Permanent relief from intermittent cold stress-induced fibromyalgia-like abnormal pain by repeated intrathecal administration of antidepressants

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is characterized by chronic widespread pain, which is often refractory to conventional painkillers. Numerous clinical studies have demonstrated that antidepressants are effective in treating FM pain. We previously established a mouse model of FM-like pain, induced by intermittent cold stress (ICS).</p> <p>Results</p> <p>In this study, we find that ICS exposure causes a transient increase in plasma corticosterone concentration, but not in anxiety or depression-like behaviors. A single intrathecal injection of an antidepressant, such as milnacipran, amitriptyline, mianserin or paroxetine, had an acute analgesic effect on ICS-induced thermal hyperalgesia at post-stress day 1 in a dose-dependent manner. In addition, repeated daily antidepressant treatments during post-stress days 1-5 gradually reversed the reduction in thermal pain threshold, and this recovery was maintained for at least 7 days after the final treatment. In addition, relief from mechanical allodynia, induced by ICS exposure, was also observed at day 9 after the cessation of antidepressant treatment. In contrast, the intravenous administration of these antidepressants at conventional doses failed to provide relief.</p> <p>Conclusions</p> <p>These results suggest that the repetitive intrathecal administration of antidepressants permanently cures ICS-induced FM pain in mice.</p

Innovation, technology and user experience in museums: insights from scientific literature

Museums play an important role in preserving the heritage and cultural legacy of humanity, however, one of their main weaknesses in regards the user is their static nature. At present, and in the face of the development of diverse technologies and the ease of access to information, museums have upgraded their implementation of technologies aimed at improving the user experience, trying more and more to access younger audiences with a sensitivity and natural capacity for the management of new technologies. This work identifies trends in the use of technological tools by museums worldwide and the effect of these on the user or visitor experience through a review of scientific literature. To complete the work, we performed a search of the publications in the Scopus® referencing database, and downloaded, processed, and visualized the data using the VOSviewer® tool. The main trends identified in this context of analysis are related to the role of museums with the development and improvement of the user experience; orientation to young audiences and innovation driven by the user through Interactive Systems, digital games, QR Codes, apps, augmented reality, virtual reality and gamification, among others. The objective of the implementation of new technologies in the context of museums is to satisfy the needs of contemporary communication, for all types of content and aimed at an increasingly digital audience, in order to ensure positive interaction and feedback from ideas with social and cultural changes

A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia

William L Pridgen,1 Carol Duffy,2 Judy F Gendreau,3 R Michael Gendreau3 1Innovative Med Concepts, LLC, 2Department of Biological Sciences, University of Alabama, Tuscaloosa, AL, 3Gendreau Consulting, LLC, Poway, CA, USA Objective: Infections and other stressors have been implicated in the development of fibromyalgia. We hypothesized that these stressors could result in recurrent reactivations of latent herpes virus infections, which could lead to the development of fibromyalgia. This study evaluated a famciclovir + celecoxib drug combination (IMC-1), active against suspected herpes virus reactivation and infection, for the treatment of fibromyalgia.Methods: A total of 143 fibromyalgia patients were enrolled at 12 sites in a 16-week, double-blinded, placebo-controlled proof-of-concept trial. Randomized patients received either IMC-1 or placebo in a 1:1 ratio. Outcome measures included a 24-hour recall pain Numerical Rating Scale, the Revised Fibromyalgia Impact Questionnaire (FIQ-R), the Patient&rsquo;s Global Impression of Change (PGIC) questionnaire, the Multidimensional Fatigue Inventory, the NIH Patient-Reported Outcomes Measurement Information System (PROMIS), and the Beck Depression Inventory-II conducted at baseline and weeks 6, 12, and 16 of the study.Results: A significant decrease in fibromyalgia-related pain was observed for patients on IMC-1 treatment versus placebo. PGIC response rates were significantly improved with IMC-1 treatment. Overall, patient self-reported functioning, as measured by the FIQ-R, was significantly improved. Fatigue was also significantly improved as measured by the PROMIS fatigue inventory. The safety profile was encouraging. Despite the celecoxib component of IMC-1, gastrointestinal and nervous system treatment emergent adverse events were reported less frequently in the IMC-1 group, and study completion rates favored IMC-1 treatment.Conclusion: IMC-1 was efficacious and safe in treating symptoms of fibromyalgia, supporting the hypothesis that herpes virus infections may contribute to this syndrome. Improved retention rates, decreased adverse event rates, and evidence of efficacy on a broad spectrum of outcome measures are suggestive that IMC-1 may represent an effective, novel treatment for fibromyalgia. Keywords: fibromyalgia, famciclovir, celecoxib, antiviral, herpes viru

A NICER Look at Strong X-Ray Obscuration in the Seyfert-2 Galaxy NGC 4388

We present an analysis of the time-averaged spectrum of the Seyfert-2 active galaxy NGC 4388, obtained by NICER. The intrinsic strength of the reflection spectrum in NGC 4388, the large collecting area and favorable pass band of NICER, and a net exposure of 105.6 ks yielded an exceptionally sensitive spectrum. Using two independent families of models, the intrinsic spectrum from the central engine is found to be highly obscured but not Compton-thick. Enforcing physical self-consistency within each model, the independent treatments give formally consistent results: N_H = 2.67 (-0.03,+0.02) E+23 cm^-2 or N_H = 2.64 (-0.03, +0.03) E+23 cm^-2. Past measurements made with Suzaku and XMM-Newton are in broad agreement with these column density values. A more recent measurement with NuSTAR (in late 2013) recorded a column density about twice as large; the robustness of this variability is reinforced by the use of consistent models and procedures. The neutral Fe K-alpha line in the NICER spectrum is nominally resolved and consistent with an origin in the optical broad line region (BLR). The data also require ionized absorption in the Fe K band, similar to the "warm absorbers" detected in Seyfert-1 active galactic nuclei (AGN). The low-energy spectrum is consistent with a set of ionized plasma components. We discuss these findings and note that the geometric inferences that derive from this analysis can be tested with XRISM and Athena.Comment: Accepted for publication in Ap