Photophobia in migraine: a symptom cluster?

Photophobia is one of the most common symptoms in migraine, and the underlying mechanism is uncertain. The discovery of the intrinsically-photosensitive retinal ganglion cells (ipRGCs) which signal the intensity of light on the retina has led to discussion of their role in the pathogenesis of photophobia. In the current review, we discuss the relationship between pain and discomfort leading to light aversion (traditional photophobia) and discomfort from flicker, patterns, and colour that are also common in migraine and cannot be explained solely by ipRGC activity. We argue that, at least in migraine, a cortical mechanism provides a parsimonious explanation for discomfort from all forms of visual stimulation, and that the traditional definition of photophobia as pain in response to light may be too restrictive. Future investigation that directly compares the retinal and cortical contributions to photophobia in migraine with that in other conditions may offer better specificity in identifying biomarkers and possible mechanisms to target for treatment

Visual stress, its treatment with spectral filters, and its relationship to visually induced motion sickness

We review the concept of visual stress and its relation to neurological disease. Visual stress can occur from the observation of images with unnatural spatial structure and an excess of contrast energy at spatial frequencies to which the visual system is generally most sensitive. Visual stress can often be reduced using spectral filters, provided the colour is selected with precision to suit each individual. The use of such filters and their effects on reading speed are reviewed. The filters have been shown to benefit patients with a variety of neurological conditions other than reading difficulty, all associated with an increased risk of seizures. © 2009 Elsevier Ltd

Intra-arterial Thrombolysis for Central Retinal Artery Occlusion: Two Cases Report

Central retinal artery occlusion (CRAO) causes severe visual loss in affected eye and vision does not recover in more than 90% of the patients. It is believed that it occurs by occlusion of the central retinal artery with small emboli from atherosclerotic plaque of internal cerebral artery. Retina is a part of the brain, thus basically CRAO is corresponding to acute occlusion of intracerebral artery and retinal ischemia is to cerebral stroke. Therefore, intra-arterial thrombolysis (IAT) has been considered as a treatment method in CRAO. Recently, we treated 2 patients diagnosed as CRAO and could achieve complete recanalization on fundus fluorescein angiogram with IAT. Of them, one recovered visual acuity to 20/25. We report our 2 CRAO cases treated with IAT and discuss technical aspects for IAT and management of patient. To the best of our knowledge, this is the first Korean report of IAT for CRAO

Reducing problem behavior during care-giving in families of preschool-aged children with developmental disabilities

This study evaluated two variants of a behavioral parent training program known as Stepping Stones Triple P (SSTP) using 74 preschool-aged children with developmental disabilities. Families were randomly allocated to an enhanced parent training intervention that combined parenting skills and care-giving coping skills (SSTP-E), standard parent training intervention alone (SSTP-S) or waitlist control (WL) condition. At post-intervention, both programs were associated with lower levels of observed negative child behavior, reductions in the number of care-giving settings where children displayed problem behavior, and improved parental competence and satisfaction in the parenting role as compared with the waitlist condition. Gains attained at post-intervention were maintained at 1-year follow-up. Both interventions produced significant reductions in child problem behavior, with 67% of children in the SSTP-E and 77% of children in the SSTPS showing clinically reliable change from pre-intervention to follow-up. Parents reported a high level of satisfaction with both interventions

Facilitative reforms, democratic accountability, social accounting and learning representative initiatives

This article considers critical accountants’ potential contribution to progressive reforms by examining how trade unions transformed workplace accountability relationships and developed social accounts as part of a workplace learning initiative. The article develops and utilizes the concept of facilitative reforms to interpret the advances brought by learning representative initiatives and accompanying changes in broader civil society, workplace relationships and social accounts in the UK and New Zealand. The article finds that the experience of the learning representative initiatives suggests that critical accountants’ support of facilitative reforms may sometimes be a fruitful strategy

Upregulated IL-1β in dysferlin-deficient muscle attenuates regeneration by blunting the response to pro-inflammatory macrophages.

BACKGROUND: Loss-of-function mutations in the dysferlin gene (DYSF) result in a family of muscle disorders known collectively as the dysferlinopathies. Dysferlin-deficient muscle is characterized by inflammatory foci and macrophage infiltration with subsequent decline in muscle function. Whereas macrophages function to remove necrotic tissue in acute injury, their prevalence in chronic myopathy is thought to inhibit resolution of muscle regeneration. Two major classes of macrophages, classical (M1) and alternative (M2a), play distinct roles during the acute injury process. However, their individual roles in chronic myopathy remain unclear and were explored in this study. METHODS: To test the roles of the two macrophage phenotypes on regeneration in dysferlin-deficient muscle, we developed an in vitro co-culture model of macrophages and muscle cells. We assayed the co-cultures using ELISA and cytokine arrays to identify secreted factors and performed transcriptome analysis of molecular networks induced in the myoblasts. RESULTS: Dysferlin-deficient muscle contained an excess of M1 macrophage markers, compared with WT, and regenerated poorly in response to toxin injury. Co-culturing macrophages with muscle cells showed that M1 macrophages inhibit muscle regeneration whereas M2a macrophages promote it, especially in dysferlin-deficient muscle cells. Examination of soluble factors released in the co-cultures and transcriptome analysis implicated two soluble factors in mediating the effects: IL-1β and IL-4, which during acute injury are secreted from M1 and M2a macrophages, respectively. To test the roles of these two factors in dysferlin-deficient muscle, myoblasts were treated with IL-4, which improved muscle differentiation, or IL-1β, which inhibited it. Importantly, blockade of IL-1β signaling significantly improved differentiation of dysferlin-deficient cells. CONCLUSIONS: We propose that the inhibitory effects of M1 macrophages on myogenesis are mediated by IL-1β signals and suppression of the M1-mediated immune response may improve muscle regeneration in dysferlin deficiency. Our studies identify a potential therapeutic approach to promote muscle regeneration in dystrophic muscle

A Novel and Lethal De Novo LQT-3 Mutation in a Newborn with Distinct Molecular Pharmacology and Therapeutic Response

SCN5A encodes the alpha-subunit (Na(v)1.5) of the principle Na(+) channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS) variant 3 (LQT-3) in adults by disrupting inactivation of the Na(v)1.5 channel. Pharmacological targeting of mutation-altered Na(+) channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS) and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C) discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+) channel blockers flecainide and mexiletine. Our goal was to determine the Na(+) channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+) channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C) and a common variant in KCNH2 (K897T). Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+) channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+) channel defects and suggest that both genetic background and age are particularly important in developing a mutation-specific therapeutic personalized approach to manage disorders in the young

The Biological Records Centre: a pioneer of citizen science

People have been recording wildlife for centuries and the resulting datasets lead to important scientific research. The Biological Records Centre (BRC), established in 1964, is a national focus for terrestrial and freshwater species recording in the United Kingdom (UK). BRC works with the voluntary recording community (i.e. a mutualistic symbiosis) through support of national recording schemes (i.e. ‘citizen science’, but unlike most citizen science it is volunteer led) and adds value to the data through analysis and reporting. Biological recording represents a diverse range of activities, involving an estimated 70 000 people annually in the UK, from expert volunteers undertaking systematic monitoring to mass participation recording. It is an invaluable monitoring tool because the datasets are long term, have large geographic extent and are taxonomically diverse (85 taxonomic groups). It supports a diverse range of outputs, e.g. atlases showing national distributions (12 127 species from over 40 taxonomic groups) and quantified trends (1636 species). BRC pioneers the use of technology for data capture (online portals and smartphone apps) and verification (including automated verification) through customisable, inter-operable database systems to facilitate efficient data flow. We are confident that biological recording has a bright future with benefits for people, science, and nature