Acute Exercise-Induced Response of Platelet-Monocyte Complexes in Obese, Postmenopausal Women

Inactivity-related diseases such as cardiovascular disease (CVD) are linked to chronic low-grade, systemic inflammation. Platelet-monocyte complexes (PMCs) are markers of in vivo platelet activation and atherosclerosis, and may be early indicators of subclinical inflammation. PURPOSE: To examine the effects of an exercise bout on PMCs in those at risk for CVD. METHODS: Twenty-five overweight-obese (BMI 32.7 ± 5.2 kg×m-2, 55-75 yr) women were randomly assigned to either the exercise (EX, n=13) or non-exercise control (CON, n=12) group. EX performed 2 sets of 8 resistance exercises and a 25-min treadmill walk at 70-80% HRR. Blood was obtained pre-exercise (PR), post- (PO), 1-hour and 2 hours post-exercise (1HR and 2HR). Blood was obtained at the same time points in CON. PMCs were identified via flow cytometry and analyzed in each monocyte phenotype. Monocyte phenotypes were defined as: Mon1 (CD14+CD16−CCR2+), Mon2 (CD14+CD16+CCR2+), and Mon3 (CD14+CD16+CCR2−). All events positive for both CD14 and CD42a (marker for platelets) were considered PMCs. RESULTS: A main effect for time revealed an increase in PMC number at PO (p=0.036) which appears to have been driven by EX (EX = 61.5%; CON = 33.8% increase). PMCs formed with Mon1 and Mon2 followed a similar response. A significant group x time interaction for Mon3 PMC number (p=0.002) indicated an increase from PR to PO (PR = 5218±1170, PO = 8195±1152 cells·ml-1), and a decrease from PO to 1HR and 2HR (1HR = 3767±820 cells·ml-1 2HR = 3818±814 cells·ml-1) in EX. PMC number remained constant for CON at all timepoints. Estimated VO2max was negatively correlated with CD42a MFI (a marker of platelet density per monocyte) (r = -0.583, p = 0.003). Systolic blood pressure (SBP) positively correlated with percent PMC (% CD42a positive monocytes; r = 0.458, p = 0.042). CONCLUSION: Aerobic fitness appears to reduce platelet activation indicated by the negative relationship between VO2max and CD42a MFI. Chronic elevations in resting SBP are linked to PMC percentage, possibly due to sheer stress-induced platelet activation. It is possible that PMC elevation at PO is at least partially driven by exercise-induced increases in BP. These results support previous literature, indicating that PMCs are a CVD risk marker and may elucidate one mechanism by which physical fitness reduces risk for CVD

Failure of Working Memory Training to Enhance Cognition or Intelligence

Fluid intelligence is important for successful functioning in the modern world, but much evidence suggests that fluid intelligence is largely immutable after childhood. Recently, however, researchers have reported gains in fluid intelligence after multiple sessions of adaptive working memory training in adults. The current study attempted to replicate and expand those results by administering a broad assessment of cognitive abilities and personality traits to young adults who underwent 20 sessions of an adaptive dual n-back working memory training program and comparing their post-training performance on those tests to a matched set of young adults who underwent 20 sessions of an adaptive attentional tracking program. Pre- and post-training measurements of fluid intelligence, standardized intelligence tests, speed of processing, reading skills, and other tests of working memory were assessed. Both training groups exhibited substantial and specific improvements on the trained tasks that persisted for at least 6 months post-training, but no transfer of improvement was observed to any of the non-trained measurements when compared to a third untrained group serving as a passive control. These findings fail to support the idea that adaptive working memory training in healthy young adults enhances working memory capacity in non-trained tasks, fluid intelligence, or other measures of cognitive abilities.</p

PET Imaging of Microglia Using PBR28suv Determines Therapeutic Efficacy of Autologous Bone Marrow Mononuclear Cells Therapy in Traumatic Brain Injury

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI

PET Imaging of Microglia Using PBR28suv Determines Therapeutic Efficacy of Autologous Bone Marrow Mononuclear Cells Therapy in Traumatic Brain Injury

Traumatic brain injury (TBI) results in activated microglia. Activated microglia can be measured in vivo by using positron emission topography (PET) ligand peripheral benzodiazepine receptor standardized uptake values (PBR28suv). Cell based therapies have utilized autologous bone marrow mononuclear cells (BMMNCs) to attenuate activated microglia after TBI. This study aims to utilize in vivo PBR28suv to assess the efficacy of BMMNCs therapy after TBI. Seventy-two hours after CCI injury, BMMNCs were harvested from the tibia and injected via tail-vein at 74 h after injury at a concentration of 2 million cells per kilogram of body weight. There were three groups of rats: Sham, CCI-alone and CCI-BMMNCs (AUTO). One hundred twenty days after injury, rodents were imaged with PBR28 and their cognitive behavior assessed utilizing the Morris Water Maze. Subsequent ex vivo analysis included brain volume and immunohistochemistry. BMMNCs therapy attenuated PBR28suv in comparison to CCI alone and it improved spatial learning as measured by the Morris Water Maze. Ex vivo analysis demonstrated preservation of brain volume, a decrease in amoeboid-shaped microglia in the dentate gyrus and an increase in the ratio of ramified to amoeboid microglia in the thalamus. PBR28suv is a viable option to measure efficacy of BMMNCs therapy after TBI

HDAC9 is implicated in atherosclerotic aortic calcification and affects vascular smooth muscle cell phenotype.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification (n = 9,417) or descending thoracic aortic calcification (n = 8,422). Two genetic loci, HDAC9 and RAP1GAP, were associated with abdominal aortic calcification at a genome-wide level (P &lt; 5.0 × 10-8). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein-deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification

Association between footwear use and neglected tropical diseases: a systematic review and meta-analysis

BACKGROUND The control of neglected tropical diseases (NTDs) has primarily focused on preventive chemotherapy and case management. Less attention has been placed on the role of ensuring access to adequate water, sanitation, and hygiene and personal preventive measures in reducing exposure to infection. Our aim was to assess whether footwear use was associated with a lower risk of selected NTDs. METHODOLOGY We conducted a systematic review and meta-analysis to assess the association between footwear use and infection or disease for those NTDs for which the route of transmission or occurrence may be through the feet. We included Buruli ulcer, cutaneous larva migrans (CLM), leptospirosis, mycetoma, myiasis, podoconiosis, snakebite, tungiasis, and soil-transmitted helminth (STH) infections, particularly hookworm infection and strongyloidiasis. We searched Medline, Embase, Cochrane, Web of Science, CINAHL Plus, and Popline databases, contacted experts, and hand-searched reference lists for eligible studies. The search was conducted in English without language, publication status, or date restrictions up to January 2014. Studies were eligible for inclusion if they reported a measure of the association between footwear use and the risk of each NTD. Publication bias was assessed using funnel plots. Descriptive study characteristics and methodological quality of the included studies were summarized. For each study outcome, both outcome and exposure data were abstracted and crude and adjusted effect estimates presented. Individual and summary odds ratio (OR) estimates and corresponding 95% confidence intervals (CIs) were calculated as a measure of intervention effect, using random effects meta-analyses. PRINCIPAL FINDINGS Among the 427 studies screened, 53 met our inclusion criteria. Footwear use was significantly associated with a lower odds of infection of Buruli ulcer (OR=0.15; 95% CI: 0.08-0.29), CLM (OR=0.24; 95% CI: 0.06-0.96), tungiasis (OR=0.42; 95% CI: 0.26-0.70), hookworm infection (OR=0.48; 95% CI: 0.37-0.61), any STH infection (OR=0.57; 95% CI: 0.39-0.84), strongyloidiasis (OR=0.56; 95% CI: 0.38-0.83), and leptospirosis (OR=0.59; 95% CI: 0.37-0.94). No significant association between footwear use and podoconiosis (OR=0.63; 95% CI: 0.38-1.05) was found and no data were available for mycetoma, myiasis, and snakebite. The main limitations were evidence of heterogeneity and poor study quality inherent to the observational studies included. CONCLUSIONS/SIGNIFICANCE Our results show that footwear use was associated with a lower odds of several different NTDs. Access to footwear should be prioritized alongside existing NTD interventions to ensure a lasting reduction of multiple NTDs and to accelerate their control and elimination. PROTOCOL REGISTRATION PROSPERO International prospective register of systematic reviews CRD42012003338

Statements of Agreement From the Targeted Evaluation and Active Management (TEAM) Approaches to Treating Concussion Meeting Held in Pittsburgh, October 15-16, 2015

Conventional management for concussion involves prescribed rest and progressive return to activity. Recent evidence challenges this notion and suggests that active approaches may be effective for some patients. Previous concussion consensus statements provide limited guidance regarding active treatment