Designing a national clinical audit of nutritional care in health and social care settings: consideration and future directions.

The aim of this review paper is to consider how the principles of clinical audit could be applied to the development of an audit of nutritional care in hospitals and care homes, based on criteria derived from the Essence of Care: Food and Drink. A literature review identified fifteen key papers that included guidance or standards for nutritional care in hospitals or care homes. These were used to supplement the ten factors suggested by the Essence of Care to develop a set of potential audit criteria covering all aspects of the nutritional care pathway including the identification of risk of malnutrition, implementation of nutritional care plans, referral to healthcare professionals for further nutritional assessment and nutritional support strategies. A series of audit tools have been developed, including an organisational level audit tool, a staff questionnaire, a patients' and residents' records audit tool and a patients' and residents' experiences questionnaire. Further issues to consider in designing a national nutritional audit include the potential role of direct observation of care, the use of trained auditors and the scope for including the results of pre-existing local audits. In conclusion, a national audit would need to encompass a very large number of health and care organisations of widely varying sizes and types and a diverse range of people.

Is the cross-bridge stiffness proportional to tension during muscle fiber activation?

The cross-bridge stiffness can be used to estimate the number of S1 that are bound to actin during contraction, which is a critical parameter for elucidating the fundamental mechanism of the myosin motor. At present, the development of active tension and the increase in muscle stiffness due to S1 binding to actin are thought to be linearly related to the number of cross-bridges formed upon activation. The nonlinearity of total stiffness with respect to active force is thought to arise from the contribution of actin and myosin filament stiffness to total sarcomere elasticity. In this work, we reexamined the relation of total stiffness to tension during activation and during exposure to N-benzyl-p-toluene sulphonamide, an inhibitor of cross-bridge formation. In addition to filament and cross-bridge elasticity, our findings are best accounted for by the inclusion of an extra elasticity in parallel with the cross-bridges, which is formed upon activation but is insensitive to the subsequent level of cross-bridge formation. By analyzing the rupture tension of the muscle (an independent measure of cross-bridge formation) at different levels of activation, we found that this additional elasticity could be explained as the stiffness of a population of no-force-generating cross-bridges. These findings call into question the assumption that active force development can be taken as directly proportional to the cross-bridge number.

Reversal of the myosin power stroke induced by fast stretching of intact skeletal muscle fibers.

Force generation and movement in skeletal muscle result from a cyclical interaction of overlapping myosin and actin filaments that permits the free energy of ATP hydrolysis to be converted into mechanical work. The rapid force recovery that occurs after a step release imposed on a muscle is thought to result from a synchronized tilting of myosin lever arms toward a position of lower free energy (the power stroke). We investigated the power stroke mechanism in intact muscle fibers of Rana esculenta using a fast stretch to detach forcibly cross-bridges. Stretches were applied either with or without a conditioning step release. Cross-bridge rupture tension was not significantly influenced by the release, whereas sarcomere elongation at the rupture point increased immediately after the release and returned to the prerelease condition within 15-20 ms, following a slower time course compared to the recovery of tension. These observations suggest that the rupture force of a bridge is unaltered by a conditioning release, but rupture must first be preceded by a power stroke reversal, which restores the prepower stroke state. The sarcomere extension at the rupture point indicates both the extent of this power stroke reversal and the time course of strained bridge replenishment.

Dilated and hypertrophic cardiomyopathy mutations in troponin and alpha-tropomyosin have opposing effects on the calcium affinity of cardiac thin filaments.

Dilated cardiomyopathy and hypertrophic cardiomyopathy (HCM) can be caused by mutations in thin filament regulatory proteins of the contractile apparatus. In vitro functional assays show that, in general, the presence of dilated cardiomyopathy mutations decreases the Ca(2+) sensitivity of contractility, whereas HCM mutations increase it. To assess whether this functional phenomenon was a direct result of altered Ca(2+) affinity or was caused by altered troponin-tropomyosin switching, we assessed Ca(2+) binding of the regulatory site of cardiac troponin C in wild-type or mutant troponin complex and thin filaments using a fluorescent probe (2-[4'-{iodoacetamido}aniline]-naphthalene-6-sulfonate) attached to Cys35 of cardiac troponin C. The Ca(2+)-binding affinity (pCa(50)=6.57+/-0.03) of reconstituted troponin complex was unaffected by all of the HCM and dilated cardiomyopathy troponin mutants tested, with the exception of the troponin I Arg145Gly HCM mutation, which caused an increase (DeltapCa(50)=+0.31+/-0.05). However, when incorporated into regulated thin filaments, all but 1 of the 10 troponin and alpha-tropomyosin mutants altered Ca(2+)-binding affinity. Both HCM mutations increased Ca(2+) affinity (DeltapCa(50)=+0.41+/-0.02 and +0.51+/-0.01), whereas the dilated cardiomyopathy mutations decreased affinity (DeltapCa(50)=-0.12+/-0.04 to -0.54+/-0.04), which correlates with our previous functional in vitro assays. The exception was the troponin T Asp270Asn mutant, which caused a significant decrease in cooperativity. Because troponin is the major Ca(2+) buffer in the cardiomyocyte sarcoplasm, we suggest that Ca(2+) affinity changes caused by cardiomyopathy mutant proteins may directly affect the Ca(2+) transient and hence Ca(2+)-sensitive disease state remodeling pathways in vivo. This represents a novel mechanism for this class of mutation.

Minute theropod eggs and embryo from the Lower Cretaceous of Thailand and the dinosaur-bird transition.

We report on very small fossil eggs from the Lower Cretaceous of Thailand, one of them containing a theropod embryo, which display a remarkable mosaic of characters. While the surficial ornamentation is typical of non-avian saurischian dinosaurs, the three-layered prismatic structure of the eggshell is currently known only in extant and fossil eggs associated with birds. These eggs, about the size of a goldfinch's, mirror at the reproductive level the retention of small body size that was paramount in the transition from non-avian theropods to birds. The egg-layer may have been a small feathered theropod similar to those recently found in China.

Changes in myosin S1 orientation and force induced by a temperature increase.

Force generation in myosin-based motile systems is thought to result from an angular displacement of the myosin subfragment 1 (S1) tail domain with respect to the actin filament axis. In muscle, raised temperature increases the force generated by S1, implying a greater change in tail domain angular displacement. We used time-resolved x-ray diffraction to investigate the structural corollary of this force increase by measuring M3 meridional reflection intensity during sinusoidal length oscillations. This technique allows definition of S1 orientation with respect to the myofilament axis. M3 intensity changes were approximately sinusoid at low temperatures but became increasingly distorted as temperature was elevated, with the formation of a double intensity peak at maximum shortening. This increased distortion could be accounted for by assuming a shift in orientation of the tail domain of actin-bound S1 toward the orientation at which M3 intensity is maximal, which is consistent with a tail domain rotation model of force generation in which the tail approaches a more perpendicular projection from the thin filament axis at higher temperatures. In power stroke simulations, the angle between S1 tail mean position during oscillations and the position at maximum intensity decreased by 4.7 degrees, corresponding to a mean tail displacement toward the perpendicular of 0.73 nm for a temperature-induced force increase of 0.28 P(0) from 4 to 22 degrees C. Our findings suggest that at least 62% of crossbridge compliance is associated with the tail domain.