Recent Research Articles from UNTHSC

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M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

Wed, 03/16/2016 - 06:31
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M2b Monocytes Provoke Bacterial Pneumonia and Gut Bacteria-Associated Sepsis in Alcoholics.

J Immunol. 2015 Dec 1;195(11):5169-77

Authors: Tsuchimoto Y, Asai A, Tsuda Y, Ito I, Nishiguchi T, Garcia MC, Suzuki S, Kobayashi M, Higuchi K, Suzuki F

Abstract
Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγ(null) mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12(+)IL-10(-)CD163(-)CD14(+) cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1(+)CD163(+)CD14(+) cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12(-)IL-10(-)CCL1(-)CD163(-)CD14(+) cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.

PMID: 26525287 [PubMed - indexed for MEDLINE]

Continuous non-cell autonomous reprogramming to generate retinal ganglion cells for glaucomatous neuropathy.

Wed, 03/16/2016 - 06:31
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Continuous non-cell autonomous reprogramming to generate retinal ganglion cells for glaucomatous neuropathy.

Stem Cells. 2015 Jun;33(6):1743-58

Authors: Parameswaran S, Dravid SM, Teotia P, Krishnamoorthy RR, Qiu F, Toris C, Morrison J, Ahmad I

Abstract
Glaucoma, where the retinal ganglion cells (RGCs) carrying the visual signals from the retina to the visual centers in the brain are progressively lost, is the most common cause of irreversible blindness. The management approaches, whether surgical, pharmacological, or neuroprotective do not reverse the degenerative changes. The stem cell approach to replace dead RGCs is a viable option but currently faces several barriers, such as the lack of a renewable, safe, and ethical source of RGCs that are functional and could establish contacts with bona fide targets. To address these barriers, we have derived RGCs from the easily accessible adult limbal cells, reprogrammed to pluripotency by a non-nucleic acid approach, thus circumventing the risk of insertional mutagenesis. The generation of RGCs from the induced pluripotent stem (iPS) cells, also accomplished non-cell autonomously, recapitulated the developmental mechanism, ensuring the predictability and stability of the acquired phenotype, comparable to that of native RGCs at biochemical, molecular, and functional levels. More importantly, the induced RGCs expressed axonal guidance molecules and demonstrated the potential to establish contacts with specific targets. Furthermore, when transplanted in the rat model of ocular hypertension, these cells incorporated into the host RGC layer and expressed RGC-specific markers. Transplantation of these cells in immune-deficient mice did not produce tumors. Together, our results posit retinal progenitors generated from non-nucleic acid-derived iPS cells as a safe and robust source of RGCs for replacing dead RGCs in glaucoma.

PMID: 25753398 [PubMed - indexed for MEDLINE]

D5S2500 is an ambiguously characterized STR: Identification and description of forensic microsatellites in the genomics age.

Tue, 03/15/2016 - 06:35

D5S2500 is an ambiguously characterized STR: Identification and description of forensic microsatellites in the genomics age.

Forensic Sci Int Genet. 2016 Mar 9;23:19-24

Authors: Phillips C, Parson W, Amigo J, King JL, Coble MD, Steffen CR, Vallone PM, Gettings KB, Butler JM, Budowle B

Abstract
In the process of establishing short tandem repeat (STR) sequence variant nomenclature guidelines in anticipation of expanded forensic multiplexes for massively parallel sequencing (MPS), it was discovered that the STR D5S2500 has multiple positions and genomic characteristics reported. This ambiguity is because the marker named D5S2500 consists of two different microsatellites forming separate components in the capillary electrophoresis multiplexes of Qiagen's HDplex (Hilden, Germany) and AGCU ScienTech's non-CODIS STR 21plex (Wuxi, Jiangsu, China). This study outlines the genomic details used to identify each microsatellite and reveals the D5S2500 marker in HDplex has the correctly assigned STR name, while the D5S2500 marker in the AGCU 21plex, closely positioned a further 1643 nucleotides in the human reference sequence, is an unnamed microsatellite. The fact that the D5S2500 marker has existed as two distinct STR loci undetected for almost ten years, even with reported discordant genotypes for the standard control DNA, underlines the need for careful scrutiny of the genomic properties of forensic STRs, as they become adapted for sequence analysis with MPS systems. We make the recommendation that precise chromosome location data must be reported for any forensic marker under development but not in common use, so that the genomic characteristics of the locus are validated to the same level of accuracy as its allelic variation and forensic performance. To clearly differentiate each microsatellite, we propose the name D5S2800 be used to identify the Chromosome-5 STR in the AGCU 21plex.

PMID: 26974236 [PubMed - as supplied by publisher]

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]

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