Recent Research Articles from UNTHSC

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

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Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Fri, 12/16/2016 - 07:32
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Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

Alzheimers Dement. 2016 Mar;12(3):292-323

Authors: Dubois B, Hampel H, Feldman HH, Scheltens P, Aisen P, Andrieu S, Bakardjian H, Benali H, Bertram L, Blennow K, Broich K, Cavedo E, Crutch S, Dartigues JF, Duyckaerts C, Epelbaum S, Frisoni GB, Gauthier S, Genthon R, Gouw AA, Habert MO, Holtzman DM, Kivipelto M, Lista S, Molinuevo JL, O'Bryant SE, Rabinovici GD, Rowe C, Salloway S, Schneider LS, Sperling R, Teichmann M, Carrillo MC, Cummings J, Jack CR, Proceedings of the Meeting of the International Working Group (IWG) and the American Alzheimer's Association on “The Preclinical State of AD”; July 23, 2015; Washington DC, USA

Abstract
During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations.

PMID: 27012484 [PubMed - indexed for MEDLINE]

TCT-204 Optimal duration of dual antiplatelet therapy (DAPT) after second generation drug-eluting stent (DES) implantation in elderly patients: the SECURITY-ELDERLY substudy.

Thu, 12/15/2016 - 07:32
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TCT-204 Optimal duration of dual antiplatelet therapy (DAPT) after second generation drug-eluting stent (DES) implantation in elderly patients: the SECURITY-ELDERLY substudy.

J Am Coll Cardiol. 2016 Nov 01;68(18S):B83

Authors: Ferri LA, Chieffo A, Giustino G, Frasheri A, Garbo R, Masotti-Centol M, Salvatella N, Oteo Dominguez JF, Steffanon L, Tarantini G, Presbitero P, Menozzi A, Pucci E, Mauri J, Sardella G, Colombo A

PMID: 27970378 [PubMed - in process]

Soluble Lectin-like Oxidized Low Density Lipoprotein Receptor-1 as A Novel Biomarker for Large-artery Atherosclerotic Stroke.

Thu, 12/15/2016 - 07:32
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Soluble Lectin-like Oxidized Low Density Lipoprotein Receptor-1 as A Novel Biomarker for Large-artery Atherosclerotic Stroke.

Int J Neurosci. 2016 Dec 14;:1-19

Authors: Huang W, Li Q, Chen X, Lin Y, Xue J, Cai Z, Zhang W, Wang H, Jin K, Shao B

Abstract
Background-Serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown associated with the progression of atherosclerosis in endothelial cells. We sought to assess whether the baseline serum sLOX-1 levels are correlated with the presence and short term functional outcome of large-artery atherosclerotic (LAA) stroke. Methods-The study recruited 241 subjects, including 148 consecutive patients with acute ischemic stroke with the subtype of LAA and 93 non-stroke controls. Clinical and laboratory data, including serum concentration of sLOX-1 were collected within 24h of admission, and the severity of LAA stroke patients was evaluated by National Institutes of Health Stroke Scale (NIHSS) score. And functional outcome was assessed by modified Rankin Scale (mRS) 3 months after stroke. The association between sLOX-1 level and the functional outcome at 3 months was analyzed by multiple logistic regression models. Results-Serum levels of sLOX-1 in the LAA stroke patients were significantly higher as compared to normal controls (2.48 ± 0.93 ng/ml vs. 2.22 ± 0.79 ng/ml in the controls, t = 2.301, p = 0.022). The levels of serum sLOX-1 in patients with good outcome were significantly lower than those with poor outcome (2.39 ± 0.94ng/ml vs. 2.77 ± 0.84 ng/ml, p = 0.032). After adjusting for potential confounders, sLOX-1 was still an independent predictor for the function outcome with an adjusted OR of 3.39 (95% CI, 1.61-7.11, p = 0.001). Conclusions-The serum sLOX-1 level was higher in patients with LAA stroke, and it was an independent predictor of functional outcome in patients with LAA ischemic stroke.

PMID: 27967338 [PubMed - as supplied by publisher]

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability.

Thu, 12/15/2016 - 07:32
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Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability.

Int J Nanomedicine. 2016;11:1451-60

Authors: Guo S, Pham K, Li D, Penzak SR, Dong X

Abstract
PURPOSE: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability.
MATERIALS AND METHODS: In one method, we prepared ritonavir (RTV) nanoparticles (NPs) by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs). We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules.
RESULTS: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability over 2.5-fold compared to RTV solution.
CONCLUSION: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development.

PMID: 27103803 [PubMed - indexed for MEDLINE]

Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers.

Thu, 12/15/2016 - 07:32
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Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers.

Molecules. 2016 Mar 29;21(4):428

Authors: Enciso AE, Neun B, Rodriguez J, Ranjan AP, Dobrovolskaia MA, Simanek EE

Abstract
Triazine and PAMAM dendrimers of similar size and number of cationic surface groups were compared for their ability to promote platelet aggregation. Triazine dendrimers (G3, G5 and G7) varied in molecular weight from 8 kDa-130 kDa and in surface groups 16-256. PAMAM dendrimers selected for comparison included G3 (7 kDa, 32 surface groups) and G6 (58 kDa, 256 surface groups). The treatment of human platelet-rich plasma (PRP) with low generation triazine dendrimers (0.01-1 µM) did not show any significant effect in human platelet aggregation in vitro; however, the treatment of PRP with larger generations promotes an effective aggregation. These results are in agreement with studies performed with PAMAM dendrimers, where large generations promote aggregation. Triazine dendrimers promote aggregation less aggressively than PAMAM dendrimers, a factor attributed to differences in cationic charge or the formation of supramolecular assemblies of dendrimers.

PMID: 27043508 [PubMed - indexed for MEDLINE]

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

Thu, 12/15/2016 - 07:32
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Restoring lumbar spine stiffness using an interspinous implant in an ovine model of instability.

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

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

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

PMID: 26963708 [PubMed - indexed for MEDLINE]

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

Thu, 12/15/2016 - 07:32
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Level of Immersion in Virtual Environments Impacts the Ability to Assess and Teach Social Skills in Autism Spectrum Disorder.

Cyberpsychol Behav Soc Netw. 2016 Apr;19(4):246-56

Authors: Miller HL, Bugnariu NL

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

PMID: 26919157 [PubMed - indexed for MEDLINE]

Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy.

Thu, 12/15/2016 - 07:32
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Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy.

Nanomedicine (Lond). 2016;11(5):479-94

Authors: Kokate RA, Chaudhary P, Sun X, Thamake SI, Maji S, Chib R, Vishwanatha JK, Jones HP

Abstract
BACKGROUND: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy.
MATERIALS & METHODS: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy.
RESULTS: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses.
CONCLUSION: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

PMID: 26892440 [PubMed - indexed for MEDLINE]

Alcohol mixed with energy drink: Use may be a consequence of heavy drinking.

Thu, 12/15/2016 - 07:32
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Alcohol mixed with energy drink: Use may be a consequence of heavy drinking.

Addict Behav. 2016 Jun;57:55-61

Authors: Rossheim ME, Thombs DL, Weiler RM, Barry AE, Suzuki S, Walters ST, Barnett TE, Paxton RJ, Pealer LN, Cannell B

Abstract
AIMS: In recent years, studies have indicated that consumers of alcohol mixed with energy drink (AmED) are more likely to drink heavily and experience more negative consequences than consumers who avoid these beverages. Although researchers have identified a number of plausible hypotheses that explain how alcohol-energy drink co-ingestion could cause greater alcohol consumption, there has been no postulation about reverse causal relations. This paper identifies several plausible hypotheses for the observed associations between AmED consumption and greater alcohol consumption, and provides initial evidence for one such hypothesis suggesting that heavy drinking may be a determinant of AmED use.
METHOD: Data collected from 511bar patrons were used to examine the plausibility of one of the proposed hypotheses, i.e., AmED is an artifact of heavy drinking. Associations between the consumption of an assortment of alcoholic beverage types and total alcohol consumption were examined at the event-level, to assess whether AmED is uniquely related with greater alcohol consumption.
RESULTS: Increased alcohol consumption was associated with greater odds of consuming most alcoholic beverage types; this association was not unique to AmED.
CONCLUSIONS: Results support the overlooked hypothesis that AmED use is an artifact of heavy drinking. Thus, AmED consumption may be a consequence or marker of heavier drinking. Much of the existing research on alcoholic beverage types is limited in its ability to implicate any specific type of drink, including AmED, as a cause of increased alcohol consumption and related harm. More rigorous study designs are needed to examine causal relationships.

PMID: 26890245 [PubMed - indexed for MEDLINE]

Ictal Coprolalia: A Case Report and Review of Ictal Speech as a Localizing Feature in Epilepsy.

Thu, 12/15/2016 - 07:32
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Ictal Coprolalia: A Case Report and Review of Ictal Speech as a Localizing Feature in Epilepsy.

Pediatr Neurol. 2016 Apr;57:88-90

Authors: Daniel C, Perry MS

Abstract
BACKGROUND: Recognizing ictal semiology is an essential component to localization of seizure onset, especially in intractable epilepsy where surgical therapies may be beneficial. Ictal speech can be a common component of seizure semiology, but the various forms of ictal speech may have different lateralizing and localizing value. Coprolalia is a very rare form of ictal speech.
METHODS: We present a 15 year old with medically intractable seizures characterized by agitation and coprolalia.
RESULTS: The patient underwent surgical evaluation including video EEG, MRI, and functional neuroimaging. These studies indicated onset within the dominant frontal lobe which was further localized using stereo-electroencephalography prior to focal cortical resection.
CONCLUSIONS: Ictal coprolalia is a rare presentation of ictal speech. We review the various forms of ictal speech and their value in localizing seizure onset.

PMID: 26880529 [PubMed - indexed for MEDLINE]

Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors.

Thu, 12/15/2016 - 07:32
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Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors.

Eur J Pharmacol. 2016 Mar 15;775:149-58

Authors: Kumar M, Dillon GH

Abstract
Meprobamate is a schedule IV anxiolytic and the primary metabolite of the muscle relaxant carisoprodol. Meprobamate modulates GABAA (γ-aminobutyric acid Type A) receptors, and has barbiturate-like activity. To gain insight into its actions, we have conducted a series of studies using recombinant GABAA receptors. In αxβzγ2 GABAA receptors (where x=1-6 and z=1-3), the ability to enhance GABA-mediated current was evident for all α subunit isoforms, with the largest effect observed in α5-expressing receptors. Direct gating was present with all α subunits, although attenuated in α3-expressing receptors. Allosteric and direct effects were comparable in α1β1γ2 and α1β2γ2 receptors, whereas allosteric effects were enhanced in α1β2 compared to α1β2γ2 receptors. In "extrasynaptic" (α1β3δ and α4β3δ) receptors, meprobamate enhanced EC20 and saturating GABA currents, and directly activated these receptors. The barbiturate antagonist bemegride attenuated direct effects of meprobamate. Whereas pentobarbital directly gated homomeric β3 receptors, meprobamate did not, and instead blocked the spontaneously open current present in these receptors. In wild type homomeric ρ1 receptors, pentobarbital and meprobamate were ineffective in direct gating; a mutation known to confer sensitivity to pentobarbital did not confer sensitivity to meprobamate. Our results provide insight into the actions of meprobamate and parent therapeutic agents such as carisoprodol. Whereas in general actions of meprobamate were comparable to those of carisoprodol, differential effects of meprobamate at some receptor subtypes suggest potential advantages of meprobamate may be exploited. A re-assessment of previously synthesized meprobamate-related carbamate molecules for myorelaxant and other therapeutic indications is warranted.

PMID: 26872987 [PubMed - indexed for MEDLINE]

Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

Thu, 12/15/2016 - 07:32
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Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles.

J Control Release. 2016 Mar 28;226:88-97

Authors: Pham K, Li D, Guo S, Penzak S, Dong X

Abstract
The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self-assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56-fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra®) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs.

PMID: 26849919 [PubMed - indexed for MEDLINE]

Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

Thu, 12/15/2016 - 07:32
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Comparison of antioxidant and antiproliferative activity between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and fraction PII separated by column chromatography.

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:169-77

Authors: Jing S, Chai W, Guo G, Zhang X, Dai J, Yan LJ

Abstract
The aim of the present study was to compare the antioxidant and antiproliferative effects on cancer cells between Kunlun Chrysanthemum flowers polysaccharides (KCCP) and its fraction PII that were separated by Biologic low pressure (LP) chromatography system followed by DEAE cellulose column chromatography. Results of in vitro experiments showed that the reducing power and the scavenging capacity of KCCP towards hydroxyl radicals (OH) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals increased in a concentration dependent manner and were stronger than that of fraction PII. Results of the antiproliferative effect of KCCP and fraction PII on cervical cancer HeLa cells, esophagus cancer Eca109 cells, and mouse ascites hepatomas H22 cells indicated that both KCCP and its fraction PII possessed inhibitory activity on all the tested cancer cells at a dose- and time-dependent manner, with KCCP showing higher inhibitory activity than that of fraction PII. The present study demonstrates that KCCP and its fraction PII have antioxidant properties that may help fight cancers.

PMID: 26809376 [PubMed - indexed for MEDLINE]

Flocculation-Related Gene Identification by Whole-Genome Sequencing of Thauera aminoaromatica MZ1T Floc-Defective Mutants.

Thu, 12/15/2016 - 07:32
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Flocculation-Related Gene Identification by Whole-Genome Sequencing of Thauera aminoaromatica MZ1T Floc-Defective Mutants.

Appl Environ Microbiol. 2015 Dec 28;82(6):1646-52

Authors: Prombutara P, Allen MS

Abstract
Thauera aminoaromatica MZ1T, a floc-forming bacterium isolated from an industrial activated-sludge wastewater treatment plant, overproduces exopolysaccharide (EPS), leading to viscous bulking. This phenomenon results in poor sludge settling and dewatering during the clarification process. To identify genes responsible for bacterial flocculation, a whole-genome phenotypic-sequencing technique was applied. Genomic DNA of MZ1T flocculation-deficient mutants was subjected to massively parallel sequencing. The resultant high-quality reads were assembled and compared to the reference genome of the wild type (WT). We identified nine nonsynonymous mutations and one nonsense mutation putatively involved in EPS biosynthesis. Complementation of the nonsense mutation located in an EPS deacetylase gene restored the flocculating phenotype. The Fourier transform infrared (FTIR) spectra of EPS isolated from the wild type showed a reduced C=O peak of the N-acetyl group at 1,665 cm(-1) compared to the spectra of MZ1T floc-deficient mutant EPS, suggesting that the WT EPS was partially deacetylated. Gene expression analysis also demonstrated that the putative deacetylase gene transcript increased before flocculation occurred. These data suggest that targeting deacetylation processes via direct chemical modification of EPS or enzyme inhibition may prove useful in combating viscous bulking in this and related bacteria.

PMID: 26712552 [PubMed - indexed for MEDLINE]

Maryland Alcohol Sales Tax and Sexually Transmitted Infections: A Natural Experiment.

Thu, 12/15/2016 - 07:32
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Maryland Alcohol Sales Tax and Sexually Transmitted Infections: A Natural Experiment.

Am J Prev Med. 2016 Mar;50(3):e73-80

Authors: Staras SA, Livingston MD, Wagenaar AC

Abstract
INTRODUCTION: Sexually transmitted infections are common causes of morbidity and mortality, including infertility and certain types of cancer. Alcohol tax increases may decrease sexually transmitted infection rates overall and differentially across population subgroups by decreasing alcohol consumption in general and prior to sex, thus decreasing sexual risk taking and sexually transmitted infection acquisition. This study investigated the effects of a Maryland increase in alcohol beverage sales tax on statewide gonorrhea and chlamydia rates overall and within age, gender, and race/ethnicity subpopulations.
METHODS: This study used an interrupted time series design, including multiple cross-state comparisons, to examine the effects of the 2011 alcohol tax increase in Maryland on chlamydia and gonorrhea cases reported to the U.S. National Notifiable Disease Surveillance System for January 2003 to December 2012 (N=120 repeated monthly observations, analyzed in 2015). Effects were assessed with Box-Jenkins autoregressive moving average models with structural parameters.
RESULTS: After the alcohol-specific sales tax increase, gonorrhea rates decreased 24% (95% CI=11%, 37%), resulting in 1,600 fewer statewide gonorrhea cases annually. Cohen's d indicated a substantial effect of the tax increase on gonorrhea rates (range across control group models, -1.25 to -1.42). The study did not find evidence of an effect on chlamydia or differential effects across age, race/ethnicity, or gender subgroups.
CONCLUSIONS: Results strengthen the evidence from prior studies of alcohol taxes influencing gonorrhea rates and extend health prevention effects from alcohol excise to sales taxes. Alcohol tax increases may be an efficient strategy for reducing sexually transmitted infections.

PMID: 26683415 [PubMed - indexed for MEDLINE]

World military expenditures and global cardiovascular mortality.

Thu, 12/15/2016 - 07:32
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World military expenditures and global cardiovascular mortality.

J Public Health Policy. 2016 Feb;37(1):20-35

Authors: Brenner MH

Abstract
Can we estimate the consequences of world military expenditures for the physical and mental health of nations that produce and purchase armaments? If anxiety and fear are promoting military expenditures, then those sentiments may well reflect poorer mental health and war-related stress as it influences cardiovascular illness rates. Further, extensive military expenditure by a society implies that other societal needs are allocated fewer resources, including nutrition, water and sanitation, health care, and economic development. We use a model focused on military expenditures to predict cardiovascular mortality in world samples of industrialized and developing countries over 2000-2011. The cardiovascular mortality model controls for economic development, smoking, body mass index, systolic blood pressure, and carbon dioxide emissions. Military expenditures as proportion of gross domestic product show significant positive relations to cardiovascular disease mortality in linear multiple regression analyses, using both cross-sectional and pooled cross-sectional time-series approaches.

PMID: 26675148 [PubMed - indexed for MEDLINE]

Combination of tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species.

Thu, 12/15/2016 - 07:32
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Combination of tolfenamic acid and curcumin induces colon cancer cell growth inhibition through modulating specific transcription factors and reactive oxygen species.

Oncotarget. 2016 Jan 19;7(3):3186-200

Authors: Sankpal UT, Nagaraju GP, Gottipolu SR, Hurtado M, Jordan CG, Simecka JW, Shoji M, El-Rayes B, Basha R

Abstract
Curcumin (Cur) has been extensively studied in several types of malignancies including colorectal cancer (CRC); however its clinical application is greatly affected by low bioavailability. Several strategies to improve the therapeutic response of Cur are being pursued, including its combination with small molecules and drugs. We investigated the therapeutic efficacy of Cur in combination with the small molecule tolfenamic acid (TA) in CRC cell lines. TA has been shown to inhibit the growth of human cancer cells in vitro and in vivo, via targeting the transcription factor specificity protein1 (Sp1) and suppressing survivin expression. CRC cell lines HCT116 and HT29 were treated with TA and/or Cur and cell viability was measured 24-72 hours post-treatment. While both agents caused a steady reduction in cell viability, following a clear dose/ time-dependent response, the combination of TA+Cur showed higher growth inhibition when compared to either single agent. Effects on apoptosis were determined using flow cytometry (JC-1 staining to measure mitochondrial membrane potential), Western blot analysis (c-PARP expression) and caspase 3/7 activity. Reactive oxygen species (ROS) levels were measured by flow cytometry and the translocation of NF-kB into the nucleus was determined using immunofluorescence. Results showed that apoptotic markers and ROS activity were significantly upregulated following combination treatment, when compared to the individual agents. This was accompanied by decreased expression of Sp1, survivin and NF-kB translocation. The combination of TA+Cur was more effective in HCT116 cells than HT29 cells. These results demonstrate that TA may enhance the anti-proliferative efficacy of Cur in CRC cells.

PMID: 26672603 [PubMed - indexed for MEDLINE]

Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats.

Thu, 12/15/2016 - 07:32
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Exercise-Mediated Increase in Nigral Tyrosine Hydroxylase Is Accompanied by Increased Nigral GFR-α1 and EAAC1 Expression in Aging Rats.

ACS Chem Neurosci. 2016 Feb 17;7(2):227-39

Authors: Arnold JC, Salvatore MF

Abstract
Exercise may alleviate locomotor impairment in Parkinson's disease (PD) or aging. Identifying molecular responses immediately engaged by exercise in the nigrostriatal pathway and allied tissue may reveal critical targets associated with its long-term benefits. In aging, there is loss of tyrosine hydroxylase (TH) and the glial cell line-derived neurotrophic factor (GDNF) receptor, GFR-α1, in the substantia nigra (SN). Exercise can increase GDNF expression, but its effect on GFR-α1 expression is unknown. Infusion of GDNF into striatum or GFR-α1 in SN, respectively, can increase locomotor activity and TH function in SN but not striatum in aged rats. GDNF may also increase glutamate transporter expression, which attenuates TH loss in PD models. We utilized a footshock-free treadmill exercise regimen to determine the immediate impact of short-term exercise on GFR-α1 expression, dopamine regulation, glutamate transporter expression, and glutamate uptake in 18 month old male Brown-Norway/Fischer 344 F1 hybrid rats. GFR-α1 and TH expression significantly increased in SN but not striatum. This exercise regimen did not affect glutamate uptake or glutamate transporter expression in striatum. However, EAAC1 expression increased in SN. These results indicate that nigral GFR-α1 and EAAC1 expression increased in conjunction with increased nigral TH expression following short-term exercise.

PMID: 26599339 [PubMed - indexed for MEDLINE]

Two-dimensional gel electrophoretic detection of protein carbonyls derivatized with biotin-hydrazide.

Thu, 12/15/2016 - 07:32
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Two-dimensional gel electrophoretic detection of protein carbonyls derivatized with biotin-hydrazide.

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Apr 15;1019:128-31

Authors: Wu J, Luo X, Jing S, Yan LJ

Abstract
Protein carbonyls are protein oxidation products that are often used to measure the magnitude of protein oxidative damage induced by reactive oxygen or reactive nitrogen species. Protein carbonyls have been found to be elevated during aging and in age-related diseases such as stroke, diabetes, and neurodegenerative diseases. In the present article, we provide detailed protocols for detection of mitochondrial protein carbonyls labeled with biotin-hydrazide followed by 2-dimensional isoelectric focusing (IEF)/SDS-PAGE and Western blotting probed with horse-radish peroxidase-conjugated streptavidin. The presented procedures can also be modified for detection of carbonylation of non-mitochondrial proteins.

PMID: 26590475 [PubMed - indexed for MEDLINE]

Spinal Stabilization Exercise Effectiveness for Low Back Pain in Adolescent Idiopathic Scoliosis: A Randomized Trial.

Thu, 12/15/2016 - 07:32
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Spinal Stabilization Exercise Effectiveness for Low Back Pain in Adolescent Idiopathic Scoliosis: A Randomized Trial.

Pediatr Phys Ther. 2015;27(4):396-402

Authors: Zapata KA, Wang-Price SS, Sucato DJ, Thompson M, Trudelle-Jackson E, Lovelace-Chandler V

Abstract
PURPOSE: To compare 8 weeks of weekly supervised spinal stabilization exercises with 1-time treatment in participants with low back pain and adolescent idiopathic scoliosis.
METHODS: Participants were randomly assigned to the supervised or unsupervised group. Seventeen participants in the supervised group received weekly physical therapy, and 17 participants in the unsupervised group received a 1-time treatment followed by home exercises.
RESULTS: Significant between-group differences were found in the Numeric Pain Rating Scale and the Patient-Specific Functional Scale scores after 8 weeks (P < .01), indicating the supervised group had significantly more pain reduction and functional improvements than the unsupervised group. However, no between-group differences were found in back muscle endurance, the revised Oswestry Back Pain Disability Questionnaire scores, or the Global Rating of Change scores.
CONCLUSIONS: Supervised physical therapy may be more effective than 1-time treatment in reducing pain and improving function in patients with adolescent idiopathic scoliosis and low back pain.
VIDEO ABSTRACT: For more insights from the authors, access Supplemental Digital Content 1, at http://links.lww.com/PPT/A85.

PMID: 26397085 [PubMed - indexed for MEDLINE]

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