Urinary Bladder Irritation Alters Efficacy of Vagal Stimulation on Rostral Medullary Neurons in Chronic T8 Spinalized Rats

ABSTRACT The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary reticular formation (MRF) neurons, 371 neurons in 15 rats responsive to pinching the ear (search stimulus) were tested for somato-visceral and viscero-visceral convergent responses to stimulation of the following nerves/territories: VAG-abd, dorsal nerve of the penis, pelvic nerve, distention of urinary bladder and colon, penile stimulation, urethral infusion, and touch/pinch of the entire body surface. In addition to these mechanical and electrical stimuli, a chemical stimulus applied to the bladder was assessed as well. Of the total neurons examined, 205 were tested before and 166 tested beginning 20 min after application of a chemical irritant (2% acetic acid) to the urinary bladder (same rats used pre/post irritation). As with intact controls, many earresponsive MRF neurons responded to the electrical stimulation of VAG-abd. Although MRF neuron responses failed to be evoked with direct (mechanical and electrical nerve) pelvic visceral stimuli, acute chemical irritation of the urinary bladder produced a significant increase in the number of MRF neurons responsive to stimulation of VAG-abd. The results of this study indicate a central effect that potentially relates to some of the generalized below level pelvic visceral sensations that have been documented in patients with complete spinal cord injury

Acute liver failure due to primary angiosarcoma: A case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Hepatic angiosarcoma is a primary sarcoma of the liver, accounting for only 2% of all primary hepatic malignancies. Acute liver failure is an extremely rare presentation of a primary liver tumour.</p> <p>Case presentation</p> <p>We report a case of a seventy year-old man who presented with a very short period of jaundice leading to fulminant hepatic failure (FHF). On further investigation he was found to have primary angiosarcoma of liver.</p> <p>Conclusion</p> <p>The treatment outcomes for hepatic angiosarcoma are poor, we discuss the options available and the need for prompt investigation and establishment of a diagnosis</p

CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.

Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus. HCV pseudoparticles infect liver-derived cells, supporting a model in which liver-specific molecules define HCV internalization. Three host cell molecules have been reported to be important entry factors or receptors for HCV internalization: scavenger receptor BI, the tetraspanin CD81, and the tight junction protein claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver, leading us to hypothesize that their organization within hepatocytes may explain receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in the entry process, we investigated their association in a variety of cell lines and human liver tissue. Imaging techniques that take advantage of fluorescence resonance energy transfer (FRET) to study protein-protein interactions have been developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red-monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET occurred between the tagged coreceptors at comparable frequencies in permissive and nonpermissive cells, consistent with the formation of coreceptor complexes. FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations, suggesting distinct roles in the viral entry process

Targeted Selection of Stimulation Parameters for Restoration of Motor and Autonomic Function in Individuals With Spinal Cord Injury

Study Design: This is a report of methods and tools for selection of task and individual configurations targeted for voluntary movement, standing, stepping, blood pressure stabilization, and facilitation of bladder storage and emptying using tonic-interleaved excitation of the lumbosacral spinal cord. Objectives: This study aimed to present strategies used for selection of stimulation parameters for various motor and autonomic functions. Conclusions: Tonic-interleaved functionally focused neuromodulation targets a myriad of consequences from spinal cord injury with surgical implantation of the epidural electrode at a single location. This approach indicates the sophistication of the human spinal cord circuitry and its important role in the regulation of motor and autonomic functions in humans

SS Ari: a shallow-contact close binary system

Two CCD epochs of light minimum and a complete R light curve of SS Ari are presented. The light curve obtained in 2007 was analyzed with the 2003 version of the W-D code. It is shown that SS Ari is a shallow contact binary system with a mass ratio $q=3.25$ and a degree of contact factor f=9.4(\pm0.8%). A period investigation based on all available data shows that there may exist two distinct solutions about the assumed third body. One, assuming eccentric orbit of the third body and constant orbital period of the eclipsing pair results in a massive third body with $M_3=1.73M_{\odot}$ and P_3=87.0$yr. On the contrary, assuming continuous period changes of the eclipsing pair the orbital period of tertiary is 37.75yr and its mass is about$0.278M_{\odot}$. Both of the cases suggest the presence of an unseen third component in the system.Comment: 28 pages, 9 figures and 5 table

The reliability of eyetracking to assess attentional bias to threatening words in healthy individuals

Eyetracking is commonly used to investigate attentional bias. Although some studies have investigated the internal consistency of eyetracking, data are scarce on the test–retest reliability and agreement of eyetracking to investigate attentional bias. This study reports the test–retest reliability, measurement error, and internal consistency of 12 commonly used outcome measures thought to reflect the different components of attentional bias: overall attention, early attention, and late attention. Healthy participants completed a preferential-looking eyetracking task that involved the presentation of threatening (sensory words, general threat words, and affective words) and nonthreatening words. We used intraclass correlation coefficients (ICCs) to measure test–retest reliability (ICC \u3e .70 indicates adequate reliability). The ICCs(2, 1) ranged from –.31to.71. Reliability varied according to the outcome measure and threat word category. Sensory words had a lower mean ICC (.08) than either affective words (.32) or general threat words (.29). A longer exposure time was associated with higher test–retest reliability. All of the outcome measures, except second-run dwell time, demonstrated low measurement error (\u3c6%). Most of the outcome measures reported high internal consistency (α \u3e.93). Recommendations are discussed for improving the reliability of eyetracking tasks in future research

CD40 Activation Induces Apoptosis in Cultured Human Hepatocytes via Induction of Cell Surface Fas Ligand Expression and Amplifies Fas-mediated Hepatocyte Death during Allograft Rejection

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68+ macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved

Movement restriction does not modulate sensory and perceptual effects of exercise-induced arm pain

BACKGROUND: Movement restriction has been proposed as an important modulator of changes in sensory and perceptual function and motor imagery performance that are observed in musculoskeletal pain syndromes. There are no empirical data to support this view. PURPOSE: The primary objective of this experiment was to determine the effects of movement restriction on local and widespread sensory, perceptual and motor imagery changes after exercise-induced muscular pain. Further objectives were to investigate whether changes in sensory perception are correlated with pain intensity and tactile acuity or motor imagery performance. METHODS: In forty healthy volunteers, delayed onset muscle soreness (DOMS) of the non-dominant elbow flexors was induced using eccentric contractions until exhaustion. Participants were then randomised into two groups: a movement restriction group (wearing a sling) or a control group (not wearing a sling). Sensory and perceptual functions were measured using a range of sensory tests and a motor imagery performance task (left/right limb judgements). RESULTS: Movement restriction did not modulate any of the measures. We found concurrent mechanical hypoesthesia (p \u3c 0.01), reduced tactile acuity (p = 0.02) and pressure hyperalgesia (p \u3c 0.01) at the painful side. We found evidence of widespread pressure hyperalgesia. Impaired tactile acuity was associated with a decrease in pain threshold to pressure (r = -0.34, p = 0.03). Motor imagery performance was unchanged (p \u3e 0.35) by pain or movement restriction. CONCLUSION: Short-term movement restriction did not influence local and widespread sensory changes induced by experimentally induced muscular pain

Systematic reviews that include only published data may overestimate the effectiveness of analgesic medicines for low back pain: A systematic review and meta-analysis

Objective: Systematic reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n = 5 individual source systematic reviews. We reproduced the meta-analyses using data available from the original reviews and then reran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared with sham, for recent-onset low back pain from −21.71 (95% CI: −28.23 to −15.19) to −2.34 (95% CI: −3.34 to −1.34) on a 0–100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared with sham, for chronic low back pain from −10.10 (95% CI: −12.81 to −7.39) to −9.31 (95% CI: −11.51 to −7.11). The effect reduced in the subgroup of enriched design studies, from −12.40 (95% CI: −16.90 to −7.91) to −11.34 (95% CI: −15.36 to −7.32), and in the subgroup of nonenriched design studies, from −7.27 (95% CI: −9.97 to −4.57) to −7.19 (95% CI: −9.24 to −5.14). Conclusion: Systematic reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful

Reviews may overestimate the effectiveness of medicines for back pain: Systematic review and meta-analysis

Objective: Systematic-reviews of analgesics for low back pain generally include published data only. Obtaining data from unpublished trials is potentially important because they may impact effect sizes in meta-analyses. We determined whether including unpublished data from trial registries changes the effect sizes in meta-analyses of analgesics for low back pain. Study Design and Setting: Trial registries were searched for unpublished data that conformed to the inclusion criteria of n=5 individual source systematic-reviews. We reproduced the meta-analyses using data available from the original reviews then re-ran the same analyses with the addition of new unpublished data. Results: Sixteen completed, unpublished, trials were eligible for inclusion in four of the source reviews. Data were available for five trials. We updated the analyses for two of the source reviews. The addition of data from two trials reduced the effect size of muscle relaxants, compared to sham, for recent-onset low back pain from -21.71 (95%CI -28.23 to -15.19) to -2.34 (95%CI -3.34 to -1.34) on a 0-100 scale for pain intensity. The addition of data from three trials (one enriched design) reduced the effect size of opioid analgesics, compared to sham, for chronic low back pain from -10.10 (95%CI -12.81 to -7.39) to -9.31 (95%CI -11.51 to -7.11). The effect reduced in the subgroup of enriched design studies, from -12.40 (95%CI -16.90 to -7.91) to 11.34 (95%CI -15.36 to -7.32), and in the subgroup of non-enriched design studies; from -7.27 (95%CI -9.97 to -4.57) to -7.19 (95%CI -9.24 to -5.14). Conclusion: Systematic-reviews should include reports of unpublished trials. The result for muscle relaxants conflicts with the conclusion of the published review and recent international guidelines. Adding unpublished data strengthens the evidence that opioid analgesics have small effects on persistent low back pain and more clearly suggests these effects may not be clinically meaningful