Gibson D. Lewis Library

Recent Research Articles from UNTHSC

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Updated: 2 hours 58 min ago

Fully Threaded Versus Partially Threaded Screws: Determining Shear in Cancellous Bone Fixation.

2 hours 58 min ago

Fully Threaded Versus Partially Threaded Screws: Determining Shear in Cancellous Bone Fixation.

J Foot Ankle Surg. 2015 Jul 23;

Authors: Downey MW, Kosmopoulos V, Carpenter BB

Abstract
Many researchers have studied and compared various forms of intraosseous fixation. No studies have examined the effects of shear through stiffness and failure strength of a fully threaded versus a partially threaded screw. Our hypothesis was that the fully threaded lag screw technique would provide greater shear strength and resistance. Thirty-six synthetic sawbone blocks were used to test screw fixation. In group 1 (n = 9), 2 blocks were fixed together using a fully threaded 4.0-mm stainless steel cancellous bone screw and the lag technique. In group 2 (n = 8), 2 blocks were fixed together using the standard manufacturer-recommended method for inserting 4.0-mm partially threaded stainless steel cancellous bone screws. The constructs were then mechanically tested. Shear was applied by compressing each construct at an axial displacement rate of 0.5 mm/s until failure. The fully threaded screw had a significantly greater (p = .026) initial stiffness (106.4 ± 15.8 N/mm) than the partially threaded screw (80.1 ± 27.5 N/mm). The yield load and displacement for the fully threaded group (429.4 ± 11.7 N and 7.2 ± 0.35 mm) were 64% and 67% greater than those for the partially threaded screw group (261.4 ± 26.1 N and 4.3 ± 1.03 mm), respectively. The results of the present study have demonstrated the importance of a full-thread construct to prevent shear and to decrease strain at the fracture. The confirmation of our hypothesis questions the future need and use of partially threaded screws for cancellous bone fixation.

PMID: 26210079 [PubMed - as supplied by publisher]

Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal Degeneration.

18 hours 58 min ago

Targeting Caspase-12 to Preserve Vision in Mice With Inherited Retinal Degeneration.

Invest Ophthalmol Vis Sci. 2015 Jul 1;56(8):4725-4733

Authors: Bhootada Y, Choudhury S, Gully C, Gorbatyuk M

Abstract
Purpose: The unfolded protein response is known to contribute to the inherited retinal pathology observed in T17M rhodopsin (T17M) mice. Recently it has been demonstrated that the endoplasmic reticulum stress-associated caspase-12 is activated during progression of retinal degeneration in different animal models. Therefore, we wanted to explore the role of caspase-12 in the mechanism of retinopathy in T17M mice and determine if inhibiting apoptosis in this way is a viable approach for halting retinal degeneration.
Methods: One, two-, and three-month-old C57BL6/J, caspase-12-/-, T17M, and T17M caspase-12-/- mice were analyzed by scotopic ERG, spectral-domain optical coherence tomography (SD-OCT), histology, quantitative (q)RT-PCR, and Western blot of retinal RNA and protein extracts. Calpain and caspase-3/7 activity assays were measured in postnatal (P) day 30 retinal extracts.
Results: Caspase-12 ablation significantly prevented a decline in the a- and b-wave ERG amplitudes in T17M mice during three months, increasing the amplitudes from 232% to 212% and from 160% to 138%, respectively, as compared to T17M retinas. The SD-OCT results and photoreceptor row counts demonstrated preservation of retinal structural integrity and postponed photoreceptor cell death. The delay in photoreceptor cell death was due to significant decreases in the activity of caspase-3/7 and calpain, which correlated with an increase in calpastatin expression.
Conclusions: We validated caspase-12 as a therapeutic target, ablation of which significantly protects T17M photoreceptors from deterioration. Although the inhibition of apoptotic activity alone was not sufficient to rescue T17M photoreceptors, in combination with other nonapoptotic targets, caspase-12 could be used to treat inherited retinopathy.

PMID: 26207309 [PubMed - as supplied by publisher]

Midcarpal Instability: A Comprehensive Review and Update.

18 hours 58 min ago
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Midcarpal Instability: A Comprehensive Review and Update.

Hand Clin. 2015 Aug;31(3):487-93

Authors: Niacaris T, Ming BW, Lichtman DM

Abstract
Midcarpal instability has been well described as a clinical entity but the pathokinematics and pathologic anatomy continue to be poorly understood. This article presents a comprehensive review of the existing knowledge and literature-based evidence for the diagnosis and management of the various entities comprising midcarpal instability. It discusses the limitations of the current understanding of midcarpal instability and proposes new directions for furthering knowledge of the causes and treatment of midcarpal instability and wrist pathomechanics in general.

PMID: 26205710 [PubMed - in process]

Bitropic D3 Dopamine Receptor Selective Compounds s Potential Antipsychotics.

18 hours 58 min ago
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Bitropic D3 Dopamine Receptor Selective Compounds s Potential Antipsychotics.

Curr Pharm Des. 2015 Jul 23;

Authors: Luedtke RR, Rangel-Barajas C, Malik M, Reichert DE, Mach RH

Abstract
Neuropsychiatric disorders represents a substantial social and health care issue. The National Institutes of Health estimates that greater than 2 million adults suffer from neuropsychiatric disorders in the USA. These individuals experience symptoms that can include auditory hallucinations, delusions, unrealistic beliefs and cognitive dysfunction. Although antipsychotic medications are available, suboptimal therapeutic responses are observed for approximately one-third of patients. Therefore, there is still a need to explore new pharmacotherapeutic strategies for the treatment of neuropsychiatric disorders. Many of the medications that are used clinically to treat neuropsychiatric disorders have a pharmacological profile that includes being an antagonist at D2-like (D2, D2 and D4) dopamine receptor subtypes. However, dopamine receptor subtypes are involved in a variety of neuronal circuits that include movement coordination, cognition, emotion, affect, memory and the regulation of prolactin. Consequently, antagonism at D2-like receptors can also contribute to some of the adverse side effects associated with the long-term use of antipsychotics including the a) adverse extrapyramidal symptoms associated with the use of typical antipsychotics and b) metabolic side effects (weight gain, hyperglycemia, increased risk of diabetes mellitus, dyslipidemia and gynecomastia) associated with atypical antipsychotic use. Preclinical studies suggest that D3 versus D2 dopamine receptor selective compounds might represent an alternative strategy for the treatment of the symptoms of schizophrenia. In this review we discuss a) how bitropic N-phenylpiperazine D3 dopamine receptor selective compounds have been developed by modification of the primary (orthosteric) and secondary (allosteric or modulatory) pharmacophores to optimize D3 receptor affinity and D2/D3 binding selectivity ratios and b) the functional selectivity of these compounds. Examples of how these compounds might be modified to develop bivalent ligands capable of interacting with receptor dimers or oligomers are also provided. Preclinical studies using bitropic D3 dopamine receptor selective ligands are also discussed as strategy to pharmacologically dissect the role of the D2 and D3 dopamine receptor subtypes in animal models of neuropsychiatric, neurological and substance abuse disorders. This research has the potential to a) advance the understanding of the role of the D2 and D3 dopamine receptor subtypes in neuropsychiatric disorders and b) lead to new treatment strategies for neuropsychiatric disorders.

PMID: 26205291 [PubMed - as supplied by publisher]

Tip110 binding to U6 small nuclear RNA and its participation in pre-mRNA splicing.

Sat, 07/25/2015 - 3:31am
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Tip110 binding to U6 small nuclear RNA and its participation in pre-mRNA splicing.

Cell Biosci. 2015;5:40

Authors: Liu Y, Liu J, Wang Z, He JJ

Abstract
BACKGROUND: RNA-protein interactions play important roles in gene expression control. These interactions are mediated by several recurring RNA-binding motifs including a well-known and characterized ribonucleoprotein motif or so-called RNA recognition motif (RRM).
RESULTS: In the current study, we set out to identify the RNA ligand(s) of a RRM-containing protein Tip110, also known as p110(nrb), SART3, or p110, using a RNA-based yeast three-hybrid cloning strategy. Six putative RNA targets were isolated and found to contain a consensus sequence that was identical to nucleotides 34-46 of U6 small nuclear RNA. Tip110 binding to U6 was confirmed to be specific and RRM-dependent in an electrophoretic mobility shift assay. Both in vitro pre-mRNA splicing assay and in vivo splicing-dependent reporter gene assay showed that the pre-mRNA splicing was correlated with Tip110 expression. Moreover, Tip110 was found in the spliceosomes containing pre-spliced pre-mRNA and spliced mRNA products. Nonetheless, the RRM-deleted mutant (ΔRRM) that did not bind to U6 showed promotion in vitro pre-mRNA splicing, whereas the nuclear localization signal (NLS)-deleted mutant ΔNLS that bound to U6 promoted the pre-mRNA splicing both in vitro and in vivo. Lastly, RNA-Seq analysis confirmed that Tip110 regulated a number of gene pre-mRNA splicing including several splicing factors.
CONCLUSIONS: Taken together, these results demonstrate that Tip110 is directly involved in constitutive eukaryotic pre-mRNA splicing, likely through its binding to U6 and regulation of other splicing factors, and provide further evidence to support the global roles of Tip110 in regulation of host gene expression.

PMID: 26203351 [PubMed]

The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders.

Sat, 07/25/2015 - 3:31am
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The prodrug DHED selectively delivers 17β-estradiol to the brain for treating estrogen-responsive disorders.

Sci Transl Med. 2015 Jul 22;7(297):297ra113

Authors: Prokai L, Nguyen V, Szarka S, Garg P, Sabnis G, Bimonte-Nelson HA, McLaughlin KJ, Talboom JS, Conrad CD, Shughrue PJ, Gould TD, Brodie A, Merchenthaler I, Koulen P, Prokai-Tatrai K

Abstract
Many neurological and psychiatric maladies originate from the deprivation of the human brain from estrogens. However, current hormone therapies cannot be used safely to treat these conditions commonly associated with menopause because of detrimental side effects in the periphery. The latter also prevents the use of the hormone for neuroprotection. We show that a small-molecule bioprecursor prodrug, 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED), converts to 17β-estradiol in the brain after systemic administration but remains inert in the rest of the body. The localized and rapid formation of estrogen from the prodrug was revealed by a series of in vivo bioanalytical assays and through in vivo imaging in rodents. DHED treatment efficiently alleviated symptoms that originated from brain estrogen deficiency in animal models of surgical menopause and provided neuroprotection in a rat stroke model. Concomitantly, we determined that 17β-estradiol formed in the brain from DHED elicited changes in gene expression and neuronal morphology identical to those obtained after direct 17β-estradiol treatment. Together, complementary functional and mechanistic data show that our approach is highly relevant therapeutically, because administration of the prodrug selectively produces estrogen in the brain independently from the route of administration and treatment regimen. Therefore, peripheral responses associated with the use of systemic estrogens, such as stimulation of the uterus and estrogen-responsive tumor growth, were absent. Collectively, our brain-selective prodrug approach may safely provide estrogen neuroprotection and medicate neurological and psychiatric symptoms developing from estrogen deficiency, particularly those encountered after surgical menopause, without the adverse side effects of current hormone therapies.

PMID: 26203081 [PubMed - in process]

Validation of a serum screen for Alzheimer's disease across assay platforms, species, and tissues.

Sat, 07/25/2015 - 3:31am
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Validation of a serum screen for Alzheimer's disease across assay platforms, species, and tissues.

J Alzheimers Dis. 2014;42(4):1325-35

Authors: O'Bryant SE, Xiao G, Zhang F, Edwards M, German DC, Yin X, Como T, Reisch J, Huebinger RM, Graff-Radford N, Dickson D, Barber R, Hall J, O'Suilleabhain P, Grammas P

Abstract
BACKGROUND: There is a significant need for rapid and cost-effective biomarkers of Alzheimer's disease (AD) for advancement of clinical practice and therapeutic trials.
OBJECTIVE: The aim of the current study was to cross-validate our previously published serum-based algorithm on an independent assay platform as well as validate across tissues and species. Preliminary analyses were conducted to examine the utility in distinguishing AD from non-AD neurological disease (Parkinson's disease, PD).
METHODS: Serum proteins from our previously published algorithm were quantified from 150 AD cases and 150 controls on the Meso Scale Discovery (MSD) platform. Serum samples were analyzed from 49 PD cases and compared to a random sample of 51 AD cases and 62 controls. Support vector machines (SVM) were used to discriminate PD versus AD versus controls. Human and AD mouse model microvessel images were quantified with HAMAMATSU imaging software. Mouse serum biomarkers were assayed via MSD.
RESULTS: Analysis of 21 serum proteins from 150 AD cases and 150 controls yielded an algorithm with sensitivity and specificity of 0.90 for correctly classifying AD. This multi-marker approach was then validated across species and tissue. Assay of the top proteins in human and AD mouse model brain microvessels correctly classified 90-100% of the samples. SVM analyses were highly accurate at distinguishing PD versus AD versus controls.
CONCLUSIONS: This serum-based biomarker panel should be tested in a community-based setting to determine its utility as a first-line screen for AD and non-AD neurological diseases for primary care providers.

PMID: 25024345 [PubMed - indexed for MEDLINE]

STRait Razor v2.0: the improved STR Allele Identification Tool--Razor.

Fri, 07/24/2015 - 3:29am
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STRait Razor v2.0: the improved STR Allele Identification Tool--Razor.

Forensic Sci Int Genet. 2015 Jan;14:182-6

Authors: Warshauer DH, King JL, Budowle B

Abstract
STRait Razor (the STR Allele Identification Tool - Razor) was developed as a bioinformatic software tool to detect short tandem repeat (STR) alleles in massively parallel sequencing (MPS) raw data. The method of detection used by STRait Razor allows it to make reliable allele calls for all STR types in a manner that is similar to that of capillary electrophoresis. STRait Razor v2.0 incorporates several new features and improvements upon the original software, such as a larger default locus configuration file that increases the number of detectable loci (now including X-chromosome STRs and Amelogenin), an enhanced custom locus list generator, a novel output sorting method that highlights unique sequences for intra-repeat variation detection, and a genotyping tool that emulates traditional electropherogram data. Users also now have the option to choose whether the program detects autosomal, X-chromosome, Y-chromosome, or all STRs. Concordance testing was performed, and allele calls produced by STRait Razor v2.0 were completely consistent with those made by the original software.

PMID: 25450790 [PubMed - indexed for MEDLINE]

Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

Fri, 07/24/2015 - 3:29am
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Combining select neuropsychological assessment with blood-based biomarkers to detect mild Alzheimer's disease: a molecular neuropsychology approach.

J Alzheimers Dis. 2014;42(2):635-40

Authors: Edwards M, Balldin VH, Hall J, O'Bryant S

Abstract
BACKGROUND: Current work has sought to establish a rapid and cost effective means of screening for Alzheimer's disease (AD) with the most recent findings showing utility of integrating blood-based biomarkers with cognitive measures.
OBJECTIVE: The current project sought to create a combined biomarker-cognitive profile to detect mild AD.
METHODS: Data was analyzed from 266 participants (129 AD cases [Early AD n = 93; Very Early AD n = 36]; 137 controls) enrolled in the Texas Alzheimer's Research and Care Consortium (TARCC). Non-fasting serum samples were collected from each participant and assayed via a multi-plex biomarker assay platform using electrochemiluminescence. Logistic Regression was utilized to detect early AD using two serum biomarkers (TNFα and IL7), demographic information (age), and one neuropsychological measure (Clock 4-point) as predictor variable. Disease severity was determined via Clinical Dementia Rating (CDR) scale global scores.
RESULTS: In the total sample (all levels of CDR scores), the combination of biomarkers, cognitive test score, and demographics yielded the obtained sensitivity (SN) of 0.94, specificity (SP) of 0.90, and an overall accuracy of 0.92. When examining early AD cases (i.e.m CDR = 0.5-1), the biomarker-cognitive profile yielded SN of 0.94, SP of 0.85, and an overall accuracy of 0.91. When restricted to very early AD cases (i.e., CDR = 0.5), the biomarker-cognitive profile yielded SN of 0.97 and SP of 0.72, with an overall accuracy of 0.91.
CONCLUSIONS: The combination of demographics, two biomarkers, and one cognitive test created a biomarker-cognitive profile that was highly accurate in detecting the presence of AD, even in the very early stages.

PMID: 24916542 [PubMed - indexed for MEDLINE]

Are positive allosteric modulators of α7 nAChRs clinically safe?

Tue, 07/21/2015 - 3:30am
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Are positive allosteric modulators of α7 nAChRs clinically safe?

J Neurochem. 2015 Jul 14;

Authors: Uteshev V

Abstract
In a recent research article published in the May 2015 issue of this journal (Journal of Neurochemistry 2015, 133: 309-319), Guerra-Alvarez et al. reported a cytotoxic potential of PNU120596, a Type-II positive allosteric modulator (PAMII) of α7 nicotinic acetylcholine receptors (α7 nAChRs). The authors used human SH-SY5Y neuroblastoma cells, rat organotypic hippocampal slice culture, electrophysiology and fluorescent Ca(2+) imaging to evaluate cellular responsiveness and survival after various treatments with nicotinic agonists and PNU120596. This article is protected by copyright. All rights reserved.

PMID: 26182952 [PubMed - as supplied by publisher]

Measurement properties of the sedentary behavior strategy self-management instrument in African-American breast cancer survivors.

Tue, 07/21/2015 - 3:30am
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Measurement properties of the sedentary behavior strategy self-management instrument in African-American breast cancer survivors.

Am J Health Behav. 2015 Mar;39(2):175-82

Authors: Paxton RJ, Gao Y, Herrmann SD, Norman GJ

Abstract
OBJECTIVES: To examine the validity and reliability of a modified Sedentary Behavior Strategy Self-Management Scale (SBSMS) in a sample of breast cancer survivors.
METHODS: A total of 291 African-American (AA) breast cancer survivors completed the SBSMS, which was subjected to tests of reliability, structural validity, and tests of measurement equivalence/invariance (ME/I).
RESULTS: A revised measurement model fit the data and demonstrated internal reliability and structural validity. Tests for ME/I revealed that the revised model had appropriate levels of invariance among weight status, educational, and years out from diagnosis groups, but not among age groups.
CONCLUSION: The reliability and structural validity of the instrument was supported overall; however, revisions may be needed to support its validity in older AA breast cancer survivors.

PMID: 25564829 [PubMed - indexed for MEDLINE]

High Alcohol Concentration Products Associated With Poverty and State Alcohol Policies.

Sat, 07/18/2015 - 3:31am

High Alcohol Concentration Products Associated With Poverty and State Alcohol Policies.

Am J Public Health. 2015 Jul 16;:e1-e7

Authors: Rossheim ME, Thombs DL, Wagenaar AC, Xuan Z, Aryal S

Abstract
OBJECTIVES: We examined the associations among zip code demographics, the state alcohol policy environment, and the retail outlet availability of multiple fruit-flavored alcoholic drinks in a can (MFAC).
METHODS: In a nationally representative sample of zip codes (n = 872), we merged data from 4 sources: publicly available marketing information from 2 major MFAC producers, the US Census Bureau, state alcohol regulatory agencies, and recent research on state alcohol policies. We used zero-inflated negative binomial regression models to examine MFAC outlet availability in the United States.
RESULTS: More than 98% of MFAC outlets were off-premises alcohol establishments. After we controlled for population size and the number of licensed on- and off-premises alcohol outlets within zip codes, more families below the poverty line and weaker state alcohol control policies were associated with greater MFAC outlet availability.
CONCLUSIONS: Economic conditions and alcohol policy environment appeared to be related to MFAC outlet availability, after adjusting for the general availability of alcohol. Research is needed to determine whether MFACs are disproportionately contributing to alcohol-related harm in socially and economically disadvantaged communities. Policies to better regulate the off-premises sale of alcohol are needed. (Am J Public Health. Published online ahead of print July 16, 2015: e1-e7. doi:10.2105/AJPH.2015.302705).

PMID: 26180984 [PubMed - as supplied by publisher]

Two novel high performing composite PMMA-CaP cements for vertebroplasty: An ex vivo animal study.

Fri, 07/17/2015 - 3:29am
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Two novel high performing composite PMMA-CaP cements for vertebroplasty: An ex vivo animal study.

J Mech Behav Biomed Mater. 2015 Jun 29;50:290-298

Authors: Aghyarian S, Hu X, Lieberman IH, Kosmopoulos V, Kim HK, Rodrigues DC

Abstract
There is a growing body of the literature on new cement formulations that address the shortcomings of PMMA bone cements approved for use in vertebroplasty (VP) and balloon kyphoplasty (BKP). The present study is a contribution to these efforts by further characterization of two pre-mixed CaP filler-reinforced PMMA bone cements intended for VP; namely, PMMA-HA and PMMA-brushite cements. Each of these cements showed acceptable levels of various properties determined in porcine vertebral bodies. These properties included radiographic contrast, maximum exotherm temperature setting time, cement extravasation, stiffness change after fatigue loading, change of VB height after fracture following fatigue loading, and interdigitation. Each property value was comparable to or better than that for a PMMA bone cement approved for use in BKP. Thus, the results for the composite bone cements are promising.

PMID: 26177392 [PubMed - as supplied by publisher]

Improving diabetic patient transition to home healthcare: leading risk factors for 30-day readmission.

Thu, 07/16/2015 - 3:29am
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Improving diabetic patient transition to home healthcare: leading risk factors for 30-day readmission.

Am J Manag Care. 2015 Jun;21(6):440-50

Authors: Chen HF, Popoola T, Radhakrishnan K, Suzuki S, Homan S

Abstract
OBJECTIVES: To identify risk factors of 30-day readmissions due to ambulatory care-sensitive conditions (ACSCs) for diabetic Medicare home healthcare beneficiaries in order to improve transition from hospital-based care to home healthcare.
STUDY DESIGN: We analyzed diabetic Medicare beneficiaries who received home healthcare within 14 days of hospital discharges in 2009. The unit of analysis is the home health episode for post acute care.
METHODS: The conceptual framework was guided by Andersen's Behavioral Model of Health Services. Data sources included: Medicare Beneficiary Summary File, Medicare Provider Analysis Review, Outcome Assessment Information Set, Home Health Agency Research Identifiable File, Hospital Readmissions Reduction Program Supplemental Data File, Provider of Services File, and Area Health Resources File. The dependent variable was time to first 30-day ACSC-related readmission. Proportional hazards regression was used for the statistical analyses.
RESULTS: The 30-day ACSC-related readmission rate was approximately 6% in our study sample, costing the Medicare program about $62 million. Predictors of readmissions due to ACSCs within 30 days of hospital discharge were: being aged 75 to 84 years, being an African American, requiring assistance in medication management, and having 1 or more of the following clinical conditions: congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, renal failure, deficiency anemia, fluid and electrolyte diseases, depression and/or anxiety, and pressure or stasis ulcer. Patients with chronic obstructive pulmonary disease or renal failure had a 40% higher risk of 30-day ACSC-related readmissions than their counterparts.
CONCLUSIONS: Knowing the risk factors identified above, hospital providers can improve care planning and transition of care to the home healthcare providers.

PMID: 26168064 [PubMed - in process]

Delayed-Onset Nodules Secondary to a Smooth Cohesive 20 mg/mL Hyaluronic Acid Filler: Cause and Management.

Thu, 07/16/2015 - 3:29am
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Delayed-Onset Nodules Secondary to a Smooth Cohesive 20 mg/mL Hyaluronic Acid Filler: Cause and Management.

Dermatol Surg. 2015 Jul 8;

Authors: Beleznay K, Carruthers JD, Carruthers A, Mummert ME, Humphrey S

Abstract
BACKGROUND: The shift from 2- to 3-dimensional soft tissue augmentation has allowed the development of hyaluronic acid (HA) fillers, which are long lasting and also reversible. Delayed-onset inflammatory nodules have recently been reported with the use of HA fillers.
OBJECTIVE: The authors document their experience with delayed-onset nodules after 3-dimensional facial injection of Juvéderm Voluma (HA-V) over 68 months.
MATERIALS AND METHODS: The authors conducted a retrospective chart review of patients who were treated with HA-V between February 1, 2009, and September 30, 2014, to evaluate for delayed-onset nodules.
RESULTS: Over 68 months, 4,702 treatments were performed using 11,460 mL of HA-V. Twenty-three patients (0.5%) experienced delayed-onset nodules. The median time from injection to reaction was 4 months, and median time to resolution was 6 weeks. Nine of the 23 (39%) had an identifiable immunologic trigger such as flu-like illness before the nodule onset. In the authors' experience, prednisone, intralesional corticosteroids, and hyaluronidase were effective treatments.
CONCLUSION: Although delayed nodules are uncommon from HA-V (0.5%), it is important to be aware of this adverse effect and have a management protocol in place. It is the authors' opinion from the patients' responses and from the literature that these nodules are immune mediated in nature.

PMID: 26166260 [PubMed - as supplied by publisher]

MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1.

Thu, 07/16/2015 - 3:29am
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MicroRNA-940 suppresses prostate cancer migration and invasion by regulating MIEN1.

Mol Cancer. 2014;13:250

Authors: Rajendiran S, Parwani AV, Hare RJ, Dasgupta S, Roby RK, Vishwanatha JK

Abstract
BACKGROUND: MicroRNAs (miRNAs) are crucial molecules that regulate gene expression and hence pathways that are key to prostate cancer progression. These non-coding RNAs are highly deregulated in prostate cancer thus facilitating progression of the disease. Among the many genes that have gained importance in this disease, Migration and invasion enhancer 1 (MIEN1), a novel gene located next to HER2/neu in the 17q12 amplicon of the human chromosome, has been shown to enhance prostate cancer cell migration and invasion, two key processes in cancer progression. MIEN1 is differentially expressed between normal and cancer cells and tissues. Understanding the regulation of MIEN1 by microRNA may enable development of better targeting strategies.
METHODS: The miRNAs that could target MIEN1 were predicted by in silico algorithms and microarray analysis. The validation for miRNA expression was performed by qPCR and northern blotting in cells and by in situ hybridization in tissues. MIEN1 and levels of other molecules upon miRNA regulation was determined by Western blotting, qPCR, and immunofluorescence. The functional effects of miRNA on cells were determined by wound healing cell migration, Boyden chamber cell invasion, clonal and colony formation assays. For knockdown or overexpression of the miRNA or overexpression of MIEN1 3'UTR, cells were transfected with the oligomiRs and plasmids, respectively.
RESULTS: A novel miRNA, hsa-miR-940 (miR-940), identified and validated to be highly expressed in immortalized normal cells compared to cancer cells, is a regulator of MIEN1. Analysis of human prostate tumors and their matched normal tissues confirmed that miR-940 is highly expressed in the normal tissues compared to its low to negligible expression in the tumors. While MIEN1 is a direct target of miR-940, miR-940 alters MIEN1 RNA, in a quantity as well as cell dependent context, along with altering its downstream effectors. The miR-940 inhibited migratory and invasive potential of cells, attenuated their anchorage-independent growth ability, and increased E-cadherin expression, implicating its role in mesenchymal-to-epithelial transition (MET).
CONCLUSIONS: These results, for the first time, implicate miR-940, a regulator of MIEN1, as a promising novel diagnostic and prognostic tool for prostate cancer.

PMID: 25406943 [PubMed - indexed for MEDLINE]

Analysis of provider specialties in the treatment of patients with clinically diagnosed back and joint problems.

Thu, 07/16/2015 - 3:29am
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Analysis of provider specialties in the treatment of patients with clinically diagnosed back and joint problems.

J Eval Clin Pract. 2015 Jul 7;

Authors: Wilson FA, Licciardone JC, Kearns CM, Akuoko M

Abstract
RATIONALE, AIMS AND OBJECTIVES: Although several studies have compared patient outcomes by provider specialty in the treatment of back and joint pain, little is known about the cost-effectiveness of improving patient outcomes across specialties. This study uses a large-scale, nationally representative database to evaluate the cost-effectiveness of being treated by specific provider specialists for back and joint pain in the United States.
METHOD: The 2002-2012 Medical Expenditure Panel Surveys were used to examine patients diagnosed with back and/or joint problems seeking treatment from doctors (internal medicine, family/general, osteopathic medicine, orthopaedics, rheumatology, neurology) or other providers (chiropractor, physical therapist, acupuncturist, massage therapist). A total of 16 546 respondents aged 18 to 85 and clinically diagnosed with back/joint pain were examined. Self-reported measures of physical and mental health and general quality of life (measured by the EuroQol-5D) were compared with average total costs of treatment across medical providers.
RESULTS: Total annual treatment costs per person ranged from $397 for family/general doctors to $1205 for rheumatologists. Cost-effectiveness analysis suggests that osteopathic, family/general, internal medicine doctors and chiropractors and massage therapists were more cost-effective than other specialties in improving physical function to back pain patients. For mental health measures, family/general and orthopaedic doctors and physical therapists were more cost-effective compared with other specialties. Similar to results on physical function, family/general, osteopathic and internal medicine doctors dominated other specialties. However, only massage therapy was cost-effective among non-doctor providers in improving quality of life measures.
CONCLUSIONS: Patients seeking care for back and joint-related health problems face a wide range of treatments, costs and outcomes depending on which specialist provider they see. This study provides important insight on the relationship between health care costs and patients' perceived physical and mental health status from receiving treatment for diagnosed back/joint problems.

PMID: 26154344 [PubMed - as supplied by publisher]

Arsenic exposure, hyperuricemia, and gout in US adults.

Thu, 07/16/2015 - 3:29am
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Arsenic exposure, hyperuricemia, and gout in US adults.

Environ Int. 2015 Mar;76:32-40

Authors: Kuo CC, Weaver V, Fadrowski JJ, Lin YS, Guallar E, Navas-Acien A

Abstract
BACKGROUND: There is very limited information on the association between arsenic and serum uric acid levels or gout. The aim of this study was to investigate the association of arsenic with hyperuricemia and gout in US adults.
METHODS: A cross-sectional study was conducted in 5632 adults aged 20years or older from the National Health and Nutrition Examination Survey (NHANES) 2003-2010 with determinations of serum uric acid and urine total arsenic and dimethylarsinate (DMA). Hyperuricemia was defined as serum uric acid higher than 7.0mg/dL for men and 6.0mg/dL for women. Gout was defined based on self-reported physician diagnosis and medication use.
RESULTS: After adjustment for sociodemographic factors, comorbidities and arsenobetaine levels, the increase in the geometric means of serum uric acid associated with one interquartile range increase in total arsenic and DMA levels was 3% (95% CI 2-5) and 3% (2-5), respectively, in men and 1% (0-3) and 2% (0-4), respectively, in women. In men, the adjusted odds ratio for hyperuricemia comparing the highest to lowest quartiles of total arsenic was 1.84 (95% CI, 1.26-2.68) and for DMA it was 1.41 (95% CI, 1.01-1.96). The corresponding odds ratios in women were 1.26 (0.77, 2.07) and 1.49 (0.96, 2.31), respectively. The odds ratio for gout comparing the highest to lowest tertiles was 5.46 (95% CI, 1.70-17.6) for total arsenic and 1.98 (0.64-6.15) for DMA among women older than 40years old. Urine arsenic was not associated with gout in men.
CONCLUSION: Low level arsenic exposures may be associated with the risk of hyperuricemia in men and with the prevalence of gout in women. Prospective research focusing on establishing the direction of the relationship among arsenic, hyperuricemia, and gout is needed.

PMID: 25499256 [PubMed - indexed for MEDLINE]

Aberrant histone acetylation promotes mitochondrial respiratory suppression in the brain of alcoholic rats.

Thu, 07/16/2015 - 3:29am
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Aberrant histone acetylation promotes mitochondrial respiratory suppression in the brain of alcoholic rats.

J Pharmacol Exp Ther. 2015 Feb;352(2):258-66

Authors: Jung ME, Metzger DB

Abstract
The acetylation of histone proteins in the core of DNA regulates gene expression, including those affecting mitochondria. Both histone acetylation and mitochondrial deficit have been implicated in neuronal damage associated with drinking problems. Many alcoholics will repeat unsuccessful attempts at abstaining, developing a pattern of repeated drinking and withdrawal. We investigated whether aberrant histone acetylation contributes to mitochondrial and cellular damage induced by repeated ethanol withdrawal (EW). We also investigated whether this effect of histone acetylation involves let-7f, a small noncoding RNA (microRNA). Male rats received two cycles of an ethanol/control diet (7.5%, 4 weeks) and withdrawal. Their prefrontal cortex was collected to measure the mitochondrial respiration and histone acetylation using extracellular flux (XF) real-time respirometry and gold immunostaining, respectively. Separately, HT22 (mouse hippocampal) cells received two cycles of ethanol exposure (100 mM, 20 hours) and withdrawal. Trichostatin A (TSA) as a histone acetylation promoter and let-7f antagomir were applied during withdrawal. The mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, quantitative polymerase chain reaction, TaqMan let-7f primers, and a calcein-acetoxymethyl assay, respectively. Repeated ethanol withdrawn rats showed a more than 2-fold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression was exacerbated by TSA treatment in a manner that was attenuated by let-7f antagomir cotreatment. TSA treatment did not alter the increasing effect of EW on the let-7f level but dramatically exacerbated the cell death induced by EW. These data suggest that the multiple episodes of withdrawal from chronic ethanol impede mitochondrial and cellular integrity through upregulating histone acetylation, independent of or additively with let-7f.

PMID: 25406171 [PubMed - indexed for MEDLINE]

Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.

Thu, 07/16/2015 - 3:29am
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Characterization of a new composite PMMA-HA/Brushite bone cement for spinal augmentation.

J Biomater Appl. 2014 Nov;29(5):688-98

Authors: Aghyarian S, Rodriguez LC, Chari J, Bentley E, Kosmopoulos V, Lieberman IH, Rodrigues DC

Abstract
Calcium phosphate fillers have been shown to increase cement osteoconductivity, but have caused drawbacks in cement properties. Hydroxyapatite and Brushite were introduced in an acrylic two-solution cement at varying concentrations. Novel composite bone cements were developed and characterized using rheology, injectability, and mechanical tests. It was hypothesized that the ample swelling time allowed by the premixed two-solution cement would enable thorough dispersion of the additives in the solutions, resulting in no detrimental effects after polymerization. The addition of Hydroxyapatite and Brushite both caused an increase in cement viscosity; however, these cements exhibited high shear-thinning, which facilitated injection. In gel point studies, the composite cements showed no detectable change in gel point time compared to an all-acrylic control cement. Hydroxyapatite and Brushite composite cements were observed to have high mechanical strengths even at high loads of calcium phosphate fillers. These cements showed an average compressive strength of 85 MPa and flexural strength of 65 MPa. A calcium phosphate-containing cement exhibiting a combination of high viscosity, pseudoplasticity and high mechanical strength can provide the essential bioactivity factor for osseointegration without sacrificing load-bearing capability.

PMID: 25085810 [PubMed - indexed for MEDLINE]

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