The Neuroscience of High-Risk Behavior: Implications for Prevention & Treatment in Youth

The average age of first use of alcohol for teen boys is 11 and 13 for teen girls. The average age of first exposure to pornography is 9. More teens are suffering from depression than any other time in our history due to too much screen time. Cyberbullying peaks in the 6th grade. What is happening in our culture and to our children’s neurodevelopment as a result of it? Engaging in high-risk behavior as a teen increases the chance of struggling with addiction as an adult by up to 90% due neurodevelopmental exposure and priming of the mesolimbic reward system. The Neuroscience of High-Risk Behavior elucidates how substances and other risky behavior, such as technology overuse, affect healthy neurodevelopment and how these effects impair adult functioning as well as implications for prevention and treatment. Practical, every-day parenting solutions and clinical techniques will be discussed

The Effects of Gene Therapy in an Ovine Osteoarthritis Model

Humans rely on the health of their joints for stability and mobility in daily life. In a normal, healthy functioning joint, complex processes maintain joint tissues, including remodeling, lubrication, and immune function among many other tasks. Osteoarthritis (OA) is the most common joint disorder in the U.S. It becomes most prevalent in adults 60+ years of age and causes decreased mobility, discomfort, and in some cases, excruciating pain. In the biological processes of osteoarthritis, the metalloproteinase enzymes responsible for the degeneration of cartilage are upregulated. The inhibitors of metalloproteinase activity are known as Tissue Inhibitor of Metalloproteinases (TIMPs), which keep metalloproteinase activity in balance. However, an increased production of metalloproteinases has been noted in osteoarthritis-influenced cartilage. The current study focused on the up-regulation of TIMP-3 protein in vivo using the introduction of a TIMP-3 transgene. It was hypothesized that up-regulation of cell-produced, TIMP-3 protein would decrease proteoglycan degradation and slow OA progression in vivo. The use of sheep as a model has proven an effective technique for characterizing diseased joint issues and with our demonstrated method of inducing osteoarthritis over a period of months instead of years, we can make strides in advancing the understanding of the disease. Our methods involve two groups of surgically altered, mature, female sheep. One half underwent ovariectomy or removal of both ovaries (n = 7) and the other half, a Cranial Cruciate Ligament Desmotomy or transection of the cranial cruciate ligament, similar to the anterior cruciate ligament in humans (n = 8). OA was observed in sheep with these surgeries that were subjected to forced exercised at an oblique angle for four months. We found that the TIMP-3 treatment decreased gait stance time, average osteophytosis score and joint widening, but did not significantly affect joint space narrowing. The TIMP-3 transgene also decreased aggrecanase activity and serum glycosaminoglycan content and had a positive effect on urine glycosaminoglycan content. Through understanding and utilizing these new methods, we hope to refine our model to further research in this field and offer a better solution for those affected by OA

Using rAAV-TIMP3 Vectors for the Improvement of Osteoarthritis in an Ovine Model

The effect of Timp-3 Transgene delivered using a viral vector on osteoarthritis in an ovine mode Crystal G. Collier, Peter Welsh, Kate C. Parkinson, Anisa Samhouri, McKenna R. Walters, Jeffrey B. Maso Department of Animal, Dairy, and Veterinary Sciences, School of Veterinary Medicine, Utah State University, Logan, Utah The aim of our current research is to investigate a study of the security and remedial potential of a Timp-3 transgene delivered by a recombinant adeno-associated viral vector (rAAV) for prevention of osteoarthritis (OA). There is radiographic evidence in more than 80% of those over the age of 65, particularly in post-menopausal women. To improve the study of this disease, a large animal model physiologically similar to human is needed for closely applicable research. Two of the most common surgical methods of induction include the ovariectomy (OVX) and cranial cruciate ligament desmotomy (CCLD). An additional approach to increasing severity of OA is forced exercise. In our design, we combine these two surgical procedures (OVX, n=7 and CCLD, n=8) and oblique-angle forced exercise to create and osteoarthritic environment where gene therapy can be analyzed. In an OA environment, degradative enzymes known as matrix metalloproteinases play a central role. In a pilot study, we established that tissue inhibitor of metalloproteinase-3 gene (Timp-3) cut off these destructive enzymes in turn diminishing break down of cartilage tissues. Our current study targets the up-regulation of Timp-3 protein in situ by the addition of a Timp-3 transgene delivered by a rAAV directly into the stifle of the surgically-altered sheep. A 14-week routine of oblique-angle forced exercise was then accomplished in all subjects and subjects were then collected for analysis. Preliminary analysis of digital radiographs suggest a significant effect from the Timp-3 transgene in both models in toward the reduction of osteophytosis, the most commonly used measure of OA progression. By study of this process, we aspire to develop an effective preventative measure to be used by those suffering from OA

Teachers’ Perceptions of a Multiple High-Risk Behavior Prevention Program and Delivery of Universal Programming

Much of the success of high-risk behavior prevention programs rests with teachers who deliver the curriculum however; few studies have investigated teachers\u27 perceptions of program implementation. The objective of this phenomenological study was to answer the question, “What are the experiences of teachers who are asked to be involved in the implementation process when their school adopts a multiple high-risk behavior prevention program”? Participants included 10 teachers at a local, private high school in the Southern United States. Five themes emerged: (a) lack of consistent historical effort, (b) need for program, (c) positive but tentative perceptions, (d) challenges with implementation, and (e) review of program counselor. The qualitative results identified factors that can promote or hinder success of the program

Generating a Mouse Model of Symptomatic and Asymptomatic Intracerebral Hemorrhage by Applying High-Pressure Focused Ultrasound

Intracerebral hemorrhage defines a category of neurological disease that spans the full range of possible clinical outcomes. At one end of the spectrum is hemorrhagic stroke, an often debilitating neurologic condition with substantial morbidity and mortality while cerebral microhemorrhage at the other end of the spectrum can go completely unnoticed as they are often asymptomatic. Despite the distinct clinical outcomes both conditions share a common risk factor, uncontrolled hypertension. Here we set out to generate a novel mouse model of intracerebral hemorrhage with pressure as the mode of hemorrhage induction. To conduct our studies, we utilize high pressure focused ultrasound in combination with injected microbubbles to cause hemorrhage. We applied this technique at two different pressures resulting in striatal hemorrhage induction with distinct phenotypic outcomes. Following induction at the higher-pressure, mice show evidence of lateral motor deficit and other signs of impairment. Mice with hemorrhage induced at the lower pressure show no behavioral signs of neurological deficit. We employ immunofluorescence and western blotting to understand the cellular responses to intracerebral hemorrhage in these mice. We find evidence of inflammation and cell death following high-pressure induction of intracerebral hemorrhage. Lower pressure induction of intracerebral hemorrhage lacks signs of cell death but shows apparent inflammation. We have created a novel pressure-dependent mouse model of symptomatic and asymptomatic intracerebral hemorrhage by applying high intensity focused ultrasound in combination with circulating microbubbles

Cranial Cruciate Ligament Desmotomies in Sheep Resulting in Peroneus Tertius Injury

Surgical destabilization of the stifle joint via cranial cruciate ligament desmotomy (CCLD) is a routine procedure for the study of osteoarthritis (OA). Traditionally performed in rats, rabbits, cats, and dogs, CCLD in sheep provides an opportunity to study the pathology and treatment of joint instability in a species whose stifle better represents the equivalent human femorotibial joint. The surgical approaches for CCLD in sheep are variable and can result in inconsistent outcomes. Eight sheep underwent CCLD for use in a gene therapy study. We report this case in which six of the eight sheep were clinically diagnosed by pathognomonic signs and later confirmed by postmortem dissection, with injury of the peroneus tertius (PT) muscle. The PT plays a crucial role in the normal gait of large animals, including sheep. Injury to the PT results in failure of the reciprocal apparatus of the hind limb in which the hock can be extended during stifle flexion creating a varied gait and an indiscriminate increase in instability of the stifle and hock joints. Restricted movement postoperatively may provide decreased variability in surgical outcomes. Alternatively, increased stifle instability via CCLD coupled with PT transection or PT transection alone could potentially provide a superior model of stifle instability and OA development in sheep

Skunk River Review 2012, vol 24

https://openspace.dmacc.edu/skunkriver/1015/thumbnail.jp

The extractive industries and development: The resource curse at the micro, meso and macro levels

The resource curse literature has necessarily evolved in a rather fragmented way. While economists, political economists and political scientists have largely focused on the role of mineral abundance in long-term growth with the analysis largely confined to the country (macro) or regional (meso) level, anthropologists, sociologists and other social scientists have explored the development impacts of extractive industries at the community (micro) level. While this has provided a rigorous and comprehensive exploration of extractive industries and their impacts, causal factors that bridge and/or leap-frog these levels tend not to be accounted for. In this paper we examine the evolution of the literature across disciplinary lines and different levels of scale to assess the current status of resource curse debates. In so doing, we aim to explore how an integration of the various multi-scale approaches can help address the persistent problem of the resource curse

Serum Response Factor Regulates Immediate Early Host Gene Expression in Toxoplasma gondii-Infected Host Cells

Toxoplasma gondii is a wide spread pathogen that can cause severe and even fatal disease in fetuses and immune-compromised hosts. As an obligate intracellular parasite, Toxoplasma must alter the environment of its host cell in order to establish its replicative niche. This is accomplished, in part, by secretion of factors into the host cell that act to modulate processes such as transcription. Previous studies demonstrated that genes encoding transcription factors such as c-jun, junB, EGR1, and EGR2 were amongst the host genes that were the most rapidly upregulated following infection. In cells stimulated with growth factors, these genes are regulated by a transcription factor named Serum Response Factor. Serum Response Factor is a ubiquitously expressed DNA binding protein that regulates growth and actin cytoskeleton genes via MAP kinase or actin cytoskeletal signaling, respectively. Here, we report that Toxoplasma infection leads to the rapid activation of Serum Response Factor. Serum Response Factor activation is a Toxoplasma-specific event since the transcription factor is not activated by the closely related protozoan parasite, Neospora caninum. We further demonstrate that Serum Response Factor activation requires a parasite-derived secreted factor that signals via host MAP kinases but independently of the host actin cytoskeleton. Together, these data define Serum Response Factor as a host cell transcription factor that regulates immediate early gene expression in Toxoplasma-infected cells

Reforming Fiscal Institutions in Resource-Rich Arab Economies: Policy Proposals

This paper traces the evolution of fiscal institutions of Resource Rich Arab Economies (RRAEs) over time since their pre-oil days, through the discovery of oil to their build-up of oil exports. It then identifies challenges faced by RRAEs and variations in their severity among the different countries over time. Finally, it articulates specific policy reforms, which, if implemented successfully, could help to overcome these challenges. In some cases, however, these policy proposals may give rise to important trade-offs that will have to be evaluated carefully in individual cases