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  • 1
    In: The Journal of Virology, 2006, Vol. 80(4), p.1773
    Description: Mammalian alphaherpesviruses normally establish latent infections in ganglia of the peripheral nervous system in their natural hosts. Occasionally, however, these viruses spread to the central nervous system (CNS), where they cause damaging, often fatal, infections. Attenuated alphaherpesvirus derivatives have been used extensively as neuronal circuit tracers in a variety of animal models. Their circuit-specific spread provides a unique paradigm to study the local and global CNS response to infection. Thus, we systematically analyzed the host gene expression profile after acute pseudorabies virus (PRV) infection of the CNS using Affymetrix GeneChip technology. Rats were injected intraocularly with one of three selected virulent and attenuated PRV strains. Relative levels of cellular transcripts were quantified from hypothalamic and cerebellar tissues at various times postinfection. The number of cellular genes responding to infection correlated with the extent of virus dissemination and relative virulence of the PRV strains. A total of 245 out of 8,799 probe sets, corresponding to 182 unique cellular genes, displayed increased expression ranging from 2- to more than 100-fold higher than in uninfected tissue. Over 60% thereof were categorized as immune, proinflammatory, and other cellular defense genes. Additionally, a large fraction of infection-induced transcripts represented cellular stress responses, including glucocorticoid- and redox-related pathways. This is the first comprehensive in vivo analysis of the global transcriptional response of the mammalian CNS to acute alphaherpesvirus infection. The differentially regulated genes reported here are likely to include potential diagnostic and therapeutic targets for viral encephalitides and other neurodegenerative or neuroinflammatory diseases.
    Keywords: Central Nervous System ; Latent Infection ; Hypothalamus ; Brain ; Cerebellum ; Animal Models ; Transcription ; Stress ; Glucocorticoids ; Inflammation ; Gene Expression ; Pseudorabies ; Virulence ; Tracers ; Peripheral Nervous System ; Ganglia ; Pseudorabies Virus ; Alphaherpesvirus ; Effects on Host Cell Metabolism ; Gene Regulation;
    ISSN: 0022-538X
    ISSN: 0022538X
    E-ISSN: 10985514
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  • 2
    Language: English
    In: General Hospital Psychiatry, September 2017, Vol.48, pp.42-50
    Description: Emotion regulation difficulties are a potentially key mechanism underlying the association between childhood maltreatment and alcohol use in adulthood. The current study examined the mediating role of emotion regulation difficulties in the association between childhood maltreatment severity (i.e., Childhood Trauma Questionnaire total score) and past-month alcohol use severity, including alcohol consumption frequency and alcohol-related problems (i.e., number of days of alcohol problems, ratings of “bother” caused by alcohol problems, ratings of treatment importance for alcohol problems). Participants included 111 acute-care psychiatric inpatients (45.0% female; age = 33.5, = 10.6), who reported at least one posttraumatic stress disorder Criterion A traumatic event, indexed via the Life Events Checklist for . Participants completed questionnaires regarding childhood maltreatment, emotion regulation difficulties, and alcohol use. A significant indirect effect of childhood maltreatment severity via emotion regulation difficulties in relation to alcohol use severity ( = 0.07, = 0.04, 99% CI [0.01, 0.21]) was documented. Specifically, significant indirect effects were found for childhood maltreatment severity via emotion regulation difficulties in relation to alcohol problems ( between 0.05 and 0.12; all 99% bootstrapped CIs with 10,000 resamples did not include 0) but not alcohol consumption. Emotion regulation difficulties may play a significant role in the association between childhood maltreatment severity and alcohol outcomes. Clinical implications are discussed.
    Keywords: Childhood Maltreatment ; Trauma ; Emotion Regulation ; Alcohol ; Psychiatric Inpatients
    ISSN: 0163-8343
    E-ISSN: 1873-7714
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  • 3
    Language: English
    In: Alcoholism, clinical and experimental research, June 2011, Vol.35(6), pp.1034-40
    Description: Although there are multiple indications that alcohol can alter many physiological brain functions, including cerebral blood flow (CBF), studies of the latter have generally used small- or modest-sized samples. Few investigations have yet evaluated how CBF changes after alcohol relate to subsets of subjects with elevated alcoholism risks, such as those with lower levels of response (LR) to alcohol. This study used arterial spin labeling (ASL) after alcohol administration to evaluate a large sample of healthy young men and women with low and high alcohol responses, and, thus, varying risks for alcohol use disorders (AUD). Healthy young adult social drinkers with low and high LR (N=88, 50% women) matched on demography and drinking histories were imaged with whole-brain resting ASL ~1 hour after ingesting ~3 drinks of ethanol and after a placebo beverage (i.e., 178 ASL sessions). The relationships of CBF changes from placebo to alcohol for subjects with low and high LR were evaluated. CBF increased after alcohol when compared to placebo in 5 frontal brain regions. Despite identical blood alcohol concentrations, these increases with alcohol were less prominent in individuals who required more drinks to experience alcohol-related effects (i.e., had a lower LR to alcohol). The LR group differences remained significant after covarying for recent drinking quantities. The results confirm that alcohol intake is associated with acute increases in CBF, particularly in frontal regions. Less intense CBF changes were seen in subjects with a genetically influenced characteristic, a low LR to alcohol, that relates to the future risk of heavy drinking and alcohol problems.
    Keywords: Alcohol Drinking -- Genetics ; Cerebrovascular Circulation -- Physiology ; Ethanol -- Administration & Dosage ; Regional Blood Flow -- Physiology
    ISSN: 01456008
    E-ISSN: 1530-0277
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  • 4
    In: Arthritis & Rheumatism, June 2013, Vol.65(6), pp.1430-1438
    Description: Objective To study changes in lipid profiles at 24 weeks among patients with early rheumatoid arthritis (RA) participating in the Treatment of Early RA (TEAR) trial and randomized to receive methotrexate (MTX) plus etanercept, triple therapy (MTX plus sulfasalazine plus hydroxychloroquine), or aggressively titrated MTX monotherapy. Methods This TEAR substudy included 459 participants with biologic specimens. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were measured at 0 and 24 weeks. Results At 24 weeks, there were statistically significant increases in mean cholesterol levels in the MTX plus etanercept, triple therapy, and MTX monotherapy arms. The observed increases were 31.4 mg/dl, 28.7 mg/dl, and 30 mg/dl in LDL cholesterol, 19.3 mg/dl, 22.3 mg/dl, and 20.6 mg/dl in HDL cholesterol, and 56.8 mg/dl, 53 mg/dl, and 57.3 mg/dl in total cholesterol (P 〈 0.0001 versus baseline for each comparison). There was a statistically significant decrease in the ratio of total cholesterol to HDL cholesterol at 24 weeks in all 3 treatment groups versus baseline. There was no difference in any lipid changes between the 3 treatment arms. After multivariable adjustment, change in C-reactive protein, but not the Disease Activity Score in 28 joints, was associated with change in LDL cholesterol (P = 0.03) and total cholesterol (P = 0.01). Baseline glucocorticoid use was associated with changes in HDL cholesterol (P = 0.03) and total cholesterol (P = 0.02). Conclusion Levels of total cholesterol, LDL cholesterol, and HDL cholesterol increased comparably shortly after initiation of MTX plus etanercept, triple therapy, and MTX monotherapy among patients with early RA with active disease participating in a clinical trial. The clinical relevance of short-term changes in traditional lipids on cardiovascular outcomes remains to be determined. [PUBLICATION ]
    Keywords: Adult–Administration & Dosage ; Aged–Therapeutic Use ; Antirheumatic Agents–Drug Therapy ; Antirheumatic Agents–Blood ; Arthritis, Rheumatoid–Blood ; Cholesterol, HDL–Administration & Dosage ; Cholesterol, LDL–Therapeutic Use ; Drug Therapy, Combination–Administration & Dosage ; Female–Therapeutic Use ; Humans–Administration & Dosage ; Hydroxychloroquine–Therapeutic Use ; Hydroxychloroquine–Administration & Dosage ; Immunoglobulin G–Therapeutic Use ; Immunoglobulin G–Administration & Dosage ; Male–Therapeutic Use ; Methotrexate–Therapeutic Use ; Methotrexate–Therapeutic Use ; Middle Aged–Therapeutic Use ; Receptors, Tumor Necrosis Factor–Therapeutic Use ; Receptors, Tumor Necrosis Factor–Therapeutic Use ; Sulfasalazine–Therapeutic Use ; Sulfasalazine–Therapeutic Use ; Treatment Outcome–Therapeutic Use ; Cholesterol ; Drug Therapy ; Methotrexate ; Antirheumatic Agents ; Cholesterol, HDL ; Cholesterol, LDL ; Immunoglobulin G ; Receptors, Tumor Necrosis Factor ; Tnfr-Fc Fusion Protein ; Sulfasalazine ; Hydroxychloroquine ; Methotrexate;
    ISSN: 0004-3591
    E-ISSN: 1529-0131
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  • 5
    Language: English
    In: Journal of Child Language, September 2012, Vol.39(4), p.777
    Description: Pronouns seem to be acquired in an asymmetrical way, where children confuse the meaning of pronouns with reflexives up to the age of six, but not vice versa. Children's production of the same referential expressions is appropriate at the age of four. However, response-based tasks, the usual...
    Keywords: Comprehension ; Child Language ; Preschool Children ; Eye Movements ; Form Classes (Languages) ; Language Acquisition ; Task Analysis ; Indo European Languages ; Responses ; Language Processing ; Education ; Social Welfare & Social Work ; Languages & Literatures ; Psychology
    ISSN: 0305-0009
    E-ISSN: 1469-7602
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  • 6
    Language: English
    In: Annals of the Rheumatic Diseases, 20 July 2012, Vol.71(7), p.1157
    Description: Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls.
    Keywords: Medicine;
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 7
    Language: English
    In: Rheumatology International, 2012, Vol.32(9), pp.2725-2729
    Description: Patient overall satisfaction with health (PSH) was measured by a subset of questions from the Arthritis Impact Measurement Scales II. Based on longitudinal observations for 267 early rheumatoid arthritis (RA) patients of the United States Western Consortium (WC) cohort receiving first non-biologic DMARD treatment, we estimated the 1-year change in PSH ( $$\Updelta$$ PSH). Logistic regression analysis was used to estimate the association of improvement in $$\Updelta$$ PSH with the core set of clinical and patient-reported components of disease activity scores (DAS). Most patients were more satisfied with health after 1 year of treatment (80%); few achieved DAS28-ESR minimal disease activity (27%) or remission (7%). Laboratory and joint count measures were not associated with improved 12-month PSH. Patients with greater HAQ-DI ( P = 0.0473) and self-reported stiffness ( P = 0.0669) were more likely to have a perceived overall health benefit from treatment. Regardless of objective disease status, patients are generally satisfied with first-line treatment, which could present a challenge to implementing DAS-guided treatment change. Patients with greater self-reported functional limitations might have lower expectations for treatment benefit and be less willing to modify their current therapy; subjective assessments of function and stiffness could be particularly useful in identifying these patients.
    Keywords: Disease activity score ; Disease-modifying antirheumatic drugs ; Remission ; Rheumatoid arthritis ; Patient-reported outcome ; Patient satisfaction ; Stiffness
    ISSN: 0172-8172
    E-ISSN: 1437-160X
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  • 8
    Language: English
    In: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, October 2016, Vol.25(10), pp.1418-1425
    Description: Metformin has been associated with improved colorectal cancer survival, but investigations are limited by small numbers of patients and confounding by diabetic severity. We examined the association between metformin use and overall survival (OS) in patients with diabetes and colorectal cancer in a large population of U.S. veterans, while adjusting for measures of diabetic severity. Patients diagnosed with colorectal cancer from January 2001 to December 2008 were identified from the Veterans Affairs Central Cancer Registry. Multivariable models were used to examine the adjusted association of OS with diabetes and use of antidiabetic medications. There were 21,352 patients diagnosed with colorectal cancer identified (n = 16,355 nondiabetic patients, n = 2,038 diabetic patients on metformin, n = 2,136 diabetic patients on medications other than metformin, n = 823 diabetic patients not on antidiabetic medication). Diabetic patients had a significantly worse OS than nondiabetic patients, but metformin users had only a 10% increase in death (HR 1.10; 95% CI, 1.03-1.17, P = 0.004), as compared with 22% for users of other antidiabetic medications (HR 1.22; 95% CI, 1.15-1.29, P 〈 0.0001). Among colorectal cancer patients with diabetes, metformin users had a 13% improved OS versus patients taking other antidiabetic medications (HR 0.87; 95% CI, 0.79-0.95, P = 0.003), while diabetic patients not on any antidiabetic medications did not differ with respect to OS (HR 1.02; 95% CI, 0.90-1.15, P = 0.76). Among diabetics with colorectal cancer, metformin use is associated with improved survival, despite adjustments for diabetes severity and other risk factors. These data lend further support to the conduct of randomized studies of possible anticancer effects of metformin among patients with colorectal cancer. Cancer Epidemiol Biomarkers Prev; 25(10); 1418-25. ©2016 AACR.
    Keywords: Colorectal Neoplasms -- Epidemiology ; Diabetes Mellitus, Type 2 -- Drug Therapy ; Hypoglycemic Agents -- Therapeutic Use ; Metformin -- Therapeutic Use
    ISSN: 10559965
    E-ISSN: 1538-7755
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  • 9
    Language: English
    In: Journal of studies on alcohol, November 2004, Vol.65(6), pp.692-700
    Description: This study examined neural correlates of the low level of response to alcohol using functional magnetic resonance imaging (FMRI) during a challenging visual working memory task. Participants were healthy adolescents (N = 35) with a range of drinking patterns recruited from local high schools. After a minimum 5 days of abstinence from alcohol and other drugs, FMRI, neuropsychological testing and the Self-Rating of the Effects of Alcohol were administered. Self-report of initial level of response to alcohol was significantly predicted by FMRI blood oxygen level dependent (BOLD) response to the visual working memory task in the right prefrontal and bilateral anterior cingulate region (12% of unique variance, p 〈 .05) and right cerebellum and parahippocampal gyrus (17% of unique variance, p 〈 .01), above and beyond effects accounted for by drinks consumed per month, age, gender and ethnicity. Young people who report having needed more alcohol to achieve specific effects during early drinking experiences show higher levels of brain response during visual working memory, perhaps suggesting less capacity to adjust cognitive processing to contextual demands.
    Keywords: Ethanol -- Administration & Dosage ; Frontal Lobe -- Drug Effects ; Memory -- Drug Effects ; Parietal Lobe -- Drug Effects ; Photic Stimulation -- Methods
    ISSN: 0096-882X
    E-ISSN: 19342683
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  • 10
    In: Arthritis & Rheumatology, March 2016, Vol.68(3), pp.577-586
    Description: OBJECTIVE: To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.METHODS: Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time.RESULTS: Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P 〈 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P 〈 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup.CONCLUSION: Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
    Keywords: Medicine;
    ISSN: 2326-5191
    E-ISSN: 2326-5205
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