Reliable Individual Change in Post Concussive Symptoms in the Year Following Mild Traumatic Brain Injury: Data From the Longitudinal, Population-based Brain Injury Incidence and Outcomes New Zealand in the Community (Bionic) Study

Objective: Post concussive syndromes (PCS) is common after mild-TBI, yet are not well studied on a population level. This study examined PCS symptoms, including reliable change over time in a population-based sample up to one year post-TBI. Methods: Prospective follow-up of 527 adults (≥16 years) with mild TBI (mTBI) and assessment data (Rivermead Post concussion Questionnaire; RPQ) at baseline, 1, 6, and/or 12-months post-TBI. Change in mean scores and clinically significant change across RPQ items for each person was calculated between assessment time points using a reliable change index (RCI). Results: While prevalence of all symptoms reduced over time, >30% of participants reported fatigue, slowed thinking, and forgetfulness 12-months postinjury. Using the RCI, <12% of individuals improved from baseline to 1-month, 50% from 1 to 6-months, and 4.2% from 6 to 12-months. Conclusions: Improvements in PCS post-mTBI were most obvious between 1 and 6-months, suggesting lengthy recovery trajectory. A third of patients experience residual cognitive problems 12-months following a mTBI, and while many individuals improve post-TBI, a large proportion remain stable or worsen

Redistribution of DAT/α-synuclein complexes visualized by “in situ” proximity ligation assay in transgenic mice modelling early Parkinson’s disease

Alpha-synuclein, the major component of Lewy bodies, is thought to play a central role in the onset of synaptic dysfunctions in Parkinson's disease (PD). In particular, α-synuclein may affect dopaminergic neuron function as it interacts with a key protein modulating dopamine (DA) content at the synapse: the DA transporter (DAT). Indeed, recent evidence from our "in vitro" studies showed that α-synuclein aggregation decreases the expression and membrane trafficking of the DAT as the DAT is retained into α-synuclein-immunopositive inclusions. This notwithstanding, "in vivo" studies on PD animal models investigating whether DAT distribution is altered by the pathological overexpression and aggregation of α-synuclein are missing. By using the proximity ligation assay, a technique which allows the "in situ" visualization of protein-protein interactions, we studied the occurrence of alterations in the distribution of DAT/α-synuclein complexes in the SYN120 transgenic mouse model, showing insoluble α-synuclein aggregates into dopaminergic neurons of the nigrostriatal system, reduced striatal DA levels and an altered distribution of synaptic proteins in the striatum. We found that DAT/α-synuclein complexes were markedly redistributed in the striatum and substantia nigra of SYN120 mice. These alterations were accompanied by a significant increase of DAT striatal levels in transgenic animals when compared to wild type littermates. Our data indicate that, in the early pathogenesis of PD, α-synuclein acts as a fine modulator of the dopaminergic synapse by regulating the subcellular distribution of key proteins such as the DAT

Development of the Standards of Reporting of Neurological Disorders (Strond) Checklist: A Guideline for the Reporting of Incidence and Prevalence Studies in Neuroepidemiology

Background: Incidence and prevalence studies of neurologic disorders play an important role in assessing the burden of disease and planning services. However, the assessment of disease estimates is hindered by problems in reporting for such studies. Despite a growth in published reports, existing guidelines relate to analytical rather than descriptive epidemiologic studies. There are also no user-friendly tools (e.g., checklists) available for authors, editors, and peer reviewers to facilitate best practice in reporting of descriptive epidemiologic studies for most neurologic disorders. Objective: The Standards of Reporting of Neurological Disorders (STROND) is a guideline that consists of recommendations and a checklist to facilitate better reporting of published incidence and prevalence studies of neurologic disorders. Methods: A review of previously developed guidance was used to produce a list of items required for incidence and prevalence studies in neurology. A 3-round Delphi technique was used to identify the “basic minimum items” important for reporting, as well as some additional “ideal reporting items.” An e-consultation process was then used in order to gauge opinion by external neuroepidemiologic experts on the appropriateness of the items included in the checklist. Findings: Of 38 candidate items, 15 items and accompanying recommendations were developed along with a user-friendly checklist. Conclusions: The introduction and use of the STROND checklist should lead to more consistent, transparent, and contextualized reporting of descriptive neuroepidemiologic studies resulting in more applicable and comparable findings and ultimately support better health care decisions

Methodology of the Stroke Self-management Rehabilitation Trial: An International, Multisite Pilot Trial

Rationale Stroke is a major cause of long-term adult disability with many survivors living in the community relying on family members for on-going support. However, reports of inadequate understanding of rehabilitation techniques are common. A self-management DVD-based observational learning tool may help improve functional outcomes for survivors of stroke and reduce caregivers' burden. Aims This article describes the methodology of the stroke self-management rehabilitation trial. The overall aim of this pilot trial is to assess the feasibility and preliminary efficacy of a DVD-based intervention for improving functional outcomes of survivors of stroke 2 months postrandomization to inform the design of a full-scale randomized clinical trial. Design Recruitment of a minimum of 20 survivors of stroke and their informal caregivers (where available) in each of the participating centers will occur across multiple international sites. After baseline assessments, participants will be randomly assigned to an intervention or standard care group. The intervention comprises a structured DVD observation and practice schedule over 8 weeks. All participants will complete follow-up assessments. Study outcomes The outcome measures will include a global shift in the Rankin Scale scores and dichotomized scores, changes in quality of life, general health, depression, and caregiver burden at 2 months postrandomization. A qualitative analysis of the effects of the intervention will also be undertaken. Discussion The results of the pilot study will provide knowledge of whether observational learning techniques delivered via DVD can effectively improve recovery after stroke and reduce caregiver burden

Reducing recurrent stroke: methodology of the motivational interviewing in stroke (MIST) randomized clinical trial

Recurrent stroke is prevalent in both developed and developing countries, contributing significantly to disability and death. Recurrent stroke rates can be reduced by adequate risk factor management. However, adherence to prescribed medications and lifestyle changes recommended by physicians at discharge after stroke is poor, leading to a large number of preventable recurrent strokes. Using behavior change methods such as Motivational Interviewing early after stroke occurrence has the potential to prevent recurrent stroke

Role of mesenchymal stromal cell-derived extracellular vesicles in tumour microenvironment

Abstract Stromal cells, deriving from mesenchymal stromal cells (MSCs), are crucial component of tumour microenvironment and represent key regulators of tumour processes. MSCs can be recruited to the tumour environment and interact with many cellular elements, thus influencing tumour biology. Cell-to-cell communication is in part mediated by the release of extracellular vesicle (EVs). EVs can induce significant molecular changes in recipient cells, delivering bioactive molecules. In this review, we describe the MSC-derived EVs content and discuss their role in different processes related to cancer biology. Furthermore, we summarize chemical or biological EVs modifications aiming to develop more efficient antitumor therapies

Veratridine produces distinct calcium response profiles in mouse Dorsal Root Ganglia neurons.

Nociceptors are a subpopulation of dorsal root ganglia (DRG) neurons that detect noxious stimuli and signal pain. Veratridine (VTD) is a voltage-gated sodium channel (VGSC) modifier that is used as an "agonist" in functional screens for VGSC blockers. However, there is very little information on VTD response profiles in DRG neurons and how they relate to neuronal subtypes. Here we characterised VTD-induced calcium responses in cultured mouse DRG neurons. Our data shows that the heterogeneity of VTD responses reflects distinct subpopulations of sensory neurons. About 70% of DRG neurons respond to 30-100 μM VTD. We classified VTD responses into four profiles based upon their response shape. VTD response profiles differed in their frequency of occurrence and correlated with neuronal size. Furthermore, VTD response profiles correlated with responses to the algesic markers capsaicin, AITC and α, β-methylene ATP. Since VTD response profiles integrate the action of several classes of ion channels and exchangers, they could act as functional "reporters" for the constellation of ion channels/exchangers expressed in each sensory neuron. Therefore our findings are relevant to studies and screens using VTD to activate DRG neurons

Depression and anxiety at 1- and 12-months post ischemic stroke: methods for examining individual change over time.

Background Depression is commonly studied post stroke, while anxiety is less studied. This study presents prevalence of depression and anxiety at 1- and 12-months post ischemic stroke alongside three methods for examining within-subjects change over time. Methods Participants were ischemic stroke patients of the Auckland Regional Community Stroke Study (ARCOS-V) with Hospital Anxiety and Depression Scale data at 1- (n = 343) and 12-months (n = 307). Change over time was examined using within-subjects repeated measures ANOVA, calculation of the Reliable Change Index, and a Sankey diagram of those meeting cut-off scores (>7) for caseness over time. Results Using repeated measures ANOVA, depression scores didn’t change significantly over time, while anxiety symptoms decreased significantly. When reliable change was calculated, 4.2% of individuals had reliable decreases in anxiety symptoms, while 5.7% had reliable decreases in depression symptoms. Those who had a reliable decrease in one tended to have a reliable decrease in the other. In the Sankey, the proportion of those meeting the cut-off score for anxiety did not change over time (12.8 and 12.7% at 1- and 12-months), while those meeting the cut-off for depression increased slightly (3.7–4.5%) and those meeting cut-offs for both decreased from 10.4 to 8.1%. Conclusion The three methods produced very different findings. Use of cut-off scores is common but has limitations. Calculation of clinically reliable change is recommended. Further work is needed to ensure depression and anxiety are monitored over time post-stroke, and both should be the subject of intervention efforts in both acute and late stages post-stroke.fals

Global regulation of alternative splicing during myogenic differentiation

Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.National Institutes of Health (U.S.) (grant number R01GM076493)Ford Foundation (Predoctoral Diversity Fellowship)Baylor College of Medicine. Graduate School of Biomedical Sciences (Baylor Research Advocates for Student Scientists

Cristaloquímica y blástesis de micas blancas en metapelitas del afloramiento de Infiernillo, Pichilemu, Chile

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