Skeletal muscle dysfunction is associated with derangements in mitochondrial bioenergetics (but not UCP3) in a rodent model of sepsis

Muscle dysfunction is a common feature of severe sepsis and multi-organ failure. Recent evidence implicates bioenergetic dysfunction and oxidative damage as important underlying pathophysiological mechanisms. Increased abundance of uncoupling protein-3 (UCP-3) in sepsis suggests increased mitochondrial proton leak, which may reduce mitochondrial coupling efficiency but limit ROS production. Using a murine model, we examined metabolic, cardiovascular and skeletal muscle contractile changes following induction of peritoneal sepsis in wild-type and Ucp3(-/-) mice. Mitochondrial membrane potential (Δψm) was measured using two-photon microscopy in living diaphragm, and contractile function was measured in diaphragm muscle strips. The kinetic relationship between membrane potential and oxygen consumption was determined using a modular kinetic approach in isolated mitochondria. Sepsis was associated with significant whole body metabolic suppression, hypothermia and cardiovascular dysfunction. Maximal force generation was reduced and fatigue accelerated in ex vivo diaphragm muscle strips from septic mice. Mitochondrial membrane potential was lower in the isolated diaphragm from septic mice despite normal substrate oxidation kinetics and proton leak in skeletal muscle mitochondria. Even though wild-type mice exhibited an absolute 26 ± 6% higher UCP-3 protein abundance at 24 hours, no differences were seen in whole animal or diaphragm physiology, nor in survival rates, between wild-type and Ucp3(-/-) mice. In conclusion, this murine sepsis model shows a hypometabolic phenotype with evidence of significant cardiovascular and muscle dysfunction. This was associated with lower Δψm and alterations in mitochondrial ATP turnover and phosphorylation pathway. However, UCP-3 does not play an important functional role, despite its upregulation

Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest

Large mammals that live in arid and/or desert environments can cope with seasonal and local variations in rainfall, food and climate1 by moving long distances, often without reliable water or food en route. The capacity of an animal for this long-distance travel is substantially dependent on the rate of energy utilization and thus heat production during locomotion—the cost of transport2,3,4. The terrestrial cost of transport is much higher than for flying (7.5 times) and swimming (20 times)4. Terrestrial migrants are usually large1,2,3 with anatomical specializations for economical locomotion5,6,7,8,9, because the cost of transport reduces with increasing size and limb length5,6,7. Here we used GPS-tracking collars10 with movement and environmental sensors to show that blue wildebeest (Connochaetes taurinus, 220 kg) that live in a hot arid environment in Northern Botswana walked up to 80 km over five days without drinking. They predominantly travelled during the day and locomotion appeared to be unaffected by temperature and humidity, although some behavioural thermoregulation was apparent. We measured power and efficiency of work production (mechanical work and heat production) during cyclic contractions of intact muscle biopsies from the forelimb flexor carpi ulnaris of wildebeest and domestic cows (Bos taurus, 760 kg), a comparable but relatively sedentary ruminant. The energetic costs of isometric contraction (activation and force generation) in wildebeest and cows were similar to published values for smaller mammals. Wildebeest muscle was substantially more efficient (62.6%) than the same muscle from much larger cows (41.8%) and comparable measurements that were obtained from smaller mammals (mouse (34%)11 and rabbit (27%)). We used the direct energetic measurements on intact muscle fibres to model the contribution of high working efficiency of wildebeest muscle to minimizing thermoregulatory challenges during their long migrations under hot arid conditions

Development of the interRAI Pressure Ulcer Risk Scale (PURS) for use in long-term care and home care settings

<p>Abstract</p> <p>Background</p> <p>In long-term care (LTC) homes in the province of Ontario, implementation of the Minimum Data Set (MDS) assessment and The Braden Scale for predicting pressure ulcer risk were occurring simultaneously. The purpose of this study was, using available data sources, to develop a bedside MDS-based scale to identify individuals under care at various levels of risk for developing pressure ulcers in order to facilitate targeting risk factors for prevention.</p> <p>Methods</p> <p>Data for developing the interRAI Pressure Ulcer Risk Scale (interRAI PURS) were available from 2 Ontario sources: three LTC homes with 257 residents assessed during the same time frame with the MDS and Braden Scale for Predicting Pressure Sore Risk, and eighty-nine Ontario LTC homes with 12,896 residents with baseline/reassessment MDS data (median time 91 days), between 2005-2007. All assessments were done by trained clinical staff, and baseline assessments were restricted to those with no recorded pressure ulcer. MDS baseline/reassessment samples used in further testing included 13,062 patients of Ontario Complex Continuing Care Hospitals (CCC) and 73,183 Ontario long-stay home care (HC) clients.</p> <p>Results</p> <p>A data-informed Braden Scale cross-walk scale using MDS items was devised from the 3-facility dataset, and tested in the larger longitudinal LTC homes data for its association with a future new pressure ulcer, giving a c-statistic of 0.676. Informed by this, LTC homes data along with evidence from the clinical literature was used to create an alternate-form 7-item additive scale, the interRAI PURS, with good distributional characteristics and c-statistic of 0.708. Testing of the scale in CCC and HC longitudinal data showed strong association with development of a new pressure ulcer.</p> <p>Conclusions</p> <p>interRAI PURS differentiates risk of developing pressure ulcers among facility-based residents and home care recipients. As an output from an MDS assessment, it eliminates duplicated effort required for separate pressure ulcer risk scoring. Moreover, it can be done manually at the bedside during critical early days in an admission when the full MDS has yet to be completed. It can be calculated with established MDS instruments as well as with the newer interRAI suite instruments designed to follow persons across various care settings (interRAI Long-Term Care Facilities, interRAI Home Care, interRAI Palliative Care).</p

The resident assessment instrument-mental health (RAI-MH): Inter-rater reliability and convergent validity

An important challenge facing behavioral health services is the lack of good quality, clinically relevant data at the individual level. The article describes a multinational research effort to develop a comprehensive, multidisciplinary mental health assessment system for use with adults in facilities providing acute, long-stay, forensic, and geriatric services. The Resident Assessment Instrument-Mental Health (RAI-MH) comprehensively assesses psychiatric, social, environmental, and medical issues at intake, emphasizing patient functioning. Data from the RAI-MH are intended to support care planning, quality improvement, outcome measurement, and case mix-based payment systems. The article provides the first set of evidence on the reliability and validity of the RAI-MH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45775/1/11414_2005_Article_BF02287348.pd

Muscle directly meets the vast power demands in agile lizards

Level locomotion in small, agile lizards is characterized by intermittent bursts of fast running. These require very large accelerations, often reaching several times g. The power input required to increase kinetic energy is calculated to be as high as 214 W kg(−1) muscle (±20 W kg(−1) s.e.; averaged over the complete locomotor cycle) and 952 W kg(−1) muscle (±89 W kg(−1) s.e.; instantaneous peak power). In vitro muscle experiments prove that these exceptional power requirements can be met directly by the lizard's muscle fibres alone; there is no need for mechanical power amplifying mechanisms

Feasibility and Acceptability of Alternate Methods of Postnatal Data Collection

This study was done in preparation for the launch of the National Children\u27s Study (NCS) main study. The goal of this study was to examine the feasibility (completion rates and completeness of data), acceptability, staff time and cost-effectiveness of three methods of data collection for the postnatal 3- and 9-month questionnaires completed as part of NCS protocol. Eligible NCS participants who were scheduled to complete a postnatal questionnaire at three and nine months were randomly assigned to receive either: (a) telephone data collection (b) web-based data collection, or (c) self-administered (mailed) questionnaires. Event completion rates and satisfaction across the three data collection methods were compared and the influence of socio-demographic factors on completion rates and satisfaction rates was examined. Cost data were compared to data for completion and satisfaction for each of the delivery methods. Completion rates and satisfaction did not differ significantly by method, but completeness of data did, with odds of data completeness higher among web than phone (p \u3c 0.001) or mail (p \u3c 0.001). Costs were highest for the phone, followed by mail and web methods (p \u3c 0.001). No significant differences in participant time (i.e. burden) across the three data collection methods were seen. Mail and phone data collection were the least complete of the three methods and were the most expensive. Mailed data collection was neither complete nor exceptionally economical. Web-based data collection was the least costly and provided the most complete data. Participants without web access could complete the questionnaire over the phone