ULTRA-TRACE DETERMINATION OF IRIDIUM BY ETV/ICP-MS USING CHEMICAL MODIFIERS

Joint Research on Environmental Science and Technology for the Eart

A putative relay circuit providing low-threshold mechanoreceptive input to lamina I projection neurons via vertical cells in lamina II of the rat dorsal horn

Background: Lamina I projection neurons respond to painful stimuli, and some are also activated by touch or hair movement. Neuropathic pain resulting from peripheral nerve damage is often associated with tactile allodynia (touch-evoked pain), and this may result from increased responsiveness of lamina I projection neurons to non-noxious mechanical stimuli. It is thought that polysynaptic pathways involving excitatory interneurons can transmit tactile inputs to lamina I projection neurons, but that these are normally suppressed by inhibitory interneurons. Vertical cells in lamina II provide a potential route through which tactile stimuli can activate lamina I projection neurons, since their dendrites extend into the region where tactile afferents terminate, while their axons can innervate the projection cells. The aim of this study was to determine whether vertical cell dendrites were contacted by the central terminals of low-threshold mechanoreceptive primary afferents. Results: We initially demonstrated contacts between dendritic spines of vertical cells that had been recorded in spinal cord slices and axonal boutons containing the vesicular glutamate transporter 1 (VGLUT1), which is expressed by myelinated low-threshold mechanoreceptive afferents. To confirm that the VGLUT1 boutons included primary afferents, we then examined vertical cells recorded in rats that had received injections of cholera toxin B subunit (CTb) into the sciatic nerve. We found that over half of the VGLUT1 boutons contacting the vertical cells were CTb-immunoreactive, indicating that they were of primary afferent origin. Conclusions: These results show that vertical cell dendritic spines are frequently contacted by the central terminals of myelinated low-threshold mechanoreceptive afferents. Since dendritic spines are associated with excitatory synapses, it is likely that most of these contacts were synaptic. Vertical cells in lamina II are therefore a potential route through which tactile afferents can activate lamina I projection neurons, and this pathway could play a role in tactile allodynia

Defining a spinal microcircuit that gates myelinated afferent input: implications for tactile allodynia

Chronic pain presents a major unmet clinical problem. The development of more effective treatments is hindered by our limited understanding of the neuronal circuits underlying sensory perception. Here, we show that parvalbumin (PV)-expressing dorsal horn interneurons modulate the passage of sensory information conveyed by low-threshold mechanoreceptors (LTMRs) directly via presynaptic inhibition and also gate the polysynaptic relay of LTMR input to pain circuits by inhibiting lamina II excitatory interneurons whose axons project into lamina I. We show changes in the functional properties of these PV interneurons following peripheral nerve injury and that silencing these cells unmasks a circuit that allows innocuous touch inputs to activate pain circuits by increasing network activity in laminae I–IV. Such changes are likely to result in the development of tactile allodynia and could be targeted for more effective treatment of mechanical pain

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Circuit dissection of the role of somatostatin in itch and pain

Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

Macro-scale transport of the excitation energy along a metal nanotrack: exciton-plasmon energy transfer mechanism

Presently we report (i) excited state (exciton) propagation in a metal nanotrack over macroscopic distances, along with (ii) energy transfer from the nanotrack to adsorbed dye molecules. We measured the rates of both of these processes. We concluded that the effective speed of exciton propagation along the nanotrack is about 8 × 107 cm/s, much lower than the surface plasmon propagation speed of 1.4 × 1010 cm/s. We report that the transmitted energy yield depends on the nanotrack length, with the energy emitted from the surface much lower than the transmitted energy, i.e. the excited nanotrack mainly emits in its end zone. Our model thus assumes that the limiting step in the exciton propagation is the energy transfer between the originally prepared excitons and surface plasmons, with the rate constant of about 5.7 × 107 s-1. We also conclude that the energy transfer between the nanotrack and the adsorbed dye is limited by the excited-state lifetime in the nanotrack. Indeed, the measured characteristic buildup time of the dye emission is much longer than the characteristic energy transfer time to the dye of 81 ns, and thus must be determined by the excited state lifetime in the nanotrack. Indeed, the latter is very close to the characteristic buildup time of the dye emission. The data obtained are novel and very promising for a broad range of future applications.PR Institute of Functionalized Nanomaterials NASA EPSCoR grant (NASA Cooperative Agreement) NNX15AK43A National Centre for Research Resources NIH-NCRR-G12-RR03035 NIMHD-G12-MD007583info:eu-repo/semantics/publishedVersio

Lifestyle factors affecting gastroesophageal reflux disease symptoms: a cross-sectional study of healthy 19864 adults using FSSG scores

<p>Abstract</p> <p>Background</p> <p>Gastroesophageal reflux disease (GERD) is a very common disorder worldwide, comprised of reflux esophagitis (RE) and non-erosive reflux disease (NERD). As more than half of GERD patients are classified into the NERD group, precise evaluation of bothersome epigastric symptoms is essential. Nevertheless, compared with many reports targeting endoscopic reflux esophagitis, large-scale studies focusing on GERD symptoms have been very scarce.</p> <p>Methods</p> <p>To elucidate lifestyle factors affecting GERD symptoms, 19,864 healthy adults in Japan were analyzed. Sub-analyses of 371 proton pump inhibitor (PPI) users and 539 histamine H₂-receptor antagonist (H₂RA) users were also performed. Using the FSSG (Frequency Scale for the Symptoms of GERD) score as a response variable, 25 lifestyle-related factors were univariately evaluated by Student's <it>t</it>-test or Pearson's correlation coefficient, and were further analyzed with multiple linear regression modelling.</p> <p>Results</p> <p>Average FSSG scores were 4.8 ± 5.2 for total subjects, 9.0 ± 7.3 for PPI users, and 8.2 ± 6.6 for H₂RA users. Among the total population, positively correlated factors and standardized coefficients (β) for FSSG scores are inadequate sleep (β = 0.158), digestive drug users (β = 0.0972 for PPI, β = 0.0903 for H₂RA, and β = 0.104 for others), increased body weight in adulthood (β = 0.081), dinner just before bedtime (β = 0.061), the habit of midnight snack (β = 0.055), lower body mass index (β = 0.054), NSAID users (β = 0.051), female gender (β = 0.048), lack of breakfast (β = 0.045), lack of physical exercise (β = 0.035), younger age (β = 0.033), antihyperglycemic agents non-users (β = 0.026), the habit of quick eating (β = 0.025), alcohol drinking (β = 0.025), history of gastrectomy (β = 0.024), history of cardiovascular disease (β = 0.020), and smoking (β = 0.018). Positively correlated factors for PPI users are female gender (β = 0.198), inadequate sleep (β = 0.150), lack of breakfast (β = 0.146), antihypertensive agent non-users (β = 0.134), and dinner just before bedtime (β = 0.129), whereas those for H₂RA users are inadequate sleep (β = 0.248), habit of midnight snack (β = 0.160), anticoagulants non-users (β = 0.106), and antihypertensive agents non-users (β = 0.095).</p> <p>Conclusions</p> <p>Among many lifestyle-related factors correlated with GERD symptoms, poor quality of sleep and irregular dietary habits are strong risk factors for high FSSG scores. At present, usual dose of PPI or H₂RA in Japan cannot fully relieve GERD symptoms.</p

Trans-oral robotic surgery and surgeon-performed trans-oral ultrasound for intraoperative location and excision of an isolated retropharyngeal lymph node metastasis of papillary thyroid carcinoma

Background Retropharyngeal metastases are uncommon but a well-known location for regional spread of well-differentiated thyroid carcinoma (WDTC). Surgeon-performed, trans-oral ultrasound (SP-TO-US) and trans-oral robot-assisted surgical (TORS) excision represent a unique combination of technology and techniques in the treatment of isolated retropharyngeal thyroid metastases. Patient findings A patient with a history of T3N1b papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy, left central and lateral neck dissection, and radioactive iodine presented with progressive elevations in serum thyroglobulin (Tg) from baseline of 0.2 to 0.6 μg/L. She was found to have an isolated 2.6 cm left retropharyngeal nodal metastasis on MRI that was confirmed to be PTC on fine needle aspiration biopsy. She underwent SP-TO-US for identification of the node in the operating room immediately prior to TORS excision. There were no complications. Additional radioactive iodine was administered. Post-treatment iodine scans revealed resolution of avid uptake in left retropharynx and return of Tg to 0.2 μg/L. Summary The combination of SP-TO-US and TORS represents a novel combination of technology and technique for treatment of isolated retropharyngeal metastasis in WDTC. Trans-oral ultrasound allows for rapid localization of the lesion in relation to the adjacent neurovascular structures in the parapharynx while the robot-assisted approach affords a safe and effective dissection through the improved visualization and dexterity in a small working space. Our patient had no complications and only short-term dysphagia that resolved after temporary diet alteration. Risks and long-term morbidities associated with classical approaches to the retropharynx including trans-cervical and trans-mandibular, particularly in a previously dissected field, are avoided through this trans-oral approach. Conclusions Retropharyngeal metastases are a known location for regional spread of WDTC and are amenable to evaluation and biopsy using TO-US by both surgical and non-surgical providers. In cases where lateral neck dissection has already been performed or when traditional transcervical or transmandibular approaches to the retropharynx represent a comparatively extensive procedure for isolated metastases, SP-TO-US and TORS are safe and effective combination for surgical management of disease

The control of alternative splicing by SRSF1 in myelinated afferents contributes to the development of neuropathic pain

Neuropathic pain results from neuroplasticity in nociceptive neuronal networks. Here we demonstrate that control of alternative pre-mRNA splicing, through the splice factor serine-arginine splice factor 1 (SRSF1), is integral to the processing of nociceptive information in the spinal cord. Neuropathic pain develops following a partial saphenous nerve ligation injury, at which time SRSF1 is activated in damaged myelinated primary afferent neurons, with minimal found in small diameter (IB4 positive) dorsal root ganglia neurons. Serine arginine protein kinase 1 (SRPK1) is the principal route of SRSF1 activation. Spinal SRPK1 inhibition attenuated SRSF1 activity, abolished neuropathic pain behaviors and suppressed central sensitization. SRSF1 was principally expressed in large diameter myelinated (NF200-rich) dorsal root ganglia sensory neurons and their excitatory central terminals (vGLUT1 + ve) within the dorsal horn of the lumbar spinal cord. Expression of pro-nociceptive VEGF-Axxxa within the spinal cord was increased after nerve injury, and this was prevented by SRPK1 inhibition. Additionally, expression of anti-nociceptive VEGF-Axxxb isoforms was elevated, and this was associated with reduced neuropathic pain behaviors. Inhibition of VEGF receptor-2 signaling in the spinal cord attenuated behavioral nociceptive responses to mechanical, heat and formalin stimuli, indicating that spinal VEGF receptor-2 activation has potent pro-nociceptive actions. Furthermore, intrathecal VEGF-A165a resulted in mechanical and heat hyperalgesia, whereas the sister inhibitory isoform VEGF-A165b resulted in anti-nociception. These results support a role for myelinated fiber pathways, and alternative pre-mRNA splicing of factors such as VEGF-A in the spinal processing of neuropathic pain. They also indicate that targeting pre-mRNA splicing at the spinal level could lead to a novel target for analgesic development