Relational Frame Theory: Some Implications for Understanding and Treating Human Psychopathology

In the current paper, we attempt to show how both the basic and applied sciences of behavior analysis have been transformed by the modern research agenda in human language and cognition, known as Relational Frame Theory (RFT). At the level of basic process, the paper argues that the burgeoning literature on derived stimulus relations calls for a reinterpretation of complex human behavior that extends beyond a purely contingencybased analysis. Specifically, the paper aims to show how a more complete account of complex human behavior includes an analysis of relational frames, relational networks, relating relations, rules, perspective-taking, and the concept of self. According to the theory, this analysis gives rise to a new interpretation of human psychopathology that necessarily transforms the applied science of behavior therapy. The current paper is divided into three parts. In Part 1, we provide a brief summary of the integrated history of behavioral psychology and behavior therapy, including their emphases on the principles of classical and operant conditioning as the basis for an account of human psychopathology. In Part 2, the core features of RFT are presented, including the three concepts of bidirectional stimulus relations, relating relations, and rule-governance that constitute critical components of the RFT approach to human psychopathology. The paper therein attempts to illustrate, with the use of clinically relevant examples, the ways in which these concepts can be used to understand psychopathology and psychotherapy. In Part 3, RFT interpretations of three central features of Acceptance and Commitment Therapy (ACT), namely acceptance, defusion, and values are provided with a view to demonstrating the utility of basic RFT concepts in the treatment of human suffering

The role played by cell-substrate interactions in the pathogenesis of osteoclast-mediated peri-implant osteolysis

Prosthetic wear debris-induced peri-implant osteolysis is a major cause of aseptic loosening after total joint replacement. In this condition, wear particles released from the implant components induce a granulomatous inflammatory reaction at the interface between implant and adjacent bone, leading to progressive bone resorption and loss of fixation. The present study was undertaken to characterize definitively the phenotype of osteoclast-like cells associated with regions of peri-implant focal bone resorption and to compare the phenotypic features of these cells with those of mononucleated and multinucleated cells associated with polyethylene wear particles. Peri-implant tissues were obtained from patients undergoing hip revision surgery for aseptic loosening after total joint replacement. Cells were examined for the expression of several markers associated with the osteoclast phenotype using immunohistochemistry, histochemistry, and/or in situ hybridization. CD68 protein, a marker expressed by multiple macrophage lineage cell types, was detected in mononucleated and multinucleated cells associated with polyethylene particles and the bone surface. Cathepsin K and tartrate-resistant acid phosphatase were expressed highly in both mononucleated and multinucleated cells associated with the bone surface. Levels of expression were much lower in cells associated with polyethylene particles. High levels of β(3 )integrin protein were detected in cells in contact with bone. Multinucleated cells associated with polyethylene particles exhibited faint positive staining. Calcitonin receptor mRNA expression was detected solely in multinucleated cells present in resorption lacunae on the bone surface and was absent in cells associated with polyethylene particles. Our findings provide further evidence that cells expressing the full repertoire of osteoclast phenotypic markers are involved in the pathogenesis of peri-implant osteolysis after total joint replacement. They also demonstrate that foreign body giant cells, although believed to be phenotypically and functionally distinct from osteoclasts, express many osteoclast-associated genes and gene products. However, the levels and patterns of expression of these genes in the two cell types differ. We speculate that, in addition to the role of cytokines and growth factors, the substrate with which these cells interact plays a critical role in their differential phenotypic and functional properties

CD34‐positive superficial myxofibrosarcoma: a potential diagnostic pitfall

Background Myxofibrosarcoma (MFS) arises most commonly in the proximal extremities of the elderly, where it may involve subcutaneous and dermal tissues and masquerade as benign entities in limited biopsy samples. We encountered such a case, in which positivity for CD34 and morphologic features were initially wrongly interpreted as a ‘low‐fat/fat‐free’ spindle cell/pleomorphic lipoma. Case series have not assessed prevalence of CD34 reactivity among cutaneous examples of MFS. Methods We performed a systematic review of our institution's experience, selecting from among unequivocal MFS resection specimens those superficial cases in which a limited biopsy sample might prove difficult to interpret. These cases were immunostained for CD34 and tabulated for clinicopathologic characteristics. Results After review of all MFS diagnoses over 5 years (n = 56), we identified a study group of superficial MFS for comparison to the index case (total n = 8). Of these, the index and three additional cases (4 of 8, 50%; 2 low, 2 high grade) demonstrated positive staining for CD34 , with diffuse staining of spindled cells including cellular processes. Four additional cases showed no or equivocal/rare staining. Conclusions CD34 positivity should be recognized as prevalent among such cases and should not be inappropriately construed as inveighing against a diagnosis of MFS in favor of benign entities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98187/1/cup12158.pd

ZnO Nanoparticles Modulate the Ionic Transport and Voltage Regulation of Lysenin Nanochannels

Background: The insufficient understanding of unintended biological impacts from nanomaterials (NMs) represents a serious impediment to their use for scientific, technological, and medical applications. While previous studies have focused on understanding nanotoxicity effects mostly resulting from cellular internalization, recent work indicates that NMs may interfere with transmembrane transport mechanisms, hence enabling contributions to nanotoxicity by affecting key biological activities dependent on transmembrane transport. In this line of inquiry, we investigated the effects of charged nanoparticles (NPs) on the transport properties of lysenin, a pore-forming toxin that shares fundamental features with ion channels such as regulation and high transport rate. Results: The macroscopic conductance of lysenin channels greatly diminished in the presence of cationic ZnO NPs. The inhibitory effects were asymmetrical relative to the direction of the electric field and addition site, suggesting electrostatic interactions between ZnO NPs and a binding site. Similar changes in the macroscopic conductance were observed when lysenin channels were reconstituted in neutral lipid membranes, implicating protein-NP interactions as the major contributor to the reduced transport capabilities. In contrast, no inhibitory effects were observed in the presence of anionic SnO2 NPs. Additionally, we demonstrate that inhibition of ion transport is not due to the dissolution of ZnO NPs and subsequent interactions of zinc ions with lysenin channels. Conclusion: We conclude that electrostatic interactions between positively charged ZnO NPs and negative charges within the lysenin channels are responsible for the inhibitory effects on the transport of ions. These interactions point to a potential mechanism of cytotoxicity, which may not require NP internalization

Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

Patient Image Data. (XLSX 19 kb

The utility of ETV1, ETV4 and ETV5 RNA inâ situ hybridization in the diagnosis of CICâ DUX sarcomas

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136260/1/his13112_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136260/2/his13112.pd

Absence of Dap12 and the αvβ3 integrin causes severe osteopetrosis

In vitro, ligand occupancy of αvβ3 integrin induces phosphorylation of Dap12, which is essential for osteoclast function. Like mice deleted of only αvβ3, Dap12(−/−) mice exhibited a slight increase in bone mass, but Dap12(−/−) mice, lacking another ITAM protein, FcRγ, were severely osteopetrotic. The mechanism by which FcRγ compensates for Dap12 deficiency is unknown. We find that co-deletion of FcRγ did not exacerbate the skeletal phenotype of β3(−/−) mice. In contrast, β3/Dap12 double-deficient (DAP/β3(−/−)) mice (but not β1/Dap12 double-deficient mice) were profoundly osteopetrotic, reflecting severe osteoclast dysfunction relative to those lacking αvβ3 or Dap12 alone. Activation of OSCAR, the FcRγ co-receptor, rescued Dap12(−/−) but not DAP/β3(−/−)osteoclasts. Thus, the absence of αvβ3 precluded compensation for Dap12 deficiency by FcRγ. In keeping with this, Syk phosphorylation did not occur in OSCAR-activated DAP/β3(−/−) osteoclasts. Thus, FcRγ requires the osteoclast αvβ3 integrin to normalize the Dap12-deficient skeleton

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

Estimating taxon-specific population dynamics in diverse microbial communities

Understanding how population-level dynamics contribute to ecosystem-level processes is a primary focus of ecological research and has led to important breakthroughs in the ecology of macroscopic organisms. However, the inability to measure population-specific rates, such as growth, for microbial taxa within natural assemblages has limited ecologists’ understanding of how microbial populations interact to regulate ecosystem processes. Here, we use isotope incorporation within DNA molecules to model taxon- specific population growth in the presence of 18O-labeled water. By applying this model to phylogenetic marker sequencing data collected from stable-isotope probing studies, we estimate rates of growth, mortal- ity, and turnover for individual microbial populations within soil assemblages. When summed across the entire bacterial community, our taxon-specific estimates are within the range of other whole-assemblage measurements of bacterial turnover. Because it can be applied to environmental samples, the approach we present is broadly applicable to measuring population growth, mortality, and associated biogeochemical process rates of microbial taxa for a wide range of ecosystems and can help reveal how individual microbial populations drive biogeochemical fluxes