Correction of Toe-Walking Gait in Children with Spastic Cerebral Palsy by using Electrical Stimulation Therapy.

Toe-walking is a very common gait abnormality seen in children with Cerebral Palsy (CP). The present study aims to improvise the toe-walking gait by applying Electrical Stimulation (ES) therapy of the Tricep Surae (TS) muscles. The study was carried out on sixteen children with spastic CP with unilateral toe-walking gait problem, divided into the intervention group that received both ES therapy along with conventional physiotherapy treatment and the control group that received only conventional physiotherapy treatment. Both groups were treated for 60 (30 + 30) minutes per day, for 5 days a week, up to 12 weeks. The gait data were analyzed for spatiotemporal and parameters influencing the walking capacity. The results showed that those children who received the intervention had a significant increase in gait speed by 17.67 % (p = 0.019) and decrease in stride length by 10.25 % (p = 0.037), resulting in improvement of body balance. There was a significant percentage increase in initial contact (heel strike) of 85.71 % (p = 0.000) and flat foot position (loading response) of 49.2 % (p = 0.005), confirming reduction in toe-walking. There was also an increase in the swing power by 39.8 % (p = 0.028) and ground impact by 19.5 % (p = 0.003) suggesting a change in foot contact pattern. The results indicate that ES therapy on TS muscle along with conventional physiotherapy may correct the toe-walking gait in children with spastic hemiplegic CP.

Oral cancer in vivo gene expression profiling assisted by laser capture microdissection and microarray analysis.

Large scale gene expression profiling was carried out on laser capture microdissected (LCM) tumor and normal oral epithelial cells and analysed on high-density oligonucleotide microarrays. About 600 genes were found to be oral cancer associated. These oral cancer associated genes include oncogenes, tumor suppressors, transcription factors, xenobiotic enzymes, metastatic proteins, differentiation markers, and genes that have not been implicated in oral cancer. The database created provides a verifiable global profile of gene expression during oral carcinogenesis, revealing the potential role of known genes as well as genes that have not been previously implicated in oral cancer.

Therapeutic effects of functional electrical stimulation on motor cortex in children with spastic Cerebral Palsy.

In the present study we have evaluated the electroencephalogram (EEG) signal recorded during ankle dorsal and plantar flexion in children with spastic Cerebral Palsy (CP) after Functional Electrical Stimulation (FES) of the Tibialis Anterior (TA) muscles. The intervention group had 10 children with spastic diaplegic/hemiplegic CP within the age group of 5 to 14 years of age who received both FES for 30 minutes and the conventional physiotherapy for 30 minutes a day, while the control group had 5 children who received only conventional physiotherapy for 60(30 + 30) minutes a day only. Both group were treated for 5 days a week, up to 12 weeks. The EEG data were analyzed for Peak Alpha Frequency (PAF), sensorimotor rhythm (SMR), mu wave suppression and power spectral density (PSD) of all the bands. The results showed a decrease in SMR and mu wave suppression in the intervention group as compared to the control group, indicating a positive/greater improvement in performance of motor activities. Therefore, from this study we could conclude that FES combined with conventional physiotherapy improves the motor activity in children with spastic CP.

Comparison of human adult and fetal expression and identification of 535 housekeeping/maintenance genes.

Gene expression levels of about 7,000 genes were measured in 11 different human adult and fetal tissues using high-density oligonucleotide arrays to identify genes involved in cellular maintenance. The tissues share a set of 535 transcripts that are turned on early in fetal development and stay on throughout adulthood. Because our goal was to identify genes that are involved in maintaining cellular function in normal individuals, we minimized the effect of individual variation by screening mRNA pooled from many individuals. This information is useful for establishing average expression levels in normal individuals. Additionally, we identified transcripts uniquely expressed in each of the 11 tissues.

A compendium of gene expression in normal human tissues.

This study creates a compendium of gene expression in normal human tissues suitable as a reference for defining basic organ systems biology. Using oligonucleotide microarrays, we analyze 59 samples representing 19 distinct tissue types. Of approximately 7,000 genes analyzed, 451 genes are expressed in all tissue types and designated as housekeeping genes. These genes display significant variation in expression levels among tissues and are sufficient for discerning tissue-specific expression signatures, indicative of fundamental differences in biochemical processes. In addition, subsets of tissue-selective genes are identified that define key biological processes characterizing each organ. This compendium highlights similarities and differences among organ systems and different individuals and also provides a publicly available resource (Human Gene Expression Index, the HuGE Index, http://www.hugeindex.org) for future studies of pathophysiology.

Improvement of gait & muscle strength with functional electrical stimulation in sub-acute & chronic stroke patients.

The main objective of this work was to evaluate and compare the effects of Functional Electrical Stimulation (FES) therapy in the walking ability and muscle strength studied by electromyography (EMG) analysis between subacute and chronic stroke patients. Eighteen consecutive hemiplegic patients suffering from foot drop were assigned either to subacute or chronic group. Patients of both groups' were treated according to conventional rehabilitation program combined with FES therapy for 12 weeks. At post-treatment, subacute subjects showed a mean increase in walking speed of 29.4% and chronic subjects of 17.1% and the physiological cost index (PCI), with a reduction of 73.1% in subacute subjects and 46.5 % in chronic subjects. Improvement was also found in cadence, step length, and mean-absolute-value (MAV) and root-mean-square (RMS) of EMG signal of tibialis anterior (TA) muscle in both groups, but subacute subjects improved better compared with chronic subjects. Thus we suggested that an early intervention of FES therapy combined with conventional rehabilitation program (CRP) could significantly improve the gait and muscle strength in stroke survivors.

Design of a programmable multi-pattern FES system for restoring foot drop in stroke rehabilitation.

A programmable and portable multi-pattern transcutaneous neuromuscular stimulator was developed and evaluated for correction of foot drop in stroke subjects. The stimulator unit was designed to optimize functionality while keeping its size and power consumption to a minimum. It had two channels of biphasic stimulation (charge-balanced and constant current), and all parameters were programmable to accommodate a range of stimulation profiles. The 'natural' electromyographic (EMG) pattern of tibialis anterior (TA) muscle stimulation envelope algorithms and constant amplitude stimulation envelope was provided for foot drop corrections in stroke patients. A foot-switch sensor was used to trigger the device in the swing phase of gait cycle. Various tests on prototype units were performed, including output power characteristics with a skin model, and tested with a stroke subject to validate the results. This paper provides a detailed description of the hardware and block-level functional electrical stimulation (FES) system design for applications in stroke rehabilitation.

Surface EMG analysis of tibialis anterior muscle in walking with FES in stroke subjects.

In this work we have examined the effect of functional electrical stimulation (FES) in the management of drop foot in stroke subjects with surface electromyographic (sEMG) analysis from the tibialis anterior (TA) muscle. Ten subjects were assigned to FES therapy combined with conventional stroke rehabilitation program 5 days a week, 60 min a day, for 12-weeks in clinical settings. Baseline and post-treatment measurements were made for temporal and spectral parameters of EMG signals of TA muscle. The evaluation results reported an increase in mean-absolute-value (MAV), root-mean-square (RMS) and also improved the amplitude and median frequency (MF) of the sEMG power spectrum in monitoring the improvement of the tibialis anterior muscle during maximum voluntary contractions (MVC). We conclude that walking with FES system combined with a conventional rehabilitation program improves the muscle strength in stroke survivors.

Recombination of alleles conferring specific resistance to powdery mildew at the Mla locus in barley.

In barley (Hordeum vulgare L.), the Mla locus conditions reaction to the powdery mildew fungus Erysiphe graminis f.sp. hordei. Enrichment for genetic recombinants in the Mla region is possible by screening for recombination events between the flanking endosperm storage proteins hordeins C and B. Reciprocal crosses were made between the Franger (C.I. 16151) and Rupee (C.I. 16155) lines carrying the (Mla6 + Mla14) and Mla13 alleles, respectively. Recombinants were identified from F2 segregants by analyzing the extracted hordein polypeptides by sodium dodecyl sulphate - polyacrylamide gel electrophoresis. Two hundred and seventy-six recombinant gametes were identified from the 1800 seeds that were screened. Recombination of Mla alleles was analyzed by inoculating F4 recombinant lines with three isolates of E. graminis (A27, 5874, and CR3), which recognize specific Mla alleles. The linkage order established is Hor1-Mla6-Mla13-Mla14-Hor2. The genetic distances between Hor1-Mla6, Mla6-Mla13, and Mla13-Hor2, obtained using Mapmaker 3.0b F3 intercross analysis, are 3.9, 0.2, and 5.2 cM, respectively.

Molecular genetic profiling of Gleason grade 4/5 prostate cancers compared to benign prostatic hyperplasia.

PURPOSE: Because Gleason grade 4/5 cancer is the primary cause of failure to cure prostate cancer, we examined the molecular profiles of this high grade cancer in search of potentially new therapeutic interventions as well as better serum markers than prostate specific antigen. MATERIALS AND METHODS: We compared the gene expressions in fresh frozen tissues from 9 men with Gleason grade 4/5 cancer to 8 men with benign prostatic hyperplasia (BPH) treated with radical retropubic prostatectomy. Labeled complementary RNA from each of the 17 tissues was applied to HuGeneFL probe arrays representing approximately 6,800 genes (Affymetrix, Inc., Santa Clara, California). After removing all genes undetectable in BPH and grade 4/5 cancers, and transforming the data into a parametric distribution, we chose only those up and down-regulated genes with a p difference in fluorescence between grade 4/5 cancer and BPH of p <0.0005. This value reduced the data set to 40 up-regulated and 111 down-regulated genes. We then eliminated all genes that were not expressed in all 8 BPH and 9 grade 4/5 tissues, which produced a final set of 86 genes, of which 22 were up-regulated and 64 were down-regulated. RESULTS: Cluster analysis cleanly separated men with grade 4/5 cancers from those with BPH. Only 17 of the 86 candidate genes (20%) were known to be prostate cancer related and 42 (49%) were related to other cancers. The most up-regulated gene is Hepsin, a trypsin-like serine protease with its enzyme catalytic domain oriented extracellularly. Prostate specific membrane antigen is the second most up-regulated gene (all other reports on prostate specific membrane antigen have been at the protein level). The genes for prostate specific antigen (hK3) and human glandular kallikrein2 (hK2) showed equivalent expression levels 10 times the average of other genes. Complete lists of all 22 up-regulated genes and 64 down-regulated genes, together with their locus on the chromosome, are presented in rank order. CONCLUSIONS: We characterize for the first time 64 down-regulated and 22 up-regulated genes in Gleason grade 4/5 cancer, using the gene profile from BPH as control tissue. A number of interesting new genes, previously undescribed in prostate cancer, are presented as possibilities for further study.

SARPs: a family of secreted apoptosis-related proteins.

Quiescent mouse embryonic C3H/10T1/2 cells are more resistant to different proapoptotic stimuli than are these cells in the exponential phase of growth. However, the exponentially growing 10T1/2 cells are resistant to inhibitors of RNA or protein synthesis, whereas quiescent cells die upon these treatments. Conditioned medium from quiescent 10T1/2 cells possesses anti-apoptotic activity, suggesting the presence of protein(s) that function as an inhibitor of the apoptotic program. Using differential display technique, we identified and cloned a cDNA designated sarp1 (secreted apoptosis-related protein) that is expressed in quiescent but not in exponentially growing 10T1/2 cells. Hybridization studies with sarp1 revealed two additional family members. Cloning and sequencing of sarp2 and sarp3 revealed 38% and 40% sequence identity to sarp1, respectively. Human breast adenocarcinoma MCF7 cells stably transfected with sarp1 or infected with SARP1-expressing adenovirus became more resistant, whereas cells transfected with sarp2 displayed increased sensitivity to different proapoptotic stimuli. Expression of sarp family members is tissue specific. sarp mRNAs encode secreted proteins that possess a cysteine-rich domain (CRD) homologous to the CRD of frizzled proteins but lack putative membrane-spanning segments. Expression of SARPs modifies the intracellular levels of beta-catenin, suggesting that SARPs interfere with the Wnt-frizzled proteins signaling pathway.

Visual task performance in blind humans with retinal prosthetic implants.

A prototype electronic retinal prosthesis has been tested in three subjects. The system features an implanted retinal stimulator and an external system for image acquisition, processing, and telemetry. The subjects in general performed better than chance on psychophysical tests involving object detection, object counting, object discrimination, and direction of movement.