Search

The brain is capable of improving from a chronically stressed state. The hippocampus in particular appears to "recover" from chronic stress-induced morphological and functional deficits following a post-stress rest period of several weeks. We previously found that hippocampal brain-derived neurotrophic factor (BDNF) was necessary for spatial ability to improve following a post-stress rest period. The following studies are the first to investigate the involvement of BDNF and its TrkB receptor on the recovery process following the end of chronic stress, as it pertains to hippocampal dendritic retraction and spatial memory deficits. In the first study, hippocampal BDNF was downregulated via RNA interference and then hippocampal CA3 and CA1 dendritic complexity were evaluated following chronic stress and a post-stress rest period in male Sprague-Dawley rats. Downregulating hippocampal BDNF prevented the enhancement of CA3 apical dendritic complexity following the rest period. Moreover, chronic stress and downregulated BDNF in the post-stress rest group led to regionally specific enhancements in CA1 dendritic complexity. In the second study, we tested whether the TrkB receptor was involved by administering daily systemic injections of ANA-12, a TrkB receptor antagonist, during the three-week post-stress rest period. ANA-12 prevented the improvement in spatial ability and CA3 apical dendritic complexity following the post-stress rest period. These data demonstrate that hippocampal BDNF acting via its TrkB receptor is necessary during the post-stress rest period in order to improve the impaired hippocampal structural and cognitive outcomes that occur in response to chronic stress.

Objectives: Policymakers, health services researchers, community leaders and health care delivery organisations are key stakeholders in addressing economic, environmental, social and systemic barriers to health equity in vulnerable communities. However, they often operate in silos, leaving gaps in efforts to effectively address health disparities. It is important to develop a new approach to influencing responsive health equity–focused policies. Design: An innovative, collaborative model is outlined that leverages strengths across these four stakeholders to reduce inequity in target populations. The model brings together undergraduate and graduate student researchers in a front-end policy partnership with elected officials based on mutually agreed-upon commitment to address local health disparities impacting the policymaker’s constituency. Setting: Students and faculty at Arizona State University partnered with the office of a Phoenix City Council member representing a constituency largely comprised of low-income and Hispanic community members. Method: Relationships were developed with the policymaker specifically targeting food insecurity and paediatric asthma. Graduate student researchers conducted academic placements within the elected official’s office, attended relevant municipal meetings, engaged with local community-based organisations and partnered with a major academic medical centre to collect data and understand current efforts related to the two focus areas. Results: Elected officials were provided with a policymaker-tailored toolkit including a current state analysis, stakeholder assessment and recommendations for action. Collective discussion took place concerning the strengths and limitations of stakeholders’ ability to improve population health and present findings from the model’s first application to local government. Conclusion: By ensuring ‘buy-in’ from policymakers at the onset of collaboration, stakeholders worked as a transdisciplinary team to translate academic research into actionable policy to benefit high-need communities. This model adopted can potentially accelerate and improve the development and implementation of actionable policies, thereby increasing social capital and building relationships with policymakers to address the root causes of health inequities.

In the pathophysiology of traumatic brain injury (TBI), the amygdala remains understudied, despite involvement in processing emotional and stressful stimuli associated with anxiety disorders, such as post-traumatic stress disorder (PTSD). Because the basolateral amygdala (BLA) integrates inputs from sensory and other limbic structures coordinating emotional learning and memory, injury-induced changes in circuitry may contribute to psychiatric sequelae of TBI. This study quantified temporal changes in dendritic complexity of BLA neurons after experimental diffuse TBI, modeled by midline fluid percussion injury. At post-injury days (PIDs) 1, 7, and 28, brain tissue from sham and brain-injured adult, male rats was processed for Golgi, glial fibrillary acidic protein (GFAP), or silver stain and analyzed to quantify BLA dendritic branch intersections, activated astrocytes, and regional neuropathology, respectively. Compared to sham, brain-injured rats at all PIDs showed enhanced dendritic branch intersections in both pyramidal and stellate BLA neuronal types, as evidenced by Sholl analysis. GFAP staining in the BLA was significantly increased at PID1 and 7 in comparison to sham. However, the BLA was relatively spared from neuropathology, demonstrated by an absence of argyrophilic accumulation over time, in contrast to other brain regions. These data suggest an early and persistent enhancement of dendritic complexity within the BLA after a single diffuse TBI. Increased dendritic complexity would alter information processing into and through the amygdala, contributing to emotional symptoms post-TBI, including PTSD.

Workflow assessment, mapping and modeling often are used in well-resourced care settings. However, we can and must also understand healthcare workflow at the edges of care, defined as workflow at or across the boundaries between healthcare organizations. Examples include from inpatient to outpatient, from large healthcare systems to external health and social services, or between clinics and pharmacies or other community settings. The edges of care may also include settings or areas of healthcare where workflow is not normally considered due to resource limitations or other systemic barriers, such as small or rural primary care practices, community health centers, and community-based health organizations. The operational definition of the “edges of care” comes with the growing understand that most healthcare takes place beyond the four walls of a hospital, into home-based, community-based, and consumer health settings. In this chapter, we will further describe this concept of the “edges of care” and discuss (1) the importance of studying workflow at the edges of care; (2) the current state of workflow study at the edges of care; and (3) opportunities to more efficiently or innovatively study workflow at the edges of care.

The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6 h/d/21 d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40 mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype.

Background: Community Paramedicine (CP) is a rapidly evolving field within prehospital care where paramedics step outside of their traditional roles of treating acute conditions to provide elements of primary and preventive care. It is unclear if current state oversight regarding the scope of practice (SOP) for paramedics provides clear guidance on the novel functions provided and skills performed by CP programs. Objective: To determine the process and authority, as currently defined by state laws and regulations in the United States, to expand paramedic SOP in order to perform CP roles and to assess state EMS agencies' interpretation of paramedic SOP as it applies to CP. Methods: We conducted a systematic review of laws, regulations, and policies from the 50 U.S. states in effect between February and June 2016 that define or apply to paramedic SOP. We determined whether each state's SOP included 21 potential skills applicable to CP within the following categories: assessment, treatment & intervention, referrals, and prevention & public health. Laws were also queried for mechanisms for expanding SOP, alternate destinations, and community paramedicine for each state. Additionally, we surveyed representatives from U.S. State Emergency Medical Services (EMS) agencies and asked which of these skills were a part of their current SOP. All data was coded into Excel™ and analyzed using descriptive statistics. Results: All 50 U.S. states have laws relating to EMS. Forty-one states have a statewide SOP (82%), and 3 states have statewide protocols from which the SOP has been inferred for purposed of this study, but may not legally constitute SOP in this jurisdiction (6%). 20 states (40%) had a clearly defined mechanism for expanding SOP. Sixteen states (32%) had laws specific to CP. Seven states (14%) allowed for patients to be transported to alternate destinations. Of the 21 skills surveyed, on average there were 8.63 (6.41–10.85) fewer skills for paramedics found in state SOP laws and regulations than were reported as being a part of a state's paramedic SOP. All skills demonstrated variability between the legal review and survey results with 13.04–96.15% concordance. Conclusion: There is a lack of guidance and consistency regarding CP programs and scope of practice. Further studies are needed to understand best practices around regulation and oversight of CP.

Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after two weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum.