Role for Astroglia-Derived BDNF and MSK1 in Homeostatic Synaptic Plasticity

Homeostatic scaling of synaptic strength in response to environmental stimuli may underlie the beneficial effects of an active lifestyle on brain function. Our previous results highlighted a key role for brain-derived neurotrophic factor (BDNF) and mitogen- and stress-activated protein kinase 1 (MSK1) in experience-related homeostatic synaptic plasticity. Astroglia have recently been shown to serve as an important source of BDNF. To elucidate a role for astroglia-derived BDNF, we explored homeostatic synaptic plasticity in transgenic mice with an impairment in the BDNF/MSK1 pathway (MSK1 kinase dead knock-in (KD) mice) and impairment of glial exocytosis (dnSNARE mice). We observed that prolonged tonic activation of astrocytes caused BDNF-dependent upregulation of excitatory synaptic currents accompanied by enlargement of synaptic boutons. We found that exposure to environmental enrichment (EE) and caloric restriction (CR) strongly upregulated excitatory but downregulated inhibitory synaptic currents in old wild-type mice, thus counterbalancing the impact of ageing on synaptic transmission. In parallel, EE and CR enhanced astrocytic Ca2+-signalling. Importantly, we observed a significant deficit in the effects of EE and CR on synaptic transmission in the MSK1 KD and dnSNARE mice. Combined, our results strongly support the importance of astrocytic exocytosis of BDNF for the beneficial effects of EE and CR on synaptic transmission and plasticity in the ageing brain

Protocol for the saMS trial (supportive adjustment for multiple sclerosis): a randomized controlled trial comparing cognitive behavioral therapy to supportive listening for adjustment to multiple sclerosis

BackgroundMultiple Sclerosis (MS) is an incurable, chronic, potentially progressive and unpredictable disease of the central nervous system. The disease produces a range of unpleasant and debilitating symptoms, which can have a profound impact including disrupting activities of daily living, employment, income, relationships, social and leisure activities, and life goals. Adjusting to the illness is therefore particularly challenging. This trial tests the effectiveness of a cognitive behavioural intervention compared to supportive listening to assist adjustment in the early stages of MS.MethodsThis is a two arm randomized multi-centre parallel group controlled trial. 122 consenting participants who meet eligibility criteria will be randomly allocated to receive either Cognitive Behavioral Therapy or Supportive Listening. Eight one hour sessions of therapy (delivered over a period of 10 weeks) will be delivered by general nurses trained in both treatments. Self-report questionnaire data will be collected at baseline (0 weeks), mid-therapy (week 5 of therapy), post-therapy (15 weeks) and at six months (26 weeks) and twelve months (52 weeks) follow-up. Primary outcomes are distress and MS-related social and role impairment at twelve month follow-up. Analysis will also consider predictors and mechanisms of change during therapy. In-depth interviews to examine participants’ experiences of the interventions will be conducted with a purposively sampled sub-set of the trial participants. An economic analysis will also take place. DiscussionThis trial is distinctive in its aims in that it aids adjustment to MS in a broad sense. It is not a treatment specifically for depression. Use of nurses as therapists makes the interventions potentially viable in terms of being rolled out in the NHS. The trial benefits from incorporating patient input in the development and evaluation stages. The trial will provide important information about the efficacy, cost-effectiveness and acceptability of the interventions as well as mechanisms of psychosocial adjustment.Trial registrationCurrent Controlled Trials ISRCTN91377356<br/

Factor analysis of self-treatment in diabetes mellitus: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Self-treatment is a treatment of oneself without professional help, which may cause health-related consequences. This investigation examined the self-treatment behaviors in patients with diabetes mellitus in Iran/kashan.</p> <p>Methods</p> <p>The patients who referred to the clinic of diabetes and those who were admitted to the General hospital in the city of Kashan due to diabetes mellitus were asked to participate in this cross-sectional study. For data collection, The 25 item questionnaire of Likert scale type with four scales was used. Factor analysis was performed to define the patterns of self-treatment.</p> <p>Results</p> <p>398 patients participated in the study. The mean age of the study population was 54.9 ± 12.9 years. The majority (97%) had type 2 diabetes. 50% of patients reported self- treatment. The self-treatment score was 45.8 ± 8.8 (25-100). Female gender, lower education and co-morbid illnesses of hypertension, hyperlipidemia and cardiac disease had significant relationship with self-treatment. The factor analysis procedure revealed seven factors that explained the 43% of variation in the self-treatment. These seven factors were categorized as knowledge, deficiencies of formal treatments, available self-treatment methods, physician related factors, the tendency to use herbal remedies, underlying factors such as gender and factors related to diabetes.</p> <p>Conclusions</p> <p>There is a medium tendency for self-treatment in diabetic patients. The assessment of self-treatment practices must be an essential part of patients' management in diabetes care.</p

Influenza A Virus Coding Regions Exhibit Host-Specific Global Ordered RNA Structure

Influenza A is a significant public health threat, partially because of its capacity to readily exchange gene segments between different host species to form novel pandemic strains. An understanding of the fundamental factors providing species barriers between different influenza hosts would facilitate identification of strains capable of leading to pandemic outbreaks and could also inform vaccine development. Here, we describe the difference in predicted RNA secondary structure stability that exists between avian, swine and human coding regions. The results predict that global ordered RNA structure exists in influenza A segments 1, 5, 7 and 8, and that ranges of free energies for secondary structure formation differ between host strains. The predicted free energy distributions for strains from avian, swine, and human species suggest criteria for segment reassortment and strains that might be ideal candidates for viral attenuation and vaccine development

Illness Schema Activation and the Effects of Illness Seasonality on Accessibility of Implicit Illness-Related Information

The Common-Sense Model (CSM) of illness self-regulation is a leading theoretical framework describing the process by which an individual recognizes that he or she is physically ill and subsequently attempts to manage that illness state. The CSM proposes that people possess schematically organized implicit cognitive representations of health threats comprising information about illness such as symptoms, causes, label, duration, consequences, and procedures for managing threat [1, 2, 3, 4]. The proposed function of these stored knowledge structures is to activate a self-regulation process that might protect or restore a state of well-being [5]. The CSM proposes that the schematic representation is centrally activated by detection of deviations from the normal functioning self (i.e., experienced symptoms). The identification of illness and the initiation of self-management attempts follow from the search for illness-relevant cognitive structures and the matching of the content of illness schema to the symptomatic experience. For example, a headache (a symptomatic deviation from normal somatic experience) might activate illness schemata containing the cognitive representation of “headache” such as “hangover,” “dehydration,” or “flu.” The matching of the symptom to a particular illness schema will follow from the search and match to other aspects of plausible illness representations, such as its probable cause or duration (timeline).Full Tex

A pilot dose-response study of the acute effects of haskap berry extract (Lonicera caerulea L.) on cognition, mood and blood pressure in older adults

Purpose Haskap (Lonicera caerulea L. or blue honeysuckle) is a plant native to the low-lying wet areas and mountains of Siberia and northeastern Asia, but is now cultivated in Canada. The dark blue berries are rich in anthocyanins, particularly cyanidin-3-O-glucoside. Previously, anthocyanin-rich fruits have been observed to benefit cognitive performance during the immediate postprandial period following a single acute dose. However, no study has currently examined the potential for haskap berries to influence cognitive performance. Here, we investigate the acute cognitive benefits of an anthocyanin-rich haskap berry extract. Methods A double-blind, counterbalanced, crossover intervention study compared the acute effects of three separate haskap berry extract doses, containing 100mg, 200mg, and 400mg anthocyanins, with a sugar-matched placebo. Participants were an opportunity sample of 20 older adults, aged 62-81 years. Measures of cognition, mood, and blood pressure were recorded at baseline and 1.5 hours postprandially. Results Compared to placebo, the 400mg dose elicited significantly lower diastolic blood pressure and heart rate. Both 200mg and 400mg doses elicited significantly higher word recall, with the 400mg dose also significantly improving word recognition scores, on an episodic memory task. However, mood, working memory and executive function task results were more equivocal. Conclusions The findings provide evidence for improvements in episodic memory and blood pressure following acute supplementation with haskap berry extract, with higher doses appearing most effective. The cognitive findings concur with previous literature that suggests episodic memory effects, and not executive function effects, are most prevalent in older adults following anthocyanin-rich berry supplementation. The blood pressure outcome is consistent with a vasodilatory mechanism of action

The Influence of Life History Milestones and Association Networks on Crop-Raiding Behavior in Male African Elephants

Factors that influence learning and the spread of behavior in wild animal populations are important for understanding species responses to changing environments and for species conservation. In populations of wildlife species that come into conflict with humans by raiding cultivated crops, simple models of exposure of individual animals to crops do not entirely explain the prevalence of crop raiding behavior. We investigated the influence of life history milestones using age and association patterns on the probability of being a crop raider among wild free ranging male African elephants; we focused on males because female elephants are not known to raid crops in our study population. We examined several features of an elephant association network; network density, community structure and association based on age similarity since they are known to influence the spread of behaviors in a population. We found that older males were more likely to be raiders than younger males, that males were more likely to be raiders when their closest associates were also raiders, and that males were more likely to be raiders when their second closest associates were raiders older than them. The male association network had sparse associations, a tendency for individuals similar in age and raiding status to associate, and a strong community structure. However, raiders were randomly distributed between communities. These features of the elephant association network may limit the spread of raiding behavior and likely determine the prevalence of raiding behavior in elephant populations. Our results suggest that social learning has a major influence on the acquisition of raiding behavior in younger males whereas life history factors are important drivers of raiding behavior in older males. Further, both life-history and network patterns may influence the acquisition and spread of complex behaviors in animal populations and provide insight on managing human-wildlife conflict

Read-through Activation of Transcription in a Cellular Genomic Context

Read-through transcription from the adjacent E1a gene region is required for wild-type (wt) activity of the downstream adenovirus E1b promoter early after infection (read-through activation). However, whether a cellular chromosomal template can support read-through activation is not known. To address this issue, read-through activation was evaluated in the context of stably expressed templates in transfected cells. Inhibition of read-through transcription by insertion of a transcription termination sequence between the E1a and E1b promoters reduced downstream gene expression from stably integrated templates. The results indicate that the mechanism of read-through activation does not depend on the structure of early adenovirus nucleoprotein complexes, a structure that is likely to be different from that of cellular chromatin. Accordingly, this regulatory interaction could participate in the coordinated control of the expression of closely linked cellular genes

Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions

Background: Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia. Methods. Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA. Results: Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens. Conclusions: Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma

The impact of patient self assessment of deformity on HRQL in adults with scoliosis

Background: Body image and HRQL are significant issues for patients with scoliosis due to cosmetic deformity, physical and psychological symptoms, and treatment factors. A selective review of scoliosis literature revealed that self report measures of body image and HRQL share unreliable correlations with radiographic measures and clinician recommendations for surgery. However, current body image and HRQL measures do not indicate which aspects of scoliosis deformity are the most distressing for patients. The WRVAS is an instrument designed to evaluate patient self assessment of deformity, and may show some promise in identifying aspects of deformity most troubling to patients. Previous research on adolescents with scoliosis supports the use of the WRVAS as a clinical tool, as the instrument shares strong correlations with radiographic measures and quality of life instruments. There has been limited use of this instrument on adult populations. Methods: The WRVAS and the SF-36v2, a HRQL measure, were administered to 71 adults with scoliosis, along with a form to report age and gender. Preliminary validation analyses were performed on the WRVAS (floor and ceiling effects, internal consistency and collinearity, correlations with the SF-36v2, and multiple regression with the WRVAS total score as the predictor, and SF-36v2 scores as outcomes). Results: The psychometric properties of the WRVAS were acceptable. Older participants perceived their deformities as more severe than younger participants. More severe deformities were associated with lower scores on the Physical Component Summary Score of the SF-36v2. Total WRVAS score also predicted Physical Component Summary scores. Conclusion: The results of the current study indicate that the WRVAS is a reliable tool to use with adult patients, and that patient self assessment of deformity shared a relationship with physical rather than psychological aspects of HRQL. The current and previous studies concur that revision of the WRVAS is necessary to more accurately represent the diversity of scoliosis deformities. Ability to identify disturbing aspects of deformity could potentially be improved by evaluating each WRVAS items against indicators of pain, physical/psychosocial function, and self image from previous measures such as the SRS, SF-36 or BSSQ-deformity