The experience of occupational therapists and physiotherapists using a prototype, evidence-informed online knowledge translation resource to learn about patient-defined, personally-meaningful chronic pain rehabilitation.

Purpose: Chronic pain is a complex biopsychosocial experience, and rehabilitation helps people to manage pain, and restore valued life roles. Evidence suggests that more positive outcomes occur when clients perceive their rehabilitation to be meaningful. People with chronic pain describe rehabilitation as personally-meaningful when they develop a genuine connection with a credible therapist who they see as a guiding partner, and when rehabilitation holds personal value, is self-defined, and relevant to their sense of self-identity.

Positive Association between Patients' Perception of Chronic Pain Rehabilitation as a Personally Meaningful Experience and the Flourishing Aspect of Well-Being.

Chronic pain rehabilitation helps to reduce pain and restore valued life roles. Patients may have more positive outcomes when they perceive rehabilitation to be personally meaningful. This study examined associations between self-reported, personally meaningful rehabilitation and well-being.

The experience of meaningful rehabilitation as perceived by people with chronic pain: A phenomenological study.

Background: People with chronic pain may seek rehabilitation to reduce pain and restore productivity and valued roles. Theoretically, a biopsychosocial approach makes rehabilitation more meaningful, however, the limited research on meaningful rehabilitation predominantly describes the perspective of therapists and researchers. The client's perspective of meaningfulness in rehabilitation is lacking.

POLQ suppresses genome instability and alterations in DNA repeat tract lengths.

DNA polymerase theta (POLQ) is a principal component of the alternative non-homologous end-joining (ANHEJ) DNA repair pathway that ligates DNA double-strand breaks. Utilizing independent models of POLQ insufficiency during telomere-driven crisis, we found that  cells are resistant to crisis-induced growth deceleration despite sustaining inter-chromosomal telomere fusion frequencies equivalent to wild-type (WT) cells. We recorded longer telomeres in than WT cells pre- and post-crisis, notwithstanding elevated total telomere erosion and fusion rates.

Affect, dis/ability and the pandemic.

The pandemic has heightened anxieties, impacted mental health and threatened to create an overwhelming sense of existential dread. We recognise the material ways in which disabled people have been differentially impacted by Covid-19 and make a case for understanding the affective dimensions of the pandemic. We develop a theoretical approach - cutting across medical sociology and critical disability studies - that understands affect as a social, cultural, relational and psychopolitical phenomenon.

Tracking telomere fusions through crisis reveals conflict between DNA transcription and the DNA damage response.

Identifying attributes that distinguish pre-malignant from senescent cells provides opportunities for targeted disease eradication and revival of anti-tumour immunity. We modelled a telomere-driven crisis in four human fibroblast lines, sampling at multiple time points to delineate genomic rearrangements and transcriptome developments that characterize the transition from dynamic proliferation into replicative crisis. Progression through crisis was associated with abundant intra-chromosomal telomere fusions with increasing asymmetry and reduced microhomology usage, suggesting shifts in DNA repair capacity.

Cross-Sectional Survey of Sleep Practices of Australian University Students.

Unlabelled: Sleep insufficiency is often associated with the life of a university student, yet it is well known that inadequate sleep can have a negative impact on physical and mental health and be detrimental to cognitive skills for learning. The aim of this study was to replicate a Canadian study to survey university student sleep practices, the way in which students address any sleep issues, and the students' preferred method to receive targeted sleep information.

Methods: An anonymous on-line survey was promoted to all enrolled students at one Australian University in August 2017.

Working the edges of Posthuman disability studies: theorising with disabled young people with life-limiting impairments.

This paper is built upon an assumption: that social theory can be generated through a meaningful engagement with a co-researcher group of disabled young people. Our co-researchers are theoretical provocateurs and theorists in their own right who, through their activism and writing, are challenging us to reconsider the meaning of life, death and disability. Their work on our funded Economic and Social Research Council (ESRC) project has enabled us to consider the promise and potential of humanist and posthuman epistemologies, theories, methodologies, interventions and activisms.

DNA Ligase 1 is an essential mediator of sister chromatid telomere fusions in G2 cell cycle phase.

Fusion of critically short or damaged telomeres is associated with the genomic rearrangements that support malignant transformation. We have demonstrated the fundamental contribution of DNA ligase 4-dependent classical non-homologous end-joining to long-range inter-chromosomal telomere fusions. In contrast, localized genomic recombinations initiated by sister chromatid fusion are predominantly mediated by alternative non-homologous end-joining activity that may employ either DNA ligase 3 or DNA ligase 1.

The mouth and dis/ability.

Our aims in this paper are threefold. First, to understand how the mouth reveals the kinds of human beings that are de/valued in specific national locations and in global discourses with special attention on disability. Second, to subject the mouth to analysis from critical disability studies, specifically, an approach we describe as dis/ability studies.

Sister chromatid telomere fusions, but not NHEJ-mediated inter-chromosomal telomere fusions, occur independently of DNA ligases 3 and 4.

Telomeres shorten with each cell division and can ultimately become substrates for nonhomologous end-joining repair, leading to large-scale genomic rearrangements of the kind frequently observed in human cancers. We have characterized more than 1400 telomere fusion events at the single-molecule level, using a combination of high-throughput sequence analysis together with experimentally induced telomeric double-stranded DNA breaks. We show that a single chromosomal dysfunctional telomere can fuse with diverse nontelomeric genomic loci, even in the presence of an otherwise stable genome, and that fusion predominates in coding regions.

Escape from telomere-driven crisis is DNA ligase III dependent.

Short dysfunctional telomeres are capable of fusion, generating dicentric chromosomes and initiating breakage-fusion-bridge cycles. Cells that escape the ensuing cellular crisis exhibit large-scale genomic rearrangements that drive clonal evolution and malignant progression. We demonstrate that there is an absolute requirement for fully functional DNA ligase III (LIG3), but not ligase IV (LIG4), to facilitate the escape from a telomere-driven crisis.

γ-Catenin is overexpressed in acute myeloid leukemia and promotes the stabilization and nuclear localization of β-catenin.

Canonical Wnt signaling regulates the transcription of T-cell factor (TCF)-responsive genes through the stabilization and nuclear translocation of the transcriptional co-activator, β-catenin. Overexpression of β-catenin features prominently in acute myeloid leukemia (AML) and has previously been associated with poor clinical outcome. Overexpression of γ-catenin mRNA (a close homologue of β-catenin) has also been reported in AML and has been linked to the pathogenesis of this disease, however, the relative roles of these catenins in leukemia remains unclear.

Macrophage heterogeneity and acute inflammation.

In this Viewpoint, we concentrate on the aspects of macrophage biology that we believe are fundamental for an appropriate contextual understanding of macrophage function during acute inflammation. These are the different origins of macrophage populations (and the implications of this for the renewal of these populations in the adult); and the impact of specific homeostatic or disease-associated microenvironments upon cellular heterogeneity, activation and effector functions.

In vivo functional analysis and genetic modification of in vitro-derived mouse neutrophils.

Mature neutrophils are notoriously short-lived immune cells that cannot be genetically manipulated. Analysis of gene function therefore requires genetically modified animals, which is expensive, time-consuming, and costly in animal life. Analysis of gene function in neutrophils in a physiologically relevant context thus represents a significant problem in the field.

OGG1 is a novel prognostic indicator in acute myeloid leukaemia.

OGG1 (8-oxoguanine DNA glycosylase) constitutes a key component of the DNA base excision repair pathway, catalysing the removal of 8-oxoguanine nucleotides from DNA, thereby suppressing mutagenesis and cell death. We found that OGG1 expression was significantly downregulated by the RUNX1-ETO fusion protein product of the t(8;21) chromosome translocation in normal haematopoietic progenitor cells and in patients with acute myeloid leukaemia (AML). Further examination of OGG1 expression in 174 AML trial patients using Affymetrix microarrays showed that the prevalence rate of OGG1 expression was 33% and correlated strongly with adverse cytogenetics.

Alternative Runx1 promoter usage in mouse developmental hematopoiesis.

The interest in stem cell based therapies has emphasized the importance of understanding the cellular and molecular mechanisms by which stem cells are generated in ontogeny and maintained throughout adult life. Hematopoietic stem cells (HSCs) are first found in clusters of hematopoietic cells budding from the luminal wall of the major arteries in the developing mammalian embryo. The transcription factor Runx1 is critical for their generation and is specifically expressed at sites of HSC generation, prior to their formation.

The induction of inflammation by dectin-1 in vivo is dependent on myeloid cell programming and the progression of phagocytosis.

Dectin-1 is the archetypal signaling, non-Toll-like pattern recognition receptor that plays a protective role in immune defense to Candida albicans as the major leukocyte receptor for beta-glucans. Dectin-1-deficiency is associated with impaired recruitment of inflammatory leukocytes and inflammatory mediator production at the site of infection. In this study, we have used mice to define the mechanisms that regulate the dectin-1-mediated inflammatory responses.

Interleukin-4 induction of the CC chemokine TARC (CCL17) in murine macrophages is mediated by multiple STAT6 sites in the TARC gene promoter.

Background: Macrophages (Mtheta) play a central role in the innate immune response and in the pathology of chronic inflammatory diseases. Macrophages treated with Th2-type cytokines such as Interleukin-4 (IL-4) and Interleukin-13 (IL-13) exhibit an altered phenotype and such alternatively activated macrophages are important in the pathology of diseases characterised by allergic inflammation including asthma and atopic dermatitis. The CC chemokine Thymus and Activation-Regulated Chemokine (TARC/CCL17) and its murine homologue (mTARC/ABCD-2) bind to the chemokine receptor CCR4, and direct T-cell and macrophage recruitment into areas of allergic inflammation.

From hemangioblast to hematopoietic stem cell: an endothelial connection?

The developmental origin of hematopoietic stem cells has been the subject of much research. Now that the developmental link between the hematopoietic system and the vasculature has been well established, questions remain regarding the precise cellular origin of definitive hematopoietic cells and at what point they branch off from the endothelial lineage. Do they emerge directly from a hemangioblast-type cell, similar to what is proposed for primitive yolk sac hematopoiesis, or are they generated via an endothelial intermediate, the hemogenic endothelium? In this review, we will give an overview of the data obtained from the mouse and avian models on the cellular origins of the hematopoietic system.

TH2 cytokines and allergic challenge induce Ym1 expression in macrophages by a STAT6-dependent mechanism.

The diverse functions of macrophages as participants in innate and acquired immune responses are regulated by the specific milieu of environmental factors, cytokines, and other signaling molecules that are encountered at sites of inflammation. Microarray analysis of the transcriptional response of mouse peritoneal macrophages to the T(H)2 cytokine interleukin-4 (IL-4) identified Ym1 and arginase as the most highly up-regulated genes, exhibiting more than 68- and 88-fold induction, respectively. Molecular characterization of the Ym1 promoter in transfected epithelial and macrophage cell lines revealed the presence of multiple signal transducers and activators of transcription 6 (STAT6) response elements that function in a combinatorial manner to mediate transcriptional responses to IL-4.