The blood labyrinthine barrier in the human normal and Meniere's disease macula utricle.

The ultrastructural organization of the blood labyrinthine barrier (BLB) was investigated in the human vestibular endorgan, the utricular macula, using postmortem specimens from individuals with documented normal auditory and vestibular function and surgical specimens from patients with intractable Meniere's disease. Transmission electron microscopic analysis of capillaries located in the normal human utricular stroma showed vascular endothelial cells with few pinocytotic vesicles, covered by a smooth and uniform basement membrane surrounded by pericyte processes. Meniere's disease specimens revealed differential ultrastructural pathological changes in the cellular elements of the microvasculature. With moderate degeneration of the BLB, there were numerous vesicles within the vascular endothelial cells (VECs), with increased numbers at the abluminal face, pericyte process detachment and disruption of the perivascular basement membrane surrounding the VECs. With severe degeneration of the BLB, there was severe vacuolization or frank apparent necrosis of VECs and loss of subcellular organelles. A higher severity of BLB degenerative changes was associated with a higher degree of basement membrane thickening and edematous changes within the vestibular stroma. This study presents the first ultrastructural analysis of the capillaries constituting the BLB in the human vestibular macula utricle from normal and Meniere's disease

Voicing an Opinion: Authorship, Collaboration and the Judgments of Justice Bertha Wilson

In this paper, we spin the question “Will Women Judges Really Make a Difference?” in another direction. While “difference” is a big preoccupation for us, our interest is less in the question of whether or not men and women judge differently, than in the fact of difference between judges: “differences of opinion” between judges that find textual expression in the form of published dissenting opinions. Using Canada’s first woman Supreme Court justice as our point of departure, we consider the nature of judicial work. In Part II, looking at statistics, we sketch a portrait of Justice Wilson’s judicial work, attending to types of opinions (unanimous, majority, dissenting, concurring), and methods of participation (signing and authoring). We contextualize this portrait by considering Wilson’s work alongside that of colleagues with whom she sat. We follow two strands in this data. The first, very visible in Part II, focuses attention on particular judges, raising questions about difference, voice and identity. In Part III, influenced by the insights of institutional ethnography, we reflect on a second strand in the data, one that suggests room for more attention to the complex collaborative and institutional dimensions to the production of law. If the empirical snapshot can encourage attention to the role of difference in the work of Canada’s first woman Supreme Court justice, it should also encourage attention to the place of difference more generally in the making of law. The judgments of Justice Bertha Wilson can enable a robust discussion about the production of opinions, as well as nuance in our thinking about the implications of collaboration, authorship and voice

Cellular antiseizure mechanisms of everolimus in pediatric tuberous sclerosis complex, cortical dysplasia, and non-mTOR-mediated etiologies.

The present study was designed to examine the potential cellular antiseizure mechanisms of everolimus, a mechanistic target of rapamycin (mTOR) pathway blocker, in pediatric epilepsy cases. Cortical tissue samples obtained from pediatric patients (n = 11, ages 0.67-6.75 years) undergoing surgical resections for the treatment of their pharmacoresistant epilepsy were examined electrophysiologically in ex vivo slices. The cohort included mTOR-mediated pathologies (tuberous sclerosis complex [TSC] and severe cortical dysplasia [CD]) as well as non-mTOR-mediated pathologies (tumor and perinatal infarct). Bath application of everolimus (2 μm) had practically no effect on spontaneous inhibitory postsynaptic activity. In contrast, long-term application of everolimus reduced spontaneous excitatory postsynaptic activity, burst discharges induced by blockade of γ-aminobutyric acid A (GABAA) receptors, and epileptiform activity generated by 4-aminopyridine, a K+ channel blocker. The antiseizure effects were more pronounced in TSC and CD cases, whereas in non-mTOR-mediated pathologies, the effects were subtle at best. These results support further clinical trials of everolimus in mTOR pathway-mediated pathologies and emphasize that the effects require sustained exposure over time

A Free Community Approach to Classifying Disease

Defining and classifying disease is at the heart of medical practice, but the process is slow and laborious. A new "open source" approach could be faster and more democrati