N-3 FATTY ACIDS AND JUVENILE TRAUMATIC BRAIN INJURY: EFFECTS OF DIETARY N-3 FATTY ACID CONTENT, N-3 FATTY ACID STATUS, AND ORALLY DOSED FISH OIL ON SENSORIMOTOR AND BIOCHEMICAL OUTCOMES

Children under five years of age are at high risk for sustaining traumatic brain injury (TBI) and tend to have poorer outcomes despite greater neuroplasticity in children. Hence, there is a great need to study TBI specifically in models of juvenile injury. Additionally, long chain n-3 polyunsaturated fatty acids (LC-PUFA) are a major component of neural membranes, and accumulate in the brain during late gestation and early childhood. Low dietary content of these essential fatty acids results in decreased n-3 LC-PUFA accumulation in the developing brain. Long-chain n-3 polyunsaturated fatty acids have multiple neuroprotective and anti-inflammatory activities, thus low dietary LC-PUFA content may put children at risk for poorer outcomes after TBI. The first aim established a juvenile TBI model with consistent, measurable deficits, without debilitating injury or mortality. In order to assess functional outcomes including severity of initial injury and the duration of deficits, a qualitative assessment of common sensorimotor behavioral tests in rats of various sizes and developmental stages (postnatal days 16-45, 35-190 g) was performed. Tests were evaluated for their developmental appropriateness, scalability for growth, necessity for extensive pre-training, and throughput capability. The tests evaluated were grid-walk, automated gait analysis (DigiGaitTM), rotarod, beam walk, spontaneous forelimb elevation test, and force-plate actometry. Both the rotarod and grid-walk tests were eliminated on their inability to scale for growth of the animal. Rotarod also required several days of pre-training that young animals were unable to perform. DigiGaitTM was eliminated due to problems associated with development and inadequate throughput. Beam walk, spontaneous forelimb elevation test, and force-plate actometry, however, are simple, complementary tests, each measuring a different aspect of motor function that met the criteria for being adequate behavior tests for use in a rodent model of juvenile TBI and were used in later studies. The second aim investigated the effects of dietary n-3 fatty acid content and, as a consequence, reduced brain fatty acid composition on outcomes of juvenile TBI. Long-Evans rats raised from conception on diets containing adequate n-3 fatty acids (Control) or low in n-3 fatty acids (Deficient), resulting in decreases in brain DHA of 25% and 54%, respectively, were subjected to a controlled cortical impact or sham surgery on postnatal day 17. Rats with decreased brain DHA levels had poorer sensorimotor outcomes, as assessed with force-plate actometry and the spontaneous forelimb elevation test, after TBI. Ccl2, Gfap, and Mmp9 mRNA levels, and MMP-2 and -9 enzymatic activities were increased after TBI regardless of brain DHA level. Lesion volume was also not affected by brain DHA level. In contrast, TBI-induced Timp1 gene expression was lower in rats fed the Deficient diet and was correlated with brain DHA level. These data suggest that decreased brain DHA content contributes to poorer outcomes after TBI through a mechanism involving modulation of Timp1 gene expression. The third aim investigated the use of a high dose oral fish oil dosing regimen on biochemical, blood-brain barrier, and sensorimotor outcomes of TBI in a juvenile rat model. Seventeen-day old Long-Evans rats were given a 15 mL/kG fish oil (2.01 g/kg EPA, 1.34 g/kg DHA) or soybean oil dose via oral gavage thirty minutes prior to being subjected to a controlled cortical impact injury or sham surgery. Doses of oil were then administered for seven days after surgery. Fish oil treatment resulted in improved hindlimb deficits after TBI as assessed with the beam walk test, decreased IgG infiltration into the ipsilateral and contralateral hemispheres, and decreased TBI-induced gene expression of Mmp9 one day after injury. TBI-induced increases in Gfap were also less persistent in rats treated with fish oil. These results indicate that fish oil may improve sensorimotor outcomes after TBI in juveniles by decreasing blood-brain barrier disruption by a mechanism involving decreased gene expression of Mmp9, and also modulating glial activation. In summary, this dissertation established a juvenile model of TBI with persistent, measurable deficits and established three behavioral tools for assessing severity of injury, persistence of deficits, and recovery from TBI. Furthermore, it determined that brain DHA content, not diet, that most influences TBI outcomes and that improved outcomes as a result of greater brain DHA content may be due to increased TBI-induced Timp1 gene expression. Lastly, it determined that acute fish oil dosing improves functional outcomes after TBI by limiting blood-brain barrier damage by preventing TBI-induced gene expression of Mmp9 and faster resolution of astrocytosis. Together, these findings support the use of an LC-PUFA-rich diet during gestation and early neonatal life to provide greater neuroprotection in the event of a TBI as well as support the use of fish oil as a therapy for juvenile TBI

Estimation of Costs of Phosphorus Removal In Wastewater Treatment Facilities: Adaptation of Existing Facilities

As part of a wider enquiry into the feasibility of offset banking schemes as a means to implement pollutant trading within Georgia watersheds, this is the second of two reports addressing the issue of estimating costs for upgrades in the performance of phosphorus removal in point-source wastewater treatment facilities. Earlier, preliminary results are presented in Jiang et al (2004) (Working Paper # 2004-010 of the Georgia Water Planning and Policy Center). The present study is much more detailed and employs an advanced software package (WEST®, Hemmis nv, Kortrijk, Belgium) for simulating a variety of treatment plant designs operating under typical Georgia conditions. Specifically, upgrades in performance, in a single step, from a plant working at an effluent limit of less than 2.0 mg/l phosphorus to one working with limits variously ranging between less than 1.0 mg/l to less than 0.05 mg/l phosphorus are simulated and the resulting costs of the upgrade estimated.Five capacities of plant are considered, from 1 MGD to 100 MGD. Three strategic, alternative designs for the facility are considered: the basic activated sludge (AS) process with chemical addition, the Anoxic/Oxic (A/O) arrangement of the AS process, and the Anaerobic/Aerobic/Oxic (A/A/O) arrangement of the AS process. Upgrades in performance are consistent with the logical alternatives for adapting these options. Cost comparisons are made primarily on the basis of the incremental cost of the upgrade, i.e., from the base-case, reference plant to that performing at the higher level, as expressed through the incremental Total Annual Economic Cost (TAEC; in $) and the marginal unit cost of phosphorus removal, expressed in ($/kg).For the most stringent upgrade, for example, to a plant generating an effluent with less than 0.05 mg/l phosphorus, these marginal costs -- the cost of the additional phosphorus removed as a result of the upgrade -- amount to something of the order of 150-425 $/kg, with the upper bound being associated with the smallest plant configuration (1 MGD). Working Paper Number 2005-001

Bayesian Spatial Binary Regression for Label Fusion in Structural Neuroimaging

Many analyses of neuroimaging data involve studying one or more regions of interest (ROIs) in a brain image. In order to do so, each ROI must first be identified. Since every brain is unique, the location, size, and shape of each ROI varies across subjects. Thus, each ROI in a brain image must either be manually identified or (semi-) automatically delineated, a task referred to as segmentation. Automatic segmentation often involves mapping a previously manually segmented image to a new brain image and propagating the labels to obtain an estimate of where each ROI is located in the new image. A more recent approach to this problem is to propagate labels from multiple manually segmented atlases and combine the results using a process known as label fusion. To date, most label fusion algorithms either employ voting procedures or impose prior structure and subsequently find the maximum a posteriori estimator (i.e., the posterior mode) through optimization. We propose using a fully Bayesian spatial regression model for label fusion that facilitates direct incorporation of covariate information while making accessible the entire posterior distribution. We discuss the implementation of our model via Markov chain Monte Carlo and illustrate the procedure through both simulation and application to segmentation of the hippocampus, an anatomical structure known to be associated with Alzheimer's disease.Comment: 24 pages, 10 figure

Comparing Validity of Body Composition Measuring Tools

The purpose of this study was to test the validity of body composition measuring machines by finding the error in percent difference. It was hypothesized that the Bod Pod would provide more valid percent body fat estimates than the Omron 306 and the Omron HBF541C.https://digitalcommons.gardner-webb.edu/exercise-science-research-proposal-posters/1046/thumbnail.jp

Impact of onabotulinumtoxinA on quality of life and practical aspects of daily living : a pooled analysis of two randomized controlled trials

Objective: To evaluate the impact of onabotulinumtoxinA on individual domains of the quality of life questionnaires in a pooled analysis of two phase 3 trials in overactive bladder patients with urinary incontinence who were inadequately managed by >= 1 anticholinergic. Methods: Patients received intradetrusor injections of onabotulinumtoxinA 100U (n = 557) or placebo (n = 548). The proportions of patients with a positive response (condition "greatly improved" or "improved") on the Treatment Benefit Scale, and changes in Incontinence Quality of Life scores and King's Health Questionnaire domain scores were analyzed in the overall population and subgroups with clean intermittent catheterization use and urinary tract infection status during the first 12 weeks of treatment. Responses to individual King's Health Questionnaire items were also assessed. Results: Significantly greater proportions of onabotulinumtoxinA-treated patients achieved positive Treatment Benefit Scale response versus placebo (61.8% vs 28.0%; P < 0.001). OnabotulinumtoxinA showed significantly greater improvements versus placebo in Incontinence Quality of Life total (22.5 vs 6.6), Incontinence Quality of Life subscale scores and all domains of the King's Health Questionnaire. Notably, a similar trend was observed regardless of clean intermittent catheterization/urinary tract infection status. Additionally, onabotulinumtoxinA resulted in significantly greater improvements than the placebo in practical aspects of patients daily lives, including pad use, need to change undergarments, sleep, relationship with partner and work life/daily activities. Conclusion: In overactive bladder patients with urinary incontinence, onabotulinumtoxinA 100U demonstrated significant improvements across the individual domains of the quality of life questionnaires, regardless of clean intermittent catheterization or urinary tract infection status, and provided a positive impact on practical aspects of patients' daily lives

Predicting relationship stability among midlife African American couples

Objective: This study examined predictors of relationship stability over 5 years among heterosexual cohabiting and married African American couples raising an elementary-school-age child. The vulnerability–stress–adaptation model of relationships (Karney & Bradbury, 1995) guided the investigation. Contextual variables were conceptualized as important determinants of education and income, which in turn influence family structure, stress, and relationship quality and stability. Religiosity was tested as a resource variable that enhances relationship stability. Method: Couples (N = 207) were drawn from the Family and Community Health Study. Variables assessed at Wave 1 (education, income, religiosity, biological vs. stepfamily status, marital status, financial strain, and relationship quality) were used to predict relationship stability 5 years later. Results: Higher levels of education were associated with higher income, lower financial strain, and family structures that research has shown to be more stable (marriage rather than cohabitation and biological-family rather than stepfamily status; Bumpass & Lu, 2000). These variables, in turn, influenced relationship quality and stability. Religiosity, an important resource in the lives of African Americans, promoted relationship stability through its association with marriage, biological-family status, and women\u27s relationship quality. Conclusions: Enhancing the stability of African American couples\u27 relationships will require changes in societal conditions that limit opportunities for education and income and weaken relationship bonds. Programs to assist couples with blended families are needed, and incorporation of spirituality into culturally sensitive relationship interventions for African American couples may also prove beneficia

Targeting the Immunomodulatory Capacity of MDS MSCs by Tasquinimod

Myelodysplastic syndromes (MDS) belong to the most common hematological neoplasms in the elderly population, characterized by ineffective hematopoiesis, peripheral cytopenia and the risk of transformation into acute myeloid leukemia. A dysregulated innate immune response and pro-inflammatory bone marrow microenvironment play a crucial role in the MDS pathogenesis by providing chronic inflammation which makes those pathways the perfect candidate for future therapeutics. Specifically, it has been shown that the alarmin S100A9, an important ligand for dri-ving inflammation and promoting tumor progression, is elevated in MDS patients. Previous expe-riments performed in the Stem Cell Lab 2 provided evidence that mesenchymal stromal cells (MSCs), an important component of the BM niche with immunomodulatory capacity, can be tar-geted by the novel oral small molecular drug Tasquinimod (TASQ, Active Biotech) which has demonstrated S100A9 inhibitory activity. The inhibition of inflammation-related molecules such as IL-1b, IL-18, PD-L1, resulted in a significant improvement of the hematopoietic support by MSCs. However, almost nothing is known about potential effects of TASQ in the context of immunomo-dulation. Therefore, we aimed in this project to understand the mechanisms of S100A9+/- TASQ concerning the immunomodulatory capacity of MDS-MSCs in response to T cell-mediated in-flammation by analyzing adhesion (ICAM1, VCAM1), immune checkpoint (PDL1, PDL2), anti-inflammatory cytokine (COX2, IDO1), chemokines (CCL2, IL8) and extracellular matrix-related (COL4A2, COL1A1) gene expression with quantitative real-time PCR. We observed a general de-crease in the aforementioned genes except for COL4A2 and COL1A1 upon treatment with TASQ, though T cell-mediated inflammation and activity remained unaffected, suggesting that inhibition of S100A9 reduces the inflammation-mediated immunomodulatory potential of MDS-MSCs.:Motivation Aim Methods Result Conclusio

Control-Group Feature Normalization for Multivariate Pattern Analysis Using the Support Vector Machine

Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We also show that control-based normalization provides better interpretation with respect to the estimated multivariate disease pattern and improves the classifier performance in many cases

Effects of Energy Drink on Metabolic Response and Exercise Performance Post Basketball Game Simulation

Intermittent sports are characterized by intermittent bursts of high-intensity exercise and are dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on carbohydrate as an important fuel source. A potential reason for athletes to use energy drinks is due to the conception that energy drinks would promote improvement of performance and this practice has been common among athletes in recent history. PURPOSE: This study examined the effects of an energy drink on metabolic parameters and exercise performance following basketball game simulation (BGS). METHODS: Six female college basketball players, aged 21.5±1.9 yrs, volunteered for this study which was designed by a randomized counterbalanced experimental design with repeated measures under two different trials: energy drink (ED, extrication glucose 20 g from corn, citrus juice 2% from pure Calamansi fruit, branched chain amino acid 600 mg and taurine 600 mg) and placebo (PO, aspartame) with a double-blind experiment. The drink, either ED or PO was provided for the participants right after BGS, and the participants had a 20 min recovery period (POST). The BGS consisted of major basketball movements such as walking, jogging, running, low and high shuffles, dribbling, jumping, sprinting, and passing which were all performed during 20 min. Height, body weight, blood pressure, heart rate, blood glucose (BG), and blood lactate (BL) were measured at a baseline (BASE). Vertical jump, 10 m× 5 shuttle run and Wingate tests were performed prior to BGC and POST to evaluate muscular power, agility, and anaerobic power, respectively. BG and BL were measured immediately after SBC (PRE) and POST. Data was analyzed by two-way ANOVA with repeated measures. RESULTS: BG decreased significantly in PO (PRE: 106.5± 13.2 mg· dL-1, POST: 91±5.1 mg· dL-1, p=.018) and BL decreased significantly in both ED (PRE: 5.5± 1.8 mmol·L-1, POST: 3.1±1.4 mmol·L-1, p=.0001) and PO (PRE: 5.0± 0.9 mmol·L-1, POST: 3.5±0.8 mmol·L-1, p=.000). Vertical jump (BASE: 58.0±7.3 cm, POST: 55.5±8.2 cm, p=.012) and anaerobic work (BASE: 12.3±1.3 KJ, POST: 11.4±1.5 KJ, p=.035) decreased significantly in PO. CONCLUSION: The results indicate that the energy drink may replenish a deficiency of fuel source and promote improvement of muscular and anaerobic power during a recovery period