Targeting Antioxidant Enzyme Expression as a Therapeutic Strategy for Ischemic Stroke

During ischemic stroke, neurons and glia are subjected to damage during the acute and neuroinflammatory phases of injury. Production of reactive oxygen species (ROS) from calcium dysregulation in neural cells and the invasion of activated immune cells are responsible for stroke-induced neurodegeneration. Scientists have failed thus far to identify antioxidant-based drugs that can enhance neural cell survival and improve recovery after stroke. However, several groups have demonstrated success in protecting against stroke by increasing expression of antioxidant enzymes in neural cells. These enzymes, which include but are not limited to enzymes in the glutathione peroxidase, catalase, and superoxide dismutase families, degrade ROS that otherwise damage cellular components such as DNA, proteins, and lipids. Several groups have identified cellular therapies including neural stem cells and human umbilical cord blood cells, which exert neuroprotective and oligoprotective effects through the release of pro-survival factors that activate PI3K/Akt signaling to upregulation of antioxidant enzymes. Other studies demonstrate that treatment with soluble factors released by these cells yield similar changes in enzyme expression after stroke. Treatment with the cytokine leukemia inhibitory factor increases the expression of peroxiredoxin IV and metallothionein III in glia and boosts expression of superoxide dismutase 3 in neurons. Through cell-specific upregulation of these enzymes, LIF and other Akt-inducing factors have the potential to protect multiple cell types against damage from ROS during the early and late phases of ischemic damage

The Role of the Leukemia Inhibitory Factor Receptor in Neuroprotective Signaling

Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison. This review examines the role of this receptor in the CNS and immune system, and its application in the treatment in stroke and other brain pathologies

What are the most practical primary care screens for post-traumatic stress disorder?

The 4-item Primary Care Post-Traumatic Stress Disorder screen (PC-PTSD) is a simple and effective tool to identify symptoms of post-traumatic stress disorder (PTSD) in primary care patients (strength of recommendation [SOR ]: B, 1 good-quality prospective cohort study and 1 good-quality retrospective cohort study). The 7-item Breslau screen also predictably identifies patients with PTSD symptoms (SOR : B, 1 good-quality prospective cohort study)

Risperidone (depot) for schizophrenia

Background: Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. Objectives To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication. To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia. Search methods: We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies. Selection criteria: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. Data collection and analysis: Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. Main results: Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidone Data for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazole Relapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapine Relapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate) Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychotics Outcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence). Authors' conclusions: Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects

Undergraduate Economics Journals: Learning By Doing

Although there are currently only a few undergraduate journals in economics, we expect their numbers to increase substantially in the future because of several developments: 1) research and writing activity is increasing in economics programs, 2) online publication is now more feasible and cost efficient than ever, and 3) students are increasingly aware of their on-line identity and desire to project a positive and professional image. Since increasing use of undergraduate journals might benefit a number of students, including potential article authors, article reviewers, and editors, there is a need to begin to assess the educational benefits of participation in journals. This paper reports results from a survey of reviewers who had reviewed articles for two undergraduate journals, The Park Place Economist and The Undergraduate Economic Review. The reviewers generally agreed that they received a range of benefits from the review process and nearly all agreed that reviewing had been a valuable use of their time. Several of the suggested benefits were positively correlated with measures of participation intensity. Nearly half the respondents thought the benefits would have been greater with more, not fewer, articles to review

Improving Access to Past & Present NASA Airborne Research Data & Information

No abstract availabl

The Poststroke Peripheral Immune Response Is Differentially Regulated by Leukemia Inhibitory Factor in Aged Male and Female Rodents

Background. The goal of this study was to determine whether leukemia inhibitory factor (LIF) promotes anti-inflammatory activity after stroke in a sex-dependent manner. Methods. Aged (18-month-old) Sprague-Dawley rats of both sexes underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals received three doses of intravenous LIF (125 μg/kg) or PBS at 6, 24, and 48 h before euthanization at 72 h. Spleen weights were measured immediately following euthanization. Western blot was used to measure protein levels of CCL8, CD11b, CXCL9, CXCL10, IL-12 p40, IL-3, and the LIF receptor (LIFR) in spleen tissue. ELISA was used to measure IL-1β, IL-6, TNFα, and IFNγ in spleen tissue. A Griess Assay was used to indirectly quantify NO levels via measurement of nitrite. Levels of cellular markers and inflammatory mediators were normalized to the baseline (sham) group from each sex. Statistical analysis was performed using two-way ANOVA and followed by Fisher’s LSD post hoc test. Results. Aged female rats showed a significantly lower spleen weight after MCAO, but showed a significant increase in spleen size after LIF treatment. This effect was observed in aged male rats, but not to as great of an extent. CD11b levels were significantly higher in the spleens of MCAO+PBS males compared to their female counterparts, but there was no significant difference in CD11b levels between MCAO+LIF males and females. LIF significantly increased CXCL9 after LIF treatment in aged male and female rats. LIFR and IL-3 were upregulated after LIF treatment in aged females. Splenic nitrate increased after MCAO but decreased after LIF treatment in aged females. Splenic nitrate levels did not increase after MCAO but did increase after LIF treatment in aged males. The following cytokines/chemokines were not altered by sex or treatment: TNFα, IL-6, IL-12 p40, CCL8, IFNγ, and CXCL10. Conclusions. LIF treatment after permanent MCAO induces sex-dependent effects on the poststroke splenic response and the production of proinflammatory cytokines among aged rats

Exile Vol. XLVI No. 1

44th Year Title Page 3 Epigraph by Ezra Pound 5 Statement of Policy 6 Table of Contents 7 Contributors Notes 37 Editorial Board 38 ART Incredible Lines by David Tulkin \u2701 8 Untitled by David Tulkin \u2701 12 Untitled by Patrick Yingling \u2703 18 Sculpted Body by David Tulkin \u2701 20 Untitled by Tanya Sheremeta \u2701 25 Untitled by David Tulkin \u2701 28 Untitled by Dena Behi \u2701 36 POETRY Wednesday by Mary Ann T. Davis \u2700 9 Music by Jessica Kramer \u2703 10-11 Worship During the Rainy Season by Allison Armbrister \u2701 19 Mercy by Mary Ann T. Davis \u2700 26-27 Albino Lizard by Matthew Martz \u2702 29 Filling of Lake Cumberland, 1951 by Allison Armbrister \u2701 35 PROSE Storm Drain by Matthew Martz \u2702 13-17 Creases by Stephanie M. Vaccaro \u2701 21-24 When It Rains by Matthew Martz \u2702 30-34 Statement of Policy This semester Exile instituted a new policy limiting submissions to those not involved in the production of the magazine. As always, all submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. -6 Cover Art Untitled by Dena Behi \u2701 / Back Cover Art Untitled by Tanya Sheremeta \u2701 -38 Printed by Printing Arts Press -38 Matthew Martz, Albino Lizard, Storm Drain and When It Rains , redacted due to copyright restrictions