POST-TRAUMATIC SLEEP FOLLOWING DIFFUSE TRAUMATIC BRAIN INJURY

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role of acute post-traumatic sleep on the recovery of neurological function after TBI. The aim of this thesis was to examine post-traumatic sleep after experimental TBI, defined as an increase in sleep during the first hours post-injury. In these studies, we non-invasively measured sleep activity following diffuse brain injury induced by midline fluid percussion injury to examine the architecture of post-traumatic sleep in mice. We detected significant injury-induced increases in acute sleep for six hours regardless of injury severity or time of day injury occurred. We found concurrent increases in cortical levels of the sleep promoting inflammatory cytokine interleukin 1-beta. We extended the timeline of post-injury sleep recording and found increases in post-traumatic sleep are distinctly acute with no changes in chronic sleep following diffuse TBI. Further, we investigated if post-traumatic sleep was beneficial to neurological outcome after brain-injury by disrupting post-traumatic sleep. Disruption of post-traumatic sleep did not worsen functional outcome (neuromotor, sensorimotor, cognition) at one week after diffuse TBI. With sufferers of TBI not always seeking medical attention, our final studies investigated over-the-counter analgesics and their effect on post-traumatic sleep and functional outcome. Acute administration of analgesics with varying anti-inflammatory properties had little effect on post-traumatic sleep and functional outcome. Overall, these studies demonstrated translational potential and suggest sleep after a concussion is part of the natural recovery from injury. While disrupting sleep does not worsen outcome, it is in no way beneficial to recovery. Additionally, a single analgesic dose for pain management following concussion plays little role in short term outcome

Decision Making Towards Maternal Health Services in Central Java, Indonesia

Background: Indonesia has always been struggling with maternal health issue even after the Millennium Development Goals (MDGs) programs were done. Prior research findings identified many factors which influenced maternal health status in developing countries such Indonesia and even though various efforts had been made, the impact of the transformation of maternal health behavior was minimal.Purpose: This study aimed to seek an understanding of the factors influencing decisions towards maternal health services.Methods: A case study with a single case embedded design was employed. Interviews and Focus Group Discussions (FGDs) were held to collect data from 3 health workers and 40 maternal women in a sub-district in Central Java, Indonesia.Results: Interviews with the village midwives as the main health providers in the Getasan sub-district concluded that there were several factors influencing the women\u27s decisions towards maternal services. The factors were options to have services with other health workers outside the area, and shaman services as alternative care and family influencing maternal health behaviors. The analysis of the FGDs also supported the village midwives\u27 statements that in spite of their awareness towards the available maternal health services, the existence of shamans and traditional beliefs strongly affected their decision.Conclusion: The findings in this study showed that cultural issues prevented the maximum maternal health status in Getasan sub-district. This study recommends Puskesmas (Primary Health Care) as the first level of health institutions in Indonesia to support the village midwives\u27 roles within their target area

Local guidelines for admission to UK midwifery units compared with national guidance: A national survey using the UK Midwifery Study System (UKMidSS)

Objectives. To describe the extent to which local guidelines for admission to UK midwifery units align with national guidance; to describe variation in individual admission criteria; and to describe the extent to which alongside midwifery units (AMUs) are the default option for eligible women. Design. National cross-sectional survey. Setting. All 122 UK maternity services with midwifery units, between October 2018 and February 2019. Outcome measures. Alignment of local admission guidelines with national guidance (NICE CG190); frequency and nature of variation in individual admission criteria; percentage of services with AMU as default birth setting for eligible women. Results. Admission guidelines were received from 87 maternity services (71%), representing 153 units, and we analysed 85 individual guideline documents. Overall, 92% of local admission guidelines varied from national guidance; 76% contained both some admission criteria that were ‘more inclusive’ and some that were ‘more restrictive’ than national guidance. The most common ‘more inclusive’ admission criteria, occurring in 40–80% of guidelines, were: explicit admission of women with parity ≥4; aged 35-40yrs; with a BMI 30-35kg/m2; selective admission of women with a BMI 35-40kg/m2; Group B Streptococcus carriers; and those undergoing induction of labour. The most common ‘more restrictive’ admission criteria, occurring in around 30% of guidelines, excluded women who: declined blood products; had experienced female genital cutting; were aged <16yrs; or had not attended for regular antenatal care. Over half of services (59%) reported the AMU as the default option for healthy women with straightforward pregnancies. Conclusions. The variation in local midwifery unit admission criteria found in this study represents a potentially confusing and inequitable basis for women making choices about planned place of birth. A review of national guidance may be indicated and where a lack of relevant evidence underlies variation in admission criteria, further research by planned place of birth is required

Exploring women's preferences for birth settings in England:a discrete choice experiment

<div><p>Objective</p><p>To explore pregnant women’s preferences for birth setting in England.</p><p>Design</p><p>Labelled discrete choice experiment (DCE).</p><p>Setting</p><p>Online survey.</p><p>Sample</p><p>Pregnant women recruited through social media and an online panel.</p><p>Methods</p><p>We developed a DCE to assess women’s preferences for four hypothetical birth settings based on seven attributes: reputation, continuity of care, distance from home, time to see a doctor, partner able to stay overnight, chance of straightforward birth and safety for baby. We used a mixed logit model, with setting modelled as an alternative-specific constant, and conducted a scenario analysis to evaluate the impact of changes in attribute levels on uptake of birth settings.</p><p>Main outcome measures</p><p>Women’s preferences for birth setting.</p><p>Results</p><p>257 pregnant women completed the DCE. All birth setting attributes, except ‘time to see doctor’, were significant in women’s choice (p<0.05). There was significant heterogeneity in preferences for some attributes. Changes to levels for ‘safety for the baby’ and ‘partner able to stay overnight’ were associated with larger changes from baseline uptake of birth setting. If the preferences identified were translated into the real-world context up to a third of those who reported planning birth in an obstetric unit might choose a midwifery unit assuming universal access to all settings, and knowledge of the differences between settings.</p><p>Conclusions</p><p>We found that ‘safety for the baby’, ‘chance of a straightforward birth’ and ‘can the woman’s partner stay overnight following birth’ were particularly important in women’s preferences for hypothetical birth setting. If all birth settings were available to women and they were aware of the differences between them, it is likely that more low risk women who currently plan birth in OUs might choose a midwifery unit.</p></div

Cognitive and Composite Behavioural Welfare Assessments of Pet Cats between the Ages of 9–22 Months, Living in Single and Multi-Cat Households

SIMPLE SUMMARY: Although agonistic interactions between cats are often regarded clinically as a source of stress, there is currently limited research evidence regarding the welfare impact of keeping multiple cats as pets. The aim of this study was to compare welfare indicators between cats living in single and multi-cat households, as well as between cats living in multi-cat households where agonistic behaviour was/was not reported by owners. Indicators included a spatial judgment bias task (JBT) and the cat stress score (CSS). CSSs were higher in cats from single compared with multi-cat households. CSSs were lower for cats that showed a more ‘pessimistic’ response in the JBT, suggesting these cats appeared to be less stressed. JBT results did not vary depending on the presence of, or reports of agonistic behaviours between, cohabiting cats. These data suggest that mood states (as measured by the JBT) were not impacted by the social groupings investigated, and that cats from single-cat households showed more signs of stress (as measured by CSS) than those in multi-cat households. Alternative explanations cannot be discounted, particularly due to the narrow sample population and broad scope of husbandry conditions that were unaccounted for. Further research is warranted to explore the extent to which variables that could not be controlled may have confounded findings. ABSTRACT: Although agonistic interactions between cats are often regarded clinically as a source of stress, there is currently limited research evidence regarding the welfare impact of keeping multiple cats as pets. The aim of this study was to compare welfare indicators between cats living in domestic single and multi-cat households, as well as between multi-cat households where agonistic behaviour was/was not reported by owners. Indicators included a spatial judgment bias task (JBT), where longer latencies to ambiguous probes are interpreted as being related to a more ‘pessimistic’ mood state, and the cat stress score (CSS), where high scores are indicative of high stress levels. Of 128 focal cats between the ages of 9–22 months, 94 were from multi-cat households, 126 had useable CSS data and 42 had JBT results suitable for analysis. CSSs were significantly lower for cats showing a more ‘pessimistic’ response in the JBT. It is possible that the cats that appeared to be the most relaxed may have been showing inactivity relating to negative affective states and/or were the least active/food motivated, and therefore slower in the JBT. CSSs were significantly higher in cats from single compared with multi-cat households, and did not vary with reports of agonistic interactions in multi-cat households. JBT results did not vary depending on the presence of, or reports of agonistic behaviours between, cohabiting cats. These data suggest that cats from single-cat households may be more likely to show signs of acute stress than those in multi-cat households. Alternative explanations are possible. For example, lower CSSs in the multi-cat group may reflect ‘relief’ effects resulting from separating cats for the test period, or inactivity relating to negative affective states. Due to the narrow sample population and broad scope of husbandry conditions, the potential for confounding variables limits the degree by which results can be used to inform causation of the relationships identified. Further research is warranted to replicate this work and explore potential confounders

The p38α MAPK Regulates Microglial Responsiveness to Diffuse Traumatic Brain Injury

Neuropathology after traumatic brain injury (TBI) is the result of both the immediate impact injury and secondary injury mechanisms. Unresolved post-traumatic glial activation is a secondary injury mechanism that contributes to a chronic state of neuroinflammation in both animal models of TBI and human head injury patients. We recently demonstrated, using in vitro models, that p38α MAPK signaling in microglia is a key event in promoting cytokine production in response to diverse disease-relevant stressors and subsequent inflammatory neuronal dysfunction. From these findings, we hypothesized that the p38α signaling pathway in microglia could be contributing to the secondary neuropathologic sequelae after a diffuse TBI. Mice where microglia were p38α-deficient (p38α KO) were protected against TBI-induced motor deficits and synaptic protein loss. In wild-type (WT) mice, diffuse TBI produced microglia morphological activation that lasted for at least 7 d; however, p38α KO mice failed to activate this response. Unexpectedly, we found that the peak of the early, acute phase cytokine and chemokine levels was increased in injured p38α KO mice compared with injured WT mice. The increased cytokine levels in the p38α KO mice could not be accounted for by more infiltration of macrophages or neutrophils, or increased astrogliosis. By 7 d after injury, the cytokine and chemokine levels remained elevated in injured WT mice but not in p38α KO mice. Together, these data suggest that p38α balances the inflammatory response by acutely attenuating the early proinflammatory cytokine surge while perpetuating the chronic microglia activation after TBI

Longitudinal optical imaging technique to visualize progressive axonal damage after brain injury in mice reveals responses to different minocycline treatments

A high-resolution, three-dimensional, optical imaging technique for the murine brain was developed to identify the effects of different therapeutic windows for preclinical brain research. This technique tracks the same cells over several weeks. We conducted a pilot study of a promising drug to treat diffuse axonal injury (DAI) caused by traumatic brain injury, using two different therapeutic windows, as a means to demonstrate the utility of this novel longitudinal imaging technique. DAI causes immediate, sporadic axon damage followed by progressive secondary axon damage. We administered minocycline for three days commencing one hour after injury in one treatment group and beginning 72 hours after injury in another group to demonstrate the method’s ability to show how and when the therapeutic drug exerts protective and/or healing effects. Fewer varicosities developed in acutely treated mice while more varicosities resolved in mice with delayed treatment. For both treatments, the drug arrested development of new axonal damage by 30 days. In addition to evaluation of therapeutics for traumatic brain injury, this hybrid microlens imaging method should be useful to study other types of brain injury and neurodegeneration and cellular responses to treatment