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Comments on 'A note on the variance of the estimate of the fixation index F'.

Recent Research Articles from UNTHSC - Wed, 06/29/2016 - 18:31
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Comments on 'A note on the variance of the estimate of the fixation index F'.

J Genet. 2016 Jun;95(2):229-30

Authors: Chakraborty R

PMID: 27350663 [PubMed - in process]

Comorbid Depression and Diabetes as a Risk for Mild Cognitive Impairment and Alzheimer's Disease in Elderly Mexican Americans.

Recent Research Articles from UNTHSC - Wed, 06/29/2016 - 18:31
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Comorbid Depression and Diabetes as a Risk for Mild Cognitive Impairment and Alzheimer's Disease in Elderly Mexican Americans.

J Alzheimers Dis. 2015;47(1):129-36

Authors: Johnson LA, Gamboa A, Vintimilla R, Cheatwood AJ, Grant A, Trivedi A, Edwards M, Hall JR, O'Bryant SE

Abstract
BACKGROUND: The links between diabetes, depression, and Alzheimer's disease (AD) has been established, but they are still poorly understood. However, little research has examined the effect that comorbidity of depression and diabetes has on cognitive impairment in an ethnically diverse sample.
OBJECTIVE: The purpose of this study was to investigate the relationship between comorbid diabetes and depression on cognitive dysfunction; and examine the relationship in an ethnically diverse population.
METHODS AND RESULTS: Analyses of data from 2,436 participants (914 men and 1,522 women) of three separate cohorts: HABLE, FRONTIER, and TARCC. In the HABLE cohort, comorbidity (odds ratio [OR] = 3.008; 95% CI = 1.358-6.667), age (OR = 1.138; 95% CI = 1.093-1.185), and education (OR = 0.915; 95% CI = 0.852-0.982) increased the risk of mild cognitive impairment (MCI) diagnosis among elderly Mexican American. In the TARCC cohort, results showed an increase risk of MCI in both non-Hispanic whites (OR = 18.795; 95% CI = 2.229-158.485) and Mexican Americans (OR = 8.417; 95% CI = 2.967-23.878). Finally, results in the FRONTIER cohort showed that in elderly Mexican Americans, comorbidity (OR = 2.754; 95% CI = 1.084-6.995) and age (OR = 1.069; 95% CI = 1.023-1.118) significantly increased risk of MCI. In non-Hispanic whites, comorbidity did not significantly increase risk of MCI.
CONCLUSIONS: Among elderly Mexican Americans, comorbid depression and diabetes significantly increased risk for MCI and AD across cohorts. Effects of comorbid diabetes and depression on MCI were inconclusive. Our results support the link between comorbid diabetes and depression and risk for cognitive decline among Mexican Americans. This finding is of critical importance as the Hispanic population is at higher risk of developing AD.

PMID: 26402761 [PubMed - indexed for MEDLINE]

Mitochondrial genome interrogation for forensic casework and research studies.

Recent Research Articles from UNTHSC - Tue, 06/28/2016 - 10:31
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Mitochondrial genome interrogation for forensic casework and research studies.

Curr Protoc Hum Genet. 2014;81:14.9.1-23

Authors: Roby RK, Sprouse M, Phillips N, Alicea-Centeno A, Shewale S, Shore S, Paul N

Abstract
This unit describes methods used in the analysis of mitochondrial DNA (mtDNA) for forensic and research applications. UNIT describes procedures specifically for forensic casework where the DNA from evidentiary material is often degraded or inhibited. In this unit, protocols are described for quantification of mtDNA before amplification; amplification of the entire control region from high-quality samples as well as procedures for interrogating the whole mitochondrial genome (mtGenome); quantification of mtDNA post-amplification; and, post-PCR cleanup and sequencing. The protocols for amplification were developed for high-throughput databasing applications for forensic DNA testing such as reference samples and population studies. However, these same protocols can be applied to biomedical research such as age-related disease and health disparities research.

PMID: 24763992 [PubMed - indexed for MEDLINE]

Inhibition of hypoxia inducible factor-1α downregulates the expression of epithelial to mesenchymal transition early marker proteins without undermining cell survival in hypoxic lens epithelial cells.

Recent Research Articles from UNTHSC - Sat, 06/25/2016 - 06:29
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Inhibition of hypoxia inducible factor-1α downregulates the expression of epithelial to mesenchymal transition early marker proteins without undermining cell survival in hypoxic lens epithelial cells.

Mol Vis. 2015;21:1024-35

Authors: Cammarata PR, Neelam S, Brooks MM

Abstract
PURPOSE: The purpose of this study was to identify potential therapeutic strategies to slow down or prevent the expression of early-onset epithelial to mesenchymal transition (EMT) marker proteins (fibronectin and alpha smooth muscle actin, α-SMA) without sacrificing the synthesis and accumulation of the prosurvival protein vascular endothelial growth factor (VEGF) in cultured virally transformed human lens epithelial (HLE) cells.
METHODS: HLE-B3 cells, maintained in a continuous hypoxic environment (1% oxygen), were treated with SB216763, a specific inhibitor of glycogen synthase kinase-3β (GSK-3β) catalytic activity. Western blot analysis was employed to detect the cytoplasmic and nuclear levels of β-catenin, as well as the total lysate content of fibronectin and α-SMA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of VEGF in cell culture medium. A hypoxia-inducible factor-1α (HIF-1α) translation inhibitor and an HIF-2α translation inhibitor were independently employed to evaluate the effect of hypoxia inducible factor inhibition on EMT marker protein and VEGF expression. XAV932 was used to assess the suppression of nuclear β-catenin and its downstream effect on EMT marker proteins and VEGF expression.
RESULTS: SB216763-treated HLE-B3 cells caused marked inhibition of GSK-3β activity prompting a significant increase in the translocation of cytoplasmic β-catenin to the nucleus. The enhancement of nuclear β-catenin looked as if it positively correlated with a significant increase in the basal expression of VEGF as well as increased expression of fibronectin and α-SMA. In conjunction with SB216763, coadministration of an HIF-1α translation inhibitor, but not an HIF-2α translation inhibitor, markedly suppressed the expression of fibronectin and α-SMA without affecting VEGF levels. Treatment with XAV932 significantly reduced the level of nuclear β-catenin, but the levels of neither the EMT marker proteins nor VEGF were changed.
CONCLUSIONS: Recently, we reported that nuclear β-catenin, but not HIF-2α, regulates the expression of fibronectin and α-SMA in atmospheric oxygen. In marked contrast, data from the hypoxic condition clearly establish that nuclear β-catenin plays little apparent role in the expression of EMT marker proteins. Instead, the loss of HIF-1α (but not HIF-2α) decreases the expression of the EMT marker proteins without sacrificing the levels of the prosurvival protein VEGF. These findings support the development of a potentially relevant therapeutic strategy to undermine the progression of normal cells to the mesenchymal phenotype in the naturally hypoxic lens without subverting cell viability.

PMID: 26392741 [PubMed - indexed for MEDLINE]

Acute inhalation of vaporized nicotine increases arterial pressure in young non-smokers: a pilot study.

Recent Research Articles from UNTHSC - Sat, 06/25/2016 - 06:29
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Acute inhalation of vaporized nicotine increases arterial pressure in young non-smokers: a pilot study.

Clin Auton Res. 2015 Aug;25(4):267-70

Authors: Cooke WH, Pokhrel A, Dowling C, Fogt DL, Rickards CA

Abstract
PURPOSE: Electronic cigarettes are growing in popularity, but the physiological consequences of vaporized nicotine are unknown.
METHODS: Twenty healthy non-smokers inhaled vaporized nicotine and placebo (randomized).
RESULTS: Nicotine inhalation was associated with higher arterial pressures in the seated position, and increased arterial pressures in the head-up positions with no other effects on autonomic control.
CONCLUSIONS: Our results show that vaporized nicotine inhalation is not innocuous. Longitudinal studies in otherwise healthy non-smokers should be conducted.

PMID: 26264837 [PubMed - indexed for MEDLINE]

Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

Recent Research Articles from UNTHSC - Fri, 06/24/2016 - 06:29
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Can Genetic Analysis of Putative Blood Alzheimer's Disease Biomarkers Lead to Identification of Susceptibility Loci?

PLoS One. 2015;10(12):e0142360

Authors: Barber RC, Phillips NR, Tilson JL, Huebinger RM, Shewale SJ, Koenig JL, Mitchel JS, O'Bryant SE, Waring SC, Diaz-Arrastia R, Chasse S, Wilhelmsen KC, Alzheimer’s Disease Neuroimaging Initiative, Texas Alzheimer’s Research and Care Consortium

Abstract
Although 24 Alzheimer's disease (AD) risk loci have been reliably identified, a large portion of the predicted heritability for AD remains unexplained. It is expected that additional loci of small effect will be identified with an increased sample size. However, the cost of a significant increase in Case-Control sample size is prohibitive. The current study tests whether exploring the genetic basis of endophenotypes, in this case based on putative blood biomarkers for AD, can accelerate the identification of susceptibility loci using modest sample sizes. Each endophenotype was used as the outcome variable in an independent GWAS. Endophenotypes were based on circulating concentrations of proteins that contributed significantly to a published blood-based predictive algorithm for AD. Endophenotypes included Monocyte Chemoattractant Protein 1 (MCP1), Vascular Cell Adhesion Molecule 1 (VCAM1), Pancreatic Polypeptide (PP), Beta2 Microglobulin (B2M), Factor VII (F7), Adiponectin (ADN) and Tenascin C (TN-C). Across the seven endophenotypes, 47 SNPs were associated with outcome with a p-value ≤1x10(-7). Each signal was further characterized with respect to known genetic loci associated with AD. Signals for several endophenotypes were observed in the vicinity of CR1, MS4A6A/MS4A4E, PICALM, CLU, and PTK2B. The strongest signal was observed in association with Factor VII levels and was located within the F7 gene. Additional signals were observed in MAP3K13, ZNF320, ATP9B and TREM1. Conditional regression analyses suggested that the SNPs contributed to variation in protein concentration independent of AD status. The identification of two putatively novel AD loci (in the Factor VII and ATP9B genes), which have not been located in previous studies despite massive sample sizes, highlights the benefits of an endophenotypic approach for resolving the genetic basis for complex diseases. The coincidence of several of the endophenotypic signals with known AD loci may point to novel genetic interactions and should be further investigated.

PMID: 26625115 [PubMed - indexed for MEDLINE]

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

Recent Research Articles from UNTHSC - Thu, 06/23/2016 - 06:29
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Analysis of provider specialties in the treatment of patients with clinically diagnosed back and joint problems.

J Eval Clin Pract. 2015 Oct;21(5):952-7

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

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

PMID: 26154344 [PubMed - indexed for MEDLINE]

Distinct Classes of Negative Alcohol-Related Consequences in a National Sample of Incoming First-Year College Students: A Latent Class Analysis.

Recent Research Articles from UNTHSC - Wed, 06/22/2016 - 06:34
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Distinct Classes of Negative Alcohol-Related Consequences in a National Sample of Incoming First-Year College Students: A Latent Class Analysis.

Alcohol Alcohol. 2016 Jun 20;

Authors: Rinker DV, Diamond PM, Walters ST, Wyatt TM, DeJong W

Abstract
: First-year college students are at particular risk for experiencing negative alcohol-related consequences that may set the stage for experiencing such consequences in later life. Latent class analysis is a person-centered approach that, based on observable indicator variables, divides a population into mutually exclusive and exhaustive groups ('classes'). To date, no studies have examined the latent class structure of negative alcohol-related consequences experienced by first-year college students just before entering college.
AIMS: The aims of this study were to (a) identify classes of first-year college students based on the patterns of negative alcohol-related consequences they experienced just before entering college, and (b) determine whether specific covariates were associated with class membership.
METHODS: Incoming freshmen from 148 colleges and universities (N = 54,435) completed a baseline questionnaire as part of an alcohol education program they completed just prior to their first year of college. Participants answered questions regarding demographics and other personal characteristics, their alcohol use in the past 2 weeks, and the negative alcohol-related consequences they had experienced during that time.
RESULTS: Four distinct classes of students emerged: (a) No Problems, (b) Academic Problems, (c) Injured Self and (d) Severe Problems. Average number of drinks per drinking day, total number of drinking days, age of drinking initiation, intention to join a fraternity or sorority and family history of alcohol problems were associated with membership in all of the problem classes relative to the No Problems class.
CONCLUSIONS: These results can inform future campus-based prevention efforts.

PMID: 27325885 [PubMed - as supplied by publisher]

Thymic involution beyond T-cell insufficiency.

Recent Research Articles from UNTHSC - Wed, 06/22/2016 - 06:34
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Thymic involution beyond T-cell insufficiency.

Oncotarget. 2015 Sep 8;6(26):21777-8

Authors: Coder B, Su DM

PMID: 26318588 [PubMed - indexed for MEDLINE]

Combination of 13 cis-retinoic acid and tolfenamic acid induces apoptosis and effectively inhibits high-risk neuroblastoma cell proliferation.

Recent Research Articles from UNTHSC - Tue, 06/21/2016 - 06:31
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Combination of 13 cis-retinoic acid and tolfenamic acid induces apoptosis and effectively inhibits high-risk neuroblastoma cell proliferation.

Int J Dev Neurosci. 2015 Nov;46:92-9

Authors: Shelake S, Eslin D, Sutphin RM, Sankpal UT, Wadwani A, Kenyon LE, Tabor-Simecka L, Bowman WP, Vishwanatha JK, Basha R

Abstract
Chemotherapeutic regimens used for the treatment of Neuroblastoma (NB) cause long-term side effects in pediatric patients. NB arises in immature sympathetic nerve cells and primarily affects infants and children. A high rate of relapse in high-risk neuroblastoma (HRNB) necessitates the development of alternative strategies for effective treatment. This study investigated the efficacy of a small molecule, tolfenamic acid (TA), for enhancing the anti-proliferative effect of 13 cis-retinoic acid (RA) in HRNB cell lines. LA1-55n and SH-SY5Y cells were treated with TA (30μM) or RA (20μM) or both (optimized doses, derived from dose curves) for 48h and tested the effect on cell viability, apoptosis and selected molecular markers (Sp1, survivin, AKT and ERK1/2). Cell viability and caspase activity were measured using the CellTiter-Glo and Caspase-Glo kits. The apoptotic cell population was determined by flow cytometry with Annexin-V staining. The expression of Sp1, survivin, AKT, ERK1/2 and c-PARP was evaluated by Western blots. The combination therapy of TA and RA resulted in significant inhibition of cell viability (p<0.0001) when compared to individual agents. The anti-proliferative effect is accompanied by a decrease in Sp1 and survivin expression and an increase in apoptotic markers, Annexin-V positive cells, caspase 3/7 activity and c-PARP levels. Notably, TA+RA combination also caused down regulation of AKT and ERK1/2 suggesting a distinct impact on survival and proliferation pathways via signaling cascades. This study demonstrates that the TA mediated inhibition of Sp1 in combination with RA provides a novel therapeutic strategy for the effective treatment of HRNB in children.

PMID: 26287661 [PubMed - indexed for MEDLINE]

The relationship between electronic goal reminders and subsequent drug use and treatment initiation in a criminal justice setting.

Recent Research Articles from UNTHSC - Tue, 06/21/2016 - 06:31
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The relationship between electronic goal reminders and subsequent drug use and treatment initiation in a criminal justice setting.

Addict Behav. 2015 Dec;51:51-6

Authors: Spohr SA, Taxman FS, Walters ST

Abstract
INTRODUCTION: Opportunities to influence behavior through the use of electronic reminders has not been examined in a criminal justice population. The purpose of this study was to assess probationer preferences for short-term goals from a web-based program and evaluate the role of voluntary electronic reminders (e.g., text messaging, email) in achieving early treatment and probation tasks.
METHODS: We used data from drug-involved offenders (n=76) participating in a clinical trial of a 2-session motivational computer program. As part of the program, participants could choose to receive text or email reminders about their probation and treatment goals for the next month. Poisson regression models were utilized to evaluate goal and reminder selection in relation to the days of substance use and treatment attendance at two-month follow-up.
RESULTS: The most common goals were related to probation and treatment tasks, relationships, and cognitive reappraisals. Forty-five percent of probationers elected to receive electronic goal reminders at Session 1 with a slight increase at Session two (49%). Probationers who opted to receive electronic goal reminders at Session one selected significantly more goals on average (M=4.4, SD=2.1) than probationers who did not want reminders (M=3.4, SD=1.8), (t=2.41, p=.019). Reminder selection and total number of goals selected predicted days of substance use and treatment attendance at a two-month follow-up. Probationers who opted not to receive electronic reminders and those who only chose to receive reminders at one visit had more days of substance use compared to those who chose to receive reminders at both visits, 1.66 and 2.31 times respectively. Probationers who chose not to receive electronic reminders attended 56% fewer days of treatment compared to those who chose to receive reminders at both visits.
CONCLUSIONS: People's choice of short-term goals and reminders can provide advance notification of the likelihood of substance use and treatment initiation. Probation systems might use such information to triage at-risk probationers to a higher level of service, before problems have emerged.

PMID: 26217929 [PubMed - indexed for MEDLINE]

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

Recent Research Articles from UNTHSC - Tue, 06/21/2016 - 06:31
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Two novel high performing composite PMMA-CaP cements for vertebroplasty: An ex vivo animal study.

J Mech Behav Biomed Mater. 2015 Oct;50:290-8

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

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

PMID: 26177392 [PubMed - indexed for MEDLINE]

Temporal Association Between Nonfatal Self-Directed Violence and Tree and Grass Pollen Counts.

Recent Research Articles from UNTHSC - Sat, 06/18/2016 - 06:34

Temporal Association Between Nonfatal Self-Directed Violence and Tree and Grass Pollen Counts.

J Clin Psychiatry. 2016 Jun 7;

Authors: Jeon-Slaughter H, Claassen CA, Khan DA, Mihalakos P, Lee KB, Brown ES

Abstract
OBJECTIVES: Prior research suggests a possible association between pollen and suicide. No studies have examined the relationship between pollen and attempted suicide. This study examines the temporal association between airborne pollen counts and nonfatal suicidal and nonsuicidal self-directed violence (SDV) requiring an emergency department visit.
METHODS: Data on daily emergency department visits due to nonfatal SDV as identified by ICD-9 diagnosis criteria were extracted from emergency department medical records of Parkland Memorial Hospital in Dallas, Texas, between January 2000 and December 2003. Concurrent daily airborne tree, grass, and ragweed pollen data from the city of Dallas were extracted from the National Allergy Bureau online database. The data were analyzed using the time series method of generalized autoregressive conditional heteroskedasticity.
RESULTS: There were statistically significant and positive temporal associations between tree pollen counts and the number of nonfatal SDV events among women (P = .04) and between grass pollen counts and number of nonfatal SDV events among both men (P = .03) and women (P < .0001). There was no significant temporal association found between ragweed pollen counts and number of nonfatal SDV events.
CONCLUSIONS: The study findings suggest that an increase in nonfatal SDV is associated with changes in tree and grass pollen counts. This is the first study that has examined an association between seasonal variation in tree and grass pollen levels and nonfatal SDV event data. The study also used a narrowly defined geographic area and temporal window. The findings suggest that pollen count may be a factor influencing seasonal patterns in suicidal behavior.

PMID: 27314288 [PubMed - as supplied by publisher]

Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study.

Recent Research Articles from UNTHSC - Thu, 06/16/2016 - 06:30

Comparison of Outcomes between Individuals with Pure and Mixed Lupus Nephritis: A Retrospective Study.

PLoS One. 2016;11(6):e0157485

Authors: Ilori TO, Enofe N, Oommen A, Cobb J, Navarrete J, Adedinsewo DA, Oshikoya O, Fevrier H, Farris AB, Plantinga L, Ojo AO

Abstract
INTRODUCTION: Lupus nephritis (LN) is a serious organ manifestation of systemic lupus erythematosus. Histologic overlap is relatively common in the six pathologic classes (I to VI) of LN. For example, mixed proliferative LN (MPLN) often includes features of classes III & V or classes IV & V combined. We performed a comparative evaluation of renal outcomes in patients with MPLN to patients with pure proliferative LN (PPLN) against pre-specified renal outcomes, and we also identified predictor of clinical outcomes among those with PPLN and MPLN.
HYPOTHESIS: Individuals with MPLN will have worse short-term renal outcomes compared to those with PPLN.
METHODS: We retrospectively reviewed 278 adult LN patients (≥18 years old) identified from an Emory University Hospital registry of native renal biopsies performed between January 2000 and December 2011. The final analytic sample consisted of individuals with a diagnosis of PPLN (n = 60) and MPLN (n = 96). We analyzed differences in clinical and laboratory characteristics at baseline. We also assessed associations between LN category and renal outcomes (complete remission and time to ESRD) with logistic and Cox proportional hazards models within two years of baseline.
RESULTS: The study population was predominantly female (83.97%) and African American (71.8%) with a mean age of 33.4 years at baseline. Over a median follow up of 1.02 years, we did not find any statistically significant associations between MPLN and the development of ESRD or remission when compared to patients with PPLN (adjusted HR = 0.30, 95% CI = 0.07, 1.26).
CONCLUSION: There was no association between mixed or pure histopathologic features of LN at presentation and rate of complete or partial remission but higher baseline eGFR was associated with a lower probability of complete remission among patients with lupus nephritis.

PMID: 27304068 [PubMed - as supplied by publisher]

Cerebral blood velocity regulation during progressive blood loss compared with lower body negative pressure in humans.

Recent Research Articles from UNTHSC - Thu, 06/16/2016 - 06:30
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Cerebral blood velocity regulation during progressive blood loss compared with lower body negative pressure in humans.

J Appl Physiol (1985). 2015 Sep 15;119(6):677-85

Authors: Rickards CA, Johnson BD, Harvey RE, Convertino VA, Joyner MJ, Barnes JN

Abstract
Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. It is unknown if cerebral blood flow responses to actual blood loss are analogous to simulated blood loss during LBNP. Nine healthy men were studied at baseline, during three levels of LBNP (5 min at -15, -30, and -45 mmHg), and during three levels of blood loss (333, 667, and 1,000 ml). LBNP and blood loss conditions were randomized. Intra-arterial mean arterial pressure (MAP) during LBNP was similar to that during blood loss (P ≥ 0.42). Central venous pressure (2.8 ± 0.7 vs. 4.0 ± 0.8, 1.2 ± 0.6 vs. 3.5 ± 0.8, and 0.2 ± 0.9 vs. 2.1 ± 0.9 mmHg for levels 1, 2, and 3, respectively, P ≤ 0.003) and stroke volume (71 ± 4 vs. 80 ± 3, 60 ± 3 vs. 74 ± 3, and 51 ± 2 vs. 68 ± 4 ml for levels 1, 2, and 3, respectively, P ≤ 0.002) were lower during LBNP than blood loss. Despite differences in central venous pressure, middle cerebral artery velocity (MCAv) and cerebrovascular conductance were similar between LBNP and blood loss at each level (MCAv at level 3: 62 ± 6 vs. 66 ± 5 cm/s, P = 0.37; cerebrovascular conductance at level 3: 0.72 ± 0.05 vs. 0.73 ± 0.05 cm·s(-1)·mmHg(-1), P = 0.53). While the slope of the MAP-MCAv relationship was slightly different between LBNP and blood loss (0.41 ± 0.03 and 0.66 ± 0.04 cm·s(-1)·mmHg(-1), respectively, P = 0.05), time domain gain between MAP and MCAv at maximal LBNP/blood loss (P = 0.23) and low-frequency MAP-mean MCAv transfer function coherence, gain, and phase were similar (P ≥ 0.10). Our results suggest that cerebral hemodynamic responses to LBNP to -45 mmHg and blood loss up to 1,000 ml follow a similar trajectory, and the arterial pressure-cerebral blood velocity relationship is not altered from baseline under these conditions.

PMID: 26139213 [PubMed - indexed for MEDLINE]

The US Cancer Moonshot initiative.

Recent Research Articles from UNTHSC - Wed, 06/15/2016 - 06:33

The US Cancer Moonshot initiative.

Lancet Oncol. 2016 May;17(5):e178-e180

Authors: Aelion CM, Airhihenbuwa CO, Alemagno S, Amler RW, Arnett DK, Balas A, Bertozzi S, Blakely CH, Boerwinkle E, Brandt-Rauf P, Buekens PM, Chandler GT, Chang RW, Clark JE, Cleary PD, Curran JW, Curry SJ, Roux AV, Dittus R, Ellerbeck EF, El-Mohandes A, Eriksen MP, Erwin PC, Evans G, Finnegan JR, Fried LP, Frumkin H, Galea S, Goff DC, Goldman LR, Guilarte TR, Rivera-Gutiérrez R, Halverson PK, Hand GA, Harris CM, Healton CG, Hennig N, Heymann J, Hunter D, Hwang W, Jones RM, Klag MJ, Klesges LM, Lahey T, Lawlor EF, Maddock J, Martin WJ, Mazzaschi AJ, Michael M, Mohammed SD, Nasca PC, Nash D, Ogunseitan OA, Perez RA, Perri M, Petersen DJ, Peterson DV, Philbert M, Pinto-Martin J, Raczynski JM, Raskob GE, Rimer BK, Rohrbach LA, Rudkin LL, Siminoff L, Szapocznik J, Thombs D, Torabi MR, Weiler RM, Wetle TF, Williams PL, Wykoff R, Ying J

PMID: 27301041 [PubMed - as supplied by publisher]

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

Recent Research Articles from UNTHSC - Wed, 06/15/2016 - 06:33

Increased Global DNA Methylation and Decreased TGFβ1 Promoter Methylation in Glaucomatous Lamina Cribrosa Cells.

J Glaucoma. 2016 Jun 13;

Authors: McDonnell FS, McNally SA, Clark AF, O'Brien CJ, Wallace DM

Abstract
BACKGROUND: Glaucoma is an optic neuropathy that affects 60 million people worldwide. There is an underlying fibrosis associated with the lamina cribrosa (LC) in glaucoma. DNA methylation is well established in regulating fibrosis and may be a therapeutic target for glaucoma. The purpose of this study was to compare global DNA methylation levels in primary human normal (NLC) and glaucomatous (GLC) cells, and to investigate DNA methylation in driving fibrosis through regulation of transforming growth factor β1 (TGFβ1).
MATERIALS AND METHODS: LC cells were cultured from normal and glaucomatous human donors. Global methylation was assessed by ELISA. qPCR was conducted for DNA methyltransferases (DNMTs), methyl-CpG-binding protein 2 (MeCP2), TGFβ 1 and 2, collagen 1α1 (COL1A1), and α-smooth muscle actin (αSMA). TGFβ1 and DNMT1 were examined by immunofluorescence. Methylation of the TGFβ1 promoter was determined by methylation-specific PCR (MSP).
RESULTS: Global DNA methylation demonstrated an increase in GLC compared with NLC cells (P<0.05). The previously mentioned methylation and matrix genes were increased in GLC compared with NLC cells (P<0.05). Immunofluorescence showed increased TGFβ1 and DNMT1 in GLC compared with NLC cells. MSP showed increased unmethylated DNA in the TGFβ1 promoter of GLC compared with NLC cells.
CONCLUSIONS: We found increased expression of fibrotic genes in GLC cells and demonstrated an increase in global DNA methylation and in associated enzymes in GLC cells. Furthermore, we showed decreased promoter methylation of TGFβ1 in GLC cells. Determining a role for methylation in glaucoma and in regulating TGFβ1 may provide a novel therapeutic approach.

PMID: 27300643 [PubMed - as supplied by publisher]

Resolving the etiology of atopic disorders by using genetic analysis of racial ancestry.

Recent Research Articles from UNTHSC - Wed, 06/15/2016 - 06:33

Resolving the etiology of atopic disorders by using genetic analysis of racial ancestry.

J Allergy Clin Immunol. 2016 Jun 10;

Authors: Gupta J, Johansson E, Bernstein JA, Chakraborty R, Khurana Hershey GK, Rothenberg ME, Mersha TB

Abstract
Atopic dermatitis (AD), food allergy, allergic rhinitis, and asthma are common atopic disorders of complex etiology. The frequently observed atopic march from early AD to asthma, allergic rhinitis, or both later in life and the extensive comorbidity of atopic disorders suggest common causal mechanisms in addition to distinct ones. Indeed, both disease-specific and shared genomic regions exist for atopic disorders. Their prevalence also varies among races; for example, AD and asthma have a higher prevalence in African Americans when compared with European Americans. Whether this disparity stems from true genetic or race-specific environmental risk factors or both is unknown. Thus far, the majority of the genetic studies on atopic diseases have used populations of European ancestry, limiting their generalizability. Large-cohort initiatives and new analytic methods, such as admixture mapping, are currently being used to address this knowledge gap. Here we discuss the unique and shared genetic risk factors for atopic disorders in the context of ancestry variations and the promise of high-throughput "-omics"-based systems biology approach in providing greater insight to deconstruct their genetic and nongenetic etiologies. Future research will also focus on deep phenotyping and genotyping of diverse racial ancestry, gene-environment, and gene-gene interactions.

PMID: 27297995 [PubMed - as supplied by publisher]

Involvement of AMPA Receptor and Its Flip and Flop Isoforms in Retinal Ganglion Cell Death Following Oxygen/Glucose Deprivation.

Recent Research Articles from UNTHSC - Wed, 06/15/2016 - 06:33
Related Articles

Involvement of AMPA Receptor and Its Flip and Flop Isoforms in Retinal Ganglion Cell Death Following Oxygen/Glucose Deprivation.

Invest Ophthalmol Vis Sci. 2016 Feb;57(2):508-26

Authors: Park YH, Broyles HV, He S, McGrady NR, Li L, Yorio T

Abstract
PURPOSE: The α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors (AMPAR) subunits can be posttranscriptionally modified by alternative splicing forming flip and flop isoforms. We determined if an ischemia-like insult to retinal ganglion cells (RGCs) increases AMPAR susceptibility to s-AMPA-mediated excitotoxicity through changes in posttranscriptional modified isoforms.
METHODS: Purified neonatal rat RGCs were subjected to either glucose deprivation (GD) or oxygen/glucose deprivation (OGD) conditions followed by treatment with either 100 μM s-AMPA or Kainic acid. A live-dead assay and caspase 3 assay was used to assess cell viability and apoptotic changes, respectively. We used JC-1 dye and dihydroethidium to measure mitochondria depolarization and reactive oxygen species (ROS), respectively. Calcium imaging with fura-2AM was used to determine intracellular calcium, while the fluorescently-labeled probe, Nanoprobe1, was used to detect calcium-permeable AMPARs. Quantitative PCR (qPCR) analysis was done to determine RNA editing sites AMPAR isoforms.
RESULTS: Glucose deprivation, as well as an OGD insult followed by AMPAR stimulation, produced a significant increase in RGC death. Retinal ganglion cell death was independent of caspase 3/7 activity, but was accompanied by increased mitochondrial depolarization and increased ROS production. This was associated with an elevated intracellular Ca(2+) and calcium permeable-AMPARs. The mRNA expression of GLUA2 and GLUA3 flop isoform decreased significantly, while no appreciable changes were found in the corresponding flip isoforms. There were no changes in the Q/R editing of GLUA2, while R/G editing of GLUA2 flop declined under these conditions.
CONCLUSIONS: Following oxidative injury, RGCs become more susceptible to AMPAR-mediated excitotoxicity. RNA editing and changes in alternative spliced flip and flop isoforms of AMPAR subunits may contribute to increased RGC death.

PMID: 26868754 [PubMed - indexed for MEDLINE]

MicroRNA-124 Targets Tip110 Expression and Regulates Hematopoiesis.

Recent Research Articles from UNTHSC - Wed, 06/15/2016 - 06:33
Related Articles

MicroRNA-124 Targets Tip110 Expression and Regulates Hematopoiesis.

Stem Cells Dev. 2015 Sep 1;24(17):2009-17

Authors: Liu Y, Huang X, Timani KA, Broxmeyer HE, He JJ

Abstract
MicroRNA (miR) regulates hematopoiesis through targeting different genes post-transcriptionally. We have recently shown that Tip110 expression is downregulated during hematopoietic stem cell differentiation. However, the underlying mechanisms are not known. In this study, we identified a conserved miR-124-binding site on the Tip110 3'-untranslated region (3'-UTR) and showed that Tip110 was downregulated by miR-124 through its 3'-UTR. We then examined the relationship among miR-124 and Tip110 expression and differentiation of human cord blood CD34(+) cells. We found that miR-124 was expressed in a low level in human cord blood CD34(+) cells, but it was considerably upregulated during culturing and differentiation of these cells. Moreover, we demonstrated that miR-124 expression decreased Tip110 expression and promoted differentiation of human cord blood CD34(+) cells, while miR-124 knockdown increased Tip110 expression, slowed down differentiation of human cord blood CD34(+) cells, and caused an expansion of hematopoietic progenitor cells in vitro. Finally, we used mouse embryonic fibroblasts derived from Tip110 transgenic mice, performed the exon array analysis, and found that Tip110 altered a number of genes in the hematopoiesis pathways. Dnmt3a as de novo methyltransferase was also significantly upregulated. That miR-124 was markedly upregulated during human cord blood CD34(+) cell differentiation could be the result of direct loss of its promoter methylation from Dnmt3a. Taken together, our study demonstrates that miR-124 regulates Tip110 expression and differentiation of human cord blood CD34(+) cells and suggests important roles of miR-124/Tip110 in hematopoiesis.

PMID: 25928721 [PubMed - indexed for MEDLINE]

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