Increasing access to pain care services to improve rural pain management: a realist review investigating factors affecting uptake, implementation, and sustainability.

Guideline-based care for chronic pain is challenging to deliver in rural settings. Evaluations of programs that increase access to pain care services in rural areas report variable outcomes. We conducted a realist review to gain a deep understanding of how and why such programs may, or may not, work.

Astrocyte transcriptomic changes along the spatiotemporal progression of Alzheimer's disease.

Astrocytes are crucial to brain homeostasis, yet their changes along the spatiotemporal progression of Alzheimer's disease (AD) neuropathology remain unexplored. Here we performed single-nucleus RNA sequencing of 628,943 astrocytes from five brain regions representing the stereotypical progression of AD pathology across 32 donors spanning the entire normal aging to severe AD continuum. We mapped out several unique astrocyte subclusters that exhibited varying responses to neuropathology across the AD-vulnerable neural network (spatial axis) or AD pathology stage (temporal axis).

Codesign and Evaluation of Pain Science Messages on Social Media With Adolescents With a History of Chronic Pain.

Pain science education (PSE) is an important component of pediatric pain care; however, access to services is limited. To disseminate pain science concepts on social media, we partnered with adolescents with chronic pain to codesign content. We engaged 7 adolescent codesigners (aged 13-18 years) with lived experience of chronic pain to take part in 4 codesign workshops.

Broad proteomics analysis of seeding-induced aggregation of α-synuclein in M83 neurons reveals remodeling of proteostasis mechanisms that might contribute to Parkinson's disease pathogenesis.

Aggregation of misfolded α-synuclein (α-syn) is a key characteristic feature of Parkinson's disease (PD) and related synucleinopathies. The nature of these aggregates and their contribution to cellular dysfunction is still not clearly elucidated. We employed mass spectrometry-based total and phospho-proteomics to characterize the underlying molecular and biological changes due to α-syn aggregation using the M83 mouse primary neuronal model of PD.

Landscape of brain myeloid cell transcriptome along the spatiotemporal progression of Alzheimer's disease reveals distinct sequential responses to Aβ and tau.

Human microglia are critically involved in Alzheimer's disease (AD) progression, as shown by genetic and molecular studies. However, their role in tau pathology progression in human brain has not been well described. Here, we characterized 32 human donors along progression of AD pathology, both in time-from early to late pathology-and in space-from entorhinal cortex (EC), inferior temporal gyrus (ITG), prefrontal cortex (PFC) to visual cortex (V2 and V1)-with biochemistry, immunohistochemistry, and single nuclei-RNA-sequencing, profiling a total of 337,512 brain myeloid cells, including microglia.

Investigating self-report and neuropsychological assessments of cognitive flexibility in people with and without persistent pain: An online, cross-sectional, observational study.

Introduction: People with persistent pain experience problems modifying their cognition and behaviours when task or environmental demands change - abilities otherwise known as . However, limitations and inconsistent results of previous studies raise concerns over the quality of that evidence. We aimed to determine whether people with and without persistent pain differ on two assessments that are commonly used to assess cognitive flexibility.

New precision medicine avenues to the prevention of Alzheimer's disease from insights into the structure and function of γ-secretases.

Two phase-III clinical trials with anti-amyloid peptide antibodies have met their primary goal, i.e. slowing of Alzheimer's disease (AD) progression.

Development of recommendations for a minimum dataset for Identifying Social factors that Stratify Health Opportunities and Outcomes (ISSHOOs) in pain research.

There is increasing recognition of the need for researchers to collect and report data that can illuminate health inequities. In pain research, routinely collecting equity-relevant data has the potential to inform about the generalisability of findings; whether the intervention has differential effects across strata of society; or it could be used to guide population targeting for clinical studies. Developing clarity and consensus on data should be collected and to collect it is required to prompt researchers to further consider equity issues in the planning, conduct, interpretation, and reporting of research.

We Are All in This Together-Whole of Community Pain Science Education Campaigns to Promote Better Management of Persistent Pain.

Persistent pain is a major public health issue-estimated to affect a quarter of the world's population. Public understanding of persistent pain is based on outdated biomedical models, laden with misconceptions that are contrary to best evidence. This understanding is a barrier to effective pain management.

Using PROGRESS-plus to identify current approaches to the collection and reporting of equity-relevant data: a scoping review.

Objectives: Our objectives were to identify what and how data relating to the social determinants of health are collected and reported in equity-relevant studies and map these data to the PROGRESS-Plus framework.

Study Design And Setting: We performed a scoping review. We ran two systematic searches of MEDLINE and Embase for equity-relevant studies published during 2021.

Distinct transcriptomic responses to Aβ plaques, neurofibrillary tangles, and APOE in Alzheimer's disease.

Introduction: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear.

Methods: We performed laser capture microdissection of amyloid beta (Aβ) plaques, the 50 μm halo around them, tangles with the 50 μm halo around them, and areas distant (> 50 μm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.

Results: Aβ plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes.

Endothelial Cells Are Heterogeneous in Different Brain Regions and Are Dramatically Altered in Alzheimer's Disease.

Vascular endothelial cells play an important role in maintaining brain health, but their contribution to Alzheimer's disease (AD) is obscured by limited understanding of the cellular heterogeneity in normal aged brain and in disease. To address this, we performed single nucleus RNAseq on tissue from 32 human AD and non-AD donors (19 female, 13 male) each with five cortical regions: entorhinal cortex, inferior temporal gyrus, prefrontal cortex, visual association cortex, and primary visual cortex. Analysis of 51,586 endothelial cells revealed unique gene expression patterns across the five regions in non-AD donors.

The ' and '' of screening for social needs in healthcare settings: a scoping review.

Background: Adverse social determinants of health give rise to individual-level social needs that have the potential to negatively impact health. Screening patients to identify unmet social needs is becoming more widespread. A review of the content of currently available screening tools is warranted.

Distinct Transcriptomic Responses to Aβ plaques, Neurofibrillary Tangles, and in Alzheimer's Disease.

Introduction: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer's disease (AD) but the spatial relationships with plaques and tangles and -linked differences remain unclear.

Methods: We performed laser capture microdissection of Aβ plaques, the 50μm halo around them, tangles with the 50μm halo around them, and areas distant (>50μm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.

Results: Aβ plaques exhibited upregulated microglial (neuroinflammation/phagocytosis) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes.

Do health education initiatives assist socioeconomically disadvantaged populations? A systematic review and meta-analyses.

Background: Health education interventions are considered critical for the prevention and management of conditions of public health concern. Although the burden of these conditions is often greatest in socio-economically disadvantaged populations, the effectiveness of interventions that target these groups is unknown. We aimed to identify and synthesize evidence of the effectiveness of health-related educational interventions in adult disadvantaged populations.

Endothelial Cells are Heterogeneous in Different Brain Regions and are Dramatically Altered in Alzheimer's Disease.

Unlabelled: Vascular endothelial cells play an important role in maintaining brain health, but their contribution to Alzheimer's disease (AD) is obscured by limited understanding of the cellular heterogeneity in normal aged brain and in disease. To address this, we performed single nucleus RNAseq on tissue from 32 AD and non-AD donors each with five cortical regions: entorhinal cortex, inferior temporal gyrus, prefrontal cortex, visual association cortex and primary visual cortex. Analysis of 51,586 endothelial cells revealed unique gene expression patterns across the five regions in non-AD donors.

Key Learning Statements for Persistent Pain Education: An Iterative Analysis of Consumer, Clinician and Researcher Perspectives and Development of Public Messaging.

Over the last decade, the content, delivery and media of pain education have been adjusted in line with scientific discovery in pain and educational sciences, and in line with consumer perspectives. This paper describes a decade-long process of exploring consumer perspectives on pain science education concepts to inform clinician-derived educational updates (undertaken by the authors). Data were collected as part of a quality audit via a series of online surveys in which consent (non-specific) was obtained from consumers for their data to be used in published research.

Best practice care for persistent pain in adults with spinal cord injuries: a systematic review and narrative synthesis of clinical practice guideline recommendations.

Purpose: To review clinical practice guidelines (CPGs) and recent literature to identify common recommendations guiding "best practice" pain care for adults with spinal cord injury (SCI).

Methods: We searched four scientific databases and four guideline repositories from January 2010 to February 2022 for CPGs relating to the management of pain following SCI. We excluded guidelines that related to a single treatment modality, complementary medicines, specific disease processes, and guidelines that were not freely available.

Exploring the Social Determinants of Health Outcomes for Adults with Low Back Pain or Spinal Cord Injury and Persistent Pain: A Mixed Methods Study.

Developing a greater understanding of the social and environmental factors that are related to differential outcomes for individuals who experience persistent pain and disability is important for achieving health equity. In this study, we aimed to develop insights into the role of the social determinants of health (SDH) in care experiences and health status for socio-economically disadvantaged adults who experience persistent low back pain or persistent pain following spinal cord injury. Our objectives were to investigate 1) relationships between the SDH and health outcomes, 2) care experiences, and 3) perceived barriers and facilitators to optimal pain care.

Back to the drawing board-The relationship between self-report and neuropsychological tests of cognitive flexibility in clinical cohorts: A systematic review and meta-analysis.

Objective: Cognitive flexibility has been previously described as the ability to adjust cognitive and behavioral strategies in response to changing contextual demands. Cognitive flexibility is typically assessed via self-report questionnaires and performance on neuropsychological tests in research and clinical practice. A common assumption among researchers and clinicians is that self-report and neuropsychological tests of cognitive flexibility assess the same or similar constructs, but the extent of the relationship between these two assessment approaches in clinical cohorts remains unknown.

The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics.

Many drugs that target amyloid-β (Aβ) in Alzheimer disease (AD) have failed to demonstrate clinical efficacy. However, four anti-Aβ antibodies have been shown to mediate the removal of amyloid plaque from brains of patients with AD, and the FDA has recently granted accelerated approval to one of these, aducanumab, using reduction of amyloid plaque as a surrogate end point. The rationale for approval and the extent of the clinical benefit from these antibodies are under intense debate.

Pain and pain management experiences following spinal cord injury - a mixed methods study of Australian community-dwelling adults.

Purpose: There is a high prevalence of persistent pain following SCI yet insights into its impact and the quality of pain care are limited. We aimed to explore, in-depth, the problem of persistent pain in Australian community-dwelling adults with a spinal cord injury (SCI). Our objectives were to investigate (i) how individuals experience persistent pain, (ii) how they experience pain care and (iii) the concordance between clinical practice guidelines for managing pain and reported care practices.

Uncovering specificity of endogenous TAU aggregation in a human iPSC-neuron TAU seeding model.

Tau pathobiology has emerged as a key component underlying Alzheimer's disease (AD) progression; however, human neuronal models have struggled to recapitulate tau phenomena observed . Here, we aimed to define the minimal requirements to achieve endogenous tau aggregation in functional neurons utilizing human induced pluripotent stem cell (hiPSC) technology. Optimized hiPSC-derived cortical neurons seeded with AD brain-derived competent tau species or recombinant tau fibrils displayed increases in insoluble, endogenous tau aggregates.

Development and measurement properties of the AxEL (attitude toward education and advice for low-back-pain) questionnaire.

Introduction: Clinician time and resources may be underutilised if the treatment they offer does not match patient expectations and attitudes. We developed a questionnaire (AxEL-Q) to guide clinicians toward elements of first-line care that are pertinent to their patients with low back pain.

Methods: We used guidance from the COSMIN consortium to develop the questionnaire and evaluated it in a sample of people with low back pain of any duration.