Citric acid cycle flux and pressure-volume work in the isolated working rat heart

It has been demonstrated previously that the mammalian heart cannot sustain physiologic levels of pressure-volume work if ketone bodies are the only substrates for respiration. In order to determine the metabolic derangement responsible for contractile failure in hearts utilizing ketone bodies, rat hearts were prefused at a near-physiologic workload in a working heart apparatus with acetoacetate and competing or alternate substrates including glucose, lactate, pyruvate, propionate, leucine, isoleucine, valine and acetate. While the pressure-volume work for hearts utilizing glucose was stable for 60 minutes of perfusion, performance fell by 30 minutes for hearts oxidizing acetoacetate as the sole substrate. The tissue content of 2-oxoglutarate and its transamination product, glutamate, were elevated in hearts utilizing acetoacetate while succinyl-CoA was decreased suggesting impaired flux through the citric acid cycle at the level of 2-oxoglutarate dehydrogenase. Further studies indicated that the inhibition of 2-oxoglutarate dehydrogenase developed prior to the onset of contractile failure and that the inhibition of the enzyme may be related to sequestration of the required cofactor, coenzyme A, as the thioesters acetoacetyl-CoA and acetyl-CoA. The contractile failure was not observed when glucose, lactate, pyruvate, propionate, valine or isoleucine were present together with acetoacetate, but the addition of acetate or leucine to acetoacetate did not improve performance indicating that improved performance is not mediated through the provision of additional acetyl-CoA. Furthermore, addition of competing substrates that improved function did not relieve the inhibition of 2-oxoglutarate dehydrogenase and actually resulted in the further accumulation of citric acid cycle intermediates "upstream" of 2-oxoglutarate dehydrogenase (2-oxoglutarate, glutamate, citrate and malate). Studies with (1-$\sp{14}$C) pyruvate indicate that the utilization of ketone bodies is associated with activation of NADP$\sp+$dependent malic enzyme and enrichment of the C4 pool of the citric acid cycle. The results suggest that contractile failure induced by ketone bodies in rat heart results from inhibition of 2-oxoglutarate dehydrogenase and that reversal of contractile failure is dissociated from relief of the inhibition, but rather is due to the entry of carbon units into the citric acid cycle as compounds other than acetyl-CoA. This mechanism of enrichment (anaplerosis) provides oxaloacetate for condensation with acetyl-CoA derived from ketone bodies allowing continued energy production by sustaining flux through a span of the citric acid cycle up to the point of inhibition at 2-oxoglutarate dehydrogenase for energy production thereby producing the reducing equivalents necessary to sustain oxidative phosphorylation. ^

Financial performance drivers and strategic control: The case of cancer treatment centers

Strategic control is defined as the use of qualitative and quantitative tools for the evaluation of strategic organizational performance. Most research in strategic planning has focused on strategy formulation and implementation, but little work has been done on strategic performance evaluation particularly in the area of cancer research. The objective of this study was to identify strategic control approaches and financial performance metrics used by major cancer centers in the country as an initial step in expanding the theory and practice behind strategic organizational performance. Focusing on hospitals which share similar mandate and resource constraints was expected to improve measurement precision. The results indicate that most cancer centers use a wide selection of evaluation tools, but sophisticated analytical approaches were less common. In addition, there was evidence that high-performing centers tend to invest a larger degree of resources in the area of strategic performance analysis than centers showing lower financial results. The conclusions point to the need for incorporating higher degree of analytical power in order to improve the tracking of strategic performance. This study is one of the first to concentrate in the area of strategic control.^

Occupational performance of Mexican Americans with end-stage-renal-disease living on dialysis in the lower Rio Grande Valley

The number of people with end-stage-renal-disease (ESRD) and living with dialysis is a growing public health concern. Most studies about the impact of ESRD on people’s lives have placed attention on the medical and clinical dimension of ESRD. Very few have given attention to the environmental and cultural context in which people with ESRD live, the adaptation that these individuals must make to adjust to living with ESRD and dialysis, or the occupations in which they engage. Additionally these studies have not focused on Mexican Americans who are disproportionately affected by this illness and condition. This qualitative study explores the needs, perceptions, and issues facing Mexican Americans with ESRD living with dialysis as well as their families. Participants were residents of the Lower Rio Grande Valley and included individuals with ESRD, family members, and the healthcare providers who give care to them. The Health Belief Model and Lifestyle Performance Model served as the theoretical frameworks. The study also explored the daily occupations of this population. ^ In-depth interviews were conducted on 15 Mexican Americans with ESRD living with dialysis, 15 family members, and six dialysis healthcare providers. A video documentary of the day-to-day life of three individuals with ESRD and their families was produced. Such data do not currently exist and will greatly enhance the understanding of the human experience of living with ESRD. The results suggest that a collective effort of the family unit is at work to deal with the demands of dialysis. An imbalance and disharmony exist among the occupational activities, which creates occupational deprivation and disruption for both the individuals and family members. Implications for practice and recommendations for further research are described. ^

A multi-site pilot test study to measure safety climate in the university work setting

Next to leisure, sport, and household activities, the most common activity resulting in medically consulted injuries and poisonings in the United States is work, with an estimated 4 million workplace related episodes reported in 2008 (U.S. Department of Health and Human Services, 2009). To address the risks inherent to various occupations, risk management programs are typically put in place that include worker training, engineering controls, and personal protective equipment. Recent studies have shown that such interventions alone are insufficient to adequately manage workplace risks, and that the climate in which the workers and safety program exist (known as the "safety climate") is an equally important consideration. The organizational safety climate is so important that many studies have focused on developing means of measuring it in various work settings. While safety climate studies have been reported for several industrial settings, published studies on assessing safety climate in the university work setting are largely absent. Universities are particularly unique workplaces because of the potential exposure to a diversity of agents representing both acute and chronic risks. Universities are also unique because readily detectable health and safety outcomes are relatively rare. The ability to measure safety climate in a work setting with rarely observed systemic outcome measures could serve as a powerful means of measure for the evaluation of safety risk management programs. ^ The goal of this research study was the development of a survey tool to measure safety climate specifically in the university work setting. The use of a standardized tool also allows for comparisons among universities throughout the United States. A specific study objective was accomplished to quantitatively assess safety climate at five universities across the United States. At five universities, 971 participants completed an online questionnaire to measure the safety climate. The average safety climate score across the five universities was 3.92 on a scale of 1 to 5, with 5 indicating very high perceptions of safety at these universities. The two lowest overall dimensions of university safety climate were "acknowledgement of safety performance" and "department and supervisor's safety commitment". The results underscore how the perception of safety climate is significantly influenced at the local level. A second study objective regarding evaluating the reliability and validity of the safety climate questionnaire was accomplished. A third objective fulfilled was to provide executive summaries resulting from the questionnaire to the participating universities' health & safety professionals and collect feedback on usefulness, relevance and perceived accuracy. Overall, the professionals found the survey and results to be very useful, relevant and accurate. Finally, the safety climate questionnaire will be offered to other universities for benchmarking purposes at the annual meeting of a nationally recognized university health and safety organization. The ultimate goal of the project was accomplished and was the creation of a standardized tool that can be used for measuring safety climate in the university work setting and can facilitate meaningful comparisons amongst institutions.^