Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Updated: 1 hour 46 min ago

Perspective: Sistas In Science - Cracking the Glass Ceiling.

Sat, 10/12/2019 - 06:29
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Perspective: Sistas In Science - Cracking the Glass Ceiling.

Ethn Dis. 2018;28(4):575-578

Authors: Starlard-Davenport A, Rich A, Fasipe T, Lance EI, Adekola K, Forray A, Steed M, Fitzgerald A, Walker S, Pace BS

Abstract
In this perspective, we describe our experience as women of color scientists from diverse backgrounds and similar struggles embarking upon the National Heart, Lung and Blood Institute-funded program called PRIDE (Programs to Increase Diversity among Underrepresented Minorities Engaged in Health-Related Research). Under the leadership of our mentor and friend, Betty Pace, MD, a renowned and successful African American physician-scientist, the PRIDE Program was designed to address the difficulties experienced by junior-level minority investigators in establishing independent research programs and negotiating tenure and full professor status at academic institutions. The strength of PRIDE's innovative formula was pairing us with external senior mentors and, importantly, allowing us to serve as peer mentors to each other. We believe this "Sister's Keeper" paradigm is one solution for women to overcome their limitations and extend understandings and best practices worldwide for science, medicine, and global health.

PMID: 30405303 [PubMed - indexed for MEDLINE]

Glucocorticoid Receptor Transactivation Is Required for Glucocorticoid-Induced Ocular Hypertension and Glaucoma.

Fri, 10/11/2019 - 06:16
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Glucocorticoid Receptor Transactivation Is Required for Glucocorticoid-Induced Ocular Hypertension and Glaucoma.

Invest Ophthalmol Vis Sci. 2019 05 01;60(6):1967-1978

Authors: Patel GC, Millar JC, Clark AF

Abstract
Purpose: Glucocorticoid (GC)-induced ocular hypertension (GC-OHT) is a serious side effect of prolonged GC therapy that can lead to glaucoma and permanent vision loss. GCs cause a plethora of changes in the trabecular meshwork (TM), an ocular tissue that regulates intraocular pressure (IOP). GCs act through the glucocorticoid receptor (GR), and the GR regulates transcription both through transactivation and transrepression. Many of the anti-inflammatory properties of GCs are mediated by GR transrepression, while GR transactivation largely accounts for GC metabolic effects and side effects of GC therapy. There is no evidence showing which of the two mechanisms plays a role in GC-OHT.
Methods: GRdim transgenic mice (which have active transrepression and impaired transactivation) and wild-type (WT) C57BL/6J mice received weekly periocular dexamethasone acetate (DEX-Ac) injections. IOP, outflow facilities, and biochemical changes to the TM were determined.
Results: GRdim mice did not develop GC-OHT after continued DEX treatment, while WT mice had significantly increased IOP and decreased outflow facilities. Both TM tissue in eyes of DEX-treated GRdim mice and cultured TM cells isolated from GRdim mice had reduced or no change in the expression of fibronectin, myocilin, collagen type I, and α-smooth muscle actin (α-SMA). GRdim mouse TM (MTM) cells also had a significant reduction in DEX-induced cytoskeletal changes, which was clearly seen in WT MTM cells.
Conclusions: We provide the first evidence for the role of GR transactivation in regulating GC-mediated gene expression in the TM and in the development of GC-OHT. This discovery suggests a novel therapeutic approach for treating ocular inflammation without causing GC-OHT and glaucoma.

PMID: 31050723 [PubMed - indexed for MEDLINE]

Current state of Alzheimer's fluid biomarkers.

Fri, 10/11/2019 - 06:16
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Current state of Alzheimer's fluid biomarkers.

Acta Neuropathol. 2018 12;136(6):821-853

Authors: Molinuevo JL, Ayton S, Batrla R, Bednar MM, Bittner T, Cummings J, Fagan AM, Hampel H, Mielke MM, Mikulskis A, O'Bryant S, Scheltens P, Sevigny J, Shaw LM, Soares HD, Tong G, Trojanowski JQ, Zetterberg H, Blennow K

Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

PMID: 30488277 [PubMed - indexed for MEDLINE]

Assessing Health Needs in African American Churches: A Mixed-Methods Study.

Wed, 10/09/2019 - 15:03
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Assessing Health Needs in African American Churches: A Mixed-Methods Study.

J Relig Health. 2019 Oct 08;:

Authors: Su D, Garg A, Wiens J, Meyer E, Cai G

Abstract
Among major racial and ethnic groups in the USA, African Americans are the most religious, and faith-based organizations play an important role in health promotion for African Americans. This study aimed to assess health needs in African American churches using a mixed-methods approach. Based on quantitative and qualitative data collected from eight African American churches in Nebraska in 2017, the most prevalent chronic conditions among participating African American church members (n = 388) included hypertension (60.8%), allergies (41.0%), arthritis (36.4%), high cholesterol (35.8%), and diabetes (28.1%). Significant predictors of fair or poor health were identified as male sex, unemployment, delayed utilization of health care in the past 12 months due to cost, lower frequency of church attendance, and feeling down, depressed, or hopeless in the past 2 weeks. Pastors from participating churches identified cost as one of the primary barriers to providing church-based health services. There were substantial unmet health needs in African American faith communities, especially in the areas of chronic disease prevention and management, and churches would need more support to realize their full potential in faith-based health promotion.

PMID: 31595445 [PubMed - as supplied by publisher]

AMPK Signaling Regulates the Age-Related Decline of Hippocampal Neurogenesis.

Wed, 10/09/2019 - 15:03
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AMPK Signaling Regulates the Age-Related Decline of Hippocampal Neurogenesis.

Aging Dis. 2019 Oct;10(5):1058-1074

Authors: Wang BZ, Yang JJ, Zhang H, Smith CA, Jin K

Abstract
The global incidence of age-associated neurological diseases is expected to rise with increasingly greying societies. In the aged brain, there is a dramatic decrease in the number of stem cells, which is a main cause for the decrease in brain function. Intrinsic factors, such as cell metabolism, have been studied but its role in neurogenesis is still unknown. Therefore, this study sought to establish whether AMP-activated protein kinase (AMPK) signaling does indeed regulate hippocampal neurogenesis in the aged brain. We found that i) AMPKα2 was the predominant catalytic subunit in the subgranular and subventricular zones; ii) AMPK activation was at a significantly higher level in the aged vs. young hippocampus; iii) short term (7 days) treatment with selective AMPK signaling inhibitor Compound C (10 mg/kg/day, i.p.) significantly increased the numbers of newborn (BrdU+), Type 2 (MCM2+), and Type 3 (DCX+) neural stem cells, but not Type 1 (GFAP+/Sox2+) cells, in the aged hippocampus. Taken together, our results demonstrate that AMPK signaling plays a critical role in the age-related decline of hippocampal neurogenesis.

PMID: 31595203 [PubMed]

Utility of Physiologically Based Pharmacokinetic Modeling in Point of Care Decisions: An Example using Digoxin dosing in Continuous Venovenous Hemodiafiltration.

Wed, 10/09/2019 - 15:03
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Utility of Physiologically Based Pharmacokinetic Modeling in Point of Care Decisions: An Example using Digoxin dosing in Continuous Venovenous Hemodiafiltration.

Ther Drug Monit. 2019 Sep 30;:

Authors: Srinivasan M, Hirani R, Tsiu M, Kabani K, Chaturvedula A, Palasik B

Abstract
We describe the case of a patient on continuous venovenous hemodiafiltration (CVVHDF) with atrial fibrillation with rapid ventricular response (RVR) and hypotension requiring vasopressor use, which warranted digoxin therapy. In the absence of guidelines specifying appropriate digoxin dosing in patients undergoing CVVHDF, anecdotal evidence-guided digoxin dosing was performed for this patient using plasma digoxin concentration-based therapeutic drug monitoring (TDM). We use this case to demonstrate the potential role of physiologically based pharmacokinetic modeling in assisting therapeutic decision making.

PMID: 31593032 [PubMed - as supplied by publisher]

The Federal Trade Commission's mandated Four Loko labeling fails to facilitate accurate estimation of alcohol content by college students.

Wed, 10/09/2019 - 15:03
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The Federal Trade Commission's mandated Four Loko labeling fails to facilitate accurate estimation of alcohol content by college students.

Am J Drug Alcohol Abuse. 2019 Oct 08;:1-8

Authors: Rossheim ME, Yurasek AM, Greene KM, Gonzalez-Pons KM, Barry AE, Thombs DL, Trangenstein PJ, Nelson C, Cavazos T, Treffers RD, Jernigan DH

Abstract
Background: Four Loko, the leading supersized alcopop brand, is a pre-mixed alcoholic beverage containing up to 5.5 standard alcoholic drinks in a can. In 2013, the Federal Trade Commission (FTC) mandated the addition to Four Loko cans of a label indicating its alcohol content in standard drinks, presented as "alcohol per serving" and "servings per container." Objective: The current study investigated whether college students accurately estimate the alcohol content in cans of Four Loko bearing the FTC mandated labels. Method: Undergraduate student drinkers (n = 833; 51.6% women) in three states (Florida, Montana, and Virginia) were provided an empty Watermelon Four Loko can and asked to determine the number of standard drinks it contained, using 12-ounce regular beer (Budweiser) equivalents. In Florida and Virginia, Watermelon Four Loko contains 4.70 standard alcoholic drinks; in Montana, it contains 3.13. Results: More than 60% of Florida students and more than 70% of Virginia students underestimated Four Loko's alcohol content by one or more standard drinks, compared to 45% of Montana students. Multivariable logistic regression analysis found the following variables were associated with greater odds of underestimating Four Loko's alcohol content by one or more standard alcoholic drinks: being female (AOR = 2.2), having never seen nor heard of Four Loko (AOR = 1.9), and residing in Florida (AOR = 1.7) or Virginia (AOR = 2.8) versus Montana. Conclusions: Students were far less likely to underestimate alcohol content for 8% alcohol-by-volume (abv) cans compared to those with higher alcohol concentrations. Thus, policies restricting supersized alcopops' abv may help consumers better estimate their alcohol content.

PMID: 31592678 [PubMed - as supplied by publisher]

Patterns of Young Adult Social Roles Transitions Across 24 Months and Subsequent Substance Use and Mental Health.

Tue, 10/08/2019 - 05:52

Patterns of Young Adult Social Roles Transitions Across 24 Months and Subsequent Substance Use and Mental Health.

J Youth Adolesc. 2019 Oct 07;:

Authors: Patrick ME, Rhew IC, Duckworth JC, Lewis MA, Abdallah DA, Lee CM

Abstract
Young adults experience social role transitions across multiple life domains, and a deeper understanding of the ways in which these simultaneous transition experiences are associated with substance use and mental health will inform targeted interventions for this population. Data from the current study include24 repeated monthly assessments of young adults (N = 778; 56% female; age range 18 to 24 at baseline; 60% White, 18% Asian, 12% Multiracial, 5% Black or African American, 1% American Indian, 1% Pacific Islander, 3% Other, 9% Latinx) and outcomes 6 months later. Monthly assessments across 2 years were used to identify latent classes of frequency of social role transitions in four key domains (education, residential, employment, and romantic relationships) and associations between these classes and later outcomes. Three classes of social role transitions were identified: Infrequent Transitions (30.4%), Transitions except in Relationships (38.5%), and Frequent Transitions (31.1%). Compared to the Infrequent Transitions class, the other classes had greater typical drinking and hazardous alcohol use six months later; the Frequent Transitions class also had more hazardous cannabis use, depressive symptoms, and anxiety symptoms. Young adults experiencing frequent transitions across multiple domains appear to be at risk for substance use and mental health problems and may benefit from targeted intervention to address substance use and mental health issues.

PMID: 31588973 [PubMed - as supplied by publisher]

How often parents make decisions with their children is associated with obesity.

Tue, 10/08/2019 - 05:52
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How often parents make decisions with their children is associated with obesity.

BMC Pediatr. 2018 09 25;18(1):311

Authors: Rahman A, Fulda KG, Franks SF, Fernando SI, Habiba N, Muzaffar O

Abstract
BACKGROUND: Evidence supports that better parental involvement and communication are related to reduced obesity in children. Parent-child collaborative decision-making is associated with lower BMI among children; while child-unilateral and parent-unilateral decision-making are associated with overweight children. However, little is known about associations between joint decision-making and obesity among Hispanic youth. The purpose of this analysis was to determine the relationship between parent-child decision making and obesity in a sample of predominantly Hispanic adolescents.
METHODS: Data from two studies focused on risk for type II diabetes were analyzed. A total of 298 adolescents 10-14 years of age and their parent/legal guardian were included. Parents completed questionnaires related to psychosocial, family functioning, and environmental factors. Multiple logistic regression was used to determine the association between obesity (≥ 95th percentile for age and gender), the dependent variable, and how often the parent felt they made decisions together with their child (rarely/never, sometimes, usually, always), the primary independent variable. Covariates included gender, age, ethnicity, total family income, and days participated in a physical activity for at least 20 min. ORs and 95% CIs were calculated.
RESULTS: Adolescent participants were predominantly Hispanic n = 233 (78.2%), and approximately half n = 150 (50.3%) were female. In multivariate analyses, adolescents who rarely/never made decisions together with their family had significantly higher odds (OR = 3.50; 95% CI [1.25-9.83]) of being obese than those who always did. No association was observed between either those who sometimes make decisions together or those who usually did and those that always did.
CONCLUSIONS: Parents and children not making decisions together, an essential aspect of parent-child communication, is associated with increased childhood obesity. The results of our study contribute to evidence of parental involvement in decision-making as an important determinant of adolescent health. Further studies should explore temporal relationships between parenting or communication style and obesity.

PMID: 30253768 [PubMed - indexed for MEDLINE]

Massively parallel sequencing of 12 autosomal STRs in Cannabis sativa.

Tue, 10/08/2019 - 05:52
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Massively parallel sequencing of 12 autosomal STRs in Cannabis sativa.

Electrophoresis. 2018 11;39(22):2906-2911

Authors: Houston R, Mayes C, King JL, Hughes-Stamm S, Gangitano D

Abstract
Massively parallel sequencing (MPS) is an emerging technology in the field of forensic genetics that provides distinct advantages compared to capillary electrophoresis. This study offers a proof of concept that MPS technologies can be applied to genotype autosomal STRs in Cannabis sativa. A custom panel for MPS was designed to interrogate 12 cannabis-specific STR loci by sequence rather than size. A simple workflow was implemented to integrate the custom PCR multiplex into a workflow compatible with the Ion Plus Fragment Library Kit, Ion™ Chef, and Ion™ S5 System. For data sorting and sequence analysis, a custom configuration file was designed for STRait Razor v3 to parse and extract STR sequence data. This study represents a preliminary investigation of sequence variation for 12 autosomal STR loci in 16 cannabis samples. Full concordance was observed between the MPS and CE data. Results revealed intra-repeat variation in eight loci where the nominal or size-based allele was identical, but variances were discovered in the sequence of the flanking region. Although only a small number of cannabis samples were evaluated, this study demonstrates that more informative STR data can be obtained via MPS.

PMID: 30221375 [PubMed - indexed for MEDLINE]

Current state-of-art of STR sequencing in forensic genetics.

Tue, 10/08/2019 - 05:52
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Current state-of-art of STR sequencing in forensic genetics.

Electrophoresis. 2018 11;39(21):2655-2668

Authors: Alonso A, Barrio PA, Müller P, Köcher S, Berger B, Martin P, Bodner M, Willuweit S, Parson W, Roewer L, Budowle B

Abstract
The current state of validation and implementation strategies of massively parallel sequencing (MPS) technology for the analysis of STR markers for forensic genetics use is described, covering the topics of the current catalog of commercial MPS-STR panels, leading MPS-platforms, and MPS-STR data analysis tools. In addition, the developmental and internal validation studies carried out to date to evaluate reliability, sensitivity, mixture analysis, concordance, and the ability to analyze challenged samples are summarized. The results of various MPS-STR population studies that showed a large number of new STR sequence variants that increase the power of discrimination in several forensically relevant loci are also presented. Finally, various initiatives developed by several international projects and standardization (or guidelines) groups to facilitate application of MPS technology for STR marker analyses are discussed in regard to promoting a standard STR sequence nomenclature, performing population studies to detect sequence variants, and developing a universal system to translate sequence variants into a simple STR nomenclature (numbers and letters) compatible with national STR databases.

PMID: 29750373 [PubMed - indexed for MEDLINE]

Report from the STRAND Working Group on the 2019 STR sequence nomenclature meeting.

Mon, 10/07/2019 - 05:44

Report from the STRAND Working Group on the 2019 STR sequence nomenclature meeting.

Forensic Sci Int Genet. 2019 Sep 21;43:102165

Authors: Gettings KB, Ballard D, Bodner M, Borsuk LA, King JL, Parson W, Phillips C

Abstract
This report summarizes topics discussed at the STR sequence nomenclature meeting hosted by the STRAND Working Group in April 2019. Invited attendees for this meeting included researchers known-to-us to be developing STR sequence-based nomenclature schemata, scientific representatives from vendors developing STR sequence bioinformatic methods, DNA intelligence database curators, and academic experts in STR genomics. The goal of this meeting was to provide a forum for individuals developing nomenclature schemata to present and discuss their ideas, encouraging mutual awareness, identification of differences in approaches, opposing aspects, and opportunities for parallelization while some approaches are still under development.

PMID: 31586814 [PubMed - as supplied by publisher]

Artificial fingerprints for cross-comparison of forensic DNA and protein recovery methods.

Fri, 10/04/2019 - 05:11

Artificial fingerprints for cross-comparison of forensic DNA and protein recovery methods.

PLoS One. 2019;14(10):e0223170

Authors: LeSassier DS, Schulte KQ, Manley TE, Smith AR, Powals ML, Albright NC, Ludolph BC, Weber KL, Woerner AE, Gardner MW, Hewitt FC

Abstract
Quantitative genomic and proteomic evaluation of human latent fingerprint depositions represents a challenge within the forensic field, due to the high variability in the amount of DNA and protein initially deposited. To better assess recovery techniques for touch depositions, we present a method to produce simple and customizable artificial fingerprints. These artificial fingerprint samples include the primary components of a typical latent fingerprint, specifically sebaceous fluid, eccrine perspiration, extracellular DNA, and proteinaceous epidermal skin material (i.e., shed skin cells). A commercially available emulsion of sebaceous and eccrine perspiration material provides a chemically-relevant suspension solution for fingerprint deposition, simplifying artificial fingerprint production. Extracted human genomic DNA is added to accurately mimic the extracellular DNA content of a typical latent print and comparable DNA yields are recovered from the artificial prints relative to human prints across surface types. Capitalizing on recent advancements in the use of protein sequence identification for human forensic analysis, these samples also contain a representative quantity of protein, originating from epidermal skin cells collected from the fingers and palms of volunteers. Proteomic sequencing by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis indicates a high level of protein overlap between artificial and latent prints. Data are available via ProteomeXchange with identifier PXD015445. By including known quantities of DNA and protein into each artificial print, this method enables total DNA and protein recovery to be quantitatively assessed across different sample collection and extraction methods to better evaluate extraction efficiency. Collectively, these artificial fingerprint samples are simple to make, highly versatile and customizable, and accurately represent the biochemical composition and biological signatures of human fingerprints.

PMID: 31581206 [PubMed - in process]

Building a Culture of Safety: Relearning Organizational Behavior.

Thu, 10/03/2019 - 05:04
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Building a Culture of Safety: Relearning Organizational Behavior.

Int Anesthesiol Clin. 2019;57(3):12-24

Authors: DeSocio PA, Garzon MP, Hicks MR

PMID: 31577234 [PubMed - in process]

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury.

Wed, 10/02/2019 - 07:53

Neuroprotection of Cyperus esculentus L. orientin against cerebral ischemia/reperfusion induced brain injury.

Neural Regen Res. 2020 Mar;15(3):548-556

Authors: Jing SQ, Wang SS, Zhong RM, Zhang JY, Wu JZ, Tu YX, Pu Y, Yan LJ

Abstract
Orientin is a flavonoid monomer. In recent years, its importance as a source of pharmacological active substance is growing rapidly due to its properties such as anti-myocardial ischemia, anti-apoptosis, anti-radiation, anti-tumor, and anti-aging. However, the neuroprotective effects of Orientin on stroke injury have not been comprehensively evaluated. The aim of the present study was thus to investigate the neuroprotective capacity and the potential mechanisms of Cyperus esculentus L. orientin (CLO) from Cyperus esculentus L. leaves against ischemia/reperfusion (I/R) injury using standard orientin as control. For in vitro studies, we treated HT22 cells with CoCl2 as an in vitro ischemic injury model. HT22 cells in the control group were treated with CoCl2. For in vivo studies, we used rat models of middle cerebral artery occlusion, and animals that received sham surgery were used as controls. We found that CLO protected CoCl2-induced HT22 cells against ischemia/reperfusion injury by lowering lipid peroxidation and reactive oxygen species formation as well as decreasing protein oxidation. However, CLO did not reduce the release of lactate dehydrogenase nor increase the activity of superoxide dismutase. Results showed that CLO could decrease neurological deficit score, attenuate brain water content, and reduce cerebral infarct volume, leading to neuroprotection during cerebral ischemia-reperfusion injury. Our studies indicate that CLO flavonoids can be taken as a natural antioxidant and bacteriostastic substance in food and pharmaceutical industry. The molecular mechanisms of CLO could be at least partially attributed to the antioxidant properties and subsequently inhibiting activation of casepase-3. All experimental procedures and protocols were approved on May 16, 2016 by the Experimental Animal Ethics Committee of Xinjiang Medical University of China (approval No. IACUC20160516-57).

PMID: 31571667 [PubMed]

Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

Wed, 10/02/2019 - 07:53
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Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation.

Free Radic Biol Med. 2018 08 20;124:104-113

Authors: Bailey DM, Rasmussen P, Evans KA, Bohm AM, Zaar M, Nielsen HB, Brassard P, Nordsborg NB, Homann PH, Raven PB, McEneny J, Young IS, McCord JM, Secher NH

Abstract
This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂, 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂, 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v < a) was accompanied by A•-/LOOH formation (v > a) and increased LDL oxidation during hypoxia (P < 0.043-0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = -0.397 to -0.459, P = 0.037-0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

PMID: 29859345 [PubMed - indexed for MEDLINE]

Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Tue, 10/01/2019 - 07:41
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Correlates of Nonmedical Prescription Opioid Use Among U.S. Adolescents.

Am J Prev Med. 2019 Sep 26;:

Authors: Barnett TE, Thompson EL, Litt DM, Lewis MA

Abstract
INTRODUCTION: The purpose of this study is to assess risk factors, including other substance use, for nonmedical prescription opioid use among U.S. adolescents.
METHODS: A secondary data analysis of the 2017 Youth Risk Behavior Survey was conducted (n=10,175) in 2018. The outcome was nonmedical prescription opioid use. Predictor variables included other substance use, mood, sleep, academic performance, and demographic characteristics. Survey-weighted procedures in SAS, version 9.4 were used, and an adjusted logistic regression model was conducted.
RESULTS: Among the sampled adolescents, 13.8% (95% confidence limit=12.4%, 15.3%) reported nonmedical prescription opioid use. Nonmedical prescription opioid use was more likely among participants aged 15 years (versus 16 years), American Indian/Alaskan Natives, and those who reported being sad or hopeless. All other substance use was significantly associated with increased odds of nonmedical prescription opioid use. Nonmedical prescription opioid use was 1.5 times more likely among electronic vapor users (AOR=1.58, 95% CI=1.34, 1.86), 2 times more likely among cigarette (AOR=2.49, 95% CI=2.16, 2.88) and marijuana users (AOR=2.45, 95% CI=2.05, 2.93), and almost 3 times as likely among alcohol users (AOR=2.98, 95% CI=2.18, 4.07).
CONCLUSIONS: Study findings suggest a need for more interventions for nonmedical prescription opioid use among adolescents in the U.S. Information on nonmedical prescription opioid use should be added to all substance use prevention programs for adolescents. Moreover, future research needs to identify longitudinal predictors of adolescent nonmedical prescription opioid use to inform prevention efforts.

PMID: 31564603 [PubMed - as supplied by publisher]

Letter to the Editor. Reversal of low prealbumin with oral branched-chain amino acids: a simple solution to an expensive problem.

Tue, 10/01/2019 - 07:41
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Letter to the Editor. Reversal of low prealbumin with oral branched-chain amino acids: a simple solution to an expensive problem.

J Neurosurg Spine. 2018 10 26;30(1):146-147

Authors: Dickerman R, Williamson J, Bennett M

PMID: 30485191 [PubMed - indexed for MEDLINE]

Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.

Tue, 10/01/2019 - 07:41
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Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors.

Pharmacol Biochem Behav. 2018 12;175:123-129

Authors: Powell GL, Bonadonna JP, Vannan A, Xu K, Mach RH, Luedtke RR, Neisewander JL

Abstract
AIMS: The dopamine D3 receptor (D3R) is a pharmacotherapeutic target for drug dependence. We have successfully imaged human D3Rs using radiolabeled LS-3-134, an arylamide phenylpiperazine with moderate selectivity for the D3R over D2R and low efficacy at the D2 and D3R. In this study, we screened for effects of LS-3-134 as a potential anti-cocaine therapeutic.
METHODS: Male rats were pretreated with LS-3-134 (0, 1.0, 3.2, or 5.6 mg/kg, IP) 15 min prior to tests for its effects on spontaneous and cocaine-induced locomotion. We next investigated the effects of LS-3-134 (0, 1.0, 3.2, 5.6, or 10.0 mg/kg, IP) on operant responding on a multiple variable-interval (VI) 60-second schedule with alternating cocaine (0.375 mg/kg, IV) and sucrose (45 mg) reinforcer components. Additionally, we tested LS-3-134 (5.6 mg/kg, IP) effects on a progressive ratio (PR) schedule of cocaine reinforcement, on extinction of cocaine-seeking behavior, and on reinstatement of extinguished cocaine-seeking behavior by cocaine-associated light/tone cues.
RESULTS: LS-3-134 did not alter spontaneous locomotion, but reduced cocaine-induced locomotion, break points on the high-effort progressive ratio schedule of reinforcement, and responding during extinction and cue reinstatement. In contrast, LS-3-134 did not alter cocaine or sucrose reinforcement on the low-effort multiple VI 60-second schedule.
CONCLUSIONS: The effects of LS-3-134 are similar to other dopamine D3 low efficacy partial agonists and antagonists in attenuating cocaine intake under high effort schedules of reinforcement and in attenuating cocaine-seeking behavior elicited by cocaine-associated cues. These findings are consistent with the anti-craving profile of other dopamine D3 drugs.

PMID: 30308214 [PubMed - indexed for MEDLINE]

High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones.

Tue, 10/01/2019 - 07:41
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High salt loading increases brain derived neurotrophic factor in supraoptic vasopressin neurones.

J Neuroendocrinol. 2018 11;30(11):e12639

Authors: Balapattabi K, Little JT, Farmer GE, Cunningham JT

Abstract
High salt loading (SL) is associated with inappropriate arginine vasopressin (AVP) release and increased mean arterial pressure. Previous work has shown that chronic high salt intake impairs baroreceptor inhibition of rat AVP neurones through brain-derived neurotrophic factor (BDNF) dependent activation of tyrosine receptor kinase B (TrkB) and down-regulation of K+/Cl- co-transporter KCC2. This mechanism diminishes the GABAA inhibition of AVP neurones in the supraoptic nucleus (SON) by increasing intracellular chloride. However, the source of BDNF leading to this ionic plasticity is unknown. In the present study, we used adeno-associated viral vectors with short hairpin RNA against BDNF to test whether SON is the source of BDNF contributing to increased AVP release and elevated mean arterial pressure in high salt loaded rats. Virally mediated BDNF knockdown (shBDNF) in the SON of salt loaded rats significantly blocked the increases in BDNF mRNA and AVP heterogeneous RNA expression. The observed increase in the activation of TrkB receptor during salt loading is consistent with previous studies. Western blot analysis of SON punches revealed that tyrosine phosphorylation of TrkB (pTrkBY515) was significantly decreased in salt shBDNF rats compared to the salt scrambled (SCR) rats. Injections of shBDNF in the SON also significantly prevented the increase in plasma AVP concentration associated with salt loading. However, the salt loading induced increase in mean arterial pressure was not decreased with BDNF knockdown in the SON. Average daily fluid intake and urine output were significantly elevated in both salt SCR and salt shBDNF rats compared to the euhydrated controls. Daily average urine sodium concentration was significantly higher in shBDNF injected salt rats than the other groups. These findings indicate that BDNF produced in the SON contributes to the increased AVP secretion during high salt loading but not with respect to the subsequent increase in mean arterial pressure.

PMID: 30129982 [PubMed - indexed for MEDLINE]

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