780 research outputs found

    Searching for new medications for the treatment of alcohol use disorder

    Get PDF
    Alcohol use disorder (AUD) affects more than 15 million people in the United States. Current pharmacotherapeutic treatments for AUD are only modestly effective, necessitating the identification of new targets for medications development. In this study, the effects of the D4 receptor antagonist, L-745,870, and the CB1 negative allosteric modulator, PSNCBAM-1, were both tested for effects in ethanol conditioned place preference (CPP) and oral ethanol self-administration. Food-restricted adult male mice were trained in operant chambers to nose poke for delivery of rewards, trained on ascending concentrations of alcohol with descending concentrations of Ensure and water, until the mixture self-administered was 8% w/v ethanol in water. L-745,870 did not significantly attenuate ethanol self-administration or ethanol CPP. These results suggest that D4R antagonism does not alter the rewarding value of ethanol. PSNCBAM-1 dose-dependently attenuated oral ethanol self-administration, significantly reducing ethanol rewards at a dose of 30 mg/kg but not at 10 or 18 mg/kg. However, 18 and 30 mg/kg PSNCBAM-1 also significantly reduced self-administration of a palatable food reward. These results suggest PSNCBAM-1 produces a non-specific anhedonic effect that may preclude its use in AUD or other neuropsychiatric conditions

    Enhancing Student Engagement in Wayne State University School of Medicine (WSUSOM) Curriculum Design, Development, Evaluation, and Implementation

    Get PDF
    Purpose: There are a variety of ways in which the 1200 medical students at Wayne State University School of Medicine (WSUSOM) can formally participate in curricular efforts. To date, a formal inventory and evaluation of these programs has not been reported. Methods: We compiled a list of students involved in courses, committees, and formal activities related to the medical school curriculum. We then developed and delivered a survey to measure student perceptions utilizing the following constructs: 1) Guidance/Support for Student Role, 2) Project Successes and Challenges, 3) Curricular Project Measurement and Monitoring, 4) Curriculum Management Committee Engagement and Accessibility, 5) Frequency of Engagement with other Students in these Roles, and 6) Strengths and Opportunities for Improvement: Curriculum Management Infrastructure. Results: With a response rate of 57.7% from 123 students, participants reported that they receive sufficient support/guidance for their roles (74%), but more than half were unaware of a process to monitor progress. Students remained siloed, communicating with other groups less than monthly, and 72% reported lacking sufficient knowledge of other groups’ curricular projects. Thematic qualitative analysis of suggestions for improving the curriculum management infrastructure yielded the following priorities: communication/feedback; transparency; and organizational efficiency. Similar analysis of suggestions for improving medical student roles showed: defining roles; increasing support, training, and guidance; and communication. Discussion: Our study represents the first inventory of student engagement in curriculum design, development, evaluation and implementation at the nation’s largest single-campus medical school. There is a clear need for greater collaboration and communication, systems to track curricular projects, and improved training/definition of roles. As primary stakeholders in their own educational environment, students involved in curricular projects are uniquely placed to make such observations and pleas for improvement. Development of a comprehensive roster specifying roles and responsibilities, an accompanying work-flow model for interacting roles, and a central hub to track projects would each greatly improve the efficacy of curricular planning

    Image-Based Treatment Planning of the Post-Lumpectomy Breast Utilizing CT and 3TMRI

    Get PDF
    Accurate lumpectomy cavity definition is critical in breast treatment planning. We compared contouring lumpectomy cavity volume and cavity visualization score (CVS) with CT versus 3T MRI. 29 patients were imaged with CT and 3T MRI. Seven additional boost planning sets were obtained for 36 image sets total. Three observers contoured the lumpectomy cavity on all images, assigning a cavity visualization score (CVS ) of 1 to 5. Measures of consistency and agreement for CT volumes were 98.84% and 98.62%, for T1 MRI were 95.65% and 95.55%, and for T2 MRI were 97.63% and 97.71%. The mean CT, T1 MRI, and T2 MRI CVS scores were 3.28, 3.38, and 4.32, respectively. There was a highly significant difference between CT and T2 scores (P < .00001) and between T1 and T2 scores (P < .00001). Interobserver consistency and agreement regarding volumes were high for all three modalities with T2 MRI CVS the highest. MRI may contribute to target definition in selected patients

    Polyphenols and non-alcoholic fatty liver disease: impact and mechanisms:impact and mechanisms

    Get PDF
    Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic component of the metabolic syndrome and its prevalence is rapidly increasing due to its strong association with insulin resistance and obesity. At present, given that NAFLD is highly prevalent and therapies are limited, much attention is focused on identifying effective dietary strategies for the prevention and treatment of the disease. Polyphenols are a group of plant bioactive compounds whose regular consumption have been associated with a reduction in the risk of a number of metabolic disorders associated with NAFLD. Here we review the emerging and relatively consistent evidence from cell culture and rodent studies showing that select polyphenols positively modulate a variety of contributors to the NAFLD phenotype, through diverse and complementary mechanisms of action. In particular, the reduction of de novo lipogenesis (via sterol regulatory element-binding protein 1c) and increased fatty acid β-oxidation, presumably involving AMP-activated protein kinase activation, will be discussed. The indirect antioxidant and anti-inflammatory properties of polyphenols which have been reported to contribute to the amelioration of NAFLD will also be addressed. In addition to a direct study of the liver, rodent studies have provided insight into the impact of polyphenols on adipose tissue function and whole body insulin sensitivity, which are likely to in part modulate their impact on NAFLD development. Finally an overview of the limited data from clinical trials will be given along with a discussion of the dose extrapolation from animal studies to human subjects

    Ariel - Volume 4 Number 4

    Get PDF
    Editors David A. Jacoby Eugenia Miller Tom Williams Associate Editors Paul Bialas Terry Burt Michael Leo Gail Tenikat Editor Emeritus and Business Manager Richard J. Bonnano Movie Editor Robert Breckenridge Staff Richard Blutstein Mary F. Buechler Meg Brunt Steve Glinks Len Grasman Alice M. Johnson J.D. Kanofsky Tom Lehman Dave Mayer Bernie Odd

    Disorder-induced microscopic magnetic memory

    Full text link
    Using coherent x-ray speckle metrology, we have measured the influence of disorder on major loop return point memory (RPM) and complementary point memory (CPM) for a series of perpendicular anisotropy Co/Pt multilayer films. In the low disorder limit, the domain structures show no memory with field cycling--no RPM and no CPM. With increasing disorder, we observe the onset and the saturation of both the RPM and the CPM. These results provide the first direct ensemble-sensitive experimental study of the effects of varying disorder on microscopic magnetic memory and are compared against the predictions of existing theories.Comment: 4 pages, 4 figures. Accepted for publication in Physical Review Letters in Nov. 200

    Seroprevalence of Zika virus in wild African green monkeys and baboons

    Get PDF
    ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available
    corecore