French validation of the Quality of life in Essential Tremor Questionnaire (QUEST) and the Essential Tremor Embarrassment Assessment (ETEA).

Two scales have been developed and validated in English to evaluate the impact of tremor on daily life, namely Quality of life in Essential Tremor Questionnaire (QUEST) and Essential Tremor Embarrassment Assessment (ETEA). The psychometric properties of the French version of these two scales were assessed for 117 patients with head tremor. Both scales showed excellent acceptability, very good internal consistency (Cronbach's alpha coefficient>0.8) and reproducibility (Lin concordance coefficient>0.8), satisfactory external validity and satisfactory sensitivity to change. In conclusion, the French versions of QUEST and ETEA are comprehensive, valid and reliable instruments for assessing patients with head tremor.

Inductive Materials for Regenerative Engineering.

Regenerative engineering has pioneered several novel biomaterials to treat critical-sized bone injuries. However, despite significant improvement in synthetic materials research, some limitations still exist. The constraints correlated with the current grafting methods signify a treatment paradigm shift to osteoinductive regenerative engineering approaches. Because of their intrinsic potential, inductive biomaterials may represent alternative approaches to treating critical bone injuries. Osteoinductive scaffolds stimulate stem cell differentiation into the osteoblastic lineage, enhancing bone regeneration. Inductive biomaterials comprise polymers, calcium phosphate ceramics, metals, and graphene family materials. This review will assess the cellular behavior toward properties of inductive materials.

Feasibility of changing for a rechargeable constant current neurostimulator in Parkinson's disease.

BACKGROUND: Little is known about outcome and settings adaptations after replacement of constant-voltage non-rechargeable implantable pulse generator (CV-nrIPG) by constant-current rechargeable IPG (CC-rIPG). OBJECTIVE: To determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome. METHODS: A prospective cohort of thirty PD patients, whose CV-nrIPG was replaced by a CC-rIPG in University Hospital of Lyon between January 2017 and December 2018 (rIPG group) and 39 PD patients, who underwent the replacement of a CV-nrIPG by the same device in 2016 (nrIPG group), were enrolled in this study. Three surgeons performed the operations. Duration of hospitalization for the replacement as well as the number of in or outpatient visits during the first 3 months after the surgery were recorded. In the rIPG group, we compared preoperative DBS settings and the theoretical amplitude estimated using Ohm's law to the amplitude used at the end of follow-up. We assessed patients' and clinicians' opinion on the patient global functioning after the replacement using Clinical Global Impression score. RESULTS: Duration of hospitalization (P=0.47) and need for additional hospitalizations (P=0.73) or consultations (P=0.71) to adapt DBS parameters did not differ between the two groups. Neurological condition (CGI score) was considered as unchanged by both patients and neurologists. Final amplitude of stimulation using CC-rIPG was not predicted by Ohm's law in most cases. CONCLUSIONS: Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.

Identification of Heparan-Sulfate Rich Cells in the Loose Connective Tissues of the Axolotl (Ambystoma mexicanum) with the Potential to Mediate Growth Factor Signaling during Regeneration.

Limb regeneration is the outcome of a complex sequence of events that are mediated by interactions between cells derived from the tissues of the amputated stump. Early in regeneration, these interactions are mediated by growth factor/morphogen signaling associated with nerves and the wound epithelium. One shared property of these proregenerative signaling molecules is that their activity is dependent on interactions with sulfated glycosaminoglycans (GAGs), heparan sulfate proteoglycan (HSPG) in particular, in the extracellular matrix (ECM). We hypothesized that there are cells in the axolotl that synthesize specific HSPGs that control growth factor signaling in time and space. In this study we have identified a subpopulation of cells within the ECM of axolotl skin that express high levels of sulfated GAGs on their cell surface. These cells are dispersed in a grid-like pattern throughout the dermis as well as the loose connective tissues that surround the tissues of the limb. These cells alter their morphology during regeneration, and are candidates for being a subpopulation of connective tissue cells that function as the cells required for pattern-formation during regeneration. Given their high level of HSPG expression, their stellate morphology, and their distribution throughout the loose connective tissues, we refer to these as the positional information GRID (Groups that are Regenerative, Interspersed and Dendritic) cells. In addition, we have identified cells that stain for high levels of expression of sulfated GAGs in mouse limb connective tissue that could have an equivalent function to GRID cells in the axolotl. The identification of GRID cells may have important implications for work in the area of Regenerative Engineering.

Initial treatment of Parkinson's disease in 2016: The 2000 consensus conference revisited.

In 2000, a French consensus conference proposed guidelines for the treatment of Parkinson's disease (PD). Since then, new drugs have been concocted, new studies have been published and clinicians have become aware of some drug-induced adverse effects that were little known in the past. This has led us to reconsider the recommendations published 16 years ago. Thus, the aim of the present review is to present the recent data related to the different medications and non-pharmacological approaches available for PD, with a special focus on early-stage PD. Levodopa (LD), dopamine agonists (DAs), catechol-O-methyltransferase inhibitors (COMT-Is), anticholinergics, monoamine oxidase inhibitors (MAOB-Is) and amantadine have been considered, and their efficacy and safety for both motor as well as non-motor aspects are reported here. This has led to our proposal for a revised therapeutic strategy for the initiation of treatment in newly diagnosed PD patients, based on the available literature and the relative benefits/side effects balance.

A rare case of SPG11 mutation with multiple sclerosis.

We describe a patient with SPG11 hereditary spastic paraplegia (HSP), who developed walking disorder in childhood. He presented three episodes of subacute gait disorders worsening between the age of 20 and 22 years. Brain and spinal MRI revealed multiple T2 hypersignal lesions, consistent with inflammatory lesions. Surprisingly, CSF analysis showed neither oligoclonal bands nor increased IgG index. He was dramatically improved by intravenous methylprednisolone. A relapsing-remitting multiple sclerosis (MS) was suspected. This is the first description of SPG11 HSP associated with MS.

Novel mechanically competent polysaccharide scaffolds for bone tissue engineering.

The success of the scaffold-based bone regeneration approach critically depends on the biomaterial's mechanical and biological properties. Cellulose and its derivatives are inherently associated with exceptional strength and biocompatibility due to their ß-glycosidic linkage and extensive hydrogen bonding. This polymer class has a long medical history as a dialysis membrane, wound care system and pharmaceutical excipient. Recently cellulose-based scaffolds have been developed and evaluated for a variety of tissue engineering applications. In general porous polysaccharide scaffolds in spite of many merits lack the necessary mechanical competence needed for load-bearing applications. The present study reports the fabrication and characterization of three-dimensional (3D) porous sintered microsphere scaffolds based on cellulose derivatives using a solvent/non-solvent sintering approach for load-bearing applications. These 3D scaffolds exhibited a compressive modulus and strength in the mid-range of human trabecular bone and underwent degradation resulting in a weight loss of 10-15% after 24 weeks. A typical stress-strain curve for these scaffolds showed an initial elastic region and a less-stiff post-yield region similar to that of native bone. Human osteoblasts cultured on these scaffolds showed progressive growth with time and maintained expression of osteoblast phenotype markers. Further, the elevated expression of alkaline phosphatase and mineralization at early time points as compared to heat-sintered poly(lactic acid-glycolic acid) control scaffolds with identical pore properties affirmed the advantages of polysaccharides and their potential for scaffold-based bone regeneration.

[Proposal of a costing method for the provision of sterilization in a public hospital]. / Proposition d'une méthode de facturation de la prestation de stérilisation dans un centre hospitalier public.

INTRODUCTION: To refine the billing to institutions whose operations of sterilization are outsourced, a sterilization cost approach was developed. The aim of the study is to determine the value of a sterilization unit (one point "S") evolving according to investments, quantities processed, types of instrumentation or packaging. MATERIALS AND METHODS: The time of preparation has been selected from all sub-processes of sterilization to determine the value of one point S. The time of preparation of sterilized large and small containers and pouches were raised. The reference time corresponds to one bag (equal to one point S). Simultaneously, the annual operating cost of sterilization was defined and divided into several areas of expenditure: employees, equipments and building depreciation, supplies, and maintenance. RESULTS: A total of 136 crossing times of containers were measured. Time to prepare a pouch has been estimated at one minute (one S). A small container represents four S and a large container represents 10S. By dividing the operating cost of sterilization by the total number of points of sterilization over a given period, the cost of one S can be determined. DISCUSSION/CONCLUSION: This method differs from traditional costing method in sterilizing services, considering each item of expenditure. This point S will be the base for billing of subcontracts to other institutions.

Tendon tissue engineering: adipose-derived stem cell and GDF-5 mediated regeneration using electrospun matrix systems.

Tendon tissue engineering with a biomaterial scaffold that mimics the tendon extracellular matrix (ECM) and is biomechanically suitable, and when combined with readily available autologous cells, may provide successful regeneration of defects in tendon. Current repair strategies using suitable autografts and freeze-dried allografts lead to a slow repair process that is sub-optimal and fails to restore function, particularly in difficult clinical situations such as zone II flexor tendon injuries of the hand. We have investigated the effect of GDF-5 on cell proliferation and gene expression by primary rat adipose-derived stem cells (ADSCs) that were cultured on a poly(DL-lactide-co-glycolide) PLAGA fiber scaffold and compared to a PLAGA 2D film scaffold. The electrospun scaffold mimics the collagen fiber bundles present in native tendon tissue, and supports the adhesion and proliferation of multipotent ADSCs. Gene expression of scleraxis, the neotendon marker, was upregulated seven- to eightfold at 1 week with GDF-5 treatment when cultured on a 3D electrospun scaffold, and was significantly higher at 2 weeks compared to 2D films with or without GDF-5 treatment. Expression of the genes that encode the major tendon ECM protein, collagen type I, was increased by fourfold starting at 1 week on treatment with 100 ng mL(-1) GDF-5, and at all time points the expression was significantly higher compared to 2D films irrespective of GDF-5 treatment. Thus stimulation with GDF-5 can modulate primary ADSCs on a PLAGA fiber scaffold to produce a soft, collagenous musculoskeletal tissue that fulfills the need for tendon regeneration.

Electrospun nanofiber scaffolds: engineering soft tissues.

Electrospinning has emerged to be a simple, elegant and scalable technique to fabricate polymeric nanofibers. Pure polymers as well as blends and composites of both natural and synthetics have been successfully electrospun into nanofiber matrices. Physiochemical properties of nanofiber matrices can be controlled by manipulating electrospinning parameters to meet the requirements of a specific application. Such efforts include the fabrication of fiber matrices containing nanofibers, microfibers, combination of nano-microfibers and also different fiber orientation/alignments. Polymeric nanofiber matrices have been extensively investigated for diversified uses such as filtration, barrier fabrics, wipes, personal care, biomedical and pharmaceutical applications. Recently electrospun nanofiber matrices have gained a lot of attention, and are being explored as scaffolds in tissue engineering due to their properties that can modulate cellular behavior. Electrospun nanofiber matrices show morphological similarities to the natural extra-cellular matrix (ECM), characterized by ultrafine continuous fibers, high surface-to-volume ratio, high porosity and variable pore-size distribution. Efforts have been made to modify nanofiber surfaces with several bioactive molecules to provide cells with the necessary chemical cues and a more in vivo like environment. The current paper provides an overlook on such efforts in designing nanofiber matrices as scaffolds in the regeneration of various soft tissues including skin, blood vessel, tendon/ligament, cardiac patch, nerve and skeletal muscle.

Formation and properties of composites comprised of calcium-deficient hydroxyapatites and ethyl alanate polyphosphazenes.

Composites comprised of calcium-deficient hydroxyapatite (HAp) and biodegradable polyphosphazenes were formed via cement-type reactions at physiologic temperature. The composite precursors were produced by blending particulate hydroxyapatite precursors with 10 wt% polymer using a solvent/non-solvent technique. HAp precursors having calcium-to-phosphate ratios of 1.5 (CDH) and 1.6 (CDS) were used. The polymeric constituents were poly[bis(ethyl alanato)phosphazene] (PNEA) and poly[(ethyl alanato)(1) (p-phenylphenoxy)(1) phosphazene] (PNEA(50)PhPh(50)). The effect of incorporating the phenyl phenoxy group was evaluated as a means of increasing the mechanical properties of the composites without retarding the rates of HAp formation. Reaction kinetics and mechanistic paths were characterized by pH determination, X-ray diffraction analyses, scanning electron microscopy, and infrared spectroscopy. The mechanical properties were analyzed by compression testing. These analyses indicated that the presence of the polymers slightly reduced the rate HAp formation. However, surface hydrolysis of polymer ester groups permitted the formation of calcium salt bridges that provide a mechanism for bonding with the HAp. The compressive strengths of the composites containing PNEA(50)PhPh(50) were superior to those containing PNEA, and were comparable to those of HAp produced in the absence of polymer. The current composites more closely match the structure of bone, and are thus strongly recommended to be used as bone cements where high loads are not expected.

Novel tubular composite matrix for bone repair.

Tissue engineering develops organ replacements to overcome the limitations associated with autografts and allografts. The work presented here details the development of biodegradable, porous, three-dimensional polymer-ceramic-sintered microsphere matrices to support bone regeneration. Poly(lactide-co-glycolide)/hydroxyapatite microspheres were formed using solvent evaporation technique. Individual microspheres were placed in a cylindrical mold and sintered at various temperatures. Scaffolds were characterized using scanning electron microscopy, mercury porosimetry, and mechanical testing in compression. After varying the temperature of sintering, a single temperature was selected and the time of sintering was varied. Mechanical testing indicated that as the sintering temperature or time was increased, the elastic modulus, compressive strength, maximum compressive load, and energy at failure significantly increased. Furthermore, increasing the sintering temperature or time resulted in a decreased porosity and the spherical morphology of the microspheres was lost as the microspheres blended together. To more closely mimic the bone marrow cavity observed in native bone tissue, tubular composite-sintered microsphere matrices were formed. These scaffolds demonstrated no statistically significant difference in compressive mechanical properties when compared with cylindrical composite-sintered microsphere matrices of the same dimension. One potential application for these scaffolds is bone regeneration.

Formation of hydroxyapatite-polyphosphazene polymer composites at physiologic temperature.

Aspects of the formation of bone analog composites at 37 degrees C are described. The composites are composed of hydroxyapatite (HAp) and the calcium salt of a biocompatible polymer and are capable of forming under in vivo conditions. Composite formation involves the formation of monolithic HAp from particulate calcium phosphate precursors while Ca ions liberated to the aqueous medium in which this reaction is occurring form crosslinks with the acidic polymer. The reactants are poly[bis(carboxylatophenoxy)phosphazene] (acid-PCPP), tetracalcium phosphate [Ca4(PO4)2O, TetCP], and anhydrous dicalcium phosphate (CaHPO4, DCPA). The effects of the proportion of polymer (5, 10, or 15 wt %) on the kinetics of HAp formation were studied. Compositional evolution of the solid calcium phosphates present was followed by X-ray diffraction and infrared spectroscopy analyses. HAp formation through a dissolution-precipitation process provided a mildly alkaline medium suitable for deprotonation of the acid-PCPP and for the formation of the calcium crosslinks, as monitored by infrared spectroscopy. Concurrence of crosslinking of the polymer and HAp formation was established, indicating true composite formation can be realized at physiologic temperature.

Composite formation from hydroxyapatite with sodium and potassium salts of polyphosphazene.

The low temperature synthesis of composites potentially suitable as bone substitutes which form in vivo, was investigated. The composites were comprised of stoichiometric hydroxyapatite (SHAp) and water-soluble poly phosphazenes. These constituents were selected because of their biocompatibility, and were mixed as powders with a phosphate buffer solution (PBS) to form the composites. The effects of poly[bis(sodium carboxylatophenoxy)phosphazene] (Na-PCPP) or poly[bis(potassium carboxylatophenoxy) phosphazene] (K-PCPP) on stoichiometric hydroxyapatite (SHAp) formation from tetracalcium phosphate and anhydrous dicalcium phosphate were assessed. The kinetics and reaction chemistries of composite formation were followed by isothermal calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. In the presence of 1% by weight of polyphosphazenes, composites comprised of SHAp and calcium cross-linked polymer salts were formed. Thus a mechanism for binding between polymer chains was established. Elevated proportions (5 and 10% by weight) of polyphosphazene, however, resulted in the inhibition of SHAp formation. This is attributed to the formation of viscous polymer solution coatings on the calcium phosphate precursors, retarding their reaction, and consequently inhibiting SHAp formation.

Orthopaedic applications of gene therapy.

Current treatment modalities for musculoskeletal injuries due to disease or trauma often implement the use of tissue grafts, cell transplantations, and artificial scaffolding. These approaches may be augmented with the use of specific biological factors, which accelerate healthy tissue regeneration. Unfortunately, the short half-life and inherent instability of proteins requires the delivery of high doses or multiple doses of these molecules, neither of which is ideal for the patient or clinician. Gene therapy, as an alternative approach, has the potential to circumvent the existing limitations associated with protein delivery by producing a sustained release of the biologic agent at therapeutic levels. This is achieved by the direct transfer of the gene encoding the therapeutic agent to the cells of the afflicted tissue or by implanting cells that have been previously genetically modified in vitro. Using these methods, several laboratories have demonstrated the ability to deliver genes in vitro and in vivo resulting in accelerated and enhanced musculoskeletal tissue regeneration or inhibited disease progression. Many of these investigations, which involved bone, ligament, tendon, and cartilage, are covered in this review. Specifically, musculoskeletal tissue anatomy, factors relevant to musculoskeletal tissue regeneration, target cells, and in vivo and ex vivo gene therapy approaches for musculoskeletal regeneration are discussed. The experience and knowledge gained from these studies have affirmed gene therapy is a promising therapeutic strategy to combat musculoskeletal tissue repair and regeneration following disease or injury.

Low temperature formation of hydroxyapatite-poly(alkyl oxybenzoate)phosphazene composites for biomedical applications.

The formation of biodegradable composites which may be suitable as bone analogs is described. Polyphosphazene-hydroxyapatite (HAp) composites were produced via an acid-base reaction of tetracalcium phosphate and anhydrous dicalcium phosphate in the presence of polyphosphazenes bearing alkyl ester containing side-groups. The polyphosphazenes used were poly(ethyl oxybenzoate)phosphazene (PN-EOB) and poly(propyl oxybenzoate) phosphazene (PN-POB). The effects of temperature and the proportions of polymers, PN-EOB and PN-POB on the kinetics, reaction chemistry and phase evolution during the formation of stoichiometric HAp were studied. Kinetics, phase evolution and microstructural development were evaluated using isothermal calorimetry, X-ray diffraction and scanning electron microscopy, respectively. Analysis of solution chemistry revealed that the increases in the pH during the formation of SHAp, resulted in partial hydrolysis of the polymer surfaces, which led in turn to the formation of a calcium cross-linked polymer surface. The calcium cross-linked polymer surface appeared to facilitate the nucleation and growth of apatite deposits on the polymer. The current study illustrates the in situ formation of HAp in the presence of polyphosphazenes, where HAp is chemically bonded to the polymer.

Tissue-engineered bone formation in vivo using a novel sintered polymeric microsphere matrix.

We have evaluated in vivo a novel, polymer-based, matrix for tissue engineering of bone. A segmental defect of 15 mm was created in the ulna of New Zealand white rabbits to determine the regenerative properties of a porous polylactide-co-glycolide matrix alone and in combination with autogenous marrow and/or the osteoinductive protein, BMP-7. In this study four implant groups were used: 1) matrix alone; 2) matrix with autogenous marrow; 3) matrix with 20 microg of BMP-7; and 4) matrix with 20 microg of BMP-7 and autogenous marrow. The results showed that the degree of bone formation was dependent on the properties of the graft material. The osteoconductive sintered matrix structure showed significant formation of bone at the implant-bone interface. The addition of autogenous marrow increased the penetration of new bone further into the central area of the matrix and also increased the degree of revascularisation. The osteoinductive growth factor BMP-7 induced penetration of new bone throughout the entire structure of the implant. The most effective treatment was with the combination of marrow cells and osteoinductive BMP-7.