Supraspinatus detachment causes musculotendinous degeneration and a reduction in bone mineral density at the enthesis in a rat model of chronic rotator cuff degeneration

BACKGROUND: To evaluate biological strategies that enhance tendon-bone healing in humans, it is imperative that suitable animal models accurately reproduce the pathological changes observed in the clinical setting following a tear. The purpose of the present study was to investigate rotator cuff degeneration in a rat, as well as assess the development of osteopenia at the enthesis following tendon detachment. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Specimens were retrieved at 4 weeks (n = 6), 6 weeks (n = 6) and 9 weeks (n = 6) postoperatively for histological analysis and peripheral quantitative computer tomography. RESULTS: Three weeks following tendon detachment, there was a significant increase in the modified Movin score, characterized by a loss of muscle mass, fatty infiltration, an increase in musculotendinous cellularity, loss of normal collagen fibre structure/arrangement, rounded tenocyte nuclei and an increase in the number of vascular bundles. This was accompanied by a reduction in bone mineral density at the tendon insertion site. After 3 weeks however, these changes were less prominent. CONCLUSIONS: The rotator cuff tendon-muscle-bone unit in a rat model 3 weeks after detachment of supraspinatus represents a valid model for investigating rotator cuff degeneration

Modifying the Sum Over Topological Sectors and Constraints on Supergravity

The standard lore about the sum over topological sectors in quantum field theory is that locality and cluster decomposition uniquely determine the sum over such sectors, thus leading to the usual theta-vacua. We show that without changing the local degrees of freedom, a theory can be modified such that the sum over instantons should be restricted; e.g. one should include only instanton numbers which are divisible by some integer p. This conclusion about the configuration space of quantum field theory allows us to carefully reconsider the quantization of parameters in supergravity. In particular, we show that FI-terms and nontrivial Kahler forms are quantized. This analysis also leads to a new derivation of recent results about linearized supergravity.Comment: 17 pages, minor change

Impact of obesity on global and regional systolic function in children: a CMR study

International audiencen.

An agency relationship under general conditions of uncertainty: A game theory application to the doctor-patient interaction

The supply of information, particularly of bad news, in an agency relationship is a sensitive issue. We employ a game theory approach to investigate conflicts in the particular case of the doctor–patient relationship when information affects the emotions of patients. The doctor does not know the type of agent and the patient does not know how much information he is given. Hence, the paper obtains results when there is conflict, rather than common interest in the objectives of the two parties. The perfect Bayesian equilibrium describes beliefs and strategies which guarantee adherence to the doctor’s recommendation. We show also that the patient may non-adhere to the recommendation not only when the doctor fails to identify the patient’s needs but also if he falsely believes that the doctor has not done so

Checkpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements

Replication fork inactivation can be overcome by homologous recombination, but this can cause gross chromosomal rearrangements that subsequently missegregate at mitosis, driving further chromosome instability. It is unclear when the chromosome rearrangements are generated and whether individual replication problems or the resulting recombination intermediates delay the cell cycle. Here we have investigated checkpoint activation during HR-dependent replication restart using a site-specific replication fork-arrest system. Analysis during a single cell cycle shows that HR-dependent replication intermediates arise in S phase, shortly after replication arrest, and are resolved into acentric and dicentric chromosomes in G2. Despite this, cells progress into mitosis without delay. Neither the DNA damage nor the intra-S phase checkpoints are activated in the first cell cycle, demonstrating that these checkpoints are blind to replication and recombination intermediates as well as to rearranged chromosomes. The dicentrics form anaphase bridges that subsequently break, inducing checkpoint activation in the second cell cycle

Cartan-Weyl 3-algebras and the BLG Theory I: Classification of Cartan-Weyl 3-algebras

As Lie algebras of compact connected Lie groups, semisimple Lie algebras have wide applications in the description of continuous symmetries of physical systems. Mathematically, semisimple Lie algebra admits a Cartan-Weyl basis of generators which consists of a Cartan subalgebra of mutually commuting generators H_I and a number of step generators E^\alpha that are characterized by a root space of non-degenerate one-forms \alpha. This simple decomposition in terms of the root space allows for a complete classification of semisimple Lie algebras. In this paper, we introduce the analogous concept of a Cartan-Weyl Lie 3-algebra. We analyze their structure and obtain a complete classification of them. Many known examples of metric Lie 3-algebras (e.g. the Lorentzian 3-algebras) are special cases of the Cartan-Weyl 3-algebras. Due to their elegant and simple structure, we speculate that Cartan-Weyl 3-algebras may be useful for describing some kinds of generalized symmetries. As an application, we consider their use in the Bagger-Lambert-Gustavsson (BLG) theory.Comment: LaTeX. 34 pages.v2. deleted some distracting paragraphs in the introduction to bring more out the main results of the paper. typos corrected and references adde

Application of a Demineralized Cortical Bone Matrix and Bone Marrow-Derived Mesenchymal Stem Cells in a Model of Chronic Rotator Cuff Degeneration

BACKGROUND: The success of rotator cuff repair is primarily dependent on tendon-bone healing. Failure is common because weak scar tissue replaces the native enthesis, rendering it prone to reruptures. A demineralized bone matrix (DBM) consists of a network of collagen fibers that provide a sustained release of growth factors such as bone morphogenetic proteins. Previous studies have demonstrated that it can regenerate a fibrocartilaginous enthesis. HYPOTHESIS: The use of a DBM and mesenchymal stem cells (MSCs) at the healing enthesis will result in a higher bone mineral density at the tendon insertion and will enhance the regeneration of a morphologically superior enthesis when compared with an acellular human dermal matrix. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 received augmentation of the repair with a cortical allogenic DBM (n = 6); group 2 received augmentation with a nonmeshed, ultrathick, acellular human dermal matrix (n = 6); and group 3 underwent tendon-bone repair without a scaffold (n = 6). All animals received 1 × 10(6) MSCs delivered in fibrin glue to the repair site. Specimens were retrieved at 6 weeks postoperatively for histological analysis and the evaluation of bone mineral density. RESULTS: All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous enthesis. Although there were no significant differences in the enthesis maturation and modified Movin scores, repair augmented with a dermal matrix + MSCs exhibited a disorganized enthesis, abnormal collagen fiber arrangement, and greater cellularity compared with other MSC groups. Only repairs augmented with a DBM + MSCs reached a bone mineral density not significantly lower than nonoperated controls. CONCLUSION: A DBM enhanced with MSCs can augment rotator cuff healing at 6 weeks and restore bone mineral density at the enthesis to its preinjury levels. CLINICAL RELEVANCE: Biological augmentation of rotator cuff repair with a DBM and MSCs may reduce the incidence of retears, although further studies are required to determine its effectiveness

The effectiveness of demineralized cortical bone matrix in a chronic rotator cuff tear model.

BACKGROUND: The purpose of this study was to assess the effect of demineralized bone matrix (DBM) on rotator cuff tendon-bone healing. The hypothesis was that compared with a commercially available dermal matrix scaffold, DBM would result in a higher bone mineral density and regenerate a morphologically superior enthesis in a rat model of chronic rotator cuff degeneration. METHODS: Eighteen female Wistar rats underwent unilateral detachment of the supraspinatus tendon. Three weeks later, tendon repair was carried out in animals randomized into 3 groups: group 1 animals were repaired with DBM (n = 6); group 2 received augmentation with the dermal scaffold (n = 6); and group 3 (controls) underwent nonaugmented tendon-bone repair (n = 6). Specimens were retrieved at 6 weeks postoperatively for histologic analysis and evaluation of bone mineral density. RESULTS: No failures of tendon-bone healing were noted throughout the study. All groups demonstrated closure of the tendon-bone gap with a fibrocartilaginous interface. Dermal collagen specimens exhibited a disorganized structure with significantly more abnormal collagen fiber arrangement and cellularity than in the DBM-based repairs. Nonaugmented repairs exhibited a significantly higher bone mineral density than in DBM and the dermal collagen specimens and were not significantly different from control limbs that were not operated on. CONCLUSION: The application of DBM to a rat model of chronic rotator cuff degeneration did not improve the composition of the healing enthesis compared with nonaugmented controls and a commercially available scaffold. However, perhaps the most important finding of this study was that the control group demonstrated a similar outcome to augmented repairs

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed