Structure of the Ca2+ pump of sarcoplasmic reticulum: a view along the lipid bilayer at 9-A resolution.

We have used multilamellar crystals of the ATP-driven calcium pump from sarcoplasmic reticulum to address the structural effects of calcium binding to the enzyme. They are stacks of disk-shaped two-dimensional crystals. A density map projected along the lipid bilayer was obtained at 9-A resolution by frozen-hydrated electron microscopy. Although only in projection, much more details of the structure were revealed than previously available, especially in the transmembrane region. Quantitative comparison was made with the model obtained from the tubular crystals of this enzyme formed in the absence of calcium. Unexpectedly large differences in conformation were found, particularly in the cytoplasmic domain.     

Acoustic myography reflects force changes during dynamic concentric and eccentric contractions of the human biceps brachii muscle.

The relationship between acoustic myography (AMG), electromyography (EMG) and force during submaximal dynamic contractions was examined in the biceps brachii muscles of eight healthy males (aged 17-26 years). Different weights were lifted and lowered at a constant speed, using a wall pulley system, to perform concentric and eccentric contractions, respectively. Integrated AMG (iAMG) and integrated EMG (iEMG) activity both increased linearly with force during concentric (iAMG r = 0.94; iEMG r = 0.99) and eccentric (iAMG r = 0.90; iEMG r = 0.94) contractions. The slopes of the concentric regression lines were significantly different from the eccentric slopes (P less than 0.01) for both iAMG and iEMG with concentric contractions showing greater levels of activity. The results indicated that AMG can be used to detect changes in force during dynamic contractions which has important implications for the use of AMG in rehabilitation. The differences in iAMG activity between concentric and eccentric contractions are discussed in relationship to the origin of the AMG signal.     

The ATP-binding site of Ca(2+)-ATPase revealed by electron image analysis.

The location of the ATP-binding site of a P-type ion pump, Ca(2+)-ATPase from rabbit sarcoplasmic reticulum, was examined by cryoelectron microscopy. A nonhydrolyzable analog of ATP, beta, gamma-bidentate chromium (III) complex of ATP (CrATP), was used to stabilize the enzyme in the Ca(2+)-occluded state. Tubular crystals were then induced by vanadate in the presence of EGTA, keeping CrATP bound to the enzyme. The three-dimensional structures of the crystals were determined at 14 A resolution by cryoelectron microscopy and helical image analysis. Statistical comparison of the structures with and without CrATP showed clear and significant differences at the groove proposed previously as the ATP-binding pocket.     

Cemental annulation enhancement: a technique for age determination in man

Cemental annulations are easily countable in teeth from animals that have an exaggerated regular change of food intake from season to season. Although present in human teeth, cemental annulations are not always easy to count. A method for preparing human teeth for evaluation involving collection, identification, measuring, sectioning, cleaning, acid etching, staining, and mounting is reported. Sections 100-microns thick were stained with cresyl fast violet as a stain of choice and were photographed using standard light microscopic techniques as well as Nomarsky interference microscopy. Countability of annulations from photographic enlargements was evaluated.     

Multimorbidity combinations,costs of hospital care and potentially preventable emergency admissions in England: A cohort study

BackgroundPatients with multimorbidities have the greatest healthcare needs and generate the highest expenditure in the health system. There is an increasing focus on identifying specific disease combinations for addressing poor outcomes. Existing research has identified a small number of prevalent “clusters” in the general population, but the limited number examined might oversimplify the problem and these may not be the ones associated with important outcomes. Combinations with the highest (potentially preventable) secondary care costs may reveal priority targets for intervention or prevention. We aimed to examine the potential of defining multimorbidity clusters for impacting secondary care costs.Methods and findingsWe used national, Hospital Episode Statistics, data from all hospital admissions in England from 2017/2018 (cohort of over 8 million patients) and defined multimorbidity based on ICD-10 codes for 28 chronic conditions (we backfilled conditions from 2009/2010 to address potential undercoding). We identified the combinations of multimorbidity which contributed to the highest total current and previous 5-year costs of secondary care and costs of potentially preventable emergency hospital admissions in aggregate and per patient. We examined the distribution of costs across unique disease combinations to test the potential of the cluster approach for targeting interventions at high costs. We then estimated the overlap between the unique combinations to test potential of the cluster approach for targeting prevention of accumulated disease. We examined variability in the ranks and distributions across age (over/under 65) and deprivation (area level, deciles) subgroups and sensitivity to considering a smaller number of diseases.There were 8,440,133 unique patients in our sample, over 4 million (53.1%) were female, and over 3 million (37.7%) were aged over 65 years. No clear “high cost” combinations of multimorbidity emerged as possible targets for intervention. Over 2 million (31.6%) patients had 63,124 unique combinations of multimorbidity, each contributing a small fraction (maximum 3.2%) to current-year or 5-year secondary care costs. Highest total cost combinations tended to have fewer conditions (dyads/triads, most including hypertension) affecting a relatively large population. This contrasted with the combinations that generated the highest cost for individual patients, which were complex sets of many (6+) conditions affecting fewer persons. However, all combinations containing chronic kidney disease and hypertension, or diabetes and hypertension, made up a significant proportion of total secondary care costs, and all combinations containing chronic heart failure, chronic kidney disease, and hypertension had the highest proportion of preventable emergency admission costs, which might offer priority targets for prevention of disease accumulation. The results varied little between age and deprivation subgroups and sensitivity analyses.Key limitations include availability of data only from hospitals and reliance on hospital coding of health conditions.ConclusionsOur findings indicate that there are no clear multimorbidity combinations for a cluster-targeted intervention approach to reduce secondary care costs. The role of risk-stratification and focus on individual high-cost patients with interventions is particularly questionable for this aim. However, if aetiology is favourable for preventing further disease, the cluster approach might be useful for targeting disease prevention efforts with potential for cost-savings in secondary care.

Jonathan Stokes and co-workers explore patterns of multimorbidity and implications for the organization and costs of care.     

Measurement of anterior tibial muscle size using real-time ultrasound imaging.

Cross-sectional images of the anterior tibial muscle group were obtained using real-time ultrasound scanning in 17 normal women. From photographs taken of the images, the cross-sectional area (CSA) and two linear measurements of muscle cross-section were determined. A measurement of the shortest distance of the muscle depth was termed DS, and a measurement of the longest distance through the muscle group was termed DL. Both linear dimensions showed a positive correlation with CSA and the best correlations were obtained when the dimensions were squared or combined (DS x DL). The correlation values were: CSA vs DS2, r = 0.9; CSA vs DL2, r = 0.75 and CSA vs DS x DL, r = 0.88. An approximate value for CSA could be calculated from DS2 by the equation 2 x DS2 + 1. A shape ratio, obtained by dividing DL by DS, was consistent within the group [mean 2.1 (SD 0.2)] and characterised the muscle geometrically. The CSA of repeated scans was assessed for repeatability between-days and between-scans by analysis of variance and the coefficient of variation (CV) calculated. Areas were repeatable between-days (CV 6.5%) and between-scans (CV 3.6%). Linear dimensions of the anterior tibial muscle group reflected CSA and their potential for assessing changes in muscle size with atrophy and hypertrophy have yet to be established.