Effects of a True Prophylactic Treatment on Hippocampal and Amygdala Synaptic Plasticity and Gene Expression in a Rodent Chronic Stress Model of Social Defeat.

Post-traumatic stress disorder (PTSD) is a complex stress-related disorder induced by exposure to traumatic stress that is characterized by symptoms of re-experiencing, avoidance, and hyper-arousal. While it is widely accepted that brain regions involved in emotional regulation and memory-e.g., the amygdala and hippocampus-are dysregulated in PTSD, the pathophysiology of the disorder is not well defined and therefore, pharmacological interventions are extremely limited. Because stress hormones norepinephrine and cortisol (corticosterone in rats) are heavily implicated in the disorder, we explored whether preemptively and systemically antagonizing ß-adrenergic and glucocorticoid receptors with propranolol and mifepristone are sufficient to mitigate pathological changes in synaptic plasticity, gene expression, and anxiety induced by a modified social defeat (SD) stress protocol. Young adult, male Sprague Dawley rats were initially pre-screened for anxiety. The rats were then exposed to SD and chronic light stress to induce anxiety-like symptoms. Drug-treated rats were administered propranolol and mifepristone injections prior to and continuing throughout SD stress. Using competitive ELISAs on plasma, field electrophysiology at CA1 of the ventral hippocampus (VH) and the basolateral amygdala (BLA), quantitative RT-PCR, and behavior assays, we demonstrate that our SD stress increased anxiety-like behavior, elevated long-term potentiation (LTP) in the VH and BLA, and altered the expression of mineralocorticoid, glucocorticoid, and glutamate receptors. These measures largely reverted to control levels with the administration of propranolol and mifepristone. Our findings indicate that SD stress increases LTP in the VH and BLA and that prophylactic treatment with propranolol and mifepristone may have the potential in mitigating these and other stress-induced effects.

The Case of the Rare Malformation and Rare Variant: An Infant with a Self-Embolized Torcular Dural Sinus Malformation and a Concomitant Prothrombin Variant.

Torcular dural sinus malformations (tDSMs) can occur in the brain during prenatal development. These rare vascular malformations occur in less than 1% of the population but can lead to a poor prognosis secondary to congestive heart failure and hydrocephalus. Many tDSM cases require surgical embolization or coiling to return normal cerebral blood flow and prevent mortality and morbidity. We describe the first case of spontaneous self-embolization of a large torcular dural sinus malformation, possibly due to hypercoagulability from a comorbid prothrombin gene variant. Despite a grim prognosis at birth, the child is alive and thriving at age 3, with only mild speech delay.

Physical Exercise and Cancer: Exploring Chemotherapy Infusion as an Opportunity for Movement.

OBJECTIVE: Exercise initiated in the early stages of cancer treatment may present as the most opportune time to reduce the detrimental side effects of treatment. Beginning exercise post-cancer treatment may not be early enough to elicit important improvements. The role of exercise alongside chemotherapy treatment, specifically during chemotherapy infusion may be an opportunity for the therapeutic delivery of exercise for cancer patients. DATA SOURCES: Narrative review of peer-reviewed literature with a focus on exercise during chemotherapy infusions and therapeutic effects of exercise on the tumor microenvironment. CONCLUSION: Exercise initiated in the early stages of chemotherapy treatment may present as the most opportune time to improve therapeutic health outcomes and patient experience. If exercise during chemotherapy infusion could be feasible more testing is warranted to explore different modes including resistance-based exercise, dosage, intensity, and its potential affect on tumor hypoxia and chemotherapy drug uptake. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses are in the ideal position to initiate the conversation about exercise during chemotherapy treatments specifically the opportunity to provide light exercise during chemotherapy infusion. Starting exercise during this time may be the most beneficial timing to decrease the myriad of treatment side effects experienced. Further research is required to explore the potential affect of exercise during chemotherapy infusion on health benefits, tumor hypoxia, and drug uptake, all of which seem to be positively affected by physical exercise.

Community engagement in the Aboriginal Families Study: Strategies to promote participation.

BACKGROUND: Aboriginal women and families are under-represented in Australian research on pregnancy and childbirth. The Aboriginal Families Study aimed to investigate the views and experiences of a representative sample of women giving birth to an Aboriginal baby in South Australia between July 2011 and June 2013, using methods designed to respect Aboriginal culture and communities. METHODS: A team of 12 Aboriginal researchers facilitated community engagement and recruitment of Aboriginal and non-Aboriginal mothers of Aboriginal infants in urban, regional and remote areas of South Australia over a two-year period. RESULTS: A total of 344 women took part, around a quarter of all Aboriginal women giving birth in South Australia in the study period (39% urban, 35% regional and 25% from remote areas). Participants were representative in relation to maternal age (mean age of 25 years, range=15-43 years). Over half of women (56%) first heard about the study via a member of the fieldwork team making contact with them through community connections. Other major sources of recruitment were: Aboriginal health services/programs (20%) and public maternity hospitals (16%). Almost all of the women (95%) recruited via community networks of the fieldwork team completed the questionnaire. In contrast, 51% of women recruited via public hospitals completed the questionnaire (odds ratio=0.1, 95% confidence interval 0.0-0.1, p<0.001). CONCLUSIONS: Aboriginal researchers' community knowledge and leadership is critical to the conduct of successful Aboriginal health research. High levels of participation in research by 'harder to reach' populations are achievable when researchers take time to build relationships and work in partnership with communities.

Running exercise mitigates the negative consequences of chronic stress on dorsal hippocampal long-term potentiation in male mice.

In the hippocampus, learning and memory are likely mediated by synaptic plasticity, known as long-term potentiation (LTP). While chronic intermittent stress is negatively correlated, and exercise positively correlated to LTP induction, we examined whether exercise could mitigate the negative consequences of stress on LTP when co-occurring with stress. Mice were divided into four groups: sedentary no stress, exercise no stress, exercise with stress, and sedentary with stress. Field electrophysiology performed on brain slices confirmed that stress alone significantly reduced dorsal CA1 hippocampal LTP and exercise alone increased LTP compared to controls. Exercise with stress mice exhibited LTP that was significantly greater than mice undergoing stress alone but were not different from sedentary no stress mice. An ELISA illustrated increased corticosterone in stressed mice compared to no stress mice. In addition, a radial arm maze was used to examine behavioral changes in memory during 6 weeks of stress and/or exercise. Exercised mice groups made fewer errors in week 2. RT-qPCR was used to examine the mRNA expression of components in the stress and exercise pathways in the four groups. Significant changes in the expression of the following targets were detected: BDNF, TrkB, glucocorticoid, mineralocorticoid, and dopamine 5 receptors. Collectively, exercise can mitigate some of the negative impact stress has on hippocampal function when both occur concurrently.

Aboriginal Families Study: a population-based study keeping community and policy goals in mind right from the start.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women are between two to five times more likely to die in childbirth than non-Aboriginal women, and two to three times more likely to have a low birthweight infant. Babies with a low birthweight are more likely to have chronic health problems in adult life. Currently, there is limited research evidence regarding effective interventions to inform new initiatives to strengthen antenatal care for Aboriginal families. METHOD/DESIGN: The Aboriginal Families Study is a cross sectional population-based study investigating the views and experiences of Aboriginal and non-Aboriginal women having an Aboriginal baby in the state of South Australia over a 2-year period. The primary aims are to compare the experiences and views of women attending standard models of antenatal care with those accessing care via Aboriginal Family Birthing Program services which include Aboriginal Maternal Infant Care (AMIC) Workers as members of the clinical team; to assess factors associated with early and continuing engagement with antenatal care; and to use the information to inform strengthening of services for Aboriginal families. Women living in urban, regional and remote areas of South Australia have been invited to take part in the study by completing a structured interview or, if preferred, a self-administered questionnaire, when their baby is between 4-12 months old. DISCUSSION: Having a baby is an important life event in all families and in all cultures. How supported women feel during pregnancy, how women and families are welcomed by services, how safe they feel coming in to hospitals to give birth, and what happens to families during a hospital stay and in the early months after the birth of a new baby are important social determinants of maternal, newborn and child health outcomes. The Aboriginal Families Study builds on consultation with Aboriginal communities across South Australia. The project has been implemented with guidance from an Aboriginal Advisory Group keeping community and policy goals in mind right from the start. The results of the study will provide a unique resource to inform quality improvement and strengthening of services for Aboriginal families.