With molecular treatments coming into reach for spinocerebellar ataxia type 3 ( SCA 3), easily accessible, cross‐species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy ( pNfH ) in ataxic and preataxic subjects of two independent multicentric SCA 3 cohorts and in a SCA 3 knock‐in mouse model. Ataxic SCA 3 subjects showed increased levels of both NfL and pNfH . In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross‐sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA 3 were each paralleled by similar changes in SCA 3 knock‐in mice, here also starting already at the presymptomatic stage, closely following ataxin‐3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross‐species validated biomarkers in both ataxic and preataxic SCA 3, associated with earliest neuropathological changes, and serve as progression, proximity‐to‐onset and, potentially, treatment‐response markers in both human and preclinical SCA3 trials.

The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO.

ObjectivesThe aim of this study was to explore the views and experiences of a group of Spanish women suffering from chronic migraine (CM).SettingHeadache clinic at a university hospital in Madrid (Spain).ParticipantsPurposeful sampling of patients that attended a specialised headache clinic for the first time between June 2016 and February 2017 was performed. The patients included were females aged 18–65 and with positive diagnoses of CM according to the International Classification of Headache disorders (third edition, beta version), with or without medication overuse. Accordingly, 20 patients participated in the study with a mean age of 38.65 years (SD 13.85).DesignQualitative phenomenological study.MethodsData were collected through in-depth interviews, researchers’ field notes and patients’ drawings. A thematic analysis was performed following appropriate guidelines for qualitative research.ResultsFive main themes describing the significance of suffering emerged: (a) the shame of suffering from an invisible condition; (b) treatment: between need, scepticism and fear; (c) looking for physicians’ support and sincerity and fighting misconceptions; (d) limiting the impact on daily life through self-control; and (e) family and work: between understanding and disbelief. The disease is experienced as an invisible process, and the journey to diagnosis can be a long and tortuous one. Drug prescription by the physician is greeted with distrust and scepticism. Patients expect sincerity, support and the involvement of their doctors in relation to their disease. Pain becomes the main focus of the patient’s life, and it requires considerable self-control. The disease has a strong impact in the work and family environment, where the patient may feel misunderstood.ConclusionsQualitative research offers insight into the way patients with CM experience their disease and it may be helpful in establishing a more fruitful relationship with these patients.

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Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

Beer is a beverage consumed worldwide. It is produced from cereals (barley or wheat) and contains a wide array of bioactive phytochemicals and nutraceutical compounds. Specifically, high melatonin concentrations have been found in beer. Beers with high alcohol content are those that present the greatest concentrations of melatonin and vice versa. In this study, gel filtration chromatography and ELISA were combined for melatonin determination. We brewed beer to determine, for the first time, the beer production steps in which melatonin appears. We conclude that the barley, which is malted and ground in the early process, and the yeast, during the second fermentation, are the largest contributors to the enrichment of the beer with melatonin.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Melatonin is a molecule endogenously produced in a wide variety of immune cells, including mast cells (RBL-2H3). It exhibits immunomodulatory, anti-inflammatory and anti-apoptotic properties. The physiologic mechanisms underlying these activities of melatonin have not been clarified in mast cells. This work is designed to determine the anti-inflammatory effect and mechanism of action of melatonin on activated mast cells. RBL-2H3 were pre-treated with exogenous melatonin (MELx) at physiological (100nM) and pharmacological (1 mM) doses for 30 min, washed and activated with PMACI (phorbol 12-myristate 13-acetate plus calcium ionophore A23187) for 2 h and 12 h. The data shows that pre-treatment of MELx in stimulated mast cells, significantly reduced the levels of endogenous melatonin production (MELn), TNF-α and IL-6. These effects are directly related with the MELx concentration used. MELx also inhibited IKK/NF-κB signal transduction pathway in stimulated mast cells. These results indicate a molecular basis for the ability of melatonin to prevent inflammation and for the treatment of allergic inflammatory diseases through the down-regulation of mast cell activation. J. Cell. Biochem. 117: 1926-1933, 2016. © 2016 Wiley Periodicals, Inc.