Modulation of Cardiac Performance by Motor Protein Gene Transfer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75444/1/annals.1420.011.pd

Outcomes of 1½- or 2-ventricle conversion for patients initially treated with single-ventricle palliation

ObjectiveAs outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere.MethodsNine patients (4 male patients) who had previously undergone the Fontan procedure (n = 3) or bidirectional cavopulmonary shunting (n = 6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n = 2), pulmonary arteriovenous malformation (n = 1), and preference for biventricular anatomy (n = 6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle–pulmonary artery conduit (Rastelli-type operation).ResultsFive patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169–352 minutes) and 129 minutes (range, 100–168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3–99.8 months), all survivors are in New York Heart Association class I.ConclusionsPatients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes

Not Just a “Touch of the Sugars”: The Use of Occupational Therapy Interventions to Promote Independence in Diabetes Self-Management

Primary Focus: Health \u26 Wellness Secondary Focus: General \u26 Professional Issues Learning Objectives: At the end of this presentation, participants will: Objective 1: Define the scope of self-management in relation to diabetes care. Objective 2: Describe how the prevalence of diabetes and complications from mismanagement impact the United States healthcare system. Objective 3: Identify 2-3 ways in which occupational therapists can facilitate diabetes self-management in clinical practice to promote health and wellness. Abstract: In the United States (U.S.), 29.1 million people have diabetes mellitus (DM) (Centers for Disease Control and Prevention [CDC], 2014) and the cost of diabetes care totaled $245 billion in 2012 in the U.S. (CDC, 2014). DM and its complications can lead to serious health problems, such as heart disease and stroke, and was the 7th leading cause of death in the U.S. in 2010 (CDC, 2014). The high prevalence of DM and its costs within the U.S. indicate a need to improve diabetes self-management (DSM). Occupational therapists (OTs) have extensive knowledge on the impact of lifestyle on disease course and overall health (American Occupational Therapy Association [AOTA], 2014). As such, OTs are well positioned to provide DSM interventions (AOTA, 2014). The purpose of this session is to determine how OT interventions can impact patient participation in DSM. A systematic review of the literature was conducted to examine current research regarding patient participation in DSM. PubMed, Ovid Medline, CINAHL, and the Cochrane Library of Clinical Trials were searched using key terms selected to identify appropriate research studies. The initial search produced 218 articles. After excluding articles and screening for eligibility, 17 articles were critiqued and analyzed for information the scope of OT practice in DSM. The systematic review revealed the following themes: (1) Empowerment and Self-Efficacy, (2) Psychosocial Factors, (3) Occupational Engagement, and (4) Individualized Care. All of the themes had moderate levels of evidence to support them. The themes suggest that practitioners should use individualized interventions that focus on empowerment to promote DSM. As OTs are trained in these themes, the profession needs to advocate for the role of OTs in DSM. One reason why OTs are not more involved in DSM may be a lack of training on the procedural aspects of DM medication management. Within OT education, there needs to be increased focus on the scope DSM so OT students are better prepared to provide care to this population. Additionally, the review found no high level evidence where OTs provided the intervention. This evidence is needed in order for practitioners to better understand the impact of OT for individuals with DM. This session will define the prevalence and impact of DM in the U.S. and describe self-management in DM care. OT’s role in facilitating DSM in clinical practice to promote health and wellness will also be identified. References: American Occupational Therapy Association [AOTA]. (2014). Occupational therapy practice framework: Domain and process. American Journal of Occupational Therapy, 68(Suppl. 1), S1–S48. doi:10.5014/ajot.2014.682006 Centers for Disease Control and Prevention [CDC]. (2014). National diabetes statistics report, 2014 (Statistics Report). Atlanta, GA: National Center for Chronic Disease Prevention and Health Promotion. Centers for Disease Control and Prevention [CDC]. (2012). Diabetes report card 2012. Atlanta, GA: Author. Retrieved from http://www.cdc.gov/diabetes/pubs/pdf/diabetesreport card.pdf Level of Material Being Presented: Introductory Target Audience: OT, OTA, Members of General Community, Health Professionals Presentation: 39:4

Early Surgical Morbidity and Mortality in Adults with Congenital Heart Disease: The University of Michigan Experience

Objectives.  To review early surgical outcomes in a contemporary series of adults with congenital heart disease (CHD) undergoing cardiac operations at the University of Michigan, and to investigate possible preoperative and intraoperative risk factors for morbidity and mortality. Methods.  A retrospective medical record review was performed for all patients ≥18 years of age who underwent open heart operations by a pediatric cardiothoracic surgeon at the University of Michigan Congenital Heart Center between January 1, 1998 and December 31, 2004. Records from a cohort of pediatric patients ages 1–17 years were matched to a subset of the adult patients by surgical procedure and date of operation. Results.  In total, 243 cardiac surgical operations were performed in 234 adult patients with CHD. Overall mortality was 4.7% (11/234). The incidence of major postoperative complications was 10% (23/234) with a 19% (45/23) minor complication rate. The most common postoperative complication was atrial arrhythmias in 10.8% (25/234). The presence of preoperative lung or liver disease, prolonged cardiopulmonary bypass and aortic cross clamp times, and postoperative elevated inotropic score and serum lactates were significant predictors of mortality in adults. There was no difference between the adult and pediatric cohorts in terms of mortality and morbidity. Conclusions.  The postoperative course in adults following surgery for CHD is generally uncomplicated and early survival should be expected. Certain risk factors for increased mortality in this patient population may include preoperative presence of chronic lung or liver dysfunction, prolonged cardiopulmonary bypass and aortic cross-clamp times, and postoperative elevated inotropic score and serum lactate levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75596/1/j.1747-0803.2008.00170.x.pd

Characterization of the ZBTB42 gene in humans and mice

A 12 kb haplotype upstream of the key signaling protein gene, AKT1, has been associated with insulin resistance and metabolic syndrome (Devaney et al. 2010). The region contains the first exon and promoter sequences of AKT1, but also includes the complete transcript unit for a highly conserved yet uncharacterized zinc finger-containing protein (ZBTB42). One of the component SNPs of the 12 kb haplotype metabolic syndrome haplotype changes a conserved amino acid in the predicted ZBTB42 protein, increasing the potential significance of the ZBTB42 transcript unit for contributing to disease risk. Using RT-PCR of human and mouse cells, we verified that the two exon ZBTB42 was expressed and correctly spliced in human skeletal muscle, and murine C2C12 cells. Production of peptide antibodies showed the expected protein in human (47 kD) and mouse (49 kD) immunoblots, and murine tissue distribution showed strongest expression in muscle and ovary. Immunostaining showed nuclear localization of the ZBTB42 protein in human muscle. Confocal imaging analyses of murine muscle showed ZBTB42 distributed in the nucleoplasm, with particular enrichment in nuclei underlying the neuromuscular junctions. The genetic association data of metabolic syndrome, coupled with the molecular characterization of the ZBTB42 transcript unit and encoded protein presented here, suggests that ZBTB42 may be involved in metabolic syndrome phenotypes

Highlights from the Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength or FAMuSS Study

The purpose of the Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength study or FAMuSS was to identify genetic factors that dictated the response of health-related fitness phenotypes to resistance exercise training (RT). The phenotypes examined were baseline muscle strength and muscle, fat, and bone volume and their response to RT. FAMuSS participants were 1300 young (24 years), healthy men (42%) and women (58%) that were primarily of European-American descent. They were genotyped for ~500 polymorphisms and completed the Paffenbarger Physical Activity Questionnaire to assess energy expenditure and time spent in light, moderate, and vigorous intensity habitual physical activity and sitting. Subjects then performed a 12-week progressive, unilateral RT program of the nondominant arm with the dominant arm used as a comparison. Before and after RT, muscle strength was measured with the maximum voluntary contraction and one repetition maximum, while MRI measured muscle, fat, and bone volume. We will discuss the history of how FAMuSS originated, provide a brief overview of the FAMuSS methods, and summarize our major findings regarding genotype associations with muscle strength and size, body composition, cardiometabolic biomarkers, and physical activity

The angiotensin-converting enzyme insertion/deletion polymorphism rs4340 associates with habitual physical activity among European American adults.

BACKGROUND: The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism (rs4340) (ACE DIP) accounts for half of the variability in plasma ACE concentrations. ACE has been widely studied for its influence on sports performance; however, research on its influence in physical activity is limited and inconsistent. We examined the influence of the ACE DIP on physical activity among 461 European Americans. METHODS: Subjects completed the Paffenbarger Physical Activity Questionnaire for weekly walking distance. Multivariate analysis of covariance (MANCOVA) tested log-transformed differences in weekly walking distance among ACE DIP genotypes (II, ID, DD) with gender as a fixed factor, and age and body mass index (BMI) as covariates. Because we found a significant ACE DIPxBMI interaction (P = 0.03), we categorized the sample by normal weight (NW: BMI RESULTS: NW adults with ACE II walked 15.8 ± 11.1 km/week, ID 13.2 ± 10.6 km/week, and DD 17.9 ± 13.0 km/week, with ID walking less than II (P = 0.03) and DD (P = 0.01). OW adults with ACE II walked 16.7 ± 12.6 km/week, ID 13.8 ± 11.6 km/week, and DD 9.7 ± 9.0 km/week, with DD walking less than II (P = 0.02). Weekly walking distance was 8.2 ± 2.4 km/week less among OW adults with ACE DD than NW (P = 0.02). CONCLUSION: BMI interacted with ACE DD such that OW walked ~8.2 km/week less than NW, potentially equating to a body weight differential of ~3.5 kg annually

PPAR alpha L162V underlies variation in serum triglycerides and subcutaneous fat volume in young males

Background: Of the five sub-phenotypes defining metabolic syndrome, all are known to have strong genetic components ( typically 50 - 80% of population variation). Studies defining genetic predispositions have typically focused on older populations with metabolic syndrome and/or type 2 diabetes. We hypothesized that the study of younger populations would mitigate many confounding variables, and allow us to better define genetic predisposition loci for metabolic syndrome. Methods: We studied 610 young adult volunteers ( average age 24 yrs) for metabolic syndrome markers, and volumetric MRI of upper arm muscle, bone, and fat pre- and post-unilateral resistance training. Results: We found the PPARa L162V polymorphism to be a strong determinant of serum triglyceride levels in young White males, where carriers of the V allele showed 78% increase in triglycerides relative to L homozygotes ( LL = 116 +/- 11 mg/ dL, LV = 208 +/- 30 mg/ dL; p = 0.004). Men with the V allele showed lower HDL ( LL = 42 +/- 1 mg/ dL, LV = 34 +/- 2 mg/ dL; p = 0.001), but women did not. Subcutaneous fat volume was higher in males carrying the V allele, however, exercise training increased fat volume of the untrained arm in V carriers, while LL genotypes significantly decreased in fat volume ( LL = - 1,707 +/- 21 mm(3), LV = 17,617 +/- 58 mm(3); p = 0.002), indicating a systemic effect of the V allele on adiposity after unilateral training. Our study suggests that the primary effect of PPARa L162V is on serum triglycerides, with downstream effects on adiposity and response to training. Conclusion: Our results on association of PPARa and triglycerides in males showed a much larger effect of the V allele than previously reported in older and less healthy populations. Specifically, we showed the V allele to increase triglycerides by 78% ( p = 0.004), and this single polymorphism accounted for 3.8% of all variation in serum triglycerides in males ( p = 0.0037)

Skunk River Review 2009-10, vol 22

Welcome to the 2009-2010 edition of The Skunk River Review! We received a record number of entries this year, making this volume one of the best and most competitive! We even added a new category called Art & Literary Analysis to include a growing number of submissions dedicated to inspiration and critique. Each year we continue to receive many fine examples of student writing. Selection is a challenging process but enjoyable as the submissions range from a variety of topics and styles. Selected entries were only minimally edited for clarity. The Skunk River Review focuses on students from various DMACC campuses. It includes selections from College Preparatory Writing classes, Composition I and Composition II classes. All entries generally begin as class assignments and are supported by the instructor.https://openspace.dmacc.edu/skunkriver/1001/thumbnail.jp

MC4R Variant Is Associated With BMI but Not Response to Resistance Training in Young Females

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/1/oby_2147_sm_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93697/2/oby.2010.180.pd