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1.  A Plant-Based Diet, Atherogenesis, and Coronary Artery Disease Prevention 
The Permanente Journal  2015;19(1):62-67.
Atherosclerosis associated with high dietary intake of meats, fat, and carbohydrates remains the leading cause of mortality in the US. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent oxidation of low-density lipoprotein. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic coronary artery disease.
A plant-based diet is increasingly becoming recognized as a healthier alternative to a diet laden with meat. Atherosclerosis associated with high dietary intake of meat, fat, and carbohydrates remains the leading cause of mortality in the US. This condition results from progressive damage to the endothelial cells lining the vascular system, including the heart, leading to endothelial dysfunction. In addition to genetic factors associated with endothelial dysfunction, many dietary and other lifestyle factors, such as tobacco use, high meat and fat intake, and oxidative stress, are implicated in atherogenesis. Polyphenols derived from dietary plant intake have protective effects on vascular endothelial cells, possibly as antioxidants that prevent the oxidation of low-density lipoprotein. Recently, metabolites of L-carnitine, such as trimethylamine-N-oxide, that result from ingestion of red meat have been identified as a potential predictive marker of coronary artery disease (CAD). Metabolism of L-carnitine by the intestinal microbiome is associated with atherosclerosis in omnivores but not in vegetarians, supporting CAD benefits of a plant-based diet. Trimethylamine-N-oxide may cause atherosclerosis via macrophage activation. We suggest that a shift toward a plant-based diet may confer protective effects against atherosclerotic CAD by increasing endothelial protective factors in the circulation while reducing factors that are injurious to endothelial cells. The relative ratio of protective factors to injurious endothelial exposure may be a novel approach to assessing an objective dietary benefit from a plant-based diet. This review provides a mechanistic perspective of the evidence for protection by a plant-based diet against atherosclerotic CAD.
PMCID: PMC4315380  PMID: 25431999
2.  A randomized, controlled trial of osteopathic manipulative treatment for acute low back pain in active duty military personnel 
Acute low back pain (ALBP) may limit mobility and impose functional limitations in active duty military personnel. Although some manual therapies have been reported effective for ALBP in military personnel, there have been no published randomized controlled trials (RCTs) of osteopathic manipulative treatment (OMT) in the military. Furthermore, current military ALBP guidelines do not specifically include OMT.
This RCT examined the efficacy of OMT in relieving ALBP and improving functioning in military personnel at Fort Lewis, Washington. Sixty-three male and female soldiers ages 18 to 35 were randomly assigned to a group receiving OMT plus usual care or a group receiving usual care only (UCO).
The primary outcome measures were pain on the quadruple visual analog scale, and functioning on the Roland Morris Disability Questionnaire. Outcomes were measured immediately preceding each of four treatment sessions and at four weeks post-trial. Intention to treat analysis found significantly greater post-trial improvement in ‘Pain Now’ for OMT compared to UCO (P = 0·026). Furthermore, the OMT group reported less ‘Pain Now’ and ‘Pain Typical’ at all visits (P = 0·025 and P = 0·020 respectively). Osteopathic manipulative treatment subjects also tended to achieve a clinically meaningful improvement from baseline on ‘Pain at Best’ sooner than the UCO subjects. With similar baseline expectations, OMT subjects reported significantly greater satisfaction with treatment and overall self-reported improvement (P<0·01).
This study supports the effectiveness of OMT in reducing ALBP pain in active duty military personnel.
PMCID: PMC3267441  PMID: 23372389
Low back pain; Manual medicine; Manipulation
3.  In Vitro Modeling of Repetitive Motion Injury and Myofascial Release 
In this study we modeled repetitive motion strain (RMS) and myofascial release (MFR) in vitro to investigate possible cellular and molecular mechanisms to potentially explain the immediate clinical outcomes associated with RMS and MFR.
Cultured human fibroblasts were strained with 8 hours RMS, 60 seconds MFR and combined treatment; RMS+MFR. Fibroblasts were immediately sampled upon cessation of strain and evaluated for cell morphology, cytokine secretions, proliferation, apoptosis, and potential changes to intracellular signaling molecules.
RMS induced fibroblast elongation of lameopodia, cellular decentralization, reduction of cell to cell contact and significant decreases in cell area to perimeter ratios compared to all other experimental groups (p<0.0001). Cellular proliferation indicated no change among any treatment group; however RMS resulted in a significant increase in apoptosis rate (p<0.05) along with increases in death-associated protein kinase (DAPK) and focal adhesion kinase (FAK) phosphorylation by 74% and 58% respectively, when compared to control. These responses were not observed in the MFR and RMS+MFR group. Of the twenty cytokines measured there was a significant increase in GRO secretion in the RMS+MFR group when compared to control and MFR alone.
Our modeled injury (RMS) appropriately displayed enhanced apoptosis activity and loss of intercellular integrity that is consistent with pro-apoptotic DAPK2 and FAK signaling. Treatment with MFR following RMS resulted in normalization in apoptotic rate and cell morphology both consistent with changes observed in DAPK2. These in vitro studies build upon the cellular evidence base needed to fully explain clinical efficacy of manual manipulative therapies.
PMCID: PMC2853774  PMID: 20226363
Cyclic strain; Human fibroblasts; Morphology; myofascial release; repetitive motion strain
4.  Osteopathic Manipulative Treatment of Back Pain and Related Symptoms during Pregnancy: A Randomized Controlled Trial 
To study osteopathic manipulative treatment (OMT) of back pain and related symptoms during the third trimester of pregnancy.
Study design:
A randomized, placebo-controlled trial was conducted to compare usual obstetrical care (UOBC) and OMT (UOBC+OMT), UOBC and sham ultrasound treatment (UOBC+SUT), and UOBC only. Outcomes included average pain levels and the Roland Morris-Disability Questionnaire (RMDQ) to assess back-specific functioning.
Intention-to-treat analyses included 144 subjects. The RMDQ scores worsened during pregnancy; however, back-specific functioning deteriorated significantly less in the UOBC+OMT group (effect size, 0.72; 95% CI, 0.31-1.14; P=.001 vs. UOBC only; and effect size, 0.35; 95% CI, −0.06-0.76; P=.09 vs. UOBC+SUT). During pregnancy, back pain decreased in the UOBC+OMT group, remained unchanged in the UOBC+SUT group, and increased in the UOBC only group, although no between-group difference achieved statistical significance.
Osteopathic manipulative treatment slows or halts the deterioration of back-specific functioning during the third trimester of pregnancy.
PMCID: PMC2811218  PMID: 19766977
osteopathic manipulative treatment; pregnancy; back pain; physical functioning; randomized controlled trial
5.  Efficacy of osteopathic manipulation as an adjunctive treatment for hospitalized patients with pneumonia: a randomized controlled trial 
The Multicenter Osteopathic Pneumonia Study in the Elderly (MOPSE) is a registered, double-blinded, randomized, controlled trial designed to assess the efficacy of osteopathic manipulative treatment (OMT) as an adjunctive treatment in elderly patients with pneumonia.
406 subjects aged ≥ 50 years hospitalized with pneumonia at 7 community hospitals were randomized using concealed allocation to conventional care only (CCO), light-touch treatment (LT), or OMT groups. All subjects received conventional treatment for pneumonia. OMT and LT groups received group-specific protocols for 15 minutes, twice daily until discharge, cessation of antibiotics, respiratory failure, death, or withdrawal from the study. The primary outcomes were hospital length of stay (LOS), time to clinical stability, and a symptomatic and functional recovery score.
Intention-to-treat (ITT) analysis (n = 387) found no significant differences between groups. Per-protocol (PP) analysis (n = 318) found a significant difference between groups (P = 0.01) in LOS. Multiple comparisons indicated a reduction in median LOS (95% confidence interval) for the OMT group (3.5 [3.2-4.0] days) versus the CCO group (4.5 [3.9-4.9] days), but not versus the LT group (3.9 [3.5-4.8] days). Secondary outcomes of duration of intravenous antibiotics and treatment endpoint were also significantly different between groups (P = 0.05 and 0.006, respectively). Duration of intravenous antibiotics and death or respiratory failure were lower for the OMT group versus the CCO group, but not versus the LT group.
ITT analysis found no differences between groups. PP analysis found significant reductions in LOS, duration of intravenous antibiotics, and respiratory failure or death when OMT was compared to CCO. Given the prevalence of pneumonia, adjunctive OMT merits further study.
PMCID: PMC2848182  PMID: 20302619
6.  A case-control study of osteopathic palpatory findings in type 2 diabetes mellitus 
Although type 2 diabetes mellitus is often managed by osteopathic physicians, osteopathic palpatory findings in this disease have not been adequately studied.
A case-control study was used to measure the association between type 2 diabetes mellitus and a series of 30 osteopathic palpatory findings. The latter included skin changes, trophic changes, tissue changes, tenderness, and immobility at spinal segmental levels T5–T7, T8–T10, and T11-L2 bilaterally. Logistic regression models that adjusted for age, sex, and comorbid conditions were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between type 2 diabetes mellitus and each of these findings.
Results and discussion
A total of 92 subjects were included in the study. After controlling for age, sex, hypertension, and clinical depression, the only significant finding was an association between type 2 diabetes mellitus and tissue changes at T11-L2 on the right side (OR, 5.54; 95% CI, 1.76–17.47; P = .003). Subgroup analyses of subjects with type 2 diabetes mellitus and hypertension demonstrated significant associations with tissue changes at T11-L2 bilaterally (OR, 27.38; 95% CI, 1.75–428; P = .02 for the left side and OR, 24.00; 95% CI, 1.51–382; P = .02 for the right side). Among subjects with type 2 diabetes mellitus and hypertension, there was also a strong diabetes mellitus duration effect for tissue changes at T11-L2 bilaterally (OR, 12.00; 95% CI, 1.02–141; P = .05 for short duration vs. OR, 32.00; 95% CI, 2.29–448; P = .01 for long duration on the left side; and OR, 17.33; 95% CI, 1.39–217; P = .03 for short duration vs. OR, 32.00; 95% CI, 2.29–448; P = .01 for long duration on the right side).
The only consistent finding in this study was an association between type 2 diabetes mellitus and tissue changes at T11-L2 on the right side. Potential explanations for this finding include reflex viscerosomatic changes directly related to the progression of type 2 diabetes mellitus, a spurious association attributable to confounding visceral diseases, or a chance observation unrelated to type 2 diabetes mellitus. Larger prospective studies are needed to better study osteopathic palpatory findings in type 2 diabetes mellitus.
PMCID: PMC1808472  PMID: 17371582
7.  Patient expectations for placebo treatments commonly used in osteopathic manipulative treatment (OMT) clinical trials: a pilot study 
Placebo treatments should be believable to ensure expectation of benefit, yet not provide a true treatment effect. One obstacle to conducting clinical trials with osteopathic manipulative treatment (OMT) is choosing an appropriate placebo. Various placebo treatments have been used in OMT clinical trials. The purpose of this study was to determine expectations of 3 treatments (HVLA, placebo light touch, placebo sub-therapeutic ultrasound) commonly used in OMT clinical research trials.
A randomized, cross-over design was utilized. Subjects were recruited from the Family Medicine Clinic, Texas College of Osteopathic Medicine. Participants watched a video with 2 minute demonstrations of a High Velocity Low Amplitude (HVLA), placebo light touch (LT), and placebo sub-therapeutic ultrasound (ULTRA) treatment for low back pain. The order of presentations was randomized to control for order effect bias. Subjects indicated the extent of their agreement (using a 4 point Likert scale) with 4 statements that were presented after each treatment was viewed: 1)I believe this treatment would allow me to get better quicker; 2)I believe this treatment would decrease my low back pain; 3)I believe this treatment would make me more able to do the things I want to do; 4)This seems like a logical way to treat low back pain. Repeated measures analysis of variance was performed, and a partial Eta squared was calculated for each statement. Effect sizes (Cohen's d) were calculated where appropriate.
Thirty of 40 eligible subjects participated. Twenty-two (73%) were female, 16 (53%) were Caucasian, and 11 (37%) had completed college. The mean age was 43 (SD = 15.). Repeated measures ANOVA revealed no significant differences for statements 2 and 4. For both statements 1 (p = 0.025) and 3 (p = 0.039), post hoc analysis revealed a difference between HVLA and LT. The partial Eta squared (ηp2) was 0.105, 0.072, 0.107, and 0.024 for each statement, respectively.
There is a difference in treatment expectation between HVLA and LT for statements 1 and 3. Participants responded more positively after viewing the HVLA treatment than the LT treatment. This suggests that sub-therapeutic ultrasound is the better placebo because the expectations were similar to those for HVLA.
PMCID: PMC1805771  PMID: 17371579

Results 1-7 (7)