Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes

BackgroundTo explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes.MethodsSixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder.ResultsHbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01).ConclusionsPoor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity

A study protocol for applying the co-creating knowledge translation framework to a population health study

BACKGROUND: Population health research can generate significant outcomes for communities, while Knowledge Translation (KT) aims to expressly maximize the outcomes of knowledge producing activity. Yet the two approaches are seldom explicitly combined as part of the research process. A population health study in Port Lincoln, South Australia offered the opportunity to develop and apply the co-KT Framework to the entire research process. This is a new framework to facilitate knowledge formation collaboratively between researchers and communities throughout a research to intervention implementation process. DESIGN: This study employs a five step framework (the co-KT Framework) that is formulated from engaged scholarship and action research principles. By following the steps a knowledge base will be cumulatively co-created with the study population that is useful to the research aims. Step 1 is the initiating of contact between the researcher and the study contexts, and the framing of the research issue, achieved through a systematic data collection tool. Step 2 refines the research issue and the knowledge base by building into it context specific details and conducting knowledge exchange events. Step 3 involves interpreting and analysing the knowledge base, and integrating evidence to inform intervention development. In Step 4 the intervention will be piloted and evaluated. Step 5 is the completion of the research process where outcomes for improvement will be instituted as regular practice with the facilitation of the community. In summary, the model uses an iterative knowledge construction mechanism that is complemented by external evidence to design interventions to address health priorities within the community. DISCUSSION: This is a systematic approach that operationalises the translational cycle using a framework for KT practice. It begins with the local context as its foundation for knowledge creation and ends with the development of contextually applicable interventions. It will be of interest to those involved in KT research, participatory action research, population health research and health care systems studies. The co-KT Framework is a method for embedding the principles of KT into all stages of a community-based research process, in which research questions are framed by emergent data from each previous stage.Kathryn Powell, Alison Kitson, Elizabeth Hoon, Jonathan Newbury, Anne Wilson and Justin Beilb

Agent-Based Model of Therapeutic Adipose-Derived Stromal Cell Trafficking during Ischemia Predicts Ability To Roll on P-Selectin

Intravenous delivery of human adipose-derived stromal cells (hASCs) is a promising option for the treatment of ischemia. After delivery, hASCs that reside and persist in the injured extravascular space have been shown to aid recovery of tissue perfusion and function, although low rates of incorporation currently limit the safety and efficacy of these therapies. We submit that a better understanding of the trafficking of therapeutic hASCs through the microcirculation is needed to address this and that selective control over their homing (organ- and injury-specific) may be possible by targeting bottlenecks in the homing process. This process, however, is incredibly complex, which merited the use of computational techniques to speed the rate of discovery. We developed a multicell agent-based model (ABM) of hASC trafficking during acute skeletal muscle ischemia, based on over 150 literature-based rules instituted in Netlogo and MatLab software programs. In silico, trafficking phenomena within cell populations emerged as a result of the dynamic interactions between adhesion molecule expression, chemokine secretion, integrin affinity states, hemodynamics and microvascular network architectures. As verification, the model reasonably reproduced key aspects of ischemia and trafficking behavior including increases in wall shear stress, upregulation of key cellular adhesion molecules expressed on injured endothelium, increased secretion of inflammatory chemokines and cytokines, quantified levels of monocyte extravasation in selectin knockouts, and circulating monocyte rolling distances. Successful ABM verification prompted us to conduct a series of systematic knockouts in silico aimed at identifying the most critical parameters mediating hASC trafficking. Simulations predicted the necessity of an unknown selectin-binding molecule to achieve hASC extravasation, in addition to any rolling behavior mediated by hASC surface expression of CD15s, CD34, CD62e, CD62p, or CD65. In vitro experiments confirmed this prediction; a subpopulation of hASCs slowly rolled on immobilized P-selectin at speeds as low as 2 µm/s. Thus, our work led to a fundamentally new understanding of hASC biology, which may have important therapeutic implications

Are Differences in Disability-Free Life Expectancy by Gender, Race, and Education Widening at Older Ages?

To examine change from 1991 to 2001 in disability-free life expectancy in the age range 60-90 by gender, race, and education in the United States. Mortality is estimated over two 10-year follow-up periods for persons in the National Health Interview Surveys of 1986/1987 and 1996/1997. Vital status is ascertained through the National Death Index. Disability prevalence is estimated from the National Health and Nutrition Examination Surveys of 1988-1994 and 1999-2002. Disability is defined as ability to perform four activities of daily living without difficulty. Disability-free life expectancy increased only among white men. Disabled life expectancy increased for all groups-black and white men and women. Racial differences in disability-free life expectancy widened among men; gender differences were reduced among whites. Expansion of socioeconomic differentials in disability-free life at older ages occurred among white men and women and black women. The 1990s was a period where the increased years of life between ages 60 and 90 were concentrated in disabled years for most population groups

Knowledge translation within a population health study: how do you do it?

BACKGROUND Despite the considerable and growing body of knowledge translation (KT) literature, there are few methodologies sufficiently detailed to guide an integrated KT research approach for a population health study. This paper argues for a clearly articulated collaborative KT approach to be embedded within the research design from the outset. DISCUSSION Population health studies are complex in their own right, and strategies to engage the local community in adopting new interventions are often fraught with considerable challenges. In order to maximise the impact of population health research, more explicit KT strategies need to be developed from the outset. We present four propositions, arising from our work in developing a KT framework for a population health study. These cover the need for an explicit theory-informed conceptual framework; formalizing collaborative approaches within the design; making explicit the roles of both the stakeholders and the researchers; and clarifying what counts as evidence. From our deliberations on these propositions, our own co-creating (co-KT) Framework emerged in which KT is defined as both a theoretical and practical framework for actioning the intent of researchers and communities to co-create, refine, implement and evaluate the impact of new knowledge that is sensitive to the context (values, norms and tacit knowledge) where it is generated and used. The co-KT Framework has five steps. These include initial contact and framing the issue; refining and testing knowledge; interpreting, contextualising and adapting knowledge to the local context; implementing and evaluating; and finally, the embedding and translating of new knowledge into practice. SUMMARY Although descriptions of how to incorporate KT into research designs are increasing, current theoretical and operational frameworks do not generally span a holistic process from knowledge co-creation to knowledge application and implementation within one project. Population health studies may have greater health impact when KT is incorporated early and explicitly into the research design. This, we argue, will require that particular attention be paid to collaborative approaches, stakeholder identification and engagement, the nature and sources of evidence used, and the role of the research team working with the local study community.Alison Kitson, Kathryn Powell, Elizabeth Hoon, Jonathan Newbury, Anne Wilson, Justin Beilb

Endurance training facilitates myoglobin desaturation during muscle contraction in rat skeletal muscle

At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O(2) to the mitochondria. Accordingly, intracellular O(2) tension (P(mb)O(2)) markedly declines in order to increase muscle O(2) uptake (m[Image: see text]O(2)). However, whether the change in P(mb)O(2) during muscle contraction modulates m[Image: see text]O(2) and whether the O(2) release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O(2) saturation of Mb (S(mb)O(2)) and P(mb)O(2) kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the m[Image: see text]O(2)peak significantly increased by 32%. Although the P(mb)O(2) during muscle contraction did not affect the increased m[Image: see text]O(2) in endurance-trained muscle, the O(2) release rate from Mb increased because of the increased Mb concentration and faster decremental rate in S(mb)O(2) at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster [Image: see text]O(2) kinetics in endurance-trained muscle