756 research outputs found

    Implantation of a Novel Cryopreserved Viable Osteochondral Allograft for Articular Cartilage Repair in the Knee

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    Restoration and repair of articular cartilage injuries remain a challenge for orthopaedic surgeons. The standard first-line treatment of articular cartilage lesions is marrow stimulation; however, this procedure can often result in the generation of fibrous repair cartilage rather than the biomechanically superior hyaline cartilage. Marrow stimulation is also often limited to smaller lesions, less than 2 cm2. Larger lesions may require implantation of a fresh osteochondal allograft, though a short shelf life, size-matched donor requirements, potential challenges of bone healing, limited availability, and the relatively high price limit the wide use of this therapeutic approach. We present a straightforward, single-stage surgical technique of a novel reparative and restorative approach for articular cartilage repair with the implantation of a cryopreserved viable osteochondral allograft (CVOCA). The CVOCA contains full-thickness articular cartilage and a thin layer of subchondral bone, and maintains the intact native cartilage architecture with viable chondrocytes, growth factors, and extracellular matrix proteins to promote articular cartilage repair. We report the results of a retrospective case series of three patients who presented with articular cartilage lesions more than 2 cm2 and were treated with the CVOCA using the presented surgical technique. Patients were followed up to 2 years after implantation of the CVOCA and all three patients had satisfactory outcomes without adverse events. Controlled randomized studies are suggested for evaluation of CVOCA efficacy, safety, and long-term outcomes

    Long-term variability in vegetation productivity in relation to rainfall, herbivory and fire in Tswalu Kalahari Reserve

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    Exploring the long-term influence of climate and land use on vegetation change allows for a more robust understanding of how vegetation is likely to respond in the future. To inform management, this study investigated the relationship between vegetation productivity trends and potential drivers of change in the 110 000 ha of the Tswalu Kalahari Reserve between 2000 and 2015, using the Moderate Resolution Imaging Spectroradiometer Enhanced Vegetation Index (EVI, MOD13Q1). Spatio-temporal variability of the EVI was mapped and then related to the historical records of precipitation, animal numbers and fire occurrences. Long-term trends in productivity were analysed by residual trend analysis (RESTREND). Significantly different EVI profiles were found between vegetation types, and this was related to the structure and function of the vegetation, as well as the effects of soil reflectance. The EVI time-series signalled spatial and temporal heterogeneity in plant productivity, which was strongly correlated with rainfall, although fire and especially herbivory had noteworthy localised effects on productivity. The RESTREND identified a significant positive trend in plant productivity in shrub-dominated vegetation types, providing evidence for the ongoing thickening of woody species. Significant negative trends in productivity were associated with artificial water points and more heavily stocked areas, leading to degradation. Conservation implications: The southern Kalahari has a highly variable rainfall regime, which is tied to a dynamic vegetation response. This variability should be taken into account when making management decisions. Field-based monitoring together with adaptive management approaches are needed in the face of an uncertain future in which significant warming is expected

    Characterization of Dysferlin Deficient SJL/J Mice to Assess Preclinical Drug Efficacy: Fasudil Exacerbates Muscle Disease Phenotype

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    The dysferlin deficient SJL/J mouse strain is commonly used to study dysferlin deficient myopathies. Therefore, we systematically evaluated behavior in relatively young (9–25 weeks) SJL/J mice and compared them to C57BL6 mice to determine which functional end points may be the most effective to use for preclinical studies in the SJL/J strain. SJL/J mice had reduced body weight, lower open field scores, higher creatine kinase levels, and less muscle force than did C57BL6 mice. Power calculations for expected effect sizes indicated that grip strength normalized to body weight and open field activity were the most sensitive indicators of functional status in SJL/J mice. Weight and open field scores of SJL/J mice deteriorated over the course of the study, indicating that progressive myopathy was ongoing even in relatively young (<6 months old) SJL/J mice. To further characterize SJL/J mice within the context of treatment, we assessed the effect of fasudil, a rho-kinase inhibitor, on disease phenotype. Fasudil was evaluated based on previous observations that Rho signaling may be overly activated as part of the inflammatory cascade in SJL/J mice. Fasudil treated SJL/J mice showed increased body weight, but decreased grip strength, horizontal activity, and soleus muscle force, compared to untreated SJL/J controls. Fasudil either improved or had no effect on these outcomes in C57BL6 mice. Fasudil also reduced the number of infiltrating macrophages/monocytes in SJL/J muscle tissue, but had no effect on muscle fiber degeneration/regeneration. These studies provide a basis for standardization of preclinical drug testing trials in the dysferlin deficient SJL/J mice, and identify measures of functional status that are potentially translatable to clinical trial outcomes. In addition, the data provide pharmacological evidence suggesting that activation of rho-kinase, at least in part, may represent a beneficial compensatory response in dysferlin deficient myopathies

    The proton pump inhibitor lansoprazole improves the skeletal phenotype in dystrophin deficient mdx mice

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    Background In Duchenne muscular dystrophy (DMD), loss of the membrane stabilizing protein dystrophin results in myofiber damage. Microinjury to dystrophic myofibers also causes secondary imbalances in sarcolemmic ion permeability and resting membrane potential, which modifies excitation-contraction coupling and increases proinflammatory/apoptotic signaling cascades. Although glucocorticoids remain the standard of care for the treatment of DMD, there is a need to investigate the efficacy of other pharmacological agents targeting the involvement of imbalances in ion flux on dystrophic pathology. Methodology/Principal Findings We designed a preclinical trial to investigate the effects of lansoprazole (LANZO) administration, a proton pump inhibitor, on the dystrophic muscle phenotype in dystrophin deficient (mdx) mice. Eight to ten week-old female mice were assigned to one of four treatment groups (n = 12 per group): (1) vehicle control; (2) 5 mg/kg/day LANZO; (3) 5 mg/kg/day prednisolone; and (4) combined treatment of 5 mg/kg/day prednisolone (PRED) and 5 mg/kg/day LANZO. Treatment was administered orally 5 d/wk for 3 months. At the end of the study, behavioral (Digiscan) and functional outcomes (grip strength and Rotarod) were assessed prior to sacrifice. After sacrifice, body, tissue and organ masses, muscle histology,in vitro muscle force, and creatine kinase levels were measured. Mice in the combined treatment groups displayed significant reductions in the number of degenerating muscle fibers and number of inflammatory foci per muscle field relative to vehicle control. Additionally, mice in the combined treatment group displayed less of a decline in normalized forelimb and hindlimb grip strength and declines in in vitro EDL force after repeated eccentric contractions. Conclusions/Significance Together our findings suggest that combined treatment of LANZO and prednisolone attenuates some components of dystrophic pathology in mdx mice. Our findings warrant future investigation of the clinical efficacy of LANZO and prednisolone combined treatment regimens in dystrophic pathology

    Blow me down:A new perspective on Aloe dichotoma mortality from windthrow

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    Background: Windthrow, the uprooting of trees during storms associated with strong winds, is a well-established cause of mortality in temperate regions of the world, often with large ecological consequences. However, this phenomenon has received little attention within arid regions and is not well documented in southern Africa. Slow rates of post-disturbance recovery and projected increases in extreme weather events in arid areas mean that windthrow could be more common and have bigger impacts on these ecosystems in the future. This is of concern due to slow rates of post-disturbance recovery in arid systems and projected increases in extreme weather events in these areas. This study investigated the spatial pattern, magnitude and likely causes of windthrown mortality in relation to other forms of mortality in Aloe dichotoma, an iconic arid-adapted arborescent succulent and southern Africa climate change indicator species. Results: We found that windthrown mortality was greatest within the equatorward summer rainfall zone (SRZ) of its distribution (mean = 31%, n = 11), and was derived almost exclusively from the larger adult age class. A logistic modelling exercise indicated that windthrown mortality was strongly associated with greater amounts of warm season (summer) rainfall in the SRZ, higher wind speeds, and leptosols. A statistically significant interaction term between higher summer rainfall and wind speeds further increased the odds of being windthrown. While these results would benefit from improvements in the resolution of wind and substrate data, they do support the hypothesised mechanism for windthrow in A. dichotoma. This involves powerful storm gusts associated with either the current or subsequent rainfall event, heavy convective rainfall, and an associated increase in soil malleability. Shallow rooting depths in gravel-rich soils and an inflexible, top-heavy canopy structure make individuals especially prone to windthrown mortality during storms. Conclusions: Results highlight the importance of this previously unrecognised form of mortality in A. dichotoma, especially since it seems to disproportionately affect reproductively mature adult individuals in an infrequently recruiting species. Smaller, more geographically isolated and adult dominated populations in the summer rainfall zone are likely to be more vulnerable to localised extinction due to windthrow events

    Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog with Measured Completeness and Reliability Based on Data Release 25

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    We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching 4 yr of Kepler time series photometry (Data Release 25, Q1–Q17). The catalog contains 8054 KOIs, of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new, including two in multiplanet systems (KOI-82.06 and KOI-2926.05) and 10 high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter, which automatically vets the DR25 threshold crossing events (TCEs). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discuss the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK-dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits, and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive
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