Role of valued living and associations with functional outcome following traumatic brain injury

Valued living (VL) is associated with improved enjoyment and engagement with daily activities despite negative emotional state or ongoing pain. However, the role of VL in recovery following traumatic brain injury (TBI) has yet to be investigated. This study aimed to examine changes in VL over the course of recovery and variables associated with VL. Participants with moderate-to-severe TBI were recruited from a rehabilitation hospital in three cohorts: “Early” (n?=?25), “Mid” (n?=?9) and “Late” (n?=?36) post-TBI. All participants were assessed at time of recruitment and 12 months later. The main measure was the Valued Living Questionnaire. Compared to pre-injury estimates, VL was significantly reduced at 12 months post-injury. Levels of VL remained reduced between 2 and 3 years and increased between 3 and 6 years post-injury. VL was strongly associated with improved functional and psychosocial outcomes. Changes in VL occur over at least 3–5 years post-injury, with 12 months post-TBI a suitable time for intervention given VL remains low over the next 24 to 36 months post injury. Targeted intervention to modify values and/or valued activities to be consistent with post-injury capacity could improve rates of return to pre-injury levels of VL.     

The effects of living in an outdoor enclosure on hippocampal plasticity and anxiety‐like behavior in response to nematode infection

The hippocampus of rodents undergoes structural remodeling throughout adulthood, including the addition of new neurons. Adult neurogenesis is sensitive to environmental enrichment and stress. Microglia, the brain's resident immune cells, are involved in adult neurogenesis by engulfing dying new neurons. While previous studies using laboratory environmental enrichment have investigated alterations in brain structure and function, they do not provide an adequate reflection of living in the wild, in which stress and environmental instability are common. Here, we compared mice living in standard laboratory settings to mice living in outdoor enclosures to assess the complex interactions among environment, gut infection, and hippocampal plasticity. We infected mice with parasitic worms and studied their effects on adult neurogenesis, microglia, and functions associated with the hippocampus, including cognition and anxiety regulation. We found an increase in immature neuron numbers of mice living in outdoor enclosures regardless of infection. While outdoor living prevented increases in microglial reactivity induced by infection in both the dorsal and ventral hippocampus, outdoor mice with infection had fewer microglia and microglial processes in the ventral hippocampus. We observed no differences in cognitive performance on the hippocampus‐dependent object location task between infected and uninfected mice living in either setting. However, we found that infection caused an increase in anxiety‐like behavior in the open field test but only in outdoor mice. These findings suggest that living conditions, as well as gut infection, interact to produce complex effects on brain structure and function.     

A retrospective review of 1495 patients with obstetric anal sphincter injuries referred for assessment of function and endoanal ultrasonography

Aim

Obstetric anal sphincter injuries are a significant risk factor for faecal incontinence. Correct identification and successful primary repair are important. The aim of this study was to review the outcome of all patients, with an obstetric anal sphincter injury, referred to our unit.

Method

This is a retrospective review of 1495 patients over a 12-year period. All had a third or fourth degree tear and were referred at 4-months postpartum.

Results

Endoanal ultrasonography demonstrated residual sphincter defect in 792 (53%) and normal sphincters, with no evidence of repair, in 661 (44%). The majority of injuries involved both the external and internal sphincters (n = 501). Significant reductions in resting pressure and voluntary squeeze pressures were seen when those with a sphincter defect were compared to those with intact sphincters. However, there was no significant difference in the mean (SD) Cleveland Clinic faecal incontinence scores (5.8 (5.8) and 4.3 (5.5), p = 0.8).

Conclusion

Third and fourth degree tears appear to be over diagnosed. Primary repair appears to be unsuccessful in the majority of cases. There appears to be poor correlation between objective and subjective assessment of sphincter function.

     

Characterization of mouthguard materials: Physical and mechanical properties of commercialized products

ObjectivesContemporary mouthguard materials need to perform consistently over a wide range of possible temperatures (?20 to 40 °C). Therefore the specific aim of this study was to characterize commercialized mouthguard materials’ properties and investigate the effect of temperature on these properties.MethodsFive commercially representative thermoplastic mouthguard materials (Essix? Resin, Erkoflex?, Proform?-regular, Proform?-laminate, and Polyshok?) were tested. The durometer hardness, water absorption, tear strength, and impact attenuation of the mouthguard materials were measured according to ASTM D2240-05, D570-98 (2005), D624-00, and ASTM D6110-06f (modified) guidelines. Tests were conducted on five separate specimens at both room 23 ± 2 °C and intra-oral 37 ± 2 °C temperatures. Independent t-tests (α = 0.05) were used to test for differences between room and intra-oral temperatures.ResultsMaterial hardness decreased (p < 0.05) from room to intra-oral temperatures for all mouthguard materials. Water absorption increased (p < 0.05) from room to intra-oral temperatures for all mouthguard materials. Tear strength decreased (p < 0.05) from room to intra-oral temperatures for all mouthguard materials. Impact attenuation between room and intra-oral temperatures was different (p < 0.05) for the Erkoflex?, Proform?-laminate, and Polyshok? material respectfully. However, there was no difference between temperatures for the Essix? Resin (p = .058) or Proform?-regular (p = .275) materials.SignificanceTemperature measureably affects the physical and mechanical properties of mouthguard materials. It is particularly noteworthy that none of the commercialized products met current ANSI and SAI standards for impact attenuation.     

Identification, characterization, and implications of species-dependent plasma protein binding for the oral Hedgehog pathway inhibitor vismodegib (GDC-0449)

Vismodegib (GDC-0449) is is an orally available selective Hedgehog pathway inhibitor in development for cancer treatment. The drug is ≥95% protein bound in plasma at clinically relevant concentrations and has an approximately 200-fold longer single dose half-life in humans than rats. We have identified a strong linear relationship between plasma drug concentrations and α-1-acid glycoprotein (AAG) in a phase I study. Biophysical and cellular techniques have been used to reveal that vismodegib strongly binds to human AAG (K(D) = 13 μM) and binds albumin with lower affinity (K(D) = 120 μM). Additionally, binding to rat AAG is reduced ～20-fold relative to human, whereas the binding affinity to rat and human albumin was similar. Molecular docking studies reveal the reason for the signficiant species dependence on binding. These data highlight the utility of biophysical techniques in creating a comprehensive picture of protein binding across species.     

The effects of acute,chronic, and withdrawal from chronic nicotine on novel and spatial object recognition in male C57BL/6J mice

Rationale  

Spatial and novel object recognition learning is different from learning that uses aversive or appetitive stimuli to shape acquisition because no overt contingencies are needed. While this type of learning occurs on a daily basis, little is known about how nicotine administration affects it.     

Targeting maladaptive glutathione responses in lung disease

The lung is unique being exposed directly to the atmospheric environment containing xenobiotics, pathogens, and other agents which are continuously inhaled on a daily basis. Additionally, the lung is exposed to higher ambient oxygen levels which can promote the formation of a complex number of reactive oxygen and nitrogen species. Due to this constant barrage of potential damaging agents, the lung has developed a high degree of plasticity in dealing with ever changing conditions. In the present commentary, we will focus on glutathione (GSH) as a key antioxidant in the lung airways and discuss mechanisms by which the lung uses GSH to adapt to its rapidly changing environment. We will then examine the evidence on how defective and inadequate adaptive responses can lead to lung injury, inflammation and disease. Lastly, we will examine some of the recent attempts to alter lung GSH levels with therapies in a number of human lung diseases and discuss some of the limitations of such approaches.     

Nicotine ameliorates NMDA receptor antagonist-induced deficits in contextual fear conditioning through high-affinity nicotinic acetylcholine receptors in the hippocampus

NMDA glutamate receptors (NMDARs) and nicotinic acetylcholine receptors (nAChRs) are both involved in learning and synaptic plasticity. Increasing evidence suggests processes mediated by these receptors may interact to modulate learning; however, little is known about the neural substrates involved in these interactive processes. The present studies investigated the effects of nicotine on MK-801 hydrogen maleate (MK-801) and DL-2-Amino-5-phosphonovaleric acid (APV)-induced disruption of contextual fear conditioning in male C57BL/6J mice, using direct drug infusion and selective nAChR antagonists to define the brain regions and the nAChR subtypes involved. Mice treated with MK-801 showed a deficit in contextual fear conditioning that was ameliorated by nicotine. Direct drug infusion demonstrated that the NMDAR antagonists disrupted hippocampal function and that nicotine acted in the dorsal hippocampus to ameliorate the deficit in learning. The high-affinity nAChR antagonist Dihydro-β-erythroidine hydrobromide (DhβE) blocked the effects of nicotine on MK-801-induced deficits while the α7 nAChR antagonist methyllycaconitine citrate salt hydrate (MLA) did not. These results suggest that NMDARs and nAChRs may mediate similar hippocampal processes involved in contextual fear conditioning. Furthermore, these results may have implications for developing effective therapeutics for the cognitive deficits associated with schizophrenia because a large subset of patients with schizophrenia exhibit cognitive deficits that may be related to NMDAR dysfunction and smoke at much higher rates than the healthy population, which may be an attempt to ameliorate cognitive deficits.     

Counsel with care

Studies have shown that mass counselling after a disaster is unnecessary, but a minority of people benefit from specialist support.