Recent Research Articles from UNTHSC

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NCBI: db=pubmed; Term="University of North Texas Health Science Center"[All Fields] OR "Univ. of North Texas Health Science Center"[All Fields] OR "UNT Health Science Center"[All Fields] OR "Osteopathic Research Center"[All Fields] OR "University of North Texas System College of Pharmacy"[All Fields] OR "UNT System College of Pharmacy"[All Fields] OR "College of Pharmacy, University of North Texas System"[All Fields]
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Changes in biomechanical dysfunction and low back pain reduction with osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Tue, 04/19/2016 - 06:31
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Changes in biomechanical dysfunction and low back pain reduction with osteopathic manual treatment: results from the OSTEOPATHIC Trial.

Man Ther. 2014 Aug;19(4):324-30

Authors: Licciardone JC, Kearns CM, Crow WT

Abstract
The purpose of this study was to measure changes in biomechanical dysfunction following osteopathic manual treatment (OMT) and to assess how such changes predict subsequent low back pain (LBP) outcomes. Secondary analyses were performed with data collected during the OSTEOPATHIC Trial wherein a randomized, double-blind, sham-controlled, 2 × 2 factorial design was used to study OMT for chronic LBP. At baseline, prevalence rates of non-neutral lumbar dysfunction, pubic shear, innominate shear, restricted sacral nutation, and psoas syndrome were determined in 230 patients who received OMT. Five OMT sessions were provided at weeks 0, 1, 2, 4, and 6, and the prevalence of each biomechanical dysfunction was again measured at week 8 immediately before the final OMT session. Moderate pain improvement (≥30% reduction on a 100-mm visual analogue scale) at week 12 defined a successful LBP response to treatment. Prevalence rates at baseline were: non-neutral lumbar dysfunction, 124 (54%); pubic shear, 191 (83%); innominate shear, 69 (30%); restricted sacral nutation, 87 (38%), and psoas syndrome, 117 (51%). Significant improvements in each biomechanical dysfunction were observed with OMT; however, only psoas syndrome remission occurred more frequently in LBP responders than non-responders (P for interaction = 0.002). Remission of psoas syndrome was the only change in biomechanical dysfunction that predicted subsequent LBP response after controlling for the other biomechanical dysfunctions and potential confounders (odds ratio, 5.11; 95% confidence interval, 1.54-16.96). These findings suggest that remission of psoas syndrome may be an important and previously unrecognized mechanism explaining clinical improvement in patients with chronic LBP following OMT.

PMID: 24704126 [PubMed - indexed for MEDLINE]

HIV/neuroAIDS biomarkers.

Sun, 04/17/2016 - 06:33

HIV/neuroAIDS biomarkers.

Prog Neurobiol. 2016 Apr 12;

Authors: Rahimian P, He JJ

Abstract
HIV infection often causes neurological symptoms including cognitive and motor dysfunction, which have been collectively termed HIV/neuroAIDS. Neuropsychological assessment and clinical symptoms have been the primary diagnostic criteria for HIV/neuroAIDS, even for the mild cognitive and motor disorder, the most prevalent form of HIV/neuroAIDS in the era of combination antiretroviral therapy. Those performance-based assessments and symptoms are generally descriptive and do not have the sensitivity and specificity to monitor the diagnosis, progression, and treatment response of the disease when compared to objective and quantitative laboratory-based biological markers, or biomarkers. In addition, effects of demographics and comorbidities such as substance abuse, psychiatric disease, nutritional deficiencies, and co-infection on HIV/neuroAIDS could be more readily determined using biomarkers than using neuropsychological assessment and clinical symptoms. Thus, there have been great efforts in identification of HIV/neuroAIDS biomarkers over the past two decades. The need for reliable biomarkers of HIV/neuroAIDS is expected to increase as the HIV-infected population ages and their vulnerability to neurodegenerative diseases, particularly Alzheimer's disease increases. Currently, three classes of HIV/neuroAIDS biomarkers are being pursued to establish objective laboratory-based definitions of HIV-associated neurologic injury: cerebrospinal fluid biomarkers, blood biomarkers, and neuroimaging biomarkers. In this review, we will focus on the current knowledge in the field of HIV/neuroAIDS biomarker discovery.

PMID: 27084354 [PubMed - as supplied by publisher]

Analysis of Short Tandem Repeat and Single Nucleotide Polymorphism Loci From Single-Source Samples Using a Custom HaloPlex Target Enrichment System Panel.

Fri, 04/15/2016 - 06:32

Analysis of Short Tandem Repeat and Single Nucleotide Polymorphism Loci From Single-Source Samples Using a Custom HaloPlex Target Enrichment System Panel.

Am J Forensic Med Pathol. 2016 Apr 12;

Authors: Wendt FR, Zeng X, Churchill JD, King JL, Budowle B

Abstract
Short tandem repeats and single nucleotide polymorphisms (SNPs) are used to individualize biological evidence samples. Short tandem repeat alleles are characterized by size separation during capillary electrophoresis (CE). Massively parallel sequencing (MPS) offers an alternative that can overcome limitations of the CE. With MPS, libraries are prepared for each sample, entailing target enrichment and bar coding, purification, and normalization. The HaloPlex Target Enrichment System (Agilent Technologies) uses a capture-based enrichment system with restriction enzyme digestion to generate fragments containing custom-selected markers. It offers another possible workflow for typing reference samples. Its efficacy was assessed using a panel of 275 human identity SNPs, 88 short tandem repeats, and amelogenin. The data analyzed included locus typing success, depth of sequence coverage, heterozygote balance, and concordance. The results indicate that the HaloPlex Target Enrichment System provides genetic data similar to that obtained by conventional polymerase chain reaction-CE methods with the advantage of analyzing substantially more markers in 1 sequencing run. The genetic typing performance of HaloPlex is comparable to other MPS-based sample preparation systems that utilize primer-based target enrichment.

PMID: 27075592 [PubMed - as supplied by publisher]

Estimating sleep from multisensory armband measurements: validity and reliability in teens.

Fri, 04/15/2016 - 06:32
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Estimating sleep from multisensory armband measurements: validity and reliability in teens.

J Sleep Res. 2015 Dec;24(6):714-21

Authors: Roane BM, Van Reen E, Hart CN, Wing R, Carskadon MA

Abstract
Given the recognition that sleep may influence obesity risk, there is increasing interest in measuring sleep parameters within obesity studies. The goal of the current analyses was to determine whether the SenseWear(®) Pro3 Armband (armband), typically used to assess physical activity, is reliable at assessing sleep parameters. The armband was compared with the AMI Motionlogger(®) (actigraph), a validated activity monitor for sleep assessment, and with polysomnography, the gold standard for assessing sleep. Participants were 20 adolescents (mean age = 15.5 years) with a mean body mass index percentile of 63.7. All participants wore the armband and actigraph on their non-dominant arm while in-lab during a nocturnal polysomnographic recording (600 min). Epoch-by-epoch sleep/wake data and concordance of sleep parameters were examined. No significant sleep parameter differences were found between the armband and polysomnography; the actigraph tended to overestimate sleep and underestimate wake compared with polysomnography. Both devices showed high sleep sensitivity, but lower wake detection rates. Bland-Altman plots showed large individual differences in armband sleep parameter concordance rates. The armband did well estimating sleep overall, with group results more similar to polysomnography than the actigraph; however, the armband was less accurate at an individual level than the actigraph.

PMID: 26126746 [PubMed - indexed for MEDLINE]

Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Thu, 04/14/2016 - 06:36
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Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

Am J Cancer Res. 2016;6(1):105-13

Authors: Tao MH, Dai Q, Millen AE, Nie J, Edge SB, Trevisan M, Shields PG, Freudenheim JL

Abstract
Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio.

PMID: 27073728 [PubMed]

Role of Tat-interacting protein of 110 kDa and microRNAs in the regulation of hematopoiesis.

Thu, 04/14/2016 - 06:36
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Role of Tat-interacting protein of 110 kDa and microRNAs in the regulation of hematopoiesis.

Curr Opin Hematol. 2016 Apr 8;

Authors: Liu Y, He JJ

Abstract
PURPOSE OF REVIEW: Hematopoiesis is regulated by cellular factors including transcription factors, microRNAs, and epigenetic modifiers. Understanding how these factors regulate hematopoiesis is pivotal for manipulating them to achieve their desired potential. In this review, we will focus on HIV-1 Tat-interacting protein of 110 kDa (Tip110) and its regulation of hematopoiesis.
RECENT FINDINGS: There are several pathways in hematopoiesis that involve Tip110 regulation. Tip110 is expressed in human cord blood CD34 cells; its expression decreases when CD34 cells begin to differentiate. Tip110 is also expressed in mouse marrow hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC). Tip110 expression increases the number, survival, and cell cycling of HPC. Tip110-mediated regulation of hematopoiesis has been linked to its reciprocal control of c-Myc expression. Small noncoding microRNAs (miRs) have been shown to play important roles in regulation of hematopoiesis. miR-124 specifically targets 3'-untranslated region of Tip110 and subsequently regulates Tip110 expression in HSC.
SUMMARY: Our recent findings for manipulating expression levels of Tip110 in HSC and HPC could be useful for expanding HSC and HPC and for improving engraftment of cord blood HSC/HPC.

PMID: 27071021 [PubMed - as supplied by publisher]

Cerebral Blood-Flow Regulation During Hemorrhage.

Thu, 04/14/2016 - 06:36
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Cerebral Blood-Flow Regulation During Hemorrhage.

Compr Physiol. 2015 Oct;5(4):1585-621

Authors: Rickards CA

Abstract
Massive uncontrolled blood loss can occur under a variety of conditions including trauma, as a complication of childbirth or surgery, ruptured ulcers, clotting disorders, and hemorrhagic fevers. Across the continuum of hemorrhage, loss of blood volume is a significant challenge to the maintenance of cerebral perfusion. During the initial stages of hemorrhage, reflex mechanisms are activated to protect cerebral perfusion, but persistent blood loss will eventually reduce global cerebral blood flow and the delivery of metabolic substrates, leading to generalized cerebral ischemia, hypoxia, and ultimately, neuronal cell death. Cerebral blood flow is controlled by various regulatory mechanisms, including prevailing arterial pressure, intracranial pressure, arterial blood gases, neural activity, and metabolic demand. Hemorrhage represents a unique physiological stress to the brain, as it influences each of these regulatory mechanisms, resulting in complex interplay that ultimately challenges the ability of the brain to maintain adequate perfusion. Early studies of actual hemorrhage in humans employed blood loss protocols up to 1000 mL, but did not include any measurements of cerebral blood flow. As ethical considerations necessarily constrain the use of human volunteers for massive blood loss studies that induce irreversible shock, most of what is known about cerebral blood-flow responses to hemorrhage has been determined from animal models. Limitations of species differences regarding regulatory mechanisms, anatomy, and the effect of anesthesia, however, must be considered. Advances in monitoring technologies, and a recent renewed interest in understanding cerebral blood-flow regulation in humans, however, is rapidly accelerating knowledge in this field.

PMID: 26426461 [PubMed - indexed for MEDLINE]

Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Tue, 04/12/2016 - 06:34
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Ionic derivatives of betulinic acid exhibit antiviral activity against herpes simplex virus type-2 (HSV-2), but not HIV-1 reverse transcriptase.

Bioorg Med Chem Lett. 2015 Aug 15;25(16):3168-71

Authors: Visalli RJ, Ziobrowski H, Badri KR, He JJ, Zhang X, Arumugam SR, Zhao H

Abstract
Betulinic acid (1) has been modified to ionic derivatives (2-5) to improve its water solubility and biological activities. The binding properties of these derivatives with respect to human serum albumin (HSA) was examined and found to be similar to current anti-HIV drugs. These compounds did not inhibit HIV reverse transcriptase, however, 1, 2 and 5 inhibited herpes simplex type 2 (HSV-2) replication at concentrations similar to those reported for acyclovir (IC50 ∼ 0.1-10 μM) and with minimal cellular cytotoxicity. IC50 values for antiviral activity against HSV-2 186 were 1.6, 0.6, 0.9, 7.2, and 0.9 μM for compounds 1-5, respectively.

PMID: 26112446 [PubMed - indexed for MEDLINE]

Kienböck Disease: Moving Forward.

Sat, 04/09/2016 - 06:43

Kienböck Disease: Moving Forward.

J Hand Surg Am. 2016 Apr 4;

Authors: Lichtman DM, Pientka WF, Bain GI

Abstract
Over the past decade, a plethora of new information has been reported regarding etiology, natural history, classification, and treatment options for lunate osteonecrosis. New disease classifications have been described based on advanced imaging determination of lunate viability as well as a cartilage-based arthroscopic classification. Here we review the newest literature regarding Kienböck disease and present a new treatment algorithm that incorporates the traditional osseous classification system with a perfusion/viability classification and an articular cartilage-based classification.

PMID: 27055625 [PubMed - as supplied by publisher]

Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers.

Sat, 04/09/2016 - 06:43
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Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers.

Cancer Causes Control. 2014 Nov;25(11):1427-37

Authors: Paxton RJ, Jung SY, Vitolins MZ, Fenton J, Paskett E, Pollak M, Hays-Grudo J, Hursting SD, Chang S

Abstract
PURPOSE: Despite evidence that prolonged periods of sitting may influence biological mediators of cancer development, few studies have considered these relationships in a cancer-specific context.
METHODS: This cross-sectional study included 755 postmenopausal women enrolled in an ancillary study of the Women's Health Initiative. Plasma levels of Insulin-like growth factor-I (IGF-I), IGF-binding protein-3, leptin, insulin, C-peptide, C-reactive protein (CRP), and Interleukin (IL)-6 were measured. The time spent sitting per day was categorized as quartiles (Qs). The relationships between sedentary time and biomarkers were modified by race, physical activity, and exogenous estrogen use.
RESULTS: IGF-I levels among African American (AA) women were higher than those of white women across the Qs of sedentary time. Likewise, IL-6 levels in AA women were higher than those in white women at Q3 and Q4 of sedentary time. IGFBP-3 levels were higher and insulin levels were lower across the Qs of sedentary time among women meeting guidelines for physical activity than women who were not. Additionally, CRP levels were higher among estrogen users than nonusers at Q1, Q2, and Q4 of sedentary time.
CONCLUSIONS: These results suggest that relationship between time spent sitting and cancer-related biomarkers may not be simply linear, but differ in the context of effect modifiers.

PMID: 25238978 [PubMed - indexed for MEDLINE]

Social support quality and availability affects risk behaviors in offenders.

Fri, 04/08/2016 - 06:29

Social support quality and availability affects risk behaviors in offenders.

Health Justice. 2016;4:2

Authors: Spohr SA, Suzuki S, Marshall B, Taxman FS, Walters ST

Abstract
BACKGROUND: People involved in the justice system are at 2.5 times the risk of HIV infection compared to the general population, which is further complicated by substance abuse. The purpose of this study was to evaluate the role of social network quality and quantity on unprotected sex, criminal risk, and substance use.
METHODS: We used data from 330 drug-involved offenders. Structural equation modeling (SEM) was used to model and test path directionality and magnitude between the latent constructs of social support quality and quantity on risky behaviors.
RESULTS: The SEM indicated the latent construct of social support quality was significantly associated with reduced sexual risk behavior (β = -0.27), criminal risk (β = -0.26), and reduced substance use (β = -0.33). Additionally, the proposed model found that social support quantity was significantly positively associated with increased sexual risk behavior (β = 0.40) and substance use (β = 0.20).
CONCLUSIONS: Social support quality is an important predictor of risky behaviors; as the quality of an offender's social support increases, engagement in risky behaviors decreases. Probationers who had broader social support availability also had increased substance use and unprotected sex. Probation systems may be able to reduce substance use and STD/HIV infection risk in offenders by strengthening the quality of social support networks.

PMID: 27054059 [PubMed - as supplied by publisher]

Dermatorynchus geneae: A seldom-described first branchial arch deformity.

Thu, 04/07/2016 - 10:36

Dermatorynchus geneae: A seldom-described first branchial arch deformity.

JAAD Case Rep. 2015 Sep;1(5):283-285

Authors: McIlwee BE, Hick RW, Weis SE

PMID: 27051754 [PubMed - as supplied by publisher]

Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

Thu, 04/07/2016 - 10:36
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Vestiges of an Ancient Border in the Contemporary Genetic Diversity of North-Eastern Europe.

PLoS One. 2015;10(7):e0130331

Authors: Neuvonen AM, Putkonen M, Översti S, Sundell T, Onkamo P, Sajantila A, Palo JU

Abstract
It has previously been demonstrated that the advance of the Neolithic Revolution from the Near East through Europe was decelerated in the northernmost confines of the continent, possibly as a result of space and resource competition with lingering Mesolithic populations. Finland was among the last domains to adopt a farming lifestyle, and is characterized by substructuring in the form of a distinct genetic border dividing the northeastern and southwestern regions of the country. To explore the origins of this divergence, the geographical patterns of mitochondrial and Y-chromosomal haplogroups of Neolithic and Mesolithic ancestry were assessed in Finnish populations. The distribution of these uniparental markers revealed a northeastern bias for hunter-gatherer haplogroups, while haplogroups associated with the farming lifestyle clustered in the southwest. In addition, a correlation could be observed between more ancient mitochondrial haplogroup age and eastern concentration. These results coupled with prior archeological evidence suggest the genetic northeast/southwest division observed in contemporary Finland represents an ancient vestigial border between Mesolithic and Neolithic populations undetectable in most other regions of Europe.

PMID: 26132657 [PubMed - indexed for MEDLINE]

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Wed, 04/06/2016 - 06:38

No association between global DNA methylation in peripheral blood and lung cancer risk in nonsmoking women: results from a multicenter study in Eastern and Central Europe.

Eur J Cancer Prev. 2016 Apr 4;

Authors: Davis A, Tao MH, Chen J, Scelo G, Bencko V, Fabianova E, Foretova L, Janout V, Lissowska J, Mates D, Mates IN, Rudnai P, Zaridze D, Boffetta P

Abstract
Alterations in global DNA methylation have been suggested to play an important role in cancer development. We evaluated the association of global DNA methylation in peripheral blood with the risk of lung cancer in nonsmoking women from six countries in Central and Eastern Europe. This multicenter case-control study included primary, incident lung cancer cases diagnosed from 1998 to 2001 and controls frequency-matched for geographic area, sex, and age. Global methylation was assessed in peripheral blood DNA from 83 nonsmoking female cases and 181 nonsmoking female controls using the luminometric methylation assay (LUMA). Unconditional logistic regression models were used to estimate associations between DNA methylation in the blood and the risk of lung cancer. LUMA methylation level was not associated with the risk of lung cancer in nonsmoking women. Associations were not significantly different according to different strata of age, BMI, alcohol drinking, or second-hand tobacco smoke exposure status. In our study of nonsmoking women, the LUMA methylation level in peripheral blood was not associated with the risk of lung cancer. Our findings do not support an association of global blood DNA methylation with the risk of lung cancer in nonsmoking women.

PMID: 27045934 [PubMed - as supplied by publisher]

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

Tue, 04/05/2016 - 10:29
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Nanoparticle Effects on Human Platelets in Vitro: A Comparison between PAMAM and Triazine Dendrimers.

Molecules. 2016;21(4)

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

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

PMID: 27043508 [PubMed - as supplied by publisher]

Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

Tue, 04/05/2016 - 10:29
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Carbon Disulfide (CS2) Interference in Glucose Metabolism from Unconventional Oil and Gas Extraction and Processing Emissions.

Environ Health Insights. 2016;10:51-7

Authors: Rich AL, Patel JT, Al-Angari SS

Abstract
Carbon disulfide (CS2) has been historically associated with the manufacturing of rayon, cellophane, and carbon tetrachloride production. This study is one of the first to identify elevated atmospheric levels of CS2 above national background levels and its mechanisms to dysregulate normal glucose metabolism. Interference in glucose metabolism can indirectly cause other complications (diabetes, neurodegenerative disease, and retinopathy), which may be preventable if proper precautions are taken. Rich et al found CS2 and 12 associated sulfide compounds present in the atmosphere in residential areas where unconventional shale oil and gas extraction and processing operations were occurring. Ambient atmospheric concentrations of CS2 ranged from 0.7 parts per billion by volume (ppbv) to 103 ppbv over a continuous 24-hour monitoring period. One-hour ambient atmospheric concentrations ranged from 3.4 ppbv to 504.6 ppbv. Using the U.S. Environmental Protection Agency Urban Air Toxic Monitoring Program study as a baseline comparison for atmospheric CS2 concentrations found in this study, it was determined that CS2 atmospheric levels were consistently elevated in areas where unconventional oil and gas extraction and processing occurred. The mechanisms by which CS2 interferes in normal glucose metabolism by dysregulation of the tryptophan metabolism pathway are presented in this study. The literature review found an increased potential for alteration of normal glucose metabolism in viscose rayon occupational workers exposed to CS2. Occupational workers in the energy extraction industry exposed to CS2 and other sulfide compounds may have an increased potential for glucose metabolism interference, which has been an indicator for diabetogenic effect and other related health impacts. The recommendation of this study is for implementation of regular monitoring of blood glucose levels in CS2-exposed populations as a preventative health measure.

PMID: 27042092 [PubMed]

Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in Diabetes and Its Complications.

Tue, 04/05/2016 - 10:29
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Protein Modifications as Manifestations of Hyperglycemic Glucotoxicity in Diabetes and Its Complications.

Biochem Insights. 2016;9:1-9

Authors: Zheng H, Wu J, Jin Z, Yan LJ

Abstract
Diabetes and its complications are hyperglycemic toxicity diseases. Many metabolic pathways in this array of diseases become aberrant, which is accompanied with a variety of posttranslational protein modifications that in turn reflect diabetic glucotoxicity. In this review, we summarize some of the most widely studied protein modifications in diabetes and its complications. These modifications include glycation, carbonylation, nitration, cysteine S-nitrosylation, acetylation, sumoylation, ADP-ribosylation, O-GlcNAcylation, and succination. All these posttranslational modifications can be significantly attributed to oxidative stress and/or carbon stress induced by diabetic redox imbalance that is driven by activation of pathways, such as the polyol pathway and the ADP-ribosylation pathway. Exploring the nature of these modifications should facilitate our understanding of the pathological mechanisms of diabetes and its associated complications.

PMID: 27042090 [PubMed]

Exosomes are unlikely involved in intercellular Nef transfer.

Tue, 04/05/2016 - 10:29
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Exosomes are unlikely involved in intercellular Nef transfer.

PLoS One. 2015;10(4):e0124436

Authors: Luo X, Fan Y, Park IW, He JJ

Abstract
HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Several recent studies including ours have demonstrated that Nef can be transferred to neighboring cells and alters the function of these cells. However, how the intercellular Nef transfer occurs is in dispute. In the current study, we attempted to address this important issue using several complementary strategies, a panel of exosomal markers, and human CD4+ T lymphocyte cell line Jurkat and a commonly used cell line 293T. First, we showed that Nef was transferred from Nef-expressing or HIV-infected Jurkat to naïve Jurkat and other non-Jurkat cells and that the transfer required the membrane targeting function of Nef and was cell density-dependent. Then, we showed that Nef transfer was cell-cell contact-dependent, as exposure to culture supernatants or exosomes from HIV-infected Jurkat or Nef-expressing Jurkat and 293T led to little Nef detection in the target cells Jurkat. Thirdly, we demonstrated that Nef was only detected to be associated with HIV virions but not with acetylcholinesterase (AChE+) exosomes from HIV-infected Jurkat and not in the exosomes from Nef-expressing Jurkat. In comparison, when it was over-expressed in 293T, Nef was detected in detergent-insoluble AChE+/CD81 low/TSG101 low exosomes, but not in detergent-soluble AChE-/CD81 high/TSG101 high exosomes. Lastly, microscopic imaging showed no significant Nef detection in exosomal vesicle-like structures in and out 293T. Taken together, these results show that exosomes are unlikely involved in intercellular Nef transfer. In addition, this study reveals existence of two types of exosomes: AChE+/CD81 low/TSG101 low exosomes and AChE-/CD81 high/TSG101 high exosomes.

PMID: 25919665 [PubMed - indexed for MEDLINE]

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

Tue, 04/05/2016 - 10:29
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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. 2015 Aug;30(8):881-6

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.

PMID: 25394326 [PubMed - indexed for MEDLINE]

U.S. Physicians' Opinions About Accommodating Religiously Based Requests for Continued Life-Sustaining Treatment.

Mon, 04/04/2016 - 06:31

U.S. Physicians' Opinions About Accommodating Religiously Based Requests for Continued Life-Sustaining Treatment.

J Pain Symptom Manage. 2016 Mar 30;

Authors: Ayeh DD, Tak HJ, Yoon JD, Curlin FA

Abstract
CONTEXT: Families of critically ill patients occasionally request that physicians continue life-sustaining treatment (LST), sometimes giving religious reasons.
OBJECTIVES: To examine whether U.S. physicians are more likely to accommodate requests for LST that are based on religious reasons.
METHODS: In 2010 we surveyed 1156 practicing U.S. physicians from specialties likely to care for adult patients with advanced illness. The questionnaire included two randomized experimental vignettes: one where a family asked that LST be continued for a patient that met brain death criteria and a second where the son of an elderly patient with cancer insists on continuing LST. In both, we experimentally varied the reasons that the family member gave to justify the request, to see if physicians are more likely to accommodate a request based on a religious requirement or hope for a miracle, compared to no mention of either. For physicians' religious characteristics, we assessed their religious affiliation and level of religiosity.
RESULTS: For the patient meeting brain death criteria, physicians were more likely to accommodate the request to continue LST when the family mentioned their Orthodox Jewish community (85% vs. 70%, P<0.001). For the patient with metastatic cancer, physicians were more likely to accommodate the request when the son said his religious faith does not permit discontinuing LST (65% vs. 46%, P<0.001), but not when he said he expected divine healing (50% vs. 46%).
CONCLUSION: Physicians appear more willing to accommodate requests to continue LST when those requests are based on particular religious communities or traditions, but not when based on expectations of divine healing.

PMID: 27039013 [PubMed - as supplied by publisher]

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