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 6 min ago

Chest Pain Risk Scores Can Reduce Emergent Cardiac Imaging Test Needs With Low Major Adverse Cardiac Events Occurrence in an Emergency Department Observation Unit.

Fri, 11/03/2017 - 07:46
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Chest Pain Risk Scores Can Reduce Emergent Cardiac Imaging Test Needs With Low Major Adverse Cardiac Events Occurrence in an Emergency Department Observation Unit.

Crit Pathw Cardiol. 2016 Dec;15(4):145-151

Authors: Wang H, Watson K, Robinson RD, Domanski KH, Umejiego J, Hamblin L, Overstreet SE, Akin AM, Hoang S, Shrivastav M, Collyer M, Krech RN, Schrader CD, Zenarosa NR

Abstract
OBJECTIVE: To compare and evaluate the performance of the HEART, Global Registry of Acute Coronary Events (GRACE), and Thrombolysis in Myocardial Infarction (TIMI) scores to predict major adverse cardiac event (MACE) rates after index placement in an emergency department observation unit (EDOU) and to determine the need for observation unit initiation of emergent cardiac imaging tests, that is, noninvasive cardiac stress tests and invasive coronary angiography.
METHODS: A prospective observational single center study was conducted from January 2014 through June 2015. EDOU chest pain patients were included. HEART, GRACE, and TIMI scores were categorized as low (HEART ≤ 3, GRACE ≤ 108, and TIMI ≤1) versus elevated based on thresholds suggested in prior studies. Patients were followed for 6 months postdischarge. The results of emergent cardiac imaging tests, EDOU length of stay (LOS), and MACE occurrences were compared. Student t test was used to compare groups with continuous data, and χ testing was used for categorical data analysis.
RESULTS: Of 986 patients, emergent cardiac imaging tests were performed on 62%. A majority of patients were scored as low risk by all tools (85% by HEART, 81% by GRACE, and 80% by TIMI, P < 0.05). The low-risk patients had few abnormal cardiac imaging test results as compared with patients scored as intermediate to high risk (1% vs. 11% in HEART, 1% vs. 9% in TIMI, and 2% vs. 4% in GRACE, P < 0.05). The average LOS was 33 hours for patients with emergent cardiac imaging tests performed and 25 hours for patients without (P < 0.05). MACE occurrence rate demonstrated no significant difference regardless of whether tests were performed emergently (0.31% vs. 0.97% in HEART, 0.27% vs. 0.95% in TIMI, and 0% vs. 0.81% in GRACE, P > 0.05).
CONCLUSIONS: Chest pain risk stratification via clinical decision tool scores can minimize the need for emergent cardiac imaging tests with less than 1% MACE occurrence, especially when the HEART score is used.

PMID: 27846006 [PubMed - indexed for MEDLINE]

Solvatochromic dye LDS 798 as microviscosity and pH probe.

Thu, 11/02/2017 - 07:46
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Solvatochromic dye LDS 798 as microviscosity and pH probe.

Phys Chem Chem Phys. 2017 Nov 01;:

Authors: Doan H, Castillo M, Bejjani M, Nurekeyev Z, Dzyuba SV, Gryczynski I, Gryczynski Z, Raut S

Abstract
Styryl dyes, specifically LDS group dyes, are known solvatochromic and electrochromic probes for monitoring mitochondrial potential in cellular environments. However, the ability of these dyes to respond to fluctuations in viscosity, pH and temperature has not been established. In this study, we demonstrated that LDS 798 (also known as Styryl-11) can sense environmental viscosity (via fluorescence lifetime changes) as well as pH changes (ratiometric intensity change) in the absence of polarity variations. Polarity changes can be probed by spectral changes using LDS 798. Therefore, all properties of the media should be considered, when these types of dyes are used as electrochromic/solvatochromic sensors in cellular environments.

PMID: 29090298 [PubMed - as supplied by publisher]

Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Wed, 11/01/2017 - 07:42
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Increasing the reference populations for the 55 AISNP panel: the need and benefits.

Int J Legal Med. 2017 Jul;131(4):913-917

Authors: Pakstis AJ, Kang L, Liu L, Zhang Z, Jin T, Grigorenko EL, Wendt FR, Budowle B, Hadi S, Al Qahtani MS, Morling N, Mogensen HS, Themudo GE, Soundararajan U, Rajeevan H, Kidd JR, Kidd KK

Abstract
Ancestry inference for an individual can only be as good as the reference populations with allele frequency data on the SNPs being used. If the most relevant ancestral population(s) does not have data available for the SNPs studied, then analyses based on DNA evidence may indicate a quite distantly related population, albeit one among the more closely related of the existing reference populations. We have added reference population allele frequencies for 14 additional population samples (with >1100 individuals studied) to the 125 population samples previously published for the Kidd Lab 55 AISNP panel. Allele frequencies are now publicly available for all 55 SNPs in ALFRED and FROG-kb for a total of 139 population samples. This Kidd Lab panel of 55 ancestry informative SNPs has been incorporated in commercial kits by both ThermoFisher Scientific and Illumina for massively parallel sequencing. Researchers employing those kits will find the enhanced set of reference populations useful.

PMID: 28070634 [PubMed - indexed for MEDLINE]

Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

Tue, 10/31/2017 - 07:33

Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

J Public Health Manag Pract. 2017 Oct 27;:

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

Abstract
CONTEXT: Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector.
OBJECTIVES: To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims.
METHODS: Medical and pharmacy claims data representing insurance-paid services rendered and prescriptions filled between January 2011 and March 2015 were analyzed.
PARTICIPANTS: Four million commercially insured individuals 0 to 64 years of age.
MAIN OUTCOME MEASURES: Six-month and 9-month treatment completion rates for isoniazid LTBI regimens.
RESULTS: There was an annual isoniazid LTBI treatment initiation rate of 12.5/100 000 insured persons. Of 1074 unique courses of treatment with isoniazid for which treatment completion could be assessed, almost half (46.3%; confidence interval, 43.3-49.3) completed 6 or more months of therapy. Of those, approximately half (48.9%; confidence interval, 44.5-53.3) completed 9 months or more.
CONCLUSIONS: Claims data can be used to identify and evaluate LTBI treatment with isoniazid occurring in the commercial sector. Completion rates were in the range of those found in public health settings. These findings suggest that the commercial sector may be a valuable adjunct to more traditional venues for tuberculosis prevention. In addition, these newly developed claims-based methods offer a means to gain important insights and open new avenues to monitor, evaluate, and coordinate tuberculosis prevention.

PMID: 29084120 [PubMed - as supplied by publisher]

The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity.

Tue, 10/31/2017 - 07:33

The Neuroprotective Effects of SIRT1 on NMDA-Induced Excitotoxicity.

Oxid Med Cell Longev. 2017;2017:2823454

Authors: Yang X, Si P, Qin H, Yin L, Yan LJ, Zhang C

Abstract
Silent information regulator 1 (SIRT1), an NAD(+)-dependent deacetylase, is involved in the regulation of gene transcription, energy metabolism, and cellular aging and has become an important therapeutic target across a range of diseases. Recent research has demonstrated that SIRT1 possesses neuroprotective effects; however, it is unknown whether it protects neurons from NMDA-mediated neurotoxicity. In the present study, by activation of SIRT1 using resveratrol (RSV) in cultured cortical neurons or by overexpression of SIRT1 in SH-SY5Y cell, we aimed to evaluate the roles of SIRT1 in NMDA-induced excitotoxicity. Our results showed that RSV or overexpression of SIRT1 elicited inhibitory effects on NMDA-induced excitotoxicity including a decrease in cell viability, an increase in lactate dehydrogenase (LDH) release, and a decrease in the number of living cells as measured by CCK-8 assay, LDH test, and Calcein-AM and PI double staining. RSV or overexpression of SIRT1 significantly improved SIRT1 deacetylase activity in the excitotoxicity model. Further study suggests that overexpression of SIRT1 partly suppressed an NMDA-induced increase in p53 acetylation. These results indicate that SIRT1 activation by either RSV or overexpression of SIRT1 can exert neuroprotective effects partly by inhibiting p53 acetylation in NMDA-induced neurotoxicity.

PMID: 29081884 [PubMed - in process]

Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.

Sat, 10/28/2017 - 07:33
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Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry.

World J Biol Psychiatry. 2017 Oct 27;:1-85

Authors: Lewczuk P, Riederer P, O'Bryant SE, Verbeek MM, Dubois B, Visser PJ, Jellinger KA, Engelborghs S, Ramirez A, Parnetti L, Jack CR, Teunissen CE, Hampel H, Lleó A, Jessen F, Glodzik L, de Leon MJ, Fagan AM, Molinuevo JL, Jansen WJ, Winblad B, Shaw LM, Andreasson U, Otto M, Mollenhauer B, Wiltfang J, Turner MR, Zerr I, Handels R, Thompson AG, Johansson G, Ermann N, Trojanowski JQ, Karaca I, Wagner H, Oeckl P, van Waalwijk van Doorn L, Bjerke M, Kapogiannis D, Kuiperij HB, Farotti L, Li Y, Gordon BA, Epelbaum S, Vos SJB, Klijn CJM, Van Nostrand WE, Minguillon C, Schmitz M, Gallo C, Lopez Mato A, Thibaut F, Lista S, Alcolea D, Zetterberg H, Blennow K, Kornhuber J, Members of the WFSBP Task Force Working on this Topic: Peter Riederer, Carla Gallo, Dimitrios Kapogiannis, Andrea Lopez Mato, Florence Thibaut

Abstract
In the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.

PMID: 29076399 [PubMed - as supplied by publisher]

Full-gene haplotypes refine CYP2D6 metabolizer phenotype inferences.

Sat, 10/28/2017 - 07:33
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Full-gene haplotypes refine CYP2D6 metabolizer phenotype inferences.

Int J Legal Med. 2017 Oct 26;:

Authors: Wendt FR, Sajantila A, Moura-Neto RS, Woerner AE, Budowle B

Abstract
CYP2D6 is a critical pharmacogenetic target, and polymorphisms in the gene region are commonly used to infer enzyme activity score and predict resulting metabolizer phenotype: poor, intermediate, extensive/normal, or ultrarapid which can be useful in determining cause and/or manner of death in some autopsies. Current genotyping approaches are incapable of identifying novel and/or rare variants, so CYP2D6 star allele definitions are limited to polymorphisms known a priori. While useful for most predictions, recent studies using massively parallel sequencing data have identified additional polymorphisms in CYP2D6 that are predicted to alter enzyme function but are not considered in current star allele nomenclature. The 1000 Genomes Project data were used to produce full-gene haplotypes, describe their distribution in super-populations, and predict enzyme activity scores. Full-gene haplotypes generated lower activity scores than current approaches due to inclusion of additional damaging polymorphisms in the star allele. These findings are critical for clinical implementation of metabolizer phenotype prediction because a fraction of the population may be incorrectly considered normal metabolizers but actually may be poor or intermediate metabolizers.

PMID: 29075918 [PubMed - as supplied by publisher]

Enhanced Cerebral Perfusion during Brief Exposures to Cyclic Intermittent Hypoxemia.

Sat, 10/28/2017 - 07:33
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Enhanced Cerebral Perfusion during Brief Exposures to Cyclic Intermittent Hypoxemia.

J Appl Physiol (1985). 2017 Oct 26;:jap.00647.2017

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 (SaO2) and cerebral tissue oxygenation (ScO2) 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 with decreases in SaO2 and ScO2 in a sigmoid fashion. 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(-1) (P=0.0001) and from 53.9±0.5 to 57.1±0.3 cm•s(-1) (P=0.0001) for the SaO2-VMCA and ScO2-VMCA curves, respectively. Cerebral oxygen extraction increased from pre-hypoxia 0.22±0.01 to 0.25±0.02 in minute 6 of the first hypoxia bout, and remained elevated at 0.25±0.01 - 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.

PMID: 29074711 [PubMed - as supplied by publisher]

Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

Sat, 10/28/2017 - 07:33
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Roles of disease severity and post-discharge outpatient visits as predictors of hospital readmissions.

BMC Health Serv Res. 2016 Oct 10;16(1):564

Authors: Wang H, Johnson C, Robinson RD, Nejtek VA, Schrader CD, Leuck J, Umejiego J, Trop A, Delaney KA, Zenarosa NR

Abstract
BACKGROUND: Risks prediction models of 30-day all-cause hospital readmissions are multi-factorial. Severity of illness (SOI) and risk of mortality (ROM) categorized by All Patient Refined Diagnosis Related Groups (APR-DRG) seem to predict hospital readmission but lack large sample validation. Effects of risk reduction interventions including providing post-discharge outpatient visits remain uncertain. We aim to determine the accuracy of using SOI and ROM to predict readmission and further investigate the role of outpatient visits in association with hospital readmission.
METHODS: Hospital readmission data were reviewed retrospectively from September 2012 through June 2015. Patient demographics and clinical variables including insurance type, homeless status, substance abuse, psychiatric problems, length of stay, SOI, ROM, ICD-10 diagnoses and medications prescribed at discharge, and prescription ratio at discharge (number of medications prescribed divided by number of ICD-10 diagnoses) were analyzed using logistic regression. Relationships among SOI, type of hospital visits, time between hospital visits, and readmissions were also investigated.
RESULTS: A total of 6011 readmissions occurred from 55,532 index admissions. The adjusted odds ratios of SOI and ROM predicting readmissions were 1.31 (SOI: 95 % CI 1.25-1.38) and 1.09 (ROM: 95 % CI 1.05-1.14) separately. Ninety percent (5381/6011) of patients were readmitted from the Emergency Department (ED) or Urgent Care Center (UCC). Average time interval from index discharge date to ED/UCC visit was 9 days in both the no readmission and readmission groups (p > 0.05). Similar hospital readmission rates were noted during the first 10 days from index discharge regardless of whether post-index discharge patient clinic visits occurred when time-to-event analysis was performed.
CONCLUSIONS: SOI and ROM significantly predict hospital readmission risk in general. Most readmissions occurred among patients presenting for ED/UCC visits after index discharge. Simply providing early post-discharge follow-up clinic visits does not seem to prevent hospital readmissions.

PMID: 27724889 [PubMed - indexed for MEDLINE]

Effects of state-level Earned Income Tax Credit laws in the U.S. on maternal health behaviors and infant health outcomes.

Fri, 10/27/2017 - 13:54
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Effects of state-level Earned Income Tax Credit laws in the U.S. on maternal health behaviors and infant health outcomes.

Soc Sci Med. 2017 Oct 16;194:67-75

Authors: Markowitz S, Komro KA, Livingston MD, Lenhart O, Wagenaar AC

Abstract
The purpose of this paper is to investigate the effects of state-level Earned Income Tax Credit (EITC) laws in the U.S. on maternal health behaviors and infant health outcomes. Using multi-state, multi-year difference-in-differences analyses, we estimated effects of state EITC generosity on maternal health behaviors, birth weight and gestation weeks. We find little difference in maternal health behaviors associated with state-level EITC. In contrast, results for key infant health outcomes of birth weight and gestation weeks show small improvements in states with EITCs, with larger effects seen among states with more generous EITCs. Our results provide evidence for important health benefits of state-level EITC policies.

PMID: 29073507 [PubMed - as supplied by publisher]

A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.

Fri, 10/27/2017 - 13:54
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A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.

Sci Rep. 2017 Oct 25;7(1):14057

Authors: Pedrini S, Gupta VB, Hone E, Doecke J, O'Bryant S, James I, Bush AI, Rowe CC, Villemagne VL, Ames D, Masters CL, Martins RN, AIBL Research Group

Abstract
Alzheimer's Disease (AD) is the most common form of dementia, characterised by extracellular amyloid deposition as plaques and intracellular neurofibrillary tangles of tau protein. As no current clinical test can diagnose individuals at risk of developing AD, the aim of this project is to evaluate a blood-based biomarker panel to identify individuals who carry this risk. We analysed the levels of 22 biomarkers in clinically classified healthy controls (HC), mild cognitive impairment (MCI) and Alzheimer's participants from the well characterised Australian Imaging, Biomarker and Lifestyle (AIBL) study of aging. High levels of IL-10 and IL-12/23p40 were significantly associated with amyloid deposition in HC, suggesting that these two biomarkers might be used to detect at risk individuals. Additionally, other biomarkers (Eotaxin-3, Leptin, PYY) exhibited altered levels in AD participants possessing the APOE ε4 allele. This suggests that the physiology of some potential biomarkers may be altered in AD due to the APOE ε4 allele, a major risk factor for AD. Taken together, these data highlight several potential biomarkers that can be used in a blood-based panel to allow earlier identification of individuals at risk of developing AD and/or early stage AD for which current therapies may be more beneficial.

PMID: 29070909 [PubMed - in process]

Letter to the Editor: comments on biostatistical power of sibling analysis by STR markers.

Fri, 10/27/2017 - 13:54
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Letter to the Editor: comments on biostatistical power of sibling analysis by STR markers.

Int J Legal Med. 2016 Jul;130(4):953-7

Authors: Chakraborty R

PMID: 27166704 [PubMed - indexed for MEDLINE]

Patient-Centered Medical Home Features and Health Care Expenditures of Medicare Beneficiaries with Chronic Disease Dyads.

Fri, 10/27/2017 - 13:54
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Patient-Centered Medical Home Features and Health Care Expenditures of Medicare Beneficiaries with Chronic Disease Dyads.

Popul Health Manag. 2016 06;19(3):206-11

Authors: Philpot LM, Stockbridge EL, Padrón NA, Pagán JA

Abstract
Three out of 4 Medicare beneficiaries have multiple chronic conditions, and managing the care of this growing population can be complex and costly because of care coordination challenges. This study assesses how different elements of the patient-centered medical home (PCMH) model may impact the health care expenditures of Medicare beneficiaries with the most prevalent chronic disease dyads (ie, co-occurring high cholesterol and high blood pressure, high cholesterol and heart disease, high cholesterol and diabetes, high cholesterol and arthritis, heart disease and high blood pressure). Data from the 2007-2011 Medical Expenditure Panel Survey suggest that increased access to PCMH features may differentially impact the distribution of health care expenditures across health care service categories depending on the combination of chronic conditions experienced by each beneficiary. For example, having no difficulty contacting a provider after regular hours was associated with significantly lower outpatient expenditures for beneficiaries with high cholesterol and diabetes (n = 635; P = 0.038), but it was associated with significantly higher inpatient expenditures for beneficiaries with high blood pressure and high cholesterol (n = 1599; P = 0.015), and no significant differences in expenditures in any category for beneficiaries with high blood pressure and heart disease (n = 1018; P > 0.05 for all categories). However, average total health care expenditures are largely unaffected by implementing the PCMH features considered. Understanding how the needs of Medicare beneficiaries with multiple chronic conditions can be met through the adoption of the PCMH model is important not only to be able to provide high-quality care but also to control costs. (Population Health Management 2016;19:206-211).

PMID: 26440215 [PubMed - indexed for MEDLINE]

Targeted sequencing of clade-specific markers from skin microbiomes for forensic human identification.

Wed, 10/25/2017 - 07:43
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Targeted sequencing of clade-specific markers from skin microbiomes for forensic human identification.

Forensic Sci Int Genet. 2017 Oct 18;32:50-61

Authors: Schmedes SE, Woerner AE, Novroski NMM, Wendt FR, King JL, Stephens KM, Budowle B

Abstract
The human skin microbiome is comprised of diverse communities of bacterial, eukaryotic, and viral taxa and contributes millions of additional genes to the repertoire of human genes, affecting human metabolism and immune response. Numerous genetic and environmental factors influence the microbiome composition and as such contribute to individual-specific microbial signatures which may be exploited for forensic applications. Previous studies have demonstrated the potential to associate skin microbial profiles collected from touched items to their individual owner, mainly using unsupervised methods from samples collected over short time intervals. Those studies utilize either targeted 16S rRNA or shotgun metagenomic sequencing to characterize skin microbiomes; however, these approaches have limited species and strain resolution and susceptibility to stochastic effects, respectively. Clade-specific markers from the skin microbiome, using supervised learning, can predict individual identity using skin microbiomes from their respective donors with high accuracy. In this study the hidSkinPlex is presented, a novel targeted sequencing method using skin microbiome markers developed for human identification. The hidSkinPlex (comprised of 286 bacterial (and phage) family-, genus-, species-, and subspecies-level markers), initially was evaluated on three bacterial control samples represented in the panel (i.e., Propionibacterium acnes, Propionibacterium granulosum, and Rothia dentocariosa) to assess the performance of the multiplex. The hidSkinPlex was further evaluated for prediction purposes. The hidSkinPlex markers were used to attribute skin microbiomes collected from eight individuals from three body sites (i.e., foot (Fb), hand (Hp) and manubrium (Mb)) to their host donor. Supervised learning, specifically regularized multinomial logistic regression and 1-nearest-neighbor classification were used to classify skin microbiomes to their hosts with up to 92% (Fb), 96% (Mb), and 100% (Hp) accuracy. All samples (n=72) regardless of body site origin were correctly classified with up to 94% accuracy, and body site origin could be predicted with up to 86% accuracy. Finally, human short tandem repeat and single-nucleotide polymorphism profiles were generated from skin swab extracts from a single subject to highlight the potential to use microbiome profiling in conjunction with low-biomass samples. The hidSkinPlex is a novel targeted enrichment approach to profile skin microbiomes for human forensic identification purposes and provides a method to further characterize the utility of skin microflora for human identification in future studies, such as the stability and diversity of the personal skin microbiome.

PMID: 29065388 [PubMed - as supplied by publisher]

Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke.

Wed, 10/25/2017 - 07:43
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Genistein: mechanisms of action for a pleiotropic neuroprotective agent in stroke.

Nutr Neurosci. 2017 Oct 24;:1-17

Authors: Schreihofer DA, Oppong-Gyebi A

Abstract
Genistein is a plant estrogen promoted as an alternative to post-menopausal hormone therapy because of a good safety profile and its promotion as a natural product. Several preclinical studies of cerebral ischemia and other models of brain injury support a beneficial role for genistein in protecting the brain from injury whether administered chronically or acutely. Like estrogen, genistein is a pleiotropic molecule that engages several different mechanisms to enhance brain health, including reduction of oxidative stress, promotion of growth factor signaling, and immune suppression. These actions occur in endothelial, glial, and neuronal cells to provide a coordinated beneficial action to ischemic challenge. Though many of these protective actions are associated with estrogen-like actions of genistein, additional activities on other receptors and intracellular targets suggest that genistein is more than a mere estrogen-mimic. Importantly, genistein lacks some of the detrimental effects associated with post-menopausal estrogen treatment and may provide an alternative to hormone therapy in those patients at risk for ischemic events.

PMID: 29063799 [PubMed - as supplied by publisher]

Maternal Vascular Physiology in Preeclampsia.

Wed, 10/25/2017 - 07:43
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Maternal Vascular Physiology in Preeclampsia.

Hypertension. 2017 Oct 23;:

Authors: Goulopoulou S

PMID: 29061723 [PubMed - as supplied by publisher]

Behavioral comparisons in Autism Spectrum Disorder and Developmental Coordination Disorder: A systematic literature review.

Tue, 10/24/2017 - 07:32
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Behavioral comparisons in Autism Spectrum Disorder and Developmental Coordination Disorder: A systematic literature review.

Res Autism Spectr Disord. 2017 Jun;38:6-18

Authors: Caçola P, Miller HL, Williamson PO

Abstract
BACKGROUND: Autism Spectrum Disorder (ASD) and Developmental Coordination Disorder (DCD) are developmental disorders that, since the DSM-5, can be diagnosed as co-occurring conditions. While some recent studies suggest that ASD and DCD have similar traits, others show clear behavioral distinctions between the two conditions. By gathering all studies that included (1) an ASD group and a DCD group, (2) an ASD+DCD group and a DCD group, or (3) ASD, ASD+DCD, and DCD groups, we aimed to identify similarities and differences in behaviors between the two disorders.
METHOD: We used a systematic search of PubMed (1946 -), Scopus (1970 -), PsycINFO (via EBSCO, 1600 -), CINAHL (via EBSCO, 1937 -), SportDiscus (via EBSCO, 1985 -), and WorldCat (via FirstSearch) in addition to reference list and author name searching PubMed, Scopus, PsycINFO, CINAHL, SportDiscus, and WorldCat to identify original studies that met the following criteria: (1) an ASD group and a DCD group, (2) an ASD+DCD group and a DCD group, or (3) ASD, ASD+DCD, and DCD groups.
RESULTS: From the 1,598 articles screened, 11 were included in the qualitative analysis. The articles included reported more differences than similarities in individuals with ASD and DCD, with clear distinctions for working memory ability, gestural performance, grip selection, and cortical thickness. Only two studies reported similarities in face processing abilities and perceived competence, and the interventional studies showed group similarities in behavior improvement, such as intelligence and attention.
CONCLUSIONS: Based on the articles reviewed, we conclude that while DCD and ASD share some behavioral symptoms, the symptom profiles of each disorder are unique and separable. We recommend that the evaluation of potential DCD in individuals with ASD be performed systematically and thoroughly, so as to distinguish this co-occurring condition from sensorimotor symptoms associated with ASD.

PMID: 29057009 [PubMed]

Paternity calculations in a di-spermy case.

Tue, 10/24/2017 - 07:32
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Paternity calculations in a di-spermy case.

Int J Legal Med. 2017 Mar;131(2):339-343

Authors: Budowle B, Capt C, Chakraborty R, Ge J

Abstract
In a criminal paternity case, which involved analysis of the product of conception, a rare circumstance was observed. The product of conception was triploidy, apparently due to an egg fertilized by two sperm. Since there is little guidance on how to calculate the probability of the DNA evidence given some basic hypotheses, the formulae were derived and are presented herein. These approaches could provide guidance for similar situations if they arise.

PMID: 27757578 [PubMed - indexed for MEDLINE]

Internal validation of the RapidHIT(®) ID system.

Mon, 10/23/2017 - 10:42

Internal validation of the RapidHIT(®) ID system.

Forensic Sci Int Genet. 2017 Sep 23;31:180-188

Authors: Wiley R, Sage K, LaRue B, Budowle B

Abstract
Traditionally, forensic DNA analysis has required highly skilled forensic geneticists in a dedicated laboratory to generate short tandem repeat (STR) profiles. STR profiles are routinely used either to associate or exclude potential donors of forensic biological evidence. The typing of forensic reference samples has become more demanding, especially with the requirement in some jurisdictions to DNA profile arrestees. The Rapid DNA (RDNA) platform, the RapidHIT(®) ID (IntegenX(®), Pleasanton, CA), is a fully automated system capable of processing reference samples in approximately 90min with minimal human intervention. Thus, the RapidHIT ID instrument can be deployed to non-laboratory environments (e.g., booking stations) and run by trained atypical personnel such as law enforcement. In order to implement the RapidHIT ID platform, validation studies are needed to define the performance and limitations of the system. Internal validation studies were undertaken with four early-production RapidHIT ID units. Reliable and concordant STR profiles were obtained from reference buccal swabs. Throughout the study, no contamination was observed. The overall first-pass success rate with an "expert-like system" was 72%, which is comparable to another current RDNA platform commercially available. The system's second-pass success rate (involving manual interpretation on first-pass inconclusive results) increased to 90%. Inhibitors (i.e., coffee, smoking tobacco, and chewing tobacco) did not appear to affect typing by the instrument system; however, substrate (i.e., swab type) did impact typing success. Additionally, one desirable feature not available with other Rapid systems is that in the event of a system failed run, a swab can be recovered and subsequently re-analyzed in a new sample cartridge. Therefore, rarely should additional sampling or swab consumption be necessary. The RapidHIT ID system is a robust and reliable tool capable of generating complete STR profiles within the forensic DNA typing laboratory or with proper training in decentralized environments by non-laboratory personnel.

PMID: 29055861 [PubMed - as supplied by publisher]

Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth in vivo.

Sat, 10/21/2017 - 07:33
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Histone deacetylase inhibitor thailandepsin-A activates Notch signaling and suppresses neuroendocrine cancer cell growth in vivo.

Oncotarget. 2017 Sep 19;8(41):70828-70840

Authors: Jang S, Janssen A, Aburjania Z, Robers MB, Harrison A, Dammalapati A, Cheng YQ, Chen H, Jaskula-Sztul R

Abstract
Novel therapies for neuroendocrine (NE) cancers are desperately needed as they frequently present as metastatic disease and cause debilitating symptoms by secreting excessive hormones. Induction of Notch isoforms has a tumor suppressive effect in NE cancer cell lines, and we have observed that histone deacetylase inhibitors (HDACi) potently activate Notch. In this study, we describe the potential for Burkholderia thailandensis-derived class I HDACi thailandepsin A (TDP-A) as a Notch activator and therapeutic agent against NE cancer. IC50 for TDP-A was determined to be 4-6 nM in NE cancer cell lines (BON, MZ-CRC-1, and TT) without cytotoxicity to lung fibroblasts. The binding characteristics of TDP-A to its target HDAC1 was examined using bioluminescence resonance energy transfer (BRET). Western blot and flow cytometry analysis showed that TDP-A induces cell cycle arrest and apoptosis in a dose-dependent manner. TDP-A dose-dependently activated the Notch pathway as measured by increasing functional CBF1-luciferase reporter signal and mRNA and protein expressions of Notch isoforms, which were attenuated by pretreatment with γ-secretase inhibitor DAPT. Furthermore, TDP-A lead to changes in expression level of downstream targets of Notch pathway and reduced expression of NE cancer markers. An in vivo study demonstrated that TDP-A suppressed NE cancer progression. These results show that TDP-A, as a Notch activator, is a promising agent against NE cancers.

PMID: 29050323 [PubMed]

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