Foot worn inertial sensors for gait assessment and rehabilitation based on motorized shoes.

Fall prevention in elderly subjects is often based on training and rehabilitation programs that include mostly traditional balance and strength exercises. By applying such conventional interventions to improve gait performance and decrease fall risk, some important factors are neglected such as the dynamics of the gait and the motor learning processes. The EU project "Self Mobility Improvement in the eLderly by counteractING falls" (SMILING project) aimed to improve age-related gait and balance performance by using unpredicted external perturbations during walking through motorized shoes that change insole inclination at each stance. This paper describes the shoe-worn inertial module and the gait analysis method needed to control in real-time the shoe insole inclination during training, as well as gait spatio-temporal parameters obtained during long distance walking before and after the 8-week training program that assessed the efficacy of training with these motorized shoes.

Rapid detection of bacterial resistance to antibiotics using AFM cantilevers as nanomechanical sensors.

The widespread misuse of drugs has increased the number of multiresistant bacteria, and this means that tools that can rapidly detect and characterize bacterial response to antibiotics are much needed in the management of infections. Various techniques, such as the resazurin-reduction assays, the mycobacterial growth indicator tube or polymerase chain reaction-based methods, have been used to investigate bacterial metabolism and its response to drugs. However, many are relatively expensive or unable to distinguish between living and dead bacteria. Here we show that the fluctuations of highly sensitive atomic force microscope cantilevers can be used to detect low concentrations of bacteria, characterize their metabolism and quantitatively screen (within minutes) their response to antibiotics. We applied this methodology to Escherichia coli and Staphylococcus aureus, showing that live bacteria produced larger cantilever fluctuations than bacteria exposed to antibiotics. Our preliminary experiments suggest that the fluctuation is associated with bacterial metabolism.

Optic perineuritis secondary to Wegener's granulomatosis.

BACKGROUND: Optic perineuritis (OPN) is an inflammatory condition involving the optic nerve sheath because of a variety of causes. We describe three patients in whom OPN was secondary to Wegener's granulomatosis (WG) and compare the clinical findings in these cases with those of idiopathic OPN. METHODS: This is a retrospective small case series derived from patients with OPN seen in an outpatient neuro-ophthalmology clinic. Medical records and imaging studies of these patients were reviewed. RESULTS: These patients shared clinical similarities with idiopathic OPN including age, sex, symptoms, radiographic findings and steroid responsiveness. However, recurrence of symptoms on lowering the prednisone dose below 40 mg distinguished these patients from those with idiopathic OPN. CONCLUSIONS: Steroid dependency in idiopathic OPN should raise suspicion of WG. Patients with OPN should be specifically questioned regarding pre-existing upper respiratory tract disorders and rheumatic symptoms and laboratory testing should include acute phase reactants, anti-neutrophil cytoplasmic antibodies and tests of renal function.

Anomalies et complications vasculaires dans les drusen du nerf optique [Vascular anomalies and complications of optic nerve drusen]

BACKGROUND: Drusen of the optic disc are associated with slowly progressive optic neuropathy, characterized by accumulation of acellular laminated concretions in the prelaminar portion of the optic nerve. Papillary hemorrhages and vascular shunts have been reported with disc drusen but their frequency and clinical significance is not well known. METHODS: Retrospective study of fundus photographs of 116 patients with disc drusen referred to the National Hospital for Neurology and Neurosurgery, London, between 1965 and 1991. RESULTS: Hemorrhages were found in 23 eyes from 16/116 (13.8%) patients. Most cases (68.8%, 11/16 cases) occurred in patients with buried drusen, and most hemorrhages were deeply located. Vascular shunts were present in 6.9% (8/116 cases), most frequently in patients with exposed drusen (6/8 cases), most being of the venous type (7/8 cases). DISCUSSION: Vascular anomalies are not rare in disc drusen, as 20.7% (24/116 cases) of our patients presented either disc hemorrhages or shunt vessels. Their presence supports the hypothesis of the slowly progressive nature of disc drusen and the more advanced stage of optic neuropathy in such eyes.

Spatio-temporal gait analysis in children with cerebral palsy using, foot-worn inertial sensors.

A child's natural gait pattern may be affected by the gait laboratory environment. Wearable devices using body-worn sensors have been developed for gait analysis. The purpose of this study was to validate and explore the use of foot-worn inertial sensors for the measurement of selected spatio-temporal parameters, based on the 3D foot trajectory, in independently walking children with cerebral palsy (CP). We performed a case control study with 14 children with CP aged 6-15 years old and 15 age-matched controls. Accuracy and precision of the foot-worn device were measured using an optical motion capture system as the reference system. Mean accuracy±precision for both groups was 3.4±4.6cm for stride length, 4.3±4.2cm/s for speed and 0.5±2.9° for strike angle. Longer stance and shorter swing phases with an increase in double support were observed in children with CP (p=0.001). Stride length, speed and peak angular velocity during swing were decreased in paretic limbs, with significant differences in strike and lift-off angles. Children with cerebral palsy showed significantly higher inter-stride variability (measured by their coefficient of variation) for speed, stride length, swing and stance. During turning trajectories speed and stride length decreased significantly (p<0.01) for both groups, whereas stance increased significantly (p<0.01) in CP children only. Foot-worn inertial sensors allowed us to analyze gait spatiotemporal data outside a laboratory environment with good accuracy and precision and congruent results with what is known of gait variations during linear walking in children with CP.

3D gait assessment in young and elderly subjects using foot-worn inertial sensors.

This study describes the validation of a new wearable system for assessment of 3D spatial parameters of gait. The new method is based on the detection of temporal parameters, coupled to optimized fusion and de-drifted integration of inertial signals. Composed of two wirelesses inertial modules attached on feet, the system provides stride length, stride velocity, foot clearance, and turning angle parameters at each gait cycle, based on the computation of 3D foot kinematics. Accuracy and precision of the proposed system were compared to an optical motion capture system as reference. Its repeatability across measurements (test-retest reliability) was also evaluated. Measurements were performed in 10 young (mean age 26.1±2.8 years) and 10 elderly volunteers (mean age 71.6±4.6 years) who were asked to perform U-shaped and 8-shaped walking trials, and then a 6-min walking test (6MWT). A total of 974 gait cycles were used to compare gait parameters with the reference system. Mean accuracy±precision was 1.5±6.8cm for stride length, 1.4±5.6cm/s for stride velocity, 1.9±2.0cm for foot clearance, and 1.6±6.1° for turning angle. Difference in gait performance was observed between young and elderly volunteers during the 6MWT particularly in foot clearance. The proposed method allows to analyze various aspects of gait, including turns, gait initiation and termination, or inter-cycle variability. The system is lightweight, easy to wear and use, and suitable for clinical application requiring objective evaluation of gait outside of the lab environment.

Anterior segment granuloma and optic nerve involvement as the presenting signs of systemic sarcoidosis.

PURPOSE: To report a case with anterior and posterior nodules associated with systemic sarcoidosis. METHODS: A patient with decreased vision underwent complete ophthalmologic examination, ultrasound biomicroscopy, fluorescein and indocyanine green (ICG) angiography. RESULTS: The patient presented a nodule of the iris of the OS and of the optic nerves of both eyes. Chest computed tomography and tissue biopsy established the diagnosis. CONCLUSIONS: Fluorescein and ICG angiography are the only objective exams to demonstrate the extent of ocular involvement in a patient with sarcoidosis.

Autophagy promotes survival of retinal ganglion cells after optic nerve axotomy in mice.

Autophagy is an essential recycling pathway implicated in neurodegeneration either as a pro-survival or a pro-death mechanism. Its role after axonal injury is still uncertain. Axotomy of the optic nerve is a classical model of neurodegeneration. It induces retinal ganglion cell death, a process also occurring in glaucoma and other optic neuropathies. We analyzed autophagy induction and cell survival following optic nerve transection (ONT) in mice. Our results demonstrate activation of autophagy shortly after axotomy with autophagosome formation, upregulation of the autophagy regulator Atg5 and apoptotic death of 50% of the retinal ganglion cells (RGCs) after 5 days. Genetic downregulation of autophagy using knockout mice for Atg4B (another regulator of autophagy) or with specific deletion of Atg5 in retinal ganglion cells, using the Atg5(flox/flox) mice reduces cell survival after ONT, whereas pharmacological induction of autophagy in vivo increases the number of surviving cells. In conclusion, our data support that autophagy has a cytoprotective role in RGCs after traumatic injury and may provide a new therapeutic strategy to ameliorate retinal diseases.

Anterior ischemic optic neuropathy in eyes with optic disc drusen.

BACKGROUND: There have been anecdotal reports of anterior ischemic optic neuropathy (AION) occurring in eyes with optic disc drusen (ODD), but the clinical features of this condition have not been well characterized. OBJECTIVES: To better describe the clinical features of AION associated with ODD and to compare the clinical features of this condition with those of "garden variety" nonarteritic AION. METHODS: We reviewed the medical records of 20 patients who experienced an episode of AION in an eye with ODD. In 4 patients, both eyes were affected; thus, 24 eyes were studied. The diagnosis of ODD was made by ophthalmoscopic identification, orbital ultrasonography, or computed tomographic scanning. We recorded age, sex, vascular risk factors, symptoms, visual acuity, visual fields, and results of the follow-up examination in all patients. These findings were compared with data from previously reported series of patients with nonarteritic AION. RESULTS: Our 20 patients included 14 men and 6 women (age range, 18-69 years; mean, 49.4 years). Vascular risk factors were identified in 10 patients (50%). Three patients reported episodes of transient visual loss before their fixed deficit. The visual acuity at the initial examination was 20/60 or better in 15 (62%) of the 24 eyes; 8 had a visual acuity of 20/20. The predominant pattern of visual field loss was an altitudinal or arcuate defect in 19 (79%) and a centrocecal scotoma in 5 (21%) of the 24 eyes. There was subjective worsening of vision before the initial neuro-ophthalmic examination in 11 eyes (46%) and objective documentation of progression in 7 eyes (29%). The final visual acuity was 20/40 or better in 13 (62%) of 21 eyes and 20/200 or worse in 3 (14%) of 21 eyes. CONCLUSIONS: Our patients were strikingly similar to those with nonarteritic AION unassociated with drusen in regard to prevalence of vascular risk factors, pattern of visual field loss, and occurrence of a subsequent similar event in the fellow eye. In contrast, however, patients with ODD-AION were younger than those with nonarteritic AION, were more likely to report preceding episodes of transient visual obscuration, and enjoyed a more favorable visual outcome.

Interstitial cells of Cajal are normally distributed in both ganglionated and aganglionic bowel in Hirschsprung's disease

Résumé Introduction : La chirurgie de la maladie de Hirschsprung est fréquemment compliquée d'une atteinte post-opératoire de la motilité intestinale. Des anomalies du système nerveux entérique (SNE) telles que la dysplasie neuronale intestinale de type B, l'hypoganglionose ou l'aganglionose, présents dans le segment abaissé, peuvent être la cause de certaines de ces complications mais aucune information n'est disponible quant au rôle des cellules interstitielles de Cajal (CIC) sur la motilité intestinale dans la phase post-opératoire. Ces cellules sont considérées avoir un rôle de pacemaker dans le tractus gastro-intestinal. L'objectif de cette étude était de décrire la distribution des CIC dans le segment proximal du côlon réséqué lors de cures chirurgicales de maladie de Hirschsprung et de confronter ces observations à l'évolution clinique post-opératoire. Matériel et Méthodes : L'incidence des complications post-opératoires a été déterminée par une revue rétrospective des dossiers de 48 patients opérés pour maladie de Hirschspung entre 1977 et 1999 et par l'étude histologique et immuno-histochimique des pièces réséquées chez ces patients. Nous avons comparé la distribution des CIC dans le segment proximal du côlon avec celle du côlon sain de 16 enfants contrôles par microscopie optique. L'immunohistochimie au c-Kit a été utilisée pour marquer spécifiquement les CIC sur échantillons paraffinés. Ces résultats ont ensuite été corrélés avec l'étude du SNE de ces mêmes segments, déterminée par immunohistochimie au CD56 et au protein gene product 9.5. Résultats Les complications post-opératoires suivantes furent identifiées : constipation 46%, constipation avec incontinence 15%, entérocolite 8%, décès 4% (probablement sur entérocolite). La distribution des CIC dans les segments proximaux réséqués chez les enfants avec maladie de Hirschsprung était identique à celle observée dans les segments de côlon sain, et ce indépendamment de la distribution normale ou anormale du SNE. Chez les enfants opérés pour maladie de Hirschsprung les segments réséqués présentaient les anomalies d'innervation suivantes : aganglionose 10.4%, hypoganglionose 12.5%, dysplasie neuronale intestinale de type B 6.3%, autres dysganglionoses 14.6%. Aucune relation entre ces anomalies d'innervation et les complications post-opératoires n'a été mise en évidence. Conclusion : La distribution des CIC est normale chez les patient opérés pour maladie de Hirschsprung, et ne contribue donc pas aux atteintes post-opératoires de la motilité intestinale. Cela signifie aussi que le réseau de CIC se développe noinialement dans le côlon humain, même en présence d'une innervation colique anormale ou absente. Abstract: Surgery for Hirschsprung's disease is often complicated by post-operative bowel motility disorders. The impact of intestinal neural histology on the surgical outcome has been previously studied, but no information is available concerning the influence of the distribution of interstitial cells of Cajal (ICC) on these complications. These cells are considered to be pacemakers in the gastrointestinal tract. The aim of this study was to assess the distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease and confront these results with the clinical outcome. Using immunohistochemistry for light microscopy, we compared the pattern of distribution of ICC in the proximal segment of resected bowel in Hirschsprung's disease with that in normal colon. We correlated these results with the corresponding neural intestinal histology determined by CD56 and the protein gene product 9.5 immunohistochemistry. The distribution of ICC in the proximal segment of resected bowel is identical to that of normal colon, regardless of normal or abnormal colon innervation. ICC distribution does not seem to contribute to post-operative bowel motility disorders in patients operated for Hirschsprung's disease.

Genetic overlap in kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia.

Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain.

Selection on a eumelanic ornament is stronger in the tropics than in temperate zones in the worldwide-distributed barn owl.

Spatial variation in the pattern of natural selection can promote local adaptation and genetic differentiation between populations. Because heritable melanin-based ornaments can signal resistance to environmentally mediated elevation in glucocorticoids, to oxidative stress and parasites, populations may vary in the mean degree of melanic coloration if selection on these phenotypic aspects varies geographically. Within a population of Swiss barn owls (Tyto alba), the size of eumelanic spots is positively associated with survival, immunity and resistance to stress, but it is yet unknown whether Tyto species that face stressful environments evolved towards a darker eumelanic plumage. Because selection regimes vary along environmental gradients, we examined whether melanin-based traits vary clinally and are expressed to a larger extent in the tropics where parasites are more abundant than in temperate zones. To this end, we considered 39 barn owl species distributed worldwide. Barn owl species living in the tropics displayed larger eumelanic spots than those found in temperate zones. This was, however, verified in the northern hemisphere only. Parasites being particularly abundant in the tropics, they may promote the evolution of darker eumelanic ornaments.