Recent Research Articles from UNTHSC

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Role of C/EBP Homologous Protein in Retinal Ganglion Cell Death after Ischemia/Reperfusion Injury.

2 hours 59 min ago

Role of C/EBP Homologous Protein in Retinal Ganglion Cell Death after Ischemia/Reperfusion Injury.

Invest Ophthalmol Vis Sci. 2014 Nov 20;

Authors: Nashine S, Liu Y, Kim BJ, Clark AF, Pang IH

Abstract
Purpose: To investigate the role of C/EBP homologous protein (CHOP), a pro-apoptotic protein and unfolded protein response (UPR) marker that is involved in ER-stress mediated apoptosis, in mouse retinal ganglion cell (RGC) death following ischemia/reperfusion (I/R) injury. Methods: Retinal I/R was induced in adult C57BL/6J (wild type; WT) and CHOP knockout (Chop-/-) mice by raising intraocular pressure to 120 mmHg for 60 min. Expression of CHOP and other UPR markers was studied by Western blot and immunohistochemistry. RGC counts were performed in retinal flatmounts stained with an RGC marker. RGC function was evaluated by the scotopic threshold response (STR) electroretinography. Results: In WT mice, retinal CHOP was up-regulated by 30% in I/R-injured eyes compared to uninjured eyes 3 d after injury (p<0.05). Immunohistochemistry confirmed CHOP up-regulation specifically in RGCs. CHOP knockout did not affect baseline RGC density or STR amplitude. I/R decreased RGC densities and STR amplitudes in both WT and Chop-/- mice. However, survival of RGCs in I/R-injured Chop-/- mouse was 48% higher (p<0.05) than that of I/R-injured WT mouse 3 d after I/R injury. Similarly, RGC density was significantly higher in Chop-/- eyes at 7, 14, and 28 d after I/R. STR amplitudes of Chop-/- mice were significantly higher at 3 and 7 d after I/R than the WT mice. Conclusions: Absence of CHOP partially protects against RGC loss and reduction in retinal function after I/R injury, indicating that CHOP and thus ER-stress play an important role in RGC apoptosis in retinal I/R injury.

PMID: 25414185 [PubMed - as supplied by publisher]

Massively parallel sequencing of forensically relevant single nucleotide polymorphisms using TruSeq™ forensic amplicon.

Sat, 11/22/2014 - 4:05pm
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Massively parallel sequencing of forensically relevant single nucleotide polymorphisms using TruSeq™ forensic amplicon.

Int J Legal Med. 2014 Nov 19;

Authors: Warshauer DH, Davis CP, Holt C, Han Y, Walichiewicz P, Richardson T, Stephens K, Jager A, King J, Budowle B

Abstract
The TruSeq™ Forensic Amplicon library preparation protocol, originally designed to attach sequencing adapters to chromatin-bound DNA for chromatin immunoprecipitation sequencing (TruSeq™ ChIP-Seq), was used here to attach adapters directly to amplicons containing markers of forensic interest. In this study, the TruSeq™ Forensic Amplicon library preparation protocol was used to detect 160 single nucleotide polymorphisms (SNPs), including human identification SNPs (iSNPs), ancestry, and phenotypic SNPs (apSNPs) in 12 reference samples. Results were compared with those generated by a second laboratory using the same technique, as well as to those generated by whole genome sequencing (WGS). The genotype calls made using the TruSeq™ Forensic Amplicon library preparation protocol were highly concordant. The protocol described herein represents an effective and relatively sensitive means of preparing amplified nuclear DNA for massively parallel sequencing (MPS).

PMID: 25408291 [PubMed - as supplied by publisher]

Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: A finite element study.

Sat, 11/22/2014 - 4:05pm
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Dual small fragment plating improves screw-to-screw load sharing for mid-diaphyseal humeral fracture fixation: A finite element study.

Technol Health Care. 2014 Nov 18;

Authors: Kosmopoulos V, Luedke C, Nana AD

Abstract
BACKGROUND: A smaller humerus in some patients makes the use of a large fragment fixation plate difficult. Dual small fragment plate constructs have been suggested as an alternative.
OBJECTIVE: This study compares the biomechanical performance of three single and one dual plate construct for mid-diaphyseal humeral fracture fixation.
METHODS: Five humeral shaft finite element models (1 intact and 4 fixation) were loaded in torsion, compression, posterior-anterior (PA) bending, and lateral-medial (LM) bending. A comminuted fracture was simulated by a 1-cm gap. Fracture fixation was modelled by: (A) 4.5-mm 9-hole large fragment plate (wide), (B) 4.5-mm 9-hole large fragment plate (narrow), (C) 3.5-mm 9-hole small fragment plate, and (D) one 3.5-mm 9-hole small fragment plate and one 3.5-mm 7-hole small fragment plate.
RESULTS: Model A showed the best outcomes in torsion and PA bending, whereas Model D outperformed the others in compression and LM bending. Stress concentrations were located near and around the unused screw holes for each of the single plate models and at the neck of the screws just below the plates for all the models studied. Other than in PA bending, Model D showed the best overall screw-to-screw load sharing characteristics.
CONCLUSION: The results support using a dual small fragment locking plate construct as an alternative in cases where crutch weight-bearing (compression) tolerance may be important and where anatomy limits the size of the humerus bone segment available for large fragment plate fixation.

PMID: 25408282 [PubMed - as supplied by publisher]

Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression In the Brain of Alcoholic Rats.

Sat, 11/22/2014 - 4:05pm
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Aberrant Histone Acetylation Promotes Mitochondrial Respiratory Suppression In the Brain of Alcoholic Rats.

J Pharmacol Exp Ther. 2014 Nov 18;

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 repeat unsuccessful attempts at abstaining, developing a pattern of repeated withdrawal from ethanol exposure. Here, 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 a small non-coding RNA (microRNA) let-7f. Male rats receive two cycles of ethanol diet (7.5%, four weeks) and withdrawal. Prefrontal cortex was collected to measure mitochondrial respiration and histone acetylation using 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. Histone acetylation promoter (Trichostatin A, TSA) and let-7f antagomir were applied during withdrawal. Mitochondrial respiration, let-7f level, and cell viability were assessed using XF respirometry, qPCR, TaqMan let-7f primers, and Calcein-AM assay, respectively. Repeated ethanol withdrawn rats show more than a twofold increase in histone acetylation, accompanied by mitochondrial respiratory suppression. EW-induced mitochondrial respiratory suppression is exacerbated by TSA treatment in a manner that is attenuated by let-7f antagomir cotreatment. TSA treatment does not alter the increasing effect of EW on let-7f level but dramatically exacerbates 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, independently or additively with let-7f.

PMID: 25406171 [PubMed - as supplied by publisher]

Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.

Thu, 11/20/2014 - 4:05am
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Pathogenic strains of Acanthamoeba are recognized by TLR4 and initiated inflammatory responses in the cornea.

PLoS One. 2014;9(3):e92375

Authors: Alizadeh H, Tripathi T, Abdi M, Smith AD

Abstract
Free-living amoebae of the Acanthamoeba species are the causative agent of Acanthamoeba keratitis (AK), a sight-threatening corneal infection that causes severe pain and a characteristic ring-shaped corneal infiltrate. Innate immune responses play an important role in resistance against AK. The aim of this study is to determine if Toll-like receptors (TLRs) on corneal epithelial cells are activated by Acanthamoeba, leading to initiation of inflammatory responses in the cornea. Human corneal epithelial (HCE) cells constitutively expressed TLR1, TLR2, TLR3, TLR4, and TLR9 mRNA, and A. castellanii upregulated TLR4 transcription. Expression of TLR1, TLR2, TLR3, and TLR9 was unchanged when HCE cells were exposed to A. castellanii. IL-8 mRNA expression was upregulated in HCE cells exposed to A. castellanii. A. castellanii and lipopolysaccharide (LPS) induced significant IL-8 production by HCE cells as measured by ELISA. The percentage of total cells positive for TLR4 was higher in A. castellanii stimulated HCE cells compared to unstimulated HCE cells. A. castellanii induced upregulation of IL-8 in TLR4 expressing human embryonic kidney (HEK)-293 cells, but not TLR3 expressing HEK-293 cells. TLR4 neutralizing antibody inhibited A. castellanii-induced IL-8 by HCE and HEK-293 cells. Clinical strains but not soil strains of Acanthamoeba activated TLR4 expression in Chinese hamster corneas in vivo and in vitro. Clinical isolates but not soil isolates of Acanthamoeba induced significant (P< 0.05) CXCL2 production in Chinese hamster corneas 3 and 7 days after infection, which coincided with increased inflammatory cells in the corneas. Results suggest that pathogenic species of Acanthamoeba activate TLR4 and induce production of CXCL2 in the Chinese hamster model of AK. TLR4 may be a potential target in the development of novel treatment strategies in Acanthamoeba and other microbial infections that activate TLR4 in corneal cells.

PMID: 24633052 [PubMed - indexed for MEDLINE]

Internal validation of the GlobalFiler™ Express PCR Amplification Kit for the direct amplification of reference DNA samples on a high-throughput automated workflow.

Wed, 11/19/2014 - 4:06am
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Internal validation of the GlobalFiler™ Express PCR Amplification Kit for the direct amplification of reference DNA samples on a high-throughput automated workflow.

Forensic Sci Int Genet. 2014 May;10:33-9

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

Abstract
The GlobalFiler™ Express PCR Amplification Kit uses 6-dye fluorescent chemistry to enable multiplexing of 21 autosomal STRs, 1 Y-STR, 1 Y-indel and the sex-determining marker amelogenin. The kit is specifically designed for processing reference DNA samples in a high throughput manner. Validation studies were conducted to assess the performance and define the limitations of this direct amplification kit for typing blood and buccal reference DNA samples on various punchable collection media. Studies included thermal cycling sensitivity, reproducibility, precision, sensitivity of detection, minimum detection threshold, system contamination, stochastic threshold and concordance. Results showed that optimal amplification and injection parameters for a 1.2mm punch from blood and buccal samples were 27 and 28 cycles, respectively, combined with a 12s injection on an ABI 3500xL Genetic Analyzer. Minimum detection thresholds were set at 100 and 120RFUs for 27 and 28 cycles, respectively, and it was suggested that data from positive amplification controls provided a better threshold representation. Stochastic thresholds were set at 250 and 400RFUs for 27 and 28 cycles, respectively, as stochastic effects increased with cycle number. The minimum amount of input DNA resulting in a full profile was 0.5ng, however, the optimum range determined was 2.5-10ng. Profile quality from the GlobalFiler™ Express Kit and the previously validated AmpFlSTR(®) Identifiler(®) Direct Kit was comparable. The validation data support that reliable DNA typing results from reference DNA samples can be obtained using the GlobalFiler™ Express PCR Amplification Kit.

PMID: 24552885 [PubMed - indexed for MEDLINE]

Modeling one complete versus triplicate analyses in low template DNA typing.

Wed, 11/19/2014 - 4:06am
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Modeling one complete versus triplicate analyses in low template DNA typing.

Int J Legal Med. 2014 Mar;128(2):259-67

Authors: Ge J, Budowle B

Abstract
There are generally two strategies for low template DNA typing: the complete strategy, which uses all available DNA in a single PCR and subsequent typing, and the consensus strategy, in which the biological sample is divided into two or more aliquots and the genotype profile is determined by consensus from these "replicates." In this study, the consensus and complete strategies are compared by a statistical approach in terms of the accuracy of obtaining the correct genotype at a single locus for single source samples. Logistic models were employed to describe the allele drop-out and drop-in events. The parameters of the models were estimated with empirical or hypothetical data. The probabilities of obtaining the true genotype and the chances to observe drop-out and drop-in alleles were estimated and compared for both strategies. Consistent with a previous experimental study, this study found that, with relatively high input DNA (e.g., ≥ 100 pg), the complete strategy performs better than the consensus strategy to obtain the true genotype and the complete strategy will display less dropped out alleles. The consensus strategy had less drop-in alleles for ≤ 100 pg DNA samples. Moreover, the limitations of the logistic models were discussed. Ideal models with better fit of empirical data approximating casework conditions were proposed for future studies.

PMID: 24096959 [PubMed - indexed for MEDLINE]

Socioeconomic status and chemotherapy use for melanoma in older people.

Wed, 11/19/2014 - 4:06am
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Socioeconomic status and chemotherapy use for melanoma in older people.

Can J Aging. 2011 Mar;30(1):143-53

Authors: Reyes-Ortiz CA, Goodwin JS, Zhang DD, Freeman JL

Abstract
The study objective was to examine the association, among older persons with cutaneous melanoma, between areal socioeconomic status (SES) and receiving chemotherapy. SEER-Medicare-linked database (1,239 white men and women aged ≥ 66, with invasive melanoma [regional and distant stages]; 1991-1999) was used. SES was measured by census tract poverty level (average of 1990 and 2000 Census data). Covariates were sociodemographics, tumor characteristics, and comorbidity index. Residing in poorer SES areas was associated with a lower likelihood for receiving chemotherapy among patients in the overall sample (adjusted odds ratios = OR 0.97, 95% confidence interval = CI 0.95-0.99), and those with regional stage at diagnosis (OR 0.97, 95% CI 0.94-0.98). These findings reflect socioeconomic disparities in chemotherapy use for melanoma among older white patients in the United States.

PMID: 21356154 [PubMed - indexed for MEDLINE]

A depressive endophenotype of poorer cognition among cognitively healthy community-dwelling adults: results from the Western Australia memory study.

Tue, 11/18/2014 - 4:05am
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A depressive endophenotype of poorer cognition among cognitively healthy community-dwelling adults: results from the Western Australia memory study.

Int J Geriatr Psychiatry. 2014 Nov 13;

Authors: Johnson LA, Sohrabi HR, Hall JR, Kevin T, Edwards M, O'Bryant SE, Martins RN

Abstract
OBJECTIVE: The objective was to evaluate in a cognitively normal population the utility of an endophenotype of the depression-cognition link previously shown to be related to cognitive functioning in mild cognitive impairment and Alzheimer's disease.
METHODS: The data of 460 cognitively normal adults aged 32-92 years (M = 63.5, standard deviation = 9.24) from the Western Australian Memory Study with the Cross-national comparisons of the Cambridge Cognitive Examination-revised (CAMCOG-R) scores and 30-item Geriatric Depression Scale (GDS) scores were analyzed to determine the relationship between the five-item depressive endophenotype (DepE) scale drawn from the GDS and level of performance on a measure of cognitive functioning.
RESULTS: For the entire sample, there was a nonsignificant trend toward a negative relationship between DepE and CAMCOG-R scores. When analyzed for those 65 years and older, there was a significant negative relationship between the two measures (p = 0.001) with DepE scores significantly increasing the risk for performing more poorly on the CAMCOG-R (odds ratio = 1.53). Analysis of data for those 70 years and older showed that DepE was the only predictor significantly related to poorer CAMCOG-R performance (p = 0.001). For the 70 years and older group, DepE scores significantly increased the risk of poorer CAMCOG-R scores (odds ratio = 2.23). Analysis of the entire sample on the basis of ApoEε4 carrier status revealed that DepE scores were significantly negatively related only to ApoEε4 noncarrier regardless of age.
CONCLUSIONS: Elevated DepE scores are associated with poor neuropsychological performance among cognitively normal older adults. Use of the DepE may allow for the identification of a subset of older adults where depression is a primary factor in cognitive decline and who may benefit from antidepressant therapies. Copyright © 2014 John Wiley & Sons, Ltd.

PMID: 25394326 [PubMed - as supplied by publisher]

Glial scar formation occurs in the human brain after ischemic stroke.

Tue, 11/18/2014 - 4:05am
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Glial scar formation occurs in the human brain after ischemic stroke.

Int J Med Sci. 2014;11(4):344-8

Authors: Huang L, Wu ZB, Zhuge Q, Zheng W, Shao B, Wang B, Sun F, Jin K

Abstract
Reactive gliosis and glial scar formation have been evidenced in the animal model of ischemic stroke, but not in human ischemic brain. Here, we have found that GFAP, ED1 and chondroitin sulphate proteoglycans (CSPG) expression were significantly increased in the cortical peri-infarct regions after ischemic stroke, compared with adjacent normal tissues and control subjects. Double immunolabeling showed that GFAP-positive reactive astrocytes in the peri-infarct region expressed CSPG, but showed no overlap with ED1-positive activated microglia. Our findings suggest that reactive gliosis and glial scar formation as seen in animal models of stroke are reflective of what occurs in the human brain after an ischemic injury.

PMID: 24578611 [PubMed - indexed for MEDLINE]

Noninfectious Diarrhea in HIV Seropositive Individuals: a Review of Prevalence Rates, Etiology, and Management in the Era of Combination Antiretroviral Therapy.

Fri, 11/14/2014 - 4:05am
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Noninfectious Diarrhea in HIV Seropositive Individuals: a Review of Prevalence Rates, Etiology, and Management in the Era of Combination Antiretroviral Therapy.

Infect Dis Ther. 2014 Nov 12;

Authors: Clay PG, Crutchley RD

Abstract
INTRODUCTION: Diarrhea poses a substantial burden for patients with human immunodeficiency virus (HIV), negatively impacting quality-of-life (QoL) and adherence to antiretroviral therapy. During the combination antiretroviral therapy (cART) era, as incidence of opportunistic infection as a cause of diarrhea decreased, incidence of noninfectious diarrhea (including diarrhea as an adverse event [AE] of cART and HIV enteropathy) increased proportionately. A literature search was conducted for information on prevalence, etiology, and treatment options for noninfectious diarrhea in patients with HIV.
RESULTS: For marketed antiretroviral therapies, up to 28% of patients live with >4 loose or watery stools per day. The US Food and Drug Administration (FDA) does not require pharmaceutical manufacturers to include, within approved prescribing information, prevalence rates for all grades of diarrhea. Traditionally, noninfectious diarrhea management focused on avoiding use of diarrhea-associated cART; symptom management (nonpharmacologic and/or pharmacologic); and, as a last resort, changing cART. Examining the evidence upon which this approach is based reveals that most strategies rely upon anecdotal information and case reports. This review summarizes the literature and updates clinicians on the most recent options for management of noninfectious diarrhea in patients with HIV.
CONCLUSION: Diarrhea in patients with HIV is a significant unmet clinical need that contributes to worsening QoL and complicates medical management. Approaching management using a stepwise method of nonpharmacologic (diet), nonprescription (over-the-counter) and, finally, prescription agent changes (modification of cART or addition of an evidence-based antidiarrheal) appears reasonable, despite a lack of clear scientific evidence to support the initial two steps of this approach. If diet modifications, including psyllium and fiber introduction, fail to resolve noninfectious diarrhea in patients with HIV, loperamide followed by crofelemer should be considered. Clinicians are encouraged to review the most recent literature, not rely upon prescribing information. Continued vigilance by HIV providers to the presence of gastrointestinal AEs, even in patients taking the most recently approved antiretroviral agents, is warranted. Additional research is justified in identifying the etiology and management of HIV-associated diarrhea in patients on successful cART regimens.

PMID: 25388760 [PubMed - as supplied by publisher]

Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia.

Thu, 11/13/2014 - 12:04pm
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Two-week normobaric intermittent hypoxia exposures enhance oxyhemoglobin equilibrium and cardiac responses during hypoxemia.

Am J Physiol Regul Integr Comp Physiol. 2014 Sep 15;307(6):R721-30

Authors: Zhang P, Downey HF, Chen S, Shi X

Abstract
Intermittent hypoxia (IH) is extensively applied to challenge cardiovascular and respiratory function, and to induce physiological acclimatization. The purpose of this study was to test the hypothesis that oxyhemoglobin equilibrium and tachycardiac responses during hypoxemia were enhanced after 14-day IH exposures. Normobaric-poikilocapnic hypoxia was induced with inhalation of 10% O2 for 5-6 min interspersed with 4 min recovery on eight nonsmokers. Heart rate (HR), arterial O2 saturation (SaO 2), and end-tidal O2 (PetO 2) were continuously monitored during cyclic normoxia and hypoxia. These variables were compared during the first and fifth hypoxic bouts between day 1 and day 14. There was a rightward shift in the oxyhemoglobin equilibrium response following 14-day IH exposures, as indicated by the greater PetO 2 (an index of arterial Po2) at 50% of SaO 2 on day 14 compared with day 1 [33.9 ± 1.5 vs. 28.2 ± 1.3 mmHg (P = 0.005) during the first hypoxic bout and 39.4 ± 2.4 vs. 31.4 ± 1.5 mmHg (P = 0.006) during the fifth hypoxic bout] and by the augmented gains of ΔSaO 2/ΔPetO 2 (i.e., deoxygenation) during PetO 2 from 65 to 40 mmHg in the first (1.12 ± 0.08 vs. 0.80 ± 0.02%/mmHg, P = 0.001) and the fifth (1.76 ± 0.31 vs. 1.05 ± 0.06%/mmHg, P = 0.024) hypoxic bouts. Repetitive IH exposures attenuated (P = 0.049) the tachycardiac response to hypoxia while significantly enhancing normoxic R-R interval variability in low-frequency and high-frequency spectra without changes in arterial blood pressure at rest or during hypoxia. We conclude that 14-day IH exposures enhance arterial O2 delivery and improve vagal control of HR during hypoxic hypoxemia.

PMID: 25056104 [PubMed - indexed for MEDLINE]

Glutaredoxin2 (GRX2) gene deletion induced early on-set of age-dependent cataract in mice.

Fri, 11/07/2014 - 4:05am
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Glutaredoxin2 (GRX2) gene deletion induced early on-set of age-dependent cataract in mice.

J Biol Chem. 2014 Nov 1;

Authors: Wu H, Yu Y, David L, Ho YS, Lou MF

Abstract
Glutaredoxin2 (Grx2) is an isozyme of glutaredoxin1 (thioltransferase) present in the mitochondria and nucleus with disulfide reductase and peroxidase activities, and controls thiol/disulfide balance in cells. In this study, we investigated if Grx2 gene deletion could induce faster age-related cataract formation and elucidated the biochemical changes effected by Grx2 gene deletion that may contribute to lens opacity. Slit lamp was used to examine the lenses in Grx2 knockout (KO) mice and age-matched wild-type (WT) mice aged from 1 to 16 months. In the Grx2 null mice, the lens nuclear opacity began at 5 months, 3 months sooner than that of the control mice and the progression of cataract were also much faster than the age-matched controls. Lenses of KO mice contained lower levels of protein thiols and GSH with a significant accumulation of S-glutathionylated proteins. Actin, αA-crystallin, and βB2-crystallin were identified by Western blot and mass spectroscopy as the major S-glutathionylated proteins in the lenses of 16 month-old Grx2 KO mice. Compared with the WT control, the lens of Grx2 KO mouse had only 50% of the activity in complex I, and complex IV, and less than 10% of the ATP pool. It was concluded that Grx2 gene deletion altered the function of lens structural proteins through S-glutathionylation, and also caused severe disturbance in mitochondrial function. These combined alterations affected lens transparency.

PMID: 25362663 [PubMed - as supplied by publisher]

Neurogenesis in neurological and psychiatric diseases and brain injury: from bench to bedside.

Fri, 11/07/2014 - 4:05am
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Neurogenesis in neurological and psychiatric diseases and brain injury: from bench to bedside.

Prog Neurobiol. 2014 Apr;115:116-37

Authors: Ruan L, Lau BW, Wang J, Huang L, Zhuge Q, Wang B, Jin K, So KF

Abstract
Researchers who have uncovered the presence of stem cells in an adult's central nervous system have not only challenged the dogma that new neurons cannot be generated during adulthood, but also shed light on the etiology and disease mechanisms underlying many neurological and psychiatric disorders. Brain trauma, neurodegenerative diseases, and psychiatric disorders pose enormous burdens at both personal and societal levels. Although medications for these disorders are widely used, the treatment mechanisms underlying the illnesses remain largely elusive. In the past decade, an increasing amount of evidence indicate that adult neurogenesis (i.e. generating new CNS neurons during adulthood) may be involved in the pathology of different CNS disorders, and thus neurogenesis may be a potential target area for treatments. Although new neurons were shown to be a major player in mediating treatment efficacy of neurological and psychotropic drugs on cognitive functions, it is still debatable if the altered production of new neurons can cause the disorders. This review hence seeks to discuss pre and current clinical studies that demonstrate the functional impact adult neurogenesis have on neurological and psychiatric illnesses while examining the related underlying disease mechanisms.

PMID: 24384539 [PubMed - indexed for MEDLINE]

Observational Study Fails to Demonstrate the Effectiveness of OMT in Decreasing Low Back Pain.

Wed, 11/05/2014 - 4:07am
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Observational Study Fails to Demonstrate the Effectiveness of OMT in Decreasing Low Back Pain.

J Am Osteopath Assoc. 2014 Nov;114(11):e119-20

Authors: Licciardone JC

PMID: 25352411 [PubMed - in process]

Impact of a community based implementation of REACH II program for caregivers of Alzheimer's patients.

Wed, 11/05/2014 - 4:07am
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Impact of a community based implementation of REACH II program for caregivers of Alzheimer's patients.

PLoS One. 2014;9(2):e89290

Authors: Lykens K, Moayad N, Biswas S, Reyes-Ortiz C, Singh KP

Abstract
BACKGROUND: In 2009 an estimated 5.3 million people in the United States were afflicted with Alzheimer's disease, a degenerative form of dementia. The impact of this disease is not limited to the patient but also has significant impact on the lives and health of their family caregivers. The Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program was developed and tested in clinical studies. The REACH II program is now being delivered by community agencies in several locations. This study examines the impact of the REACH II program on caregiver lives and health in a city in north Texas.
STUDY DESIGN: Family caregivers of Alzheimer's patients were assessed using an instrument covering the multi-item domains of Caregiver Burden, Depression, Self-Care, and Social Support upon enrollment in the program and at the completion of the 6 month intervention. The domain scores were analyzed using a multivariate paired t-test and Bonferroni confidence interval for the differences in pre- and post-service domain scores.
RESULTS: A total of 494 families were enrolled in the program during the period January 1, 2011 through June 30, 2012. Of these families 177 completed the 6 month program and have pre - and post service domain scores. The median age for the caregivers was 62 years. The domain scores for Depression and Caregiver Burden demonstrated statistically significant improvements upon program completion.
CONCLUSION: The REACH II intervention was successfully implemented by a community agency with comparable impacts to those of the clinical trial warranting wider scale implementation.

PMID: 24586664 [PubMed - indexed for MEDLINE]

Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

Wed, 11/05/2014 - 4:07am
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Characterization and reduction of cardiac- and respiratory-induced noise as a function of the sampling rate (TR) in fMRI.

Neuroimage. 2014 Apr 1;89:314-30

Authors: Cordes D, Nandy RR, Schafer S, Wager TD

Abstract
It has recently been shown that both high-frequency and low-frequency cardiac and respiratory noise sources exist throughout the entire brain and can cause significant signal changes in fMRI data. It is also known that the brainstem, basal forebrain and spinal cord areas are problematic for fMRI because of the magnitude of cardiac-induced pulsations at these locations. In this study, the physiological noise contributions in the lower brain areas (covering the brainstem and adjacent regions) are investigated and a novel method is presented for computing both low-frequency and high-frequency physiological regressors accurately for each subject. In particular, using a novel optimization algorithm that penalizes curvature (i.e. the second derivative) of the physiological hemodynamic response functions, the cardiac- and respiratory-related response functions are computed. The physiological noise variance is determined for each voxel and the frequency-aliasing property of the high-frequency cardiac waveform as a function of the repetition time (TR) is investigated. It is shown that for the brainstem and other brain areas associated with large pulsations of the cardiac rate, the temporal SNR associated with the low-frequency range of the BOLD response has maxima at subject-specific TRs. At these values, the high-frequency aliased cardiac rate can be eliminated by digital filtering without affecting the BOLD-related signal.

PMID: 24355483 [PubMed - indexed for MEDLINE]

FRET based ratio-metric sensing of hyaluronidase in synthetic urine as a biomarker for bladder and prostate cancer.

Thu, 10/30/2014 - 7:05am
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FRET based ratio-metric sensing of hyaluronidase in synthetic urine as a biomarker for bladder and prostate cancer.

Curr Pharm Biotechnol. 2013;14(4):470-4

Authors: Chib R, Raut S, Fudala R, Chang A, Mummert M, Rich R, Gryczynski Z, Gryczynski I

Abstract
Elevated hyaluronidase levels are found in the urine of bladder and prostate cancer patients. Therefore, HA-ase is regarded as an important biomarker for the detection of these cancers. In this report, we use a FRET based ratiometric sensing approach to detect the level of HA-ase in synthetic urine. For this, we have used a HA-FRET probe (hyaluronan) labeled with fluorescein as a donor and rhodamine as an acceptor. We monitor the digestion of our HA-FRET probe with different concentrations of HA-ase in synthetic urine via fluorescence emission. The extent to which FRET is released depends on the concentration of HA-ase. Our fluorescence intensity results are also supported with time resolved fluorescence decay data. This assay can be used to develop a non-invasive technique for the detection of bladder and/or prostate cancer progression.

PMID: 23360262 [PubMed - indexed for MEDLINE]

Are you bleeding? Validation of a machine-learning algorithm for determination of blood volume status: application to remote triage.

Wed, 10/29/2014 - 3:06am
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Are you bleeding? Validation of a machine-learning algorithm for determination of blood volume status: application to remote triage.

J Appl Physiol (1985). 2014 Mar 1;116(5):486-94

Authors: Rickards CA, Vyas N, Ryan KL, Ward KR, Andre D, Hurst GM, Barrera CR, Convertino VA

Abstract
Due to limited remote triage monitoring capabilities, combat medics cannot currently distinguish bleeding soldiers from those engaged in combat unless they have physical access to them. The purpose of this study was to test the hypothesis that low-level physiological signals can be used to develop a machine-learning algorithm for tracking changes in central blood volume that will subsequently distinguish central hypovolemia from physical activity. Twenty-four subjects underwent central hypovolemia via lower body negative pressure (LBNP), and a supine-cycle exercise protocol. Exercise workloads were determined by matching heart rate responses from each LBNP level. Heart rate and stroke volume (SV) were measured via Finometer. ECG, heat flux, skin temperature, galvanic skin response, and two-axis acceleration were obtained from an armband (SenseWear Pro2) and used to develop a machine-learning algorithm to predict changes in SV as an index of central blood volume under both conditions. The algorithm SV was retrospectively compared against Finometer SV. A model was developed to determine whether unknown data points could be correctly classified into these two conditions using leave-one-out cross-validation. Algorithm vs. Finometer SV values were strongly correlated for LBNP in individual subjects (mean r = 0.92; range 0.75-0.98), but only moderately correlated for exercise (mean r = 0.50; range -0.23-0.87). From the first level of LBNP/exercise, the machine-learning algorithm was able to distinguish between LBNP and exercise with high accuracy, sensitivity, and specificity (all ≥90%). In conclusion, a machine-learning algorithm developed from low-level physiological signals could reliably distinguish central hypovolemia from exercise, indicating that this device could provide battlefield remote triage capabilities.

PMID: 24408992 [PubMed - indexed for MEDLINE]

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer.

Tue, 10/28/2014 - 3:06am

ERG Oncoprotein Inhibits ANXA2 Expression and Function in Prostate Cancer.

Mol Cancer Res. 2014 Oct 24;

Authors: Griner NB, Young D, Chaudhary P, Mohamed A, Huang W, Chen Y, Sreenath T, Dobi A, Petrovics G, Vishwanatha JK, Sesterhenn IA, Srivastava S, Tan SH

Abstract
Overexpression of ERG in the prostate epithelium, due to chromosomal translocations, contributes to prostate tumorigenesis. Here, genomic analysis of ERG siRNA-treated prostate cells harboring the endogenous TMPRSS2-ERG fusion revealed an inverse relationship between ERG and Annexin A2 (ANXA2) expression at both the RNA and protein level. ANXA2, a Ca2+-dependent and phospholipid-binding protein, is involved in various cellular functions, including maintenance of epithelial cell polarity. Mechanistic studies defined the prostate-specific transcription start site of ANXA2 and showed that the recruitment of ERG to the ANXA2 promoter is required for transcriptional repression by ERG. Knockdown of ERG enhanced the apical localization of ANXA2, the bundling of actin filaments at cell-cell junctions and formation of a polarized epithelial phenotype. ERG overexpression disrupted ANXA2 mediated cell polarity and promoted epithelial mesenchymal transition (EMT) by inhibiting CDC42 and RHOA, and by activating cofilin. Immunohistochemistry (IHC), demonstrated a reciprocal relationship of ANXA2 and ERG expression in a large fraction of primary prostate cancer clinical specimens. ANXA2 was absent or markedly reduced in ERG(+) tumors, which were mostly well-differentiated. ERG(-) tumors, meanwhile, expressed moderate to high levels of ANXA2, and were either poorly-differentiated or displayed subsets of poorly-differentiated cells. Taken together, the transcriptional repression of ANXA2 by ERG in prostate epithelial cells plays a critical role in abrogating differentiation, promoting EMT, and in the reciprocal correlation of ERG and ANXA2 expression observed in human prostate cancer. Implications: ANXA2 is a new component of the ERG network with potential to enhance biological stratification and therapeutic targeting of ERG stratified prostate cancers.

PMID: 25344575 [PubMed - as supplied by publisher]