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Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that is caused by inactivating mutations in the Survival of motor neuron 1 (SMN1) gene, resulting in decreased SMN protein expression. Humans possess a paralog gene, SMN2, which contains a splicing defect in exon 7 leading to diminished expression of full-length, fully functional SMN protein. Increasing SMN2 expression has been a focus of therapeutic development for SMA. Multiple studies have reported the efficacy of histone deacetylase inhibitors (HDACi) in this regard. However, clinical trials involving HDACi have been unsatisfactory, possibly because previous efforts to identify HDACi to treat SMA have employed non-neuronal cells as the screening platform. To address this issue, we generated an SMA-patient specific, induced pluripotent stem cell (iPSC) derived neuronal cell line that contains homogenous Tuj1 + neurons. We screened a small library of cyclic tetrapeptide HDACi using this SMA neuronal platform and discovered compounds that elevate SMN2 expression by an impressive twofold or higher. These candidates are also capable of forming gems intranuclearly in SMA neurons, demonstrating biological activity. Our study identifies new potential HDACi therapeutics for SMA screened using a disease-relevant SMA neuronal cellular model.

Background Sports anemia is a widely observed phenomenon after prolonged running. There are various factors that contribute to sports anemia, including hemodilution, exercise-induced oxidative stress, iron deficiency, gastrointestinal bleeding, hematuria, and hemolysis resulting from foot-strike and/or from compression of contracting muscles on capillaries. Until now, there has been no published report that describes the overall hematological, urinary, and fecal consequences in Asian male ultramarathoners after a 100-km (62.5-mile) ultramarathon event. Methods A total of 25 male runners were recruited into our study. Blood was drawn 1 week before, immediately after, and then 24 hours subsequent to the race. Hematological samples were analyzed for the anemia phenomenon. Additionally, urinary and fecal samples were collected before and after the race for detection of occult blood. Results The blood hemoglobin and erythropoietin values of the recruited runners showed a statistically significant rise in the immediate post-race values and a rapid drop in values at 24 hours post-race. Blood concentrations of red blood cells and hematocrit were significantly lower at 24 hours post-race compared with pre-race. The white blood cell count, interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, and ferritin all showed significant increases both immediately after and 24 hours post-race compared with pre-race hematological values. There were immediate decreases of both haptoglobin and iron, as well as an increase of total iron-binding capacity levels in post-race blood tests. For both urinary and fecal samples, there was a statistically significant difference between the pre- and post-race results in occult blood. Conclusion Running a 100-km ultramarathon will induce substantial sports anemia, and oxidative stress response, hemolysis, hematuria, and gastrointestinal bleeding are typical factors that contribute to its onset.

Background: Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis. The relationship between the geriatric population and tuberculous pleural effusion has rarely been studied. Methods: This is a retrospective study. From January 2005 through February 2009, we retrospectively enrolled 51 patients older than 18 years of age that were diagnosed with tuberculous pleurisy. We analyzed the clinical presentations and laboratory data of pleural effusion in elderly and adult groups. Results: Of these patients, 32 were more than 65 years of age (elderly group) and 19 were less than 65 years of age (adult group). Chest pain occurred more frequently in the adult group than the elderly group (52.6 % vs. 15.6 %; p