Non-geometric fluxes and mixed-symmetry potentials

We discuss the relation between generalised fluxes and mixed-symmetry potentials. We first consider the NS fluxes, and point out that the `non-geometric' $R$ flux is dual to a mixed-symmetry potential with a set of nine antisymmetric indices. We then consider the T-duality family of fluxes whose prototype is the Scherk-Schwarz reduction of the S-dual of the RR scalar of IIB supergravity. Using the relation with mixed-symmetry potentials, we are able to give a complete classification of these fluxes, including the ones that are non-geometric. The non-geometric fluxes again turn out to be dual to potentials containing nine antisymmetric indices. Our analysis suggests that all these fluxes can be understood in the context of double field theory, although for the non-geometric ones one expects a violation of the strong constraint.Comment: 19 pages, refs. adde

Spectral-Domain Optical Coherence Tomography Features of Acute Syphilitic Posterior Placoid Chorioretinitis: The Role of Autoimmune Response in Pathogenesis

Purpose: Syphilis is an infectious disease that can cause a wide variety of ocular signs. One of the rarest manifestations of ocular syphilis is acute syphilitic posterior placoid chorioretinitis (ASPPC). We report on the spectral-domain optical coherence tomography (SD-OCT) features of a case diagnosed with unilateral ASPPC. Methods: A 64-year-old man presented with a sudden loss of visual acuity (VA) in the right eye. His only clinical sign was a large, geographic, yellow-white lesion centered on the right fovea. Our patient was studied with SD-OCT on presentation and during follow-up, as well as with fluorescein and indocyanine green angiography, electrophysiological study, and serologic and autoimmune screening. Results: Laboratory workup revealed positive serology for active syphilis and elevated anti-beta2 glycoprotein I antibodies. SD-OCT showed a marked distortion of both the choroidal and outer retinal architecture. After treatment, best-corrected VA improved to 20/25. Pattern electroretinography displayed a severe reduction of P50 amplitude, which improved in late follow-up. Six months after presentation, VA was 20/25 and anti-beta2 glycoprotein I antibodies returned to normal levels. Conclusions: Our findings are compatible with immunologically mediated temporary physiological impairment of the neuroretina, since the changes seen by SD-OCT could not have normalized if they were due to anatomical injury. The results of our study provide clues to understanding the pathogenesis of this disease and allow us to define a characteristic temporal sequence of events in ASPPC

Diversity of oat varieties in eliciting the early inflammatory events in celiac disease

Purpose Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic\u2013tryptic digests of the proteins of the oat cultivars. Methods K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42\u201344 in T84 cells were the early gliadin-dependent events studied. Results The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti-gliadin antibodies. Conclusion We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety

Effectiveness of manual therapy compared to usual care by the general practitioner for chronic tension-type headache: design of a randomised clinical trial

<p>Abstract</p> <p>Background</p> <p>Patients with Chronic Tension Type Headache (CTTH) report functional and emotional impairments (loss of workdays, sleep disturbances, emotional well-being) and are at risk for overuse of medication. Manual therapy may improve symptoms through mobilisation of the spine, correction of posture, and training of cervical muscles.</p> <p>We present the design of a randomised clinical trial (RCT) evaluating the effectiveness of manual therapy (MT) compared to usual care by the general practitioner (GP) in patients with CTTH.</p> <p>Methods and design</p> <p>Patients are eligible for participation if they present in general practice with CTTH according to the classification of the International Headache Society (IHS).</p> <p>Participants are randomised to either usual GP care according to the national Dutch general practice guidelines for headache, or manual therapy, consisting of mobilisations (high- and low velocity techniques), exercise therapy for the cervical and thoracic spine and postural correction. The primary outcome measures are the number of headache days and use of medication. Secondary outcome measures are severity of headache, functional status, sickness absence, use of other healthcare resources, active cervical range of motion, algometry, endurance of the neckflexor muscles and head posture. Follow-up assessments are conducted after 8 and 26 weeks.</p> <p>Discussion</p> <p>This is a pragmatic trial in which interventions are offered as they are carried out in everyday practice. This increases generalisability of results, but blinding of patients, GPs and therapists is not possible.</p> <p>The results of this trial will contribute to clinical decision making of the GP regarding referral to manual therapy in patients with chronic tension headache.</p

The combined impact of sauerkraut with Leuconostoc mesenteroides to enhance immunomodulatory activity in Escherichia coli-infected mice

This study investigated the combined impact of sauerkraut and Leuconostoc mesenteroides culture on immunomodulatory activity in experimental animal. The in vivo immunomodulatory activity of Escherichia coli-infected Balb-C mice was ascertained in fermented sauerkrauts [test vs. control]. Both sauerkrauts enhanced the adaptive immune response [evidenced by an increase in CD4+ CD8+ IFN-γ, TNFα] and innate immune response [represented by a decrease of CD68-IL-6]. Nev- ertheless, the in vivo immunomodulatory activity of sauerkraut combined with L. mesenteroides was higher than that shown in sauerkraut control solely

ANTHOCYANIN PROFILE AND ANTIOXIDANT ACTIVITY OF UNFERMENTED GRAPE DERIVATIVES

Since the first observations of the \u201cFrench paradox\u201d, numerous studies have been developed to test the antioxidant and health-promoting effects of phenolic compounds present in grapes and wine. These findings, together with the negative campaign against alcoholic beverages, have led to a considerable interest in the evaluation of unfermented grape by-products as skin, seeds and juices. These products are also being employed as ingredients of dietary supplements, but in most cases data about the actual polyphenol content are scarce. To support scientifically the biological activity of unfermented beverages and dietary supplements, it is important to know the associated profile of the active compounds. The aim of this study was to evaluate in parallel the antioxidant activity, the total polyphenol content (TPC) and the HPLC anthocyanin profiles of grape derivatives: fresh grape juices and dietary supplements. The antioxidant activity was measured spectrophotometrically at 517 nm after reaction with 1,1-diphenyl-2-picrylhydrazyl free radical. The TPC was determined with the Folin-Ciocalteu colorimetric assay, measuring the absorbance at 765 nm. Anthocyanins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) were analyzed by HPLC using a gradient elution and a diode-array detector. Anthocyanins were identified and quantified in grape derivatives by comparing their chromatographic behaviour with purified standards (retention times and the UV spectra). Among grape juices, the highest value of TPC was 1570.5\ub11.60 g GA/L (gallic acid equivalent/L) found in a fresh red grape juice, and the lowest 212.4\ub16.25 g GA/L in a fresh white grape juice. Our data show that red grape juices show a good polyphenol content justifying their use as an alternative source of antioxidant compounds. Comparison between anthocyanin profiles of grape derivatives and grape-based food supplements will be discussed taking into account data on bioavailability reported in the scientific literature

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Mapa de series, geoseries y geopermaseries de vegetación de España (Memoria del mapa de vegetación potencial de España). Parte II

Peer Reviewe

Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer : final results of a randomised phase 2 clinical trial

The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC). A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS. Results: Two hundred and twenty-one patients were randomised and 190 (101 and 89 patients in the placebo and the Vx-001 arm, respectively) were analysed for efficacy. There was not treatment-related toxicity >grade 2. The study did not meet its primary endpoint (median OS 11.3 and 14.3 months for the placebo and the Vx-001, respectively; p = 0.86) whereas the median Time to Treatment Failure (TTF) was 3.5 and 3.6 months, respectively. Disease control for >6months was observed in 30 (33.7%) and 26 (25.7%) patients treated with Vx-001 and placebo, respectively. There was no documented objective CR or PR. Long lasting TERT-specific immune response was observed in 29.2% of vaccinated patients who experienced a significantly longer OS compared to non-responders (21.3 and 13.4 months, respectively; p = 0.004). Vx-001 could induce specific CD8 immune response but failed to meet its primary endpoint. Subsequent studies have to be focused on the identification and treatment of subgroups of patients able to mount an effective immunological response to Vx-001. Clinical trial registration: NCT0193515