Treatment of glenohumeral instability in rugby players

Rugby is a high-impact collision sport, with impact forces. Shoulder injuries are common and result in the longest time off sport for any joint injury in rugby. The most common injuries are to the glenohumeral joint with varying degrees of instability. The degree of instability can guide management. The three main types of instability presentations are: (1) frank dislocation, (2) subluxations and (3) subclinical instability with pain and clicking. Understanding the exact mechanism of injury can guide diagnosis with classical patterns of structural injuries. The standard clinical examination in a large, muscular athlete may be normal, so specific tests and techniques are needed to unearth signs of pathology. Taking these factors into consideration, along with the imaging, allows a treatment strategy. However, patient and sport factors need to be also considered, particularly the time of the season and stage of sporting career. Surgery to repair the structural damage should include all lesions found. In chronic, recurrent dislocations with major structural lesions, reconstruction procedures such as the Latarjet procedure yields better outcomes. Rehabilitation should be safe, goal-driven and athlete- specific. Return to sport is dependent on a number of factors, driven by the healing process, sport requirements and extrinsic pressures

Comparative Genomic Analyses of Copper Transporters and Cuproproteomes Reveal Evolutionary Dynamics of Copper Utilization and Its Link to Oxygen

Copper is an essential trace element in many organisms and is utilized in all domains of life. It is often used as a cofactor of redox proteins, but is also a toxic metal ion. Intracellular copper must be carefully handled to prevent the formation of reactive oxygen species which pose a threat to DNA, lipids, and proteins. In this work, we examined patterns of copper utilization in prokaryotes by analyzing the occurrence of copper transporters and copper-containing proteins. Many organisms, including those that lack copper-dependent proteins, had copper exporters, likely to protect against copper ions that inadvertently enter the cell. We found that copper use is widespread among prokaryotes, but also identified several phyla that lack cuproproteins. This is in contrast to the use of other trace elements, such as selenium, which shows more scattered and reduced usage, yet larger selenoproteomes. Copper transporters had different patterns of occurrence than cuproproteins, suggesting that the pathways of copper utilization and copper detoxification are independent of each other. We present evidence that organisms living in oxygen-rich environments utilize copper, whereas the majority of anaerobic organisms do not. In addition, among copper users, cuproproteomes of aerobic organisms were larger than those of anaerobic organisms. Prokaryotic cuproproteomes were small and dominated by a single protein, cytochrome c oxidase. The data are consistent with the idea that proteins evolved to utilize copper following the oxygenation of the Earth

Modeling the Afferent Dynamics of the Baroreflex Control System

In this study we develop a modeling framework for predicting baroreceptor firing rate as a function of blood pressure. We test models within this framework both quantitatively and qualitatively using data from rats. The models describe three components: arterial wall deformation, stimulation of mechanoreceptors located in the BR nerve-endings, and modulation of the action potential frequency. The three sub-systems are modeled individually following well-established biological principles. The first submodel, predicting arterial wall deformation, uses blood pressure as an input and outputs circumferential strain. The mechanoreceptor stimulation model, uses circumferential strain as an input, predicting receptor deformation as an output. Finally, the neural model takes receptor deformation as an input predicting the BR firing rate as an output. Our results show that nonlinear dependence of firing rate on pressure can be accounted for by taking into account the nonlinear elastic properties of the artery wall. This was observed when testing the models using multiple experiments with a single set of parameters. We find that to model the response to a square pressure stimulus, giving rise to post-excitatory depression, it is necessary to include an integrate-and-fire model, which allows the firing rate to cease when the stimulus falls below a given threshold. We show that our modeling framework in combination with sensitivity analysis and parameter estimation can be used to test and compare models. Finally, we demonstrate that our preferred model can exhibit all known dynamics and that it is advantageous to combine qualitative and quantitative analysis methods

Strength and hypertrophy responses to constant and decreasing rest intervals in trained men using creatine supplementation

<p>Abstract</p> <p>Background</p> <p>The purpose of the current study was to compare strength and hypertrophy responses to resistance training programs that instituted constant rest intervals (CI) and decreasing rest intervals (DI) between sets over the course of eight weeks by trained men who supplemented with creatine monohydrate (CR).</p> <p>Methods</p> <p>Twenty-two recreationally trained men were randomly assigned to a CI group (n = 11; 22.3 ± 1 years; 77.7 ± 5.4 kg; 180 ± 2.2 cm) or a DI group (n = 11; 22 ± 2.5 years; 75.8 ± 4.9 kg; 178.8 ± 3.4 cm). Subjects in both groups supplemented with CR; the only difference between groups was the rest interval instituted between sets; the CI group used 2 minutes rest intervals between sets and exercises for the entire 8-weeks of training, while the DI group started with a 2 minute rest interval the first two weeks; after which the rest interval between sets was decreased 15 seconds per week (i.e. 2 minutes decreasing to 30 seconds between sets). Pre- and post-intervention maximal strength for the free weight back squat and bench press exercises and isokinetic peak torque were assessed for the knee extensors and flexors. Additionally, muscle cross-sectional area (CSA) of the right thigh and upper arm was measured using magnetic resonance imaging.</p> <p>Results</p> <p>Both groups demonstrated significant increases in back squat and bench press maximal strength, knee extensor and flexor isokinetic peak torque, and upper arm and right thigh CSA from pre- to post-training (p ≤ 0.0001); however, there were no significant differences between groups for any of these variables. The total volume for the bench press and back squat were significantly greater for CI group versus the DI group.</p> <p>Conclusions</p> <p>We report that the combination of CR supplementation and resistance training can increase muscular strength, isokinetic peak torque, and muscle CSA, irrespective of the rest interval length between sets. Because the volume of training was greater for the CI group versus the DI group, yet strength gains were similar, the creatine supplementation appeared to bolster adaptations for the DI group, even in the presence of significantly less volume. However, further research is needed with the inclusion of a control group not receiving supplementation combined and resistance training with decreasing rest intervals to further elucidate such hypotheses.</p

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Quaternary structure of the hydroxylamine oxidoreductase from Nitrosomonas europaea

The hydroxylamine oxidoreductase from Nitrosomonas europaea was prepared to apparent electrophoretic homogeneity. Electron microscopy of negatively stained preparations of the sample revealed an overall diameter of about 8.8 nm of the enzyme particle. The native structure was determined as a tetrahedron-like assembly of identical subunits exhibiting four protein masses