Brain oscillations differentially encode noxious stimulus intensity and pain intensity

Noxious stimuli induce physiological processes which commonly translate into pain. However, under certain conditions, pain intensity can substantially dissociate from stimulus intensity, e.g. during longer-lasting pain in chronic pain syndromes. How stimulus intensity and pain intensity are differentially represented in the human brain is, however, not yet fully understood. We therefore used electroencephalography (EEG) to investigate the cerebral representation of noxious stimulus intensity and pain intensity during 10 min of painful heat stimulation in 39 healthy human participants. Time courses of objective stimulus intensity and subjective pain ratings indicated a dissociation of both measures. EEG data showed that stimulus intensity was encoded by decreases of neuronal oscillations at alpha and beta frequencies in sensorimotor areas. In contrast, pain intensity was encoded by gamma oscillations in the medial prefrontal cortex. Contrasting right versus left hand stimulation revealed that the encoding of stimulus intensity in contralateral sensorimotor areas depended on the stimulation side. In contrast, a conjunction analysis of right and left hand stimulation revealed that the encoding of pain in the medial prefrontal cortex was independent of the side of stimulation. Thus, the translation of noxious stimulus intensity into pain is associated with a change from a spatially specific representation of stimulus intensity by alpha and beta oscillations in sensorimotor areas to a spatially independent representation of pain by gamma oscillations in brain areas related to cognitive and affective-motivational processes. These findings extend the understanding of the brain mechanisms of nociception and pain and their dissociations during longer-lasting pain as a key symptom of chronic pain syndromes

Prefrontal gamma oscillations encode tonic pain in humans

Under physiological conditions, momentary pain serves vital protective functions. Ongoing pain in chronic pain states, on the other hand, is a pathological condition that causes widespread suffering and whose treatment remains unsatisfactory. The brain mechanisms of ongoing pain are largely unknown. In this study, we applied tonic painful heat stimuli of varying degree to healthy human subjects, obtained continuous pain ratings, and recorded electroencephalograms to relate ongoing pain to brain activity. Our results reveal that the subjective perception of tonic pain is selectively encoded by gamma oscillations in the medial prefrontal cortex. We further observed that the encoding of subjective pain intensity experienced by the participants differs fundamentally from that of objective stimulus intensity and from that of brief pain stimuli. These observations point to a role for gamma oscillations in the medial prefrontal cortex in ongoing, tonic pain and thereby extend current concepts of the brain mechanisms of pain to the clinically relevant state of ongoing pain. Furthermore, our approach might help to identify a brain marker of ongoing pain, which may prove useful for the diagnosis and therapy of chronic pain

Subakuter und chronischer Rückenschmerz in der hausärztlichen Versorgung: Eine systematische Übersichtsarbeit symptomevaluierender Studien

Hintergrund: Subakuter und chronischer Rückenschmerz ist ein häufiges Symptom in der Allgemeinmedizin. Symptome wiederum sind meist der Grund für eine Vorstellung beim Hausarzt. Dementsprechend liefern symptomevaluierende Studien wichtige Daten für dieses Patientenkollektiv. Interessante Zielgrößen sind unter anderem die Prävalenz, die Ätiologie und die Prognose. Ziel: In dieser systematischen Übersichtsarbeit wird die Literatur der letzten 50 Jahre durchsucht und symptomevaluierende Studien zum Thema subakuter und chronischer Rückenschmerzen beim Hausarzt analysiert, um den aktuellen Wissensstand zu diesem Thema zu erarbeiten. Methode: Studien wurden durch eine systematische Literatursuche in Pubmed identifiziert. Die gefundenen Studienzusammenfassungen wurden anhand zuvor definierter Ein- und Ausschlusskriterien von zwei Beurteilen bewertet. Die Volltexte der einschlägigen Studienzusammenfassungen wurde in gleicher Weise bewertet. Die Daten, der schließlich eingeschlossenen Studien/Publikationen wurden strukturiert extrahiert und die Studienqualität bewertet. Um eine Vergleichbarkeit der verschiedenen Ergebnisse zu gewährleisten wurde ein prozentueller Ergebniswert verwendet. Ergebnisse: 885 der 3794 Studienzusammenfassungen waren einschlägig. Von diesen 885 Publikation entsprachen 26 Publikationen von 15 Studien den Ein- und Ausschlusskriterien dieser Arbeit. Da die Daten der Arbeiten sehr inhomogen waren, wurde keine Metaanalyse durchgeführt, sondern eine deskriptive Auswertung durchgeführt. Der überwiegende Teil der Studien erhielt eine gute bis durchschnittliche Qualitätsbewertung. Eine Studien lieferte Daten zur Ätiologie chronischer Rückenschmerz und fand, dass 23.6 % der Patientin axiale Spondyloarthritis hatten, 22 % von diesen wiederum hatten Spondylitis ankylosans. Zwei Studien erbrachten Daten zur Prävalenz. Eine Studie zeigte, dass 1.3 % der Hausarztpatienten sich wegen chronischer Rückenschmerzen vorstellen. Die zweite Studie zeigte, dass 5.95 % der Chronisch-Kranken chronischen Rückenschmerz haben. Der überwiegende Teil der Ergebnisse ergab Prognosedaten. Die wesentlichen Ergebniskategorien waren: Schmerz, Lebensqualität, funktionelle Beeinträchtigung, arbeitsbezogene Ergebnisse und Stimmung. Die mittlere prozentuale Veränderung über 6 Monate betrug -2.9 bis +23.6 % im Bereich Lebensqualität, mit einer großen Spannweite innerhalb der einzelnen Subskalen. Im Bereich Schmerz war die mittlere prozentuale Veränderung -2.1 bis +11 % nach 6 Monaten. Nur eine Studie zeigte eine Verschlechterung der Schmerzsymptomatik. Die funktionelle Beeinträchtigung verbesserte sich im Mittel um +5.8 bis +6.8 % nach 6 Monaten. 48 bis 58 % der initial krankgeschriebenen Patientin waren auch noch nach 12 Monaten krank geschriebenen. Fazit: Diese systematische Übersichtsarbeit symptomevaluierender Studien zeigt eine Verbesserung der verschiedenen Ergebniskategorien über die Zeit. Es gibt wenig Literatur über Prävalenz und Ätiologie im Bezug auf das Symptom subakuter und chronischer Rückenschmerz in der Hausarztpraxis

ASASSN-16ae: A Powerful White-Light Flare on an Early-L Dwarf

We report the discovery and classification of SDSS~J053341.43+001434.1 (SDSS0533), an early-L dwarf first discovered during a powerful $\Delta V < -11$ magnitude flare observed as part of the ASAS-SN survey. Optical and infrared spectroscopy indicate a spectral type of L0 with strong H$\alpha$ emission and a blue NIR spectral slope. Combining the photometric distance, proper motion, and radial velocity of SDSS0533 yields three-dimensional velocities of $(U,V,W)=(14\pm13,-35\pm14,-94\pm22)$~km~s$^{-1}$, indicating that it is most likely part of the thick disk population and probably old. The three detections of SDSS0533 obtained during the flare are consistent with a total $V$-band flare energy of at least $4.9\times10^{33}$~ergs (corresponding to a total thermal energy of at least $E_{\rm tot}>3.7\times10^{34}$~erg), placing it among the strongest detected M dwarf flares. The presence of this powerful flare on an old L0 dwarf may indicate that stellar-type magnetic activity persists down to the end of the main sequence and on older ML transition dwarfs.Comment: 7 pages, 3 tables, 2 figures; accepted to ApJ Letters; updated to reflect referee response and proof correction

Thermal activation of catalytic microjets in blood samples using microfluidic chips

We demonstrate that catalytic microjet engines can out-swim high complex media composed of red blood cells and serum. Despite the challenge presented by the high viscosity of the solution at room temperature, the catalytic microjets can be activated at physiological temperature and, consequently, self-propel in diluted solutions of blood samples. We prove that these microjets self-propel in 10× diluted blood samples using microfluidic chips

A Stellar Population Gradient in VII Zw 403 - Implications for the Formation of Blue Compact Dwarf Galaxies

We present evidence for the existence of an old stellar halo in the Blue Compact Dwarf galaxy VII Zw 403. VII Zw 403 is the first Blue Compact Dwarf galaxy for which a clear spatial segregation of the resolved stellar content into a "core-halo" structure is detected. Multicolor HST/WFPC2 observations indicate that active star formation occurs in the central region, but is strikingly absent at large radii. Instead, a globular-cluster-like red giant branch suggests the presence of an old (> 10 Gyr) and metal poor (=-1.92) stellar population in the halo. While the vast majority of Blue Compact Dwarf galaxies has been recognized to possess halos of red color in ground-based surface photometry, our observations of VII Zw 403 establish for the first time a direct correspondence between a red halo color and the presence of old, red giant stars. If the halos of Blue Compact Dwarf galaxies are all home to such ancient stellar populations, then the fossil record conflicts with delayed-formation scenarios for dwarfs.Comment: Accepted for publication in the Ap

Association of a Workplace Sales Ban on Sugar-Sweetened Beverages With Employee Consumption of Sugar-Sweetened Beverages and Health.

ImportanceReductions in sugar-sweetened beverage (SSB) intake can improve health, but are difficult for individuals to achieve on their own.ObjectivesTo evaluate whether a workplace SSB sales ban was associated with SSB intake and cardiometabolic health among employees and whether a brief motivational intervention provides added benefits to the sales ban.Design, setting, and participantsThis before-after study and additional randomized trial conducted from July 28, 2015, to October 16, 2016, at a Northern California university and hospital assessed SSB intake, anthropometrics, and cardiometabolic biomarkers among 214 full-time English-speaking employees who were frequent SSB consumers (≥360 mL [≥12 fl oz] per day) before and 10 months after implementation of an SSB sales ban in a large workplace, with half the employees randomized to receive a brief motivational intervention targeting SSB reduction.InterventionsThe employer stopped selling SSBs in all workplace venues, and half the sample was randomized to receive a brief motivational intervention and the other half was a control group that did not receive the intervention. This intervention was modeled on standard brief motivational interventions for alcohol used in the workplace that promote health knowledge and goal setting.Main outcomes and measuresOutcomes included changes in SSB intake, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), and measures of abdominal adiposity. The primary associations tested were the correlation between changes in SSB intake and changes in HOMA-IR.ResultsAmong the 214 study participants, 124 (57.9%) were women, with a mean (SD) age of 41.2 (11.0) years and a baseline mean (SD) body mass index of 29.4 (6.5). They reported a mean daily intake of 1050 mL (35 fl oz) of SSBs at baseline and 540 mL (18 fl oz) at follow-up-a 510-mL (17-fl oz) (48.6%) decrease (P &lt; .001). Reductions in SSB intake correlated with improvements in HOMA-IR (r = 0.16; P = .03). Those not randomized to receive the brief intervention reduced their SSB intake by a mean (SD) of 246.0 (84.0) mL (8.2 [2.8] fl oz), while those also receiving the brief intervention reduced SSB intake by 762.0 (84.0) mL (25.4 [2.8] fl oz). From baseline to follow-up, there were significant reductions in mean (SE) waist circumference (2.1 [2.8] cm; P &lt; .001).Conclusions and relevanceThis study's findings suggest that the workplace sales ban was associated with a reduction in SSB intake and a significant reduction in waist circumference among employees within 10 months. The randomized clinical trial portion of this study found that targeting those at high risk with a brief motivational intervention led to additional improvements. Workplace sales bans may offer a promising new private-sector strategy for reducing the health harms of SSB intake.Trial registrationClinicalTrials.gov identifier: NCT02585336

Tumor suppressor FLCN inhibits tumorigenesis of a FLCN-null renal cancer cell line and regulates expression of key molecules in TGF-β signaling

<p>Abstract</p> <p>Background</p> <p>Germline mutations in the <it>FLCN </it>gene are responsible for the development of fibrofolliculomas, lung cysts and renal neoplasia in Birt-Hogg-Dube' (BHD) syndrome. The encoded protein folliculin (FLCN) is conserved across species but contains no classic motifs or domains and its function remains unknown. Somatic mutations or loss of heterozygosity in the remaining wild type copy of the <it>FLCN </it>gene have been found in renal tumors from BHD patients suggesting that <it>FLCN </it>is a classic tumor suppressor gene.</p> <p>Results</p> <p>To examine the tumor suppressor function of <it>FLCN</it>, wild-type or mutant <it>FLCN </it>(H255R) was stably expressed in a <it>FLCN-null </it>renal tumor cell line, UOK257, derived from a BHD patient. When these cells were injected into nude mice, tumor development was inversely dependent upon the level of wild-type <it>FLCN </it>expression. We identified genes that were differentially expressed in the cell lines with or without wild-type <it>FLCN</it>, many of which are involved in TGF-β signaling, including <it>TGF-β2 </it>(<it>TGFB2</it>)<it>, inhibin β A chain </it>(<it>INHBA</it>)<it>, thrombospondin 1 </it>(<it>THBS1</it>), <it>gremlin </it>(<it>GREM1</it>), and <it>SMAD3</it>. In support of the <it>in vitro </it>data, <it>TGFB2</it>, <it>INHBA</it>, <it>THBS1 </it>and <it>SMAD3 </it>expression levels were significantly lower in BHD-associated renal tumors compared with normal kidney tissue. Although receptor mediated SMAD phosphorylation was not affected, basal and maximal TGF-β-induced levels of <it>TGFB2</it>, <it>INHBA </it>and <it>SMAD7 </it>were dramatically reduced in <it>FLCN-null </it>cells compared with <it>FLCN</it>-restored cells. Secreted TGF-β2 and activin A (homo-dimer of INHBA) protein levels were also lower in <it>FLCN-null </it>cells compared with <it>FLCN</it>-restored cells. Consistent with a growth suppressive function, activin A (but not TGF-β2) completely suppressed anchorage-independent growth of <it>FLCN-null </it>UOK257 cells.</p> <p>Conclusions</p> <p>Our data demonstrate a role for <it>FLCN </it>in the regulation of key molecules in TGF-β signaling and confirm deregulation of their expression in BHD-associated renal tumors. Thus, deregulation of genes involved in TGF-β signaling by <it>FLCN </it>inactivation is likely to be an important step for tumorigenesis in BHD syndrome.</p