Pre-clinical evaluation of advanced nerve guide conduits using a novel 3D in vitro testing model

Autografts are the current gold standard for large peripheral nerve defects in clinics despite the frequentlyoccurring side effects like donor site morbidity. Hollow nerve guidance conduits (NGC) are proposed alternatives toautografts, but failed to bridge gaps exceeding 3 cm in humans. Internal NGC guidance cues like microfibresare believed to enhance hollow NGCs by giving additional physical support for directed regeneration of Schwann cellsand axons. In this study, we report a new 3D in vitro model that allows the evaluation of different intraluminal fibrescaffolds inside a complete NGC. The performance of electrospun polycaprolactone (PCL) microfibres inside 5 mmlong polyethylene glycol (PEG) conduits were investigated in neuronal cell and dorsal root ganglion (DRG) cultures invitro. Z-stack confocal microscopy revealed the aligned orientation of neuronal cells along the fibres throughout thewhole NGC length and depth. The number of living cells in the centre of the scaffold was not significantly different tothe tissue culture plastic (TCP) control. For ex vivo analysis, DRGs were placed on top of fibre-filled NGCs to simulatethe proximal nerve stump. In 21 days of culture, Schwann cells and axons infiltrated the conduits along the microfibreswith 2.2 ± 0.37 mm and 2.1 ± 0.33 mm, respectively. We conclude that this in vitro model can help define internal NGCscaffolds in the future by comparing different fibre materials, composites and dimensions in one setup prior to animaltesting

UV-Casting on methacrylated PCL for the production of a peripheral nerve implant containing an array of porous aligned microchannels

Peripheral nerves are basic communication structures guiding motor and sensory information from the central nervous system to receptor units. Severed peripheral nerve injuries represent a large clinical problem with relevant challenges to successful synthetic nerve repair scaffolds as substitutes to autologous nerve grafting. Numerous studies reported the use of hollow tubes made of synthetic polymers sutured between severed nerve stumps to promote nerve regeneration while providing protection for external factors, such as scar tissue formation and inflammation. Few approaches have described the potential use of a lumen structure comprised of microchannels or microfibers to provide axon growth avoiding misdirection and fostering proper healing. Here, we report the use of a 3D porous microchannel-based structure made of a photocurable methacrylated polycaprolactone, whose mechanical properties are comparable to native nerves. The neuro-regenerative properties of the polymer were assessed in vitro, prior to the implantation of the 3D porous structure, in a 6-mm rat sciatic nerve gap injury. The manufactured implants were biocompatible and able to be resorbed by the host’s body at a suitable rate, allowing the complete healing of the nerve. The innovative design of the highly porous structure with the axon guiding microchannels, along with the observation of myelinated axons and Schwann cells in the in vivo tests, led to a significant progress towards the standardized use of synthetic 3D multichannel-based structures in peripheral nerve surgery

Aligned polyhydroxyalkanoate blend electrospun fibers as intraluminal guidance scaffolds for peripheral nerve repair

The use of nerve guidance conduits (NGCs) to treat peripheral nerve injuries is a favorable approach to the current “gold standard” of autografting. However, as simple hollow tubes, they lack specific topographical and mechanical guidance cues present in nerve grafts and therefore are not suitable for treating large gap injuries (30–50 mm). The incorporation of intraluminal guidance scaffolds, such as aligned fibers, has been shown to increase neuronal cell neurite outgrowth and Schwann cell migration distances. A novel blend of PHAs, P(3HO)/P(3HB) (50:50), was investigated for its potential as an intraluminal aligned fiber guidance scaffold. Aligned fibers of 5 and 8 μm diameter were manufactured by electrospinning and characterized using SEM. Fibers were investigated for their effect on neuronal cell differentiation, Schwann cell phenotype, and cell viability in vitro. Overall, P(3HO)/P(3HB) (50:50) fibers supported higher neuronal and Schwann cell adhesion compared to PCL fibers. The 5 μm PHA blend fibers also supported significantly higher DRG neurite outgrowth and Schwann cell migration distance using a 3D ex vivo nerve injury model

Continuum-mechanical, Anisotropic Flow model for polar ice masses, based on an anisotropic Flow Enhancement factor

A complete theoretical presentation of the Continuum-mechanical, Anisotropic Flow model, based on an anisotropic Flow Enhancement factor (CAFFE model) is given. The CAFFE model is an application of the theory of mixtures with continuous diversity for the case of large polar ice masses in which induced anisotropy occurs. The anisotropic response of the polycrystalline ice is described by a generalization of Glen's flow law, based on a scalar anisotropic enhancement factor. The enhancement factor depends on the orientation mass density, which is closely related to the orientation distribution function and describes the distribution of grain orientations (fabric). Fabric evolution is governed by the orientation mass balance, which depends on four distinct effects, interpreted as local rigid body rotation, grain rotation, rotation recrystallization (polygonization) and grain boundary migration (migration recrystallization), respectively. It is proven that the flow law of the CAFFE model is truly anisotropic despite the collinearity between the stress deviator and stretching tensors.Comment: 22 pages, 5 figure

Genetic diversity of the myrtle rust pathogen (Austropuccinia psidii) in the Americas and Hawaii : global implications for invasive threat assessments

Since the myrtle rust pathogen (Austropuccinia psidii) was first reported (as Puccinia psidii) in Brazil on guava (Psidium guajava) in 1884, it has been found infecting diverse myrtaceous species. Because A. psidii has recently spread rapidly worldwide with an extensive host range, genetic and genotypic diversities were evaluated within and among A. psidii populations in its putative native range and other areas of myrtle rust emergence in the Americas and Hawaii. Microsatellite markers revealed several unique multilocus genotypes (MLGs), which grouped isolates into nine distinct genetic clusters [C1–C9 comprising C1: from diverse hosts from Costa Rica, Jamaica, Mexico, Puerto Rico, and USA‐Hawaii, and USA‐California; C2: from eucalypts (Eucalyptus spp.) in Brazil/Uruguay and rose apple (Syzygium jambos) in Brazil; C3: from eucalypts in Brazil; C4: from diverse hosts in USA‐Florida; C5: from Java plum (Syzygium cumini) in Brazil; C6: from guava and Brazilian guava (Psidium guineense) in Brazil; C7: from pitanga (Eugenia uniflora) in Brazil; C8: from allspice (Pimenta dioica) in Jamaica and sweet flower (Myrrhinium atropurpureum) in Uruguay; C9: from jabuticaba (Myrciaria cauliflora) in Brazil]. The C1 cluster, which included a single MLG infecting diverse host in many geographic regions, and the closely related C4 cluster are considered as a “Pandemic biotype,” associated with myrtle rust emergence in Central America, the Caribbean, USA‐Florida, USA‐Hawaii, Australia, China‐Hainan, New Caledonia, Indonesia and Colombia. Based on 19 bioclimatic variables and documented occurrences of A. psidii contrasted with reduced sets of specific genetic clusters (subnetworks, considered as biotypes), maximum entropy bioclimatic modelling was used to predict geographic locations with suitable climate for A. psidii which are at risk from invasion. The genetic diversity of A. psidii throughout the Americas and Hawaii demonstrates the importance of recognizing biotypes when assessing the invasive threats posed by A. psidii around the globe.USDA-Forest Service, RMRS-Forest and Woodlands Ecosystem Program, Western Wildlands Environmental Threat Assessment Center, Special Technology Development Program, State and Private Forestry, Forest Health Protection-Region 5; Conselho Nactional de Desenvolvimento Científico e Tecnológico, Brasil (CNPq); Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG); Research Joint Venture Agreements RMRS 15-JV-11221633-160 (Jane Stewart, Colorado State University) and RMRS 14-JV-11221633-117 (Western Forest Conservation Association).http://wileyonlinelibrary.com/journal/efp2019-02-01hj2018Forestry and Agricultural Biotechnology Institute (FABI)Plant Production and Soil Scienc

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

The Deformation of Ice Single Crystals at Low Temperatures

International Conference on Low Temperature Science. I. Conference on Physics of Snow and Ice, II. Conference on Cryobiology. (August, 14-19, 1966, Sapporo, Japan