Recent Research Articles from UNTHSC

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Indoor air pollution from solid fuels and peripheral Blood DNA methylation: Findings from a population study in Warsaw, Poland.

Fri, 09/12/2014 - 4:05am
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Indoor air pollution from solid fuels and peripheral Blood DNA methylation: Findings from a population study in Warsaw, Poland.

Environ Res. 2014 Sep 5;134C:325-330

Authors: Tao MH, Zhou J, Rialdi AP, Martinez R, Dabek J, Scelo G, Lissowska J, Chen J, Boffetta P

Abstract
DNA methylation is a potential mechanism linking indoor air pollution to adverse health effects. Fetal and early-life environmental exposures have been associated with altered DNA methylation and play a critical role in progress of diseases in adulthood. We investigated whether exposure to indoor air pollution from solid fuels at different lifetime periods was associated with global DNA methylation and methylation at the IFG2/H19 imprinting control region (ICR) in a population-based sample of non-smoking women from Warsaw, Poland. Global methylation and IFG2/H19 ICR methylation were assessed in peripheral blood DNA from 42 non-smoking women with Luminometric Methylation Assay (LUMA) and quantitative pyrosequencing, respectively. Linear regression models were applied to estimate associations between indoor air pollution and DNA methylation in the blood. Compared to women without exposure, the levels of LUMA methylation for women who had ever exposed to both coal and wood were reduced 6.70% (95% CI: -13.36, -0.04). Using both coal and wood before age 20 was associated with 6.95% decreased LUMA methylation (95% CI: -13.79, -0.11). Further, the negative correlations were more significant with exposure to solid fuels for cooking before age 20. There were no clear associations between indoor solid fuels exposure before age 20 and through the lifetime and IFG2/H19 ICR methylation. Our study of non-smoking women supports the hypothesis that exposure to indoor air pollution from solid fuels, even early-life exposure, has the capacity to modify DNA methylation that can be detected in peripheral blood.

PMID: 25199973 [PubMed - as supplied by publisher]

Alcohol Withdrawal and Cerebellar Mitochondria.

Fri, 09/12/2014 - 4:05am
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Alcohol Withdrawal and Cerebellar Mitochondria.

Cerebellum. 2014 Sep 9;

Authors: Jung ME

Abstract
Cerebellar disorders trigger the symptoms of movement problems, imbalance, incoordination, and frequent fall. Cerebellar disorders are shown in various CNS illnesses including a drinking disorder called alcoholism. Alcoholism is manifested as an inability to control drinking in spite of adverse consequences. Human and animal studies have shown that cerebellar symptoms persist even after complete abstinence from drinking. In particular, the abrupt termination (ethanol withdrawal) of long-term excessive ethanol consumption has shown to provoke a variety of neuronal and mitochondrial damage to the cerebellum. Upon ethanol withdrawal, excitatory neurotransmitter molecules such as glutamate are overly released in brain areas including cerebellum. This is particularly relevant to the cerebellar neuronal network as glutamate signals are projected to Purkinje neurons through granular cells that are the most populated neuronal type in CNS. This excitatory neuronal signal may be elevated by ethanol withdrawal stress, which promotes an increase in intracellular Ca(2+) level and a decrease in a Ca(2+)-binding protein, both of which result in the excessive entry of Ca(2+) to the mitochondria. Subsequently, mitochondria undergo a prolonged opening of mitochondrial permeability transition pore and the overproduction of harmful free radicals, impeding adenosine triphosphate (ATP)-generating function. This in turn provokes the leakage of mitochondrial molecule cytochrome c to the cytosol, which triggers a cascade of adverse cytosol reactions. Upstream to this pathway, cerebellum under the condition of ethanol withdrawal has shown aberrant gene modifications through altered DNA methylation, histone acetylation, or microRNA expression. Interplay between these events and molecules may result in functional damage to cerebellar mitochondria and consequent neuronal degeneration, thereby contributing to motoric deficit. Mitochondria-targeting research may help develop a powerful new therapy to manage cerebellar disorders associated with hyperexcitatory CNS disorders like ethanol withdrawal.

PMID: 25195804 [PubMed - as supplied by publisher]

Future directions of forensic DNA databases.

Fri, 09/12/2014 - 4:05am
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Future directions of forensic DNA databases.

Croat Med J. 2014 Apr;55(2):163-6

Authors: Ge J, Sun H, Li H, Liu C, Yan J, Budowle B

PMID: 24778103 [PubMed - indexed for MEDLINE]

Allele frequencies for 15 autosomal STR loci and haplotype data for 17 Y-STR loci in a population from Belize.

Wed, 09/10/2014 - 4:05am
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Allele frequencies for 15 autosomal STR loci and haplotype data for 17 Y-STR loci in a population from Belize.

Int J Legal Med. 2014 Sep 6;

Authors: Flores S, Sun J, King J, Eisenberg A, Budowle B

Abstract
Allele frequencies for 15 autosomal STR loci (N = 290) and haplotype data for 17 Y-STR loci (N = 157) were determined for an admixed population from Belize. There were no detectable departures from Hardy-Weinberg equilibrium expectations at any autosomal STR loci except for the D8S1179 locus (p = 0.002). The combined power of discrimination (PD) and combined power of exclusion (PE) were greater than 0.99999999 and 0.99999951, respectively. In addition, a total of 144 distinct Y-STR haplotypes were observed with 133 Y-STR haplotypes observed only once. The most common Y-STR haplotype was observed three times for two separate haplotypes. The various analyses of these forensically relevant STR loci showed that these markers are informative in the Belize population for forensic and parentage testing applications.

PMID: 25193820 [PubMed - as supplied by publisher]

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Sun, 09/07/2014 - 4:04am
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Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Nat Genet. 2014 Jul;46(7):726-30

Authors: Zhang L, Chen LH, Wan H, Yang R, Wang Z, Feng J, Yang S, Jones S, Wang S, Zhou W, Zhu H, Killela PJ, Zhang J, Wu Z, Li G, Hao S, Wang Y, Webb JB, Friedman HS, Friedman AH, McLendon RE, He Y, Reitman ZJ, Bigner DD, Yan H

Abstract
Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic gliomas. We also performed targeted mutational analysis of an additional 24 such tumors and genome-wide methylation profiling of 45 gliomas. This study led to the discovery of tumor-specific mutations in PPM1D, encoding wild-type p53-induced protein phosphatase 1D (WIP1), in 37.5% of the BSGs that harbored hallmark H3F3A mutations encoding p.Lys27Met substitutions. PPM1D mutations were mutually exclusive with TP53 mutations in BSG and attenuated p53 activation in vitro. PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2. These results define PPM1D as a frequent target of somatic mutation and as a potential therapeutic target in brainstem gliomas.

PMID: 24880341 [PubMed - indexed for MEDLINE]

Changes in retinal aquaporin-9 (AQP9) expression in glaucoma.

Sun, 09/07/2014 - 4:04am
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Changes in retinal aquaporin-9 (AQP9) expression in glaucoma.

Biosci Rep. 2013;33(2)

Authors: Yang MH, Dibas A, Tyan YC

Abstract
The eye contains numerous water channel proteins and the roles of AQPs (aquaporins) in the retina are blurred, especially under disease conditions. The purpose of this study was to investigate the expression of AQP9 gene and proteins affected by elevated IOP (intraocular pressure) in a rat model of glaucoma induced by intravitreous injection of hypertonic saline into the episcleral veins. The gene and protein expressions of AQP9 were investigated by real-time PCR and Western blotting. The immunoreactive expression of AQP9, AQP4 and GFAP (glial fibrillary acidic protein) in the optic nerve of rats exposed to experimentally elevated IOP was detected by immunofluorescence microscopy. The mRNA and protein expression levels of AQP9 were up-regulated in the retina of an animal model of glaucoma. The immunoreactivities of the AQP9, AQP4 and GFAP were also detected and increased in the optic nerve region. The expression of AQP9 was up-regulated in this glaucoma model and the immunoreactivities of the AQP4 and GFAP were also detected as co-localizing with AQP9 in the optic nerve region, indicating retina ganglion cells were surrounded by activated astrocytes. This may indicate that the injured neurons may rely on the astrocytes. The alterations of AQP expression may compensate the glaucomatous damage.

PMID: 23464865 [PubMed - indexed for MEDLINE]

Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

Fri, 09/05/2014 - 4:04am
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Protease-activated receptor 2 (PAR2) is upregulated by Acanthamoeba plasminogen activator (aPA) and induces proinflammatory cytokine in human corneal epithelial cells.

Invest Ophthalmol Vis Sci. 2014 Jun;55(6):3912-21

Authors: Tripathi T, Abdi M, Alizadeh H

Abstract
PURPOSE: Acanthamoeba plasminogen activator (aPA) is a serine protease elaborated by Acanthamoeba trophozoites that facilitates the invasion of trophozoites to the host and contributes to the pathogenesis of Acanthamoeba keratitis (AK). The aim of this study was to explore if aPA stimulates proinflammatory cytokine in human corneal epithelial (HCE) cells via the protease-activated receptors (PARs) pathway.
METHODS: Acanthamoeba castellanii trophozoites were grown in peptone-yeast extract glucose for 7 days, and the supernatants were collected and centrifuged. The aPA was purified using the fast protein liquid chromatography system, and aPA activity was determined by zymography assays. Human corneal epithelial cells were incubated with or without aPA (100 μg/mL), PAR1 agonists (thrombin, 10 μM; TRAP-6, 10 μM), and PAR2 agonists (SLIGRL-NH2, 100 μM; AC 55541, 10 μM) for 24 and 48 hours. Inhibition of PAR1 and PAR2 involved preincubating the HCE cells for 1 hour with the antagonist of PAR1 (SCH 79797, 60 μM) and PAR2 (FSLLRY-NH2, 100 μM) with or without aPA. Human corneal epithelial cells also were preincubated with PAR1 and PAR2 antagonists and then incubated with or without PAR1 agonists (thrombin and TRAP-6) and PAR2 agonists (SLIGRL-NH2 and AC 55541). Expression of PAR1 and PAR2 was examined by quantitative RT-PCR (qRT-PCR), flow cytometry, and immunocytochemistry. Interleukin-8 expression was quantified by qRT-PCR and ELISA.
RESULTS: Human corneal epithelial cells constitutively expressed PAR1 and PAR2 mRNA. Acanthamoeba plasminogen activator and PAR2 agonists significantly upregulated PAR2 mRNA expression (1- and 2-fold, respectively) (P < 0.05). Protease-activated receptor 2 antagonist significantly inhibited aPA, and PAR2 agonists induced PAR2 mRNA expression in HCE cells (P < 0.05). Protease-activated receptor 1 agonists, but not aPA, significantly upregulated PAR1 mRNA expression, which was significantly inhibited by PAR1 antagonist in HCE cells. Acanthamoeba plasminogen activator and PAR2 agonists stimulated IL-8 mRNA expression and protein production, which is significantly diminished by PAR2 antagonist (P < 0.05). Protease-activated receptor 1 antagonist did not alter aPA-stimulated IL-8 mRNA expression and protein production in HCE cells. Flow cytometry and immunocytochemistry showed that aPA and SLIGRL-NH2 (PAR2 agonist) upregulated PAR2 surface protein as compared to that in unstimulated HCE cells. Thrombin, but not aPA, stimulated PAR1 surface protein in HCE cells.
CONCLUSIONS: Acanthamoeba plasminogen activator specifically induces expression and production of IL-8 in HCE cells via PAR2 pathway, and PAR2 antagonists may be used as a therapeutic target in AK.

PMID: 24876278 [PubMed - indexed for MEDLINE]

Patient-centered medical home features and expenditures by medicare beneficiaries.

Thu, 09/04/2014 - 4:04am
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Patient-centered medical home features and expenditures by medicare beneficiaries.

Am J Manag Care. 2014 May;20(5):379-385

Authors: Stockbridge EL, Philpot LM, Pagán JA

Abstract
Objectives To determine the impact of individual features of the patient-centered medical home (PCMH) care model on next-year healthcare expenditures including outpatient, inpatient, emergency department, pharmacy, and total healthcare expenditures among Medicare beneficiaries 65 years and older. Study Design Analysis of retrospective longitudinal survey data. Methods Longitudinal files from the Medical Expenditure Panel Survey were analyzed. Differences in expenditures for individuals whose usual sources of care did or did not have different PCMH features were estimated using recycled predictions from generalized linear regression models. Results Having little to no difficulty contacting the regular source of care over the telephone during regular business hours was associated with significantly lower total and inpatient expenditures over the next year (differences of $2867 and $3736, respectively). Having a regular source of care with office hours at night or on weekends was associated with significantly lower outpatient, emergency department, and other expenditures (differences of $535, $103, and $328, respectively). Pharmacy expenditures were significantly higher for individuals whose usual source of care inquired about medications and treatments prescribed by other doctors (difference of $362). Conclusions This study points out the need to identify how individual PCMH features impact healthcare expenditures across different policy-relevant categories. Practices that have not fully adopted a PCMH model can still make progress in improving quality and controlling costs by adopting even some modest features of the PCMH model.

PMID: 25181567 [PubMed - as supplied by publisher]

c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Thu, 09/04/2014 - 4:04am
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c-Jun NH2-terminal kinase-induced proteasomal degradation of c-FLIPL/S and Bcl2 sensitize prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine.

Biochem Pharmacol. 2014 Aug 30;

Authors: Chaudhary P, Vishwanatha JK

Abstract
Tetrandrine, a constituent of Chinese herb Stephania tetrandra, causes cell death in prostate cancer, but the molecular mechanisms leading to apoptosis is not known. Here we demonstrated that tetrandrine selectively inhibits the growth of prostate cancer PC3 and DU145 cells compared to normal prostate epithelial PWR-1E cells. Tetrandrine-induced cell death in prostate cancer cells is caused by reactive oxygen species (ROS)-mediated activation of c-Jun NH2-terminal kinase (JNK1/2). JNK1/2-mediated proteasomal degradation of c-FLIPL/S and Bcl2 proteins are key events in the sensitization of prostate cancer cells to Fas- and mitochondria-mediated apoptosis by tetrandrine. Tetrandrine-induced JNK1/2 activation caused the translocation of Bax to mitochondria by disrupting its association with Bcl2 which was accompanied by collapse of mitochondrial membrane potential (MMP), cytosolic release of cytochrome c and Smac, and apoptotic cell death. Additionally, tetrandrine-induced JNK1/2 activation increased the phosphorylation of Bcl2 at Ser70 and facilitated its degradation via the ubiquitin-mediated proteasomal pathway. In parallel, tetrandrine-mediated ROS generation also caused the induction of ligand-independent Fas-mediated apoptosis by activating procaspase-8 and Bid cleavage. Inhibition of procaspase-8 activation attenuated the cleavage of Bid, loss of MMP and caspase-3 activation suggest that tetrandrine-induced Fas-mediated apoptosis is associated with the mitochondrial pathway. Furthermore, most of the signaling effects of tetrandrine on apoptosis were significantly attenuated in the presence of antioxidant N-acetyl-L-cysteine, thereby confirming the involvement of ROS in these events. In conclusion, the results of the present study indicate that tetrandrine-induced apoptosis in prostate cancer cells is initiated by ROS generation and that both intrinsic and extrinsic pathway contributes to cell death.

PMID: 25181458 [PubMed - as supplied by publisher]

Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

Thu, 09/04/2014 - 4:04am
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Neural stem cell protects aged rat brain from ischemia-reperfusion injury through neurogenesis and angiogenesis.

J Cereb Blood Flow Metab. 2014 Jul;34(7):1138-47

Authors: Tang Y, Wang J, Lin X, Wang L, Shao B, Jin K, Wang Y, Yang GY

Abstract
Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (P<0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P>0.05) and most of them were differentiated into glial fibrillary acidic protein(+) (GFAP(+)) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (P<0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.

PMID: 24714034 [PubMed - indexed for MEDLINE]

Molecular genetic investigative leads to differentiate monozygotic twins.

Wed, 09/03/2014 - 4:05am

Molecular genetic investigative leads to differentiate monozygotic twins.

Investig Genet. 2014;5:11

Authors: Budowle B

PMID: 25177480 [PubMed]

Risk Factors for and Assessment of Symptomatic Pseudarthrosis After Lumbar Pedicle Subtraction Osteotomy in Adult Spinal Deformity.

Tue, 09/02/2014 - 4:06am

Risk Factors for and Assessment of Symptomatic Pseudarthrosis After Lumbar Pedicle Subtraction Osteotomy in Adult Spinal Deformity.

Spine (Phila Pa 1976). 2014 Jul 1;39(15):1190-1195

Authors: Dickson DD, Lenke LG, Bridwell KH, Koester LA

Abstract
STUDY DESIGN.: Retrospective review of prospectively collected data.
OBJECTIVE.: To assess the prevalence, risk factors, and clinical outcomes for pseudarthrosis after a lumbar pedicle subtraction osteotomy (PSO).
SUMMARY OF BACKGROUND DATA.: There exists no large series that examines pseudarthrosis rates of PSOs.
METHODS.: Data of 171 consecutive patients with adult deformity who underwent a lumbar PSO by 2 surgeons at a single institution with a minimum 2-year follow-up were analyzed. Pseudarthrosis diagnosed through sagittal malalignment and instrumentation failure noted on radiograph was confirmed intraoperatively.
RESULTS.: Eighteen (10.5%) of 171 patients developed pseudarthrosis after a PSO. Eleven of the 18 patients (6.4% of all patients, 61.1% of the 18 patients with pseudarthrosis) had pseudarthrosis at the PSO site, L3 being the most common; other locations included the lumbosacral junction (4/18), thoracolumbar junction (2/18), and upper thoracic spine (1/18). Preoperative pseudarthrosis level was a predictor of the postoperative level of pseudarthrosis (93%). Fifteen of the 18 patients (83%) had no interbody fusion directly above or below the PSO site, 16 (88%) had a history of pseudarthrosis at the time of PSO surgery and 2 of 3 patients who had prior radiation to the lumbar region developed pseudarthrosis. Most pseudarthroses occurred within the first 2 years (n = 13/18), between 2 and 5 years (n = 3/18), and more than 5 years (n = 2/18) postoperatively. Prior pseudarthrosis (P < 0.0001), pseudarthrosis at the PSO site (P < 0.0001), prior decompression in the lumbar region (P = 0.0037), prior radiation to the lumbar region (P < 0.0001), and presence of inflammatory/neurological disorders (P < 0.0036) were identified as risk factors. All 18 patients with pseudarthroses required revision surgery (posterior-only surgery, n = 12; anteroposterior surgery, n = 6) due to loss of sagittal alignment and pain. The mean pre-revision Scoliosis Research Society score was 85, post-revision score was 95 (P = 0.0166), and the mean pre-revision Oswestry Disability Index score was 42.5, post-revision score was 34.5 (P = 0.0203).
CONCLUSION.: The overall prevalence of pseudarthrosis was 10.5% of which 61% occurred at the actual PSO site and Scoliosis Research Society and Oswestry Disability Index scores improved significantly after pseudarthrosis repair.Level of Evidence: 4.

PMID: 25171067 [PubMed - as supplied by publisher]

Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma.

Sat, 08/30/2014 - 4:06am
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Evidence of brain tumor stem progenitor-like cells with low proliferative capacity in human benign pituitary adenoma.

Cancer Lett. 2014 Jul 10;349(1):61-6

Authors: Chen L, Ye H, Wang X, Tang X, Mao Y, Zhao Y, Wu Z, Mao XO, Xie L, Jin K, Yao Y

Abstract
Tumor stem cells have been implicated as cancer-initiating cells in malignant brain tumors. However, whether benign brain tumors also contain tumor stem cells are largely unexplored. Here, we investigated whether tumor stem-like cells were present in pituitary adenoma similar to malignant brain tumors. By immunocytochemistry, we found that pituitary adenoma tissues expressed neural stem cell marker. These cells could form neurospheres in vitro, expressed neural stem/progenitor cell markers and generated daughter cells with the capacity to differentiate into three neural lineages. Importantly, compared with non-invasive pituitary adenomas, we found that CD133 expression was significantly increased in invasive pituitary adenomas, suggesting that the proliferative capacity was correlated with the malignance of pituitary adenomas. Finally, invasive pituitary adenomas cells displayed lower proliferative ability than glioblastoma. Our data indicate that a subpopulation of stem/progenitor-like cells are present in pituitary adenomas, and these cells may be responsible for benign tumor initiation and maintenance.

PMID: 24732807 [PubMed - indexed for MEDLINE]

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

Fri, 08/29/2014 - 4:05am
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Simultaneous quantification of mitochondrial DNA copy number and deletion ratio: a multiplex real-time PCR assay.

Sci Rep. 2014;4:3887

Authors: Phillips NR, Sprouse ML, Roby RK

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

PMID: 24463429 [PubMed - indexed for MEDLINE]

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

Fri, 08/29/2014 - 4:05am
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Outcomes of osteopathic manual treatment for chronic low back pain according to baseline pain severity: results from the OSTEOPATHIC Trial.

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

Authors: Licciardone JC, Kearns CM, Minotti DE

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

PMID: 23759340 [PubMed - indexed for MEDLINE]

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

Wed, 08/27/2014 - 4:05am
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Coenzyme Q10 and α-tocopherol reversed age-associated functional impairments in mice.

Exp Gerontol. 2014 Aug 18;

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

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

PMID: 25149567 [PubMed - as supplied by publisher]

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

Wed, 08/27/2014 - 4:05am
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Preoperative Decision Making in the Treatment of High-Angle "Vertical" Femoral Neck Fractures in Young Adult Patients: An Expert Opinion Survey of the Orthopaedic Trauma Association's (OTA) Membership.

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

Authors: Luttrell K, Beltran M, Collinge CA

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

PMID: 25148589 [PubMed - in process]

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

Wed, 08/27/2014 - 4:05am
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Prognostic models to detect and monitor the near-term risk of suicide: state of the science.

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

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

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

PMID: 25145737 [PubMed - in process]

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

Wed, 08/27/2014 - 4:05am
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Introduction to the suicide prevention research prioritization task force special supplement: the topic experts.

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

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

PMID: 25145726 [PubMed - in process]

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

Tue, 08/26/2014 - 4:06am
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Effects of conditional central expression of HIV-1 tat protein to potentiate cocaine-mediated psychostimulation and reward among male mice.

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

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

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

PMID: 23945478 [PubMed - indexed for MEDLINE]