Staurosporine‐induced collapse of cochlear hair bundles

Early postnatal mouse cochlear cultures were treated with a small panel of kinase inhibitors to elucidate the mechanisms underlying the maintenance of hair‐bundle structure in the developing inner ear. At low concentrations (1–10 nM), staurosporine causes the collapse and loss of hair bundles without provoking hair‐cell death, as judged by lack of terminal transferase dUTP nick end labeling (TUNEL) labeling or reactivity to anti‐activated caspase‐3. Staurosporine exposure results in the fusion of the hair bundle's stereocilia, a resorption of the parallel actin bundles of the stereocilia into the cytoplasm of the hair cell, a detachment of the apical, non‐stereociliary membrane of the hair cell from the underlying cuticular plate, and a severing of the hair‐bundle's rootlets from the actin cores of the stereocilia. It does not block membrane retrieval at the apical pole of the hair cells, nor does it elicit the externalization of phosphatidylserine. Staurosporine treatment causes a reduction in levels of the phosphorylated forms of ezrin, radixin, and moesin in cochlear cultures during the period of hair‐bundle loss, indicating the integrity of the hair bundle may be actively maintained by the phosphorylation status of these proteins. J. Comp. Neurol. 522:3281–3294, 2014. © 2014 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.     

Epiretinal membrane: a treatable cause of visual disability in myotonic dystrophy type 1

A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p < 0.001)]. Macular thickness was significantly greater (p < 0.005) in five of the nine macular regions. The increase in macular thickness was due to the increased prevalence of epiretinal membranes in the myotonic dystrophy patient group (p = 0.0002): 48.2 % of myotonic dystrophy patient eyes had evidence of epiretinal membrane, compared with 12.5 % of control eyes. Examination revealed that 56.7 % of myotonic dystrophy patients had an epiretinal membrane in at least one eye. Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity.     

Changing gender roles and attitudes and their implications for well-being around the new millennium

Purpose

Given evidence that gender role attitudes (GRAs) and actual gender roles impact on well-being, we examine associations between GRAs, three roles (marital status, household chore division, couple employment) and psychological distress in working-age men and women. We investigate time-trends reflecting broader social and economic changes, by focusing on three age groups at two dates.

Methods

We used British Household Panel Survey data from 20- to 64-year-olds in heterosexual couple households in 1991 (N = 5,302) and 2007 (N = 6,621). We examined: levels of traditional GRAs according to gender, age, date, household and employment roles; associations which GRAs and roles had with psychological distress (measured via the GHQ-12); whether psychological distress increased when GRAs conflicted with actual roles; and whether any of these associations differed according to gender, age or date.

Results

Gender traditionalism was lower among women, younger people, those participating in 2007 and in ‘less traditional’ relationships and households. Psychological distress was higher among those with more traditional GRAs and, particularly among men, for those not employed, and there was some evidence of different patterns of association according to age-group. There was limited evidence, among women only, of increased psychological distress when GRAs and actual roles conflicted and/or reductions when GRAs and roles agreed, particularly in respect of household chores and paid employment.

Conclusions

Although some aspects of gender roles and attitudes (traditionalism and paid employment) are associated with well-being, others (marital status and household chores), and attitude-role consistency, may have little impact on the well-being of contemporary UK adults.     

Screening,Intervention and Outcome in Autism and Other Developmental Disorders: The Role of Randomized Controlled Trials

We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism—or of other developmental disorders—that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated.     

Internally Displaced “Victims of Armed Conflict” in Colombia: The Trajectory and Trauma Signature of Forced Migration

While conflict-induced forced migration is a global phenomenon, the situation in Colombia, South America, is distinctive. Colombia has ranked either first or second in the number of internally displaced persons for 10 years, a consequence of decades of armed conflict compounded by high prevalence of drug trafficking. The displacement trajectory for displaced persons in Colombia proceeds through a sequence of stages: (1) pre-expulsion threats and vulnerability, (2) expulsion, (3) migration, (4) initial adaptation to relocation, (5) protracted resettlement (the end point for most forced migrants), and, rarely, (6) return to the community of origin. Trauma signature analysis, an evidence-based method that elucidates the physical and psychological consequences associated with exposures to harm and loss during disasters and complex emergencies, was used to identify the psychological risk factors and potentially traumatic events experienced by conflict-displaced persons in Colombia, stratified across the phases of displacement. Trauma and loss are experienced differentially throughout the pathway of displacement.     

Reduced thymic output and peripheral naïve CD4 T-cell alterations in primary progressive multiple sclerosis (PPMS)

We compared na?ve CD4 and CD8 T-cell homeostasis in primary progressive multiple sclerosis (PPMS), relapsing-remitting MS (RRMS) and controls. Quantitation of signal joint T-cell receptor (TCR) excision circles (sjTRECs) and quantitative estimates of daily thymic export confirm our previous report of reduced thymic output in RRMS and demonstrate reduced thymic output in PPMS. In PPMS, the decreasing % CD31+ na?ve CD4 T-cells but constant sjTRECs and constant na?ve CD4 T-cell numbers with age, together with increased Bcl-2 expression suggest increased TCR signaling with increased na?ve T-cell survival. We conclude PPMS patients have peripheral immune alterations related to reduced thymic output.     

Dietary treatments: the road from Phoenix to Edinburgh

The ketogenic diet is now an established treatment in children for drug resistant epilepsy. Although in use for almost 100 years, it has taken time for us to determine an evidence base to verify its use in these children. However, increasing research both from a clinical and basic science perspective as well as a wide clinical interest has now enabled its use throughout the world. This aside, there remains lack of resources to guarantee its availability to all those who may be suitable. It is also now quite clear that it may have benefit in wider areas of neurology beyond epilepsy, specifically in metabolic disorders where glucose cannot be used as a primary energy source.     

Alzheimer's disease and epilepsy: insight from animal models

Alzheimer's disease (AD) and epilepsy are separated in the medical community, but seizures occur in some patients with AD, and AD is a risk factor for epilepsy. Furthermore, memory impairment is common in patients with epilepsy. The relationship between AD and epilepsy remains an important question because ideas for therapeutic approaches could be shared between AD and epilepsy research laboratories if AD and epilepsy were related. Here we focus on one of the many types of epilepsy, temporal lobe epilepsy (TLE), because patients with TLE often exhibit memory impairment, depression and other comorbidities that occur in AD. Moreover, the seizures that occur in patients with AD may be nonconvulsive, which occur in patients with TLE. Here we first compare neuropathology in TLE and AD with an emphasis on the hippocampus, which is central to both AD and TLE research. Then we compare animal models of AD pathology with animal models of TLE. Although many aspects of the comparisons are still controversial, there is one conclusion that we suggest is clear: some animal models of TLE could be used to help address questions in AD research, and some animal models of AD pathology are bona fide animal models of epilepsy.     

A study of neurocognition in bulimia nervosa and eating disorder not otherwise specified-bulimia type

Neurocognition in bulimia nervosa (BN) is under-researched. This study investigated aspects of attention (d2-Letter Cancellation Task), inhibitory control (Stroop and go/no-go task), and decision making (Game of Dice Task) in 40 people with BN, 30 with eating disorder not otherwise specified-BN type (EDNOS-BN), and 65 healthy controls (HCs). The National Adult Reading Test (NART) and Depression Anxiety Stress Scale (DASS-21) were also administered. Analyses of covariance (covariates: age, NART, and DASS-21) showed that people with BN and EDNOS-BN performed as well as HCs on all tasks. Attention task performance was poorer in the EDNOS-BN than in the BN group.