A biomechanical assessment of superior shoulder translation after reconstruction of anterior glenoid bone defects: The Latarjet procedure versus allograft reconstruction

BACKGROUND: The coracoacromial ligament (CAL) is an important restraint to superior shoulder translation. The effect of CAL release on superior stability following the Latarjet is unknown; therefore, our purpose was to compare the effect of two Latarjet techniques and allograft reconstruction on superior instability. MATERIALS AND METHODS: Eight cadaveric specimens were tested on a simulator. Superior translation was monitored following an axial force in various glenohumeral rotations (neutral, internal, and external) with and without muscle loading. Three intact CAL states were tested (intact specimen, 30% glenoid bone defect, and allograft reconstruction) and two CAL deficient states (classic Latarjet (classicLAT) and congruent-arc Latarjet (congruentLAT)). RESULTS: In neutral without muscle loading, a significant increase in superior translation occurred with the classicLAT as compared to 30% defect (P = 0.046) and allograft conditions (P = 0.041). With muscle loading, the classicLAT (P = 0.005, 0.002) and the congruentLAT (P = 0.018, 0.021) had significantly greater superior translation compared to intact and allograft, respectively. In internal rotation, only loaded tests produced significant results; specifically, classicLAT increased translation compared to all intact CAL states (P < 0.05). In external rotation, only unloaded tests produced significant results with classicLAT and congruentLAT allowing greater translations than intact (P ≤ 0.028). For all simulations, the allograft was not significantly different than intact (P > 0.05) and no differences (P = 1.0) were found between classicLAT and congruentLAT. DISCUSSION: In most simulations, CAL release with the Latarjet lead to increased superior humeral translation. CONCLUSION: The choice of technique for glenoid bone loss reconstruction has implications on the magnitude of superior humeral translation. This previously unknown effect requires further study to determine its clinical and kinematic outcomes

Breed-Specific Hematological Phenotypes in the Dog: A Natural Resource for the Genetic Dissection of Hematological Parameters in a Mammalian Species

Remarkably little has been published on hematological phenotypes of the domestic dog, the most polymorphic species on the planet. Information on the signalment and complete blood cell count of all dogs with normal red and white blood cell parameters judged by existing reference intervals was extracted from a veterinary database. Normal hematological profiles were available for 6046 dogs, 5447 of which also had machine platelet concentrations within the reference interval. Seventy-five pure breeds plus a mixed breed control group were represented by 10 or more dogs. All measured parameters except mean corpuscular hemoglobin concentration (MCHC) varied with age. Concentrations of white blood cells (WBCs), neutrophils, monocytes, lymphocytes, eosinophils and platelets, but not red blood cell parameters, all varied with sex. Neutering status had an impact on hemoglobin concentration, mean corpuscular hemoglobin (MCH), MCHC, and concentrations of WBCs, neutrophils, monocytes, lymphocytes and platelets. Principal component analysis of hematological data revealed 37 pure breeds with distinctive phenotypes. Furthermore, all hematological parameters except MCHC showed significant differences between specific individual breeds and the mixed breed group. Twenty-nine breeds had distinctive phenotypes when assessed in this way, of which 19 had already been identified by principal component analysis. Tentative breed-specific reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis. This study represents the first large-scale analysis of hematological phenotypes in the dog and underlines the important potential of this species in the elucidation of genetic determinants of hematological traits, triangulating phenotype, breed and genetic predisposition

Colon Capsule Endoscopy compared to Conventional Colonoscopy under routine screening conditions

Colonoscopy (CSPY) for colorectal cancer screening has several limitations. Colon Capsule Endoscopy (PillCam Colon, CCE) was compared to CSPY under routine screening conditions

Local-Scale Patterns of Genetic Variability, Outcrossing, and Spatial Structure in Natural Stands of Arabidopsis thaliana

As Arabidopsis thaliana is increasingly employed in evolutionary and ecological studies, it is essential to understand patterns of natural genetic variation and the forces that shape them. Previous work focusing mostly on global and regional scales has demonstrated the importance of historical events such as long-distance migration and colonization. Far less is known about the role of contemporary factors or environmental heterogeneity in generating diversity patterns at local scales. We sampled 1,005 individuals from 77 closely spaced stands in diverse settings around Tübingen, Germany. A set of 436 SNP markers was used to characterize genome-wide patterns of relatedness and recombination. Neighboring genotypes often shared mosaic blocks of alternating marker identity and divergence. We detected recent outcrossing as well as stretches of residual heterozygosity in largely homozygous recombinants. As has been observed for several other selfing species, there was considerable heterogeneity among sites in diversity and outcrossing, with rural stands exhibiting greater diversity and heterozygosity than urban stands. Fine-scale spatial structure was evident as well. Within stands, spatial structure correlated negatively with observed heterozygosity, suggesting that the high homozygosity of natural A. thaliana may be partially attributable to nearest-neighbor mating of related individuals. The large number of markers and extensive local sampling employed here afforded unusual power to characterize local genetic patterns. Contemporary processes such as ongoing outcrossing play an important role in determining distribution of genetic diversity at this scale. Local “outcrossing hotspots” appear to reshuffle genetic information at surprising rates, while other stands contribute comparatively little. Our findings have important implications for sampling and interpreting diversity among A. thaliana accessions

The impact of training and working conditions on junior doctors' intention to leave clinical practice

Background: The shortage of physicians is an evolving problem throughout the world. In this study we aimed to identify to what extent junior doctors' training and working conditions determine their intention to leave clinical practice after residency training. Methods: A prospective cohort study was conducted in 557 junior doctors undergoing residency training in German hospitals. Self-reported specialty training conditions, working conditions and intention to leave clinical practice were measured over three time points. Scales covering training conditions were assessed by structured residency training, professional support, and dealing with lack of knowledge; working conditions were evaluated by work overload, job autonomy and social support, based on the Demand-Control-Support model. Multivariate ordinal logistic regression analyses with random intercept for longitudinal data were applied to determine the odds ratio of having a higher level of intention to leave clinical practice. Results: In the models that considered training and working conditions separately to predict intention to leave clinical practice we found significant baseline effects and change effects. After modelling training and working conditions simultaneously, we found evidence that the change effect of job autonomy (OR 0.77, p = .005) was associated with intention to leave clinical practice, whereas for the training conditions, only the baseline effects of structured residency training (OR 0.74, p = .017) and dealing with lack of knowledge (OR 0.74, p = .026) predicted intention to leave clinical practice. Conclusions: Junior doctors undergoing specialty training experience high workload in hospital practice and intense requirements in terms of specialty training. Our study indicates that simultaneously improving working conditions over time and establishing a high standard of specialty training conditions may prevent junior doctors from considering leaving clinical practice after residency training

In Vitro Identification of Novel Plasminogen-Binding Receptors of the Pathogen Leptospira interrogans

Background: Leptospirosis is a multisystem disease caused by pathogenic strains of the genus Leptospira. We have reported that Leptospira are able to bind plasminogen (PLG), to generate active plasmin in the presence of activator, and to degrade purified extracellular matrix fibronectin. Methodology/Principal Findings: We have now cloned, expressed and purified 14 leptospiral recombinant proteins. The proteins were confirmed to be surface exposed by immunofluorescence microscopy and were evaluated for their ability to bind plasminogen (PLG). We identified eight as PLG-binding proteins, including the major outer membrane protein LipL32, the previously published rLIC12730, rLIC10494, Lp29, Lp49, LipL40 and MPL36, and one novel leptospiral protein, rLIC12238. Bound PLG could be converted to plasmin by the addition of urokinase-type PLG activator (uPA), showing specific proteolytic activity, as assessed by its reaction with the chromogenic plasmin substrate, D-Val-Leu-Lys 4-nitroanilide dihydrochloride. The addition of the lysine analog 6-aminocaproic acid (ACA) inhibited the protein-PLG interaction, thus strongly suggesting the involvement of lysine residues in plasminogen binding. The binding of leptospiral surface proteins to PLG was specific, dose-dependent and saturable. PLG and collagen type IV competed with LipL32 protein for the same binding site, whereas separate binding sites were observed for plasma fibronectin. Conclusions/Significance: PLG-binding/activation through the proteins/receptors on the surface of Leptospira could help the bacteria to specifically overcome tissue barriers, facilitating its spread throughout the host.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo)CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)Fundacao Butantan, BrazilFAPESP (Brazil

Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years

<p>Abstract</p> <p>Background</p> <p>Early onset lung cancer shows some familial aggregation, pointing to a genetic predisposition. This study was set up to investigate the role of candidate genes in the susceptibility to lung cancer patients younger than 51 years at diagnosis.</p> <p>Methods</p> <p>246 patients with a primary, histologically or cytologically confirmed neoplasm, recruited from 2000 to 2003 in major lung clinics across Germany, were matched to 223 unrelated healthy controls. 11 single nucleotide polymorphisms of genes with reported associations to lung cancer have been genotyped.</p> <p>Results</p> <p>Genetic associations or gene-smoking interactions was found for <it>GPX1(Pro200Leu) </it>and <it>EPHX1(His113Tyr)</it>. Carriers of the Leu-allele of <it>GPX1(Pro200Leu) </it>showed a significant risk reduction of OR = 0.6 (95% CI: 0.4–0.8, p = 0.002) in general and of OR = 0.3 (95% CI:0.1–0.8, p = 0.012) within heavy smokers. We could also find a risk decreasing genetic effect for His-carriers of <it>EPHX1(His113Tyr) </it>for moderate smokers (OR = 0.2, 95% CI:0.1–0.7, p = 0.012). Considered both variants together, a monotone decrease of the OR was found for smokers (OR of 0.20; 95% CI: 0.07–0.60) for each protective allele.</p> <p>Conclusion</p> <p>Smoking is the most important risk factor for young lung cancer patients. However, this study provides some support for the T-Allel of <it>GPX1(Pro200Leu) </it>and the C-Allele of <it>EPHX1(His113Tyr) </it>to play a protective role in early onset lung cancer susceptibility.</p

Microglial activation and chronic neurodegeneration

Microglia, the resident innate immune cells in the brain, have long been implicated in the pathology of neurode-generative diseases. Accumulating evidence points to activated microglia as a chronic source of multiple neurotoxic factors, including tumor necrosis factor-α, nitric oxide, interleukin-1β, and reactive oxygen species (ROS), driving progressive neuron damage. Microglia can become chronically activated by either a single stimulus (e.g., lipopolysaccharide or neuron damage) or multiple stimuli exposures to result in cumulative neuronal loss with time. Although the mechanisms driving these phenomena are just beginning to be understood, reactive microgliosis (the microglial response to neuron damage) and ROS have been implicated as key mechanisms of chronic and neurotoxic microglial activation, particularly in the case of Parkinson’s disease. We review the mechanisms of neurotoxicity associated with chronic microglial activation and discuss the role of neuronal death and microglial ROS driving the chronic and toxic microglial phenotype