Recent Research Articles from UNTHSC

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

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Population resequencing of European mitochondrial genomes highlights sex-bias in Bronze Age demographic expansions.

Wed, 07/03/2019 - 07:37
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Population resequencing of European mitochondrial genomes highlights sex-bias in Bronze Age demographic expansions.

Sci Rep. 2017 09 21;7(1):12086

Authors: Batini C, Hallast P, Vågene ÅJ, Zadik D, Eriksen HA, Pamjav H, Sajantila A, Wetton JH, Jobling MA

Abstract
Interpretations of genetic data concerning the prehistory of Europe have long been a subject of great debate, but increasing amounts of ancient and modern DNA data are now providing new and more informative evidence. Y-chromosome resequencing studies in Europe have highlighted the prevalence of recent expansions of male lineages, and focused interest on the Bronze Age as a period of cultural and demographic change. These findings contrast with phylogeographic studies based on mitochondrial DNA (mtDNA), which have been interpreted as supporting expansions from glacial refugia. Here we have undertaken a population-based resequencing of complete mitochondrial genomes in Europe and the Middle East, in 340 samples from 17 populations for which Y-chromosome sequence data are also available. Demographic reconstructions show no signal of Bronze Age expansion, but evidence of Paleolithic expansions in all populations except the Saami, and with an absence of detectable geographical pattern. In agreement with previous inference from modern and ancient DNA data, the unbiased comparison between the mtDNA and Y-chromosome population datasets emphasizes the sex-biased nature of recent demographic transitions in Europe.

PMID: 28935946 [PubMed - indexed for MEDLINE]

Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis.

Tue, 07/02/2019 - 07:27
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Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis.

Mol Biol Rep. 2019 Feb;46(1):83-95

Authors: Haridas V, Shetty P, Sarathkumar E, Bargale A, Vishwanatha JK, Patil V, Dinesh US

Abstract
Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.

PMID: 30426384 [PubMed - indexed for MEDLINE]

Using machine learning to examine the relationship between asthma and absenteeism.

Sun, 06/30/2019 - 06:57
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Using machine learning to examine the relationship between asthma and absenteeism.

Environ Monit Assess. 2019 Jun 28;191(Suppl 2):332

Authors: Lary MA, Allsopp L, Lary DJ, Sterling DA

Abstract
In this study, we found that machine learning was able to effectively estimate student learning outcomes geo-spatially across all the campuses in a large, urban, independent school district. The machine learning showed that key factors in estimating the student learning outcomes included the number of days students were absent from school. In turn, one of the most important factors in estimating the number of days a student was absent was whether or not the student had asthma. This highlights the importance of environmental public health for student learning outcomes.

PMID: 31254081 [PubMed - in process]

Improvement in mental health following total hip arthroplasty: the role of pain and function.

Sun, 06/30/2019 - 06:57
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Improvement in mental health following total hip arthroplasty: the role of pain and function.

BMC Musculoskelet Disord. 2019 Jun 29;20(1):307

Authors: Nguyen UDT, Perneger T, Franklin PD, Barea C, Hoffmeyer P, Lübbeke A

Abstract
BACKGROUND: Mental health has been shown to improve after total hip arthroplasty (THA). Little is known about the role of pain and function in this context. We assessed whether change in mental health was associated with improvement in pain and function 1 year post-surgery.
METHODS: This prospective study included patients enrolled in a THA registry from 2010 to 2014. We examined the mental component score (MCS) before and 1 year post-surgery, and 1-year change, in association with Western Ontario McMaster Universities (WOMAC) pain and function scores. All scores were normalized, ranging from 0 to 100 (larger score indicating better outcome). Analyses were adjusted for potential confounders.
RESULTS: Our study included 610 participants, of which 53% were women. Descriptive statistics are as follows: the average (SD) for age (years) was 68.5 (11.8), and for BMI was 26.9 (4.9). In addition, the MCS average (SD) at baseline was 44.7 (11.2), and at 1-year after THA was 47.5 (10.5). The average change from baseline to 1-year post-THA in MCS was 2.8 (95% CI: 1.9, 3.6), for an effect size of 0.26. As for the WOMAC pain score, the average change from baseline to 1-year post-THA was 44.2 (95%CI: 42.4, 46.0), for an effect size of 2.5. The equivalent change in WOMAC function was 38.1 (95% CI: 36.2, 40.0), for an effect size of 2.0. Results from multivariable analysis controlling for covariates showed that an improvement of 10 points in the 1-year change in pain score resulted in a 0.78 point (95%: CI 0.40, 1.26) increase in the 1-year change in MCS, whereas a 10-point improvement in the 1-year change in function was associated with a 0.94 point (95% CI: 0.56, 1.32) increase.
CONCLUSIONS: Mental health significantly improved from baseline to 1-year post-THA. Greater improvement in pain and function was associated with greater improvement in mental health 1 year post-THA.

PMID: 31253128 [PubMed - in process]

Massively parallel sequence data of 31 autosomal STR loci from 496 Spanish individuals revealed concordance with CE-STR technology and enhanced discrimination power.

Sun, 06/30/2019 - 06:57
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Massively parallel sequence data of 31 autosomal STR loci from 496 Spanish individuals revealed concordance with CE-STR technology and enhanced discrimination power.

Forensic Sci Int Genet. 2019 Jun 14;42:49-55

Authors: Barrio PA, Martín P, Alonso A, Müller P, Bodner M, Berger B, Parson W, Budowle B, DNASEQEX Consortium

Abstract
This study reports Short Tandem Repeat (STR) sequence-based allele data from 496 Spanish individuals across 31 autosomal STR (auSTR) loci included in the Precision ID GlobalFiler™ NGS STR Panel v2: D12S391, D13S317, D8S1179, D21S11, D3S1358, D5S818, D1S1656, D2S1338, vWA, D2S441, D5S2800, D7S820, D16S539, D6S474, D12ATA63, D4S2408, D6S1043, D19S433, D14S1434, CSF1PO, D10S1248, D18S51, D1S1677, D22S1045, D2S1776, D3S4529, FGA, Penta D, Penta E, TH01 and TPOX. The sequence of each allele was aligned to the reference sequence GRCh37 (hg19) and formatted according to the guidance of the International Society for Forensic Genetics. A subset of 221 samples was evaluated for testing concordance with allele calls derived from CE-based analysis using PowerPlex Fusion 6C, and there was 99.95% allele concordance. Twenty-five out of 31 auSTR loci showed an increased number of alleles due to repeat region sequence variation and/or single nucleotide polymorphisms (SNP) residing in the flanking regions. A total of 18 loci showed increased observed heterozygosity due to sequence variation; the loci exhibiting the greatest increase were: D13S317 (12% points), D5S818 (10% points), D8S1179 (7% points), D3S1358 (7% points), and D21S11 (6% points). The combined match probability decreased from 2.022E-24 (length-based data) to 1.042E-27 (sequence-based data) for the 20 CODIS core STR loci. The combined match probability (sequence-based data) for the 31 STR loci studied was 4.777E-40. The combined typical paternity index increased from 1.118E + 12 to 8.179E + 13 using length and sequence-based data, respectively. This Spanish population study performed in the framework of the EU-funded DNASEQEX project is expected to provide STR sequence-based allele frequencies for forensic casework and support implementation of massively parallel sequencing (MPS) technology in forensic laboratories.

PMID: 31252251 [PubMed - as supplied by publisher]

Identifying diverse concepts of discharge failure patients at emergency department in the USA: a large-scale retrospective observational study.

Sun, 06/30/2019 - 06:57
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Identifying diverse concepts of discharge failure patients at emergency department in the USA: a large-scale retrospective observational study.

BMJ Open. 2019 Jun 27;9(6):e028051

Authors: Schrader CD, Robinson RD, Blair S, Shaikh S, d'Etienne JP, Kirby JJ, Cheeti R, Zenarosa NR, Wang H

Abstract
OBJECTIVES: Identifying patients who are at high risk for discharge failure allows for implementation of interventions to improve their care. However, discharge failure is currently defined in literature with great variability, making targeted interventions more difficult. We aim to derive a screening tool based on the existing diverse discharge failure models.
DESIGN, SETTING AND PARTICIPANTS: This is a single-centre retrospective cohort study in the USA. Data from all patients discharged from the emergency department were collected from 1 January 2015 through 31 December 2017 and followed up within 30 days.
METHODS: Scoring systems were derived using modified Framingham methods. Sensitivity, specificity and area under the receiver operational characteristic (AUC) were calculated and compared using both the broad and restricted discharge failure models.
RESULTS: A total of 227 627 patients were included. The Screening for Healthcare fOllow-Up Tool (SHOUT) scoring system was derived based on the broad and restricted discharge failure models and applied back to the entire study cohort. A sensitivity of 80% and a specificity of 71% were found in SHOUT scores to identify patients with broad discharge failure with AUC of 0.83 (95% CI 0.83 to 0.84). When applied to a 3-day restricted discharge failure model, a sensitivity of 86% and a specificity of 60% were found to identify patients with AUC of 0.79 (95% CI 0.78 to 0.80).
CONCLUSION: The SHOUT scoring system was derived and used to screen and identify patients that would ultimately become discharge failures, especially when using broad definitions of discharge failure. The SHOUT tool was internally validated and can be used to identify patients across a wide spectrum of discharge failure definitions.

PMID: 31248927 [PubMed - in process]

Predictors of latent tuberculosis infection treatment completion in the US private sector: an analysis of administrative claims data.

Sun, 06/30/2019 - 06:57
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Predictors of latent tuberculosis infection treatment completion in the US private sector: an analysis of administrative claims data.

BMC Public Health. 2018 05 29;18(1):662

Authors: Stockbridge EL, Miller TL, Carlson EK, Ho C

Abstract
BACKGROUND: Factors that affect latent tuberculosis infection (LTBI) treatment completion in the US have not been well studied beyond public health settings. This gap was highlighted by recent health insurance-related regulatory changes that are likely to increase LTBI treatment by private sector healthcare providers. We analyzed LTBI treatment completion in the private healthcare setting to facilitate planning around this important opportunity for tuberculosis (TB) control in the US.
METHODS: We analyzed a national sample of commercial insurance medical and pharmacy claims data for people ages 0 to 64 years who initiated daily dose isoniazid treatment between July 2011 and March 2014 and who had complete data. All individuals resided in the US. Factors associated with treatment completion were examined using multivariable generalized ordered logit models and bivariate Kruskal-Wallis tests or Spearman correlations.
RESULTS: We identified 1072 individuals with complete data who initiated isoniazid LTBI treatment. Treatment completion was significantly associated with less restrictive health insurance, age < 15 years, patient location, use of interferon-gamma release assays, non-poverty, HIV diagnosis, immunosuppressive drug therapy, and higher cumulative counts of clinical risk factors.
CONCLUSIONS: Private sector healthcare claims data provide insights into LTBI treatment completion patterns and patient/provider behaviors. Such information is critical to understanding the opportunities and limitations of private healthcare in the US to support treatment completion as this sector's role in protecting against and eliminating TB grows.

PMID: 29843664 [PubMed - indexed for MEDLINE]

Discovery of a Bone-Like Blood Particle in the Peripheral Circulation of Humans and Rodents.

Fri, 06/28/2019 - 06:31
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Discovery of a Bone-Like Blood Particle in the Peripheral Circulation of Humans and Rodents.

Microcirculation. 2019 Jun 27;:e12579

Authors: Prisby R, Ross J, Opdenaker L, McLane MA, Lee S, Sun X, Guderian S

Abstract
OBJECTIVE: Characterize ossified bone marrow blood vessels and confirm the presence of ossified particles (OSP) in humans and rodents.
METHODS: Human bone marrow blood vessels were processed for scanning and transmission electron microscopy. Whole blood samples were collected from younger (26-39 years; n=6) and older (55-63 years; n=6) volunteers and male Fischer-344 rats (1 month, n= 7; 6 months, n=7; 12 months, n=7; 18-months, n=6; 24 months, n=8). OSP in the whole blood samples were sorted and imaged with microscopy to determine diameter, circularity and solidity. Additionally, the chemical composition of OSP was determined via elemental analysis.
RESULTS: SEM revealed two types of ossified bone marrow blood vessels; i.e., "transitioning" and "ossified". OSP were adhered to the surface of transitioning vessels, and theoretically gain access to and circulate within the blood. The majority of OSP were <15 μm in diameter, but many were of sufficient size to serve as emboli (i.e., >15 μm). OSP were predominately oblong in shape and several had jagged tips and edges.
CONCLUSIONS: We introduce a novel, bone-like blood particle that may be diagnostic of bone marrow blood vessel ossification. Further, OSP may associate with several disease states (e.g., atherosclerosis). This article is protected by copyright. All rights reserved.

PMID: 31246334 [PubMed - as supplied by publisher]

Multivariate Higher-Order IRT Model and MCMC Algorithm for Linking Individual Participant Data From Multiple Studies.

Fri, 06/28/2019 - 06:31
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Multivariate Higher-Order IRT Model and MCMC Algorithm for Linking Individual Participant Data From Multiple Studies.

Front Psychol. 2019;10:1328

Authors: Mun EY, Huo Y, White HR, Suzuki S, de la Torre J

Abstract
Many clinical and psychological constructs are conceptualized to have multivariate higher-order constructs that give rise to multidimensional lower-order traits. Although recent measurement models and computing algorithms can accommodate item response data with a higher-order structure, there are few measurement models and computing techniques that can be employed in the context of complex research synthesis, such as meta-analysis of individual participant data or integrative data analysis. The current study was aimed at modeling complex item responses that can arise when underlying domain-specific, lower-order traits are hierarchically related to multiple higher-order traits for individual participant data from multiple studies. We formulated a multi-group, multivariate higher-order item response theory (HO-IRT) model from a Bayesian perspective and developed a new Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the (a) structural parameters of the first- and second-order latent traits across multiple groups and (b) item parameters of the model. Results from a simulation study support the feasibility of the MCMC algorithm. From the analysis of real data, we found that a bivariate HO-IRT model with different correlation/covariance structures for different studies fit the data best, compared to a univariate HO-IRT model or other alternate models with unreasonable assumptions (i.e., the same means and covariances across studies). Although more work is needed to further develop the method and to disseminate it, the multi-group multivariate HO-IRT model holds promise to derive a common metric for individual participant data from multiple studies in research synthesis studies for robust inference and for new discoveries.

PMID: 31244727 [PubMed]

Role of pseudohypoxia in the pathogenesis of type 2 diabetes.

Thu, 06/27/2019 - 06:25
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Role of pseudohypoxia in the pathogenesis of type 2 diabetes.

Hypoxia (Auckl). 2019;7:33-40

Authors: Song J, Yang X, Yan LJ

Abstract
Type 2 diabetes is caused by persistent high blood glucose, which is known as diabetic hyperglycemia. This hyperglycemic situation, when not controlled, can overproduce NADH and lower nicotinamide adenine dinucleotide (NAD), thereby creating NADH/NAD redox imbalance and leading to cellular pseudohypoxia. In this review, we discussed two major enzymatic systems that are activated by diabetic hyperglycemia and are involved in creation of this pseudohypoxic condition. One system is aldose reductase in the polyol pathway, and the other is poly (ADP ribose) polymerase. While aldose reductase drives overproduction of NADH, PARP could in contrast deplete NAD. Therefore, activation of the two pathways underlies the major mechanisms of NADH/NAD redox imbalance and diabetic pseudohypoxia. Consequently, reductive stress occurs, followed by oxidative stress and eventual cell death and tissue dysfunction. Additionally, fructose formed in the polyol pathway can also cause metabolic syndrome such as hypertension and nonalcoholic fatty liver disease. Moreover, pseudohypoxia can also lower sirtuin protein contents and induce protein acetylation which can impair protein function. Finally, we discussed the possibility of using nicotinamide riboside, an NAD precursor, as a promising therapeutic agent for restoring NADH/NAD redox balance and for preventing the occurrence of diabetic pseudohypoxia.

PMID: 31240235 [PubMed]

Bacterial microbiomes of Ixodes scapularis ticks collected from Massachusetts and Texas, USA.

Thu, 06/27/2019 - 06:25
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Bacterial microbiomes of Ixodes scapularis ticks collected from Massachusetts and Texas, USA.

BMC Microbiol. 2019 Jun 24;19(1):138

Authors: Thapa S, Zhang Y, Allen MS

Abstract
BACKGROUND: The blacklegged tick, Ixodes scapularis, is the primary vector of the Lyme disease spirochete Borrelia burgdorferi in North America. Though the tick is found across the eastern United States, Lyme disease is endemic to the northeast and upper midwest and rare or absent in the southern portion of the vector's range. In an effort to better understand the tick microbiome from diverse geographic and climatic regions, we analysed the bacterial community of 115 I. scapularis adults collected from vegetation in Texas and Massachusetts, representing extreme ends of the vector's range, by massively parallel sequencing of the 16S V4 rRNA gene. In addition, 7 female I. scapularis collected from dogs in Texas were included in the study.
RESULTS: Male I. scapularis ticks had a more diverse bacterial microbiome in comparison to the female ticks. Rickettsia spp. dominated the microbiomes of field-collected female I. scapularis from both regions, as well as half of the males from Texas. In addition, the male and female ticks captured from Massachusetts contained high proportions of the pathogens Anaplasma and Borrelia, as well as the arthropod endosymbiont Wolbachia. None of these were found in libraries generated from ticks collected in Texas. Pseudomonas, Acinetobacter and Mycobacterium were significantly differently abundant (p < 0.05) between the male ticks from Massachusetts and Texas. Anaplasma and Borrelia were found in 15 and 63% of the 62 Massachusetts ticks, respectively, with a co-infection rate of 11%. Female ticks collected from Texas dogs were particularly diverse, and contained several genera including Rickettsia, Pseudomonas, Bradyrhizobium, Sediminibacterium, and Ralstonia.
CONCLUSIONS: Our results indicate that the bacterial microbiomes of I. scapularis ticks vary by sex and geography, with significantly more diversity in male microbiomes compared to females. We found that sex plays a larger role than geography in shaping the composition/diversity of the I. scapularis microbiome, but that geography affects what additional taxa are represented (beyond Rickettsia) and whether pathogens are found. Furthermore, recent feeding may have a role in shaping the tick microbiome, as evident from a more complex bacterial community in female ticks from dogs compared to the wild-caught questing females. These findings may provide further insight into the differences in the ability of the ticks to acquire, maintain and transmit pathogens. Future studies on possible causes and consequences of these differences will shed additional light on tick microbiome biology and vector competence.

PMID: 31234774 [PubMed - in process]

Blood Biomarkers for Use in Alzheimer Disease-Moving From "If" to "How?"

Tue, 06/25/2019 - 05:59

Blood Biomarkers for Use in Alzheimer Disease-Moving From "If" to "How?"

JAMA Neurol. 2019 Jun 24;:

Authors: O'Bryant SE

PMID: 31233119 [PubMed - as supplied by publisher]

Effect of β-blocker Therapy on Hospital Readmission and Mortality in Heart Failure Patients With Concurrent Cocaine Use.

Tue, 06/25/2019 - 05:59
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Effect of β-blocker Therapy on Hospital Readmission and Mortality in Heart Failure Patients With Concurrent Cocaine Use.

J Cardiovasc Pharmacol Ther. 2018 11;23(6):518-523

Authors: Egbuche O, Ekechukwu I, Effoe V, Maduabum N, Millard HR, Maihemuti A, Cross JA, Adedinsewo D, Onwuanyi AE

Abstract
BACKGROUND: β-Blockers are first-line agents for reduction in symptoms, hospitalization, and mortality in patients with heart failure having reduced ejection fraction (HFrEF). However, the safety and efficacy of continuous β-blocker therapy (BBT) in patients who actively use cocaine remain controversial, and available literature is limited. We aimed to evaluate the effect of BBT on hospital readmission and mortality in patients having HFrEF with concurrent cocaine use.
METHODS: We conducted a retrospective study of patients with a diagnosis of HFrEF between 2011 and 2014 based on International Classification of Diseases 9-Clinical Modification codes. We included patients aged 18 and older who tested positive for cocaine on a urine toxicology test obtained at the time of index admission. Patients were followed for 1 year. Multivariate logistic regression was used to assess the effect of BBT on the 30-day, all-cause and heart failure-related readmissions.
RESULTS: The 30-day readmission rates for BBT versus no BBT groups were 20% versus 41% (odds ratio [OR]: 0.17, 95% confidence interval [CI] = 0.05-0.56, P = .004) for heart failure-related readmissions and 25% versus 46% (OR: 0.19, 95% CI = 0.06-0.64, P = .007) for all-cause readmissions.
CONCLUSION: The BBT reduced 30-day, all-cause and heart failure-related readmission rate but not 1-year mortality in patients having HFrEF with concurrent cocaine use.

PMID: 29793347 [PubMed - indexed for MEDLINE]

Impact of a low-cost simulated electronic medical record on perceptions of APPE readiness.

Sun, 06/23/2019 - 05:29
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Impact of a low-cost simulated electronic medical record on perceptions of APPE readiness.

Curr Pharm Teach Learn. 2019 Jul;11(7):736-741

Authors: Gibson CM, Kwon HI, Tatachar A

Abstract
BACKGROUND: Meaningful use of electronic medical records (EMRs) is critical for providing high-quality, patient-centered care. However, many pharmacy students are not exposed to EMRs until the experiential components of the curriculum.
EDUCATIONAL ACTIVITY AND SETTING: We created a low-cost simulated EMR (SEMR) using Microsoft PowerPoint software (Microsoft, Redmond, WA, Version 16.16) to use in a case-based application course for second-year pharmacy students for two consecutive years.
FINDINGS: Pre- and post-assessment surveys of 162 students indicated that perceived confidence and efficiency navigating EMRs improved after the activity. Students agreed that the activity enhanced learning, improved understanding of how to extract meaningful data from EMRs, benefited their preparation for the fourth professional year, and demonstrated the role of informatics in patient care.
SUMMARY: Incorporation of a SEMR using Microsoft PowerPoint enhances student perceptions of proficiency in navigating the patient medical record. Adoption of similar activities into pharmacy curricula may be an attractive option when adequate financial resources for simulation are unavailable.

PMID: 31227098 [PubMed - in process]

Association of Vitamin D and Magnesium Status with Cognitive Function in Older Adults: Results from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2014 (FS05-03-19).

Sat, 06/22/2019 - 05:15

Association of Vitamin D and Magnesium Status with Cognitive Function in Older Adults: Results from the National Health and Nutrition Examination Survey (NHANES) 2011 to 2014 (FS05-03-19).

Curr Dev Nutr. 2019 Jun;3(Suppl 1):

Authors: Peeri N, Egan K, Tao M

Abstract
Objectives: Vitamin D protects neuronal structure and aids in neuronal calcium regulation and may play a role in neurodegeneration and aging. Magnesium plays an important role in multiple neurological disorders including cognitive impairment, and is linked with the synthesis and metabolism of vitamin D. Whether vitamin D and magnesium status influence cognitive function in older adults is poorly studied. We examined potential associations of these nutrients with cognitive status in a population-based cross-sectional study.
Methods: Utilizing data from the National Health and Nutrition Survey (NHANES) 2011 to 2014, 2984 participants aged 60 years and older who completed the Digit Symbol Substitution Test (DSST) were analyzed. Cognitive function was assessed using DSST scores. Cases were defined as participants with a 25th percentile or lower score on the DSST. Total vitamin D and magnesium intake were determined from 24-hour dietary recalls and supplemental interviews. Serum 25-hydroxyvitamin D (25(OH)D) was used to define vitamin D status. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).
Results: After adjustment for confounders, total energy and magnesium intake, a higher serum 25(OH)D level was associated with decreased odds of having a low DSST score (OR: 0.66; 95% CI: 0.50, 0.87) comparing highest vs. lowest tertile (P trend < 0.01). A similar association was observed for total vitamin D intake, with a reduced risk of lower DSST score with higher vitamin D intake. An inverse association of higher serum 25(OH)D with cognitive function was observed primarily among participants with a daily total magnesium intake of <254 mg (OR: 0.50; 95% CI: 0.32, 0.78) or ≥375 mg (OR: 0.60; 95% CI: 0.38, 0.95). There were no clear associations for cognitive function with total magnesium intake overall.
Conclusions: We found that higher serum 25(OH)D levels were associated with reduced risk of low cognitive function in older adults, and this association appeared to be modified by the intake level of magnesium. These findings warrant further studies investigating magnesium and vitamin D and their combined effects on cognitive function.
Funding Sources: UNTHSC.
Supporting Tables Images and/or Graphs:

PMID: 31225401 [PubMed]

Sniffer cells for the detection of neural Angiotensin II in vitro.

Fri, 06/21/2019 - 05:02
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Sniffer cells for the detection of neural Angiotensin II in vitro.

Sci Rep. 2019 Jun 19;9(1):8820

Authors: Farmer GE, Amune A, Bachelor ME, Duong P, Yuan JP, Cunningham JT

Abstract
Neuropeptide release in the brain has traditionally been difficult to observe. Existing methods lack temporal and spatial resolution that is consistent with the function and size of neurons. We use cultured "sniffer cells" to improve the temporal and spatial resolution of observing neuropeptide release. Sniffer cells were created by stably transfecting Chinese Hamster Ovary (CHO) cells with plasmids encoding the rat angiotensin type 1a receptor and a genetically encoded Ca2+ sensor. Isolated, cultured sniffer cells showed dose-dependent increases in fluorescence in response to exogenously applied angiotensin II and III, but not other common neurotransmitters. Sniffer cells placed on the median preoptic nucleus (a presumptive site of angiotensin release) displayed spontaneous activity and evoked responses to either electrical or optogenetic stimulation of the subfornical organ. Stable sniffer cell lines could be a viable method for detecting neuropeptide release in vitro, while still being able to distinguish differences in neuropeptide concentration.

PMID: 31217439 [PubMed - in process]

Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

Fri, 06/21/2019 - 05:02
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Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

Parkinsonism Relat Disord. 2018 07;52:37-42

Authors: Weng R, Wei X, Yu B, Zhu S, Yang X, Xie F, Zhang M, Jiang Y, Feng ZP, Sun HS, Xia Y, Jin K, Chan P, Wang Q, Gao X

Abstract
INTRODUCTION: Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity.
METHODS: We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects.
RESULTS: Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter.
CONCLUSIONS: Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP.

PMID: 29574085 [PubMed - indexed for MEDLINE]

Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia.

Fri, 06/21/2019 - 05:02
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Enhanced cerebral perfusion during brief exposures to cyclic intermittent hypoxemia.

J Appl Physiol (1985). 2017 12 01;123(6):1689-1697

Authors: Liu X, Xu D, Hall JR, Ross S, Chen S, Liu H, Mallet RT, Shi X

Abstract
Cerebral vasodilation and increased cerebral oxygen extraction help maintain cerebral oxygen uptake in the face of hypoxemia. This study examined cerebrovascular responses to intermittent hypoxemia in eight healthy men breathing 10% O2 for 5 cycles, each 6 min, interspersed with 4 min of room air breathing. Hypoxia exposures raised heart rate ( P < 0.01) without altering arterial pressure, and increased ventilation ( P < 0.01) by expanding tidal volume. Arterial oxygen saturation ([Formula: see text]) and cerebral tissue oxygenation ([Formula: see text]) fell ( P < 0.01) less appreciably in the first bout (from 97.0 ± 0.3% and 72.8 ± 1.6% to 75.5 ± 0.9% and 54.5 ± 0.9%, respectively) than the fifth bout (from 94.9 ± 0.4% and 70.8 ± 1.0% to 66.7 ± 2.3% and 49.2 ± 1.5%, respectively). Flow velocity in the middle cerebral artery ( VMCA) and cerebrovascular conductance increased in a sigmoid fashion with decreases in [Formula: see text] and [Formula: see text]. These stimulus-response curves shifted leftward and upward from the first to the fifth hypoxia bouts; thus, the centering points fell from 79.2 ± 1.4 to 74.6 ± 1.1% ( P = 0.01) and from 59.8 ± 1.0 to 56.6 ± 0.3% ( P = 0.002), and the minimum VMCA increased from 54.0 ± 0.5 to 57.2 ± 0.5 cm/s ( P = 0.0001) and from 53.9 ± 0.5 to 57.1 ± 0.3 cm/s ( P = 0.0001) for the [Formula: see text]- VMCA and [Formula: see text]- VMCA curves, respectively. Cerebral oxygen extraction increased from prehypoxia 0.22 ± 0.01 to 0.25 ± 0.02 in minute 6 of the first hypoxia bout, and remained elevated between 0.25 ± 0.01 and 0.27 ± 0.01 throughout the fifth hypoxia bout. These results demonstrate that cerebral vasodilation combined with enhanced cerebral oxygen extraction fully compensated for decreased oxygen content during acute, cyclic hypoxemia. NEW & NOTEWORTHY Five bouts of 6-min intermittent hypoxia (IH) exposures to 10% O2 progressively reduce arterial oxygen saturation ([Formula: see text]) to 67% without causing discomfort or distress. Cerebrovascular responses to hypoxemia are dynamically reset over the course of a single IH session, such that threshold and saturation for cerebral vasodilations occurred at lower [Formula: see text] and cerebral tissue oxygenation ([Formula: see text]) during the fifth vs. first hypoxia bouts. Cerebral oxygen extraction is augmented during acute hypoxemia, which compensates for decreased arterial O2 content.

PMID: 29074711 [PubMed - indexed for MEDLINE]

The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders.

Thu, 06/20/2019 - 07:55
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The negative and detrimental effects of high fructose on the liver, with special reference to metabolic disorders.

Diabetes Metab Syndr Obes. 2019;12:821-826

Authors: Mai BH, Yan LJ

Abstract
The increased consumption of fructose in the average diet through sweeteners such as high-fructose corn syrup (HFCS) and sucrose has resulted in negative outcomes in society through producing a considerable economic and medical burden on our healthcare system. Ingestion of fructose chronically has contributed to multiple health consequences, such as insulin resistance, obesity, liver disorders, and diabetes. Fructose metabolism starts with fructose phosphorylation by fructose kinase in the liver, and this process is not feedback regulated. Therefore, ingestion of high fructose can deplete ATP, increase uric acid production, and increase nucleotide turnover. This review focuses the discussion on the hepatic manifestations of high fructose-implicated liver metabolic disorders such as insulin resistance, obesity due to enhanced lipogenesis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and type 2 diabetes. The detrimental effects of high fructose on the liver, contributed potentially by microbiome and leptin, were also discussed. The authors believe that, together with diet management, further studies focusing on disrupting or blocking fructose metabolism in the liver may help with designing novel strategies for prevention and treatment of fructose-induced chronic liver metabolic diseases.

PMID: 31213868 [PubMed]

Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma.

Wed, 06/19/2019 - 07:45
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Effect of ocular hypertension on the pattern of retinal ganglion cell subtype loss in a mouse model of early-onset glaucoma.

Exp Eye Res. 2019 Jun 15;:107703

Authors: Daniel S, Meyer KJ, Clark AF, Anderson MG, McDowell CM

Abstract
Glaucoma is a neurodegenerative disease with elevated intraocular pressure as one of the major risk factors. Glaucoma leads to irreversible loss of vision and its progression involves optic nerve head cupping, axonal degeneration, retinal ganglion cell (RGC) loss, and visual field defects. Despite its high global prevalence, glaucoma still remains a major neurodegenerative disease. Introduction of mouse models of experimental glaucoma has become integral to glaucoma research due to well-studied genetics as well as ease of manipulations. Many established inherent and inducible mouse models of glaucoma are used to study the molecular and physiological progression of the disease. One such model of spontaneous mutation is the nee model, which is caused by mutation of the Sh3pxd2b gene. In both humans and mice, mutations disrupting function of the SH3PXD2B adaptor protein cause a developmental syndrome including secondary congenital glaucoma. The purpose of this study was to characterize the early onset nee glaucoma phenotype on the C57BL/6J background and to evaluate the pattern of RGC loss and axonal degeneration in specific RGC subtypes. We found that the B6.Sh3pxd2bnee mutant animals exhibit glaucoma phenotypes of elevated intraocular pressure, RGC loss and axonal degeneration. Moreover, the non-image forming RGCs survived longer than the On-Off direction selective RGCs (DSGC), and the axonal death in these RGCs was independent of their respective RGC subtype. In conclusion, through this study we characterized an experimental model of early onset glaucoma on a C57BL/6J background exhibiting key glaucoma phenotypes. In addition, we describe that RGC death has subtype-specific sensitivities and follows a specific pattern of cell death under glaucomatous conditions.

PMID: 31211954 [PubMed - as supplied by publisher]

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