Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study.

BackgroundThe current methods of assessing motor function rely primarily on the clinician's judgment of the patient's physical examination and the patient's self-administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand.MethodsEleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients' adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either "functional" or "nonfunctional" in order to validate the system's responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated.ResultsThe control participants had lower MediSens MAE scores of 8.09%±1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%±6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%±1.60%, while the nonfunctional CSM patients had an average score of 12.41%±6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14×10⁻⁵). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04).ConclusionsThe MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand

Modified Huo-Luo-Xiao-Ling Dan Suppresses Adjuvant Arthritis by Inhibiting Chemokines and Matrix-Degrading Enzymes

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints that can lead to deformities and disability. The prolonged use of conventionally used drugs is associated with severe adverse reactions. Therefore, safer and less expensive therapeutic products are continually being sought. Huo-Luo-Xiao-Ling dan (HLXL), a traditional Chinese herbal mixture, and its modified versions possess anti-arthritic activity. In this paper, we examined the influence of modified HLXL on two of the key mediators of arthritic inflammation and tissue damage, namely, chemokines and matrix-metalloproteinases (MMPs) in the rat adjuvant-induced arthritis (AA) model of RA. We treated arthritic Lewis rats with HLXL (2.3 g/kg) by daily gavage beginning at the onset of AA. The control rats received the vehicle. At the peak phase of AA, rats were sacrificed and their draining lymph node cells (LNC) and spleen adherent cells (SAC) were tested. The HLXL-treated rats showed a significant reduction in the levels of chemokines (RANTES, MCP-1, MIP-1α, and GRO/KC), MMPs (MMP 2 and 9), as well as cytokines (IL-6 and IL-17) that induce them, compared to the control vehicle-treated rats. Thus, HLXL controls arthritis in part by suppressing the mediators of immune pathology, and it might offer a promising alternative/adjunct treatment for RA

Duality and Non-linear Response for Quantum Hall Systems

We derive the implications of particle-vortex duality for the electromagnetic response of Quantum Hall systems beyond the linear-response regime. This provides a first theoretical explanation of the remarkable duality which has been observed in the nonlinear regime for the electromagnetic response of Quantum Hall systems.Comment: 7 pages, 1 figure, typeset in LaTe

Central Powering of the Largest Lyman-alpha Nebula is Revealed by Polarized Radiation

High-redshift Lyman-alpha blobs are extended, luminous, but rare structures that appear to be associated with the highest peaks in the matter density of the Universe. Their energy output and morphology are similar to powerful radio galaxies, but the source of the luminosity is unclear. Some blobs are associated with ultraviolet or infrared bright galaxies, suggesting an extreme starburst event or accretion onto a central black hole. Another possibility is gas that is shock excited by supernovae. However some blobs are not associated with galaxies, and may instead be heated by gas falling into a dark matter halo. The polarization of the Ly-alpha emission can in principle distinguish between these options, but a previous attempt to detect this signature returned a null detection. Here we report on the detection of polarized Ly-alpha from the blob LAB1. Although the central region shows no measurable polarization, the polarized fraction (P) increases to ~20 per cent at a radius of 45 kpc, forming an almost complete polarized ring. The detection of polarized radiation is inconsistent with the in situ production of Ly-alpha photons, and we conclude that they must have been produced in the galaxies hosted within the nebula, and re-scattered by neutral hydrogen.Comment: Published in the August 18 issue of Nature. 1750 words, 3 figures, and full Supplementary Information. Version has not undergone proofing. Reduced and processed data products are available here: http://obswww.unige.ch/people/matthew.hayes/LymanAlpha/LabPol

Suppression of Ongoing Experimental Arthritis by a Chinese Herbal Formula (Huo-Luo-Xiao-Ling Dan) Involves Changes in Antigen-Induced Immunological and Biochemical Mediators of Inflammation

Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.11) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1β but enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients

The On-Orbit Performance of the Galaxy Evolution Explorer

We report the first year on-orbit performance results for the Galaxy Evolution Explorer (GALEX), a NASA Small Explorer that is performing a survey of the sky in two ultraviolet bands. The instrument comprises a 50 cm diameter modified Ritchey-Chretien telescope with a 1.25 degree field of view, selectable imaging and objective grism spectroscopic modes, and an innovative optical system with a thin-film multilayer dichroic beam splitter that enables simultaneous imaging by a pair of photon counting, microchannel plate, delay line readout detectors. Initial measurements demonstrate that GALEX is performing well, meeting its requirements for resolution, efficiency, astrometry, bandpass definition and survey sensitivity.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issu

Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes

SummaryMaster transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies

Bilinear modulation models for seasonal tables of counts

We propose generalized linear models for time or age-time tables of seasonal counts, with the goal of better understanding seasonal patterns in the data. The linear predictor contains a smooth component for the trend and the product of a smooth component (the modulation) and a periodic time series of arbitrary shape (the carrier wave). To model rates, a population offset is added. Two-dimensional trends and modulation are estimated using a tensor product B-spline basis of moderate dimension. Further smoothness is ensured using difference penalties on the rows and columns of the tensor product coefficients. The optimal penalty tuning parameters are chosen based on minimization of a quasi-information criterion. Computationally efficient estimation is achieved using array regression techniques, avoiding excessively large matrices. The model is applied to female death rate in the US due to cerebrovascular diseases and respiratory diseases