Lateral balance control for robotic gait training.

For the rehabilitation of neurological patients robot-aided gait training is increasingly being used. Lack of balance training in these robotic gait trainers might contribute to the fact that they do not live up to the expectations. Therefore, in this study we developed and evaluated an algorithm to support lateral balance during walking, through controlling pelvis motions. This algorithm assists the pelvis, according to a natural pelvic sway pattern, rather than attracting it to the middle of the treadmill. The support algorithm was tested on six healthy young subjects who walked on a treadmill, while different support gains were introduced. Using a higher support gain resulted in a closer approximation of the pelvic sway towards the reference pattern. Step width and step width variability reduced when the external stabilization was provided, and the stability margin increased. This indicates that artificial stabilization reduces the need for active lateral balance control. The presented algorithm to support lateral balance provides a way to assist balance in a more physiological way, compared to attracting the subject to the centre of the treadmill. Here the user is attracted/assisted towards a more natural weight shift pattern. This also facilitates a more natural input of the load receptors, which are largely involved in the regulation of muscle activation patterns and the transitions between the different gait phases.

Advanced spraying techniques in fruit growing--the ISAFRUIT project--towards safer and better quality of fruit.

In 2006 the project ISAFRUIT (www.isafruit.org)--"Increasing fruit consumption through a trans disciplinary approach leading to high quality produce from environmentally safe, sustainable methods"--was launched within the 6th Framework Program of the EC. Within the project's work package ECOFRUIT (WP 5.1 - Safe European fruit from a healthy environment) a Crop Adapted Spray Application (CASA) system is developed. This system is developed to ensure efficient and safe spray application in orchards according to actual needs and with respect to the environment. The system consists of three components: 1. Crop Identification System (CIS), 2. Environmentally Dependent Application System (EDAS), and 3. Crop Health Sensor (CHS). A sprayer prototype able to automatically adapt spray and air distribution according to the characteristics of the target, to the level of crop disease and to the environmental conditions is under development.

Effects of inertia and wrist oscillations on contralateral neurological postural tremor using the wristalyzer, a new myohaptic device.

Upper limb postural tremor consists of mechanical-reflex and central-neurogenic oscillations, superimposed upon a background of irregular fluctuations in muscle force. Muscle spindles play key-roles in the information flow to supra-spinal and spinal generators. Oscillations were delivered using a new generation portable myohaptic device, called ldquowristalyzer,rdquo taking into account the ergonomy of upper limbs and allowing a fine adjustment to each configuration of upper limb segments. The nominal torque of the first generation device is 4 Nm, with a maximal rotation velocity of 300 degrees/s and a range of motion of plusmn45 degrees. Reliability was assessed in basal condition and during loading conditions. We assessed the effects of the addition of inertia on postural tremor of the finger in a group of 26 neurological patients and the effects of wrist oscillations upon contralateral postural tremor in 6 control subjects and in 7 neurological patients exhibiting a postural tremor. Patients showed two different behaviors in response to inertia and exhibited an increased variability of postural tremor during fast oscillations (13.3 Hz). One patient with overactivity of the olivocerebellar pathways exhibited a drop in the peak frequency of more than 20%. The relative power of the 8-12 Hz subband was significantly higher in controls both in basal condition and during oscillations (p = 0.028 and p = 0.015, respectively). The second generation wristalyzer allows to investigate the effects of mechanical oscillations up to frequency of 50 Hz. This mechatronic device can assess the responsiveness of tremor generators to stimulation of muscle spindles and biomechanical loading. Potential applications are the monitoring of dysmetria under various inertial or damping conditions, the assessment of rigidity in Parkinson's disease and the characterization of voluntary muscle force.

Crumbs homologue 1 in polarity and blindness.

Several retinal dystrophies, including retinitis pigmentosa type 12 and Leber congenital amaurosis, are caused by a large variety of mutations in the CRB1 (Crumbs homologue 1) gene. This discovery led to an increased focus on the function of CRB1 and the Drosophila homologue Crumbs. In the present study, we review the current knowledge on Crumbs and its vertebrate homologues, their function in cell polarity and their pathogenicity in retinal degeneration.

[Hereditary neuropathy with liability to pressure palsies: study of six Spanish families]. / Neuropathies héréditaires sensibles à la pression: étude de six familles espagnoles.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited demyelinating neuropathy typically characterized by recurrent episodes of acute painless peripheral nerve palsies often preceded by minor trauma or compression at entrapment sites. However, less classical phenotypes have been reported. A 1.5 Mb deletion in chromosome 17 p11.2 has been shown to be the genetic basis of the disease in the majority of HNPP patients. The few families without this deletion harbored a mutation in the PMP22 gene. We performed a clinical, neurophysiological and molecular genetic study of 6 Spanish HNPP families. Five families (22 individuals) showed the classical chromosome 17 p11.2 deletion and one family (3 individuals) had a novel 3'splice-site mutation in PMP22. Neurophysiological abnormalities were detected in all symptomatic (n=21) and asymptomatic (n=4) deletion or mutation carriers, even in childhood. In addition to the typical presentation we observed other phenotypes: recurrent focal short-term sensory symptoms, a progressive mononeuropathy, a Charcot-Marie-Tooth (CMT) disease-like chronic progressive polyneuropathy, a chronic sensory polyneuropathy and a chronic inflammatory demyelinating polyneuropathy. We report new or very rare phenotypesThese atypical clinical aspects and intrafamilial heterogeneity are present in families with the HNPP deletion as well as in the family with the PMP22 mutation. However, the CMT disease-like chronic polyneuropathy was more common in the PMP22 mutation family. Intrafamilial heterogeneity also seemed to be more pronounced in this kinship. Patients in this family had a mild chronic motor and sensory polyneuropathy neurophysiologically characterized by delayed distal latencies, reduced nerve conduction velocities (NCV) within the demyelinating range, mildly decreased amplitudes of motor and sensory evoked potentials and absence of conduction blocks. In contrast, patients with the common HNPP deletion, regardless of their phenotype, had a diffuse increase in distal motor latencies contrasting with moderately reduced motor NCVs, preserved sensory nerve action potentials, slowing of NCVs at the common entrapment sites and occasionally conduction blocks. In this study we confirm the clinical and molecular heterogeneity of HNPP, emphasizing the need for a mutation analysis of the PMP22 gene when the common 17p11.2 deletion is not found in clinically suspected HNPP patients. We conclude that the 3'splice-site mutation in PMP22 and the common HNPP deletion have largely the same functional consequences although some clinical and neurophysiological differences were observed.

Hereditary Neuralgic Amyotrophy (HNA) is genetically heterogeneous.

Hereditary Neuralgic Amyotrophy (HNA) is an autosomal dominantly inherited recurrent focal neuropathy affecting mainly the brachial plexus. Linkage to markers on chromosome 17q25 was found in 1996 and subsequent reports confirmed linkage of HNA to this locus. Recently a family with a chronic undulating rather than remitting-relapsing clinical course of HNA was described by a Dutch group. This family did not have linkage to the 17q25 locus. Here we describe for the first time clinically and genetically two families with classic remitting-relapsing HNA that are not linked to the previously described HNA locus on chromosome 17q25. These results demonstrate that clinically homogeneous classical HNA is genetically heterogeneous.

Caspr1/Paranodin/Neurexin IV is most likely not a common disease-causing gene for inherited peripheral neuropathies.

Contactin associated protein 1 (Caspr1/Paranodin/Neurexin IV) is an axonal transmembrane molecule mainly localised at the paranodal junction. Since molecular alterations in septate-like junctions at the paranodes might have important consequences for the function of the nerve fiber, we considered that Caspr1 could be involved in the pathogenesis of inherited peripheral neuropathies. In this study, we physically mapped the Caspr1 gene on chromosome 17q21.1 and determined its genomic structure. We performed a mutation analysis of the Caspr1 gene in a cohort of 64 unrelated patients afflicted with distinct inherited peripheral neuropathies. Since no disease causing mutations were found, we suggest that Caspr1 is probably not a common cause of inherited peripheral neuropathies.

Hereditary neuralgic amyotrophy.

Hereditary neuralgic amyotrophy (HNA) belongs to the group of recurrent focal neuropathies, the other major representative being hereditary neuropathy with liability to pressure palsies. The search for the HNA gene has now focused on a locus on chromosome 17q24-q25. Most HNA families show linkage to this locus, but recent evidence indicates that HNA is genetically heterogeneous. Detailed analysis of these unlinked families has broadened our perception of the HNA phenotype, and currently two different clinical courses can be discerned: the classical relapsing-remitting course and a chronic undulating course. After 5 years of molecular genetic research, this disease remains enigmatic. At present, we can only speculate how such very diverse stimuli as immunizations, childbirth, infections, strenuous exercise, and immobilization can trigger painful attacks of brachial plexus palsies in genetically susceptible individuals.

Mutation analysis of 4 candidate genes for hereditary neuralgic amyotrophy (HNA).

Hereditary neuralgic amyotrophy (HNA) is a rare autosomal dominant disorder. It is characterised by recurrent episodes of focal neuropathy involving the brachial plexus. Genetic linkage analysis has mapped HNA to chromosome 17q25 within a 3.5-cM interval flanked by the short tandem repeat markers D17S785 and D17S802. Here, we report the mutation analysis of four candidate genes. Mutation analysis was performed on the complete coding regions of these genes. Several exonic and intronic single nucleotide polymorphisms were detected. However, no disease-causing mutations were found, indicating that these genes are most probably not involved in the pathogenesis of HNA. In addition, we have characterised and localised a putative pseudogene of the SEC14-like 1 gene.

A novel 3'-splice site mutation in peripheral myelin protein 22 causing hereditary neuropathy with liability to pressure palsies.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant, demyelinating peripheral neuropathy. Clinical hallmarks are recurrent painless focal neuropathies mostly preceded by minor trauma or compression at entrapment sites of peripheral nerves. In the majority of the patients, HNPP is caused by a 1.5 Mb deletion on chromosome 17p11.2-p12 containing the peripheral myelin protein 22 (PMP22) gene. Point mutations within this gene are reported in only a few families. We report a novel mutation in the PMP22 gene in a Spanish family with HNPP. The mutation is a 3' splice-site mutation, preceding coding exon 3 (c.179-1 G>C), causing a mild HNPP phenotype.

Exclusion of 5 functional candidate genes for distal hereditary motor neuropathy type II (distal HMN II) linked to 12q24.3.

Distal hereditary motor neuropathies (distal HMNs) are characterised by degeneration of anterior horn cells of the spinal cord resulting in muscle weakness and atrophy. Distal HMN type II is genetically linked to chromosome 12q24.3 and located within a 13 cM region flanked by markers D12S86 and D12S340. We previously excluded the human phospholipase A2 group 1B gene (PLA2G1B) as the disease causing gene. Here, we report the mutation analysis of five other candidate genes localised within the distal HMN II region: the cytoskeletal proteins paxillin (PXN) and restin (RSN); the acidic ribosomal phosphoprotein, large P0 subunit (RPLP0); a nucleoside diphosphate kinase (NME2B); and the beta 3 subunit of the voltage-gated calcium channel (CACNB3). DNA sequencing of the coding regions was performed but no disease causing mutations could be identified, hence excluding these five genes for distal HMN type II.

Molecular genetics of inherited peripheral neuropathies: who are the actors?

Charcot-Marie-Tooth disease, the most common variant of the inherited peripheral neuropathies, has a prevalence of 1/2500. Clinical, electrophysiological, neuropathological and molecular genetic studies have demonstrated extensive heterogeneity. Currently, 30 genetic loci are known for distinct CMT types and related inherited peripheral neuropathies, while many other types have been excluded for linkage to these loci. Recent molecular genetic studies have demonstrated the involvement of 8 genes that encode proteins with very diverse functions. These include a structural protein confined to the compact myelin, a cytoskeletal protein, an adhesion molecule, a gap-junction protein, a transcription factor, a receptor for a neurotrophic factor, a phosphatase and a protein involved in signal transduction and cell cycle regulation.

Exercise training in the debilitated aged: strength and functional outcomes.

OBJECTIVE: Resistance and endurance training result in gains in fitness in the aged. It is unclear whether the debilitated elderly can perform moderate-intensity training and whether such training results in short-term improvements in strength, endurance, and function in this population. DESIGN: Randomized, controlled trial. SETTINGS AND PATIENTS: Subjects were from a Veterans Affairs nursing home and rehabilitation unit and a community nursing home. They were older than 60 yrs with impairment in at least one physical activity of daily living. Seventy-eight subjects volunteered and 58 (mean age, 75 yrs; 9 women, 49 men) completed the intervention and initial posttest. Only one subject withdrew because of injury or disinterest. INTERVENTION: Thrice-weekly resistance training (using an isokinetic dynamometer) and twice-weekly endurance training for 4 to 8 weeks. MAIN OUTCOMES: Isometric strength in dominant arm and leg, heart rate response to timed endurance test, and activities of daily living score. RESULTS: The mean change in isometric strength across the muscle movements tested was 32.8% in the training group and 10.2% in the control group (difference, 22.6%; 95% confidence interval, 6.2% to 39.0%). No change in heart rate during exercise was seen in the training group. Trained subjects tended to have a greater improvement in functional activity than control subjects, which was statistically significant (p = .04) for those subjects who at enrollment were most dysfunctional (i.e., activities of daily living score less than 13 [maximum score 26]). CONCLUSION: This group of debilitated elderly patients effectively performed resistance training and increased their strength, with the most impaired gaining the most function. Few in the group could effectively perform endurance training.

A sequence-ready BAC/PAC contig and partial transcript map of approximately 1.5 Mb in human chromosome 17q25 comprising multiple disease genes.

Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant recurrent neuropathy mapped to a 4-cM interval on chromosome 17q25 between the short tandem repeat (STR) markers D17S1603 and D17S802. Chromosome 17q25 in general and the 4-cM HNA region in particular are also implicated in the pathogenesis of a number of tumors (tylosis with esophageal cancer, sporadic breast and ovarian tumors) and harbor a psoriasis susceptibility locus. Initial attempts to construct a yeast artificial chromosome contig failed. Therefore, we have now constructed a complete P1 artificial chromosome (PAC) and bacterial artificial chromosome (BAC) contig of the region flanked by the STR markers D17S1603 and D17S802. The contig contains 22 PAC and 64 BAC clones and covers a physical distance of approximately 1. 5 Mb. A total of 83 sequence-tagged site (STS) markers (10 known STSs and STRs, 56 STSs generated from clone end-fragments, 12 expressed sequence tags, and 5 known genes) were mapped on the contig, resulting in an extremely dense physical map with approximately 1 STS per 20 kb. This sequence-ready PAC and BAC contig will be pivotal for the positional cloning of the HNA gene as well as other disease genes mapping to this region.

Mortality one-year postdischarge from a Veterans Affairs geriatric evaluation and management unit: assessing mortality risks.

OBJECTIVE: To assess at Geriatric Evaluation and Management Unit (GEM) admission factors that affect mortality 12-months postdischarge and to develop a preliminary risk scoring protocol to guide targeting of GEM care. SETTING: A 24 bed-GEM at a Veterans Affairs (VA) Medical Center. DESIGN: Relative risks (RR) were assessed using prospective data; a risk protocol from 1988-1989 data was tested on 1990-1991 patients. SUBJECTS: A total of 283 male patients, aged 60 to 102, discharged over 4 years. RESULTS: Age at GEM admission did not correlate with death (r = .14; P = .145), but did correlate with risk scores (r = .33, P < .001). The risk protocol had a sensitivity of .67 and specificity of 1.00. High and low risk patients had mortalities of 51% versus 20%, a Wilcoxon (Gehan) statistic of 15.22, df = 1, and P < .001. Differences in mortality ceased about 100 days postdischarge. Three univariate RR exceeded 1.00 at a 99% Confidence Interval (CI): IADL score (RR: 1.12; CI, 1.03-1.21); nursing acuity score (RR: 1.78; CI: 1.02-3.11); and a primary diagnosis of pneumonia/sepsis (RR: 3.95; CI, 1.60-9.78). Four RRs exceeded 1.00 at a 90% CI: dementia (RR: 1.78; CI, 1.02-3.09); transfer into the GEM from a medical service (RR: 1.47; CI, 1.02-2.12); deconditioning/functional decline (RR: 1.67; CI, 1.12-2.48); and use of a Foley catheter (RR: 2.22; CI, 1.11-4.45). Thirteen other potential risk factors were found in a multivariate analysis. CONCLUSIONS: The point estimates of risk factors may help clinicians target GEM care, but the development of a useable risk protocol requires additional work. Causal models may be needed to assess patient conditions related to successful treatment in GEMs.

Influenza vaccination and warfarin anticoagulation: a comparison of subcutaneous and intramuscular routes of administration in elderly men.

STUDY OBJECTIVES: To determine if subcutaneous administration of influenza vaccine is as immunogenic as the intramuscular route, and to evaluate the frequency of local adverse events associated with both routes in elderly anticoagulated men. DESIGN: Single-blind, prospective study of consecutively enrolled subjects. SETTING: Ambulatory clinic at a university-affiliated Veterans Affairs medical center. PATIENTS: Twenty-six men age 60 years or older, receiving therapeutic dosages of warfarin. INTERVENTIONS: Subjects were randomized to receive either intramuscular or subcutaneous injection of a standard trivalent influenza vaccine. MEASUREMENTS AND MAIN RESULTS: Serum antibody titers to the vaccine's components were measured at baseline, and 6 weeks and 4 months after vaccination. Both routes of administration induced comparable serum antibody titers. There were no differences in adverse events at administration sites between routes of administration. CONCLUSIONS: Elderly individuals are able to mount an immune response to influenza vaccine and produce antibody concentrations deemed protective. The routes of administration are similarly effective at inducing an immune response. The intramuscular route in anticoagulated elderly men does not commonly result in local bleeding complications.

[Hereditary neural amyotrophy (HNA): clinical and molecular genetic basis]. / Hereditäre Neuralgische Amyotrophie (HNA): Klinische und molekulargenetische Befunde.

Hereditary neuralgic amyotrophy (HNA) and hereditary neuropathy with liability to pressure palsies (HNPP) are hereditary focal neuropathies. In this study we describe three families suffering from HNA. These families were examined clinically and electrophysiologically. Linkage analysis with markers from distal chromosome 17 was performed in a three-generation family. HNA could be separated from HNPP in all three families based on clinical and electrophysiological findings. HNA was characterised by recurrent episodes of painful brachial plexus lesions. In contrast to HNPP, no evidence for generalised neuropathy was found in the HNA families. Linkage analysis confirmed the HNA locus on distal chromosome 17. Additionally, we were able to refine the HNA locus to a 16 cM region on chromosome 17q24-q25.

Mutation analysis of a putative sialyltransferase gene, the SFRS2 splicing factor gene and the c-myb ET-locus in two families with hereditary neuralgic amyotrophy (HNA).

HNA is an autosomal dominant recurrent focal neuropathy involving the brachial plexus. The etiology of HNA is unknown but the genetic defect most likely affects a non-neuronal tissue. We previously described linkage to chromosome 17q24-q25 in two HNA-families. Here we report the mutation analysis of two candidate genes: a cDNA encoding a putative sialyltransferase and the SFRS2 splicing factor including the c-myb ET-locus which is encoded on the opposite strand of the SFRS2 gene. The complete protein coding regions of both genes were studied by direct DNA sequencing. We did not find a disease associated mutation indicating that these genes are most likely not involved in the pathogenesis of HNA. However, we identified and characterized a rare AvaII polymorphism in the SFRS2 gene and detected a sequencing error, leading to an amino acid change (Val11Leu) in the published sequence of the putative sialyltransferase.