Neuropsychiatric signs and symptoms occur frequently in individuals with multiple sclerosis (MS), either as the initial presenting complaint prior to a definitive neurological diagnosis or more commonly with disease progression. However, the pathogenesis of these comorbid conditions remains unclear and it remains difficult to accurately elucidate if neuropsychiatric symptoms or conditions are indicators of MS illness severity. Furthermore, both the disease process and the treatments of MS can adversely impact an individual's mental health. In this review, we discuss the common neuropsychiatric syndromes that occur in MS and describe the clinical symptoms, aetiology, neuroimaging findings and management strategies for these conditions.

Purpose of Review Despite over a third of the world’s population being chronically infected with Toxoplasma gondii, little is known about this largely asymptomatic phase of infection. This stage is mediated in vivo by bradyzoites within tissue cysts. The absence of overt symptoms has been attributed to the dormancy of bradyzoites. In this review, we reexamine the conventional view of chronic toxoplasmosis in light of emerging evidence challenging both the nature of dormancy and the consequences of infection in the CNS. Recent Findings New and emerging data reveal a previously unrecognized level of physiological and replicative capacity of bradyzoites within tissue cysts. These findings have emerged in the context of a reexamination of the chronic infection in the brain that correlates with changes in neuronal architecture, neurochemistry, and behavior that suggest that the chronic infection is not without consequence. Summary The emerging data driven by the development of new approaches to study the progression of chronic toxoplasma infection reveals significant physiological and replicative capacity for what has been viewed as a dormant state. The emergence of bradyzoite and tissue cyst biology from what was viewed as a physiological “black box” offers exciting new areas for investigation with direct implications on the approaches to drug development targeting this drug-refractory state. In addition, new insights from studies on the neurobiology on chronic infection reveal a complex and dynamic interplay between the parasite, brain microenvironment, and the immune response that results in the detente that promotes the life-long persistence of the parasite in the host.

Seven fledging Adélie penguin Pygoscelis adeliae chicks and 4 post-moult adults were satellite tracked using the Argos system during the winters of 1995-97 and 1998, respectively. Six fledglings departed from Béchervaise Island near Mawson station (67°35' S, 62°49' E) during late February of 1996 and 1997 and were tracked for up to 5 mo before transmissions stopped. The 7th fledgling left Magnetic Island near Davis station (68°33' S, 77°54' E) in February 1995 and was tracked for 32 d. All fledglings travelled northward initially, then westward along the edge of the fast ice or in the pack-ice. Fledglings had travelled between 536 and 1931 km to the west of their natal colonies by the time transmissions ceased. Adult Adélie penguins were tracked between March and October 1998, following completion of their annual moult at Bechérvaise Island. Instruments were set to transmit for 2 h every 10th day over the first 5 mo and 1 d in 4 thereafter. Adult birds travelled westward until July, after which time they moved north within the expanding pack-ice into known areas of high krill concentration before returning eastward toward their breeding sites. Penguin movements over the winter months were closely related to those of sea ice in the region. Ice motion patterns were in turn influenced by gyral oceanic current systems and wind. We propose that large gyral oceanic systems provide a means for Adélie penguins to reduce costs of transport as they travel into regions of high productivity during winter and return to their breeding colonies in spring.

The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of poly(l-lysine) arms as potential nonviral gene delivery vectors for MSCs. We demonstrate that star-PLL vectors are capable of self-assembling with pDNA to form stable, cationic nanomedicines. Utilizing high content screening, live cell imaging, and mechanistic uptake studies we confirm the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which likely proceeds via a clathrin-independent mechanism. We identify a star-PLL composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a particularly efficient vector that is capable of delivering both reporter genes and the therapeutic transgenes bone morphogenetic protein-2 and vascular endothelial growth factor to MSCs. This composition facilitated a 1000-fold increase in transgene expression in MSCs compared to its linear analogue, linear poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to the widely used vector polyethylenimine using a lower pDNA dose with significantly less cytotoxicity. Overall, this study illustrates the ability of the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to MSCs thereby functioning as an innovative nanomedicine platform for tissue engineering applications.