A functional magnetic resonance imaging study of visuomotor processing in a virtual reality‐based paradigm: Rehabilitation Gaming System

The Rehabilitation Gaming System (RGS) has been designed as a flexible, virtual‐reality (VR)‐based device for rehabilitation of neurological patients. Recently, training of visuomotor processing with the RGS was shown to effectively improve arm function in acute and chronic stroke patients. It is assumed that the VR‐based training protocol related to RGS creates conditions that aid recovery by virtue of the human mirror neuron system. Here, we provide evidence for this assumption by identifying the brain areas involved in controlling the catching of approaching colored balls in the virtual environment of the RGS. We used functional magnetic resonance imaging of 18 right‐handed healthy subjects (24 ± 3 years) in both active and imagination conditions. We observed that the imagery of target catching was related to activation of frontal, parietal, temporal, cingulate and cerebellar regions. We interpret these activations in relation to object processing, attention, mirror mechanisms, and motor intention. Active catching followed an anticipatory mode, and resulted in significantly less activity in the motor control areas. Our results provide preliminary support for the hypothesis underlying RGS that this novel neurorehabilitation approach engages human mirror mechanisms that can be employed for visuomotor training.     

Permeability measurements with closed vesicles from rat liver nuclear envelopes.

Closed nuclear envelope ghosts in the physiological orientation were prepared from rat liver and nuclei as previously described. Here we report transport measurements of various proteins and ribonucleic acids across the envelope of these vesicles. Histones were accumulated rapidly in the ghosts, in contrast to other, nonnuclear, proteins. Triton X-100 removal of the external nuclear membrane from loaded vesicles, as well as comparative studies with open vesicles, excluded the effects of external adsorption. The exchange rate of histones across the nuclear envelope is strongly depressed in the presence of GTP and GDP. The vesicles contain the translocation mechanism for poly(A)-containing RNA. The translocation of poly(A), messenger RNA, and ribosomal RNA was investigated after entrapment of these nucleic acids during the preparation of vesicles. Our data show that the complete export of only poly(A)-containing RNA from the vesicles is enhanced in the presence of 2 mM ATP. This RNA, as well as poly(A), is transported unidirectionally.     

ERCC1, XPF and XPA—locoregional differences and prognostic value of DNA repair protein expression in patients with head and neck squamous cell carcinoma

Clinical Oral Investigations - Nucleotide excision repair protein expression has been claimed to be responsible for platinum-based chemotherapy resistance. ERCC1, XPF and XPA, core proteins in DNA...     

Replacement of a single cysteine in the fourth transmembrane region of zebrafish pannexin1 alters hemichannel gating behavior

Pannexin1 (Panx1) is a novel candidate for an electrical synapse protein in the retina. At present Panx1 is considered to function as a hemichannel. Since information about the gating properties of Panx1 channels to date rely on blocker pharmacology, we have begun to establish a structural context of channel function starting with site directed mutagenesis of cysteine residues in transmembrane domains of Panx1. Dye uptake and whole cell voltage clamp recordings of transfected N2a cells demonstrate that zfPanx1 forms voltage activated hemichannels with a large unitary conductance in vitro. The function of this channel was significantly reduced following mutation of a single cysteine residue (C282W) in the fourth transmembrane region. This result suggests a role of this domain in gating of the Panx1 hemichannel.     

The association of trauma and PTSD with the substance use profiles of alcohol- and cocaine-dependent out-of-treatment women

The association of trauma and posttraumatic stress disorder (PTSD) with alcohol and cocaine use is explored to determine if there is additive risk associated with dual dependence. Data were collected from out-of-treatment women enrolled in an HIV-prevention study. Women who experienced a DSM-IV qualifying event (n = 791) were stratified into four substance use groups based on lifetime alcohol and cocaine use. Women with lifetime comorbid alcohol and cocaine dependence experienced significantly more traumatic events and had a higher prevalence of violent events and lifetime diagnosis of PTSD and PTSD-related impairment. There is added risk for associated trauma and subsequent PTSD among women who have dual substance dependence.     

Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array

Purpose

The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application.

Methods

3M??s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability.

Results

Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations.

Conclusions

3M??s hMTS can provide rapid, intradermal delivery of 300?C1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery.     

Simultaneous Quantification of Perfusion and Permeability in the Prostate Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging with an Inversion-Prepared Dual-Contrast Sequence

The aim of the present study was to quantify both perfusion and extravasation in the prostate to discriminate tumor from healthy tissue, which might be achieved by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a nonspecific low-molecular-weight contrast medium (CM). To determine extravasation as well as tissue perfusion an inversion-prepared dual-contrast sequence employing a parallel acquisition technique (PAT) was designed for interleaved acquisition of T ₁-weighted images for extravasation measurement and T2-weighted images for determination of the highly concentrated bolus with a sufficiently high temporal and spatial resolution at an acceptable signal-to-noise ratio. Thirteen patients with proven prostate cancer were examined with the sequence using a combined body-array prostate coil. Before pharmacokinetic evaluation the images were intensity-corrected and, if required, motion-corrected. The pharmacokinetic model used to calculate perfusion, permeability, blood volume, interstitial volume, transit time, and vessel size index included two compartments and a correction of delay and dispersion of the arterial input function. The information provided by the dual-contrast sequence allowed application of a more elaborate model for evaluation and enabled quantification of all parameters. Peripheral prostate tumors were found to differ from peripheral healthy prostate tissue in perfusion (1.38 mL/(min cm³) vs. 0.23 mL/(min cm³), p = 0.004), mean transit time (2.88 vs. 4.88 s, p = 0.039), and blood volume (1.9  vs. 0.7%, p = 0.019). A inversion-prepared dual-contrast sequence acquiring T ₁- and -weighted images with sufficient temporal resolution and signal-to-noise ratio was successfully applied in patients with prostate cancer to quantify all pharmacokinetic parameters of inflow and extravasation of a low-molecular-weight inert tracer.