Person: Macklin, Eric
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Macklin
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Eric
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Macklin, Eric
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Publication Complexity-Based Measures Inform Effects of Tai Chi Training on Standing Postural Control: Cross-Sectional and Randomized Trial Studies(Public Library of Science, 2014) Wayne, Peter; Gow, Brian J.; Costa, Madalena; Peng, C.-K.; Lipsitz, Lewis; Hausdorff, Jeffrey M.; Davis, Roger; Walsh, Jacquelyn N.; Lough, Matthew; Novak, Vera; Yeh, Gloria; Ahn, Andrew; Macklin, Eric; Manor, BradBackground: Diminished control of standing balance, traditionally indicated by greater postural sway magnitude and speed, is associated with falls in older adults. Tai Chi (TC) is a multisystem intervention that reduces fall risk, yet its impact on sway measures vary considerably. We hypothesized that TC improves the integrated function of multiple control systems influencing balance, quantifiable by the multi-scale “complexity” of postural sway fluctuations. Objectives: To evaluate both traditional and complexity-based measures of sway to characterize the short- and potential long-term effects of TC training on postural control and the relationships between sway measures and physical function in healthy older adults. Methods: A cross-sectional comparison of standing postural sway in healthy TC-naïve and TC-expert (24.5±12 yrs experience) adults. TC-naïve participants then completed a 6-month, two-arm, wait-list randomized clinical trial of TC training. Postural sway was assessed before and after the training during standing on a force-plate with eyes-open (EO) and eyes-closed (EC). Anterior-posterior (AP) and medio-lateral (ML) sway speed, magnitude, and complexity (quantified by multiscale entropy) were calculated. Single-legged standing time and Timed-Up–and-Go tests characterized physical function. Results: At baseline, compared to TC-naïve adults (n = 60, age 64.5±7.5 yrs), TC-experts (n = 27, age 62.8±7.5 yrs) exhibited greater complexity of sway in the AP EC (P = 0.023), ML EO (P<0.001), and ML EC (P<0.001) conditions. Traditional measures of sway speed and magnitude were not significantly lower among TC-experts. Intention-to-treat analyses indicated no significant effects of short-term TC training; however, increases in AP EC and ML EC complexity amongst those randomized to TC were positively correlated with practice hours (P = 0.044, P = 0.018). Long- and short-term TC training were positively associated with physical function. Conclusion: Multiscale entropy offers a complementary approach to traditional COP measures for characterizing sway during quiet standing, and may be more sensitive to the effects of TC in healthy adults. Trial Registration ClinicalTrials.gov NCT01340365Publication Craniofacial features as assessed by lateral cephalometric measurements in children with Down syndrome(Springer Berlin Heidelberg, 2016) Allareddy, Veerasathpurush; Ching, Nicholas; Macklin, Eric; Voelz, Lauren; Weintraub, Gil; Davidson, Emily; Prock, Lisa; Rosen, Dennis; Brunn, Richard; Skotko, BrianObjective: The objective of the present study is to examine the craniofacial development of patients with Down syndrome (DS) and compare them with a neurotypical population. Methods: This study is a cross-sectional analysis of lateral cephalometric radiographs of participants with DS. The study population consisted of children and young adults with DS aged 3–25 years. Cephalometric data were summarized by age and sex. Raw and normalized z-scores were computed. One-sample t tests were used to test whether mean z-scores differed from zero. The demographic characteristics between those with or without lateral cephalograms among all study participants were compared by Fisher’s exact tests. Results: The study sample comprised of 27 participants with DS. Study subjects demonstrated a class III skeletal pattern. This was more pronounced in the older age groups as compared to younger age groups. Subjects also had an increased proportionate lower anterior face height to total facial height compared to normative standards. Gonial angles, mandibular plane angles, and airway measurements increased with age. Conclusions: Patients with Down syndrome present typically with class III skeletal pattern and long lower anterior facial heights. In patients with Down syndrome, comprehensive phase of orthodontic treatment may be best initiated following cessation of growth.Publication Genomic and Clinical Effects Associated with a Relaxation Response Mind-Body Intervention in Patients with Irritable Bowel Syndrome and Inflammatory Bowel Disease(Public Library of Science, 2015) Kuo, Braden; Bhasin, Manoj; Jacquart, Jolene; Scult, Matthew A.; Slipp, Lauren; Riklin, Eric Isaac Kagan; Lepoutre, Veronique; Comosa, Nicole; Norton, Beth-Ann; Dassatti, Allison; Rosenblum, Jessica; Thurler, Andrea H.; Surjanhata, Brian C.; Hasheminejad, Nicole N.; Kagan, Leslee; Slawsby, Ellen; Rao, Sowmya R.; Macklin, Eric; Fricchione, Gregory; Benson, Herbert; Libermann, Towia; Korzenik, Joshua; Denninger, JohnIntroduction: Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD) can profoundly affect quality of life and are influenced by stress and resiliency. The impact of mind-body interventions (MBIs) on IBS and IBD patients has not previously been examined. Methods: Nineteen IBS and 29 IBD patients were enrolled in a 9-week relaxation response based mind-body group intervention (RR-MBI), focusing on elicitation of the RR and cognitive skill building. Symptom questionnaires and inflammatory markers were assessed pre- and post-intervention, and at short-term follow-up. Peripheral blood transcriptome analysis was performed to identify genomic correlates of the RR-MBI. Results: Pain Catastrophizing Scale scores improved significantly post-intervention for IBD and at short-term follow-up for IBS and IBD. Trait Anxiety scores, IBS Quality of Life, IBS Symptom Severity Index, and IBD Questionnaire scores improved significantly post-intervention and at short-term follow-up for IBS and IBD, respectively. RR-MBI altered expression of more genes in IBD (1059 genes) than in IBS (119 genes). In IBD, reduced expression of RR-MBI response genes was most significantly linked to inflammatory response, cell growth, proliferation, and oxidative stress-related pathways. In IBS, cell cycle regulation and DNA damage related gene sets were significantly upregulated after RR-MBI. Interactive network analysis of RR-affected pathways identified TNF, AKT and NF-κB as top focus molecules in IBS, while in IBD kinases (e.g. MAPK, P38 MAPK), inflammation (e.g. VEGF-C, NF-κB) and cell cycle and proliferation (e.g. UBC, APP) related genes emerged as top focus molecules. Conclusions: In this uncontrolled pilot study, participation in an RR-MBI was associated with improvements in disease-specific measures, trait anxiety, and pain catastrophizing in IBS and IBD patients. Moreover, observed gene expression changes suggest that NF-κB is a target focus molecule in both IBS and IBD—and that its regulation may contribute to counteracting the harmful effects of stress in both diseases. Larger, controlled studies are needed to confirm this preliminary finding. Trial Registration ClinicalTrials.Gov NCT02136745Publication Tai Chi Training may Reduce Dual Task Gait Variability, a Potential Mediator of Fall Risk, in Healthy Older Adults: Cross-Sectional and Randomized Trial Studies(Frontiers Media S.A., 2015) Wayne, Peter; Hausdorff, Jeffrey M.; Lough, Matthew; Gow, Brian J.; Lipsitz, Lewis; Novak, Vera; Macklin, Eric; Peng, Chung-Kang; Manor, BradBackground: Tai Chi (TC) exercise improves balance and reduces falls in older, health-impaired adults. TC’s impact on dual task (DT) gait parameters predictive of falls, especially in healthy active older adults, however, is unknown. Purpose To compare differences in usual and DT gait between long-term TC-expert practitioners and age-/gender-matched TC-naïve adults, and to determine the effects of short-term TC training on gait in healthy, non-sedentary older adults. Methods: A cross-sectional study compared gait in healthy TC-naïve and TC-expert (24.5 ± 12 years experience) older adults. TC-naïve adults then completed a 6-month, two-arm, wait-list randomized clinical trial of TC training. Gait speed and stride time variability (Coefficient of Variation %) were assessed during 90 s trials of undisturbed and cognitive DT (serial subtractions) conditions. Results: During DT, gait speed decreased (p < 0.003) and stride time variability increased (p < 0.004) in all groups. Cross-sectional comparisons indicated that stride time variability was lower in the TC-expert vs. TC-naïve group, significantly so during DT (2.11 vs. 2.55%; p = 0.027); by contrast, gait speed during both undisturbed and DT conditions did not differ between groups. Longitudinal analyses of TC-naïve adults randomized to 6 months of TC training or usual care identified improvement in DT gait speed in both groups. A small improvement in DT stride time variability (effect size = 0.2) was estimated with TC training, but no significant differences between groups were observed. Potentially important improvements after TC training could not be excluded in this small study. Conclusion: In healthy active older adults, positive effects of short- and long-term TC were observed only under cognitively challenging DT conditions and only for stride time variability. DT stride time variability offers a potentially sensitive metric for monitoring TC’s impact on fall risk with healthy older adults.Publication Immunization of HIV-1-Infected Persons With Autologous Dendritic Cells Transfected With mRNA Encoding HIV-1 Gag and Nef: Results of a Randomized, Placebo-Controlled Clinical Trial(JAIDS Journal of Acquired Immune Deficiency Syndromes, 2015) Gandhi, Rajesh; Kwon, Douglas; Macklin, Eric; Shopis, Janet R.; McLean, Anna P.; McBrine, Nicole; Flynn, Theresa; Peter, Lauren; Sbrolla, Amy; Kaufmann, Daniel E.; Porichis, Filippos; Walker, Bruce; Bhardwaj, Nina; Barouch, Dan; Kavanagh, Daniel G.Background: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. Methods: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10. All participants also received DCs pulsed with keyhole limpet hemocyanin (KLH) to assess whether responses to a neo-antigen could be induced. Results: After immunization, there were no differences in interferon-gamma enzyme-linked immunospot responses to HIV-1 Gag or Nef in the vaccine or placebo group. CD4 proliferative responses to KLH increased 2.4-fold (P = 0.026) and CD8 proliferative responses to KLH increased 2.5-fold (P = 0.053) after vaccination. There were increases in CD4 proliferative responses to HIV-1 Gag (2.5-fold vs. baseline, 3.4-fold vs. placebo, P = 0.054) and HIV-1 Nef (2.3-fold vs. baseline, 6.3-fold vs. placebo, P = 0.009) among vaccine recipients, but these responses were short-lived. Conclusion: Immunization with DCs transfected with mRNA encoding HIV-1 Gag and Nef did not induce significant interferon-gamma enzyme-linked immunospot responses. There were increases in proliferative responses to HIV-1 antigens and to a neo-antigen, KLH, but the effects were transient. Dendritic cell vaccination should be optimized to elicit stronger and long-lasting immune responses for this strategy to be effective as an HIV-1 therapeutic vaccine.Publication How common are ALS plateaus and reversals?(Lippincott Williams & Wilkins, 2015) Bedlack, Richard S.; Vaughan, Timothy; Wicks, Paul; Heywood, Jamie; Sinani, Ervin; Selsov, Roger; Macklin, Eric; Schoenfeld, David; Cudkowicz, Merit; Sherman, AlexObjective: To determine the frequency of amyotrophic lateral sclerosis (ALS) plateaus and reversals in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database. Methods: We analyzed Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and ALSFRS–revised (ALSFRS-R) data from PRO-ACT participants. The frequencies of participants experiencing plateaus (periods where scores did not change) were calculated over 6-, 12-, and 18-month epochs. The percentage of participants ever experiencing reversals (periods where scores improved) of different lengths were also calculated and plotted. Results: Over 6 months, 25% of 3,132 participants did not decline. Over 12 months, 16% of 2,105 participants did not decline. Over 18 months, 7% of 1,218 participants did not decline. Small ALS reversals were also common, especially over shorter follow-up intervals; 14% of 1,343 participants had a 180-day interval where their ALSFRS-R slope was greater than zero. Fewer than 1% of participants ever experienced improvements of 4 or more ALSFRS-R points lasting at least 12 months. Conclusion: ALS plateaus and small reversals are common, especially over brief intervals. In light of these data, stable disease, especially for a short period of time, should not be interpreted as an ALS treatment effect. Large sustained ALS reversals, on the other hand, are rare, potentially important, and warrant further study.Publication Interaction of the Onset of Spring and Elevated Atmospheric CO2 on Ragweed (Ambrosia artemisiifolia L.) Pollen Production(National Institute of Environmental Health Sciences, 2006) Rogers, Christine Anne; Wayne, Peter; Macklin, Eric; Muilenberg, Michael; Wagner, Christopher J.; Epstein, Paul; Bazzaz, Fakhri A.Increasing atmospheric carbon dioxide is responsible for climate changes that are having widespread effects on biological systems. One of the clearest changes is earlier onset of spring and lengthening of the growing season. We designed the present study to examine the interactive effects of timing of dormancy release of seeds with low and high atmospheric CO2 on biomass, reproduction, and phenology in ragweed plants (Ambrosia artemisiifolia L.), which produce highly allergenic pollen. We released ragweed seeds from dormancy at three 15-day intervals and grew plants in climate-controlled glasshouses at either ambient or 700-ppm CO2 concentrations, placing open-top bags over inflorescences to capture pollen. Measurements of plant height and weight; inflorescence number, weight, and length; and days to anthesis and anthesis date were made on each plant, and whole-plant pollen productivity was estimated from an allometric-based model. Timing and CO2 interacted to influence pollen production. At ambient CO2 levels, the earlier cohort acquired a greater biomass, a higher average weight per inflorescence, and a larger number of inflorescences; flowered earlier; and had 54.8% greater pollen production than did the latest cohort. At high CO2 levels, plants showed greater biomass and reproductive effort compared with those in ambient CO2 but only for later cohorts. In the early cohort, pollen production was similar under ambient and high CO2, but in the middle and late cohorts, high CO2 increased pollen production by 32% and 55%, respectively, compared with ambient CO2 levels. Overall, ragweed pollen production can be expected to increase significantly under predicted future climate conditions.Publication Tai Chi for Reducing Dual-task Gait Variability, a Potential Mediator of Fall Risk in Parkinson’s Disease: A Pilot Randomized Controlled Trial(SAGE Publications, 2018) Vergara-Diaz, Gloria; Osypiuk, Kamila; Hausdorff, Jeffrey M; Bonato, Paolo; Gow, Brian J; Miranda, Jose GV; Sudarsky, Lewis; Tarsy, Daniel; Fox, Michael; Gardiner, Paula; Thomas, Cathi A; Macklin, Eric; Wayne, PeterObjectives: To assess the feasibility and inform design features of a fully powered randomized controlled trial (RCT) evaluating the effects of Tai Chi (TC) in Parkinson’s disease (PD) and to select outcomes most responsive to TC assessed during off-medication states. Design: Two-arm, wait-list controlled RCT. Settings Tertiary care hospital. Subjects Thirty-two subjects aged 40–75 diagnosed with idiopathic PD within 10 years. Interventions Six-month TC intervention added to usual care (UC) versus UC alone. Outcome Measures Primary outcomes were feasibility-related (recruitment rate, adherence, and compliance). Change in dual-task (DT) gait stride-time variability (STV) from baseline to 6 months was defined, a priori, as the clinical outcome measure of primary interest. Other outcomes included: PD motor symptom progression (Unified Parkinson’s Disease Rating Scale [UPDRS]), PD-related quality of life (PDQ-39), executive function (Trail Making Test), balance confidence (Activity-Specific Balance Confidence Scale, ABC), and Timed Up and Go test (TUG). All clinical assessments were made in the off-state for PD medications. Results: Thirty-two subjects were enrolled into 3 sequential cohorts over 417 days at an average rate of 0.08 subjects per day. Seventy-five percent (12/16) in the TC group vs 94% (15/16) in the UC group completed the primary 6-month follow-up assessment. Mean TC exposure hours overall: 52. No AEs occurred during or as a direct result of TC exercise. Statistically nonsignificant improvements were observed in the TC group at 6 months in DT gait STV (TC [20.1%] vs UC [−0.1%] group [effect size 0.49; P = .47]), ABC, TUG, and PDQ-39. UPDRS progression was modest and very similar in TC and UC groups. Conclusions: Conducting an RCT of TC for PD is feasible, though measures to improve recruitment and adherence rates are needed. DT gait STV is a sensitive and logical outcome for evaluating the combined cognitive-motor effects of TC in PD.Publication Effects of Metformin on Spatial and Verbal Memory in Children with ASD and Overweight Associated with Atypical Antipsychotic Use(Mary Ann Liebert, Inc., 2018) Aman, Michael G.; Hollway, Jill A.; Veenstra-VanderWeele, Jeremy; Handen, Benjamin L.; Sanders, Kevin B.; Chan, James; Macklin, Eric; Arnold, L. Eugene; Wong, Taylor; Newsom, Cassandra; Hastie Adams, Rianne; Marler, Sarah; Peleg, Naomi; Anagnostou, Evdokia A.Abstract Objectives: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use. Methods: We studied the effects of metformin (Riomet®) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management. Phase 1 was a 16-week, randomized, double-blind, placebo-controlled, parallel-group comparison of metformin (500–850 mg given twice a day) versus placebo. During Phase 2, all participants took open-label metformin from week 17 through week 32. We assessed spatial and verbal memory using the Neuropsychological Assessment 2nd Edition (NEPSY–II) and a modified children's verbal learning task. Results: No measures differed between participants randomized to metformin versus placebo, at either 16 or 32 weeks, after adjustment for multiple comparisons. Sixteen-week change in memory for spatial location on the NEPSY–II was nominally better among participants randomized to placebo. However, patterns of treatment response across all measures revealed no systematic differences in performance, suggesting that metformin had no effect on spatial or verbal memory in these children. Conclusions: Although further study is needed to support these null effects, the overall impression is that metformin does not affect memory in overweight youth with ASD who were taking atypical antipsychotic medications.Publication Can Tai Chi training impact fractal stride time dynamics, an index of gait health, in older adults? Cross-sectional and randomized trial studies(Public Library of Science, 2017) Gow, Brian J.; Hausdorff, Jeffrey M.; Manor, Brad; Lipsitz, Lewis; Macklin, Eric; Bonato, Paolo; Novak, Vera; Peng, Chung-Kang; Ahn, Andrew; Wayne, PeterPurpose To determine if Tai Chi (TC) has an impact on long-range correlations and fractal-like scaling in gait stride time dynamics, previously shown to be associated with aging, neurodegenerative disease, and fall risk. Methods: Using Detrended Fluctuation Analysis (DFA), this study evaluated the impact of TC mind-body exercise training on stride time dynamics assessed during 10 minute bouts of overground walking. A hybrid study design investigated long-term effects of TC via a cross-sectional comparison of 27 TC experts (24.5 ± 11.8 yrs experience) and 60 age- and gender matched TC-naïve older adults (50–70 yrs). Shorter-term effects of TC were assessed by randomly allocating TC-naïve participants to either 6 months of TC training or to a waitlist control. The alpha (α) long-range scaling coefficient derived from DFA and gait speed were evaluated as outcomes. Results: Cross-sectional comparisons using confounder adjusted linear models suggest that TC experts exhibited significantly greater long-range scaling of gait stride time dynamics compared with TC-naïve adults. Longitudinal random-slopes with shared baseline models accounting for multiple confounders suggest that the effects of shorter-term TC training on gait dynamics were not statistically significant, but trended in the same direction as longer-term effects although effect sizes were very small. In contrast, gait speed was unaffected in both cross-sectional and longitudinal comparisons. Conclusion: These preliminary findings suggest that fractal-like measures of gait health may be sufficiently precise to capture the positive effects of exercise in the form of Tai Chi, thus warranting further investigation. These results motivate larger and longer-duration trials, in both healthy and health-challenged populations, to further evaluate the potential of Tai Chi to restore age-related declines in gait dynamics. Trial registration The randomized trial component of this study was registered at ClinicalTrials.gov (NCT01340365).