Recent Research Articles from UNTHSC

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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]

Displaced Ischial Stress Fracture Following Revision Total Hip Arthroplasty.

Fri, 09/26/2014 - 4:05am
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Displaced Ischial Stress Fracture Following Revision Total Hip Arthroplasty.

Am J Orthop (Belle Mead NJ). 2014 Sep;43(9):E214-E216

Authors: Merchant AM, Wagner RA

Abstract
Stress fractures of the ischium are uncommon and are most likely caused by excessive stretching or contracture of the hamstring muscles. In addition, revision total hip arthroplasty (THA) may weaken the ilium, and metabolic bone disease may also contribute to a fracture. Treatment is usually conservative and prognosis is favorable. We present a rare case of spontaneous displaced fracture of the entire ischium following revision THA that healed without requiring operative intervention.

PMID: 25251536 [PubMed - as supplied by publisher]

Modulation of cellular signaling pathways in P23H rhodopsin photoreceptors.

Fri, 09/26/2014 - 4:05am
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Modulation of cellular signaling pathways in P23H rhodopsin photoreceptors.

Cell Signal. 2014 Apr;26(4):665-72

Authors: Sizova OS, Shinde VM, Lenox AR, Gorbatyuk MS

Abstract
We previously reported activation of the unfolded protein response (UPR) in P23H rhodopsin (RHO) retinas with autosomal dominant retinitis pigmentosa (ADRP). Knowing that the UPR can trigger Ca(2+) release from the endoplasmic reticulum and regulate cellular signaling we examined the level of Ca(2+)-regulated proteins. We also looked for changes in the expression of Bcl2 family proteins, autophagy proteins and the mTOR/AKT pathways, as well as for the induction of mitochondria-associated apoptosis in the P23H RHO retina. Our data demonstrated that the elevation of calpain and caspase-12 activity was concomitantly observed with a decrease in the BCL2-XL/BAX ratio and an increase in mTor levels in the P23H-3 RHO retina suggesting a vulnerability of P23H RHO photoreceptors to apoptosis. The translocation of BAX to the mitochondria, as well as the release of cytochrome C and AIF into the cytosol supports this conclusion and indicates the involvement of mitochondria-induced apoptosis in the progression of ADRP. The level of autophagy proteins in general was found to be decreased in the P21-P30 P23H RHO retina. Injections of rapamycin, however, protected the P23H RHO rod photoreceptors from experiencing physiological decline. Despite this fact, the downregulation of mTOR did not alter the level of autophagy proteins. Our results imply that in addition to activation of the UPR during ADRP progression, photoreceptors also experience alterations in major proapoptotic pathways.

PMID: 24378535 [PubMed - indexed for MEDLINE]

Attitudes Associated with Alcohol and Marijuana Referral Actions by Resident Assistants.

Thu, 09/25/2014 - 4:04am
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Attitudes Associated with Alcohol and Marijuana Referral Actions by Resident Assistants.

J Prim Prev. 2014 Sep 23;

Authors: Thombs DL, Osborn CJ, Rossheim ME, Suzuki S

Abstract
This exploratory study examined associations between resident assistant (RA) attitudes and referral actions to identify training strategies for strengthening the ability of these paraprofessionals to recognize and refer college students in their living units who misuse alcohol and marijuana. The study's hypotheses were that (1) referral self-efficacy and perceived referral norms would be positively associated with RA referral actions and (2) perceived referral barriers and referral anticipatory anxiety would be negatively associated with RAs' referral actions. A total of 317 RAs at eight residential campuses in different regions of the U.S. took part in the study. All participating RAs had at least one semester of work experience. Just prior to the Fall semester of 2012, RA's responded to an online survey that assessed their alcohol and marijuana referral attitudes and referral actions. Overall, RAs reported considerable anxiety about approaching and referring students who may have an alcohol and/or marijuana problem. Perceived referral norms among RAs indicated substantial variability in perceptions about others' expectations of them for referring students who may have alcohol and marijuana problems. Results from two multivariable logistic regression analyses showed that referral self-efficacy distinguished RAs who took alcohol referral actions and marijuana referral actions from those who did not do so. Neither length of RA service nor time spent on campus was associated with referral actions. RA training programs could give attention to strengthening referral self-efficacy through a series of increasingly difficult skill-building activities during pre- and in-service training. In addition, senior residence life and housing professional staff may consider assessing the extent to which RAs under their supervision follow established protocols for assisting students with possible alcohol and marijuana problems. The development of evidence-based RA training programs will require additional research.

PMID: 25245491 [PubMed - as supplied by publisher]

Characterization of 114 insertion/deletion (INDEL) polymorphisms, and selection for a global INDEL panel for human identification.

Thu, 09/25/2014 - 4:04am
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Characterization of 114 insertion/deletion (INDEL) polymorphisms, and selection for a global INDEL panel for human identification.

Leg Med (Tokyo). 2014 Jan;16(1):26-32

Authors: LaRue BL, Lagacé R, Chang CW, Holt A, Hennessy L, Ge J, King JL, Chakraborty R, Budowle B

Abstract
Bi-Allelic Insertions and Deletions (INDELs) are a powerful set of genetic markers for Human Identification (HID). They have certain desirable features, such as low mutation rates, no stutter, and potentially small amplicon sizes that could prove effective in some circumstances. In this study, we analyzed the distribution of 114 INDELs in four North American populations (Caucasian, African American, Southwest Hispanic, and Asian) to estimate their distribution in major global populations. Of the 114 INDELs a primary panel of 38 candidate markers was selected that met the criteria of (1) a minimum allele frequency of greater than 0.20 across the populations studied; (2) general concordance with Hardy-Weinberg equilibrium (HWE) expectations; (3) relatively low FST based on the major populations; (4) physical distance between markers greater than 40 Mbp; and (5) a lack of linkage disequilibria between syntenic markers. Additionally, another 11 supplemental markers were selected for an expanded panel of 49 markers which met the above criteria, with the exception that they are separated at least by 20 Mbp. The resulting panels had Random Match Probabilities that were at least 10(-16) and 10(-19), respectively, and combined FST values of approximately 0.02. Given these findings, these INDELs should be useful for HID.

PMID: 24296037 [PubMed - indexed for MEDLINE]

Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Wed, 09/24/2014 - 4:05am
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Autopsy rate in suicide is low among elderly in Denmark compared with Finland.

Forensic Sci Int. 2014 Sep 6;244C:158-165

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

Abstract
National differences in the legislation on cause and manner of death investigation are reflected in a high autopsy rate in suicides in Finland and a low corresponding rate in Denmark. The consequences for mortality statistics of these different investigation practices on deaths classified as suicides in Denmark and Finland, respectively, are not known in detail. The aim of this article was to analyse autopsy rates in deaths classified as suicides, and to identify any differences in investigation practices in deaths with a comparable cause of death, but classified as unnatural deaths other than suicide. Data from the mortality registries were summarised for the years 2000, 2005 and 2010. Autopsy rates (total, forensic and medical) were analysed with regard to deaths classified as suicide, and they were compared for three age groups (1-50 years, 51-70 years and ≥71 years) and for causes of death. Deaths classified as suicide were compared with other unnatural classifications, and comparable causes of death were coded into six subgroups: poisonings, suffocations/strangulations, firearm discharges, drowning/submersions, explosions/flames and other/unspecified causes. The total autopsy rate for suicides was 99.8% in Finland and 13.2% in Denmark. Almost all of these autopsies were conducted as forensic autopsies. In the age group ≥71 years, Danish suicides outnumbered Finnish suicides (410 versus 283). The total autopsy rate was lower in the more senior age group in Denmark (19.5%, 9.9%, 5.6%), whereas it was consistently high in Finland (99.8%, 99.9%, 99.6%). Among Danish deaths due to poisonings, the autopsy rate was 89.5% when these were classified as accidents, but only 20.7% for cases classified as suicides. The number of deaths in the two Danish subgroups was comparable (550 versus 553). In Denmark, the decision regarding the need, if any, for a forensic autopsy is made during the external forensic examination of the body. Our study showed that the limited use of forensic autopsy to confirm the cause of death in deaths classified as suicides raises doubts about the accuracy of the Danish suicide mortality statistics. Our finding is emphasised by those cases in which the cause of death was registered as intentional self-poisoning. The high number of suicides among the elderly in Denmark is striking and begs further investigation and research. Overall, our data from Finland and Denmark reveal striking differences between the two countries and warrant further comparative studies on the subject in other countries.

PMID: 25244292 [PubMed - as supplied by publisher]

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

Wed, 09/24/2014 - 4:05am
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Associations between time spent sitting and cancer-related biomarkers in postmenopausal women: an exploration of effect modifiers.

Cancer Causes Control. 2014 Sep 20;

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

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

PMID: 25238978 [PubMed - as supplied by publisher]

Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder.

Wed, 09/24/2014 - 4:05am
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Cognitive Set Shifting Deficits and Their Relationship to Repetitive Behaviors in Autism Spectrum Disorder.

J Autism Dev Disord. 2014 Sep 19;

Authors: Miller HL, Ragozzino ME, Cook EH, Sweeney JA, Mosconi MW

Abstract
The neurocognitive impairments associated with restricted and repetitive behaviors (RRBs) in autism spectrum disorder (ASD) are not yet clear. Prior studies indicate that individuals with ASD show reduced cognitive flexibility, which could reflect difficulty shifting from a previously learned response pattern or a failure to maintain a new response set. We examined different error types on a test of set-shifting completed by 60 individuals with ASD and 55 age- and nonverbal IQ-matched controls. Individuals with ASD were able to initially shift sets, but they exhibited difficulty maintaining new response sets. Difficulty with set maintenance was related to increased severity of RRBs. General difficulty maintaining new response sets and a heightened tendency to revert to old preferences may contribute to RRBs.

PMID: 25234483 [PubMed - as supplied by publisher]

Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses and immunopathology in lungs during the pathogenesis of murine Mycoplasma pneumonia.

Wed, 09/24/2014 - 4:05am
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Antigen-pulsed bone marrow-derived and pulmonary dendritic cells promote Th2 cell responses and immunopathology in lungs during the pathogenesis of murine Mycoplasma pneumonia.

J Immunol. 2014 Aug 1;193(3):1353-63

Authors: Dobbs NA, Zhou X, Pulse M, Hodge LM, Schoeb TR, Simecka JW

Abstract
Mycoplasmas are a common cause of pneumonia in humans and animals, and attempts to create vaccines have not only failed to generate protective host responses, but they have exacerbated the disease. Mycoplasma pulmonis causes a chronic inflammatory lung disease resulting from a persistent infection, similar to other mycoplasma respiratory diseases. Using this model, Th1 subsets promote resistance to mycoplasma disease and infection, whereas Th2 responses contribute to immunopathology. The purpose of the present study was to evaluate the capacity of cytokine-differentiated dendritic cell (DC) populations to influence the generation of protective and/or pathologic immune responses during M. pulmonis respiratory disease in BALB/c mice. We hypothesized that intratracheal inoculation of mycoplasma Ag-pulsed bone marrow-derived DCs could result in the generation of protective T cell responses during mycoplasma infection. However, intratracheal inoculation (priming) of mice with Ag-pulsed DCs resulted in enhanced pathology in the recipient mice when challenged with mycoplasma. Inoculation of immunodeficient SCID mice with Ag-pulsed DCs demonstrated that this effect was dependent on lymphocyte responses. Similar results were observed when mice were primed with Ag-pulsed pulmonary, but not splenic, DCs. Lymphocytes generated in uninfected mice after the transfer of either Ag-pulsed bone marrow-derived DCs or pulmonary DCs were shown to be IL-13(+) Th2 cells, known to be associated with immunopathology. Thus, resident pulmonary DCs most likely promote the development of immunopathology in mycoplasma disease through the generation of mycoplasma-specific Th2 responses. Vaccination strategies that disrupt or bypass this process could potentially result in a more effective vaccination.

PMID: 24973442 [PubMed - indexed for MEDLINE]

Iatrogenic esophageal injuries: evidence-based management for diagnosis and timing of contrast studies after repair.

Fri, 09/19/2014 - 4:04am
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Iatrogenic esophageal injuries: evidence-based management for diagnosis and timing of contrast studies after repair.

Int Surg. 2012 Jan-Mar;97(1):1-5

Authors: Ko E, O-Yurvati AH

Abstract
Leakage from gastroesophageal repair is considered a major complication and is often associated with increased hospital stay, morbidity, and mortality. Management of these patients is variable among surgeons. Cases managed by the thoracic surgical service from March 1, 2010 to March 1, 2011 were retrospectively reviewed. Eight patients met criteria for inclusion: 4 were repaired primarily, 2 by debridement with diversion, and 2 by Ivor-Lewis resection and reconstruction. Esophograms were completed between 1 and 7 days postoperatively. Of the 8 patients treated, there was 1 mortality (12%) due to fungal mediastinitis. Soluble contrast imaging revealed 2 leaks (25%), 1 contained and 1 diffuse, which was the only mortality. Changes in clinical status, even minor, require contrast imaging of the esophagus to assess repair integrity. Timing of contrast study is variable in the literature, averaging 5 to 14 days. A conservative time frame is 7 days, unless any clinical suspicion of an esophageal leak exists.

PMID: 23101993 [PubMed - indexed for MEDLINE]