Recent Research Articles from UNTHSC

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Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: a multiplex real-time PCR assay.

Fri, 08/29/2014 - 3:05am
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Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: a multiplex real-time PCR assay.

Sci Rep. 2014;4:3887

Authors: Phillips NR, Sprouse ML, Roby RK

Abstract
Mitochondrial dysfunction is implicated in a vast array of diseases and conditions, such as Alzheimer's disease, cancer, and aging. Alterations in mitochondrial DNA (mtDNA) may provide insight into the processes that either initiate or propagate this dysfunction. Here, we describe a unique multiplex assay which simultaneously provides assessments of mtDNA copy number and the proportion of genomes with common large deletions by targeting two mitochondrial sites and one nuclear locus. This probe-based, single-tube multiplex provides high specificity while eliminating well-to-well variability that results from assaying nuclear and mitochondrial targets individually.

PMID: 24463429 [PubMed - indexed for MEDLINE]

Outcomes of osteopathic manual treatment for chronic low back pain according to baseline pain severity: results from the OSTEOPATHIC Trial.

Fri, 08/29/2014 - 3:05am
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Outcomes of osteopathic manual treatment for chronic low back pain according to baseline pain severity: results from the OSTEOPATHIC Trial.

Man Ther. 2013 Dec;18(6):533-40

Authors: Licciardone JC, Kearns CM, Minotti DE

Abstract
PURPOSE: To assess response to osteopathic manual treatment (OMT) according to baseline severity of chronic low back pain (LBP).
METHODS: The OSTEOPATHIC Trial used a randomized, double-blind, sham-controlled, 2×2 factorial design to study OMT for chronic LBP. A total of 269 (59%) patients reported low baseline pain severity (LBPS) (<50 mm/100 mm), whereas 186 (41%) patients reported high baseline pain severity (HBPS) (≥50 mm/100 mm). Six OMT sessions were provided over eight weeks and outcomes were assessed at week 12. The primary outcome was substantial LBP improvement (≥50% pain reduction). The Roland-Morris Disability Questionnaire (RMDQ) and eight other secondary outcomes were also studied. Response ratios (RRs) and 95% confidence intervals (CIs) were used in conjunction with Cochrane Back Review Group criteria to determine OMT effects.
RESULTS: There was a large effect size for OMT in providing substantial LBP improvement in patients with HBPS (RR, 2.04; 95% CI, 1.36-3.05; P<0.001). This was accompanied by clinically important improvement in back-specific functioning on the RMDQ (RR, 1.80; 95% CI, 1.08-3.01; P=0.02). Both RRs were significantly greater than those observed in patients with LBPS. Osteopathic manual treatment was consistently associated with benefits in all other secondary outcomes in patients with HBPS, although the statistical significance and clinical relevance of results varied.
CONCLUSIONS: The large effect size for OMT in providing substantial pain reduction in patients with chronic LBP of high severity was associated with clinically important improvement in back-specific functioning. Thus, OMT may be an attractive option in such patients before proceeding to more invasive and costly treatments.

PMID: 23759340 [PubMed - indexed for MEDLINE]

Coenzyme Q10 and α-tocopherol reversed age-associated functional impairments in mice.

Wed, 08/27/2014 - 3:05am
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Coenzyme Q10 and α-tocopherol reversed age-associated functional impairments in mice.

Exp Gerontol. 2014 Aug 18;

Authors: Shetty RA, Ikonne US, Forster MJ, Sumien N

Abstract
The purpose of this study was to determine if intake of the antioxidants coenzyme Q10 (CoQ10) or α-tocopherol (Toc), either alone or in combination, could ameliorate cognitive and psychomotor impairments of aged mice, as well as reduce oxidative burden in tissues. For a period of 10weeks, male C57BL/6J mice (3 or 18months) were fed either a control diet, or one of three diets supplemented with Toc, CoQ10 or their combination, and were tested for cognitive and psychomotor functions. Old mice on the Toc or Toc/CoQ10 diets showed improved coordinated running performance. Mice on the diet containing Toc/CoQ10 demonstrated improved performance in the discriminated avoidance task. CoQ10 and Toc alone also resulted in improved performance, albeit to a lesser degree. Protein damage was decreased especially when the mice received Toc+CoQ10 combination. Overall, these results suggest that, Toc and CoQ supplementation can ameliorate age-related impairment and reduce protein oxidation. Moreover, concurrent supplementation of CoQ10 and Toc may be more effective than either antioxidant alone.

PMID: 25149567 [PubMed - as supplied by publisher]

Preoperative Decision Making in the Treatment of High-Angle "Vertical" Femoral Neck Fractures in Young Adult Patients: An Expert Opinion Survey of the Orthopaedic Trauma Association's (OTA) Membership.

Wed, 08/27/2014 - 3:05am
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Preoperative Decision Making in the Treatment of High-Angle "Vertical" Femoral Neck Fractures in Young Adult Patients: An Expert Opinion Survey of the Orthopaedic Trauma Association's (OTA) Membership.

J Orthop Trauma. 2014 Sep;28(9):e221-5

Authors: Luttrell K, Beltran M, Collinge CA

Abstract
OBJECTIVE: To identify the current implant and diagnostic imaging preferences among orthopaedic trauma experts for the treatment of high-energy vertical femoral neck fractures in young adult patients.
DESIGN: Web-based survey.
SETTING: Not available.
PARTICIPANTS: Active members of the OTA.
METHODS: A cross-sectional expert opinion survey was administered to the active members of the OTA to determine their preferences for implant use and imaging in the surgical treatment of a vertical femoral neck fracture in a young adult patient (eg, 60-degree Pauwels angle fracture in a healthy 30-year-old patient). Questions were also asked regarding the reason why this implant was selected, whether the surgeon felt that their choice was supported by the literature, and what imaging studies are routinely obtained to guide decision making. Data were collected using simple multiple-choice questions and/or a 5-point Likert item.
RESULTS: Two hundred seventy-two surgeons (47%) responded to the survey. The preferred constructs for a vertical femoral neck fracture in a healthy young patient were a sliding hip screw with or without an anti-rotation screw (47%), parallel cannulated screws with an off-axis screw (28%), and parallel cannulated screw constructs (15%). When asked if their designated construct "was clearly supported by the literature," 46% were either unsure or disagreed. Seventy percent of surgeons chose their preferred implant because it was "biomechanically most stable." Most surgeons required anteroposterior pelvis (70%) and standard hip (88%) radiographs; however only 29% of surgeons required a computed tomography (59% found computed tomography helpful but not required). Twenty-seven percent of surgeons have changed their implant choice intraoperatively.
CONCLUSIONS: Femoral neck fractures in young adult patients are a challenging problem with high rates of failed treatment. Many options for treatment exist and a consensus on the best method remains elusive. Our survey demonstrates the diversity and disagreement among OTA member "expert" orthopaedic traumatologists for the "best" treatment choice for this important clinical scenario. Our survey shows a divided level of confidence in the current literature and highlights the need for further study of this problem.
LEVEL OF EVIDENCE: Therapeutic Level V. See Instructions for Authors for a complete description of levels of evidence.

PMID: 25148589 [PubMed - in process]

Prognostic models to detect and monitor the near-term risk of suicide: state of the science.

Wed, 08/27/2014 - 3:05am
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Prognostic models to detect and monitor the near-term risk of suicide: state of the science.

Am J Prev Med. 2014 Sep;47(3 Suppl 2):S181-5

Authors: Claassen CA, Harvilchuck-Laurenson JD, Fawcett J

Abstract
Aspirational Goal 3 of the National Action Alliance for Suicide Prevention's Research Prioritization Task Force research agenda is to "find ways to assess who is at risk for attempting suicide in the immediate future." Suicide risk assessment is the practice of detecting patient-level conditions that may rapidly progress toward suicidal acts. With hundreds of thousands of risk assessments occurring every year, this single activity arguably represents the most broadly implemented, sustained suicide prevention activity practiced in the U.S. Given this scope of practice, accurate and reliable risk assessment capabilities hold a central and irreplaceable position among interventions mounted as part of any public health approach to suicide prevention. Development of more reliable methods to detect and measure the likelihood of impending suicidal behaviors, therefore, represents one of the more substantial advancements possible in suicide prevention science today. Although past "second-generation" risk models using largely static risk factors failed to show predictive capabilities, the current "third-generation" dynamic risk prognostic models have shown initial promise. Methodologic improvements to these models include the advent of real-time, in vivo data collection processes, common data elements across studies and data sharing to build knowledge around key factors, and analytic methods designed to address rare event outcomes. Given the critical need for improved risk detection, these promising recent developments may well foreshadow advancement toward eventual achievement of this Aspirational Goal.

PMID: 25145737 [PubMed - in process]

Introduction to the suicide prevention research prioritization task force special supplement: the topic experts.

Wed, 08/27/2014 - 3:05am
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Introduction to the suicide prevention research prioritization task force special supplement: the topic experts.

Am J Prev Med. 2014 Sep;47(3 Suppl 2):S102-5

Authors: Pearson JL, Claassen CA, Booth CL, Research Prioritization Task Force of the National Action Alliance for Suicide Prevention

PMID: 25145726 [PubMed - in process]

Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.

Tue, 08/26/2014 - 3:06am
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Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.

Neuropsychopharmacology. 2014 Jan;39(2):380-8

Authors: Paris JJ, Carey AN, Shay CF, Gomes SM, He JJ, McLaughlin JP

Abstract
As a major neuropathogenic factor associated with human immunodeficiency virus (HIV) infection, HIV-1 Tat protein is known to synergize with psychostimulant drugs of abuse to cause neurotoxicity and exacerbate the progression of central nervous system pathology. However, the functional consequences of the interaction between HIV-1 Tat and abused drugs on behavior are little known. We tested the hypothesis that HIV-1 Tat expression in brain would modulate the psychostimulant effects of cocaine. Using the GT-tg bigenic mouse model, where brain-selective Tat expression is induced by activation of a doxycycline (Dox) promotor, we tested the effects of Tat on cocaine (10 mg/kg, s.c.) induced locomotion and conditioned place preference (CPP). Compared with uninduced littermates or C57BL/6J controls, cocaine-induced hyperlocomotion was sustained for a significantly longer duration among Tat-induced mice. Moreover, although all groups displayed similar saline-CPP, Tat-induced GT-tg mice demonstrated a three-fold increase in cocaine-CPP over the response of either uninduced littermates or Dox-treated C57BL/6J control mice. Induction of Tat also increased the magnitude of a previously established cocaine-CPP after an additional cycle of cocaine place-conditioning. Despite Tat-induced potentiation, extinction of place preference occurred within 21 days, commensurate with cocaine-extinction among saline-treated littermates and C57BL/6J controls. Re-exposure to cocaine produced reinstatement of an equivalent place preference in Tat-induced GT-tg or C57BL/6J mice; however, induction of Tat protein after the extinction of CPP also produced reinstatement without additional exposure to cocaine. Together, these data suggest that central HIV-1 Tat expression can potentiate the psychostimulant behavioral effects of cocaine in mice.

PMID: 23945478 [PubMed - indexed for MEDLINE]

Multiple biomarker panels for early detection of breast cancer in peripheral blood.

Fri, 08/22/2014 - 3:05am
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Multiple biomarker panels for early detection of breast cancer in peripheral blood.

Biomed Res Int. 2013;2013:781618

Authors: Zhang F, Deng Y, Drabier R

Abstract
Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

PMID: 24371830 [PubMed - indexed for MEDLINE]

mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia.

Fri, 08/22/2014 - 3:05am
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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 Jun 15;192(12):6009-19

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 - indexed for MEDLINE]

Neuronal injury from cardiac arrest: aging years in minutes.

Tue, 08/19/2014 - 3:06am
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Neuronal injury from cardiac arrest: aging years in minutes.

Age (Dordr). 2014 Aug;36(4):9680

Authors: Cherry BH, Sumien N, Mallet RT

Abstract
Cardiac arrest is a leading cause of death and permanent disability. Most victims succumb to the oxidative and inflammatory damage sustained during cardiac arrest/resuscitation, but even survivors typically battle long-term neurocognitive impairment. Although extensive research has delineated the complex mechanisms that culminate in neuronal damage and death, no effective treatments have been developed to interrupt these mechanisms. Of importance, many of these injury cascades are also active in the aging brain, where neurons and other cells are under persistent oxidative and inflammatory stress which eventually damages or kills the cells. In light of these similarities, it is reasonable to propose that the brain essentially ages the equivalent of several years within the few minutes taken to resuscitate a patient from cardiac arrest. Accordingly, cardiac arrest-resuscitation models may afford an opportunity to study the deleterious mechanisms underlying the aging process, on an accelerated time course. The aging and resuscitation fields both stand to gain pivotal insights from one another regarding the mechanisms of injury sustained during resuscitation from cardiac arrest and during aging. This synergism between the two fields could be harnessed to foster development of treatments to not only save lives but also to enhance the quality of life for the elderly.

PMID: 25104136 [PubMed - as supplied by publisher]

Capsule Commentary on Albrecht et al., Hospital Discharge Instructions: Comprehension and Compliance Among Older Adults.

Tue, 08/19/2014 - 3:06am
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Capsule Commentary on Albrecht et al., Hospital Discharge Instructions: Comprehension and Compliance Among Older Adults.

J Gen Intern Med. 2014 Aug 8;

Authors: Tak HJ

PMID: 25103123 [PubMed - as supplied by publisher]

The future of blood-based biomarkers for Alzheimer's disease.

Tue, 08/19/2014 - 3:06am
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The future of blood-based biomarkers for Alzheimer's disease.

Alzheimers Dement. 2014 Jan;10(1):115-31

Authors: Henriksen K, O'Bryant SE, Hampel H, Trojanowski JQ, Montine TJ, Jeromin A, Blennow K, Lönneborg A, Wyss-Coray T, Soares H, Bazenet C, Sjögren M, Hu W, Lovestone S, Karsdal MA, Weiner MW, Blood-Based Biomarker Interest Group

Abstract
Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease progression or treatment response, and most are measured in cerebrospinal fluid, which limits their applicability. With these aspects in mind, the aim of this article is to underscore the concerted efforts of the Blood-Based Biomarker Interest Group, an international working group of experts in the field. The points addressed include: (1) the major challenges in the development of blood-based biomarkers of AD, including patient heterogeneity, inclusion of the "right" control population, and the blood-brain barrier; (2) the need for a clear definition of the purpose of the individual markers (e.g., prognostic, diagnostic, or monitoring therapeutic efficacy); (3) a critical evaluation of the ongoing biomarker approaches; and (4) highlighting the need for standardization of preanalytical variables and analytical methodologies used by the field.

PMID: 23850333 [PubMed - indexed for MEDLINE]

Validation of high throughput sequencing and microbial forensics applications.

Tue, 08/12/2014 - 3:05am

Validation of high throughput sequencing and microbial forensics applications.

Investig Genet. 2014;5:9

Authors: Budowle B, Connell ND, Bielecka-Oder A, Colwell RR, Corbett CR, Fletcher J, Forsman M, Kadavy DR, Markotic A, Morse SA, Murch RS, Sajantila A, Schmedes SE, Ternus KL, Turner SD, Minot S

Abstract
High throughput sequencing (HTS) generates large amounts of high quality sequence data for microbial genomics. The value of HTS for microbial forensics is the speed at which evidence can be collected and the power to characterize microbial-related evidence to solve biocrimes and bioterrorist events. As HTS technologies continue to improve, they provide increasingly powerful sets of tools to support the entire field of microbial forensics. Accurate, credible results allow analysis and interpretation, significantly influencing the course and/or focus of an investigation, and can impact the response of the government to an attack having individual, political, economic or military consequences. Interpretation of the results of microbial forensic analyses relies on understanding the performance and limitations of HTS methods, including analytical processes, assays and data interpretation. The utility of HTS must be defined carefully within established operating conditions and tolerances. Validation is essential in the development and implementation of microbial forensics methods used for formulating investigative leads attribution. HTS strategies vary, requiring guiding principles for HTS system validation. Three initial aspects of HTS, irrespective of chemistry, instrumentation or software are: 1) sample preparation, 2) sequencing, and 3) data analysis. Criteria that should be considered for HTS validation for microbial forensics are presented here. Validation should be defined in terms of specific application and the criteria described here comprise a foundation for investigators to establish, validate and implement HTS as a tool in microbial forensics, enhancing public safety and national security.

PMID: 25101166 [PubMed]

Assessing long-term health and cost outcomes of patient-centered medical homes serving adults with poor diabetes control.

Fri, 08/08/2014 - 3:05am
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Assessing long-term health and cost outcomes of patient-centered medical homes serving adults with poor diabetes control.

J Prim Care Community Health. 2013 Oct;4(4):281-5

Authors: Pagán JA, Carlson EK

Abstract
The patient-centered medical home (PCMH) is an integrated primary care delivery model particularly suited for patients with poor diabetes control. Although PCMH models targeting adults with diabetes have shown some early success, little is known about the long-term benefits of medical homes in terms of health and cost outcomes. The performance of a PCMH model in adults with poor diabetes control was assessed using simulated controlled trial data obtained from the Archimedes model of disease progression and health care utilization. Using the Cardio-Metabolic Risk data set, we compared health and cost outcomes over a 20-year period between adults with poor diabetes control (HbA1c >9%) receiving standard care and these same adults receiving care under a PCMH model with a 49% HbA1c intervention improvement rate at a per-beneficiary per-month care management cost of $20 per month. The results suggest that the PCMH model has the potential to not only reduce the proportion of the population with bilateral blindness, foot amputations, and myocardial infarctions-and the mortality rate-but it can also do so in a cost-effective manner ($7898 per quality-adjusted life year). The PCMH model is cost saving for the population 50 to 64 years old and it is particularly cost-effective for men ($883 per quality-adjusted life year). Moreover, these effects are relatively large for adults 30 to 49 years old (lower bilateral blindness and death rates), women (lower foot amputation and death rates), and men (lower bilateral blindness and myocardial infarction rates). The PCMH model has potential long-term benefits to both patients with poor diabetes control as well as health care systems and providers willing to invest in this health care delivery approach.

PMID: 23799676 [PubMed - indexed for MEDLINE]