214 research outputs found
Historical Poem, to be Read at the Dedication of the Soldiers\u27 monument, in Westminster, Mass., July 4th, 1868
From the cover, This Poem is founded on the history of the country from the landing of the Pilgrims on Plymouth Rock, in 1620, to the present time.https://scholarsjunction.msstate.edu/fvw-pamphlets/1614/thumbnail.jp
Kappa opioid receptor antagonism: Are opioids the answer for treatment resistant depression?
Introduction: Past trials of buprenorphine (BUP) in the treatment of major depressive disorder (MDD) have displayed favorable results, although its clinical utility was limited by the risk of abuse or physical dependence. By combining BUP with samidorphan (SAM), the euphoric high is negated by an opposing mechanism, which theoretically reduces addictive-like properties while allowing the antidepressant properties to remain. As such, the objective of this article is to analyze the results of BUP/SAM premarketing clinical trials as adjunctive treatment for treatment-resistant MDD.
Methods: A comprehensive PubMed/MEDLINE search was conducted through November 9, 2017, using the following search terms: depression, samidorphan, buprenorphine, ALKS-5461. Additional data were obtained from Clinicaltrials.gov and resources included in the present study. All English-language clinical trials evaluating the combination of BUP/SAM in the treatment of MDD were included.
Results: A few premarketing studies have evaluated the efficacy and safety of BUP/SAM combination as adjunctive treatment in patients with treatment-resistant MDD. The FORWARD-1 through FORWARD-5 trials concluded (1) the most effective dosing ratio of BUP/SAM to reduce abuse potential was 1:1; (2) statistically significant changes in scores from baseline on the Montgomery-Asberg Depression Rating Scale were noted for the 2 mg/2 mg dose compared with placebo; and (3) the most commonly reported adverse effects were nausea, dizziness, and fatigue.
Discussion: Buprenorphine/samidorphan has shown favorable results for efficacy and tolerability in premarketing studies evaluating its use as adjunctive therapy for treatment-resistant MDD. Its novel mechanism targeting the opioid pathway may serve as a promising antidepressant devoid of abuse potential
Occurrence of primary lymphocytic hypophysitis in two horses and presence of scattered T-lymphocytes in the normal equine pituitary gland
The postmortem examination of a 14-year-old Appaloosa gelding with clinically diagnosed pituitary pars intermedia dysfunction showed a unique finding of moderate multifocal lymphocytic hypophysitis (LH). The pituitary glands of 24 horses submitted for postmortem examination were examined grossly and examined histologically for the presence of lymphocytes. Of these 23 horses, 1 additional case suffered from moderate LH. The 2 cases with LH tested negative for Equid herpesvirus 1 and 4 by polymerase chain reaction and immunohistochemistry (IHC), and no viral particles were observed by electron microscopy in 1 case examined. The cause of LH remains unknown, but based on the T-lymphocytic nature of the inflammation and the human literature, an immune-mediated origin is hypothesized. In addition, the review of 24 cases revealed that 10 horses had few and small multifocal lymphocytic infiltrates within the pituitary gland; the remaining 12 horses showed no evident lymphocytes when examined by hematoxylin and eosin. IHC for CD3 showed the presence of a small number of individual T-lymphocytes scattered through the gland in all examined horses, which appears therefore to be a normal feature of the pituitary gland in horses
Water and Land-surface Feedbacks in a Polygonal Tundra Environment
The Arctic, including Alaska, is currently experiencing an unprecedented degree of environmental change with increases in both the mean annual surface temperature and precipitation. These observed changes in the climate regime has resulted in a permafrost condition that is particularly sensitive to changes in both Changes in the surface energy balance and water balances and is susceptible to degradation. Thermokarst topography forms whenever ice-rich permafrost thaws and the ground subsides into the resulting voids. Extensive areas of thermokarst activity are currently being observed throughout the arctic and sub-arctic environments. The important processes involved with thermokarsting include surface ponding, surface subsidence, changes in drainage patterns, and related erosion. In this research, we are applying the land-surface evolution model, ERODE (http://csdms.colorado.edu/wiki/Model:Erode), to an area dominated by low- center, ice-wedge polygons. We are modifying the ERODE model to include land surface subsistence in areas where the maximum active layer depth exceeds the protective layer â the layer of soil above ice-rich soils that acts as a buffer to surface energy processes. The goal of this modeling study is to better understand and quantify the development of thermokarst features in the polygonal tundra environment, emphasizing the resulting feedbacks and connections between hydrologic processes and a dynamic surface topography. Further, we are working on understanding the balance between thermal and mechanical processes with regard to thermokarst processes. This unique application of a landscape evolution model may provide valuable insight related to the rates and spatial extent of thermokarst development and the subsequent hydrologic responses to degrading permafrost in a changing climate.Office of Biological and Environmental Research, Department of Energy Office of Science, Alaska Climate Science Cente
Perceived parental permissiveness toward gambling and risky behaviors in adolescents
Abstract
Background and aims
Perceived parental permissiveness toward gambling may relate to adolescentsâ engagement in various risky behaviors. To examine this possibility, we analyzed data from a high-school based risk-behavior survey to assess relationships between perceived parental permissiveness toward gambling and adolescent gambling behavior, substance use and related problems. We also evaluated predictions that relationships between perceived parental permissiveness toward gambling and risky behaviors would be particularly strong amongst adolescents reporting high sensation-seeking or impulsivity.
Methods
High-school students (n = 2,805) provided data on risky behaviors, perceived parental permissiveness toward gambling, impulsivity and sensation-seeking. Bivariate and logistic regression analyses were conducted to examine relationships with gambling and alcohol, cigarette and marijuana use.
Results
Perceived parental permissiveness toward gambling related significantly to adolescent gambling, all substance-use behaviors as well as alcohol and drug problems. There were significant parental-permissiveness-by-sensation-seeking interactions in multiple models. Relationships between perceived parental permissiveness toward gambling and alcohol-use frequency were particularly strong among those with high sensation-seeking. This relationship also applied to gambling and heavy cigarette smoking, albeit to a lesser extent. Impulsivity related strongly to drug problems among those who perceived their parents to be more and less permissive toward gambling.
Discussion and conclusions
These findings support the relevance of perceived parental permissiveness toward gambling to adolescent risky behaviors. Parenting perceived as less permissive toward gambling appeared to have protective effects on gambling, alcohol and cigarette use, even among those with high sensation-seeking. Reducing parental permissiveness toward gambling may be a valuable intervention goal, particularly for parents of sensation-seeking adolescents
Enhancing the Scrutiny Role of Select Committees: The House of Commons Health and Social Care Select Committeeâs New Independent Expert Panel
We report on a recent innovation for one Departmental Select Committee. While government policy commitments are well publicised, little attention is paid to the quality of commitments made or to assessing progress against those commitments. In 2020, the Health and Social Care Select Committee commissioned an Expert Panel to conduct independent, in-depth evaluations of government progress on selected policy commitments. The first evaluations in 2021/22 assessed commitments in maternity, mental health and cancer services, and workforce and it was the first time a government department has been systematically graded against its own commitments. This is an important new method of scrutiny with the potential to complement and enhance the work of Select Committee inquiries. This paper reviews the development of select committees highlighting issues relating to their operation and, in particular, assessment of evidence. We describe the innovation of the Expert Panel and its role in reviewing policy commitments and discuss implications for parliamentary scrutiny, leadership and improvements to health service
Understanding the experience of initiating community-based group physical activity by people with serious mental illness: a systematic review using a meta-ethnographic approach
Background
People living with serious mental illness (SMI) experience debilitating symptoms that worsen their physical health and quality of life. Regular physical activity (PA) may bring symptomatic improvements and enhance wellbeing. When undertaken in community-based group settings, PA may yield additional benefits such as reduced isolation. Initiating PA can be difficult for people with SMI and so PA engagement is commonly low. Designing acceptable and effective PA programmes requires a better understanding of the lived experiences of PA initiation among people with SMI.
Methods
This systematic review of qualitative studies used the meta-ethnography approach by Noblit and Hare (1988). Electronic databases were searched from inception to November 2017. Eligible studies used qualitative methodology; involved adults (â„18 years) with schizophrenia, bipolar affective disorder, major depressive disorder or psychosis; reported community-based group PA; and captured the experience of PA initiation, including key features of social support. Study selection and quality assessment was performed by four reviewers.
Results
Sixteen studies were included in the review. We identified a âjourney' that depicted a long sequence of phases involved in initiating PA. The journey demonstrated the thought processes, expectations, barriers and support needs of people with SMI. In particular, social support from a trusted source played an important role in getting people to the activity, both physically and emotionally.
Discussion
The journey illustrated that initiation of PA for people with SMI is a long complex transition. This complex process needs to be understood before ongoing participation in PA can be addressed
Finding balance : an evaluation governance model to ease tension between independence and inclusion
Includes abstract in FrenchPractitioners and theorists have documented the benefits of user engagement and participation in evaluation and, at the same time, the value of neutral and impartial evaluative evidence. Yet producing both an independent and inclusive evaluation is a leading challenge in our field. In this practice note, we present one solution. We describe the design of an evaluation governance structure that was used to find balance between these two themes. We also identify key elements of this experience and present these for adaptation by others, given appropriate tailoring. We have documented our experience as we believe that governance provides currently uncharted potential for this discipline spanning challenge.Les spĂ©cialistes et les thĂ©oriciens ont documentĂ© les avantages de la participation des utilisateurs en Ă©valuation et, de la mĂȘme façon, la valeur dedonnĂ©es dâĂ©valuation neutres et impartiales. Il reste que rĂ©aliser une Ă©valuation aussi indĂ©pendante quâinclusive est encore un dĂ©fi de taille dans notre domaine. Dans la prĂ©sente note de pratique, nous prĂ©sentons une solution. Nous dĂ©crivons le design dâune structure dâĂ©valuation de la gouvernance qui a servi Ă trouver un Ă©quilibre entre les deux thĂšmes. Nous nommons aussi les Ă©lĂ©ments clĂ©s de cette expĂ©rience et expliquons comment ils peuvent ĂȘtre adaptĂ©s pour rĂ©pondre Ă des besoins particuliers. Nous avons documentĂ© notre expĂ©rience puisque nous croyons que la gouvernance est une avenue prometteuse pour relever ce dĂ©fi qui touche de nombreuses disciplines
Polarized localization of phosphatidylserine in the endothelium regulates Kir2.1
Lipid regulation of ion channels is largely explored using in silico modeling with minimal experimentation in intact tissue; thus, the functional consequences of these predicted lipid-channel interactions within native cellular environments remain elusive. The goal of this study is to investigate how lipid regulation of endothelial Kir2.1 - an inwardly rectifying potassium channel that regulates membrane hyperpolarization - contributes to vasodilation in resistance arteries. First, we show that phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), crucial signaling microdomains that regulate vasodilation in resistance arteries, and in silico data have implied that PS may compete with phosphatidylinositol 4,5-bisphosphate (PIP2) binding on Kir2.1. We found that Kir2.1-MEJs also contained PS, possibly indicating an interaction where PS regulates Kir2.1. Electrophysiology experiments on HEK cells demonstrate that PS blocks PIP2 activation of Kir2.1 and that addition of exogenous PS blocks PIP2-mediated Kir2.1 vasodilation in resistance arteries. Using a mouse model lacking canonical MEJs in resistance arteries (Elnfl/fl/Cdh5-Cre), PS localization in endothelium was disrupted and PIP2 activation of Kir2.1 was significantly increased. Taken together, our data suggest that PS enrichment to MEJs inhibits PIP2-mediated activation of Kir2.1 to tightly regulate changes in arterial diameter, and they demonstrate that the intracellular lipid localization within the endothelium is an important determinant of vascular function
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