Questioning Classic Patient Classification Techniques in Gait Rehabilitation: Insights from Wearable Haptic Technology

Classifying stroke survivors based on their walking abilities is an important part of the gait rehabilitation process. It can act as powerful indicator of function and prognosis in both the early days after a stroke and long after a survivor receives rehabilitation. This classification often relies solely on walking speed; a quick and easy measure, with only a stopwatch needed. However, walking speed may not be the most accurate way of judging individual’s walking ability. Advances in technology mean we are now in a position where ubiquitous and wearable technologies can be used to elicit much richer measures to characterise gait. In this paper we present a case study from one of our studies, where within a homogenous group of stroke survivors (based on walking speed classification) important differences in individual results and the way they responded to rhythmic haptic cueing were identified during the piloting of a novel gait rehabilitation technique

A Gait Rehabilitation pilot study using tactile cueing following Hemiparetic Stroke

Recovery of walking function is a major goal of post-stroke rehabilitation. Audio metronomic cueing has been shown to improve gait, but can be impractical and inconvenient to use in a community setting, for example outdoors where awareness of traffic is needed, as well as being unsuitable in environments with high background noise, or for those with a hearing impairment. Silent lightweight portable tactile cueing, if similarly successful, has the potential to take the benefits out of the lab and into everyday life. The Haptic Bracelets, designed and built at the Open University originally for musical purposes, are self- contained lightweight wireless devices containing a computer, Wi-Fi chip, accelerometers and low-latency vibrotactiles with a wide dynamic range. In this paper we outline gait rehabilitation problems and existing solutions, and present an early pilot in which the Haptic Bracelets were applied to post-stroke gait rehabilitation

A pilot study using tactile cueing for gait rehabilitation following stroke

Recovery of walking function is a vital goal of post-stroke rehabilitation. Cueing using audio metronomes has been shown to improve gait, but can be impractical when interacting with others, particularly outdoors where awareness of vehicles and bicycles is essential. Audio is also unsuitable in environments with high background noise, or for those with a hearing impairment. If successful, lightweight portable tactile cueing has the potential to take the benefits of cueing out of the laboratory and into everyday life. The Haptic Bracelets are lightweight wireless devices containing a computer, accelerometers and low-latency vibrotactiles with a wide dynamic range. In this paper we review gait rehabilitation problems and existing solutions, and present an early pilot in which the Haptic Bracelets were applied to post-stroke gait rehabilitation. Tactile cueing during walking was well received in the pilot, and analysis of motion capture data showed immediate improvements in gait

Ion-exchanged planar lossless splitter for analog CATV distribution systems at 1.5µm

We demonstrate for the first time an ion-exchanged, planar lossless splitter pumped at 980 nm in an analog CATV distribution system at 1.5 µm

Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients

Background: Dysregulated expression of Kallikrein-related peptidase 6 (KLK6) is a common feature for many human malignancies and numerous studies evaluated KLK6 as a promising biomarker for early diagnosis or unfavorable prognosis. However, the expression of KLK6 in carcinomas derived from mucosal epithelia, including head and neck squamous cell carcinoma (HNSCC), and its mode of action has not been addressed so far. Methods: Stable clones of human mucosal tumor cell lines were generated with shRNA-mediated silencing or ectopic overexpression to characterize the impact of KLK6 on tumor relevant processes in vitro. Tissue microarrays with primary HNSCC samples from a retrospective patient cohort (n = 162) were stained by immunohistochemistry and the correlation between KLK6 staining and survival was addressed by univariate Kaplan-Meier and multivariate Cox proportional hazard model analysis. Results: KLK6 expression was detected in head and neck tumor cell lines (FaDu, Cal27 and SCC25), but not in HeLa cervix carcinoma cells. Silencing in FaDu cells and ectopic expression in HeLa cells unraveled an inhibitory function of KLK6 on tumor cell proliferation and mobility. FaDu clones with silenced KLK6 expression displayed molecular features resembling epithelial-to-mesenchymal transition, nuclear β-catenin accumulation and higher resistance against irradiation. Low KLK6 protein expression in primary tumors from oropharyngeal and laryngeal SCC patients was significantly correlated with poor progression-free (p = 0.001) and overall survival (p < 0.0005), and served as an independent risk factor for unfavorable clinical outcome. Conclusions: In summary, detection of low KLK6 expression in primary tumors represents a promising tool to stratify HNSCC patients with high risk for treatment failure. These patients might benefit from restoration of KLK6 expression or pharmacological targeting of signaling pathways implicated in EMT

Quiescence and γH2AX in neuroblastoma are regulated by ouabain/Na,K-ATPase

Cellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways. To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies. The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21Waf1/Cip1 and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed. Conclusion: These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies

Bioinformatic identification of proteins with tissue-specific expression for biomarker discovery

<p>Abstract</p> <p>Background</p> <p>There is an important need for the identification of novel serological biomarkers for the early detection of cancer. Current biomarkers suffer from a lack of tissue specificity, rendering them vulnerable to non-disease-specific increases. The present study details a strategy to rapidly identify tissue-specific proteins using bioinformatics.</p> <p>Methods</p> <p>Previous studies have focused on either gene or protein expression databases for the identification of candidates. We developed a strategy that mines six publicly available gene and protein databases for tissue-specific proteins, selects proteins likely to enter the circulation, and integrates proteomic datasets enriched for the cancer secretome to prioritize candidates for further verification and validation studies.</p> <p>Results</p> <p>Using colon, lung, pancreatic and prostate cancer as case examples, we identified 48 candidate tissue-specific biomarkers, of which 14 have been previously studied as biomarkers of cancer or benign disease. Twenty-six candidate biomarkers for these four cancer types are proposed.</p> <p>Conclusions</p> <p>We present a novel strategy using bioinformatics to identify tissue-specific proteins that are potential cancer serum biomarkers. Investigation of the 26 candidates in disease states of the organs is warranted.</p

B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

B cells are known to contribute to the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized in these cancers to detail. Here we show comprehensive phenotyping in samples of circulating and tumor-resident B cells as well as serum antibodies in melanoma patients. Memory B cells are enriched in tumors compared to blood in paired samples and feature distinct antibody repertoires, linked to specific isotypes. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation and receptor revision. Compared with blood, tumor-associated B cells produce antibodies with proportionally higher levels of unproductive sequences and distinct complementarity determining region 3 properties. The observed features are signs of affinity maturation and polyreactivity and suggest an active and aberrant autoimmune-like reaction in the tumor microenvironment. Consistent with this, tumor-derived antibodies are polyreactive and characterized by autoantigen recognition. Serum antibodies show reactivity to antigens attributed to autoimmune diseases and cancer, and their levels are higher in patients with active disease compared to post-resection state. Our findings thus reveal B cell lineage dysregulation with distinct antibody repertoire and specificity, alongside clonally-expanded tumor-infiltrating B cells with autoimmune-like features, shaping the humoral immune response in melanoma