Medicine Posters - 2019

Medicine Posters - 2019https://scholarlycommons.libraryinfo.bhs.org/research_education/1004/thumbnail.jp

Circulating Inflammatory and Oxidative Stress Responses to Steady-State Moderate-Intensity and High-Intensity Interval Exercise in Mid-Spectrum Chronic Kidney Disease

Inflammation and oxidative stress can be potent modulators of vascular function. These factors may transiently respond to moderate-intensity steady state exercise (SSE) in a manner that improves post-exercise vascular function in healthy adults. Whether exercise imparts similar effects in adults with Stage 3 or 4 chronic kidney disease (CKD) remains understudied. Moreover, a comparison of SSE and high-intensity interval exercise (HIIE) may add to clinically-relevant findings for improving vascular function in mid-spectrum CKD. PURPOSE: To determine the influence of SSE and a comparable amount of HIIE on post-exercise inflammation and oxidative stress in patients diagnosed with secondary Stage 3 or 4 CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Blood samples were obtained by the same technician under standardized conditions just before, 1hr and 24hrs after exercise. Total antioxidant capacity (TAC), paraoxonase1 (PON1), asymmetric dimethylarginine (ADMA), 3nitrotyrosine (3NT) and interleukin-6 (IL6) responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs. RESULTS: Relative to pre-exercise measures: TAC increased by 4.3% 24hr after exercise (p = 0.012). PON1 was maintained 1hr and elevated by 6.1% 24hr after SSE, but not HIIE (p = 0.035). When corrected for plasma volume shifts, ADMA increased 30 ng/ml at 1hr but was 58 ng/ml lower 24hrs after exercise (p = 0.0006). 3NT and IL6 remained stable in the hours after exercise (p \u3e 0.05). CONCLUSION: Modest inflammatory and oxidative stress marker responses to either SSE and HIIE may contribute to improved vascular function in mid-spectrum CKD

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary E M B A R G O E D

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia

Original Articles National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 1 -executive summary

Abstract: Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol-non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol-as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia. Ó 2014 National Lipid Association. All rights reserved. Various organizations and agencies have issued recommendations for the management of dyslipidemia. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel. The Executive Summary does not include a comprehensive reference list, but citations have been included for several key publications. The full report will include additional details on the rationale for the recommendations and citations to published research considered in the panel's deliberations. A presentation containing the main elements of these recommendations was made available to the public and other organizations involved with the prevention of atherosclerotic cardiovascular disease (ASCVD) to solicit input during an open comment period. Comments and suggestions were received from many members of the NLA as well as other individuals and organizations and were collated for consideration and adjudication by the panel in formulating the final set of recommendations contained herein. Part 1 of the NLA Expert Panel Recommendations for Patient-Centered Management of Dyslipidemia, will cover: Background and conceptual framework for formulation of the NLA Expert Panel recommendations; Screening and classification of lipoprotein lipid levels in adults; Targets for intervention in dyslipidemia management; ASCVD risk assessment and treatment goals based on risk category; Atherogenic cholesterol-non-high-density lipoprotein cholesterol (non-HDL-C) and low-density lipoprotein cholesterol (LDL-C)-as the primary targets of therapy; and Lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia

Acute Responses in Agonists of uEGF to Moderate-Intensity and High-Intensity Interval Exercise in Mid-Spectrum CKD

Urine epidermal growth factor (uEGF) is a novel biomarker utilized in assessing renal health in various renal diseases, specifically chronic kidney disease (CKD). uEGF promotes multiple intracellular pathways, stimulating renal cell growth, survival, and replication. uEGF production is activated by multiple agonists that bind to the uEGF receptor. Aerobic exercise initiates the upregulation of several of these agonists to increase the production of uEGF. Depending on the mode and intensity of aerobic exercise, uEGF agonists may activate differently in CKD populations. PURPOSE: To determine the influence of an acute bout of steady-state exercise (SSE) and high-intensity interval exercise (HIIE) on concentrations of uEGF agonists (serum insulin-like growth factor 1 (IGF-1), angiotensin II receptor type 1 (AGTR-1), and transforming growth factor beta 1 (TGF-β1)) in mid-spectrum CKD. METHODS: Twenty participants (n = 6 men; n = 14 women; age 62.0 + 9.9 yr; weight 80.9 + 16.2 kg; body fat 37.3 + 8.5% of weight; VO2max 19.4 + 4.7 ml/kg/min) completed 30 min of SSE at 65% VO2reserve or HIIE by treadmill walking (90% and 20% of VO2reserve in 3:2 min ratio) in a randomized crossover design. Both exercise conditions averaged ~ 65% VO2reserve. Blood and urine samples were obtained under standardized conditions just before, 1hr, and 24hrs after exercise. uEGF (ng/mL), serum IGF-1 (ng/mL), AGTR-1 (ng/mL), and TGF-β1 (pg/mL) responses were analyzed using 2 (condition) by 3 (sample point) repeated measures ANOVAs and Pearson Correlations. RESULTS: Serum IGF-1 and AGTR-1 increased 1hr and 24hr post-exercise in both exercise conditions; however, statistical significance was not achieved (p = 0.28 and p = 0.09). Similarly, serum TGF-β1 decreased at 24hrs in both exercise conditions but statistically remained unaltered (p = 0.42). IGF-1 was significantly correlated to uEGF in both conditions at all three-time points (p = 0.03), while AGTR-1 was significantly correlated to uEGF at 1hr in HIIE. uEGF findings were previously reported in ACSM abstract (DOI: 10.1249/01.mss.0000560710.72569.11). CONCLUSION: Agonists of uEGF remained unaltered following an acute bout of SSE and HIIE in mid-spectrum CKD. Further research is needed to understand better uEGF response activation to aerobic exercise in mid-spectrum CKD

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs

Mobility properties of the Hermes transposable element in transgenic lines of Aedes aegypti

The Hermes transposable element has been used to genetically transform a wide range of insect species, including the mosquito, Aedes aegypti, a vector of several important human pathogens. Hermes integrations into the mosquito germline are characterized by the non-canonical integration of the transposon and flanking plasmid and, once integrated, Hermes is stable in the presence of its transposase. In an effort to improve the post-integration mobility of Hermes in the germline of Ae. aegypti, a transgenic helper Mos1 construct expressing Hermes transposase under the control of a testis-specific promoter was crossed to a separate transgenic strain containing a target Hermes transposon. In less than 1% of the approximately 1,500 progeny from jumpstarter lines analyzed, evidence of putative Hermes germline remobilizations were detected. These recovered transposition events occur through an aberrant mechanism and provide insight into the non-canonical cut-and-paste transposition of Hermes in the germ line of Ae. aegypti

Heritability and Phenotypic Variation of Canine Hip Dysplasia Radiographic Traits in a Cohort of Australian German Shepherd Dogs

Canine Hip Dysplasia (CHD) is a common, painful and debilitating orthopaedic disorder of dogs with a partly genetic, multifactorial aetiology. Worldwide, potential breeding dogs are evaluated for CHD using radiographically based screening schemes such as the nine ordinally-scored British Veterinary Association Hip Traits (BVAHTs). The effectiveness of selective breeding based on screening results requires that a significant proportion of the phenotypic variation is caused by the presence of favourable alleles segregating in the population. This proportion, heritability, was measured in a cohort of 13,124 Australian German Shepherd Dogs born between 1976 and 2005, displaying phenotypic variation for BVAHTs, using ordinal, linear and binary mixed models fitted by a Restricted Maximum Likelihood method. Heritability estimates for the nine BVAHTs ranged from 0.14–0.24 (ordinal models), 0.14–0.25 (linear models) and 0.12–0.40 (binary models). Heritability for the summed BVAHT phenotype was 0.30±0.02. The presence of heritable variation demonstrates that selection based on BVAHTs has the potential to improve BVAHT scores in the population. Assuming a genetic correlation between BVAHT scores and CHD-related pain and dysfunction, the welfare of Australian German Shepherds can be improved by continuing to consider BVAHT scores in the selection of breeding dogs, but that as heritability values are only moderate in magnitude the accuracy, and effectiveness, of selection could be improved by the use of Estimated Breeding Values in preference to solely phenotype based selection of breeding animals

Optimum allocation of resources for QTL detection using a nested association mapping strategy in maize

In quantitative trait locus (QTL) mapping studies, it is mandatory that the available financial resources are spent in such a way that the power for detection of QTL is maximized. The objective of this study was to optimize for three different fixed budgets the power of QTL detection 1 − β* in recombinant inbred line (RIL) populations derived from a nested design by varying (1) the genetic complexity of the trait, (2) the costs for developing, genotyping, and phenotyping RILs, (3) the total number of RILs, and (4) the number of environments and replications per environment used for phenotyping. Our computer simulations were based on empirical data of 653 single nucleotide polymorphism markers of 26 diverse maize inbred lines which were selected on the basis of 100 simple sequence repeat markers out of a worldwide sample of 260 maize inbreds to capture the maximum genetic diversity. For the standard scenario of costs, the optimum number of test environments (Eopt) ranged across the examined total budgets from 7 to 19 in the scenarios with 25 QTL. In comparison, the Eopt values observed for the scenarios with 50 and 100 QTL were slightly higher. Our finding of differences in 1 − β* estimates between experiments with optimally and sub-optimally allocated resources illustrated the potential to improve the power for QTL detection without increasing the total resources necessary for a QTL mapping experiment. Furthermore, the results of our study indicated that also in studies using the latest genomics tools to dissect quantitative traits, it is required to evaluate the individuals of the mapping population in a high number of environments with a high number of replications per environment