Transcranial magnetic stimulation

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenTranscranial Magnetic Stimulation (TMS) is a new non-invasive method to investigate the central nervous system. Initially it was used to assess the functional integrity of the pyramidal pathways but more recently various other aspects of brain function have been studied including cortical excitability. By localised interference with brain function, it is possible to use TMS to assess the relationship between various brain regions and cognitive functions. The therapeutic effect of TMS has been explored in the treatment of neurological diseases and psychiatric disorders such as epilepsy, cerebellar ataxia and depressive illness.Segulörvun heila í gegnum höfuðkúpu er notuð til rannsókna á miðtaugakerfi. Upphaflega var þessi aðferð þróuð til að meta starfsemi og ástand hreyfitauga­brauta milli heila og mænu, en er nú einnig notuð til margvíslegra rannsókna á heilastarfsemi. Meta má hömlunar- og örvunarástand heilabarkar sem getur breyst vegna heilasjúkdóma og við lyfjagjöf. Með staðbundinni truflun á starfsemi taugafrumna eftir segulörvun hefur verið hægt að kanna tengsl milli heilasvæða og hugrænna ferla. Í ljós hefur komið möguleg notkun segulörvunar í meðferð taugasjúkdóma og geðraskana. Rannsóknir hvað þetta varðar hafa meðal annars beinst að flogaveiki, mænu- og hnykilhrörnun og djúpri geðlægð

An intervention with dance and yoga for girls with functional abdominal pain disorders (Just in TIME): Protocol for a randomized controlled trial

©Anna Philipson, Stefan Särnblad, Lars Ekstav, Mats Eriksson, Ulrika L Fagerberg, Margareta Möller, Evalotte Mörelius, Anna Duberg. Background: Functional abdominal pain disorders (FAPDs) affect many children worldwide, predominantly girls, and cause considerable long-term negative consequences for individuals and society. Evidence-based and cost-effective treatments are therefore strongly needed. Physical activity has shown promising effects in the practical management of FAPDs. Dance and yoga are both popular activities that have been shown to provide significant psychological and pain-related benefits with minimal risk. The activities complement each other, in that dance involves dynamic, rhythmic physical activity, while yoga enhances relaxation and focus. Objective: This study aims to evaluate the effects of a dance and yoga intervention among girls aged 9 to 13 years with FAPDs. Methods: The study is a prospective randomized controlled trial among girls aged 9 to 13 years with functional abdominal pain, irritable bowel syndrome, or both. The target sample size was 150 girls randomized into 2 arms: an intervention arm that receives dance and yoga sessions twice weekly for 8 months and a control arm that receives standard care. Outcomes will be measured at baseline and after 4, 8, 12, and 24 months, and long-term follow-up will be conducted 5 years from baseline. Questionnaires, interviews, and biomarker measures, such as cortisol in saliva and fecal microbiota, will be used. The primary outcome is the proportion of girls in each group with reduced pain, as measured by the faces pain scale-revised in a pain diary, immediately after the intervention. Secondary outcomes are gastrointestinal symptoms, general health, mental health, stress, and physical activity. The study also includes qualitative evaluations and health economic analyses. This study was approved by the Regional Ethical Review Board in Uppsala (No. 2016/082 1-2). Results: Data collection began in October 2016. The intervention has been performed in 3 periods from 2016 through 2019. The final 5-year follow-up is anticipated to be completed by fall 2023. Conclusions: Cost-effective and easily accessible interventions are warranted to reduce the negative consequences arising from FAPDs in young girls. Physical activity is an effective strategy, but intervention studies are needed to better understand what types of activities facilitate regular participation in this target group. The Just in TIME (Try, Identify, Move, and Enjoy) study will provide insights regarding the effectiveness of dance and yoga and is anticipated to contribute to the challenging work of reducing the burden of FAPDs for young girls

An exploratory study looking at the relationship marketing techniques used in the music festival industry

There are current issues and trends in the music festival market, which may affect the success of an event, and market saturation is at the forefront of these issues. Previous literature, maintaining the need for a marketing approach to festivals, identifi es the need for maintaining strong stakeholder relationships in order to succeed in a business environment; attention has been focused to the theory of relationship marketing (RM) because of the recognition that this practice is complementary to the marketing of festivals. The very nature of the music festival as an annual, usually, 4-day event means that effective marketing is needed to keep connections with the consumer throughout the year. This article focuses on the RM techniques utilised within the music festival industry from the viewpoint of the festival organiser in an attempt to establish how festival organisations value and monitor organisational relationships. This article explores the extent to which these relationships are valued and managed; furthermore, the variations between these intricate relationships are considered by focusing on those held with the organisation ’ s consumers and sponsors, the results of which have provided the ability to establish the importance and relevance of RM to the industry and further identify the marketing communication methods employed to establish and maintain such relationships. In-depth, convergent interviews have been conducted with a segment of music festival organisers from a range of events. The results have been integrated with the study of current literature to best exemplify these issues. It has been established that RM has a strong role in today ’ s commercial and independent music festival industry; technological advances are enabling the organiser to support online relationships further and increase consumer loyalty. There is a need to expand the research further because of the complexity of organisational relationships and the varying categories of festivals

Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes

Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3′-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity

The lancet weight determines wheal diameter in response to skin prick testing with histamine

BACKGROUND:Skin prick test (SPT) is a common test for diagnosing immunoglobulin E-mediated allergies. In clinical routine, technicalities, human errors or patient-related biases, occasionally results in suboptimal diagnosis of sensitization. OBJECTIVE:Although not previously assessed qualitatively, lancet weight is hypothesized to be important when performing SPT to minimize the frequency of false positives, false negatives, and unwanted discomfort. METHODS:Accurate weight-controlled SPT was performed on the volar forearms and backs of 20 healthy subjects. Four predetermined lancet weights were applied (25 g, 85 g, 135 g and 265 g) using two positive control histamine solutions (1 mg/mL and 10 mg/mL) and one negative control (saline). A total of 400 SPTs were conducted. The outcome parameters were: wheal size, neurogenic inflammation (measured by superficial blood perfusion), frequency of bleeding, and the lancet provoked pain response. RESULTS:The mean wheal diameter increased significantly as higher weights were applied to the SPT lancet, e.g. from 3.2 ± 0.28 mm at 25 g to 5.4 ± 1.7 mm at 265 g (p<0.01). Similarly, the frequency of bleeding, the provoked pain, and the neurogenic inflammatory response increased significantly. At 265 g saline evoked two wheal responses (/160 pricks) below 3 mm. CONCLUSION AND CLINICAL RELEVANCE:The applied weight of the lancet during the SPT-procedure is an important factor. Higher lancet weights precipitate significantly larger wheal reactions with potential diagnostic implications. This warrants additional research of the optimal lancet weight in relation to SPT-guidelines to improve the specificity and sensitivity of the procedure

How do we improve men’s mental health via primary care? An evaluation of the Atlas Men’s Well-being Pilot Programme for stressed/distressed men

Background Over three-quarters of all suicides are men (England and Wales), this is despite higher levels of anxiety and depression being reported by women. This disparity may in part be explained by atypical presentations of distress in men, and gendered issues around help-seeking. Consequently, the Atlas Men’s Well-being Programme was designed to engage stressed/distressed men who were patients at a London-based GP surgery. Atlas encouraged GPs to identify and refer men for counselling and/or acupuncture by raising their awareness of men’s distress. The aim of this pilot study was to evaluate Atlas in terms of patients’ characteristics, service utilisation, patient outcomes and cost implications. Methods All patients using the Programme were asked to complete a questionnaire before and after their Atlas sessions. Outcome measures included the Hospital Anxiety and Depression scale, Perceived Stress Scale, Warwick-Edinburgh Mental Well-being Scale, a 11-point scale measuring physical health, and the Psychological Outcome Profiles (PSYCHLOPS), a patient-generated outcome measure. Additionally, for cost calculations, participants were asked about their employment, number of days off work due to illness, and their health and social care service use. Results 102 participants were recruited, 82 completed pre- and post-treatment questionnaires. Comparisons pre- and post-treatment revealed a statistically significant improvement in anxious mood (p <0.001), perceived stress (p < 0.001), positive well-being (p = <0.001), PSYCHLOPS (p = <0.001) and physical health (p = 0.001), though not depressed mood (p = 0.660). Additionally, reductions in costs related to lost employment and health and social care use, exceeded the cost of Atlas counselling and acupuncture sessions, with an average saving of nearly £700 per patient. Conclusions Atlas attendance was associated with improvements in patients’ mental and physical health, and demonstrated likely cost savings. It is now important to understand patient and stakeholder perspectives. Further research could compare usual care with the Atlas approach, and investigate full cost-effectiveness

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction:Plasma biomarkers for Alzheimer’s disease (AD) diagnosis/stratification are a“Holy Grail” of AD research and intensively sought; however, there are no well-established plasmamarkers.Methods:A hypothesis-led plasma biomarker search was conducted in the context of internationalmulticenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL;259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed.Results:Ten analytes showed significant intergroup differences. Logistic regression identified five(FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APOε4 adjusted, optimally differentiated AD andCTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI(AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Twoanalytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71).Discussion:Plasma markers of inflammation and complement dysregulation support diagnosis andoutcome prediction in AD and MCI. Further replication is needed before clinical translatio