Serious games are computer-based games designed for training purposes. They are poised to expand their role in medical education. This systematic review, conducted in accordance with PRISMA guidelines, aimed to synthesize current serious gaming trends in health care training, especially those pertaining to developmental methodologies and game evaluation. PubMed, EMBASE, and Cochrane databases were queried for relevant documents published through December 2014. Of the 3737 publications identified, 48 of them, covering 42 serious games, were included. From 2007 to 2014, they demonstrate a growth from 2 games and 2 genres to 42 games and 8 genres. Overall, study design was heterogeneous and methodological quality by MERQSI score averaged 10.5/18, which is modest. Seventy-nine percent of serious games were evaluated for training outcomes. As the number of serious games for health care training continues to grow, having schemas that organize how educators approach their development and evaluation is essential for their success.

Latrepirdine (Dimebon™) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer’s disease, with a dramatically positive outcome in a Russian clinical trial that was unconfirmed in a replication trial in the United States. We sought to determine whether latrepirdine-stimulated APP catabolism is at least partially attributable to regulation of macroautophagy, a highly conserved protein catabolism pathway that is known to be impaired in brains of patients with Alzheimer’s disease (AD). We utilized several mammalian cellular models to determine whether latrepirdine regulates mTOR- and Atg5-dependent autophagy. Male TgCRND8 mice were chronically administered latrepirdine prior to behavior analysis in the cued and contextual fear conditioning paradigm, as well as immunohistological and biochemical analysis of AD-related neuropathology. Treatment of cultured mammalian cells with latrepirdine led to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine treatment of TgCRND8 transgenic mice was associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. We conclude that latrepirdine possesses pro-autophagic properties in addition to the previously reported pro-neurogenic properties, both of which are potentially relevant to the treatment and/or prevention of neurodegenerative diseases. We suggest that elucidation of the molecular mechanism(s) underlying latrepirdine effects on neurogenesis, autophagy, and behavior might warranty the further study of latrepirdine as a potentially viable lead compound that might yield more consistent clinical benefit following optimization of its pro-neurogenic, pro-autophagic, and/or pro-cognitive activities.

Latrepirdine (Dimebon; dimebolin) is a neuroactive compound that was associated with enhanced cognition, neuroprotection, and neurogenesis in laboratory animals, and has entered phase II clinical trials for both Alzheimer’s (AD) and Huntington’s diseases (HD). Based on recent indications that latrepirdine protects cells against cytotoxicity associated with expression of aggregatable neurodegeneration-related proteins, including Aβ42 and γ-synuclein, we sought to determine whether latrepirdine offers protection to Saccharomyces cerevisiae (S. cerevisiae). We utilized separate and parallel expression in yeast of several neurodegeneration-related proteins, including α-synuclein, the amyotrophic lateral sclerosis-associated genes TDP43 and FUS, and the HD-associated protein huntingtin with a 103 copy-polyglutamine expansion (HTT gene; htt-103Q). Latrepirdine effects on α-synuclein clearance and toxicity were also measured following treatment of SH-SY5Y cells or chronic treatment of wildtype mice. Latrepirdine only protected yeast against the cytotoxicity associated with α-synuclein, and this appeared to occur via induction of autophagy. We further report that latrepirdine stimulated the degradation of α-synuclein in differentiated SH-SY5Y neurons, and in mouse brain following chronic administration, in parallel with elevation of the levels of markers autophagic activity. Ongoing experiments will determine the utility of latrepirdine to abrogate α-synuclein accumulation in transgenic mouse models of α-synuclein neuropathology. We propose that latrepirdine may represent a novel scaffold for discovery of robust pro-autophagic/anti-neurodegeneration compounds, that might yield clinical benefit for synucleinopathies including PD, Lewy body dementia, REM sleep disorder, and/or multiple system atrophy, following optimization of its pro-autophagic and pro-neurogenic activities.

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