Recent Research Articles from UNTHSC

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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Enhancing nurses' knowledge regarding the complex care of hospitalized patients on insulin.

Tue, 03/15/2016 - 06:35
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Enhancing nurses' knowledge regarding the complex care of hospitalized patients on insulin.

J Nurses Prof Dev. 2014 Jul-Aug;30(4):174-80

Authors: Wakefield PL, Wilson MA

Abstract
A randomized controlled study assessed a self-paced, online educational course addressing the complex nursing care of hospitalized patients on basal-bolus insulin. Interactive quizzes and scenarios were used to reinforce learning. Knowledge in the intervention group increased significantly and was retained 3-months postintervention. Nursing professional development educators will find this article useful regarding methods for annual competency evaluation and for increasing staff's knowledge as part of a system approach for safely caring for patients with diabetes.

PMID: 24823888 [PubMed - indexed for MEDLINE]

Restoring lumbar spine stiffness using an interspinous implant in an ovine model of instability.

Fri, 03/11/2016 - 06:34

Restoring lumbar spine stiffness using an interspinous implant in an ovine model of instability.

Clin Biomech (Bristol, Avon). 2016 Feb 24;33:85-91

Authors: Szpalski M, Gunzburg R, Colloca CJ, Kosmopoulos V, Hegazy MA, Freeman BJ, Fabeck L

Abstract
BACKGROUND: The objective of this study was to determine the effect of an interspinous implant on lumbar spine stability and stiffness during dorsoventral loading.
METHODS: Twelve Merino lambs were mechanically tested in vivo. Oscillatory (2Hz) loads were applied to L2 under load control while displacements were monitored. Tri-axial accelerometers further quantified adjacent L3-L4 accelerations. Dorsoventral lumbar spine stiffness and L3 and L4 dorsoventral and axial displacements were determined over six trials of 20cycles of loading. Four conditions were examined: 1) initial intact, 2) following destabilization at L3-L4, 3) following the insertion of an InSwing(®) interspinous device at L3-L4, and 4) with the implant secured with a tension band. Comparisons were performed using a one-way ANOVA with repeated measures and post-hoc Bonferroni correction.
FINDINGS: Compared to the intact condition, destabilization significantly decreased lumbar stiffness by 4.5% (P=.001) which was only recovered by the interspinous device with tension band. The interspinous device caused a significant 9.75% (P=.001) increase in dorsoventral stiffness from destabilization that increased 14% with the tension band added (P=.001). The tension band was responsible for decreased displacements from the intact (P=.038), instability (P=.001), and interspinous device (P=.005) conditions. Dorsoventral L3-L4 motion significantly improved with the interspinous device (P=.01) and the addition of the tension band (P=.001). No significant differences in L3-L4 intersegmental stability were noted for axial motion in the sagittal plane.
INTERPRETATION: This ovine model provided objective in vivo biomechanical evidence of lumbar instability and its restoration by means of an interspinous implant during dorsoventral spinal loading.

PMID: 26963708 [PubMed - as supplied by publisher]

Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis.

Fri, 03/11/2016 - 06:34
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Over-the-counter fish oil use in a county hospital: Medication use evaluation and efficacy analysis.

J Clin Lipidol. 2015 May-Jun;9(3):326-33

Authors: Tatachar A, Pio M, Yeung D, Moss E, Chow D, Boatright S, Quinones M, Mathew A, Hulstein J, Adams-Huet B, Ahmad Z

Abstract
BACKGROUND: Little is known about the use and effectiveness of over-the-counter (OTC) fish oil supplements for triglyceride (TG) lowering.
OBJECTIVES: To (1) perform a medication-use evaluation (MUE) and (2) assess the efficacy of OTC fish oil.
METHODS: Retrospective, observational cohort study using electronic medical records and the pharmacy database from Parkland Health and Hospital System in Dallas, Texas. Parkland is a tax-supported county institution that provides patients with single-brand OTC fish oil. Two separate analyses were conducted. Six hundred seventeen patients (prescribed fish oil between July 1, 2012, and August 31, 2012) were included in the MUE analysis and 235 patients (109 fish oil, 72 fenofibrate, and 54 gemfibrozil, prescribed between January 1, 2012, and July 31, 2013) were included in the efficacy analysis. The main outcome measure for the MUE was fish oil prescribing habits including dosages and patient adherence, as defined by medication possession ratio. The main outcome measure for the efficacy analysis was change in lipids measured using the last value before fish oil treatment and the first value after fish oil treatment.
RESULTS: MUE: 617 patients received prescriptions for OTC fish oil. Sixty-four percent were prescribed a total daily dose of 2000 mg. Only 25% of patients were adherent. Efficacy analysis: despite being prescribed suboptimal doses, fish oil reduced TGs by 29% (95% confidence interval, 34.3-22.7). Compared with fish oil therapy, fibrate therapy resulted in a greater TG reduction: 48.5% (55.1-41.0) with fenofibrate and 49.8% (57.6-40.5) with gemfibrozil (P < .0001, both medications compared with fish oil).
CONCLUSIONS: Health care providers prescribe suboptimal doses of fish oil, and adherence is poor. Even at low doses (2 g/d), though, fish oil lowers TGs by 29%.

PMID: 26073390 [PubMed - indexed for MEDLINE]

Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland.

Fri, 03/11/2016 - 06:34
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Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland.

Forensic Sci Int. 2014 Nov;244:289-94

Authors: Ylijoki-Sørensen S, Sajantila A, Lalu K, Bøggild H, Boldsen JL, Boel LW

Abstract
Exact cause and manner of death determination improves legislative safety for the individual and for society and guides aspects of national public health. In the International Classification of Diseases, codes R00-R99 are used for "symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified" designated as "ill-defined" or "with unknown etiology". The World Health Organisation recommends avoiding the use of ill-defined and unknown causes of death in the death certificate as this terminology does not give any information concerning the possible conditions that led to the death. Thus, the aim of the study was, firstly, to analyse the frequencies of R00-R99-coded deaths in mortality statistics in Finland and in Denmark and, secondly, to compare these and the methods used to investigate the cause of death. To do so, we extracted a random 90% sample of the Finnish death certificates and 100% of the Danish certificates from the national mortality registries for 2000, 2005 and 2010. Subsequently, we analysed the frequencies of forensic and medical autopsies and external clinical examinations of the bodies in R00-R99-coded deaths. The use of R00-R99 codes was significantly higher in Denmark than in Finland; OR 18.6 (95% CI 15.3-22.4; p<0.001) for 2000, OR 9.5 (95% CI 8.0-11.3; p<0.001) for 2005 and OR 13.2 (95% CI 11.1-15.7; p<0.001) for 2010. More than 80% of Danish deaths with R00-R99 codes were over 70 years of age at the time of death. Forensic autopsy was performed in 88.3% of Finnish R00-R99-coded deaths, whereas only 3.5% of Danish R00-R99-coded deaths were investigated with forensic or medical autopsy. The codes that were most used in both countries were R96-R99, meaning "unknown cause of death". In Finland, all of these deaths were investigated with a forensic autopsy. Our study suggests that if all deaths in all age groups with unclear cause of death were systematically investigated with a forensic autopsy, only 2-3/1000 deaths per year would be coded as an ill-defined and unknown cause of death in national mortality statistics. At the same time the risk to overlook unnatural deaths is decreased to a minimum. To achieve this in Denmark requires that the existing legislation on cause of death investigation would need to be changed to ensure that all deaths with unknown cause of death are investigated with a forensic autopsy.

PMID: 25300069 [PubMed - indexed for MEDLINE]

Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Fri, 03/11/2016 - 06:34
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Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Forensic Sci Int. 2014 Nov;244:158-65

Authors: Ylijoki-Sørensen S, Boldsen JL, Boel LW, Bøggild H, Lalu K, Sajantila A

Abstract
National differences in the legislation on cause and manner of death investigation are reflected in a high autopsy rate in suicides in Finland and a low corresponding rate in Denmark. The consequences for mortality statistics of these different investigation practices on deaths classified as suicides in Denmark and Finland, respectively, are not known in detail. The aim of this article was to analyse autopsy rates in deaths classified as suicides, and to identify any differences in investigation practices in deaths with a comparable cause of death, but classified as unnatural deaths other than suicide. Data from the mortality registries were summarised for the years 2000, 2005 and 2010. Autopsy rates (total, forensic and medical) were analysed with regard to deaths classified as suicide, and they were compared for three age groups (1-50 years, 51-70 years and ≥71 years) and for causes of death. Deaths classified as suicide were compared with other unnatural classifications, and comparable causes of death were coded into six subgroups: poisonings, suffocations/strangulations, firearm discharges, drowning/submersions, explosions/flames and other/unspecified causes. The total autopsy rate for suicides was 99.8% in Finland and 13.2% in Denmark. Almost all of these autopsies were conducted as forensic autopsies. In the age group ≥71 years, Danish suicides outnumbered Finnish suicides (410 versus 283). The total autopsy rate was lower in the more senior age group in Denmark (19.5%, 9.9%, 5.6%), whereas it was consistently high in Finland (99.8%, 99.9%, 99.6%). Among Danish deaths due to poisonings, the autopsy rate was 89.5% when these were classified as accidents, but only 20.7% for cases classified as suicides. The number of deaths in the two Danish subgroups was comparable (550 versus 553). In Denmark, the decision regarding the need, if any, for a forensic autopsy is made during the external forensic examination of the body. Our study showed that the limited use of forensic autopsy to confirm the cause of death in deaths classified as suicides raises doubts about the accuracy of the Danish suicide mortality statistics. Our finding is emphasised by those cases in which the cause of death was registered as intentional self-poisoning. The high number of suicides among the elderly in Denmark is striking and begs further investigation and research. Overall, our data from Finland and Denmark reveal striking differences between the two countries and warrant further comparative studies on the subject in other countries.

PMID: 25244292 [PubMed - indexed for MEDLINE]

Mycobacterium Tuberculosis Infection, Immigration Status, and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON(®)-TB Gold In-Tube Test Among Immigrants to the U.S.

Thu, 03/10/2016 - 06:31

Mycobacterium Tuberculosis Infection, Immigration Status, and Diagnostic Discordance: A Comparison of Tuberculin Skin Test and QuantiFERON(®)-TB Gold In-Tube Test Among Immigrants to the U.S.

Public Health Rep. 2016 Mar-Apr;131(2):303-10

Authors: Wilson FA, Miller TL, Stimpson JP

Abstract
OBJECTIVE: We used a recent source of nationally representative population data on tuberculosis (TB) infection to characterize concordance between the tuberculin skin test (TST) and the QuantiFERON(®)-TB Gold In-Tube (QFT-GIT) blood test for immigrants in the United States.
METHODS: We used TB screening data from the 2011-2012 National Health and Nutrition Examination Survey to examine concordance between the TST and QFT-GIT-an interferon-gamma release assay (IGRA) blood test-for 7,097 U.S. natives, naturalized citizens, and noncitizens.
RESULTS: Consistent with prior findings, one in five immigrants in the survey was identified with latent TB infection (LTBI), a rate 14 times higher than for U.S. natives. We also found higher rates of discordant TST/IGRA results among immigrants than among U.S. natives. Unadjusted discordance between TST and IGRA was 3% among U.S. natives (weighted N=5,684,274 of 191,179,213) but ranged up to 19% for noncitizens (weighted N=3,722,960 of 19,377,147). Adjusting for age, sex, and race/ethnicity, noncitizens had more than nine times the odds of having a positive TST result but negative QFT-GIT result compared with U.S. natives.
CONCLUSIONS: Our findings suggest that whether and how either of these tests should be deployed is highly context sensitive. Significant discordance in test results when used among immigrants raises the possibility of missed opportunities for harm reduction in this already at-risk population. However, we found little distinction between the tests in terms of diagnostic outcome when used in a U.S. native population, suggesting little benefit to the adoption and use of the QFT-GIT test in place of TST on the basis of test performance alone for this population.

PMID: 26957665 [PubMed - in process]

Comparison of the Effectiveness of Interactive Didactic Lecture Versus Online Simulation-Based CME Programs Directed at Improving the Diagnostic Capabilities of Primary Care Practitioners.

Thu, 03/10/2016 - 06:31
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Comparison of the Effectiveness of Interactive Didactic Lecture Versus Online Simulation-Based CME Programs Directed at Improving the Diagnostic Capabilities of Primary Care Practitioners.

J Contin Educ Health Prof. 2016;36(1):32-7

Authors: McFadden P, Crim A

Abstract
INTRODUCTION: Diagnostic errors in primary care contribute to increased morbidity and mortality, and billions in costs each year. Improvements in the way practicing physicians are taught so as to optimally perform differential diagnosis can increase patient safety and lower the costs of care. This study represents a comparison of the effectiveness of two approaches to CME training directed at improving the primary care practitioner's diagnostic capabilities against seven common and important causes of joint pain.
METHODS: Using a convenience sampling methodology, one group of primary care practitioners was trained by a traditional live, expert-led, multimedia-based training activity supplemented with interactive practice opportunities and feedback (control group). The second group was trained online with a multimedia-based training activity supplemented with interactive practice opportunities and feedback delivered by an artificial intelligence-driven simulation/tutor (treatment group).
RESULTS: Before their respective instructional intervention, there were no significant differences in the diagnostic performance of the two groups against a battery of case vignettes presenting with joint pain. Using the same battery of case vignettes to assess postintervention diagnostic performance, there was a slight but not statistically significant improvement in the control group's diagnostic accuracy (P = .13). The treatment group, however, demonstrated a significant improvement in accuracy (P < .02; Cohen d, effect size = 0.79).
DISCUSSION: These data indicate that within the context of a CME activity, a significant improvement in diagnostic accuracy can be achieved by the use of a web-delivered, multimedia-based instructional activity supplemented by practice opportunities and feedback delivered by an artificial intelligence-driven simulation/tutor.

PMID: 26954243 [PubMed - in process]

The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Thu, 03/10/2016 - 06:31
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The Y-chromosome tree bursts into leaf: 13,000 high-confidence SNPs covering the majority of known clades.

Mol Biol Evol. 2015 Mar;32(3):661-73

Authors: Hallast P, Batini C, Zadik D, Maisano Delser P, Wetton JH, Arroyo-Pardo E, Cavalleri GL, de Knijff P, Destro Bisol G, Dupuy BM, Eriksen HA, Jorde LB, King TE, Larmuseau MH, López de Munain A, López-Parra AM, Loutradis A, Milasin J, Novelletto A, Pamjav H, Sajantila A, Schempp W, Sears M, Tolun A, Tyler-Smith C, Van Geystelen A, Watkins S, Winney B, Jobling MA

Abstract
Many studies of human populations have used the male-specific region of the Y chromosome (MSY) as a marker, but MSY sequence variants have traditionally been subject to ascertainment bias. Also, dating of haplogroups has relied on Y-specific short tandem repeats (STRs), involving problems of mutation rate choice, and possible long-term mutation saturation. Next-generation sequencing can ascertain single nucleotide polymorphisms (SNPs) in an unbiased way, leading to phylogenies in which branch-lengths are proportional to time, and allowing the times-to-most-recent-common-ancestor (TMRCAs) of nodes to be estimated directly. Here we describe the sequencing of 3.7 Mb of MSY in each of 448 human males at a mean coverage of 51×, yielding 13,261 high-confidence SNPs, 65.9% of which are previously unreported. The resulting phylogeny covers the majority of the known clades, provides date estimates of nodes, and constitutes a robust evolutionary framework for analyzing the history of other classes of mutation. Different clades within the tree show subtle but significant differences in branch lengths to the root. We also apply a set of 23 Y-STRs to the same samples, allowing SNP- and STR-based diversity and TMRCA estimates to be systematically compared. Ongoing purifying selection is suggested by our analysis of the phylogenetic distribution of nonsynonymous variants in 15 MSY single-copy genes.

PMID: 25468874 [PubMed - indexed for MEDLINE]

Preterm birth and air pollution: Critical windows of exposure for women with asthma.

Sun, 03/06/2016 - 06:40

Preterm birth and air pollution: Critical windows of exposure for women with asthma.

J Allergy Clin Immunol. 2016 Feb 23;

Authors: Mendola P, Wallace M, Hwang BS, Liu D, Robledo C, Mӓnnistӧ T, Sundaram R, Sherman S, Ying Q, Grantz KL

Abstract
BACKGROUND: Ambient air pollutants may increase preterm birth (PTB) risk, but critical exposure windows are uncertain. The interaction of asthma and pollutant exposure is rarely studied.
OBJECTIVE: We sought to assess the interaction of maternal asthma and air pollutant exposures in relation to PTB risk.
METHODS: Electronic medical records for 223,502 US deliveries were linked with modified Community Multiscale Air Quality model outputs. Logistic regression with generalized estimating equations estimated the odds ratio and 95% CIs for PTB on the basis of the interaction of maternal asthma and particulate matter with aerodynamic diameter of less than 2.5 microns and particulate matter with aerodynamic diameter of less than 10 microns, ozone (O3), nitrogen oxides (NOx), sulfur dioxide (SO2), and carbon monoxide (CO) per interquartile range. For each gestational week 23 to 36, exposures among women who delivered were compared with those remaining pregnant. Three-month preconception, whole pregnancy, weeks 1 to 28, and the last 6 weeks of gestation averages were also evaluated.
RESULTS: On assessing PTB by gestational week, we found that significant asthma interactions were sporadic before 30 weeks but more common during weeks 34 to 36, with higher risk among mothers with asthma for NOx, CO, and SO2 exposure and an inverse association with O3 in week 34. Odds of PTB were significantly higher among women with asthma for CO and NOx exposure preconception and early in pregnancy. In the last 6 weeks of pregnancy, PTB risk associated with particulate matter with aerodynamic diameter of less than 10 microns was higher among women with asthma.
CONCLUSIONS: Mothers with asthma may experience a higher risk for PTB after exposure to traffic-related pollutants such as CO and NOx, particularly for exposures 3-months preconception and in the early weeks of pregnancy.

PMID: 26944405 [PubMed - as supplied by publisher]

DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Sat, 03/05/2016 - 06:42
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DNA quality and quantity from up to 16 years old post-mortem blood stored on FTA cards.

Forensic Sci Int. 2016 Feb 23;261:148-153

Authors: Rahikainen AL, Palo JU, de Leeuw W, Budowle B, Sajantila A

Abstract
Blood samples preserved on FTA cards offer unique opportunities for genetic research. DNA recovered from these cards should be stable for long periods of time. However, it is not well established as how well the DNA stored on FTA card for substantial time periods meets the demands of forensic or genomic DNA analyses and especially so for from post-mortem (PM) samples in which the quality can vary upon initial collection. The aim of this study was to evaluate the time-dependent degradation on DNA quality and quantity extracted from up to 16 years old post-mortem bloodstained FTA cards. Four random FTA samples from eight time points spanning 1998 to 2013 (n=32) were collected and extracted in triplicate. The quantity and quality of the extracted DNA samples were determined with Quantifiler(®) Human Plus (HP) Quantification kit. Internal sample and sample-to-sample variation were evaluated by comparing recovered DNA yields. The DNA from the triplicate samplings were subsequently combined and normalized for further analysis. The practical effect of degradation on DNA quality was evaluated from normalized samples both with forensic and pharmacogenetic target markers. Our results suggest that (1) a PM change, e.g. blood clotting prior to sampling, affects the recovered DNA yield, creating both internal and sample-to-sample variation; (2) a negative correlation between the FTA card storage time and DNA quantity (r=-0.836 at the 0.01 level) was observed; (3) a positive correlation (r=0.738 at the level 0.01) was found between FTA card storage time and degradation levels. However, no inhibition was observed with the method used. The effect of degradation was manifested clearly with functional applications. Although complete STR-profiles were obtained for all samples, there was evidence of degradation manifested as decreased peak heights in the larger-sized amplicons. Lower amplification success was notable with the large 5.1kb CYP2D6 gene fragment which strongly supports degradation of the stored samples. According to our results, DNA stored on FTA cards is rather stable over a long time period. DNA extracted from this storage medium can be used as human identification purposes as the method used is sufficiently sensitive and amplicon sizes tend to be <400bp. However, DNA integrity was affected during storage. This effect should be taken into account depending on the intended application especially if high quality DNA and long PCR amplicons are required.

PMID: 26937857 [PubMed - as supplied by publisher]

Canonical transient receptor potential 6 (TRPC6) channel, a new target of reactive oxygen species in renal physiology and pathology.

Sat, 03/05/2016 - 06:42
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Canonical transient receptor potential 6 (TRPC6) channel, a new target of reactive oxygen species in renal physiology and pathology.

Antioxid Redox Signal. 2016 Mar 3;

Authors: Ma R, Chaudhari S, Li W

Abstract
SIGNIFICANCE: Regulation of Ca2+ signaling cascade by reactive oxygen species (ROS) is becoming increasingly evident and this regulation represents a key mechanism for control of many fundamental cellular functions. Canonical transient receptor potential (TRPC) 6, a member of Ca2+ conductive channel in TRPC family, is widely expressed in kidney cells, including glomerular mesangial cells, podocytes, tubular epithelial cells and vascular myocytes in renal microvasculatures. Both overproduction of ROS and dysfunction of TRPC6 channel are involved in renal injury in animal models and human subjects. Although regulation of TRPC channel function by ROS has been well described in other tissues and cell types, such as vascular smooth muscle, this important cell regulatory mechanism has not been fully reviewed in kidney cells. Recent Advances: Accumulating evidence has shown that TRPC6 is a redox-sensitive channel, and modulation of TRPC6 Ca2+ signaling by altering TRPC6 protein expression or TRPC6 channel activity in kidney cells is a downstream mechanism by which ROS induce renal damage.
CRITICAL ISSUES: This review highlights how recent studies analyzing function and expression of TRPC6 channels in kidney and their response to ROS improve our mechanistic understanding of oxidative stress-related kidney diseases.
FUTURE DIRECTIONS: Although it is evident that ROS regulate TRPC6-mediated Ca2+ signaling in several types of kidney cells, further study is needed to identify the underlying molecular mechanism. We hope that the newly-identified ROS/TRPC6 pathway will pave the way to new, promising therapeutic strategies to target kidney diseases such as diabetic nephropathy.

PMID: 26937558 [PubMed - as supplied by publisher]

Evaluating the Disposition of a Mixed Aldehyde Oxidase/Cytochrome P450 Substrate in Rats with Attenuated P450 Activity.

Sat, 03/05/2016 - 06:42
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Evaluating the Disposition of a Mixed Aldehyde Oxidase/Cytochrome P450 Substrate in Rats with Attenuated P450 Activity.

Drug Metab Dispos. 2016 Mar 2;

Authors: Crouch RD, Morrison RD, Byers FW, Lindsley CW, Emmitte KA, Daniels JS

Abstract
Marketed drugs cleared by aldehyde oxidase (AO) are few, with no known clinically relevant pharmacokinetic drug interactions associated with AO inhibition, while cytochrome P450 inhibition or induction mediates a number of clinical drug interactions. Little attention has been given to consequences of co-administering a P450 inhibitor with a compound metabolized by both AO and P450. Upon discovering that VU0409106 ( 1: ) was metabolized by AO (to M1) and P450 enzymes (to M4-M6), we sought to evaluate the in vivo disposition of 1: and its metabolites in rats with attenuated P450 activity. Male rats were orally pretreated with the pan-P450 inactivator, 1-aminobenzotriazole (ABT), prior to an intraperitoneal dose of 1: . Interestingly, the plasma(AUC)of M1 was increased 15-fold in ABT-treated rats, indicating a metabolic shunt towards AO resulted from the drug interaction condition. The AUC of 1: also increased 7.8-fold. Accordingly, plasma clearance of 1: decreased from 53.5 to 15.3 mL/min/kg in ABT-pretreated rats receiving an intravenous dose of 1: . Consistent with these data, M1 formation in hepatic S9 increased with NADPH-exclusion to eliminate P450 activity (50% over reactions containing NADPH). These studies reflect possible consequences of a drug interaction between P450 inhibitors and compounds cleared by both AO and P450 enzymes. Notably, increased exposure to an AO metabolite may hold clinical relevance for active metabolites or those mediating toxicity at elevated concentrations. The recent rise in clinical drug candidates metabolized by AO underscores the importance of these findings and the need for clinical studies to fully understand these risks.

PMID: 26936972 [PubMed - as supplied by publisher]

Racial disparities in reaching the renal transplant waitlist: is geography as important as race?

Sat, 03/05/2016 - 06:42
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Racial disparities in reaching the renal transplant waitlist: is geography as important as race?

Clin Transplant. 2015 Jun;29(6):531-8

Authors: Saunders MR, Lee H, Alexander GC, Tak HJ, Thistlethwaite JR, Ross LF

Abstract
BACKGROUND: In the United States, African Americans and whites differ in access to the deceased donor renal transplant waitlist. The extent to which racial disparities in waitlisting differ between United Network for Organ Sharing (UNOS) regions is understudied.
METHODS: The US Renal Data System (USRDS) was linked with US census data to examine time from dialysis initiation to waitlisting for whites (n = 188,410) and African Americans (n = 144,335) using Cox proportional hazards across 11 UNOS regions, adjusting for potentially confounding individual, neighborhood, and state characteristics.
RESULTS: Likelihood of waitlisting varies significantly by UNOS region, overall and by race. Additionally, African Americans face significantly lower likelihood of waitlisting compared to whites in all but two regions (1 and 6). Overall, 39% of African Americans with ESRD reside in Regions 3 and 4--regions with a large racial disparity and where African Americans comprise a large proportion of the ESRD population. In these regions, the African American-white disparity is an important contributor to their overall regional disparity.
CONCLUSIONS: Race remains an important factor in time to transplant waitlist in the United States. Race contributes to overall regional disparities; however, the importance of race varies by UNOS region.

PMID: 25818547 [PubMed - indexed for MEDLINE]

A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

Wed, 03/02/2016 - 06:34
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A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

Bioorg Med Chem Lett. 2015;25(10):2065-7

Authors: Mukerjee A, Iyidogan P, Castellanos-Gonzalez A, Cisneros JA, Czyzyk D, Ranjan AP, Jorgensen WL, White AC, Vishwanatha JK, Anderson KS

Abstract
Cryptosporidiosis, a gastrointestinal disease caused by protozoans of the genus Cryptosporidium, is a common cause of diarrheal diseases and often fatal in immunocompromised individuals. Bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis (C. hominis) has been a molecular target for inhibitor design. C. hominis TS-DHFR inhibitors with nM potency at a biochemical level have been developed however drug delivery to achieve comparable antiparasitic activity in Cryptosporidium infected cell culture has been a major hurdle for designing effective therapies. Previous mechanistic and structural studies have identified compound 906 as a nM C. hominis TS-DHFR inhibitor in vitro, having μM antiparasitic activity in cell culture. In this work, proof of concept studies are presented using a nanotherapy approach to improve drug delivery and the antiparasitic activity of 906 in cell culture. We utilized PLGA nanoparticles that were loaded with 906 (NP-906) and conjugated with antibodies to the Cryptosporidium specific protein, CP2, on the nanoparticle surface in order to specifically target the parasite. Our results indicate that CP2 labeled NP-906 (CP2-NP-906) reduces the level of parasites by 200-fold in cell culture, while NP-906 resulted in 4.4-fold decrease. Moreover, the anticryptosporidial potency of 906 improved 15 to 78-fold confirming the utility of the antibody conjugated nanoparticles as an effective drug delivery strategy.

PMID: 25900220 [PubMed - indexed for MEDLINE]

Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Wed, 03/02/2016 - 06:34
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Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Psychopharmacology (Berl). 2015 Apr;232(7):1197-205

Authors: Gatch MB, Rutledge MA, Forster MJ

Abstract
RATIONALE: Synthetic cathinones continue to be sold as "legal" alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds.
OBJECTIVES: The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine.
METHODS: Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline.
RESULTS: Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 h. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 h. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine.
CONCLUSIONS: All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine, or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects.

PMID: 25281225 [PubMed - indexed for MEDLINE]

Current perspectives on the link between neuroinflammation and neurogenesis.

Wed, 03/02/2016 - 06:34
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Current perspectives on the link between neuroinflammation and neurogenesis.

Metab Brain Dis. 2015 Apr;30(2):355-65

Authors: Wang B, Jin K

Abstract
The link between neuroinflammation and neurogenesis is an area of intensive research in contemporary neuroscience. The burgeoning amount of evidence accumulated over the past decade has been incredible, and now there remains the figuring out of minutia to give us a more complete picture of what individual, synergistic, and antagonistic events are occurring between neurogenesis and neuroinflammation. An intricate study of the inflammatory microenvironment influenced by the presence of the various inflammatory components like cytokines, chemokines, and immune cells is essential for: 1) understanding how neurogenesis can be affected in such a specialized niche and 2) applying the knowledge gained for the treatment of cognitive and/or motor deficits arising from inflammation-associated diseases like stroke, traumatic brain injury, Alzheimer's disease, and Parkinson's disease. This review is written to provide the reader with up-to-date information explaining how these inflammatory components are effecting changes on neurogenesis.

PMID: 24623361 [PubMed - indexed for MEDLINE]

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon.

Tue, 03/01/2016 - 06:41

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon.

Primates. 2015 Dec;4(2)

Authors: Szabó CÁ, Patel M, Uteshev VV

Abstract
The baboon represents a natural model for genetic generalized epilepsy and sudden unexpected death in epilepsy (SUDEP). In this retrospective study, cerebrospinal fluid (CSF) monoamine metabolites and scalp electroencephalography (EEG) were evaluated in 263 baboons of a pedigreed colony. CSF monoamine abnormalities have been linked to reduced seizure thresholds, behavioral abnormalities and SUDEP in various animal models of epilepsy. The levels of 3-hydroxy-4-methoxyphenylglycol, 5-hydroxyindolacetic acid and homovanillic acid in CSF samples drawn from the cisterna magna were analyzed using high-performance liquid chromatography. These levels were compared between baboons with seizures (SZ), craniofacial trauma (CFT) and asymptomatic, control (CTL) baboons, between baboons with abnormal and normal EEG studies. We hypothesized that the CSF levels of major monoaminergic metabolites (i.e., dopamine, serotonin and norepinephrine) associate with the baboons' electroclinical status and thus can be used as clinical biomarkers applicable to seizures/epilepsy. However, despite apparent differences in metabolite levels between the groups, usually lower in SZ and CFT baboons and in baboons with abnormal EEG studies, we did not find any statistically significant differences using a logistic regression analysis. Significant correlations between the metabolite levels, especially between 5-HIAA and HVA, were preserved in all electroclinical groups. While we were not able to demonstrate significant differences in monoamine metabolites in relation to seizures or EEG markers of epilepsy, we cannot exclude the monoaminergic system as a potential source of pathogenesis in epilepsy and SUDEP. A prospective study evaluating serial CSF monoamine levels in baboons with recently witnessed seizures, and evaluation of abnormal expression and function of monoaminergic receptors and transporters within epilepsy-related brain regions, may impact the electroclinical status.

PMID: 26924854 [PubMed - as supplied by publisher]

Level of Immersion in Virtual Environments Impacts the Ability to Assess and Teach Social Skills in Autism Spectrum Disorder.

Sat, 02/27/2016 - 07:18

Level of Immersion in Virtual Environments Impacts the Ability to Assess and Teach Social Skills in Autism Spectrum Disorder.

Cyberpsychol Behav Soc Netw. 2016 Feb 26;

Authors: Miller HL, Bugnariu NL

Abstract
Virtual environments (VEs) may be useful for delivering social skills interventions to individuals with autism spectrum disorder (ASD). Immersive VEs provide opportunities for individuals with ASD to learn and practice skills in a controlled replicable setting. However, not all VEs are delivered using the same technology, and the level of immersion differs across settings. We group studies into low-, moderate-, and high-immersion categories by examining five aspects of immersion. In doing so, we draw conclusions regarding the influence of this technical manipulation on the efficacy of VEs as a tool for assessing and teaching social skills. We also highlight ways in which future studies can advance our understanding of how manipulating aspects of immersion may impact intervention success.

PMID: 26919157 [PubMed - as supplied by publisher]

Empirical testing of a 23-AIMs panel of SNPs for ancestry evaluations in four major US populations.

Fri, 02/26/2016 - 07:00

Empirical testing of a 23-AIMs panel of SNPs for ancestry evaluations in four major US populations.

Int J Legal Med. 2016 Feb 25;

Authors: Zeng X, Warshauer DH, King JL, Churchill JD, Chakraborty R, Budowle B

Abstract
Ancestry informative markers (AIMs) can be used to determine population affiliation of the donors of forensic samples. In order to examine ancestry evaluations of the four major populations in the USA, 23 highly informative AIMs were identified from the International HapMap project. However, the efficacy of these 23 AIMs could not be fully evaluated in silico. In this study, these 23 SNPs were multiplexed to test their actual performance in ancestry evaluations. Genotype data were obtained from 189 individuals collected from four American populations. One SNP (rs12149261) on chromosome 16 was removed from this panel because it was duplicated on chromosome 1. The resultant 22-AIMs panel was able to empirically resolve the four major populations as in the in silico study. Eight individuals were assigned to a different group than indicated on their samples. The assignments of the 22 AIMs for these samples were consistent with AIMs results from the ForenSeq(TM) panel. No departures from Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) were detected for all 22 SNPs in four US populations (after removing the eight problematic samples). The principal component analysis (PCA) results indicated that 181 individuals from these populations were assigned to the expected groups. These 22 SNPs can contribute to the candidate AIMs pool for potential forensic identification purposes in major US populations.

PMID: 26914801 [PubMed - as supplied by publisher]

Expansion of Microbial Forensics.

Fri, 02/26/2016 - 07:00

Expansion of Microbial Forensics.

J Clin Microbiol. 2016 Feb 24;

Authors: Schmedes SE, Sajantila A, Budowle B

Abstract
Microbial forensics has been defined as the discipline of applying scientific methods to analyzing evidence related to bioterrorism, biocrimes, hoaxes, or the accidental release of a biological agent or toxin for attribution purposes. Over the past 15 years technology, particularly massively parallel sequencing, and bioinformatics advances now allow characterization of microorganisms for a variety of human forensic applications, such as human identification, body fluid characterization, post-mortem interval estimation, and biocrimes involving tracking of infectious agents. Thus, microbial forensics should be more broadly described as the discipline of applying scientific methods to analyzing microbial evidence in criminal and civil cases for investigative purposes.

PMID: 26912746 [PubMed - as supplied by publisher]

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