How do Australian osteopaths manage migraines? Outcomes from a national practice-based research network.

BACKGROUND: Individuals who experience migraines often seek out a variety of treatment options including manual or physical therapy. Evidence suggests that manual therapy, including osteopathy, can play a role in the management of migraines. Whilst there is some literature on the role osteopathy therapy plays in migraine management, none describes the treatment approaches used by practitioners. OBJECTIVES: To explore the demographic, practice and clinical management characteristics of Australian osteopaths who report treating migraine 'often' in clinical practice. METHODS: Secondary analysis of a cross-sectional survey of 988 osteopaths from the Osteopathy Research and Innovation Network (ORION), an Australian practice-based research network. Regression analysis was used to identify demographic, practice and clinical management characteristics of Australian osteopaths who reported 'often' treating migraine patients. RESULTS: Over 40% of respondents (n = 400) indicated treating patients with migraines 'often'. These osteopaths were less likely to be involved in research and be co-located with a dietician compared to osteopaths who do 'not often' treat migraine. Osteopaths who reported 'often' treating migraine were: five times as likely to treat non-English speaking ethnic groups; 2.5 times as likely to treat chronic pain, temporomandibular joint disorders and hand musculoskeletal complaints; compared to those that do not treat migraines 'often'. CONCLUSION: Australian osteopaths who treat migraine are five times more likely to treat non-English speaking ethnic groups; twice as likely to treat chronic pain; temporomandibular joint disorders, and hand musculoskeletal complaints. More research is needed to identify the practices and patient outcomes associated with osteopathy care for those experiencing migraines.

Organometallic Pillarplexes That Bind DNA 4-Way Holliday Junctions and Forks.

Holliday 4-way junctions are key to important biological DNA processes (insertion, recombination, and repair) and are dynamic structures that adopt either open or closed conformations, the open conformation being the biologically active form. Tetracationic metallo-supramolecular pillarplexes display aryl faces about a cylindrical core, an ideal structure to interact with open DNA junction cavities. Combining experimental studies and MD simulations, we show that an Au pillarplex can bind DNA 4-way (Holliday) junctions in their open form, a binding mode not accessed by synthetic agents before. Pillarplexes can bind 3-way junctions too, but their large size leads them to open up and expand that junction, disrupting the base pairing, which manifests in an increased hydrodynamic size and lower junction thermal stability. At high loading, they rearrange both 4-way and 3-way junctions into Y-shaped forks to increase the available junction-like binding sites. Isostructural Ag pillarplexes show similar DNA junction binding behavior but lower solution stability. This pillarplex binding contrasts with (but complements) that of metallo-supramolecular cylinders, which prefer 3-way junctions and can rearrange 4-way junctions into 3-way junction structures. The pillarplexes' ability to bind open 4-way junctions creates exciting possibilities to modulate and switch such structures in biology, as well as in synthetic nucleic acid nanostructures. In human cells, the pillarplexes do reach the nucleus, with antiproliferative activity at levels similar to those of cisplatin. The findings provide a new roadmap for targeting higher-order junction structures using a metallo-supramolecular approach, as well as expanding the toolbox available to design bioactive junction binders into organometallic chemistry.

Pulsatile MAPK Signaling Modulates p53 Activity to Control Cell Fate Decisions at the G2 Checkpoint for DNA Damage.

Cell-autonomous changes in p53 expression govern the duration and outcome of cell-cycle arrest at the G2 checkpoint for DNA damage. Here, we report that mitogen-activated protein kinase (MAPK) signaling integrates extracellular cues with p53 dynamics to determine cell fate at the G2 checkpoint. Optogenetic tools and quantitative cell biochemistry reveal transient oscillations in MAPK activity dependent on ataxia-telangiectasia-mutated kinase after DNA damage. MAPK inhibition alters p53 dynamics and p53-dependent gene expression after checkpoint enforcement, prolonging G2 arrest. In contrast, sustained MAPK signaling induces the phosphorylation of CDC25C, and consequently, the accumulation of pro-mitotic kinases, thereby relaxing checkpoint stringency and permitting cells to evade prolonged G2 arrest and senescence induction. We propose a model in which this MAPK-mediated mechanism integrates extracellular cues with cell-autonomous p53-mediated signals, to safeguard genomic integrity during tissue proliferation. Early steps in oncogene-driven carcinogenesis may imbalance this tumor-suppressive mechanism to trigger genome instability.

Analysis of waste hierarchy in the European waste directive 2008/98/EC.

Loss of recoverable resources in linear resource flow systems is likely to contribute to the depletion of natural resources and environmental degradation. The 'waste hierarchy' in the European Commission's latest Waste Framework Directive 2008/98/EC (WFD2008) makes recommendations on how to address this issue. The WFD2008 is analysed in this work for its adequacy in ensuring return of 'recoverable waste' as a 'resource' into the productive system. Despite the release of guidance documents by the DG Environment, DEFRA and WRAP UK on the interpretation of key provisions of the WFD2008, lack of clarity still exists around the WFD2008 'waste hierarchy'. There is also an overlap between measures such as 'prevention' and 'reduction', 'preparing for reuse' and 'reuse' and lack of clarity on why the measure of 'reuse' is included in the WFD2008 definition of 'prevention'. Finally, absence of the measures of 'recovery' and 'reuse' from the WFD2008 'waste hierarchy' reduces its effectiveness as a resource efficiency tool. Without clarity on the WFD2008 'waste hierarchy', it is challenging for decision makers to take direct action to address inefficiencies existing within their operations or supply chains. This paper proposes the development of an alternative 'hierarchy of resource use' and alternative 'definitions' that attempt to fill identified gaps in the WFD2008 and bring clarity to the key measures of waste prevention, reduction and recovery. This would help the key stakeholders in driving resource effectiveness, which in turn would assist in conservation of natural resources and prevention of environmental degradation.

A foundation for reliable spatial proteomics data analysis.

Quantitative mass-spectrometry-based spatial proteomics involves elaborate, expensive, and time-consuming experimental procedures, and considerable effort is invested in the generation of such data. Multiple research groups have described a variety of approaches for establishing high-quality proteome-wide datasets. However, data analysis is as critical as data production for reliable and insightful biological interpretation, and no consistent and robust solutions have been offered to the community so far. Here, we introduce the requirements for rigorous spatial proteomics data analysis, as well as the statistical machine learning methodologies needed to address them, including supervised and semi-supervised machine learning, clustering, and novelty detection. We present freely available software solutions that implement innovative state-of-the-art analysis pipelines and illustrate the use of these tools through several case studies involving multiple organisms, experimental designs, mass spectrometry platforms, and quantitation techniques. We also propose sound analysis strategies for identifying dynamic changes in subcellular localization by comparing and contrasting data describing different biological conditions. We conclude by discussing future needs and developments in spatial proteomics data analysis.

Fluid Shear Stress Modulation of Gene Expression in Endothelial Cells.

The vascular endothelium, lining the blood vessel wall, is constantly exposed to wall shear stresses generated by flowing blood. Gene regulation, critical for endothelial cell function, depends on complex interactions at the promoter level and utilizes overlapping signal transduction cascades to activate the expression of genes involved in many biological processes.