Recent Research Articles from UNTHSC

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Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland.

Sun, 10/12/2014 - 4:04am
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Coding ill-defined and unknown cause of death is 13 times more frequent in Denmark than in Finland.

Forensic Sci Int. 2014 Sep 28;244C:289-294

Authors: Ylijoki-Sørensen S, Sajantila A, Lalu K, Bøggild H, Boldsen JL, Boel LW

Abstract
Exact cause and manner of death determination improves legislative safety for the individual and for society and guides aspects of national public health. In the International Classification of Diseases, codes R00-R99 are used for "symptoms, signs and abnormal clinical and laboratory findings, not elsewhere classified" designated as "ill-defined" or "with unknown etiology". The World Health Organisation recommends avoiding the use of ill-defined and unknown causes of death in the death certificate as this terminology does not give any information concerning the possible conditions that led to the death. Thus, the aim of the study was, firstly, to analyse the frequencies of R00-R99-coded deaths in mortality statistics in Finland and in Denmark and, secondly, to compare these and the methods used to investigate the cause of death. To do so, we extracted a random 90% sample of the Finnish death certificates and 100% of the Danish certificates from the national mortality registries for 2000, 2005 and 2010. Subsequently, we analysed the frequencies of forensic and medical autopsies and external clinical examinations of the bodies in R00-R99-coded deaths. The use of R00-R99 codes was significantly higher in Denmark than in Finland; OR 18.6 (95% CI 15.3-22.4; p<0.001) for 2000, OR 9.5 (95% CI 8.0-11.3; p<0.001) for 2005 and OR 13.2 (95% CI 11.1-15.7; p<0.001) for 2010. More than 80% of Danish deaths with R00-R99 codes were over 70 years of age at the time of death. Forensic autopsy was performed in 88.3% of Finnish R00-R99-coded deaths, whereas only 3.5% of Danish R00-R99-coded deaths were investigated with forensic or medical autopsy. The codes that were most used in both countries were R96-R99, meaning "unknown cause of death". In Finland, all of these deaths were investigated with a forensic autopsy. Our study suggests that if all deaths in all age groups with unclear cause of death were systematically investigated with a forensic autopsy, only 2-3/1000 deaths per year would be coded as an ill-defined and unknown cause of death in national mortality statistics. At the same time the risk to overlook unnatural deaths is decreased to a minimum. To achieve this in Denmark requires that the existing legislation on cause of death investigation would need to be changed to ensure that all deaths with unknown cause of death are investigated with a forensic autopsy.

PMID: 25300069 [PubMed - as supplied by publisher]

Longevity loss among cured tuberculosis patients and the potential value of prevention.

Sun, 10/12/2014 - 4:04am
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Longevity loss among cured tuberculosis patients and the potential value of prevention.

Int J Tuberc Lung Dis. 2014 Nov;18(11):1347-1352

Authors: Hoger S, Lykens K, Beavers SF, Katz D, Miller TL

Abstract
BACKGROUND: Evidence of substantial, quantifiable and preventable burdens of mortality hazard even after anti-tuberculosis treatment and cure would be a compelling, concrete, and useful measure of the value of prevention.
METHODS: We compared years of potential life lost between a cohort of 3 933 cured tuberculosis (TB) patients and 9 166 persons with latent tuberculous infection. We constructed a regression model to predict the expected years of potential life lost in each cohort and for demographic subgroups.
RESULTS: Among decedents, a history of fully treated TB is associated with a predicted average 3.6 more years of potential life loss than a comparable population without active TB. Greater longevity losses were predicted among those identified as White and Hispanic than among Black and Asian counterparts.
CONCLUSION: We found significant differences in predicted longevity of treated TB survivors relative to a similar group without active TB. These excess losses are substantial: a total of 14 158 life-years or the equivalent of more than 188 75-year lifespans. These findings illustrate an important opportunity cost associated with each preventable TB case - an average of 3.6 potential years of life. We conclude that substantial preventable mortality burdens remain despite adequate anti-tuberculosis treatment, a compelling rationale for more widespread and systematic use of prevention.

PMID: 25299869 [PubMed - as supplied by publisher]

Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice.

Sun, 10/12/2014 - 4:04am
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Biological significance of FoxN1 gain-of-function mutations during T and B lymphopoiesis in juvenile mice.

Cell Death Dis. 2014;5:e1457

Authors: Ruan L, Zhang Z, Mu L, Burnley P, Wang L, Coder B, Zhuge Q, Su DM

Abstract
FoxN1 is cell-autonomously expressed in skin and thymic epithelial cells (TECs), essential for their development. Inborn mutation of FoxN1 results in hair follicle and TEC development failure, whereas insufficient postnatal FoxN1 expression induces thymic atrophy, resulting in declined T lymphopoiesis. Although upregulating FoxN1 expression in the aged FoxN1-declined thymus rejuvenates T lymphopoiesis, whether its over- and ectopic-expression in early life is beneficial for T lymphopoiesis is unknown. Using our newly generated Rosa26-STOP(flox)-FoxN1 mice, in which over- and ectopic-expression of FoxN1 can be induced by various promoter-driven Cre-mediated deletions of the roadblock STOP(flox) in early life, we found that K14Cre-mediated inborn FoxN1 overexpression induced neonatal lethality, exhibited abnormal permeability in the skin and abnormal nursing. Ubiquitous deletion of the STOP(flox) mediated by progressive uCreER(T) leakage in juvenile mice affected thymus and bone marrow normality, resulting in an increased ratio of medullary/cortical TECs, along with declined T and B lymphopoiesis. Although the K5CreER(T)-mediated FoxN1 overexpression mice had a normal lifespan, induction of K5CreER(T) activation in juveniles adversely influenced total thymoycte development and produced ichthyosis-like skin. Therefore, FoxN1 has temporal and tissue-specific activity. Over- and ectopic-expression of FoxN1 in early life adversely influence immature TEC, T and B cell, and skin epithelial development.

PMID: 25299782 [PubMed - as supplied by publisher]

Arsenic exposure, AS3MT polymorphism, and neuropsychological functioning among rural dwelling adults and elders: a cross-sectional study.

Sun, 10/12/2014 - 4:04am
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Arsenic exposure, AS3MT polymorphism, and neuropsychological functioning among rural dwelling adults and elders: a cross-sectional study.

Environ Health. 2014;13(1):15

Authors: Edwards M, Hall J, Gong G, O'Bryant SE

Abstract
BACKGROUND: The aim was to examine the link between low-level arsenic exposure and cognitive functioning, and the potential role of a single nucleotide polymorphism (SNP A35991G, rs10748835) of the AS3MT gene in modifying this link.
METHODS: Data were analyzed on 526 participants from Project FRONTIER. Hierarchical linear regressions were created with neuropsychological raw index scores as the outcome variable and arsenic exposure and AS3MT SNP as different predictor variables.
RESULTS: Within the total sample, arsenic exposure was negatively associated with language (p < 0.001) and executive functioning (p < 0.001). Among those with the AA genotype of the AS3MT gene, arsenic levels were negatively associated with language (p < 0.001), attention (p = 0.01), and executive functioning (p = 0.04). Among those with the AG genotype, arsenic levels were positively associated with immediate (p = 0.04) and delayed memory (p < 0.001) and negatively associated with executive functioning (p = 0.03). Among those with the GG genotype, arsenic levels were negatively associated with visuospatial functioning (p = 0.02).
CONCLUSIONS: Low-level arsenic exposure is associated with cognitive functioning; however, this association is modified by an AS3MT gene.

PMID: 24621105 [PubMed - indexed for MEDLINE]

Molecular neuropsychology: creation of test-specific blood biomarker algorithms.

Sun, 10/12/2014 - 4:04am
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Molecular neuropsychology: creation of test-specific blood biomarker algorithms.

Dement Geriatr Cogn Disord. 2014;37(1-2):45-57

Authors: O'Bryant SE, Xiao G, Barber R, Cullum CM, Weiner M, Hall J, Edwards M, Grammas P, Wilhelmsen K, Doody R, Diaz-Arrastia R, Texas Alzheimer’s Research and Care Consortium

Abstract
BACKGROUND: Prior work on the link between blood-based biomarkers and cognitive status has largely been based on dichotomous classifications rather than detailed neuropsychological functioning. The current project was designed to create serum-based biomarker algorithms that predict neuropsychological test performance.
METHODS: A battery of neuropsychological measures was administered. Random forest analyses were utilized to create neuropsychological test-specific biomarker risk scores in a training set that were entered into linear regression models predicting the respective test scores in the test set. Serum multiplex biomarker data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients and 198 controls) from the Texas Alzheimer's Research and Care Consortium.
RESULTS: The biomarker risk scores were significant predictors (p < 0.05) of scores on all neuropsychological tests. With the exception of premorbid intellectual status (6.6%), the biomarker risk scores alone accounted for a minimum of 12.9% of the variance in neuropsychological scores. Biomarker algorithms (biomarker risk scores and demographics) accounted for substantially more variance in scores. Review of the variable importance plots indicated differential patterns of biomarker significance for each test, suggesting the possibility of domain-specific biomarker algorithms.
CONCLUSIONS: Our findings provide proof of concept for a novel area of scientific discovery, which we term 'molecular neuropsychology'.

PMID: 24107792 [PubMed - indexed for MEDLINE]

Wikipedia vs Peer-Reviewed Medical Literature for Information About the 10 Most Costly Medical Conditions-III.

Fri, 10/10/2014 - 4:05am
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Wikipedia vs Peer-Reviewed Medical Literature for Information About the 10 Most Costly Medical Conditions-III.

J Am Osteopath Assoc. 2014 Oct;114(10):764-5

Authors: Chen GS, Xiong Y

PMID: 25288709 [PubMed - in process]

Psychological distress and emergency department utilization in the United States: evidence from the Medical Expenditure Panel Survey.

Fri, 10/10/2014 - 4:05am
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Psychological distress and emergency department utilization in the United States: evidence from the Medical Expenditure Panel Survey.

Acad Emerg Med. 2014 May;21(5):510-9

Authors: Stockbridge EL, Wilson FA, Pagán JA

Abstract
OBJECTIVES: Psychological distress not only has substantial health and social consequences, but is also associated with emergency department (ED) use. Previous studies have typically used cross-sectional data to focus on the relation between serious psychological distress and dichotomized ED utilization measures, without assessing the volume of ED use or examining nonserious levels of psychological distress. The objective of this study was to explore the association between ED utilization volume and the full spectrum of psychological distress.
METHODS: Data from Panel 14 of the Medical Expenditure Panel Survey (MEPS; 2009-2010, n = 9,743) provided a nationally representative sample of U.S. individuals. ED utilization volume and three specifications of the Kessler Psychological Distress Scale (K6) were analyzed: a dichotomous serious/no serious psychological distress measure, a five-category ordinal measure, and a scale measure with a range of 0 to 24. Negative binomial-logit hurdle regression models were used to analyze how the different specifications of the K6 psychological distress measure were related to ED use.
RESULTS: Adults with serious psychological distress in 2009 had 1.59 (95% confidence interval [CI] = 1.15 to 2.20) times greater adjusted odds of having one or more ED visits in 2010 than those without serious psychological distress. Nonserious psychological distress levels in 2009 were also associated with increased adjusted odds of having at least one ED visit in 2010. The K6 scores showed a dose-response relationship in terms of the adjusted odds of having one or more ED visits. The adjusted odds ratios (ORs) were 1.86 (95% CI = 1.37 to 2.54) for adults with K6 scores at or above 11, OR 1.76 (95% CI = 1.38 to 2.25) for adults with K6 scores between 6 and 10, OR 1.33 (95% CI = 1.05 to 1.68) for adults with K6 scores between 3 and 5, and OR 1.17 (95% CI = 0.92 to 1.48) for adults with K6 scores of 1 or 2. In addition, the adjusted odds of having one or more ED visits in 2010 significantly increased with increasing psychological distress in 2009 (OR = 1.04, 95% CI = 1.03 to 1.06). Each additional point added to the K6 scale results in an increase in the adjusted odds of an ED visit.
CONCLUSIONS: Even a low level of psychological distress, and not just serious psychological distress, may be an early indicator of future ED use. These results highlight the need to develop novel responses to better manage or avert ED use not only for adults with serious psychological distress but also for those who are experiencing even mild symptoms of psychological distress.

PMID: 24842501 [PubMed - indexed for MEDLINE]

Meta-analysis: underutilisation and disparities of treatment among patients with hepatocellular carcinoma in the United States.

Fri, 10/10/2014 - 4:05am
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Meta-analysis: underutilisation and disparities of treatment among patients with hepatocellular carcinoma in the United States.

Aliment Pharmacol Ther. 2013 Oct;38(7):703-12

Authors: Tan D, Yopp A, Beg MS, Gopal P, Singal AG

Abstract
BACKGROUND: Despite wide availability of treatment options for hepatocellular carcinoma (HCC), several studies have suggested underutilisation in clinical practice.
AIMS: To quantify utilisation rates for HCC treatment among patients with HCC in the United States, and to summarise patterns of association between utilisation rates and patient socio-demographic characteristics.
METHODS: We performed a systematic literature review using the Medline database from January 1989 to March 2013. Two investigators independently extracted data on patient populations, study methods and results using standardised forms. Pooled treatment rates for any treatment and curative treatment, with 95% confidence intervals, were calculated. Prespecified subgroup analysis was performed to identify patient-level correlates of treatment utilisation.
RESULTS: We identified 24 studies that met inclusion criteria. The pooled rates of any treatment and curative treatment were 52.8% (95% CI 52.2-53.4%) and 21.8% (95% CI 21.4-22.1%) respectively. Among patients diagnosed at an early stage, the pooled curative treatment rate was 59.0% (95% CI 58.1-59.9%). Elderly, non-Caucasians and patients of low socioeconomic status had lower treatment rates than their counterparts.
CONCLUSIONS: Rates of HCC treatment in the United States, including curative treatment rates among patients detected at an early stage, are disappointingly low. Future efforts should focus on identifying appropriate intervention targets to increase treatment rates and reduce socio-demographic disparities.

PMID: 23957569 [PubMed - indexed for MEDLINE]

Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Wed, 10/08/2014 - 4:05am
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Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research.

Alzheimers Dement. 2014 Sep 27;

Authors: O'Bryant SE, Gupta V, Henriksen K, Edwards M, Jeromin A, Lista S, Bazenet C, Soares H, Lovestone S, Hampel H, Montine T, Blennow K, Foroud T, Carrillo M, Graff-Radford N, Laske C, Breteler M, Shaw L, Trojanowski JQ, Schupf N, Rissman RA, Fagan AM, Oberoi P, Umek R, Weiner MW, Grammas P, Posner H, Martins R, STAR-B and BBBIG working groups

Abstract
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebrospinal fluid biomarker approaches. Despite the fact that preanalytical processing is the largest source of variability in laboratory testing, there are no currently available standardized preanalytical guidelines. The current international working group provides the initial starting point for such guidelines for standardized operating procedures (SOPs). It is anticipated that these guidelines will be updated as additional research findings become available. The statement provides (1) a synopsis of selected preanalytical methods utilized in many international AD cohort studies, (2) initial draft guidelines/SOPs for preanalytical methods, and (3) a list of required methodological information and protocols to be made available for publications in the field to foster cross-validation across cohorts and laboratories.

PMID: 25282381 [PubMed - as supplied by publisher]

Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Mon, 10/06/2014 - 4:04am
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Discriminative and locomotor effects of five synthetic cathinones in rats and mice.

Psychopharmacology (Berl). 2014 Oct 5;

Authors: Gatch MB, Rutledge MA, Forster MJ

Abstract
RATIONALE: Synthetic cathinones continue to be sold as "legal" alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds.
OBJECTIVES: The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine.
METHODS: Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline.
RESULTS: Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 h. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 h. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine.
CONCLUSIONS: All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine, or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects.

PMID: 25281225 [PubMed - as supplied by publisher]

Associations between drug use and motorcycle helmet use in fatal crashes.

Sun, 10/05/2014 - 4:04am
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Associations between drug use and motorcycle helmet use in fatal crashes.

Traffic Inj Prev. 2014;15(7):678-84

Authors: Rossheim ME, Wilson F, Suzuki S, Rodriguez M, Walters S, Thombs DL

Abstract
OBJECTIVE: Helmet use reduces mortality risk for motorcyclists, regardless of drug and alcohol use. However, the association between drug use and motorcycle helmet utilization is not well known. This study examines the relationship between drug use and motorcycle helmet use among fatally injured motorcycle riders.
METHODS: Using data from the 2005-2009 Fatality Analysis Reporting System (FARS), we examined the association between drug use and motorcycle helmet use in a multivariable logistic regression analysis of 9861 fatally injured motorcycle riders in the United States.
RESULTS: For fatally injured motorcycle riders, use of alcohol, marijuana, or other drugs was associated with increased odds of not wearing a motorcycle helmet, controlling for the effects of state motorcycle helmet laws and other confounding variables. Predicted probabilities indicate that helmet use substantially decreases among fatally injured riders mixing alcohol with marijuana and other drugs. Furthermore, the likelihood of helmet use between marijuana-only users and other drug users is virtually the same across all blood alcohol content (BAC) levels.
CONCLUSIONS: This study provides evidence that alcohol, marijuana, and other drug use is associated with not wearing a motorcycle helmet in fatal motorcycle crashes. There is a clear need for additional prevention and intervention efforts that seek to change helmet and drug use norms among motorcycle riders.

PMID: 24245609 [PubMed - indexed for MEDLINE]

African-American breast cancer survivors' preferences for various types of physical activity interventions: a Sisters Network Inc. web-based survey.

Sun, 10/05/2014 - 4:04am
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African-American breast cancer survivors' preferences for various types of physical activity interventions: a Sisters Network Inc. web-based survey.

J Cancer Surviv. 2014 Mar;8(1):31-8

Authors: Paxton RJ, Nayak P, Taylor WC, Chang S, Courneya KS, Schover L, Hodges K, Jones LA

Abstract
BACKGROUND: Needs assessments are essential to developing lifestyle interventions for minority populations. To our knowledge, no physical activity (PA) needs assessment studies have been conducted for African-American (AA) breast cancer survivors. The purpose of this study was to determine the PA intervention preferences of AA breast cancer survivors and determine whether these preferences differ according to medical and sociodemographic factors.
METHODS: AA breast cancer survivors (n = 475, mean age = 54 years) were recruited using ads sent via email and social media sites. Preferences for the mode of intervention delivery were assessed via web-based questionnaires. Descriptive statistics were used to characterize their interests in PA interventions, and subgroup differences were assessed.
RESULTS: About 49 % (142 out of 291) of the participants who completed the survey were obese and 54 % did not meet the recommended guidelines for PA. Most (90 %) participants reported that they could participate in PA, and many (67 %) indicated that they were interested in receiving program materials. Participants expressed the greatest interest in email (50 %)-, web (48 %)-, or mail-based (45 %) over group (39 %), and telephone (10 %). Women also expressed the greatest interest in participating in studies that promoted walking and resistance or strength training. Intervention preferences did not differ significantly (P > 0.05) across sociodemographic or medical factors.
CONCLUSION: Most AA breast cancer survivors can participate in PA, and many are interested in interventions that promoted walking and resistance training and were delivered via the email or web. The development of culturally sensitive interventions that provide activities consistent with preferences can assist AA breast cancer survivors to adopt and maintain a healthy lifestyle.
IMPLICATIONS FOR CANCER SURVIVORS: Despite evidence that AA breast cancer survivors are at increased risk for poor breast cancer-specific outcomes, they are underrepresented in clinical trials promoting positive health behaviors. In this study, we propose to assess their exercise preferences and receptivity to a culturally appropriate PA intervention developed in collaboration with the Sisters Network Inc. Health promotion programs developed in collaboration with a community-based organization may aid in the development of research tools and resources that AA breast cancer survivors are receptive to using.

PMID: 24043292 [PubMed - indexed for MEDLINE]

Lysyl Oxidases in the Trabecular Meshwork.

Sat, 10/04/2014 - 4:07am
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Lysyl Oxidases in the Trabecular Meshwork.

J Glaucoma. 2014 October/November;23 Proceedings of the 20th Annual Think Tank: "Exfoliation Syndrome: What We Know and Where We Need To Go" September 19-21, 2013 New York, NY Sponsored by The Glaucoma Foundation (TGF):S55-S58

Authors: Wordinger RJ, Clark AF

Abstract
The mechanical properties of the extracellular matrix (ECM) play an important role in maintaining cellular function and overall tissue homeostasis. Emerging evidence suggests that biomechanical modifications of the ECM may be initiators and/or drivers of disease, exemplified by increased tissue stiffness. Specific ECM cross-linking enzymes (tissue transglutaminase, lysyl oxidase, and lysyl oxidase-like 1) are expressed in the trabecular meshwork and are regulated by transforming growth factor beta (TGF-β) isoforms. As TGF-β isoforms are elevated in the aqueous humor of glaucoma patients, trabecular meshwork stiffness mediated by ECM cross-linking may be responsible for increased aqueous humor outflow resistance and elevated intraocular pressure.

PMID: 25275908 [PubMed - as supplied by publisher]

Chronic psychological stress suppresses contact hypersensitivity: potential roles of dysregulated cell trafficking and decreased IFN-γ production.

Sat, 10/04/2014 - 4:07am
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Chronic psychological stress suppresses contact hypersensitivity: potential roles of dysregulated cell trafficking and decreased IFN-γ production.

Brain Behav Immun. 2014 Feb;36:156-64

Authors: Hall JM, Witter AR, Racine RR, Berg RE, Podawiltz A, Jones H, Mummert ME

Abstract
Increasing evidence shows that psychological stress can have dramatic impacts on the immune system, particularly the cutaneous immune response in dermatological disorders. While there have been many studies examining the impact of acute psychological stress on contact hypersensitivity there are relatively few studies concerning the impact of chronic psychological stress. Furthermore, the local immunological mechanisms by which chronic psychological stress impacts contact hypersensitivity still remain to be explored. Here we show that restraint-induced chronic psychological stress stimulates activation of the hypothalamus-pituitary-adrenal axis and delays weight gain in female BALB/c mice. We observed that chronic psychological stress reduces the cutaneous immune response as evidence by reduced ear swelling. This correlated with a significant decrease in the inflammatory cell infiltrate. On the other hand, chronic psychological stress does not influence T cell proliferation, activation, or sensitivity to corticosterone but does increase CD4(+) and CD8(+) T cell percentages in draining lymph nodes during a contact hypersensitivity reaction. Chronic psychological stress induces a decrease in overall circulating white blood cells, lymphocytes, and monocytes during a contact hypersensitivity reaction suggesting extravasation from the circulation. Finally, we found markedly reduced local IFN-γ production in chronically stressed animals. Based on these findings we propose that chronic psychological stress reduces contact hypersensitivity due to dysregulated cell trafficking and reduced production of IFN-γ.

PMID: 24184400 [PubMed - indexed for MEDLINE]

Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-κB signaling and excitatory amino acid transporter-2 repression.

Fri, 10/03/2014 - 4:05am
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Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-κB signaling and excitatory amino acid transporter-2 repression.

J Biol Chem. 2014 Jul 11;289(28):19599-612

Authors: Vartak-Sharma N, Gelman BB, Joshi C, Borgamann K, Ghorpade A

Abstract
Astrocyte elevated gene-1 (AEG-1), a novel human immunodeficiency virus (HIV)-1 and tumor necrosis factor (TNF)-α-inducible oncogene, has generated significant interest in the field of cancer research as a therapeutic target for many metastatic aggressive tumors. However, little is known about its role in astrocyte responses during HIV-1 central nervous system (CNS) infection and whether it contributes toward the development of HIV-associated neurocognitive disorders (HAND). Therefore, in this study, we investigated changes in AEG-1 CNS expression in HIV-1-infected brain tissues and elucidated a potential mechanism of AEG-1-mediated regulation of HAND. Immunoblotting and immunohistochemical analyses of HIV-1 seropositive and HIV-1 encephalitic human brain tissues revealed significantly elevated levels of AEG-1 protein. Immunohistochemical analyses of HIV-1 Tat transgenic mouse brain tissues also showed a marked increase in AEG-1 staining. Similar to in vivo observations, cultured astrocytes expressing HIV-1 Tat also revealed AEG-1 and cytokine up-regulation. Astrocytes treated with HAND-relevant stimuli, TNF-α, interleukin (IL)-1β, and HIV-1, also significantly induced AEG-1 expression and nuclear translocation via activation of the nuclear factor (NF)-κB pathway. Co-immunoprecipitation studies demonstrated IL-1β- or TNF-α-induced AEG-1 interaction with NF-κB p65 subunit. AEG-1 knockdown decreased NF-κB activation, nuclear translocation, and transcriptional output in TNF-α-treated astrocytes. Moreover, IL-1β treatment of AEG-1-overexpressing astrocytes significantly lowered expression of excitatory amino acid transporter 2, increased expression of excitatory amino acid transporter 2 repressor ying yang 1, and reduced glutamate clearance, a major transducer of excitotoxic neuronal damage. Findings from this study identify a novel transcriptional co-factor function of AEG-1 and further implicate AEG-1 in HAND-associated neuroinflammation.

PMID: 24855648 [PubMed - indexed for MEDLINE]

Central inflammatory response to experimental stroke is inhibited by a neuroprotective dose of dietary soy.

Tue, 09/30/2014 - 4:06am

Central inflammatory response to experimental stroke is inhibited by a neuroprotective dose of dietary soy.

Brain Res. 2014 Sep 24;

Authors: Shambayati M, Patel M, Ma Y, Cunningham RL, Schreihofer DA

Abstract
Dietary soy and soy isoflavones ar e neuroprotective in experimental cerebral ischemia. Because the isoflavones in soy that are responsible for this neuroprotective effect act as phytoestrogens, we hypothesized that they would mimic the beneficial effects of estrogens on the innate inflammatory response to cerebral ischemia. Ovariectomized Sprague-Dawley rats were fed a soy free diet or a diet containing high dietary levels of soy for 5 weeks, after which they were subjected to transient middle cerebral artery occlusion (tMCAO) for 90min. Dietary soy was associated with a reduced inflammatory response in the cerebral cortex during the acute innate period 4 and 24h after tMCAO, including significant (>2-fold) reductions in interleukins 1 beta, 2, and 13, and the chemokine CXCL1. However, there was no effect of soy on tumor necrosis factor-alpha or interferon-gamma. Dietary soy was also associated with a 40 percent reduction in the nuclear translocation of p65 nuclear factor kappa B despite an increase in the expression of p65 RELA mRNA. In support of an early effect on the innate immune response to stroke, soy-fed rats had 44 percent fewer activated microglia in the infarct core than soy free rats. Interestingly, despite increased expression following injury, the steady state mRNA levels of inflammatory factors were not altered in soy-fed rats even though inflammatory proteins were. These data suggest that dietary soy isoflavones, like estrogens, inhibit of the innate immune response to injury. However, post-transcriptional mechanisms may play an important role in the mechanism of this action. Coupled with previously published data, these results support an early and rapid effect of dietary soy on the evolution of brain injury following stroke.

PMID: 25261694 [PubMed - as supplied by publisher]

Use of virtual reality gaming systems for children who are critically ill.

Tue, 09/30/2014 - 4:06am

Use of virtual reality gaming systems for children who are critically ill.

J Pediatr Rehabil Med. 2014 Jan 1;7(3):273-6

Authors: Salem Y, Elokda A

Abstract
Children who are critically ill are frequently viewed as "too sick" to tolerate physical activity. As a result, these children often fail to develop strength or cardiovascular endurance as compared to typically developing children. Previous reports have shown that early participation in physical activity in is safe and feasible for patients who are critically ill and may result in a shorter length of stay and improved functional outcomes. The use of the virtual reality gaming systems has become a popular form of therapy for children with disabilities and has been supported by a growing body of evidence substantiating its effectiveness with this population. The use of the virtual reality gaming systems in pediatric rehabilitation provides the children with opportunity to participate in an exercise program that is fun, enjoyable, playful, and at the same time beneficial. The integration of those systems in rehabilitation of children who are critically ill is appealing and has the potential to offer the possibility of enhancing physical activities. The lack of training studies involving children who are critically ill makes it difficult to set guidelines on the recommended physical activities and virtual reality gaming systems that is needed to confer health benefits. Several considerations should be taken into account before recommended virtual reality gaming systems as a training program for children who are critically ill. This article highlighted guidelines, limitations and challenges that need to be considered when designing exercise program using virtual reality gaming systems for critically ill children. This information is helpful given the popular use of virtual reality gaming systems in rehabilitation, particularly in children who are critically ill.

PMID: 25260510 [PubMed - in process]

Total knee arthroplasty with concurrent femoral and tibial osteotomies in osteogenesis imperfecta.

Sun, 09/28/2014 - 4:05am
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Total knee arthroplasty with concurrent femoral and tibial osteotomies in osteogenesis imperfecta.

Am J Orthop (Belle Mead NJ). 2014 Jan;43(1):37-42

Authors: Wagner R, Luedke C

Abstract
Three total knee arthroplasties (TKA) with concurrent femoral and/or tibial osteotomies in 2 patients with osteogenesis imperfecta were performed from 2004 to 2009. The 2 patients were followed for a mean of 6 years. One patient with concurrent TKA, and femoral and tibial osteotomies developed a nonunion of the tibial site that responded to open reduction and internal fixation with iliac crest bone graft. The second patient underwent right TKA with bi-level tibial osteotomies, which healed uneventfully, allowing pain free, unassisted ambulation. The same patient then elected to undergo left TKA with bi-level tibial osteotomies. Intraoperatively he sustained a minor tibial plateau fracture requiring the use of a stemmed component and postoperatively, he developed a nonunion at the proximal site and valgus malunion of the distal site. Revision of fixation was performed at both osteotomy sites, and both healed within 3 months. Both patients are now pain free and ambulate without assistance.

PMID: 24490185 [PubMed - indexed for MEDLINE]

Fracture morphology of high shear angle "vertical" femoral neck fractures in young adult patients.

Sun, 09/28/2014 - 4:05am
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Fracture morphology of high shear angle "vertical" femoral neck fractures in young adult patients.

J Orthop Trauma. 2014 May;28(5):270-5

Authors: Collinge CA, Mir H, Reddix R

Abstract
OBJECTIVE: Management of vertical femoral neck fractures in young adults has been a challenging clinical problem, resulting in mixed clinical outcomes. A thorough understanding of the fracture morphology for this injury pattern is lacking, which may contribute to frequent failures of treatment. This study is designed to produce a detailed description of the pathoanatomy of these fractures, which may ultimately be helpful in developing more informed reduction and fixation strategies.
DESIGN: Retrospective study of patient records, plain radiographs, and computed tomography scans to determine the morphology the Pauwels III femoral neck fractures (coronal angle >50 degrees) in young adults.
SETTING: Two level I and 1 level II regional trauma centers.
PATIENTS: All patients 18-49 years of age with a surgically repaired, high-energy high shear angle (>50 degrees) femoral neck fracture from January 1, 2007, to December 31, 2010.
METHODS: One hundred thirty-six adult patients younger than 50 years were identified with a femoral neck fracture in the study period, of whom 33 met all study criteria. We evaluated plain radiography and computed tomography data including fracture orientation, comminution, deformity, characteristics of the inferomedial fracture spike, and the associated inferomedial calcar's cortical buttress.
RESULTS: The vertical (coronal) fracture averaged 60 degrees and axial fracture obliquity averaged 24 degrees with relative deficiency of the posterior neck on the head-neck fragment. Major femoral neck comminution (>1.5 cm in any dimension) was identified in 96% of cases, mostly located in the inferior (94%) and posterior (82%) quadrants. The apical fracture spike of the head segment was found to be in line (within 10 degrees) of the neck-shaft axis on the proximal femur 63% of the time. Deformity in external rotation averaged 44 degrees (range, 10-68 degrees) and shortening of the femur averaged 1.8 cm (range, 0.9-4.4 cm).
CONCLUSIONS: This study investigated the fracture morphology of isolated, high shear angle femoral neck fractures in young adults, which may ultimately lead to improved operative reduction and fixation tactics. Given this injury's characteristic findings, including fracture orientation, deformity, and comminution, surgeons should be cognizant of this pattern's innate instability and potential for treatment failure with typical implant constructs.

PMID: 24096307 [PubMed - indexed for MEDLINE]

Association of body burden of mercury with liver function test status in the U.S. population.

Sun, 09/28/2014 - 4:05am
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Association of body burden of mercury with liver function test status in the U.S. population.

Environ Int. 2014 Sep;70:88-94

Authors: Lin YS, Ginsberg G, Caffrey JL, Xue J, Vulimiri SV, Nath RG, Sonawane B

Abstract
The majority of mercury (Hg) exposure in the US population is from consumption of fish contaminated with methylmercury (MeHg). Since inorganic Hg is the predominant form excreted in the feces and urine, hepatic biotransformation is a critical step in its normal clearance. This study was set to test the hypothesis that compromised liver function is associated with body burden of Hg as indirectly reflected by Hg sampled in blood and urine. From the National Health and Nutrition Examination Survey (NHANES, 2003-2008), 3769 adults aged 20 years and above were selected for analysis. Hepatic function was inferred from the three standard serum liver-related enzyme activities, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltransferase (GGT). Multivariate regression models were used to examine the associations of interest. Although urinary Hg was significantly correlated with serum Hg, the blood-urinary Hg relationship was influenced by liver function, which is also a function of demographic and lifestyle factors (e.g., gender). Although the results were only marginally significant for examined enzymes (p=0.06-0.08), urinary Hg tended to be lower among subjects with elevated liver enzymes, as compared to those with normal enzyme measurements. Conversely, MeHg generally represents a higher fraction of the total circulating Hg among those with elevated liver enzyme levels, especially among participants with elevations in all three enzymes (p=0.01). In conclusion, this population-based study identified an association between liver function, serum Hg and urinary Hg. Urinalysis may not be the optimal approach to monitor Hg elimination toxicokinetics or Hg exposure, since the majority of Hg excretion is fecal and the fidelity of urinary excretion may depend on healthy liver function. Future prospective studies are warranted to expand these findings.

PMID: 24908642 [PubMed - indexed for MEDLINE]