Our results reveal that frequent occurrence of SD in MS patients prominently affects all aspects of their quality of life.

Lesions in strategic brain WM tracts contribute to cognitive impairment in MS through a multisystem disconnection syndrome.

The in vitro generation of neural cells from human embryonic stem cells is a powerful tool to acquire better knowledge of the cellular and molecular events involved in early human neural and brain development under physiological and pathological conditions. Prenatal alcohol exposure can induce important anomalies in the developing brain, the embryogenesis being an important critical period for the craniofacial defects and mental disabilities associated with fetal alcohol syndrome. Here, we report the generation of neural progenitors (NPs) from human embryonic stem cells. Neuroepithelial progenitors display the morphological and functional characteristics of their embryonic counterparts and the proper timing of neurons and glia cells generation. Immunocytochemical and real time (RT)-polymerase chain reaction analyses reveal that cells appeared as clusters during neuroepithelial cell proliferation and that the genes associated with the neuroectodermal (Pax-6) and the endodermic (α-fetoprotein) lineages decreased in parallel to the upregulation of the genes of NPs (nestin and Tuj1), followed by their differentiation into neurons (MAP-2+, GABA+), oligodendrocytes [galactocerebroside (GalC+)], and astrocytes (GFAP+). We further demonstrate, for the first time, that human NPs express the endocannabinoid receptors (CB1 and CB2) and the enzymes involved in endocannabinoids synthesis (NAPE-PLD) and degradation (FAAH). Using this in vitro culture, we demonstrate that ethanol exposure impairs NPs survival, affects the differentiation of NPs into neurons and astrocytes, disrupts the actin cytoskeleton, and affects the expression of different genes associated with neural differentiation. The results provide new insights into the effects of ethanol on human embryogenesis and neuroprogenitors and offer an opportunity to delineate potential therapeutic strategies to restore early ethanol-induced brain damage.

The objective of this study was to translate the MSQOL-54 into Serbian, and investigate the validity of the translated and cross-culturally adapted inventory in Serbian MS patients. The questionnaire was validated in 200 consecutive MS patients seen between February and September 2005 at the Institute of Neurology, Clinical center of Serbia, in Belgrade. The translation followed an internationally accepted methodology. Associations between age, gender, education, marital and employment status, disease course, the expanded disability status scale (EDSS) score, and the MSQOL-54 physical and mental health composite scores were determined. Patients' participation in the assessment was satisfactory and all scales fulfilled the usual psychometric standards. Highly significant inverse relationship was found between both composite scores and clinical characteristics of the disease, the EDSS and the disease course. Additionally, both composite scores, correlated significantly with patients' age, education and employment status. The Serbian-translated version of this questionnaire may be useful as clinical outcome measures in patients with MS.

Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal‐free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions. A simple medium formula including insulin induces the direct conversion of >98% of hESCs and hiPSCs into expandable, transplantable, and functional neural progenitors with neural rosette characteristics. Further differentiation of neural progenitors into dopaminergic and spinal motoneurons as well as astrocytes and oligodendrocytes indicates that these neural progenitors retain responsiveness to instructive cues revealing the robust applicability of the protocol in the treatment of different neurodegenerative diseases. The fact that this protocol includes animal‐free medium and human extracellular matrix components avoiding embryoid bodies makes this protocol suitable for the use in clinic. Stem Cells Translational Medicine 2017;6:1217–1226