A robust and reproducible human pluripotent stem cell derived model of neurite outgrowth in a three-dimensional culture system and its application to study neurite inhibition.

The inability of neurites to grow and restore neural connections is common to many neurological disorders, including trauma to the central nervous system and neurodegenerative diseases. Therefore, there is need for a robust and reproducible model of neurite outgrowth, to provide a tool to study the molecular mechanisms that underpin the process of neurite inhibition and to screen molecules that may be able to overcome such inhibition. In this study a novel in vitro pluripotent stem cell based model of human neuritogenesis was developed.

Radiological differentiation of optic neuritis with myelin oligodendrocyte glycoprotein antibodies, aquaporin-4 antibodies, and multiple sclerosis.

Background: Recognizing the cause of optic neuritis (ON) affects treatment decisions and visual outcomes.

Objective: We aimed to define radiological features of first-episode demyelinating ON.

Methods: We performed blinded radiological assessment of 50 patients presenting with first-episode myelin oligodendrocyte glycoprotein (MOG) antibody-associated ON (MOG-ON; n=19), aquaporin-4 (AQP4) antibody-associated ON (AQP4-ON; n=11), multiple sclerosis (MS)-associated ON (MS-ON; n=13), and unclassified ON (n=7).

Successful treatment of Cryptococcus neoformans immune reconstitution inflammatory syndrome in an immunocompetent host using thalidomide.

Immune reconstitution inflammatory syndrome (IRIS) can complicate antifungal treatment of cryptococcosis. There are limited data on managing cryptococcal-associated IRIS. We describe an immunocompetent patient who developed IRIS complicating Cryptococcus neoformans meningitis, successfully treated with thalidomide following failure of corticosteroid therapy.

Design and biological evaluation of synthetic retinoids: probing length vs. stability vs. activity.

All trans-retinoic acid (ATRA) is widely used to direct the differentiation of cultured stem cells. When exposed to the pluripotent human embryonal carcinoma (EC) stem cell line, TERA2.cl.

The action of all-trans-retinoic acid (ATRA) and synthetic retinoid analogues (EC19 and EC23) on human pluripotent stem cells differentiation investigated using single cell infrared microspectroscopy.

All trans-retinoic acid (ATRA) is widely used to direct the differentiation of cultured stem cells. When exposed to the pluripotent human embryonal carcinoma (EC) stem cell line, TERA2.cl.

Early factors associated with axonal loss after optic neuritis.

Objective: Acute optic neuritis due to an inflammatory demyelinating lesion of the optic nerve is often seen in association with multiple sclerosis. Although functional recovery usually follows the acute episode of visual loss, persistent visual deficits are common and are probably due to axonal loss. The mechanisms of axonal loss and early features that predict it are not well defined.

Novel silicon-containing analogues of the retinoid agonist bexarotene: syntheses and biological effects on human pluripotent stem cells.

Twofold sila-substitution (C/Si exchange) of the clinically used RXR-selective retinoid agonist bexarotene leads to disila-bexarotene, which displays pharmacological potency similar to that of the parent carbon compound, as shown in a HeLa-cell-based RXR assay. Formal exchange of the SiCH₂CH₂ Si group in disila-bexarotene with a SiCH₂Si or SiOSi moiety leads to the disila-bexarotene analogues 8 and 9. The silicon compounds 8 and 9 were synthesized in multistep syntheses, starting from HC≡C(CH₃)₂SiCH₂Si(CH₃)₂C≡CH and HC≡C(CH₃)₂SiOSi(CH₃)₂C≡CH, respectively.

Retinoid supplementation of differentiating human neural progenitors and embryonic stem cells leads to enhanced neurogenesis in vitro.

Retinoids are important molecules involved in the development and homeostasis of the nervous system. As such, various retinoid derivatives are often found in culture media and supplement formulations to support the growth and maintenance of neural cells. However, all-trans-retinoic acid (ATRA) and its associated derivatives are light sensitive and are highly susceptible to isomerisation.

A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials.

Following an episode of optic neuritis, thinning of the retinal nerve fibre layer, which indicates axonal loss, is observed using optical coherence tomography. The longitudinal course of the retinal changes has not been well characterized. We performed a serial optical coherence tomography study in patients presenting with optic neuritis in order to define the temporal evolution of retinal nerve fibre layer changes and to estimate sample sizes for proof-of-concept trials of neuroprotection using retinal nerve fibre layer loss as the outcome measure.

Neuroplasticity predicts outcome of optic neuritis independent of tissue damage.

Objectives: To determine whether lateral occipital complex (LOC) activation with functional magnetic resonance imaging (fMRI) predicts visual outcome after clinically isolated optic neuritis (ON). To investigate the reasons behind good recovery following ON, despite residual optic nerve demyelination and neuroaxonal damage.

Methods: Patients with acute ON and healthy volunteers were studied longitudinally over 12 months.

A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis.

Thinning of the retinal nerve fiber layer (RNFL) of clinically unaffected eyes is seen in patients with multiple sclerosis (MS). It is uncertain when this thinning occurs, and whether ongoing RNFL loss can be measured over time with optical coherence tomography (OCT). Using time-domain OCT, we studied 34 patients with progressive MS (16 primary progressive MS, 18 secondary progressive; 14 male; 20 female; mean age at study entry 51 years; median EDSS 6; mean disease duration at study entry 12 years) on two occasions with a median interval of 575 (range 411-895) days apart.

Multiple sclerosis: distribution of inflammatory cells in newly forming lesions.

Objective: CD4 T-cell-dependent macrophage activation directed against a myelin or oligodendrocyte antigen is generally thought to be the mechanism causing myelin destruction in multiple sclerosis (MS). However, areas within expanding MS lesions may exhibit prominent oligodendrocyte loss and apoptosis in the absence of infiltrating lymphocytes. The present study was designed to further investigate the inflammatory profile of different regions within rapidly expanding MS lesions.

Assessing structure and function of the afferent visual pathway in multiple sclerosis and associated optic neuritis.

The afferent visual pathway is commonly affected in MS. Assessment of the afferent visual pathway using clinical, imaging and electrophysiological methods not only provides insights into the pathophysiology of MS, but also provides a method of investigating potential therapeutic measures in MS. This review summarises the various assessment methods, in particular imaging techniques of the visual pathway.

A novel isotherm, modeling self-assembled monolayer adsorption and structural changes.

Self-assembled monolayers (SAMs) have numerous applications, for example, engine wear inhibitors, surface profiling signal enhancement, nanostructure production, sensor production, and catalysis. The adsorbed SAM structure has a major impact on the properties of the outer monolayer surface which dictates the performance and viability of the SAM for individual applications. Substrate growth phases of SAMs have been extensively studied, and two structures have been identified.

An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography.

Axonal loss is thought to be the predominant cause of disability in progressive multiple sclerosis (MS). The retinal nerve fibre layer (RNFL) is composed largely of unmyelinated axons of retinal ganglion cells, and is accessible to study with optical coherence tomography (OCT), giving a measure of axonal loss. OCT measures of the RNFL thickness (RNFLT) and macular volume were studied in 23 patients with primary progressive multiple sclerosis (primary progressive MS) (13 male; 10 female; mean age 52 years; median EDSS 6.