Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations.

BACKGROUND: We assessed the clinimetric properties of ataxia rating scales and functional tests, and made recommendations regarding their use. METHODS: A systematic literature search was conducted to identify the instruments used to rate ataxia symptoms. The identified rating scales and functional ability tests were reviewed and ranked by the panel as "recommended," "suggested," or "listed" for the assessment of patients with discrete cerebellar disorders, using previously established criteria. RESULTS: We reviewed 14 instruments (9 rating scales and 5 functional tests). "Recommended" rating scales for the assessment of symptoms severity were: for Friedreich's ataxia, the Friedreich's Ataxia Rating Scale, the International Cooperative Ataxia Rating Scale (ICARS), and the Scale for the Assessment and Rating of Ataxia (SARA); for spinocerebellar ataxias, ICARS and SARA; for ataxia telangiectasia: ICARS and SARA; for brain tumors, SARA; for congenital disorder of glycosylation-phosphomannomutase-2 deficiency, ICARS; for cerebellar symptoms in multiple sclerosis, ICARS; for cerebellar symptoms in multiple system atrophy: Unified Multiple System Atrophy Rating Scale and ICARS; and for fragile X-associated tremor ataxia syndrome, ICARS. "Recommended" functional tests were: for Friedreich's ataxia, Ataxia Functional Composite Score and Composite Cerebellar Functional Severity Score; and for spinocerebellar ataxias, Ataxia Functional Composite Score, Composite Cerebellar Functional Severity Score, and SCA Functional Index. CONCLUSIONS: We identified some "recommended" scales and functional tests for the assessment of patients with major hereditary ataxias and other cerebellar disorders. The main limitations of these instruments include the limited assessment of patients in the more severe end of the spectrum and children. Further research in these populations is warranted. © 2020 International Parkinson and Movement Disorder Society.

Clinical and molecular findings in a cohort of ANO5-related myopathy.

OBJECTIVE: ANO5-related myopathy is an important cause of limb-girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients. METHODS: A national cross-sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied. RESULTS: Thirty-seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss-of-function variants were not associated with specific phenotypes. INTERPRETATION: We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.

Degradation of bare and silanized silicon wafer surfaces by constituents of biological fluids.

The 24 h stability of bare silicon wafers as such or silanized with CH(3)O-(CH(2)-CH(2)-O)(n)-C(3)H(6)-trichlorosilane (n=6-9) was investigated in water, NaCl, phosphate and carbonate solutions, and in phosphate buffered saline (PBS) at 37 °C (close to biological conditions regarding temperature, high ionic strength, and pH). The resulting surfaces were analyzed using ellipsometry, X-ray Reflectometry (XRR), X-ray Photoelectron Spectroscopy (XPS), and Atomic Force Microscopy (AFM). Incubation of the silanized wafers in phosphate solution and PBS provokes a detachment of the silane layer. This is due to a hydrolysis of Si-O bonds which is favored by the action of phosphate, also responsible for a corrosion of non-silanized wafers. The surface alteration (detachment of silane layer and corrosion of the non-silanized wafer) is also important with carbonate solution, due to a higher pH (8.3). The protection of the silicon oxide layer brought by silane against the action of the salts is noticeable for phosphate but not for carbonate.

Growth mechanism of confined polyelectrolyte multilayers in nanoporous templates.

We investigate the mechanism of polyelectrolyte multilayer (PEM) assembly in nanoporous templates with a view to synthesizing nanotubes or nanowires under optimal conditions. For this purpose, we focus on the effect of parameters related to the geometrical constraints (pore diameter), the size of the macromolecules (their molar mass and the ionic strength), and the interaction between the pore walls and the adsorbed chains (modulated by the ionic strength). Our results reveal the existence of two regimes in the mechanism of PEM growth: (i) the first regime is comparable to that observed on flat substrates, including the influence of ionic strength and (ii) the second regime, which is slower in terms of kinetics, results from the interconnection established between polyelectrolyte chains across the pores and leads to the formation of a dense gel. As a consequence, the diffusion of polyelectrolytes in nanopores becomes the controlling factor of PEM growth in this second regime. The dense gel, owing to its peculiar structure, enhances the formation of nanowires or of partially occluded nanotubes in some cases, depending on initial pore dimensions.

Functionalization of magnetic nanowires by charged biopolymers.

We report on a facile method for the preparation of biocompatible and bioactive magnetic nanowires. The method consists of the direct deposition of polysaccharides by layer-by-layer (LbL) assembly onto a brush of metallic nanowires obtained by electrodeposition of the metal within the nanopores of an alumina template supported on a silicon wafer. Carboxymethylpullulan (CMP) and chitosan (CHI) multilayers were grown on brushes of Ni nanowires; subsequent grafting of an enzyme was performed by conjugating free amine side groups of chitosan with carboxylic groups of the enzyme. The nanowires are finally released by a gentle ultrasonic treatment. Transmission electron microscopy, electron energy-dispersive loss spectroscopy, and x-ray photoelectron spectroscopy indicate the formation of an homogeneous coating onto the nickel nanowires when one, two, or three CMP/CHI bilayers are deposited. This easy and efficient route to the biochemical functionalization of magnetic nanowires could find widespread use for the preparation of a broad range of nanowires with tailored surface properties.

Oligo(ethylene glycol) monolayers by silanization of silicon wafers: Real nature and stability.

Grafting silicon wafers with CH(3)O(CH(2)CH(2)O)(n)C(3)H(6)-trimethoxysilane and -trichlorosilane (n=6 to 9) was performed in different conditions (solvent, reaction time, washing) in order to select procedures compatible with the design of nanostructured surfaces for biomaterial applications, using electron-beam lithography. After a first screening by principal component analysis (PCA), the X-ray photoelectron spectroscopy (XPS) data were analyzed by plotting the carbon to oxygen molar ratio vs the molar ratio of carbon singly bound to oxygen [CO] over carbon bound only to carbon and hydrogen [C(C,H)]. This was found to be a convenient method for discarding samples containing free polymerized silane. Such excess occurred as a result of insufficient washing or unsuitable solvent for the reaction (ether), as confirmed by AFM and thickness measured by X-ray reflectometry. Angle resolved XPS analysis indicated that the grafted silane layer had a 1-2 nm thickness and was covered by a thin layer of adventitious contaminant. As a result, the surface chemical composition obtained covered a broad range (O/C of 0.4 to 1.1; CO/C(C,H) of 2.5 to 6.5); variations could not be related to the nature of the silane reagent and no significant difference was found between hexane and toluene as solvent for the reaction. The grafted silane layer was not stable upon incubation during 24 h in phosphate buffered saline (PBS) at 37 degrees C, which mimics biological environments. As a consequence, the grafted wafers did not show protein repellent properties. This alteration was not observed at room temperature. XPS analysis demonstrated that silane layer detachment was due to a hydrolysis within the SiO(2) layer initially present at the wafer surface.

Mechanical properties of nanotubes of polyelectrolyte multilayers.

The elastic properties of nanotubes fabricated by layer-by-layer (LbL) assembly of polyelectrolytes in the nanopores of polycarbonate track-etched membranes have been investigated by resonant contact Atomic Force Microscopy (AFM), for nanotube diameters in the range of 100 to 200 nm. The elastic modulus of the nanotubes was computed from the resonance frequencies of a cantilever resting on freely suspended LbL nanotubes. An average value of 115 MPa was found in air for Young's modulus of these nanostructures, well below the values reported for dry, flat multilayers, but in the range of values reported for water-swollen flat multilayers. These low values are most probably due to the lower degree of ionic cross-linking of LbL nanotubes and their consequently higher water content in air, resulting from the peculiar mode of growth of nanoconfined polyelectrolyte multilayers.

Nanopatterned monolayers of an adsorbed chromophore.

A simple lift-off process was developed to rapidly fabricate nanopatterned photofunctional surfaces. Dye molecules of a perylene derivative (PDID) were adsorbed irreversibly on clean silicon through the holes of an electron-beam lithographied polymer mask. The subsequent removal of the mask in a proper solvent results in PDID nanosized regions of width as small as 30 nm for stripes and of diameter as small as 120 nm for dots. Numerical analyses of atomic force microscopy and laser-scanning confocal microscopy images show that the dye molecules are confined to the regions defined by the lithographic process, with the integrated fluorescence intensity being essentially proportional to the size of the nanofeatures. This demonstrates that a simple organic lift-off process compatible with clean-room technology, and not involving any chemical step, is able to produce photofunctional nanopatterned surfaces, even though the dye is not chemically bonded to the silicon surface.

Layer-by-layer coating of degradable microgels for pulsed drug delivery.

Recently, we reported on "self-rupturing" microcapsules which consist of a biodegradable dextran-based microgel surrounded by a polyelectrolyte membrane. Degradation of the microgel increases the swelling pressure in the microcapsules which, when sufficiently high, ruptures the surrounding polyelectrolyte membrane. The membrane surrounding the microgels is deposited using the layer-by-layer (LbL) technique, which is based on the alternate adsorption of oppositely charged polyelectrolytes onto a charged substrate. In this paper, we characterize with confocal microscopy, electrophoretic mobility, scanning electron microscopy and atomic force microscopy in detail the deposition and the properties of the LbL coatings on the dextran microgels. We show that by fine-tuning the properties of both the microgel core and the LbL membrane the swelling pressure which is evoked by the degradation of the microgel is indeed able to rupture the surrounding LbL membrane. Further, we show that the application of an LbL coating on the surface of the microgels dramatically lowers the burst release from the microcapsules and results in massive release at the time the microcapsules rupture.

Spinodal-like dewetting of thermodynamically-stable thin polymer films.

Energetic considerations indicate that long-range Van der Waals forces stabilize thin polystyrene (PS) films against height fluctuations on silicon substrates. Nevertheless, we report here on the amplification of capillary waves of specific wavelengths for 15 nm thick PS films on silicon, ultimately leading to dewetting in a "spinodal-like" process. However, the temporal dependence of the wavelength of the growing instability does not agree with the "classical" spinodal dewetting mechanism. Therefore, this phenomenon is ascribed to the existence of "structural" forces resulting either from the restructuring of the films or from density variations within the films during annealing, in accordance with recent theoretical treatments. The process is shown not to be limited to polystyrene films, which indicates the generality of our findings.

[Language comprehension by children with profound congenital deafness after cochlear implant]. / Compréhension du langage par les enfants sourds profonds congénitaux au moyen de l'implant cochléaire.

The consequences of profound deafness on oral language development in children are drastic and well-known. Modern multichannel cochlear implant (CI) has been proven to enhance speech production skills in prelingually deaf children. Speech production skills, however, are known not to be a reliable reflection of oral language competence as a whole. Language is an acquired common code in a specific group, enabling exchange of ideas, feelings and knowledge. In humans, speech is one of the channels conveying language. Assessing language development in CI children is more difficult than simply assessing speech production skills. Many factors may contribute to a poor or an excellent outcome, making it difficult to compare groups of children wearing or not wearing CI. The present study compared receptive language levels in paired matched children from CI and non-CI groups. The main conclusion of this study is that language comprehension scores grow significantly higher over time post-surgery in CI than in paired-matched non-CI children, despite better initial pure tone audiometric thresholds of the latter.

Comprehension of language in congenitally deaf children with and without cochlear implants.

The consequences of profound early deafness on oral language in children are drastic. The modern cochlear implant (CI) has been shown to enhance speech production skills in prelingually deaf children. Many factors may contribute to a poor or an excellent outcome, making it difficult to compare groups of children wearing or not wearing cochlear implants. The present study compared receptive language levels in matched pairs of children from CI group and non-CI groups. The pre-op receptive language development curve suggest a possible growth over time with the maturation and the speech therapy. Comparison showed that the slope for post-op CI children to be greater than for non-CI children, and that this difference is statistically significant, and that the slope for CI children to be greater post- than pre-operatively. The main conclusion is that receptive language scores grow significantly higher over time after surgery in CI than in pair-matched non-CI children, despite better initial pure tone audiometric thresholds of the latter.

Naturally occurring lethal parvovirus infection of juvenile and young-adult rats.

A lethal disease characterized by hemorrhage and necrosis of the brain, testes, and epididymides developed in young adult rats housed in specific pathogen free quarters. Morphological, virological, and serological investigations of the outbreak indicated that the probable causative agent was rat virus (Kilham), a common parvovirus of rats that usually induces persistent, asymptomatic infection in adult rats.

Differential effects of chemical and physical restraint on carbohydrate tolerance testing in nonhuman primates.

Ketamine hydrochloride, used during glucose or lactose tolerance tests to aid restraint of rhesus and stumptail macaques unconditioned to handling, prevented the establishment of definitive baseline plasma glucose tolerance curves from which meaningful interpretations could be derived. Repetition of the tests after the animals were restraint-chair conditioned provided clear baseline control data. It is suggested that ketamine might invalidate those carbohydrate tolerance tests which are based on the absorption of glucose from the gastrointestinal tract.

Health assessment in the procurement of laboratory rodents.

A health assessment procurement program should be well matched with an ongoing in-house health monitoring and evaluation program. Programs for health assessment include ordering, receiving and quarantining of animals, or the placement of vendor animals directly into colony rooms. Health assessment methods for procured laboratory rodents consist of statistical sampling, clinical evaluation, laboratory evaluation, reporting results to veterinarians, interpretation of data, communication to investigators and vendors and action.

Lactose intolerance in the stumptail macaque (Macaca arctoides): case report.

A female stumptail macaque had signs of intermittant diarrhea and chronic weight loss over a 2-year period during which she was fed a commercial laboratory maintenance diet. Intolerance of this individual to lactose, a ubiquitous constituent of most commercial primate diets, was diagnosed on the basis of lactose tolerance tests and favorable clinical response to dietary carbohydrate substitution with glucose. Oral administration of varying doses of glucose to this animal consistently produced elevations in plasma glucose concentrations exceeding 20 mg/dl, while orally-administered doses of lactose did not cause significant elevations in blood glucose concentrations.