Synaptic Zn2+ release during spreading depolarizations : implications for ischemic brain injury

The expansion of the ischemic core into surrounding penumbral tissue has prompted researchers to finds ways to limit this progression in hopes of providing better outcomes for patients suffering from stroke. Current therapeutic strategies are limited, and new therapies that can be delivered at late time-points are needed. Zn2+ has been well documented to contribute to ischemic injury progression, and chelation of Zn2+ significantly improves neuronal survival, even when administered hours after the initial insult. However, determining the source of this Zn2+ and the toxic mechanisms involved in ischemia remain unclear. Over the past 10 years, clinical recordings have provided strong evidence that the occurrence of spreading depolarizations (SD) significantly contributes to the progression of numerous forms of brain injuries, including ischemic stroke. As these events occur repetitively for hours to days following the initial ischemic event, they pose as a prime candidate for the development of new therapeutic targets. These depolarizing events have the potential capability to release large amounts of synaptic Zn2+ into the extracellular space. The dissertation work presented here addresses whether synaptic Zn2+ release occurs during SD and if this source of Zn2+ is neurotoxic in the post-ischemic period. SD generated by either localized K+ applications or an in vitro model of ischemia (oxygen/glucose deprivation, OGD), resulted in large releases of synaptic Zn2+ in both hippocampal and neocortical tissues in vitro and led to postsynaptic accumulation. Zn2+ chelation was sufficient to delay the onset of OGD-SD, providing a mechanism for the beneficial effects of Zn2+ chelation seen previously. Additionally, elevating intracellular Zn2+ levels worsened the recovery after SD, likely through impaired metabolic function. Finally, synaptic Zn2+ release was detected following SD in vivo and this source of Zn2+ significantly contributed to ischemic injury. These results suggest that targeting synaptic Zn2+ stores or release during SD events could be a novel approach in treating ischemic brain injury. As SD events continue to occur days following the initial ischemic event, this suggests the ability to target these events at late time-points where current therapeutics are limited

Appropriate Social Behavior: Teaching Expectations to Young Children

Young children\u27s challenging behavior can impact all aspects of the classroom environment, including relationships (peer–peer, student–teacher), learning, and safety. Positive Behavior Interventions and Supports (PBIS) is a program that focuses on supporting pro-social behaviors and preventing challenging behavior. PBIS begins with building a foundation of universal practices and creating a common language that teachers, children, and families can use to talk about behavior. The identification and defining of appropriate behavioral expectations and the systematic teaching of those behavioral expectations is paramount to preventing challenging behavior. This article describes the steps involved in identifying classroom behavioral expectations and the development of developmentally appropriate lesson plans to teach those behaviors to young children

Discipline Disparities Series: Overview

Disparities in the use of school discipline by race, gender, and sexual orientation have been well-documented and continue to place large numbers of students at risk for short- and long-term negative outcomes. In order to improve the state of our knowledge and encourage effective interventions, the Discipline Disparities Research to Practice Collaborative, a group of 26 nationally known researchers, educators, advocates, and policy analysts, came together to address the problem of disciplinary disparities. Funded by Atlantic Philanthropies and Open Society Foundations, the Collaborative has spent nearly three years conducting a series of meetings with groups of stakeholders -- advocates, educators, juvenile justice representatives, intervention agents, researchers, and policymakers -- in order to increase the availability of interventions that are both practical and evidence-based, and to develop and support a policy agenda for reform to improve equity in school discipline. The project has funded 11 new research projects to expand the knowledge base, particularly in the area of intervention, and commissioned papers from noted researchers presented at the Closing the School Discipline Gap Conference. A culminating report of the Collaborative's work is the formal release of the Discipline Disparities Briefing Paper Series, three papers on policy, practice, and new research summarizing the state of our knowledge and offering practical, evidence-based recommendations for reducing disparities in discipline in our nation's schools. This report is an overview of the research

Federal Criminal Conspiracy

Under 18 U.S.C. § 371, it is a crime for two or more persons [to] conspire . . . to commit any offense against the United States, or to defraud the United States, or any agency thereof in any manner or for any purpose. This Article first outlines, in Section I, the basic elements of a conspiracy offense under § 371. Defenses available to challenge charges brought under the statute are discussed in Section III of the Article. Section IV presents the evidentiary and constitutional guidelines governing admissibility of co-conspirator hearsay testimony at trials involving conspiracy charges. Section V surveys various procedural and substantive rules regarding enforcement of the statute. Finally, the rules governing a conspiracy conviction under the Federal Sentencing Guidelines are reviewed in Section VI

Renal function, calcium regulation, and time to hospitalization of patients with chronic kidney disease

BACKGROUND: Chronic kidney disease is associated with disruption of the endocrine system that distorts the balance between calcitriol, calcium, phosphate and parathyroid hormone in the calcium regulation system. This can lead to calcification of the arterial tree and increased risk of cardiovascular disease and death. In this study we develop a health metric, based on biomarkers involved in the calcium regulation system, for use in identifying patients at high risk for future high-cost complications. METHODS: This study is a retrospective observational study involving a secondary analysis of data from the kidney disease registry of a regional managed care organization. Chronic kidney disease patients in the registry from November 2007 through November 2011 with a complete set of observations of estimated glomerular filtration rate, calcitriol, albumin, free calcium, phosphate, and parathyroid hormone were included in the study (n = 284). Weibull regression model was used to identify the most significant lab tests in predicting “waiting time to hospitalization”. A multivariate linear path model was then constructed to investigate direct and indirect effects of the biomarkers on this outcome. RESULTS: The results showed negative significant direct effects of phosphate and parathyroid hormone on “waiting time to hospitalization”. Base on this result, the risk of hospitalization increases 16.8% for each 0.55 mg/dl increase in phosphate level and 13.5% for each 0.467 increase in the natural logarithm of parathyroid hormone. Positive indirect effects of calcitriol surrogate (calcidiol), free calcium, albumin and estimated glomerular filtration rate were observed but were relatively small in magnitude. CONCLUSION: Variables involved in the calcium regulation system should be included in future efforts to develop a quality of care index for Chronic Kidney disease patients

Rights-based reasoning in discussions about lesbian and gay issues: implications for moral educators

Despite a paucity of psychological research exploring the interface between lesbian and gay issues and human rights, a human rights framework has been widely adopted in debates to gain equality for lesbians and gay men. Given this prominence within political discourse of human rights as a framework for the promotion of positive social change for lesbians and gay men, the aim of this study was to explore the extent to which rights-based arguments are employed when talking about lesbian and gay issues in a social context. An analysis of six focus group discussions with students showed that when lesbian and gay issues are discussed, rights-based reasoning is employed intermittently, and in relation to certain issues more so than others. The implications of these findings for moral education aimed at promoting positive social change for lesbians and gay men are discussed.</p