Recent Research Articles from UNTHSC

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Astrocyte Elevated Gene-1 is a Novel Modulator of HIV-1-Associated Neuroinflammation via Regulation of Nuclear Factor-κB Signaling and Excitatory Amino Acid Transporter-2 Repression.

Tue, 05/27/2014 - 4:04am
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Astrocyte Elevated Gene-1 is a Novel Modulator of HIV-1-Associated Neuroinflammation via Regulation of Nuclear Factor-κB Signaling and Excitatory Amino Acid Transporter-2 Repression.

J Biol Chem. 2014 May 22;

Authors: Vartak-Sharma N, Gelman BB, Joshi C, Borgmann K, Ghorpade A

Abstract
Astrocyte Elevated Gene-1 (AEG-1), a novel HIV-1 and TNF-α inducible oncogene, has generated significant interest in the field of cancer research as a therapeutic target for many metastatic aggressive tumors. However, little is known about its role in astrocyte responses during HIV-1 CNS infection, and whether it contributes towards the development of HIV-1-associated neurocognitive disorders (HAND). Therefore, in this study, we investigated changes in AEG-1 CNS expression in HIV-1 infected brain tissues, and elucidated a potential mechanism of AEG-1-mediated regulation of HIV-1-associated neuroinflammation. Immunoblotting and immunohistochemical analyses of HIV-1 seropositive and HIV-1 encephalitic human brain tissues revealed significantly elevated levels of AEG-1 protein. Immunohistochemical analyses of HIV-1 Tat transgenic mouse brain tissues also showed a marked increase in AEG-1 staining. Similar to in vivo observations, cultured astrocytes expressing HIV-1 Tat also revealed AEG-1 and cytokine upregulation. Astrocytes treated with HAND-relevant stimuli, TNF-α, IL-1β and HIV-1, also significantly induced AEG-1 expression and nuclear translocation via activation of the nuclear factor (NF)-κB pathway. Co-immunoprecipitation studies demonstrated IL-1β or TNF-α-induced AEG-1 interaction with NF-κB p65 subunit. AEG-1 knockdown decreased NF-κB activation, nuclear translocation and transcriptional output in TNF-α-treated astrocytes. Moreover, IL-1β treatment of AEG-1 overexpressing astrocytes significantly lowered expression of excitatory amino acid transporter-2 (EAAT2), increased expression of EAAT2 repressor, YY1, and reduced glutamate clearance, a major transducer of excitotoxic neuronal damage. Findings from this study identify a novel transcriptional cofactor function of AEG-1 and further implicate AEG-1 in HIV-1-associated neuroinflammation.

PMID: 24855648 [PubMed - as supplied by publisher]

Monitoring retinal morphological and functional changes in mice following optic nerve crush.

Tue, 05/27/2014 - 4:04am
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Monitoring retinal morphological and functional changes in mice following optic nerve crush.

Invest Ophthalmol Vis Sci. 2014 May 22;

Authors: Liu Y, McDowell CM, Zhang Z, Tebow HE, Wordinger RJ, Clark AF

Abstract
Purpose:To characterize the morphological and functional changes in optic nerve crushed mice and evaluate electroretinogram (ERG) responses as tools to monitor retinal ganglion cell (RGC) dysfunction. Methods:Optic nerve crush (ONC) was performed unilaterally in adult BALB/cJ mice. The neuronal loss in the retinal ganglion cell layer (GCL) and superior colliculus (SC) was determined by Nissl staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) imaging. Retinal function was determined by pattern ERG and full-field flash ERG. Responses of pattern ERG, positive scotopic threshold response (pSTR), scotopic oscillatory potentials (OPs) and photopic negative response (PhNR) were analyzed. Results:ONC induced progressive neuronal loss in both GCL and contralateral SC starting from 7 and 28 days following ONC, respectively. A linear correlation was observed between combined thickness of nerve fiber layer (NFL), GCL and inner plexiform layer (IPL) imaged by SD-OCT and cell numbers in GCL. Only half of the normal BALB/cJ mice exhibited pattern ERG response, which was smaller and later compared to C57BL/6J mice. ONC reduced both pattern ERG and pSTR, but the reduction of pattern ERG was earlier than pSTR, preceding the anatomical cell loss in the GCL. PhNR and scotopic OPs were not affected by ONC. Conclusions:SD-OCT and ERG can be used to noninvasively monitor retinal morphological and functional changes induced by ONC. Pattern ERG and pSTR are both able to detect early RGC dysfunction, but pattern ERG exhibits higher sensitivity. Our results support the use of these tools in studies using the mouse ONC model.

PMID: 24854856 [PubMed - as supplied by publisher]

Nomenclature update and allele repeat structure for the markers DYS518 and DYS449.

Tue, 05/27/2014 - 4:04am
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Nomenclature update and allele repeat structure for the markers DYS518 and DYS449.

Forensic Sci Int Genet. 2014 May 19;

Authors: Mulero J, Ballantyne J, Ballantyne K, Budowle B, Coble M, Gusmão L, Roewer L, Kayser M

PMID: 24854343 [PubMed - as supplied by publisher]

Utility of amplification enhancers in low copy number DNA analysis.

Sat, 05/24/2014 - 4:07am
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Utility of amplification enhancers in low copy number DNA analysis.

Int J Legal Med. 2014 May 22;

Authors: Marshall PL, King JL, Budowle B

Abstract
One parameter that impacts the robustness and reliability of forensic DNA analyses is the amount of template DNA used in the polymerase chain reaction (PCR). With short tandem repeat (STR) typing, low copy number (LCN) DNA samples can present exaggerated stochastic effects during the PCR that result in heterozygote peak height imbalance, allele drop out, and increased stutter. Despite these effects, there has been little progress toward decreasing the formation of stutter products and heterozygote peak imbalance effects during PCR. In an attempt to develop a more robust system that is less refractory to stochastic effects, the PCR additives, betaine, DMSO, PEG, and PCRboost®, were investigated on low-quantity DNA samples. The effects of the additives were assessed by evaluating STR typing results. Of the four additives, the only positive effects were observed with betaine treatment. Betaine, at a final concentration of 1.25 mol/L, was found to improve the robustness of the amplification, specifically by decreasing stutter in a dual locus system. In contrast, the addition of 1.25 mol/L betaine to commercial STR amplification kits did not affect stutter ratios. However, the addition of betaine did lead to increased yield of PCR products in all commercial kits tested. The results support that betaine can improve amplification efficiency of LCN DNA samples.

PMID: 24848516 [PubMed - as supplied by publisher]

Psychological Distress and Emergency Department Utilization in the United States: Evidence from the Medical Expenditure Panel Survey.

Fri, 05/23/2014 - 4:05am
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Psychological Distress and Emergency Department Utilization in the United States: Evidence from the Medical Expenditure Panel Survey.

Acad Emerg Med. 2014 May;21(5):510-519

Authors: Stockbridge EL, Wilson FA, Pagán JA

Abstract
OBJECTIVES: Psychological distress not only has substantial health and social consequences, but is also associated with emergency department (ED) use. Previous studies have typically used cross-sectional data to focus on the relation between serious psychological distress and dichotomized ED utilization measures, without assessing the volume of ED use or examining nonserious levels of psychological distress. The objective of this study was to explore the association between ED utilization volume and the full spectrum of psychological distress.
METHODS: Data from Panel 14 of the Medical Expenditure Panel Survey (MEPS; 2009-2010, n = 9,743) provided a nationally representative sample of U.S. individuals. ED utilization volume and three specifications of the Kessler Psychological Distress Scale (K6) were analyzed: a dichotomous serious/no serious psychological distress measure, a five-category ordinal measure, and a scale measure with a range of 0 to 24. Negative binomial-logit hurdle regression models were used to analyze how the different specifications of the K6 psychological distress measure were related to ED use.
RESULTS: Adults with serious psychological distress in 2009 had 1.59 (95% confidence interval [CI] = 1.15 to 2.20) times greater adjusted odds of having one or more ED visits in 2010 than those without serious psychological distress. Nonserious psychological distress levels in 2009 were also associated with increased adjusted odds of having at least one ED visit in 2010. The K6 scores showed a dose-response relationship in terms of the adjusted odds of having one or more ED visits. The adjusted odds ratios (ORs) were 1.86 (95% CI = 1.37 to 2.54) for adults with K6 scores at or above 11, OR 1.76 (95% CI = 1.38 to 2.25) for adults with K6 scores between 6 and 10, OR 1.33 (95% CI = 1.05 to 1.68) for adults with K6 scores between 3 and 5, and OR 1.17 (95% CI = 0.92 to 1.48) for adults with K6 scores of 1 or 2. In addition, the adjusted odds of having one or more ED visits in 2010 significantly increased with increasing psychological distress in 2009 (OR = 1.04, 95% CI = 1.03 to 1.06). Each additional point added to the K6 scale results in an increase in the adjusted odds of an ED visit.
CONCLUSIONS: Even a low level of psychological distress, and not just serious psychological distress, may be an early indicator of future ED use. These results highlight the need to develop novel responses to better manage or avert ED use not only for adults with serious psychological distress but also for those who are experiencing even mild symptoms of psychological distress.

PMID: 24842501 [PubMed - as supplied by publisher]

Organizational downsizing and depressive symptoms in the European recession: the experience of workers in france, hungary, sweden and the United kingdom.

Fri, 05/23/2014 - 4:05am
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Organizational downsizing and depressive symptoms in the European recession: the experience of workers in france, hungary, sweden and the United kingdom.

PLoS One. 2014;9(5):e97063

Authors: Brenner MH, Andreeva E, Theorell T, Goldberg M, Westerlund H, Leineweber C, Hanson LL, Imbernon E, Bonnaud S

Abstract
BACKGROUND: Organizational downsizing has become highly common during the global recession of the late 2000s with severe repercussions on employment. We examine whether the severity of the downsizing process is associated with a greater likelihood of depressive symptoms among displaced workers, internally redeployed workers and lay-off survivors.
METHODS: A cross-sectional survey involving telephone interviews was carried out in France, Hungary, Sweden and the United Kingdom. The study analyzes data from 758 workers affected by medium- and large-scale downsizing, using multiple logistic regression.
MAIN RESULTS: Both unemployment and surviving layoffs were significantly associated with depressive symptoms, as compared to reemployment, but the perceived procedural justice of a socially responsible downsizing process considerably mitigated the odds of symptoms. Perception of high versus low justice was assessed along several downsizing dimensions. In the overall sample, chances to have depressive symptoms were significantly reduced if respondents perceived the process as transparent and understandable, fair and unbiased, well planned and democratic; if they trusted the employer's veracity and agreed with the necessity for downsizing. The burden of symptoms was significantly greater if the process was perceived to be chaotic. We further tested whether perceived justice differently affects the likelihood of depressive symptoms among distinct groups of workers. Findings were that the odds of symptoms largely followed the same patterns of effects across all groups of workers. Redeploying and supporting surplus employees through the career change process-rather than forcing them to become unemployed-makes a substantial difference as to whether they will suffer from depressive symptoms.
CONCLUSIONS: While depressive symptoms affect both unemployed and survivors, a just and socially responsible downsizing process is important for the emotional health of workers.

PMID: 24841779 [PubMed - in process]

The unique protein kinase Cη: Implications for breast cancer (Review).

Fri, 05/23/2014 - 4:05am
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The unique protein kinase Cη: Implications for breast cancer (Review).

Int J Oncol. 2014 May 19;

Authors: Pal D, Basu A

Abstract
Deregulation of key signal transduction pathways that govern important cellular processes leads to cancer. The development of effective therapeutics for cancer warrants a comprehensive understanding of the signaling pathways that are deregulated in cancer. The protein kinase C (PKC) family has served as an attractive target for cancer therapy for decades owing to its crucial roles in several cellular processes. PKCη is a novel member of the PKC family that plays critical roles in various cellular processes such as growth, proliferation, differentiation and cell death. The regulation of PKCη appears to be unique compared to other PKC isozymes, and there are conflicting reports regarding its role in cancer. This review focuses on the unique aspects of PKCη in terms of its structure, regulation and subcellular distribution and speculates on how these features could account for its distinct functions. We have also discussed the functional implications of PKCη in cancer with particular emphasis on breast cancer.

PMID: 24841225 [PubMed - as supplied by publisher]

Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation.

Fri, 05/23/2014 - 4:05am
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Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation.

Age (Dordr). 2013 Oct;35(5):1821-34

Authors: Shetty RA, Forster MJ, Sumien N

Abstract
Coenzyme Q10 (CoQ) is widely available as a dietary supplement and remains under consideration as a treatment for age-associated neurodegenerative conditions. However, no studies have determined if supplementation, initiated relatively late in life, could have beneficial effects on mild functional impairments associated with normal brain aging. Accordingly, the current study assessed the effect of CoQ intake in older mice for which cognitive and psychomotor impairments were already evident. Separate groups of young (3.5 months) and relatively old mice (17.5 months) were fed a control diet or a diet supplemented with low (0.72 mg/g) or high (2.81 mg/g) concentrations of CoQ for 15 weeks. After 6 weeks, the mice were given tests for spatial learning (Morris water maze), spontaneous locomotor activity, motor coordination, and startle reflex. Age-related impairments in cognitive and psychomotor functions were evident in the 17.5-month-old mice fed the control diet, and the low-CoQ diet failed to affect any aspect of the impaired performance. However, in the Morris water maze test, old mice on the high-CoQ diet swam to the safe platform with greater efficiency than the mice on the control diet. The old mice supplemented with the high-CoQ diet did not show improvement when spatial performance was measured using probe trials and failed to show improvement in other tests of behavioral performance. Protein oxidative damage was decreased in the mitochondria from the heart, liver, and skeletal muscle of the high-CoQ-supplemented mice and, to some extent, in the brain mitochondria. Contrasting with the deleterious effect of long-term CoQ supplementation initiated during young adulthood previously published, this study suggests that CoQ improves spatial learning and attenuates oxidative damage when administered in relatively high doses and delayed until early senescence, after age-related declines have occurred. Thus, in individuals with age-associated symptoms of cognitive decline, high-CoQ intake may be beneficial.

PMID: 23138632 [PubMed - indexed for MEDLINE]

Membrane Topology of Human Presenilin-1 in SK-N-SH Cells Determined by Fluorescence Correlation Spectroscopy and Fluorescent Energy Transfer.

Wed, 05/21/2014 - 4:04am

Membrane Topology of Human Presenilin-1 in SK-N-SH Cells Determined by Fluorescence Correlation Spectroscopy and Fluorescent Energy Transfer.

Cell Biochem Biophys. 2014 May 18;

Authors: Midde K, Rich R, Saxena A, Gryczynski I, Borejdo J, Das HK

Abstract
Presenilin-1 (PS1) protein acts as passive ER Ca(2+) leak channels that facilitate passive Ca(2+) leak across ER membrane. Mutations in the gene encoding PS1 protein cause neurodegeneration in the brains of patients with familial Alzheimer's disease (FAD). FADPS1 mutations abrogate the function of ER Ca(2+) leak channel activity in human neuroblastoma SK-N-SH cells in vitro (Das et al., J Neurochem 122(3):487-500, 2012) and in mouse embryonic fibroblasts. Consequently, genetic deletion or mutations of the PS1 gene cause calcium (Ca(2+)) signaling abnormalities leading to neurodegeneration in FAD patients. By analogy with other known ion channels it has been proposed that the functional PS1 channels in ER may be multimers of several PS1 subunits. To test this hypothesis, we conjugated the human PS1 protein with an NH2-terminal YFP-tag and a COOH-terminal CFP-tag. As expected YFP-PS1, and PS1-CFP were found to be expressed on the plasma membranes by TIRF microscopy, and both these fusion proteins increased ER Ca(2+) leak channel activity similar to PS1 (WT) in SK-N-SH cells, as determined by functional calcium imaging. PS1-CFP was either expressed alone or together with YFP-PS1 into SK-N-SH cell line and the interaction between YFP-PS1 and PS1-CFP was determined by Förster resonance energy transfer analysis. Our results suggest interaction between YFP-PS1 and PS1-CFP confirming the presence of a dimeric or multimeric form of PS1 in SK-N-SH cells. Lateral diffusion of PS1-CFP and YFP-PS1 in the plasma membrane of SK-N-SH cells was measured in the absence or in the presence of glycerol by fluorescence correlation spectroscopy to show that both COOH-terminal and NH2-terminal of human PS1 are located on the cytoplasmic side of the plasma membrane. Therefore, we conclude that both COOH-terminal and NH2-terminal of human PS1 may also be oriented on the cytosolic side of ER membrane.

PMID: 24839116 [PubMed - as supplied by publisher]

mTOR Signaling Inhibition Modulates Macrophage/Microglia-Mediated Neuroinflammation and Secondary Injury via Regulatory T Cells after Focal Ischemia.

Tue, 05/20/2014 - 4:04am
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mTOR Signaling Inhibition Modulates Macrophage/Microglia-Mediated Neuroinflammation and Secondary Injury via Regulatory T Cells after Focal Ischemia.

J Immunol. 2014 May 14;

Authors: Xie L, Sun F, Wang J, Mao X, Xie L, Yang SH, Su DM, Simpkins JW, Greenberg DA, Jin K

Abstract
Signaling by the mammalian target of rapamycin (mTOR) plays an important role in the modulation of both innate and adaptive immune responses. However, the role and underlying mechanism of mTOR signaling in poststroke neuroinflammation are largely unexplored. In this study, we injected rapamycin, a mTOR inhibitor, by the intracerebroventricular route 6 h after focal ischemic stroke in rats. We found that rapamycin significantly reduced lesion volume and improved behavioral deficits. Notably, infiltration of γδ T cells and granulocytes, which are detrimental to the ischemic brain, was profoundly reduced after rapamycin treatment, as was the production of proinflammatory cytokines and chemokines by macrophages and microglia. Rapamycin treatment prevented brain macrophage polarization toward the M1 type. In addition, we also found that rapamycin significantly enhanced anti-inflammation activity of regulatory T cells (Tregs), which decreased production of proinflammatory cytokines and chemokines by macrophages and microglia. Depletion of Tregs partially elevated macrophage/microglia-induced neuroinflammation after stroke. Our data suggest that rapamycin can attenuate secondary injury and motor deficits after focal ischemia by enhancing the anti-inflammation activity of Tregs to restrain poststroke neuroinflammation.

PMID: 24829408 [PubMed - as supplied by publisher]

Enhancing Nurses' Knowledge Regarding the Complex Care of Hospitalized Patients on Insulin.

Tue, 05/20/2014 - 4:04am
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Enhancing Nurses' Knowledge Regarding the Complex Care of Hospitalized Patients on Insulin.

J Nurses Prof Dev. 2014 May 12;

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 - as supplied by publisher]

Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Tue, 05/20/2014 - 4:04am
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Pyruvate-enriched resuscitation: metabolic support of post-ischemic hindlimb muscle in hypovolemic goats.

Exp Biol Med (Maywood). 2014 Feb;239(2):240-9

Authors: Gurji HA, White DW, Hoxha B, Sun J, Harbor JP, Schulz DR, Williams AG, Olivencia-Yurvati AH, Mallet RT

Abstract
Tourniquet-imposed ischemia-reperfusion of extremities generates reactive oxygen and nitrogen species (RONS), which can disrupt intermediary metabolism and ATP production. This study tested the hypothesis that fluid resuscitation with pyruvate, a natural antioxidant and metabolic fuel, ameliorates the deleterious effects of ischemia-reperfusion on intermediary metabolism in skeletal muscle. Anesthetized male goats (∼25 kg) were bled to a mean arterial pressure of 48 ± 1 mmHg and then subjected to 90 min hindlimb ischemia with a tourniquet and femoral crossclamp, followed by 4-h reperfusion. Lactated Ringers (LR) or pyruvate Ringers (PR) was infused intravenous for 90 min, from 30 min ischemia to 30 min reperfusion, to deliver 0.05 mmol kg(-1) min(-1) lactate or pyruvate. Time controls (TC) underwent neither hemorrhage nor hindlimb ischemia. Lipid peroxidation product 8-isoprostane, RONS-sensitive aconitase and creatine kinase activities, antioxidant superoxide dismutase activity, and phosphocreatine phosphorylation potential ([PCr]/[{Cr}{P(i)}]), an index of tissue energy state, were measured in reperfused gastrocnemius at 90 min resuscitation (n = 6 all groups) and 3.5 h post-resuscitation (n = 8 TC, 9 LR, 10 PR). PR more effectively than LR suppressed 8-isoprostane formation, prevented inactivation of aconitase and creatine kinase, doubled superoxide dismutase activity, and augmented [PCr]/([Cr][P(i)]). Pyruvate-enriched Ringer's is metabolically superior to Ringer's lactate for fluid resuscitation of tourniqueted muscle.

PMID: 24414481 [PubMed - indexed for MEDLINE]

Evaluating factors affecting patellar component fixation strength in total knee arthroplasty.

Tue, 05/20/2014 - 4:04am
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Evaluating factors affecting patellar component fixation strength in total knee arthroplasty.

Am J Orthop (Belle Mead NJ). 2013 Sep;42(9):416-9

Authors: Wagner RA, Lesley NE, Coté RE, Tayag TJ

Abstract
Complications related to the patellofemoral joint after total knee arthroplasty (TKA) represent up to 50% of TKA reoperations. Shear forces across the knee produce wear and occasionally result in failure of fixation of all-polyethylene patellar components. We conducted a study to evaluate the effect of 2 factors on the shear strength of patellar component fixation: time between cement mixing and application of the patellar component, and amount of pressure applied during implantation. Fifty-four patellae were harvested from 27 cadavers and were prepared as for a TKA, allowing 3 different amounts of time for the cement to set or cure before application, and using 3 different pressures. The patellae were mounted and tested for fixation strength with a materials testing machine. Fixation was significantly stronger (P = .006) at 42 pounds of pressure after curing the cement for 8 minutes (compared with 2 minutes) and was significantly stronger (P = .005) after 2 minutes of curing at 42 pounds of pressure (compared with 62 pounds of pressure). We concluded that allowing the cement to cure while cementing the femoral and tibial components does not jeopardize fixation of the patellar component and that excessive compression of a patellar clamp may weaken fixation.

PMID: 24078966 [PubMed - indexed for MEDLINE]

Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Fri, 05/16/2014 - 4:05am

Bilateral symmetrical supernumerary heads of biceps brachii with rare pectoralis major insertion.

Surg Radiol Anat. 2014 May 10;

Authors: Fraser PR, Howard LW, Rosales AA, Guttmann GD

Abstract
During a routine dissection of a 51-year-old Caucasian male cadaver, bilateral symmetrical supernumerary heads (SH) of the biceps brachii muscles with insertion into the pectoralis major (PM) muscles were discovered. Multiple case reports have documented supernumerary heads for the biceps brachii; however, none have shown bilateral insertion into the pectoralis major. This study describes a previously undocumented variation of the SH that has potential for clinical impact. Healthcare providers could be confounded by patients presenting with shoulder pain or muscle tears as a result of the anomaly. Furthermore, MRI studies on patients with possible shoulder muscle tears could reveal unexpected results. Such cases would warrant consideration of SH anomaly and treatment should be adjusted accordingly. The significant bulk and angle of the SH insertion on the PM we observed changes force vectors which would have an unknown effect in performance, surgical interventions and pain syndromes. A second biceps brachii anomaly was observed on the left brachium in addition to the bilateral SH. We postulate that these variants provide the potential for clinical complications regarding muscular injury to these aforementioned muscle groups.

PMID: 24817560 [PubMed - as supplied by publisher]

Developmental validation of the EX20+4 system.

Fri, 05/16/2014 - 4:05am

Developmental validation of the EX20+4 system.

Forensic Sci Int Genet. 2014 Mar 19;11C:207-213

Authors: Li S, Liu C, Liu H, Ge J, Budowle B, Liu C, Zheng W, Li F, Ge B

Abstract
The EX20+4Y System is a polymerase chain reaction (PCR)-based amplification kit that enables typing of 19 autosomal short tandem repeat (STR) loci (i.e., CSF1PO, D13S317, D16S539, D18S51, D21S11, D3S1358, D5S818, D7S820, D8S1179, FGA, TH01, TPOX, vWA, Penta D, Penta E, D2S1338, D19S433, D12S391, D6S1043), four widely used Y chromosome-specific STR (Y-STR) loci (DYS458, DYS456, DYS391, DYS635), and amelogenin. In this study, this multiplex system was validated for sensitivity of detection, DNA mixtures, inhibitor tolerance, species specificity based on the Scientific Working Group on DNA Analysis methods (SWGDAM) developmental validation guidelines, and the Chinese criteria for the human fluorescent STR multiplex PCR reagent. The results show that the EX20+4 System is a robust and reliable amplification kit which can be used for human identification testing.

PMID: 24815370 [PubMed - as supplied by publisher]

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Fri, 05/16/2014 - 4:05am

Pharmacology, benefits, unaddressed questions, and pragmatic issues of the newer oral anticoagulants for stroke prophylaxis in non-valvular atrial fibrillation and proposal of a management algorithm.

Int J Cardiol. 2014 Apr 26;

Authors: Rosanio S, Keylani AM, D'Agostino DC, Delaughter CM, Vitarelli A

Abstract
This systematic review aims to provide an update on pharmacology, efficacy and safety of the newer oral direct thrombin and factor Xa inhibitors, which have emerged for the first time in ~60years as cogent alternatives to warfarin for stroke prophylaxis in non-valvular atrial fibrillation. We also discuss on four of the most common clinical scenarios with several unsolved questions and areas of uncertainty that may play a role in physicians' reluctance to prescribe the newer oral anticoagulants such as 1) patients with renal failure; 2) the elderly; 3) patients presenting with atrial fibrillation and acute coronary syndromes and/or undergoing coronary stenting; and 4) patients planning to receive AF ablation with the use of pulmonary vein isolation. New aspects presented in current guidelines are covered and we also propose an evidence-based anticoagulation management algorithm.

PMID: 24814537 [PubMed - as supplied by publisher]

Assessment of the role of DNA repair in damaged forensic samples.

Tue, 05/13/2014 - 4:04am

Assessment of the role of DNA repair in damaged forensic samples.

Int J Legal Med. 2014 May 3;

Authors: Ambers A, Turnbough M, Benjamin R, King J, Budowle B

Abstract
Previous studies on DNA damage and repair have involved in vitro laboratory procedures that induce a single type of lesion in naked templates. Although repair of singular, sequestered types of DNA damage has shown some success, forensic and ancient specimens likely contain a number of different types of lesions. This study sought to (1) develop protocols to damage DNA in its native state, (2) generate a pool of candidate samples for repair that more likely emulate authentic forensic samples, and (3) assess the ability of the PreCR(TM) Repair Mix to repair the resultant lesions. Complexed, native DNA is more difficult to damage than naked DNA. Modified procedures included the use of higher concentrations and longer exposure times. Three types of samples, those that demonstrated damage based on short tandem repeat (STR) profile signals, were selected for repair experiments: environmentally damaged bloodstains, bleach-damaged whole blood, and human skeletal remains. Results showed trends of improved performance of STR profiling of bleach-damaged DNA. However, the repair assay did not improve DNA profiles from environmentally damaged bloodstains or bone, and in some cases resulted in lower RFU values for STR alleles. The extensive spectrum of DNA damage and myriad combinations of lesions that can be present in forensic samples appears to pose a challenge for the in vitro PreCR(TM) assay. The data suggest that the use of PreCR in casework should be considered with caution due to the assay's varied results.

PMID: 24792635 [PubMed - as supplied by publisher]

Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Tue, 05/13/2014 - 4:04am
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Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model.

Neurobiol Dis. 2013 Nov;59:18-25

Authors: Li W, Huang R, Shetty RA, Thangthaeng N, Liu R, Chen Z, Sumien N, Rutledge M, Dillon GH, Yuan F, Forster MJ, Simpkins JW, Yang SH

Abstract
Vascular dementia ranks as the second leading cause of dementia in the United States. However, its underlying pathophysiological mechanism is not fully understood and no effective treatment is available. The purpose of the current study was to evaluate long-term cognitive deficits induced by transient middle cerebral artery occlusion (tMCAO) in rats and to investigate the underlying mechanism. Sprague-Dawley rats were subjected to tMCAO or sham surgery. Behavior tests for locomotor activity and cognitive function were conducted at 7 or 30days after stroke. Hippocampal long term potentiation (LTP) and involvement of GABAergic neurotransmission were evaluated at 30days after sham surgery or stroke. Immunohistochemistry and Western blot analyses were conducted to determine the effect of tMCAO on cell signaling in the hippocampus. Transient MCAO induced a progressive deficiency in spatial performance. At 30days after stroke, no neuron loss or synaptic marker change in the hippocampus were observed. LTP in both hippocampi was reduced at 30days after stroke. This LTP impairment was prevented by blocking GABAA receptors. In addition, ERK activity was significantly reduced in both hippocampi. In summary, we identified a progressive decline in spatial learning and memory after ischemic stroke that correlates with suppression of hippocampal LTP, elevation of GABAergic neurotransmission, and inhibition of ERK activation. Our results indicate that the attenuation of GABAergic activity or enhancement of ERK/MAPK activation in the hippocampus might be potential therapeutic approaches to prevent or attenuate cognitive impairment after ischemic stroke.

PMID: 23845275 [PubMed - indexed for MEDLINE]

Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Tue, 05/13/2014 - 4:04am
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Comparison of the accuracy of kriging and IDW interpolations in estimating groundwater arsenic concentrations in Texas.

Environ Res. 2014 Apr;130:59-69

Authors: Gong G, Mattevada S, O'Bryant SE

Abstract
Exposure to arsenic causes many diseases. Most Americans in rural areas use groundwater for drinking, which may contain arsenic above the currently allowable level, 10µg/L. It is cost-effective to estimate groundwater arsenic levels based on data from wells with known arsenic concentrations. We compared the accuracy of several commonly used interpolation methods in estimating arsenic concentrations in >8000 wells in Texas by the leave-one-out-cross-validation technique. Correlation coefficient between measured and estimated arsenic levels was greater with inverse distance weighted (IDW) than kriging Gaussian, kriging spherical or cokriging interpolations when analyzing data from wells in the entire Texas (p<0.0001). Correlation coefficient was significantly lower with cokriging than any other methods (p<0.006) for wells in Texas, east Texas or the Edwards aquifer. Correlation coefficient was significantly greater for wells in southwestern Texas Panhandle than in east Texas, and was higher for wells in Ogallala aquifer than in Edwards aquifer (p<0.0001) regardless of interpolation methods. In regression analysis, the best models are when well depth and/or elevation were entered into the model as covariates regardless of area/aquifer or interpolation methods, and models with IDW are better than kriging in any area/aquifer. In conclusion, the accuracy in estimating groundwater arsenic level depends on both interpolation methods and wells' geographic distributions and characteristics in Texas. Taking well depth and elevation into regression analysis as covariates significantly increases the accuracy in estimating groundwater arsenic level in Texas with IDW in particular.

PMID: 24559533 [PubMed - indexed for MEDLINE]

Dual plating of humeral shaft fractures: orthogonal plates biomechanically outperform side-by-side plates.

Tue, 05/06/2014 - 4:04am
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Dual plating of humeral shaft fractures: orthogonal plates biomechanically outperform side-by-side plates.

Clin Orthop Relat Res. 2014 Apr;472(4):1310-7

Authors: Kosmopoulos V, Nana AD

Abstract
BACKGROUND: Single large-fragment plate constructs currently are the norm for internal fixation of middiaphyseal humerus fractures. In cases where humeral size is limited, however, dual small-fragment locking plate constructs may serve as an alternative. The mechanical effects of different possible plate configurations around the humeral diaphysis may be important, but to our knowledge, have yet to be investigated.
QUESTIONS/PURPOSES: We used finite element analysis to compare the simulated mechanical performance of five different dual small-fragment locking plate construct configurations for humeral middiaphyseal fracture fixation in terms of (1) stiffness, (2) stress shielding of bone, (3) hardware stresses, and (4) interfragmentary strain.
METHODS: Middiaphyseal humeral fracture fixation was simulated using the finite element method. Three 90° and two side-by-side seven-hole and nine-hole small-fragment dual locking plate configurations were tested in compression, torsion, and combined loading. The configurations chosen are based on implantation using either a posterior or anterolateral approach.
RESULTS: All three of the 90° configurations were more effective in restoring the intact compressive and torsional stiffness as compared with the side-by-side configurations, resulted in less stress shielding and stressed hardware, and showed interfragmentary strains between 5% to 10% in torsion and combined loading.
CONCLUSIONS: The nine-hole plate anterior and seven-hole plate lateral (90° apart) configuration provided the best fixation. Our findings show the mechanical importance of plate placement with relation to loading in dual-plate fracture-fixation constructs.
CLINICAL RELEVANCE: The results presented provide novel biomechanical information for the orthopaedic surgeon considering different treatment options for middiaphyseal humeral fractures.

PMID: 24218163 [PubMed - indexed for MEDLINE]