The My Active and Healthy Aging ICT platform prevents quality of life decline in older adults: a randomised controlled study.

INTRODUCTION: Prevention of frailty is paramount in older adults. We evaluated the efficacy of a tailored multidomain intervention, monitored with the My Active and Healthy Aging platform, in reducing conversion from a prefrail status to overt frailty and preventing decline in quality of life. METHODS: We performed a multicentre, multicultural, randomised control study. The effects of multidomain interventions on frailty parameters, quality of life, physical, cognitive, psychosocial function, nutrition and sleep were evaluated in a group of 101 prefrail older subjects and compared with 100 prefrail controls, receiving general health advice. RESULTS: At the 12-month assessment, controls showed a decline in quality of life that was absent in the active group. In addition, active participants showed an increase in mood and nutrition function. No effect on remaining parameter was observed. DISCUSSION: Our study supports the use of personalised multidomain intervention, monitored with an information and communication technology platform, in preventing quality of life decline in older adults.

Differentiation of human telencephalic progenitor cells into MSNs by inducible expression of Gsx2 and Ebf1.

Medium spiny neurons (MSNs) are a key population in the basal ganglia network, and their degeneration causes a severe neurodegenerative disorder, Huntington's disease. Understanding how ventral neuroepithelial progenitors differentiate into MSNs is critical for regenerative medicine to develop specific differentiation protocols using human pluripotent stem cells. Studies performed in murine models have identified some transcriptional determinants, including GS Homeobox 2 (Gsx2) and Early B-cell factor 1 (Ebf1). Here, we have generated human embryonic stem (hES) cell lines inducible for these transcription factors, with the aims of (i) studying their biological role in human neural progenitors and (ii) incorporating TF conditional expression in a developmental-based protocol for generating MSNs from hES cells. Using this approach, we found that Gsx2 delays cell-cycle exit and reduces Pax6 expression, whereas Ebf1 promotes neuronal differentiation. Moreover, we found that Gsx2 and Ebf1 combined overexpression in hES cells achieves high yields of MSNs, expressing Darpp32 and Ctip2, in vitro as well in vivo after transplantation. We show that hES-derived striatal progenitors can be transplanted in animal models and can differentiate and integrate into the host, extending fibers over a long distance.

The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol.

INTRODUCTION: Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%-12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults. METHOD: The My Active and Healthy Aging (My-AHA) consortium has developed an information and communications technology-based platform to support active and healthy aging through early detection of prefrailty and provision of individually tailored interventions, targeting multidomain risks for frailty across physical activity, cognitive activity, diet and nutrition, sleep, and psychosocial activities. Six hundred adults aged 60 years and older will be recruited to participate in a multinational, multisite 18-month randomized controlled trial to test the efficacy of the My-AHA platform to detect prefrailty and the efficacy of individually tailored interventions to prevent development of clinical frailty in this cohort. A total of 10 centers from Italy, Germany, Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and Australia will participate in the randomized controlled trial. RESULTS: Pilot testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been completed with a small group of older adults in Europe with the full randomized controlled trial scheduled to commence in 2018. DISCUSSION: The My-AHA study will expand the understanding of antecedent risk factors for clinical frailty so as to deliver targeted interventions to adults with prefrailty. Through the use of an information and communications technology platform that can connect with multiple devices within the older adult's own home, the My-AHA platform is designed to measure an individual's risk factors for frailty across multiple domains and then deliver personalized domain-specific interventions to the individual. The My-AHA platform is technology-agnostic, enabling the integration of new devices and sensor platforms as they emerge.

High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly.

Hydrocephalus is a common and variegated pathology often emerging in newborn children after genotoxic insults during pregnancy (Hicks and D'Amato, 1980). Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle and survival. Here we show, by using three independent nestin Cre transgenic lines, that high levels of Cre recombinase expression into the nucleus of neuronal progenitors can compromise normal brain development. The transgenics analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase with a nuclear localization signal, and two nestin CreER(T2) (Cre recombinase fused with a truncated estrogen receptor) mice lines with different levels of expression of a hybrid CreER(T2) recombinase that translocates into the nucleus after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed reduced neuronal proliferation, increased aneuploidy and cell death, as well as defects in ependymal lining and lamination of the cortex, leading to microencephaly and to a form of communicating hydrocephalus. An essentially overlapping phenotype was observed in the two nestin CreER(T2) transgenic lines after tamoxifen mediated-CreER(T2) translocation into the nucleus. Neither tamoxifen-treated wild-type nor nestin CreER(T2) oil-treated control mice displayed these defects. These results indicate that some forms of hydrocephalus may derive from a defect in neuronal precursors proliferation. Furthermore, they underscore the potential risks for developmental studies of high levels of nuclear Cre in neurogenic cells.

Somatodendritic minicolumns of output neurons in the rat visual cortex.

The apical dendrites of the pyramidal neurons of the cerebral cortex form radial bundles in all species and areas. Using microtubule-associated protein (MAP)2 immunostaining and Voronoi tessellation analysis in the rat visual cortex, we obtained objective criteria to define dendritic bundles in tangential sections: in supragranular layers of the rat visual cortex we found bundles of 6-6.4 dendrites, at a density of 1929 bundles/mm(2) and a centre-to-centre distance of 27 micro m. Using lipophilic tracers to label different pyramidal cell populations, based on the same criteria as in MAP2-immunostained material, we found that in the rat visual cortex the bundles consist of neurons with specific targets. Neurons projecting to the ipsi- or contralateral cortex form bundles together and with neurons projecting to the striatum, but not with those projecting to the superior colliculus, dorsal division of the lateral geniculate nucleus or through the cerebral peduncle. The latter neurons form bundles with neurons projecting to the striatum. Thus, the cerebral cortex is organized in minicolumns of output neurons visible at the earliest ages studied (P3), which might have a higher probability of being interconnected than those outside.