Quantitative ultrasound to assess efficacy of treatment for neck somatic dysfunctions: a feasibility study.

CONTEXT: Neck pain is a common complaint in healthcare clinics. Although the pathogenesis of neck pain is often multifactorial, trapezius muscle dysfunction has been commonly linked to neck pain. Osteopathic manipulative treatment (OMT) has been demonstrated to be an effective treatment modality in treating trapezius muscle dysfunction and neck pain. However, there is a current lack of objective, quantitative measures to assess the effectiveness of OMT. Through previous research, ultrasound technology has been shown to be promising in its ability to quantify tissue changes both pre- and post-OMT. OBJECTIVES: The objectives of this study are to evaluate the feasibility of shear wave elastography (SWE) in assessing upper trapezius muscles with pain and hypertonicity, as well as the changes in these muscles post-OMT for cervical somatic dysfunctions. METHODS: After obtaining approval from the Rocky Vista University Institutional Review Board and written informed consent from participants, SWE and osteopathic assessments were performed on 22 adult participants with and without cervical spine somatic dysfunction. Participants with positive osteopathic assessments of tissue texture, asymmetry, restricted motion, and/or tenderness (TART) were treated utilizing OMT. Shear wave velocity (SWV, m/s) and shear wave velocity rate [SWVR = (SWV contraction - SWV relaxation)/ SWV relaxation] of the upper trapezius muscles with and without pain and hypertonicity, and before and after OMT, were examined utilizing a two-tailed t-test. RESULTS: SWV in muscle contraction and SWVR were significantly lower in muscles with pain compared to muscles without pain (p≤0.01). SWV in muscle contraction was also significantly lower in hypertonic muscles compared to normotonic muscles (p<0.01). Following OMT, SWV in muscle contraction and SWVR in muscles with pain and hypertonic increased significantly (p≤0.01). Overall TART score of all muscles with somatic dysfunction (SD) after OMT significantly decreased (p<0.01). SWV in muscle contraction and SWVR in hypertonic muscles were also significantly increased (p≤0.03), with an improvement index of 0.11 and 0.20. CONCLUSIONS: This study's results demonstrate the feasibility of utilizing SWE to evaluate somatic dysfunctions of the upper trapezius musculature and the efficacy of OMT for neck somatic dysfunctions.

γ-H2AX kinetics as a novel approach to high content screening for small molecule radiosensitizers.

BACKGROUND: Persistence of γ-H2AX after ionizing radiation (IR) or drug therapy is a robust reporter of unrepaired DNA double strand breaks in treated cells. METHODS: DU-145 prostate cancer cells were treated with a chemical library ±IR and assayed for persistence of γ-H2AX using an automated 96-well immunocytochemistry assay at 4 hours after treatment. Hits that resulted in persistence of γ-H2AX foci were tested for effects on cell survival. The molecular targets of hits were validated by molecular, genetic and biochemical assays and in vivo activity was tested in a validated Drosophila cancer model. RESULTS: We identified 2 compounds, MS0019266 and MS0017509, which markedly increased persistence of γ-H2AX, apoptosis and radiosensitization in DU-145 cells. Chemical evaluation demonstrated that both compounds exhibited structurally similar and biochemical assays confirmed that these compounds inhibit ribonucleotide reductase. DNA microarray analysis and immunoblotting demonstrates that MS0019266 significantly decreased polo-like kinase 1 gene and protein expression. MS0019266 demonstrated in vivo antitumor activity without significant whole organism toxicity. CONCLUSIONS: MS0019266 and MS0017509 are promising compounds that may be candidates for further development as radiosensitizing compounds as inhibitors of ribonucleotide reductase.