Nanoparticle Treatment to Counter Reactive Oxygen Species after Traumatic Brain Injury

Traumatic brain injury (TBI) is defined as damage to the brain, resulting from an external mechanical force, such as an impact to the head (Kievit et. al, 2016).There are several examples that could result in a potential TBI; such as falling with contact to the head, car accidents and even physical activities including football, wrestling, and boxing. Because of the several different scenarios that an individual could impact their head, TBI’s have become an all too common aspect of everyday life. TBI is currently the leading cause of death and disability in children and adults under the age of 45, with 1.7 million reported cases annually in the United States alone(Bharadwaj et. al, 2016). The major problem that causes TBIs to be so lethal is the combination of both the initial damage and the secondary corrosive damage on the surrounding brain tissue. The initial damage is capable of being prevented by wearing helmets, seat belts and taking other safety precautions. However, there are currently no treatments that protect the brain from secondary deterioration, spread of the injury beyond primary damage (Kievit et. al, 2016). While some individuals are capable of fully recovering from a TBI without secondary brain damage, unfortunately, roughly 35% of TBI survivors face long-term disabilities (McConeghy et. al, 2012). The lethal progression of this secondary injury is in part caused by the release of reactive oxygen species (ROS) into the surroundings of the normal brain (Kievit et. al, 2016). From this information, it seems that the best way to prevent this secondary spread to the brain would be to reduce or eliminate the spread of ROS. In order to control this release of ROS, there must be a chemical, or biological entity, placed into the brain that reacts with these ROS so that they are incapable of reacting with the healthy portions of the brain. Currently, Dr. Kievit’s lab is developing nanoparticles that can react with these ROS and prevent them from spreading into other areas of the brain

Requiem: Variations on Eighteenth-Century Themes

In eleven provocative essays Forrest McDonald and his wife, Ellen Shapiro McDonald, cover a wide range of the intellectual, political, military, and social history of the eighteenth century to present both a picture of the age in which our Constitution was crafted and commentary on developments that have caused American government to stray from the Founders’ principles. Appearing here in print for the first time is Forrest McDonald’s widely acclaimed 1987 NEH Jefferson lecture, “The Intellectual World of the Founding Fathers.” In other essays the McDonalds examine such topics as the writing of the Constitution, the central role of such little-known Founders as John Dickinson (“the most underrated of all the Founders”), and the constitutional principles of Alexander Hamilton. Also presented is an exploration of the ritualistic aspects of eighteenth-century warfare and an analysis of Shays’ Rebellion as a tax revolt. In chapters focusing on the separation of powers, the political economy, and the death of federalism, the McDonalds argue the urgent need to “return to limited government under law.” Description Forrest McDonald (1927–2016) was professor of history at the University of Alabama for more than twenty-five years. He is the author or coauthor of fourteen books, including Novus OrdoSeclorum: The Intellectual Origins of the Constitution, which was a Pulitzer Prize finalist in history. Joining him formally as coauthor is his wife and longtime intellectual partner, Ellen Shapiro McDonald. Though she worked with her husband on all of his publications, she chose to only be formally credited as coauthor on this project and as coeditor of Confederation and Constitution, 1781–1789. This Kansas Open Books title is funded by a grant from the National Endowment for the Humanities and the Andrew W. Mellon Foundation Humanities Open Book Program.https://digitalcommons.pittstate.edu/kansas_open_books/1043/thumbnail.jp

The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury

Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI.We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field

Food Security Network Modeling

Food security creates a complex issue for American interests. Within a constantly expanding operational environment, food security remains a vital lifeline both domestically and abroad.  Current methods of mapping an area’s food system rely on ad-hoc assessments that produce skewed results and minimal metric analysis. Previous assessments methodologies failed to incorporate components of a food system that influences the overall stability of an area. The research conducted utilized the Systems Decision Process (SDP) to create a value hierarchy and model that provide an assessment for an areas food system. The findings from the research showcase that a food system relies on several variables such as infrastructure, dietary needs, and the national stability of a region. A more enhanced assessment model was developed that placed an overarching value to a food network that allows ground commanders to gain a holistic overview of the condition of an areas food system

An Economic Interpretation of Rhode Island’s 1788 Referendum on the Constitution

In their 1788 popular referendum, Rhode Island voters overwhelmingly rejected ratification of the Federal Constitution: 92 percent against and 8 percent for adoption. The town-by-town voter lists, correlated with tax and estate records, show that yea voters were significantly wealthier than “nay” voters. Available data also indicates that yea wealth was concentrated in personal estate rather than real estate. Both these findings support Charles Beard\u27s original economic interpretation of the Constitution. Our detailed data provides new evidence about town-level voters, supplementing the usual data Beard’s supporters and critics have used from state ratifying conventions and the Philadelphia constitutional convention. We trace the outlines of the scholarly debate, provide political and economic context for the Rhode Island referendum, report on our initial findings, and suggest further avenues of research and analysis

Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group.

In 1985 a second randomisation was initiated for women in the treatment arm of the Scottish Tamoxifen Trial either to stop tamoxifen at 5 years or to continue indefinitely. A preliminary analysis of outcome in 342 patients at a median follow-up of 6 years suggests that a worthwhile gain in disease control from continuing adjuvant tamoxifen beyond 5 years is unlikely. [Hazard ratio for events (relapse or death without relapse) is 1.27, 95% CI = 0.87 - 1.85.] There is a suggestion that therapy for longer than 5 years may increase the risk of endometrial carcinoma (P = 0.064)

Effect of hands-on interprofessional simulation training for local emergencies in Scotland:the THISTLE stepped-wedge design randomised controlled trial

OBJECTIVE: To assess whether the implementation of an intrapartum training package (PROMPT (PRactical Obstetric Multi-Professional Training)) across a health service reduced the proportion of term babies born with Apgar score <7 at 5 min (<75mins). // DESIGN: Stepped-wedge cluster randomised controlled trial. SETTING: Twelve randomised maternity units with ≥900 births/year in Scotland. Three additional units were included in a supplementary analysis to assess the effect across Scotland. The intervention commenced in March 2014 with follow-up until September 2016. // INTERVENTION: The PROMPT training package (Second edition), with subsequent unit-level implementation of PROMPT courses for all maternity staff. // MAIN OUTCOME MEASURES: The primary outcome was the proportion of term babies with Apgar<75mins. // RESULTS: 87 204 eligible births (99.2% with an Apgar score), of which 1291 infants had an Apgar<75mins were delivered in the 12 randomised maternity units. Two units did not implement the intervention. The overall Apgar<75mins rate observed in the 12 randomised units was 1.49%, increasing from 1.32% preintervention to 1.59% postintervention. Once adjusted for a secular time trend, the 'intention-to-treat' analysis indicated a moderate but non-significant reduction in the rate of term babies with an Apgar scores <75mins following PROMPT training (OR=0.79 95%CI(0.63 to 1.01)). However, some units implemented the intervention earlier than their allocated step, whereas others delayed the intervention. The content and authenticity of the implemented intervention varied widely at unit level. When the actual date of implementation of the intervention in each unit was considered in the analysis, there was no evidence of improvement (OR=1.01 (0.84 to 1.22)). No intervention effect was detected by broadening the analysis to include all 15 large Scottish maternity units. Units with a history of higher rates of Apgar<75mins maintained higher Apgar rates during the study (OR=2.09 (1.28 to 3.41)) compared with units with pre-study rates aligned to the national rate. // CONCLUSIONS: PROMPT training, as implemented, had no effect on the rate of Apgar <75mins in Scotland during the study period. Local implementation at scale was found to be more difficult than anticipated. Further research is required to understand why the positive effects observed in other single-unit studies have not been replicated in Scottish maternity units, and how units can be best supported to locally implement the intervention authentically and effectively

Theranostic Copolymers Neutralize Reactive Oxygen Species and Lipid Peroxidation Products for the Combined Treatment of Traumatic Brain Injury

Traumatic brain injury (TBI) results in the generation of reactive oxygen species (ROS) and lipid peroxidation product (LPOx), including acrolein and 4-hydroxynonenal (4HNE). The presence of these biochemical derangements results in neurodegeneration during the secondary phase of the injury. The ability to rapidly neutralize multiple species could significantly improve outcomes for TBI patients. However, the difficulty in creating therapies that target multiple biochemical derangements simultaneously has greatly limited therapeutic efficacy. Therefore, our goal was to design a material that could rapidly bind and neutralize both ROS and LPOx following TBI. To do this, a series of thiol-functionalized biocompatible copolymers based on lipoic acid methacrylate and polyethylene glycol monomethyl ether methacrylate (FW ∼950 Da) (O950) were prepared. A polymerizable gadolinium-DOTA methacrylate monomer (Gd-MA) was also synthesized starting from cyclen to facilitate direct magnetic resonance imaging and in vivo tracking of accumulation. These neuroprotective copolymers (NPCs) were shown to rapidly and effectively neutralize both ROS and LPOx. Horseradish peroxidase absorbance assays showed that the NPCs efficiently neutralized H2O2, while R-phycoerythrin protection assays demonstrated their ability to protect the fluorescent protein from oxidative damage. 1H NMR studies indicated that the thiol-functional NPCs rapidly form covalent bonds with acrolein, efficiently removing it from solution. In vitro cell studies with SH-SY5Y-differentiated neurons showed that NPCs provide unique protection against toxic concentrations of both H2O2and acrolein. NPCs rapidly accumulate and are retained in the injured brain in controlled cortical impact mice and reduce post-traumatic oxidative stress. Therefore, these materials show promise for improved target engagement of multiple biochemical derangements in hopes of improving TBI therapeutic outcomes