Recent Research Articles from UNTHSC

Recent research articles indexed in PubMed from authors affiliated with the UNT Health Science Center.

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Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

Fri, 09/09/2016 - 07:32
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Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

J Arthroplasty. 2016 Jan;31(1):103-6

Authors: Chambers AW, Wood AR, Kosmopoulos V, Sanchez HB, Wagner RA

Abstract
Reduced posterior tibial slope (PTS) and posterior tibiofemoral translation (PTFT) in posterior cruciate-retaining (PCR) total knee arthroplasty (TKA) may result in suboptimal flexion. We evaluated the relationship between PTS, PTFT, and total knee flexion after PCR TKA in a cadaveric model. We performed a balanced PCR TKA using 9 transfemoral cadaver specimens and changed postoperative PTS in 1° increments. We measured maximal flexion and relative PTFT at maximal flexion. We determined significant changes in flexion and PTFT as a function of PTS. Findings showed an average increase in flexion of 2.3° and average PTFT increase of 1mm per degree of PTS increase when increasing PTS from 1° to 4° (P<.05). Small initial increases in PTS appear to significantly increase knee flexion and PTFT.

PMID: 26476469 [PubMed - indexed for MEDLINE]

Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats.

Thu, 09/08/2016 - 07:32

Estrogen therapy increases BDNF expression and improves post-stroke depression in ovariectomy-treated rats.

Exp Ther Med. 2016 Sep;12(3):1843-1848

Authors: Su Q, Cheng Y, Jin K, Cheng J, Lin Y, Lin Z, Wang L, Shao B

Abstract
The present study investigated the effect of exogenous estrogen on post-stroke depression. Rats were exposed to chronic mild stress following middle cerebral artery occlusion. The occurrence of post-stroke depression was evaluated according to the changes in preference for sucrose and performance in a forced swimming test. Estrogen therapy significantly improved these neurological symptoms, indicating that estrogen is effective in treating post-stroke depression. Increased brain-derived neurotrophic factor (BDNF) expression was reported in the hippocampus of rats that had been treated with estrogen for two weeks, suggesting that BDNF expression may be an important contributor to the improvement of post-stroke depression that is observed following estrogen therapy.

PMID: 27602095 [PubMed - as supplied by publisher]

Extracellular Superoxide Dismutase Enhances the Recruitment of Immature Neutrophils to the Liver.

Thu, 09/08/2016 - 07:32

Extracellular Superoxide Dismutase Enhances the Recruitment of Immature Neutrophils to the Liver.

Infect Immun. 2016 Sep 6;

Authors: Break TJ, Witter AR, Indramohan M, Mummert ME, Dory L, Berg RE

Abstract
Listeria monocytogenes is a gram-positive intracellular pathogen that causes spontaneous abortion in pregnant women, as well as septicemia, meningitis, and gastroenteritis, primarily in immunocompromised individuals. Although L. monocytogenes can usually be effectively treated with antibiotics, there is still around a 25% mortality rate with individuals that develop clinicial listeriosis. Neutrophils are innate immune cells required for the clearance of pathogenic organisms, including L. monocytogenes The diverse roles of neutrophils during both infectious and non-infectious inflammation have recently gained much attention. However, the impact of reactive oxygen species, and the enzymes that control their production, on neutrophil recruitment and function is not well understood. Using congenic mice with varying levels of extracellular superoxide dismutase (ecSOD) activity, we have recently shown that the presence of ecSOD decreases clearance of L. monocytogenes, while increasing the recruitment of neutrophils that are not protective in the liver. The data presented here show that ecSOD activity does not lead to a cell-intrinsic increase in neutrophil-homing potential or decrease in protection against L. monocytogenes Instead, ecSOD activity enhances the production of neutrophil-attracting factors and protects hyaluronic acid (HA) from damage. Furthermore, neutrophils from the livers of ecSOD-expressing mice have decreased intracellular and surface-bound myeloperoxidase, are less capable of killing phagocytosed L. monocytogenes, and have decreased oxidative burst. Collectively, our data reveal that ecSOD activity modulates neutrophil recruitment and function in a cell-extrinsic fashion, thus highlighting the importance of this enzyme in protecting tissues from oxidative damage.

PMID: 27600509 [PubMed - as supplied by publisher]

Sandwich type plasmonic platform for MEF using silver fractals.

Thu, 09/08/2016 - 07:32
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Sandwich type plasmonic platform for MEF using silver fractals.

Nanoscale. 2015 Nov 14;7(42):17729-34

Authors: Raut SL, Rich R, Shtoyko T, Bora I, Laursen BW, Sørensen TJ, Borejdo J, Gryczynski Z, Gryczynski I

Abstract
In this report, we describe a plasmonic platform with silver fractals for metal enhanced fluorescence (MEF) measurements. When a dye containing surface was brought into contact with silver fractals, a significantly enhanced fluorescence signal from the dye was observed. Fluorescence enhancement was studied with the N-methyl-azadioxatriangulenium chloride salt (Me-ADOTA·Cl) in PVA films made from 0.2% PVA (w/v) solution spin-coated on a clean glass coverslip. The Plasmonic Platforms (PP) were assembled by pressing together silver fractals on one glass slide and a separate glass coverslip spin-coated with a uniform Me-ADOTA·Cl in PVA film. In addition, we also tested ADOTA labeled human serum albumin (HSA) deposited on a glass slide for potential PP bioassay applications. Using the new PP, we could achieve more than a 20-fold fluorescence enhancement (bright spots) accompanied by a decrease in the fluorescence lifetime. The experimental results were used to calculate the extinction (excitation) enhancement factor (GA) and fluorescence radiative rate enhancements factor (GF). No change in emission spectrum was observed for a dye with or without contact with fractals. Our studies indicate that this type of PP can be a convenient approach for constructing assays utilizing metal enhanced fluorescence (MEF) without the need for depositing the material directly on metal structures platforms.

PMID: 26452215 [PubMed - indexed for MEDLINE]

A Cadaveric Investigation of the Dorsal Scapular Nerve.

Wed, 09/07/2016 - 07:32

A Cadaveric Investigation of the Dorsal Scapular Nerve.

Anat Res Int. 2016;2016:4106981

Authors: Nguyen VH, Liu HH, Rosales A, Reeves R

Abstract
Compression of the dorsal scapular nerve (DSN) is associated with pain in the upper extremity and back. Even though entrapment of the DSN within the middle scalene muscle is typically the primary cause of pain, it is still easily missed during diagnosis. The purpose of this study was to document the DSN's anatomy and measure the oblique course it takes with regard to the middle scalene muscle. From 20 embalmed adult cadavers, 23 DSNs were documented regarding the nerve's spinal root origin, anatomical route, and muscular innervations. A transverse plane through the laryngeal prominence was established to measure the distance of the DSN from this plane as it enters, crosses, and exits the middle scalene muscle. Approximately 70% of the DSNs originated from C5, with 74% piercing the middle scalene muscle. About 48% of the DSNs supplied the levator scapulae muscle only and 52% innervated both the levator scapulae and rhomboid muscles. The average distances from a transverse plane at the laryngeal prominence where the DSN entered, crossed, and exited the middle scalene muscle were 1.50 cm, 1.79 cm, and 2.08 cm, respectively. Our goal is to help improve clinicians' ability to locate the site of DSN entrapment so that appropriate management can be implemented.

PMID: 27597900 [PubMed]

Macrophage polarization and MRSA infection in burned mice.

Wed, 09/07/2016 - 07:32

Macrophage polarization and MRSA infection in burned mice.

Immunol Cell Biol. 2016 Sep 6;

Authors: Nishiguchi T, Ito I, Lee JO, Suzuki S, Suzuki F, Kobayashi M

Abstract
Mortality associated with Staphylococcus aureus infection remains high during the sub-acute phase of burn injury. In this study, we aimed to improve antibacterial resistance of sub-acutely burned mice through macrophage polarization. Sepsis did not develop in mice at the sub-acute phase of 5% total body surface area (TBSA) burn after being infected with methicillin-resistant S. aureus (MRSA), and M1 macrophages [IL-10(-)IL-12(+) inducible nitric oxide synthase (iNOS)(+) Mφ] were isolated from these mice. In contrast, predominantly M2b macrophages (CCL1(+)IL-10(+)IL-12(-) Mφ) were isolated from mice with>15% TBSA burn, and all of these mice died after the same MRSA infection. Comparing NOD scid gamma (NSG) mice inoculated with Mφ with 25% TBSA burns, all mice treated with C-C motif chemokine ligand 1 (CCL1) antisense oligodeoxynucleotide (ODN) survived after MRSA infection, while all untreated mice given the same infection died within 4 days. CCL1 antisense ODN has been characterized as a specific polarizer of M2bMφ. M1Mφ were isolated from MRSA-infected mice with 25% TBSA burn after treatment with CCL1 antisense ODN, and these mice were shown to be resistant against a lethal dose of MRSA infection. M1Mφ were also isolated from 25% TBSA burned mice infected with MRSA when the ODN was administered therapeutically, and subsequent sepsis was effectively controlled in these mice. These results indicate that the M2bMφ polarizer is beneficial for controlling MRSA infection in mice at the sub-acute phase of severe burn injury.Immunology and Cell Biology accepted article preview online, 06 September 2016. doi:10.1038/icb.2016.84.

PMID: 27596946 [PubMed - as supplied by publisher]

Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.

Wed, 09/07/2016 - 07:32

Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.

Am Heart J. 2016 Sep;179:1-9

Authors: Khine H, Yuet WC, Adams-Huet B, Ahmad Z

Abstract
UNLABELLED: Patients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms.
METHODS: We queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy.
RESULTS: The risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]).
CONCLUSION: Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

PMID: 27595674 [PubMed - in process]

Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats.

Wed, 09/07/2016 - 07:32
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Exposure to stimulatory CpG oligonucleotides during gestation induces maternal hypertension and excess vasoconstriction in pregnant rats.

Am J Physiol Heart Circ Physiol. 2016 Apr 15;310(8):H1015-25

Authors: Goulopoulou S, Wenceslau CF, McCarthy CG, Matsumoto T, Webb RC

Abstract
Bacterial infections increase risk for pregnancy complications, such as preeclampsia and preterm birth. Unmethylated CpG DNA sequences are present in bacterial DNA and have immunostimulatory effects. Maternal exposure to CpG DNA induces fetal demise and craniofacial malformations; however, the effects of CpG DNA on maternal cardiovascular health have not been examined. We tested the hypothesis that exposure to synthetic CpG oligonucleotides (ODNs) during gestation would increase blood pressure and cause vascular dysfunction in pregnant rats. Pregnant and nonpregnant female rats were treated with CpG ODN (ODN 2395) or saline (Veh) starting on gestational day 14or corresponding day for the nonpregnant groups. Exposure to CpG ODN increased systolic blood pressure in pregnant (Veh: 121 ± 2 mmHg vs. ODN 2395: 134 ± 2 mmHg,P< 0.05) but not in nonpregnant rats (Veh: 111 ± 2 mmHg vs. ODN 2395: 108 ± 5 mmHg,P> 0.05). Mesenteric resistance arteries from pregnant CpG ODN-treated rats had increased contractile responses to U46619 [thromboxane A2(TxA2) mimetic] compared with arteries from vehicle-treated rats [Emax(%KCl), Veh: 87 ± 4 vs. ODN 2395: 104 ± 4,P< 0.05]. Nitric oxide synthase (NOS) inhibition increased contractile responses to U46619, and CpG ODN treatment abolished this effect in arteries from pregnant ODN 2395-treated rats. CpG ODN potentiated the involvement of cyclooxygenase (COX) to U46619-induced contractions. In conclusion, exposure to CpG ODN during gestation induces maternal hypertension, augments resistance artery contraction, increases the involvement of COX-dependent mechanisms and reduces the contribution of NOS-dependent mechanisms to TxA2-induced contractions in mesenteric resistance arteries.

PMID: 26873968 [PubMed - indexed for MEDLINE]

Hispanic Subgroups, Acculturation, and Substance Abuse Treatment Outcomes.

Wed, 09/07/2016 - 07:32
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Hispanic Subgroups, Acculturation, and Substance Abuse Treatment Outcomes.

J Subst Abuse Treat. 2015 Dec;59:74-82

Authors: Chartier KG, Carmody T, Akhtar M, Stebbins MB, Walters ST, Warden D

Abstract
This study explored Hispanic subgroup differences in substance use treatment outcomes, and the relationship of acculturation characteristics to these outcomes. Data were from a multisite randomized clinical trial of motivational enhancement therapy versus treatment as usual in a sample of Spanish-speaking substance abusers. Participants were Cuban American (n=34), Mexican American (n=209), Puerto Rican (n=78), and other Hispanic American (n=54). Results suggested that Cuban Americans and individuals with more connection to Hispanic culture had lower treatment retention. Hispanics born in the U.S and those who spoke English at home had a lower percentage of days abstinent during weeks 5-16, although Puerto Ricans born in the U.S. and Cuban Americans living more years in the U.S. had a higher percentage of days abstinent in weeks 1-4 and 5-16, respectively. Results may inform future hypothesis-driven studies in larger Hispanic treatment seeking samples of the relationship between acculturation and treatment outcome.

PMID: 26362001 [PubMed - indexed for MEDLINE]

Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

Wed, 09/07/2016 - 07:32
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Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

Mol Pharm. 2015 Oct 5;12(10):3588-96

Authors: Munaweera I, Shi Y, Koneru B, Saez R, Aliev A, Di Pasqua AJ, Balkus KJ

Abstract
Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.

PMID: 26325115 [PubMed - indexed for MEDLINE]

Is motivational interviewing effective at reducing alcohol misuse in young adults? A critical review of Foxcroft et al. (2014).

Wed, 09/07/2016 - 07:32
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Is motivational interviewing effective at reducing alcohol misuse in young adults? A critical review of Foxcroft et al. (2014).

Psychol Addict Behav. 2015 Dec;29(4):836-46

Authors: Mun EY, Atkins DC, Walters ST

Abstract
Foxcroft, Coombes, Wood, Allen, and Almeida Santimano (2014) recently conducted a meta-analysis evaluating the effectiveness of motivational interviewing (MI) in reducing alcohol misuse for youth up to Age 25. They concluded that the overall effect sizes of MI in this population were too small to be clinically meaningful. The present article critically reviews the Foxcroft et al. meta-analysis, highlighting weaknesses such as problems with search strategies, flawed screening and reviews of full-text articles, incorrect data abstraction and coding, and, accordingly, improper effect size estimation. In addition, between-study heterogeneity and complex data structures were not thoughtfully considered or handled using best practices for meta-analysis. These limitations undermine the reported estimates and broad conclusion made by Foxcroft et al. about the lack of MI effectiveness for youth. We call for new evidence on this question from better-executed studies by independent researchers. Meta-analysis has many important utilities for translational research. When implemented well, the overall effectiveness, as well as different effectiveness for different populations, can be examined via meta-analysis. Emerging methods utilizing individual participant-level data, such as integrative data analysis, may be particularly helpful for identifying the sources of clinical and methodological heterogeneity that matter. The need to better understand the mechanisms of alcohol interventions has never been louder in the addiction field. Through more concerted efforts throughout all phases of generating evidence, we may achieve large-scale evidence that is efficient and robust and provides critical answers for the field.

PMID: 26237287 [PubMed - indexed for MEDLINE]

Effectiveness of a Screening and Brief Intervention protocol for heavy drinkers in dental practice: A cluster-randomized trial.

Wed, 09/07/2016 - 07:32
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Effectiveness of a Screening and Brief Intervention protocol for heavy drinkers in dental practice: A cluster-randomized trial.

J Health Psychol. 2015 Dec;20(12):1534-48

Authors: Neff JA, Kelley ML, Walters ST, Cunningham TD, Paulson JF, Braitman AL, Brickhouse TH, Gunsolley JC, Darby ML, Lemaster MF, Vandersluis JP, Walsh MM, Bolen H

Abstract
Results of a cluster-randomized trial of a Screening and Brief Intervention for heavy drinkers in dental practice are reported. Data were obtained from 103 heavy drinking patients recruited from randomized intervention (7; n = 50) and control (6; n = 53) practices. Analysis of data revealed that 6-month decreases in total drinks per week were significantly (p < .05) greater for heavy drinking intervention (43%) than control patients (21%)-a 4 drink per week difference. Similar decreases were obtained for quantity and frequency among intervention patients compared to control patients. Despite power limitations, the 6-month results support the effectiveness of the Screening and Brief Intervention.

PMID: 24423575 [PubMed - indexed for MEDLINE]

Barriers in detecting elder abuse among emergency medical technicians.

Sun, 09/04/2016 - 07:35

Barriers in detecting elder abuse among emergency medical technicians.

BMC Emerg Med. 2016;16(1):36

Authors: Reingle Gonzalez JM, Cannell MB, Jetelina KK, Radpour S

Abstract
BACKGROUND: Elder abuse and neglect are highly under-reported in the United States. This may be partially attributed to low incidence of reporting among emergency medical technicians' (EMTs), despite state-mandated reporting of suspected elder abuse. Innovative solutions are needed to address under-reporting. The objective was to describe EMTs' experience detecting and reporting elder abuse.
METHODS: Qualitative data were collected from 11 EMTs and 12 Adult Protective Services (APS) caseworkers that participated in one of five semi-structured focus groups. Focus group data were iteratively coded by two coders.
RESULTS: Findings suggest a number of barriers prevent EMTs from reporting elder abuse to APS. Participants suggested that limited training on elder abuse detection or reporting has been provided to them. EMTs suggested that training, creation of an automated reporting system or brief screening tool could be used to enhance EMT's ability to detect and communicate suspected cases of elder abuse to APS.
CONCLUSIONS: Results from the present study suggest that EMTs may be uniquely situated to serve as elder abuse and neglect surveillance personnel. EMTs are eager to work with APS to address the under-reporting of elder abuse and neglect, but training is minimal and current reporting procedures are time-prohibitive given their primary role as emergency healthcare providers. Future studies should seek to translate these findings into practice by identifying specific indicators predictive of elder abuse and neglect for inclusion on an automated reporting instrument for EMTs.

PMID: 27590310 [PubMed - as supplied by publisher]

MIEN1 is tightly regulated by SINE Alu methylation in its promoter.

Sat, 09/03/2016 - 07:33

MIEN1 is tightly regulated by SINE Alu methylation in its promoter.

Oncotarget. 2016 Aug 29;

Authors: Rajendiran S, Gibbs LD, Van Treuren T, Klinkebiel DL, Vishwanatha JK

Abstract
Migration and invasion enhancer 1 (MIEN1) is a novel gene involved in prostate cancer progression by enhancing prostate cancer cell migration and invasion. DNA methylation, an important epigenetic regulation, is one of the most widely altered mechanisms in prostate cancer. This phenomenon frames the basis to study the DNA methylation patterns in the promoter region of MIEN1. Bisulfite pyrosequencing demonstrates the MIEN1 promoter contains a short interspersed nuclear Alu element (SINE Alu) repeat sequence. Validation of methylation inhibition on MIEN1 was performed using nucleoside analogs and non-nucleoside inhibitors and resulted in an increase in both MIEN1 RNA and protein in normal cells. MIEN1 mRNA and protein increases upon inhibition of individual DNA methyltransferases using RNA interference technologies. Furthermore, dual luciferase reporter assays, in silico analysis, and chromatin immunoprecipitation assays identified a sequence upstream of the transcription start site that has a site for binding of the USF transcription factors. These results suggest the MIEN1 promoter has a SINE Alu region that is hypermethylated in normal cells leading to repression of the gene. In cancer, the hypomethylation of a part of this repeat, in addition to the binding of USF, results in MIEN1 expression.

PMID: 27589566 [PubMed - as supplied by publisher]

The Effects of Traditional Chinese Exercise in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

Sat, 09/03/2016 - 07:33

The Effects of Traditional Chinese Exercise in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

PLoS One. 2016;11(9):e0161564

Authors: Luo X, Zhang J, Castelberg R, Wu T, Yu P, He C, Wang P

Abstract
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide. However, several studies that have assessed the role of traditional Chinese exercise in the management of this disease include broad variations in sample sizes and results. Therefore, this meta-analysis was conducted to assess the effects of traditional Chinese exercise on patients with COPD.
METHODS: Two investigators independently identified and extracted data from selected articles. A computerized search of electronic databases through August 2015 was conducted. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated to analyze the combined data. The methodological quality was evaluated using the Cochrane risk-of-bias tool. Heterogeneity was assessed with the I2 test.
RESULTS: Ten randomized, controlled trials (RCTs) involving 622 patients met the inclusion criteria. There were significant improvements in the 6-minute walking distance test (6 MWD;MWD = 12.10 m; 95% CI, 7.56-16.65 m; p<0.001); forced expiratory volume in one second (FEV1% predicted; WMD = 9.02; 95% CI, 6.80-11.23; p<0.00001); forced expiratory volume in 1 second/forced vital capacity (FEV(1)/FVC) ratio (Tiffenau Index; WMD = 6.67; 95% CI, 5.09-8.24; p<0.00001); and quality of life, as evaluated by the Chronic Respiratory Disease Questionnaire (CRDQ; WMD = 0.85 score; 95% CI, 0.52-1.18; p<0.00001).
CONCLUSIONS: Traditional Chinese exercise could provide an effective alternative method for managing COPD. Larger and higher-quality trials are required.

PMID: 27589054 [PubMed - as supplied by publisher]

Mechanisms by Which 17β-Estradiol (E2) Suppress Neuronal cox-2 Gene Expression.

Sat, 09/03/2016 - 07:33

Mechanisms by Which 17β-Estradiol (E2) Suppress Neuronal cox-2 Gene Expression.

PLoS One. 2016;11(9):e0161430

Authors: Stacey W, Bhave S, Uht RM

Abstract
E2 attenuates inflammatory responses by suppressing expression of pro-inflammatory genes. Given that inflammation is increasingly being associated with neurodegenerative and psychiatric processes, we sought to elucidate mechanisms by which E2 down-regulates a component of an inflammatory response, cyclooxygenase- 2 (COX-2) expression. Although inflammatory processes in the brain are usually associated with microglia and astrocytes, we found that the COX-2 gene (cox-2) was expressed in a neuronal context, specifically in an amygdalar cell line (AR-5). Given that COX-2 has been reported to be in neurons in the brain, and that the amygdala is a site involved in neurodegenerative and neuropsychiatric processes, we investigated mechanisms by which E2 could down-regulate cox-2 expression in the AR-5 line. These cells express estrogen receptors alpha (ERα) and beta (ERβ), and as shown here cox-2. At the level of RNA, E2 and the ERβ selective ligand diarylpropionitrile (DPN) both attenuated gene expression, whereas the ERα selective ligand propyl pyrazole triol (PPT) had no effect. Neither ligand increased ERβ at the cox-2 promoter. Rather, DPN decreased promoter occupancy of NF-κB p65 and histone 4 (H4) acetylation. Treatment with the non-specific HDAC inhibitor Trichostatin A (TSA) counteracted DPN's repressive effects on cox-2 expression. In keeping with the TSA effect, E2 and DPN increased histone deacetylase one (HDAC1) and switch-independent 3A (Sin3A) promoter occupancy. Lastly, even though E2 increased CpG methylation, DPN did not. Taken together, the pharmacological data indicate that ERβ contributes to neuronal cox-2 expression, as measured by RNA levels. Furthermore, ER ligands lead to increased recruitment of HDAC1, Sin3A and a concomitant reduction of p65 occupancy and Ac-H4 levels. None of the events, however, are associated with a significant recruitment of ERβ at the promoter. Thus, ERβ directs recruitment to the cox-2 promoter, but does so in the absence of being recruited itself.

PMID: 27588681 [PubMed - as supplied by publisher]

Predictors of Recall Error in Self-Report of Age at Alcohol Use Onset.

Sat, 09/03/2016 - 07:33

Predictors of Recall Error in Self-Report of Age at Alcohol Use Onset.

J Stud Alcohol Drugs. 2016 Sep;77(5):811-818

Authors: Livingston MD, Xu X, Komro KA

Abstract
OBJECTIVE: The present study examined factors associated with recall error in the measurement of alcohol use onset and whether there was a tendency toward earlier or later self-reported age at alcohol use onset.
METHOD: This study estimated the effect of predictors on the presence and direction of recall error for age at alcohol use onset. The sample (n = 1,044) was from an existing longitudinal alcohol prevention trial in urban Chicago. Estimates were derived from a series of logistic regression models comparing agreement between a retrospective and a prospective measure of age at alcohol use onset.
RESULTS: Eligibility for free or reduced-price lunch in 6th grade, alcohol use in 6th grade, cigarette use in 12th grade, and alcohol use in 12th grade were significantly associated with recall error of age at alcohol use onset. Self-reported substance use (alcohol and tobacco) in 12th grade was also found to predict a later self-reported age at alcohol use onset when recalled.
CONCLUSIONS: Those most at risk for the negative outcomes associated with early alcohol initiation are also those most likely to misreport their age at alcohol use onset.

PMID: 27588540 [PubMed - as supplied by publisher]

Similarities in the Etiology of Alcohol Use Among Native American and Non-Native Young Women.

Sat, 09/03/2016 - 07:33

Similarities in the Etiology of Alcohol Use Among Native American and Non-Native Young Women.

J Stud Alcohol Drugs. 2016 Sep;77(5):782-791

Authors: Komro KA, Livingston MD, Garrett BA, Boyd ML

Abstract
OBJECTIVE: This study examined social-and individual-level factors associated with alcohol use among young women and tested whether differences exist between Native American and non-Native young women.
METHOD: School-based surveys were conducted among 952 young women (ages 14-19) attending four high schools within the tribal jurisdictional service area of the Cherokee Nation in northeastern Oklahoma. Structural equation modeling using Mplus was used to assess the direct and indirect effects of social-and individual-level factors on subsequent alcohol use among Native and non-Native young women.
RESULTS: We found no differences in the level of risk and protective factors among Native and non-Native young women. Among Native and non-Native young women, alcohol access, parental communication, and best friends' alcohol use had statistically significant direct and/or indirect effects on alcohol use. Indirect effects were mediated through alcohol expectancies and norms. A history of alcohol problems by an adult in the household and depression were not retained as independent risk factors in either model.
CONCLUSIONS: We found more similarities than differences in level of and relations to alcohol use among social and individual risk and protective factors between Native American and non-Native young women from northeastern Oklahoma. The results provide support for universal prevention strategies, suggesting the importance of increasing perceptions that it is difficult to obtain alcohol and increasing parent-child communication.

PMID: 27588537 [PubMed - as supplied by publisher]

Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Sat, 09/03/2016 - 07:33

Bcl-2, Bcl-xL, and p-AKT are involved in neuroprotective effects of transcription factor Brn3b in an ocular hypertension rat model of glaucoma.

Mol Vis. 2016;22:1048-61

Authors: Phatak NR, Stankowska DL, Krishnamoorthy RR

Abstract
PURPOSE: Brn3b is a class IV POU domain transcription factor that plays an important role in the development of retinal ganglion cells (RGCs), RGC survival, and particularly axon growth and pathfinding. Our previous study demonstrated that recombinant adenoassociated virus serotype 2 (rAAV-2)-mediated overexpression of Brn3b in RGCs promoted neuroprotection in a rodent model of glaucoma. However, the mechanisms underlying neuroprotection of RGCs in rats overexpressing Brn3b in animal models of glaucoma remain largely unknown. The goal of this study was to understand some of the mechanisms underlying the neuroprotection of RGCs overexpressing Brn3b during intraocular pressure (IOP) elevation in Brown Norway rats.
METHODS: One eye of Brown Norway rats (Rattus norvegicus) was injected with an AAV construct encoding either green fluorescent protein (GFP; recombinant adenoassociated virus-green fluorescent protein, rAAV-hSyn-GFP) or Brn3b (rAAV-hSyn-Brn3b). Expression of antiapoptotic proteins, including B cell lymphoma/leukemia-2 (Bcl-2) family proteins (Bcl-2 and Bcl-xL), and p-AKT, was observed following immunostaining of rat retinas that overexpress Brn3b. In a different set of experiments, intraocular pressure was elevated in one eye of Brown Norway rats, which was followed by intravitreal injection with AAV constructs encoding either GFP (rAAV-CMV-GFP) or Brn3b (rAAV-CMV-Brn3b). Retinal sections were stained for prosurvival factors, including Bcl-2, Bcl-XL, and p-AKT.
RESULTS: AAV-mediated expression of transcription factor Brn3b promoted statistically significant upregulation of the Bcl-2 protein and increased expression of p-AKT in RGCs of Brown Norway rats. In addition, following IOP elevation, AAV-mediated Brn3b expression also statistically significantly increased levels of Bcl-2 in the RGC layer in Brown Norway rats.
CONCLUSIONS: Adenoassociated virus-mediated Brn3b protein overexpression may promote neuroprotection by upregulating key antiapoptotic proteins, including Bcl-2, Bcl-xL, and p-AKT, in animal models of glaucoma.

PMID: 27587945 [PubMed - in process]

A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture.

Sat, 09/03/2016 - 07:33
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A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture.

Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):1939-50

Authors: Zadoo S, Nguyen A, Zode G, Hulleman JD

Abstract
PURPOSE: Primary open angle glaucoma-associated mutations in myocilin (MYOC) cause protein "nonsecretion," rendering secreted MYOC difficult to detect using conventional techniques. This study focused on developing and using an assay that can quickly and easily detect mutant MYOC secretion.
METHODS: We fused Gaussia luciferase (eGLuc2) to MYOC variants and expressed the constructs in HEK-293T and NTM-5 cells. Secreted and intracellular levels of MYOC eGLuc2 variants were evaluated by Western blotting and compared to untagged and FLAG-tagged MYOC constructs. Secreted and soluble intracellular MYOC eGLuc2 were measured by a GLuc assay. The secretion of nine additional MYOC mutants was assayed in conditioned media from transfected cells to test the applicability of the assay for monitoring other MYOC variants.
RESULTS: Myocilin eGLuc2 behaved similarly to untagged and FLAG-tagged MYOC with respect to secretion, soluble intracellular levels, and in response to drug treatment. The GLuc assay could sensitively detect Y437H MYOC secretion 30 minutes after media change. Gaussia luciferase fused variants followed anticipated trends; nonpathogenic variants (D208E, G244V) were secreted at wild-type (WT) levels, whereas predicted disease-causing variants (C245Y, G246R, E300K, Y437H, I477N) demonstrated substantial secretion defects. Secretion defects caused by the C245Y, G246R, and Y437H mutations were partially rescued by permissive growth temperature. Interestingly, however, this increase in secretion was independent of newly synthesized protein.
CONCLUSIONS: Fusion of eGLuc2 to MYOC does not significantly change the behavior of MYOC. This newly developed MYOC reporter system can be used to study engineered MYOC variants and potentially to identify modulators of MYOC secretion and function.

PMID: 27092720 [PubMed - indexed for MEDLINE]

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