Osteopathy and Mental Health: An Embodied, Predictive, and Interoceptive Framework.

Globally, mental and musculoskeletal disorders present with high prevalence, disease burden, and comorbidity. In order to improve the quality of care for patients with persistent physical and comorbid mental health conditions, person-centered care approaches addressing psychosocial factors are currently advocated. Central to successful person-centered care is a multidisciplinary collaboration between mental health and musculoskeletal specialists underpinned by a robust therapeutic alliance. Such a collaborative approach might be found in osteopathy, which is typically utilized to treat patients with musculoskeletal disorders but may arguably also benefit mental health outcomes. However, research and practice exploring the reputed effect of osteopathy on patients with mental health problems lack a robust framework. In this hypothesis and theory article, we build upon research from embodied cognition, predictive coding, interoception, and osteopathy to propose an embodied, predictive and interoceptive framework that underpins osteopathic person-centered care for individuals with persistent physical and comorbid mental health problems. Based on the premise that, for example, chronic pain and comorbid depression are underlined by overly precise predictions or imprecise sensory information, we hypothesize that osteopathic treatment may generate strong interoceptive prediction errors that update the generative model underpinning the experience of pain and depression. Thus, physical and mental symptoms may be reduced through active and perceptual inference. We discuss how these theoretical perspectives can inform future research into osteopathy and mental health to reduce the burden of comorbid psychological factors in patients with persistent physical symptoms and support person-centered multidisciplinary care in mental health

Structure of the neutron-rich N=7 isotones 10Li and 9He

The near threshold structure of the unbound N=7 isotones 10Li and 9He has been investigated using proton removal and breakup from intermediate energy (35 MeV/nucleon) secondary beams of 11Be and 14,15B. The coincident detection of the beam velocity 9Li and 8He fragments and neutrons permitted the relative energy of the in-flight decay of 10Li and 9He to be reconstructed. Both systems were found to exhibited virtual s-wave strength near threshold together with a higher-lying resonance.Comment: 4 pages, 2 figures, Contribution to INPC2010 - "International Nuclear Physics Conference", Vancouver, Canada, 4-9 July 2010, Proceedings to be published in Journal of Physics: Conference Serie

Evaluation of a Habitat Suitability Model to predict the geospatial distribution of Olympia oyster presence in Yaquina Bay, Oregon

A massive reduction in historic populations of Olympia oysters (Ostrea lurida), the only native oyster found on the west coast of North America, has contributed to a loss of ecosystem and cultural services once provided by this species. Resource management agencies and environmental organizations are working to protect and enhance remaining populations, but in many locations, information to characterize the current geospatial distribution of Olympia oysters is lacking. Advances in mapping technology and increased availability of geospatial, ecological data allow for more effective tracking and monitoring of Olympia oysters, which can support protection efforts. However, resource management agencies often face financial and staffing constraints that limit their ability to inventory the species across its range. Habitat Suitability Modeling (HSM) provides a promising approach for making predictions about the geospatial distribution of wild Olympia oyster populations by understanding and analyzing the physical environmental variables that influence its specific habitat. This project evaluates the use of an HSM, developed using geospatial raster layers of salinity, substrate, and elevation, in Yaquina Bay, Oregon to predict locations of Olympia oyster presence. This study was unable to make a conclusive determination regarding the predictive capacity of the HSM due to a small number of field samples. Recommendations are provided for expanding the HSM and supporting several other management applications, including characterizing the abiotic and biotic attributes of the habitat occupied by Olympia oysters and identifying biological monitoring sites

Heterobimetallic Au(I)/Y(III) single chain nanoparticles as recyclable homogenous catalysts

Heterobimetallic single chain nanoparticles were synthesized and applied as recyclable homogenous catalysts. A terpolymer containing two orthogonal ligand moieties, phosphines and carboxylates, was obtained via nitroxide-mediated polymerization. Single chain nanoparticle (SCNP) formation is induced by selective metal complexation of Y(III) by the carboxylate functions, while Au(I) is selectively coordinated to phosphine moieties. In contrast to previous work, the two functionalities, SCNP folding and formation of a catalytic center, were distributed over two metals, which critically increases the flexibility of the system. The formation of Au(I)/Y(III)-SCNPs is evidenced by size exclusion chromatography, dynamic light scattering, nuclear magnetic resonance (1H, 31P{1H}) and infrared spectroscopy. Importantly, the activity of the Au(I)/Y(III)-SCNPs as homogenous, yet recyclable catalyst, bridging the gap between homogenous and heterogeneous catalysis, was demonstrated using the hydroamination of aminoalkynes as an example

Assembly of the Complex between Archaeal RNase P Proteins RPP30 and Pop5

RNase P is a highly conserved ribonucleoprotein enzyme that represents a model complex for understanding macromolecular RNA-protein interactions. Archaeal RNase P consists of one RNA and up to five proteins (Pop5, RPP30, RPP21, RPP29, and RPP38/L7Ae). Four of these proteins function in pairs (Pop5-RPP30 and RPP21–RPP29). We have used nuclear magnetic resonance (NMR) spectroscopy and isothermal titration calorimetry (ITC) to characterize the interaction between Pop5 and RPP30 from the hyperthermophilic archaeon Pyrococcus furiosus (Pfu). NMR backbone resonance assignments of free RPP30 (25 kDa) indicate that the protein is well structured in solution, with a secondary structure matching that observed in a closely related crystal structure. Chemical shift perturbations upon the addition of Pop5 (14 kDa) reveal its binding surface on RPP30. ITC experiments confirm a net 1 : 1 stoichiometry for this tight protein-protein interaction and exhibit complex isotherms, indicative of higher-order binding. Indeed, light scattering and size exclusion chromatography data reveal the complex to exist as a 78 kDa heterotetramer with two copies each of Pop5 and RPP30. These results will inform future efforts to elucidate the functional role of the Pop5-RPP30 complex in RNase P assembly and catalysis

Linking the exotic structure of 17{}^{17}C to its unbound mirror 17{}^{17}Na

The structure of ${}^{17}$C is used to define a nuclear interaction that, when used in a multichannel algebraic scattering theory for the $n+{}^{16}$C system, gives a credible definition of the (compound) excitation spectra. When couplings to the low-lying collective excitations of the ${}^{16}$C-core are taken into account, both sub-threshold and resonant states about the $n+{}^{16}$C threshold are found. Adding Coulomb potentials to that nuclear interaction, the method is used for the mirror system of $p+{}^{16}$Ne to specify the low-excitation spectrum of the particle unstable $^{17}$Na. We compare the results with those of a microscopic cluster model. A spectrum of low excitation resonant states in ${}^{17}$Na is found with some differences to that given by the microscopic-cluster model. The calculated resonance half-widths (for proton emission) range from $\sim 2$ to $\sim 672$ keV.Comment: 13 pages, 5 figure

Dysregulation of metabolic-associated pathways in muscle of breast cancer patients: preclinical evaluation of interleukin-15 targeting fatigue

Background Breast cancer patients report a perception of increased muscle fatigue, which can persist following surgery and standardized therapies. In a clinical experiment, we tested the hypothesis that pathways regulating skeletal muscle fatigue are down-regulated in skeletal muscle of breast cancer patients and that different muscle gene expression patterns exist between breast tumour subtypes. In a preclinical study, we tested the hypothesis that mammary tumour growth in mice induces skeletal muscle fatigue and that overexpression of the cytokine interleukin-15 (IL-15) can attenuate mammary tumourinduced muscle fatigue. Methods Early stage non-metastatic female breast cancer patients (n = 14) and female non-cancer patients (n = 6) provided a muscle biopsy of the pectoralis major muscle during mastectomy, lumpectomy, or breast reconstruction surgeries. The breast cancer patients were diagnosed with either luminal (ER+ /PR+ , n = 6), triple positive (ER+ /PR+ /Her2/neu+ , n = 5), or triple negative (ER/PR/Her2/neu, n = 3) breast tumours and were being treated with curative intent either with neoadjuvant chemotherapy followed by surgery or surgery followed by standard post-operative therapy. Biopsies were used for RNA-sequencing to compare the skeletal muscle gene expression patterns between breast cancer patients and non-cancer patients. The C57BL/6 mouse syngeneic mammary tumour cell line, E0771, was used to induce mammary tumours in immunocompetent mice, and isometric muscle contractile properties and fatigue properties were analysed following 4 weeks of tumour growth. Results RNA-sequencing and subsequent bioinformatics analyses revealed a dysregulation of canonical pathways involved in oxidative phosphorylation, mitochondrial dysfunction, peroxisome proliferator-activated receptor signalling and activation, and IL-15 signalling and production. In a preclinical mouse model of breast cancer, the rate of muscle fatigue was greater in mice exposed to mammary tumour growth for 4 weeks, and this greater muscle fatigue was attenuated in transgenic mice that overexpressed the cytokine IL-15. Conclusions Our data identify novel genes and pathways dysregulated in the muscles of breast cancer patients with early stage non-metastatic disease, with particularly aberrant expression among genes that would predispose these patients to greater muscle fatigue. Furthermore, we demonstrate that IL-15 overexpression can attenuate muscle fatigue associated with mammary tumour growth in a preclinical mouse model of breast cancer. Therefore, we propose that skeletal muscle fatigue is an inherent consequence of breast tumour growth, and this greater fatigue can be targeted therapeutically

High salt diet impairs cerebral blood flow regulation via salt‐induced angiotensin II suppression

ObjectivesThis study sought to determine whether salt‐induced ANG II suppression contributes to impaired CBF autoregulation.MethodsCerebral autoregulation was evaluated with LDF during graded reductions of blood pressure. Autoregulatory responses in rats fed HS (4% NaCl) diet vs LS (0.4% NaCl) diet were analyzed using linear regression analysis, model‐free analysis, and a mechanistic theoretical model of blood flow through cerebral arterioles.ResultsAutoregulation was intact in LS‐fed animals as MAP was reduced via graded hemorrhage to approximately 50 mm Hg. Short‐term (3 days) and chronic (4 weeks) HS diet impaired CBF autoregulation, as evidenced by progressive reductions of laser Doppler flux with arterial pressure reduction. Chronic low dose ANG II infusion (5 mg/kg/min, i.v.) restored CBF autoregulation between the pre‐hemorrhage MAP and 50 mm Hg in rats fed short‐term HS diet. Mechanistic‐based model analysis showed a reduced myogenic response and reduced baseline VSM tone with short‐term HS diet, which was restored by ANG II infusion.ConclusionsShort‐term and chronic HS diet lead to impaired autoregulation in the cerebral circulation, with salt‐induced ANG II suppression as a major factor in the initiation of impaired CBF regulation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149286/1/micc12518_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149286/2/micc12518.pd

Targeting atypical protein kinase C iota reduces viability in glioblastoma stem-like cells via a notch signaling mechanism

In a previous study, Protein Kinase C iota (PRKCI) emerged as an important candidate gene for glioblastoma (GBM) stem-like cell (GSC) survival. Here, we show that PKCι is overexpressed and activated in patient derived GSCs compared with normal neural stem cells and normal brain lysate, and that silencing of PRKCI in GSCs causes apoptosis, along with loss of clonogenicity and reduced proliferation. Notably, PRKCI silencing reduces tumor growth in vivo in a xenograft mouse model. PKCι has been intensively studied as a therapeutic target in non-small cell lung cancer, resulting in the identification of an inhibitor, aurothiomalate (ATM), which disrupts the PKCι/ERK signaling axis. However, we show that, although sensitive to pharmacological inhibition via a pseudosubstrate peptide inhibitor, GSCs are much less sensitive to ATM, suggesting that PKCι acts along a different signaling axis in GSCs. Gene expression profiling of PRKCI-silenced GSCs revealed a novel role of the Notch signaling pathway in PKCι mediated GSC survival. A proximity ligation assay showed that Notch1 and PKCι are in close proximity in GSCs. Targeting PKCι in the context of Notch signaling could be an effective way of attacking the GSC population in GBM

Reinvestigation and application of olivine-quartz-orthopyroxene barometry

Experiments in a piston-cylinder apparatus have been carried out at 700-1050[deg]C, 10-16 kbar to determine the stability of ferrosilite (FeSiO3) relative to fayalite + quartz. Reaction reversals within 0.1-kbar intervals locate the equilibrium at 10.5, 11.0, 11.5, 12.0, 12.6, 13.3, 14.1 and 14.8 kbar at 700, 750, 800, 850, 900, 950, 1000, and 1050[deg]C, respectively, reflecting the intercept with the [alpha]-[beta] quartz transition at about 880[deg]C. The tight reversals severely constrain the reaction slope, providing a basis for limited extrapolation and calculations. However, the lack of accurate activity and cation-distribution data for orthopyroxene and olivine generates substantial uncertainties when considering the effects of large proportions of additional components such as MgO. Experiments and calculations indicate that additional components dramatically extend the pyroxene stability field and that pressures that have been inferred from ferrosilite-rich pyroxenes in natural assemblages are 1-3 kbar too high.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23295/1/0000232.pd