we and others have previously observed. Show less