Recent Research Articles from UNTHSC

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Evaluation of a novel material, Diomics X-Swab™, for collection of DNA.

Wed, 07/16/2014 - 4:04am
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Evaluation of a novel material, Diomics X-Swab™, for collection of DNA.

Forensic Sci Int Genet. 2014 Jun 24;12C:192-198

Authors: Marshall PL, Stoljarova M, Larue BL, King JL, Budowle B

Abstract
Success of DNA typing is related to the amount of target material recovered from an evidentiary item. Generally, the more DNA that is recovered, the better the chance is of obtaining a typing result that will be robust and reliable. One method of collecting stain materials is by swabbing. Recovery of DNA from a number of commercially available swabs is not an efficient process. The X-Swab™ (Diomics Corporation, La Jolla, CA) is a unique bio-specimen collection material with highly absorptive properties and can be dissolved during certain extraction conditions. Therefore, more DNA may be collected from a substrate and be released from the swab matrix than other swabs. The ability to recover DNA from X-Swab material and success in STR typing were compared with the Copan 4N6FLOQSwab™ (Brescia, Italy), a device which utilizes a proprietary flocked-swab technology to maximize DNA collection and elution efficiency. Both types of swabs were impregnated with known amounts of DNA and body fluids and allowed to air dry. In addition, blood was placed onto glass slides, allowed to dry and collected using both types of swabs. DNA recovery was assessed by DNA quantitation and by STR typing. Results suggested that X-Swab material yielded greater DNA recovery, particularly of low quantity samples (defined as diluted neat samples), compared with the 4N6FLOQSwab. Results also indicated that X-Swab material itself enhances yield of PCR products.

PMID: 25016249 [PubMed - as supplied by publisher]

ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

Wed, 07/16/2014 - 4:04am
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ERK5/KLF4 signaling as a common mediator of the neuroprotective effects of both nerve growth factor and hydrogen peroxide preconditioning.

Age (Dordr). 2014 Aug;36(4):9685

Authors: Su C, Sun F, Cunningham RL, Rybalchenko N, Singh M

Abstract
Oxidative stress has long been implicated in the pathogenesis of various neurodegenerative disorders such as Alzheimer's disease and stroke. While high levels of oxidative stress are generally associated with cell death, a slight rise of reactive oxygen species (ROS) levels can be protective by "preconditioning" cells to develop a resistance against subsequent challenges. However, the mechanisms underlying such preconditioning (PC)-induced protection are still poorly understood. Previous studies have supported a role of ERK5 (mitogen-activated protein [MAP] kinase 5) in neuroprotection and ischemic tolerance in the hippocampus. In agreement with these findings, our data suggest that ERK5 mediates both hydrogen peroxide (H2O2)-induced PC as well as nerve growth factor (NGF)-induced neuroprotection. Activation of ERK5 partially rescued pheochromocytoma PC12 cells as well as primary hippocampal neurons from H2O2-caused death, while inhibition of ERK5 abolished NGF or PC-induced protection. These results implicate ERK5 signaling as a common downstream pathway for NGF and PC. Furthermore, both NGF and PC increased the expression of the transcription factor, KLF4, which can initiate an anti-apoptotic response in various cell types. Induction of KLF4 by NGF or PC was blocked by siERK5, suggesting that ERK5 is required in this process. siKLF4 can also attenuate NGF- or PC-induced neuroprotection. Overexpression of active MEK5 or KLF4 in H2O2-stressed cells increased Bcl-2/Bax ratio and the expression of NAIP (neuronal apoptosis inhibitory protein). Taken together, our data suggest that ERK5/KLF4 cascade is a common signaling pathway shared by at least two important mechanisms by which neurons can be protected from cell death.

PMID: 25015774 [PubMed - as supplied by publisher]

Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies.

Sun, 07/13/2014 - 4:04am
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Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies.

Biomed Res Int. 2014;2014:743868

Authors: Rosanio S, Pelliccia F, Gaudio C, Greco C, Keylani AM, D'Agostino DC

Abstract
This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure.

PMID: 25013799 [PubMed - as supplied by publisher]

The Association between Patient-Centered Attributes of Care and Patient Satisfaction.

Sun, 07/13/2014 - 4:04am
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The Association between Patient-Centered Attributes of Care and Patient Satisfaction.

Patient. 2014 Jul 11;

Authors: Tak H, Ruhnke GW, Shih YC

Abstract
BACKGROUND AND OBJECTIVE: Little is known about the attributes of care that most strongly impact satisfaction in real-world settings where patients' limited medical knowledge may restrict their ability to ascertain the true quality of care. We therefore examined the association between patient-centered attributes of physician care (thoroughness, explanation, and listening), in-office waiting time, and patient satisfaction.
METHODS: We used the Community Tracking Study Household Survey, a US nationally representative dataset (n = 71,594). Using logistic regression models, we analyzed the association between patient ratings of care attributes and patient satisfaction for the total sample and by subgroups, according to health status, physician type, and visit type.
RESULTS: Patients' perception of excellent or very good care attributes was strongly associated with being very satisfied with care received (thoroughness of care, odds ratio [OR] 2.64, 95 % confidence interval [CI] 2.31-3.02; listening, OR 2.04, 95 % CI 1.77-2.36; explanation, OR 1.63, 95 % CI 1.42-1.86), as was a waiting time of ≤10 min (OR 1.50, 95 % CI 1.39-1.63). The effect magnitude of thoroughness on satisfaction is particularly strong relative to high-quality listening and explanation among respondents in poor health, and for whom the most recent office visit was to see a generalist or for curative care.
CONCLUSIONS: Thoroughness of care was the strongest determinant of patient satisfaction, followed by physician listening and explanation. Especially with patients' improved access to current medical information, it is important for physicians to recognize that excellent communication cannot serve as a substitute for high-quality, thorough care.

PMID: 25011683 [PubMed - as supplied by publisher]

Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender.

Sun, 07/13/2014 - 4:04am
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Total Cholesterol and Neuropsychiatric Symptoms in Alzheimer's Disease: The Impact of Total Cholesterol Level and Gender.

Dement Geriatr Cogn Disord. 2014 Jul 4;38(5-6):300-309

Authors: Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Cunningham R, Singh M, O'Bryant SE

Abstract
Background: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD. Methods: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed. Results: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC. Conclusion: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC. © 2014 S. Karger AG, Basel.

PMID: 25011444 [PubMed - as supplied by publisher]

ANGIOTENSIN II RECEPTOR SUBTYPE 1A (AT1AR) GENE KNOCKDOWN IN THE SUBFORNICAL ORGAN (SFO) PREVENTS INCREASED DRINKING BEHAVIOR IN BILE DUCT LIGATED RATS.

Sat, 07/12/2014 - 4:05am
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ANGIOTENSIN II RECEPTOR SUBTYPE 1A (AT1AR) GENE KNOCKDOWN IN THE SUBFORNICAL ORGAN (SFO) PREVENTS INCREASED DRINKING BEHAVIOR IN BILE DUCT LIGATED RATS.

Am J Physiol Regul Integr Comp Physiol. 2014 Jul 9;

Authors: Walch JD, Nedungadi TP, Cunningham JT

Abstract
Bile duct ligation (BDL) causes congestive liver failure that initiates hemodynamic changes resulting in dilutional hyponatremia due to increased water intake and vasopressin release. This project tested the hypothesis that angiotensin signaling at the subfornical organ (SFO) augments drinking behavior in BDL rats. A genetically modified adeno-associated virus containing shRNA for angiotensin II receptor subtype 1a (AT1aR) gene was microinjected into the subfornical organ (SFO) of rats to knockdown expression. Two weeks later, BDL or sham surgery was performed. Rats were housed in metabolic chambers for measurement of fluid and food intake and urine output. The rats were euthanized 28 days after BDL surgery for analysis. A group of rats was perfused for immunohistochemistry and a second group was used for laser-capture microdissection for analysis of SFO AT1aR gene expression. BDL rats showed increased water intake that was attenuated in rats that received SFO microinjection of AT1aR shRNA. Among BDL rats treated with scrambled (control) and AT1aR shRNA, we observed an increased number of vasopressin positive cells in the supraoptic nucleus (SON) that colocalized with ΔFosB staining suggesting increased vasopressin release in both groups. These results indicate that angiotensin signalling through the SFO contributes to increased water intake, but not dilutional hyponatremia, during congestive liver failure.

PMID: 25009217 [PubMed - as supplied by publisher]

Response: Observational Study Demonstrates That OMT Is Associated With Reduced Analgesic Prescribing and Fewer Missed Work Days.

Fri, 07/11/2014 - 12:04pm

Response: Observational Study Demonstrates That OMT Is Associated With Reduced Analgesic Prescribing and Fewer Missed Work Days.

J Am Osteopath Assoc. 2014 Jul;114(7):530-1

Authors: Prinsen JK, Hensel KL, Snow RJ

PMID: 25002441 [PubMed - in process]

The OSTEOPATHIC Trial Demonstrates Significant Improvement in Patients With Chronic Low Back Pain as Manifested by Decreased Prescription Rescue Medication Use.

Fri, 07/11/2014 - 12:04pm

The OSTEOPATHIC Trial Demonstrates Significant Improvement in Patients With Chronic Low Back Pain as Manifested by Decreased Prescription Rescue Medication Use.

J Am Osteopath Assoc. 2014 Jul;114(7):528-9

Authors: Licciardone JC

PMID: 25002440 [PubMed - in process]

A high volume extraction and purification method for recovering DNA from human bone.

Wed, 07/09/2014 - 12:05pm
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A high volume extraction and purification method for recovering DNA from human bone.

Forensic Sci Int Genet. 2014 Jun 18;12C:155-160

Authors: Marshall PL, Stoljarova M, Schmedes SE, King JL, Budowle B

Abstract
DNA recovery, purity and overall extraction efficiency of a protocol employing a novel silica-based column, Hi-Flow(®) (Generon Ltd., Maidenhead, UK), were compared with that of a standard organic DNA extraction methodology. The quantities of DNA recovered by each method were compared by real-time PCR and quality of DNA by STR typing using the PowerPlex(®) ESI 17 Pro System (Promega Corporation, Madison, WI) on DNA from 10 human bone samples. Overall, the Hi-Flow method recovered comparable quantities of DNA ranging from 0.8ng±1 to 900ng±159 of DNA compared with the organic method ranging from 0.5ng±0.9 to 855ng±156 of DNA. Complete profiles (17/17 loci tested) were obtained for at least one of three replicates for 3/10 samples using the Hi-Flow method and from 2/10 samples with the organic method. All remaining bone samples yielded partial profiles for all replicates with both methods. Compared with a standard organic DNA isolation method, the results indicated that the Hi-Flow method provided equal or improved recovery and quality of DNA without the harmful effects of organic extraction. Moreover, larger extraction volumes (up to 20mL) can be employed with the Hi-Flow method which enabled more bone sample to be extracted at one time.

PMID: 24997320 [PubMed - as supplied by publisher]

Hypertrophic Cardiomyopathy Associated Lys104Glu Mutation in the Myosin Regulatory Light Chain Causes Diastolic Disturbance in Mice.

Wed, 07/09/2014 - 12:05pm
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Hypertrophic Cardiomyopathy Associated Lys104Glu Mutation in the Myosin Regulatory Light Chain Causes Diastolic Disturbance in Mice.

J Mol Cell Cardiol. 2014 Jun 30;

Authors: Huang W, Liang J, Kazmierczak K, Muthu P, Duggal D, Farman GP, Sorensen L, Pozios I, Abraham TP, Moore JR, Borejdo J, Szczesna-Cordary D

Abstract
We have examined, for the first time, the effects of the familial hypertrophic cardiomyopathy (HCM)- associated Lys104Glu mutation in the myosin regulatory light chain (RLC). Transgenic mice expressing the Lys104Glu substitution (Tg-MUT) were generated and the results compared to Tg-WT (wild-type human ventricular RLC) mice. Echocardiography with pulse wave Doppler in 6month-old Tg-MUT showed early signs of diastolic disturbance with significantly reduced E/A transmitral velocities ratio. Invasive hemodynamics in 6month-old Tg-MUT mice also demonstrated a borderline significant prolonged isovolumic relaxation time (Tau) and a tendency for slower rate of pressure decline, suggesting alterations in diastolic function in Tg-MUT. Six month-old mutant animals had no LV hypertrophy; however, at >13months they displayed significant hypertrophy and fibrosis. In skinned papillary muscles from 5-6 month-old mice a mutation induced reduction in maximal tension and slower muscle relaxation rates were observed. Mutated cross-bridges showed increased rates of binding to the thin filaments and a faster rate of the power stroke. In addition, ~2-fold lower level of RLC phosphorylation was observed in the mutant compared to Tg-WT. In line with the higher mitochondrial content seen in Tg-MUT hearts, the MUT-myosin ATPase activity was significantly higher than WT-myosin, indicating increased energy consumption. In the in vitro motility assay, MUT-myosin produced higher actin sliding velocity under zero load, but the velocity drastically decreased with applied load in the MUT vs. WT myosin. Our results suggest that diastolic disturbance (impaired muscle relaxation, lower E/A) and inefficiency of energy use (reduced contractile force and faster ATP consumption) may underlie the Lys104Glu-mediated HCM phenotype.

PMID: 24992035 [PubMed - as supplied by publisher]

Cancer-associated Isocitrate Dehydrogenase 1 (IDH1) R132H Mutation and D-2-hydroxyglutarate Stimulate Glutamine Metabolism under Hypoxia.

Wed, 07/09/2014 - 12:05pm
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Cancer-associated Isocitrate Dehydrogenase 1 (IDH1) R132H Mutation and D-2-hydroxyglutarate Stimulate Glutamine Metabolism under Hypoxia.

J Biol Chem. 2014 Jul 1;

Authors: Reitman ZJ, Duncan CG, Poteet E, Winters A, Yan LJ, Gooden DM, Spasojevic I, Boros LG, Yang SH, Yan H

Abstract
Mutations in the cytosolic NADP+-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations target a critical step in reductive glutamine metabolism, the metabolic pathway that converts glutamine ultimately to acetyl-CoA for biosynthetic processes. While IDH1-mutated cells are sensitive to therapies that target glutamine metabolism, the effect of IDH1 mutations on reductive glutamine metabolism remains poorly understood. To explore this issue, we investigated the effect of a knock-in, single-codon IDH1-R132H mutation on the metabolism of the HCT116 colorectal adenocarcinoma cell line. Here we report the R132H-isobolome by using targeted 13C isotopomer tracer fate analysis to trace the metabolic fate of glucose and glutamine in this system. We show that introduction of the R132H mutation into IDH1 upregulates the contribution of glutamine to lipogenesis in hypoxia, but not in normoxia. Treatment of cells with a D-2-hydroxyglutarate (D-2HG) ester recapitulated these changes, indicating that the alterations observed in the knocked-in cells were mediated by D-2HG produced by the IDH1 mutant. These studies provide a dynamic mechanistic basis for metabolic alterations observed in IDH1-mutated tumors and uncover potential therapeutic targets in IDH1-mutated cancers.

PMID: 24986863 [PubMed - as supplied by publisher]

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Wed, 07/09/2014 - 12:05pm
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The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Psychopharmacology (Berl). 2014 Jul 3;

Authors: Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB

Abstract
RATIONALE: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens.
OBJECTIVE: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT).
METHODS: Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT.
RESULTS: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro.
CONCLUSIONS: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

PMID: 24985890 [PubMed - as supplied by publisher]

Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15.

Sun, 07/06/2014 - 4:04am
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Regulation of ubiquitin-proteasome system-mediated Tip110 protein degradation by USP15.

Int J Biochem Cell Biol. 2014 Jun 28;

Authors: Timani KA, Liu Y, Suvannasankha A, He JJ

Abstract
Tip110 is a nuclear protein and has been shown to function in tumor antigenicity, regulation of gene transcription, pre-mRNA splicing, stem cell proliferation and differentiation, and embryonic development. To characterize the in vivo functions of Tip110, a transgene cassette expressing human Tip110 protein (hTip110) was used to generate hTip110 transgenic (Tg) mice. Unexpectedly, only Tip110 mRNA but not Tip110 protein was expressed in Tg MEF and tissues. Treatment of Tg MEF with proteasome inhibitors led to detection of hTip110 protein, which prompted us to investigate the regulatory mechanisms of Tip110 degradation in mouse cells. We found that hTip110 was more sensitive to ubiquitin-proteasome system (UPS)-mediated protein degradation than mouse Tip110 (mTip110), likely resulting from more hTip110 ubiquitination. Using affinity chromatography and proteomics, we identified USP15, a deubiquitinating enzyme, to be associated with Tip110. Tip110 expression led to re-distribution of USP15 from the cytoplasm to the nucleus and complete co-localization of Tip110 with USP15 in the nucleus, whereas USP15 expression resulted in hTip110 deubiquitination. Interestingly, USP15 knockdown restored hTip110 protein expression in Tg MEF and USP15 expression had little effects. Taken together, these results provide insights into the regulatory mechanism of human Tip110 degradation by USP15.

PMID: 24984263 [PubMed - as supplied by publisher]

Nanobiosensors: role in cancer detection and diagnosis.

Sun, 07/06/2014 - 4:04am
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Nanobiosensors: role in cancer detection and diagnosis.

Adv Exp Med Biol. 2014;807:33-58

Authors: Gdowski A, Ranjan AP, Mukerjee A, Vishwanatha JK

Abstract
The ability to detect many cancers at an early stage in its clinical course has the potential to improve patient outcomes in terms of morbidity and mortality. Nanosized components incorporated into existing clinical diagnostic and detection systems as well as novel nanobiosensors have demonstrated improved sensitivity and specificity compared with traditional cancer testing approaches. Nanoparticles, nanowires, nanotubes, and nanocantilevers are examples of four nanobiosensor systems that have been used experimentally in the context of detection and diagnosis of prostate, breast, pancreatic, lung, and brain cancers over the past few years. Nanobiosensors will begin to transition into clinically validated tests as experimental and engineering techniques advance. This paper presents examples of some such nanobiosensors for cancer diagnosis and detection.

PMID: 24619617 [PubMed - indexed for MEDLINE]

Acute Effects of Muscle Fatigue on Anticipatory and Reactive Postural Control in Older Individuals: A Systematic Review of the Evidence.

Wed, 07/02/2014 - 4:05am
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Acute Effects of Muscle Fatigue on Anticipatory and Reactive Postural Control in Older Individuals: A Systematic Review of the Evidence.

J Geriatr Phys Ther. 2014 Jun 27;

Authors: Papa EV, Garg H, Dibble LE

Abstract
BACKGROUND:: Falls are the leading cause of traumatic brain injury and fractures and the No. 1 cause of emergency department visits by older adults. Although declines in muscle strength and sensory function contribute to increased falls in older adults, skeletal muscle fatigue is often overlooked as an additional contributor to fall risk. In an effort to increase awareness of the detrimental effects of skeletal muscle fatigue on postural control, we sought to systematically review research studies examining this issue.
PURPOSE:: The specific purpose of this review was to provide a detailed assessment of how anticipatory and reactive postural control tasks are influenced by acute muscle fatigue in healthy older individuals.
METHODS:: An extensive search was performed using the CINAHL, Scopus, PubMed, SPORTDiscus, and AgeLine databases for the period from inception of each database to June 2013. This systematic review used standardized search criteria and quality assessments via the American Academy for Cerebral Palsy and Developmental Medicine Methodology to Develop Systematic Reviews of Treatment Interventions (2008 version, revision 1.2, AACPDM, Milwaukee, Wisconsin).
RESULTS:: A total of 334 citations were found. Six studies were selected for inclusion, whereas 328 studies were excluded from the analytical review. The majority of articles (5 of 6) utilized reactive postural control paradigms. All studies incorporated extrinsic measures of muscle fatigue, such as declines in maximal voluntary contraction or available active range of motion. The most common biomechanical postural control task outcomes were spatial measures, temporal measures, and end-points of lower extremity joint kinetics.
CONCLUSION:: On the basis of systematic review of relevant literature, it appears that muscle fatigue induces clear deteriorations in reactive postural control. A paucity of high-quality studies examining anticipatory postural control supports the need for further research in this area. These results should serve to heighten awareness regarding the potential negative effects of acute muscle fatigue on postural control and support the examination of muscle endurance training as a fall risk intervention in future studies.

PMID: 24978932 [PubMed - as supplied by publisher]

High-quality and high-throughput massively parallel sequencing of the human mitochondrial genome using the Illumina MiSeq.

Tue, 07/01/2014 - 4:05am
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High-quality and high-throughput massively parallel sequencing of the human mitochondrial genome using the Illumina MiSeq.

Forensic Sci Int Genet. 2014 Jun 7;12C:128-135

Authors: King JL, LaRue BL, Novroski NM, Stoljarova M, Seo SB, Zeng X, Warshauer DH, Davis CP, Parson W, Sajantila A, Budowle B

Abstract
Mitochondrial DNA typing in forensic genetics has been performed traditionally using Sanger-type sequencing. Consequently sequencing of a relatively-large target such as the mitochondrial genome (mtGenome) is laborious and time consuming. Thus, sequencing typically focuses on the control region due to its high concentration of variation. Massively parallel sequencing (MPS) has become more accessible in recent years allowing for high-throughput processing of large target areas. In this study, Nextera(®) XT DNA Sample Preparation Kit and the Illumina MiSeq™ were utilized to generate quality whole genome mitochondrial haplotypes from 283 individuals in a both cost-effective and rapid manner. Results showed that haplotypes can be generated at a high depth of coverage with limited strand bias. The distribution of variants across the mitochondrial genome was described and demonstrated greater variation within the coding region than the non-coding region. Haplotype and haplogroup diversity were described with respect to whole mtGenome and HVI/HVII. An overall increase in haplotype or genetic diversity and random match probability, as well as better haplogroup assignment demonstrates that MPS of the mtGenome using the Illumina MiSeq system is a viable and reliable methodology.

PMID: 24973578 [PubMed - as supplied by publisher]

Antigen-Pulsed Bone Marrow-Derived and Pulmonary Dendritic Cells Promote Th2 Cell Responses and Immunopathology in Lungs during the Pathogenesis of Murine Mycoplasma Pneumonia.

Tue, 07/01/2014 - 4:05am
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Antigen-Pulsed Bone Marrow-Derived and Pulmonary Dendritic Cells Promote Th2 Cell Responses and Immunopathology in Lungs during the Pathogenesis of Murine Mycoplasma Pneumonia.

J Immunol. 2014 Jun 27;

Authors: Dobbs NA, Zhou X, Pulse M, Hodge LM, Schoeb TR, Simecka JW

Abstract
Mycoplasmas are a common cause of pneumonia in humans and animals, and attempts to create vaccines have not only failed to generate protective host responses, but they have exacerbated the disease. Mycoplasma pulmonis causes a chronic inflammatory lung disease resulting from a persistent infection, similar to other mycoplasma respiratory diseases. Using this model, Th1 subsets promote resistance to mycoplasma disease and infection, whereas Th2 responses contribute to immunopathology. The purpose of the present study was to evaluate the capacity of cytokine-differentiated dendritic cell (DC) populations to influence the generation of protective and/or pathologic immune responses during M. pulmonis respiratory disease in BALB/c mice. We hypothesized that intratracheal inoculation of mycoplasma Ag-pulsed bone marrow-derived DCs could result in the generation of protective T cell responses during mycoplasma infection. However, intratracheal inoculation (priming) of mice with Ag-pulsed DCs resulted in enhanced pathology in the recipient mice when challenged with mycoplasma. Inoculation of immunodeficient SCID mice with Ag-pulsed DCs demonstrated that this effect was dependent on lymphocyte responses. Similar results were observed when mice were primed with Ag-pulsed pulmonary, but not splenic, DCs. Lymphocytes generated in uninfected mice after the transfer of either Ag-pulsed bone marrow-derived DCs or pulmonary DCs were shown to be IL-13(+) Th2 cells, known to be associated with immunopathology. Thus, resident pulmonary DCs most likely promote the development of immunopathology in mycoplasma disease through the generation of mycoplasma-specific Th2 responses. Vaccination strategies that disrupt or bypass this process could potentially result in a more effective vaccination.

PMID: 24973442 [PubMed - as supplied by publisher]

Cerebral Palsy of the Elbow and Forearm.

Sun, 06/29/2014 - 4:05am

Cerebral Palsy of the Elbow and Forearm.

J Hand Surg Am. 2014 Jul;39(7):1425-1432

Authors: Bunata R, Icenogle K

Abstract
Management of elbow and forearm involvement in cerebral palsy has evolved over the last 3 decades with a better understanding of its neuropathophysiology, improved outcome measures, and evolving therapy protocols. Current nonoperative and surgical treatment methods are discussed. The use of standard function measuring instruments and encouragement of the participation in research will hopefully result in more accurate outcome information and, thereby, refine our techniques and rehabilitation methods.

PMID: 24969499 [PubMed - as supplied by publisher]

Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: Results from the OSTEOPATHIC Trial.

Sat, 06/28/2014 - 4:05am
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Clinical response and relapse in patients with chronic low back pain following osteopathic manual treatment: Results from the OSTEOPATHIC Trial.

Man Ther. 2014 Jun 5;

Authors: Licciardone JC, Aryal S

Abstract
Clinical response and relapse following a regimen of osteopathic manual treatment (OMT) were assessed in patients with chronic low back pain (LBP) within the OSTEOPATHIC Trial, a randomized, double-blind, sham-controlled study. Initial clinical response and subsequent stability of response, including final response and relapse status at week 12, were determined in 186 patients with high baseline pain severity (≥50 mm on a 100-mm visual analogue scale). Substantial improvement in LBP, defined as 50% or greater pain reduction relative to baseline, was used to assess clinical response at weeks 1, 2, 4, 6, 8, and 12. Sixty-two (65%) patients in the OMT group attained an initial clinical response vs. 41 (45%) patients in the sham OMT group (risk ratio [RR], 1.45; 95% confidence interval [CI], 1.11-1.90). The median time to initial clinical response to OMT in these patients was 4 weeks. Among patients with an initial clinical response prior to week 12, 13 (24%) patients in the OMT group vs. 18 (51%) patients in the sham OMT group relapsed (RR, 0.47; 95% CI, 0.26-0.83). Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.

PMID: 24965494 [PubMed - as supplied by publisher]

Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

Sat, 06/28/2014 - 4:05am
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Mitigating prolonged QT interval in cancer nanodrug development for accelerated clinical translation.

J Nanobiotechnology. 2013;11:40

Authors: Ranjan AP, Mukerjee A, Helson L, Vishwanatha JK

Abstract
BACKGROUND: Cardiac toxicity is the foremost reason for drug discontinuation from development to clinical evaluation and post market surveillance [Fung 35:293-317, 2001; Piccini 158:317-326 2009]. The Food and Drug Administration (FDA) has rejected many potential pharmaceutical agents due to QT prolongation effects. Since drug development and FDA approval takes an enormous amount of time, money and effort with high failure rates, there is an increased focus on rescuing drugs that cause QT prolongation. If these otherwise safe and potent drugs were formulated in a unique way so as to mitigate the QT prolongation associated with them, these potent drugs may get FDA approval for clinical use. Rescuing these compounds not only benefit the patients who need them but also require much less time and money thus leading to faster clinical translation. In this study, we chose curcumin as our drug of choice since it has been shown to posses anti-tumor properties against various cancers with limited toxicity. The major limitations with this pharmacologically active drug are (a) its ability to prolong QT by inhibiting the hERG channel and (b) its low bioavailability. In our previous studies, we found that lipids have protective actions against hERG channel inhibition and therefore QT prolongation.
RESULTS: Results of the manual patch clamp assay of HEK 293 cells clearly illustrated that our hybrid nanocurcumin formulation prevented the curcumin induced inhibition of hERG K+ channel at concentrations higher than the therapeutic concentrations of curcumin. Comparing the percent inhibition, the hybrid nanocurcumin limited inhibition to 24.8% at a high curcumin equivalent concentration of 18 μM. Liposomal curcumin could only decrease this inhibition upto 30% only at lower curcumin concentration of 6 μM but not at 18 μM concentration.
CONCLUSIONS: Here we show a curcumin encapsulated lipopolymeric hybrid nanoparticle formulation which could protect against QT prolongation and also render increased bioavailability and stability thereby overcoming the limitations associated with curcumin.

PMID: 24330336 [PubMed - indexed for MEDLINE]