2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Assessing Risk in Focal Arboviral Infections: Are We Missing the Big or Little Picture?

Focal arboviral infections affecting a subset of the overall population present an often overlooked set of challenges in the assessment and reporting of risk and the detection of spatial patterns. Our objective was to assess the variation in risk when using different at-risk populations and geographic scales for the calculation of incidence risk and the detection of geographic hot-spots of infection. We explored these variations using a pediatric arbovirus, La Crosse virus (LACV), as our model.Descriptive and cluster analyses were performed on probable and confirmed cases of LACV infections reported to the Tennessee Department of Health from 1997 to 2006, using three at-risk populations (the total population, the population 18 years and younger, and the population 15 years and younger) and at two geographic levels (county and census tract) to assess the variation in incidence risk and to investigate evidence of clustering using both global and local spatial statistics. We determined that the most appropriate at-risk population to calculate incidence risk and to assess the evidence of clustering was the population 15 years and younger. Based on our findings, the most appropriate geographical level to conduct spatial analyses and report incidence risk is the census tract level. The incidence risk in the population 15 years and younger at the county level ranged from 0 to 226.5 per 100,000 persons (median 41.5) in those counties reporting cases (n = 14) and at the census tract level it ranged from 50.9 to 673.9 per 100,000 persons (median 126.7) in those census tracts reporting cases (n = 51). To our knowledge, this is the highest reported incidence risk for this population at the county level for Tennessee and at the census tract level nationally.The results of this study indicate the possibility of missing disease clusters resulting from performing incidence risk investigations of focal diseases using inappropriate at-risk populations and/or at large geographic scales. Improved disease surveillance and health planning will result through the use of well defined at-risk populations and the use of appropriate geographic scales for the analysis and reporting of diseases. The finding of a high incidence risk of LACV infections in eastern Tennessee demonstrates that the vast majority of these infections continue to be under-diagnosed and/or underreported in this region. Persistent prevention and surveillance efforts will be required to reduce exposure to infectious vectors and to detect new cases of infection in this region. Application of this study's observations in future investigations will enhance the quantification of incidence risk and the identification of high-risk groups within the population