Do Patterns of Adolescent Participation in Arts, Culture and Entertainment Activities Predict Later Wellbeing? A Latent Class Analysis.

Participation in arts, culture, and entertainment (PACE) activities may promote adolescent wellbeing. However, little is known about how such activities cluster together, and previous research has used small samples, cross-sectional designs, focused on single activities, and/or has not considered the influence of socio-demographic factors on participation. Using latent class analysis, the aims of this study were to establish: (i) classes of adolescent PACE activities; (ii) associations between socio-demographic characteristics and PACE classification; and, (iii) whether PACE classification predicts later wellbeing. Longitudinal data from the #BeeWell study (N = 18,224 adolescents; mean age at T1 = 12 years 7 months (±3.56 months); 50.54% female) were analyzed. Four latent classes were established: the 'Dynamic Doers' (high, wide-ranging participation; 11.87%); the 'Mind and Body Crew' (reading, arts, videogames, sports/exercise; 39.81%); the 'Game and Gain Squad' (videogames and sports/exercise; 29.05%); and the 'Activity Free Adolescents' (uniformly low participation; 19.27%). Associations between socio-demographic characteristics and PACE classification were observed (e.g., socio-economic disadvantage increased the likelihood of Activity Free Adolescents classification, compared to Game and Gain Squad classification). Finally, PACE classification predicted later wellbeing (e.g., Dynamic Doers reported significantly higher wellbeing than Activity Free Adolescents). These findings are discussed in relation to the need to improve accessibility and appeal of arts, culture, and entertainment provision for adolescents as a means to optimize their wellbeing. PRE-REGISTRATION: The analysis plan for this study was pre-registered on the Open Science Framework and can be found here: https://osf.io/2jtpd.

Does Early Child Language Predict Internalizing Symptoms in Adolescence? An Investigation in Two Birth Cohorts Born 30 Years Apart.

Language is vital for social interaction, leading some to suggest early linguistic ability paves the way for good adolescent mental health. The relation between age-5 vocabulary and adolescent internalizing symptoms was examined in two U.K. birth cohorts that are nationally representative in terms of sex, ethnicity, and socioeconomic status: the 1970 British Cohort Study (BCS; N = 11,640) and the Millennium Cohort Study (MCS born ~2001; N = 14,754). In the BCS, no relation between receptive vocabulary and age-16 self-reported symptoms was observed (ß = 0.00 [-0.03; 0.03]). In the MCS, better expressive vocabulary was associated with more age-14 self-reported symptoms (ß = 0.05 [0.02; 0.07]). The direction of this effect was reversed for parent-reported symptoms. All effect sizes were small. The relation between childhood vocabulary and internalizing symptoms varies by generation and reporter.

The neuroprotective activity of the amyloid precursor protein against traumatic brain injury is mediated via the heparin binding site in residues 96-110.

We have previously shown that following traumatic brain injury (TBI) the presence of the amyloid precursor protein (APP) may be neuroprotective. APP knockout mice have increased neuronal death and worse cognitive and motor outcomes following TBI, which is rescued by treatment with exogenous sAPPα (the secreted ectodomain of APP generated by α-secretase cleavage). Two neuroprotective regions were identified in sAPPα, the N and C-terminal domains D1 and D6a/E2 respectively. As both D1 and D6a/E2 contain heparin binding activity it was hypothesized that this is responsible for the neuroprotective activity. In this study, we focused on the heparin binding site, encompassed by residues 96-110 in D1, which has previously been shown to have neurotrophic properties. We found that treatment with APP96-110 rescued motor and cognitive deficits in APP-/- mice following focal TBI. APP96-110 also provided neuroprotection in Sprague-Dawley rats following diffuse TBI. Treatment with APP96-110 significantly improved functional outcome as well as preserve histological cellular morphology in APP-/- mice following focal controlled cortical impact injury. Furthermore, following administration of APP96-110 in rats after diffuse impact acceleration TBI, motor and cognitive outcomes were significantly improved and axonal injury reduced. These data define the heparin binding site in the D1 domain of sAPPα, represented by the sequence APP96-110, as the neuroprotective site to confer neuroprotection following TBI. The product of α-secretase cleavage of the amyloid precursor protein, sAPPα is neuroprotective following traumatic brain injury (TBI). Of interest was whether this neuroprotective activity could be further delineated to a heparin binding region within sAPPα, corresponding to the region APP96-110 (see diagram demonstrating the domain structure of sAPPα). Indeed treatment with APP96-110 improved functional outcome following TBI, an effect that was not seen with a mutated version of the peptide that had reduced heparin binding affinity.

Clinical and cost-effectiveness of DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives) for people living with dementia and their carers: a study protocol for a parallel multicentre randomised controlled trial.

INTRODUCTION: Many people living with dementia experience sleep disturbance and there are no known effective treatments. Non-pharmacological treatment options should be the first-line sleep management. For family carers, relatives' sleep disturbance leads to interruption of their sleep, low mood and breakdown of care. Our team developed and delivered DREAMS START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives), a multimodal non-pharmacological intervention, showing it to be feasible and acceptable. The aim of this randomised controlled trial is to establish whether DREAMS START is clinically cost-effective in reducing sleep disturbances in people living with dementia living at home compared with usual care. METHODS AND ANALYSIS: We will recruit 370 participant dyads (people living with dementia and family carers) from memory services, community mental health teams and the Join Dementia Research Website in England. Those meeting inclusion criteria will be randomised (1:1) either to DREAMS START or to usual treatment. DREAMS START is a six-session (1 hour/session), manualised intervention delivered every 1-2 weeks by supervised, non-clinically trained graduates. Outcomes will be collected at baseline, 4 months and 8 months with the primary outcome being the Sleep Disorders Inventory score at 8 months. Secondary outcomes for the person with dementia (all proxy) include quality of life, daytime sleepiness, neuropsychiatric symptoms and cost-effectiveness. Secondary outcomes for the family carer include quality of life, sleep disturbance, mood, burden and service use and caring/work activity. Analyses will be intention-to-treat and we will conduct a process evaluation. ETHICS AND DISSEMINATION: London-Camden & Kings Cross Ethics Committee (20/LO/0894) approved the study. We will disseminate our findings in high-impact peer-reviewed journals and at national and international conferences. This research has the potential to improve sleep and quality of life for people living with dementia and their carers, in a feasible and scalable intervention. TRIAL REGISTRATION NUMBER: ISRCTN13072268.

NK1 tachykinin receptor antagonist treatment reduces cerebral edema and intracranial pressure in an ovine model of ischemic stroke.

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep (n = 24) were subject to 2-hours tMCAo and randomized (n = 6/group) to receive early NK1-R treatment (days 1-3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation.

Substance P antagonists as a novel intervention for brain edema and raised intracranial pressure.

Increased intracranial pressure (ICP) following acute brain injury requires the accumulation of additional water in the intracranial vault. One source of such water is the vasculature, although the mechanisms associated with control of blood-brain barrier permeability are unclear. We have recently shown that acute brain injury, such as neurotrauma and stroke, results in perivascular accumulation of the neuropeptide, substance P. This accumulation is associated with increased blood-brain barrier permeability and formation of vasogenic edema. Administration of a substance P antagonist targeting the tachykinin NK1 receptor profoundly reduced the increased blood-brain barrier permeability and edema formation, and in small animal models of acute brain injury, improved functional outcome. In a large, ovine model of experimental traumatic brain injury, trauma resulted in a significant increase in ICP. Administration of an NK1 antagonist caused a profound reduction in post--traumatic ICP, with levels returning to normal within 4 h of drug administration. Substance P NK1 antagonists offer a novel therapeutic approach to the treatment of acute brain injury.

Undergraduate nursing students' experiences of online education: A cross-sectional survey.

During the coronavirus pandemic, UK Academics were required to adjust their learning and teaching environment and pedagogical approaches, with little guidance or time. Feelings of frustration and uncertainty around student engagement were commonplace across Higher Education Institutions. This was heightened in professionally regulated courses, such as nursing. The shift to online learning created a situation where academics were frequently faced with a 'sea of black screens' and unable to ascertain student engagement. This study investigated undergraduate nursing students' experience of online education during the COVID-19 pandemic. An anonymous survey was distributed to each year of the undergraduate nursing programme and data subsequently analysed. Responses from 54 students revealed that engagement varied between different year groups. There were significant differences between those with pre-COVID (traditional face-to-face) teaching experience (years 2 and 3) and those without (year 1) in regard to self-reported engagement with online learning. The findings from this study revealed some powerful and emotional insights into the experience of online learning amongst UK students undertaking an undergraduate nursing programme during the COVID-19 pandemic.

Promoting mental health and well-being in schools: examining mindfulness, relaxation and strategies for safety and well-being in English primary and secondary schools-study protocol for a multi-school, cluster randomised controlled trial (INSPIRE).

There are increasing rates of internalising difficulties, particularly anxiety and depression, being reported in children and young people in England. School-based universal prevention programmes are thought to be one way of helping tackle such difficulties. This paper describes an update to a four-arm cluster randomised controlled trial ( http://www.isrctn.com/ISRCTN16386254 ), investigating the effectiveness of three different interventions when compared to usual provision, in English primary and secondary pupils. Due to the COVID-19 pandemic, the trial was put on hold and subsequently prolonged. Data collection will now run until 2024. The key changes to the trial outlined here include clarification of the inclusion and exclusion criteria, an amended timeline reflecting changes to the recruitment period of the trial due to the COVID-19 pandemic and clarification of the data that will be included in the statistical analysis, since the second wave of the trial was disrupted due to COVID-19.Trial registration ISRCTN Registry ISRCTN16386254. Registered on 30 August 2018.

Changes in Behaviour and Voluntary Physical Activity Exhibited by Sled Dogs throughout Incremental Exercise Conditioning and Intermittent Rest Days.

Participation in repetitive endurance training decreases sled dogs' voluntary activity and locomotive behaviours; however, the changes in their voluntary physical activity over consecutive rest days has not been examined to assess exercise-recovery. The objective of this study was to examine the changes in behaviour and voluntary activity of sled dogs throughout repetitive incremental conditioning and intermittent rest days. Fourteen dogs (6 males, 8 females; age 3.7 ± 2.7 years; BW 21.5 ± 2.8 kg) underwent 10 weeks of conditioning. Once a week, 5-min video recordings were taken pre- and post-exercise to measure the time spent performing agonistic behaviours, chewing on the gangline, digging, jumping, lunging, posture changing, sitting, standing and lying. Additionally, voluntary physical activity was measured on a day with an exercise bout during baseline, week 4, 5 and 7 and two consecutive rest days during baseline, week 1, 4, 5 and 7. A repeated-measures mixed model was used to analyse data in SAS (v 9.4.). As dogs progressed through their conditioning, the time spent changing posture prior to an exercise bout decreased (p < 0.05), suggesting that dogs may reduce their voluntary locomotive behaviours with increasing exercise. Additionally, dogs were more active during the second consecutive rest day than the first (p < 0.05), suggesting that rest days may provide a short-term recovery period.

Supplemental Fiber Affects Body Temperature and Fecal Metabolites but Not Respiratory Rate or Body Composition in Mid-Distance Training Sled Dogs.

Dietary fiber affects canine physiology in many ways, such as increasing colonic absorption of water and improving gut health, both of which may positively impact exercise performance. The objectives of this study were to investigate the effects of increased dietary soluble fiber and incremental training on respiratory rate (RR), internal body temperature (BT), body composition, and fecal metabolites in mid-distance training sled dogs. Fourteen dogs (12 Siberian and 2 Alaskan Huskies) were blocked by age, sex, and body weight (BW) and then randomly allocated into one of two diet groups. Seven dogs were fed a dry extruded control diet (Ctl) with an insoluble:soluble fiber ratio of 4:1 (0.74% soluble fiber on a dry-matter basis), and seven dogs were fed a dry extruded treatment diet (Trt) with an insoluble:soluble fiber ratio of 3:1 (2.12% soluble fiber on a dry-matter basis). Fecal samples were taken once a week. All dogs underwent 9 weeks of incremental exercise conditioning where the running distance was designed to increase each week. Every 3 weeks, external telemetry equipment was used to non-invasively measure and record RR and internal BT at resting, working, and post-exercise recovery states. Body composition was measured on weeks -1 and 9 using quantitative magnetic resonance. Body composition, RR, BT, and fecal metabolites were analyzed using a mixed model with dog as a random effect and week and diet group as fixed effects. Dogs on Trt had lower working and post-exercise BT than Ctl (P < 0.05). In addition, Trt dogs had lower recovery BT at weeks 2 and 5 than Ctl dogs (P < 0.05). Treatment dogs had greater fecal short-chain fatty acid concentrations than Ctl (P < 0.05). Diet had no effect on RR or body composition (P > 0.10), but exercise resulted in an overall 7% increase in lean and 3.5% decrease in fat mass (P < 0.05). These data suggest that increasing dietary soluble fiber may positively influence BT and gut health; however, it has no effect on RR or body composition. Soluble fiber did not negatively impact any measures of overall health and performance and should be considered for use in performance dogs.

Kinin receptor antagonists as potential neuroprotective agents in central nervous system injury.

Injury to the central nervous system initiates complex physiological, cellular and molecular processes that can result in neuronal cell death. Of interest to this review is the activation of the kinin family of neuropeptides, in particular bradykinin and substance P. These neuropeptides are known to have a potent pro-inflammatory role and can initiate neurogenic inflammation resulting in vasodilation, plasma extravasation and the subsequent development of edema. As inflammation and edema play an integral role in the progressive secondary injury that causes neurological deficits, this review critically examines kinin receptor antagonists as a potential neuroprotective intervention for acute brain injury, and more specifically, traumatic brain and spinal cord injury and stroke.

Investigating the effects of incremental conditioning and supplemental dietary tryptophan on the voluntary activity and behaviour of mid-distance training sled dogs.

Serotonin is a neurotransmitter synthesized by the amino acid tryptophan, that has the potential to impact the behaviour and activity of dogs. The objective of this study was to assess the effects of supplemental tryptophan and a 12-week incremental training regimen on the voluntary activity and behaviour of client-owned Siberian Huskies. Sixteen dogs were blocked for age, BW and sex and then randomly allocated to either the control or treatment group. Both groups were fed the same dry extruded diet; however, the treatment group were supplemented with tryptophan to achieve a tryptophan: large neutral amino acid ratio of 0.075:1. Once a week, a 5-minute video recording was taken immediately pre- and post- exercise to evaluate dogs' behaviours. Activity monitors were used to record voluntary activity on both training and rest days. Linear regression analysis was used to assess the relationship between training week and time spent performing each behaviour. Additionally, a repeated measure mixed model was used to test differences between diet groups and training week for both behavioural and activity count data. The time spent performing agonistic behaviours prior to exercise was negatively associated with week for treatment dogs (ß = -0.32, 95% CI [-0.55, -0.10], P < 0.05) and no change was observed for control dogs (ß = -0.13, 95% CI [-0.41, 0.15], P > 0.10). Treatment did not have any effect on activity levels (P > 0.10). For all dogs, locomotive behaviours decreased prior to exercise as weeks progressed (P < 0.05), while run day voluntary activity depended on the distance run that day (P < 0.05). These data suggest that sled dogs experience an exercise-induced reduction in voluntary locomotion in response to both single bouts and repetitive bouts of exercise. Additionally, tryptophan supplementation may decrease agonistic behaviours, without having any effect on voluntary activity.

Exercise but Not Supplemental Dietary Tryptophan Influences Heart Rate and Respiratory Rate in Sled Dogs.

Tryptophan (Trp), an indispensable amino acid for dogs, is the precursor of serotonin, a neurotransmitter with a variety of effects throughout the body, including the ability to modulate cardiac and pulmonary activity. This study aimed to investigate the effects of a 12-week incremental exercise regimen and supplemental dietary Trp on heart rate (HR) and respiratory rate (RR) in client-owned sled dogs. Sixteen Siberian huskies were randomly allocated to either treatment or control diet groups. Both groups were fed a control diet (Trp to large neutral amino acid ratio of 0.047:1); however, treatment dogs received a Trp supplement to achieve a Trp to large neutral amino acid ratio of 0.075:1. Every three weeks, external telemetry equipment was used to non-invasively measure and record HR and RR at a resting, working, and post-exercise state in a controlled exercise challenge. A mixed model was used to test differences between diet, activity parameter, and week. Dietary Trp supplementation had no effect on HR or RR. Independent of diet, resting, working, post-exercise HR, and time to recover post-exercise HR decreased from week -1 to week 11 (p < 0.05). Resting HR had the greatest reduction from week -1 to week 11 (21%, p < 0.05). Working RR did not change with exercise (p > 0.10), but rRR and postRR decreased from week -1 to week 11 (p < 0.05). These data suggest that the exercise regimen the dogs were subjected to may have positively impacted the dogs' capacity to sustain aerobic exercise, whereas Trp supplementation had no effect on HR or RR.

Effects of incremental exercise and dietary tryptophan supplementation on the amino acid metabolism, serotonin status, stool quality, fecal metabolites, and body composition of mid-distance training sled dogs.

Exercise improves the health of dogs; however, the extreme exertion experienced by sled dogs may lead to variable metabolic and fecal characteristics. Nutritional interventions, such as dietary tryptophan (Trp), may reduce the prevalence of these exercise-induced disturbances. Sporting diets tend to have high crude protein concentrations in contrast to adult maintenance diets and this results in less Trp relative to other amino acids (AA). Therefore, sporting dogs represent an ideal cohort to assess the effects of supplemental Trp. The objective was to evaluate the effects of supplemental dietary Trp and an incremental training regimen on AA and serotonin status, fecal scores and metabolites, and body composition in client-owned Siberian huskies. Sixteen dogs (nine females and seven males) were used, with a mean age of 4.8 ± 2.5 yr and body weight (BW) of 24.3 ± 4.3 kg. Dogs were blocked for sex, age, and BW and randomly allocated into two groups with eight fed a dry extruded control diet (Ctl) and eight fed Ctl supplemented with Trp to reach a Trp:large-neutral AA (LNAA) ratio of 0.075:1 (treatment, Trt). The exercise regimen was designed to increase in distance each week, but weather played a role in setting the daily distance. Each week BW was recorded and food allotments were adjusted to maintain initial BW. Pre and post-exercise blood samples were taken every 3 wk, dogs then received a meal followed by 1, 2, and 4 h post meal blood collections (serum AA, serotonin). Stool collection and scoring occurred each week and body composition was measured on weeks -1 and 11. Serotonin, AA, fecal metabolite, and body composition data were analyzed using PROC MIXED of SAS with dog as a random effect and week and Trt as fixed effects. Stool score data were analyzed using PROC FREQ to compare stool score and Trt, and PROC CORR was used to analyze associations between fecal score, temperature, humidity, and run distance. Dogs on Trt had greater fasted Trp compared with baseline, greater post-meal Trp and serotonin compared with baseline, greater post-meal Trp compared with fasted, and greater post-meal Trp and serotonin compared with Ctl (P < 0.05). Fecal data indicated that Trp improved stool scores (P < 0.05) yet had no effect on fecal metabolites. An overall increase in lean and decrease in fat mass was found (P < 0.05), but Trt had no effect on body composition. Optimization of the dietary Trp:LNAA ratio may help to improve GI health without compromising performance in actively training sled dogs.

Determining the Temporal Profile of Intracranial Pressure Changes Following Transient Stroke in an Ovine Model.

BACKGROUND AND PURPOSE: Cerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model. METHODS: Merino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA. RESULTS: Intracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO. CONCLUSION: We have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5-6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.

The amyloid precursor protein derivative, APP96-110, is efficacious following intravenous administration after traumatic brain injury.

Following traumatic brain injury (TBI) neurological damage is ongoing through a complex cascade of primary and secondary injury events in the ensuing minutes, days and weeks. The delayed nature of secondary injury provides a valuable window of opportunity to limit the consequences with a timely treatment. Recently, the amyloid precursor protein (APP) and its derivative APP96-110 have shown encouraging neuroprotective activity following TBI following an intracerebroventricular administration. Nevertheless, its broader clinical utility would be enhanced by an intravenous (IV) administration. This study assessed the efficacy of IV APP96-110, where a dose-response for a single dose of 0.005mg/kg- 0.5mg/kg APP96-110 at either 30 minutes or 5 hours following moderate-severe diffuse impact-acceleration injury was performed. Male Sprague-Dawley rats were assessed daily for 3 or 7 days on the rotarod to examine motor outcome, with a separate cohort of animals utilised for immunohistochemistry analysis 3 days post-TBI to assess axonal injury and neuroinflammation. Animals treated with 0.05mg/kg or 0.5mg/kg APP96-110 after 30 minutes demonstrated significant improvements in motor outcome. This was accompanied by a reduction in axonal injury and neuroinflammation in the corpus callosum at 3 days post-TBI, whereas 0.005mg/kg had no effect. In contrast, treatment with 0.005m/kg or 0.5mg/kg APP96-110 at 5 hours post-TBI demonstrated significant improvements in motor outcome over 3 days, which was accompanied by a reduction in axonal injury in the corpus callosum. This demonstrates that APP96-110 remains efficacious for up to 5 hours post-TBI when administered IV, and supports its development as a novel therapeutic compound following TBI.

Traumatic brain injury and Alzheimer's disease: a review.

In an effort to identify the factors that are involved in the pathogenesis of Alzheimer's disease (AD), epidemiological studies have featured prominently in contemporary research. Of those epidemiological factors, accumulating evidence implicates traumatic brain injury (TBI) as a possible predisposing factor in AD development. Exactly how TBI triggers the neurodegenerative cascade of events in AD remains controversial. There has been extensive research directed towards understanding the potential relationship between TBI and AD and the putative influence that apolipoprotein E (APOE) genotype has on this relationship. The aim of the current paper is to provide a critical summary of the experimental and human studies regarding the association between TBI, AD and APOE genotype. It will be shown that despite significant discrepancies in the literature, there still appears to be an increasing trend to support the hypothesis that TBI is a potential risk factor for AD. Furthermore, although it is known that APOE genotype plays an important role in AD, its link to a deleterious outcome following TBI remains inconclusive and ambiguous.

The Role of Substance P in Secondary Pathophysiology after Traumatic Brain Injury.

It has recently been shown that substance P (SP) plays a major role in the secondary injury process following traumatic brain injury (TBI), particularly with respect to neuroinflammation, increased blood-brain barrier (BBB) permeability, and edema formation. Edema formation is associated with the development of increased intracranial pressure (ICP) that has been widely associated with increased mortality and morbidity after neurotrauma. However, a pharmacological intervention to specifically reduce ICP is yet to be developed, with current interventions limited to osmotic therapy rather than addressing the cause of increased ICP. Given that previous publications have shown that SP, NK1 receptor antagonists reduce edema after TBI, more recent studies have examined whether these compounds might also reduce ICP and improve brain oxygenation after TBI. We discuss the results of these studies, which demonstrate that NK1 antagonists reduce posttraumatic ICP to near normal levels within 4 h of drug administration, as well as restoring brain oxygenation to near normal levels in the same time frame. The improvements in these parameters occurred in association with an improvement in BBB integrity to serum proteins, suggesting that SP-mediated increases in vascular permeability significantly contribute to the development of increased ICP after acute brain injury. NK1 antagonists may therefore provide a novel, mechanistically targeted approach to the management of increased ICP.

The relationship between empathy and burnout - lessons for paramedics: a scoping review.

BACKGROUND: The concepts of empathy and burnout are critical for practicing paramedics and the profession. While there has been an increasing body of research on the relationship between empathy and burnout with physicians and nurses, surprisingly, no research has been undertaken with paramedics. The aim of this scoping review was to explore the relationship between empathy and burnout. METHOD: A scoping review was performed based on Arskey and O'Malley's framework. Five databases were searched: CINAHL plus, EMBASE, MEDLINE, PsycINFO, and Scopus. Google Scholar was searched for gray literature. Two reviewers independently assessed eligibility and extracted the data. RESULTS: The initial search produced a yield of 1270 articles after removal of duplicates. All abstracts were screened for relevance, and 30 articles were selected for further screening. Twenty six articles were deemed relevant, of which there were 23 cross-sectional studies, two editorials, and one description article on the multidimensional aspect of burnout and empathy. The studies were conducted in Europe, USA, North America, and Asia. In most studies, there was an inverse correlation between empathy and emotional exhaustion and depersonalization but a positive correlation with personal accomplishment. CONCLUSION: Although there seems to be a real relationship between empathy and burnout in physicians and nurses, the strength of the relationship differs to some extent depending on the samples and settings. Due to similarities between health professions, the relationship between empathy and burnout may also be relevant to the paramedic profession. Future paramedic research should focus on longitudinal studies to determine the factors that might influence empathy and burnout levels to provide a better understanding of these two key factors.

Soluble amyloid precursor protein alpha reduces neuronal injury and improves functional outcome following diffuse traumatic brain injury in rats.

Amyloid precursor protein (APP) has previously been shown to increase following traumatic brain injury (TBI). Whereas a number of investigators assume that increased APP may lead to the production of neurotoxic Abeta and be deleterious to outcome, the soluble alpha form of APP (sAPPalpha) is a product of the non-amyloidogenic cleavage of amyloid precursor protein that has previously been shown in vitro to have many neuroprotective and neurotrophic functions. However, no study to date has addressed whether sAPPalpha may be neuroprotective in vivo. The present study examined the effects of in vivo, posttraumatic sAPPalpha administration on functional motor outcome, cellular apoptosis, and axonal injury following severe impact-acceleration TBI in rats. Intracerebroventricular administration of sAPPalpha at 30 min posttrauma significantly improved motor outcome compared to vehicle-treated controls as assessed using the rotarod task. Immunohistochemical analysis using antibodies directed toward caspase-3 showed that posttraumatic treatment with sAPPalpha significantly reduced the number of apoptotic neuronal perikarya within the hippocampal CA3 region and within the cortex 3 days after injury compared to vehicle-treated animals. Similarly, sAPPalpha-treated animals demonstrated a reduction in axonal injury within the corpus callosum at all time points, with the reduction being significant at both 3 and 7 days postinjury. Our results demonstrate that in vivo administration of sAPPalpha improves functional outcome and reduces neuronal cell loss and axonal injury following severe diffuse TBI in rats. Promotion of APP processing toward sAPPalpha may thus be a novel therapeutic strategy in the treatment of TBI.