Here, we describe that lysine-specific demethylase 1 (Lsd1/KDM1a), which demethylates histone H3 on Lys4 or Lys9 (H3K4/K9), is an indispensible epigenetic governor of hematopoietic differentiation. Integrative genomic analysis, combining global occupancy of Lsd1, genome-wide analysis of its substrates H3K4 monomethylation and dimethylation, and gene expression profiling, reveals that Lsd1 represses hematopoietic stem and progenitor cell (HSPC) gene expression programs during hematopoietic differentiation. We found that Lsd1 acts at transcription start sites, as well as enhancer regions. Loss of Lsd1 was associated with increased H3K4me1 and H3K4me2 methylation on HSPC genes and gene derepression. Failure to fully silence HSPC genes compromised differentiation of hematopoietic stem cells as well as mature blood cell lineages. Collectively, our data indicate that Lsd1-mediated concurrent repression of enhancer and promoter activity of stem and progenitor cell genes is a pivotal epigenetic mechanism required for proper hematopoietic maturation.DOI: http://dx.doi.org/10.7554/eLife.00633.001

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To investigate the major injury patterns associated with traffic accidents and evaluate the risk factors of the main injury, a survey of Taiwan's national insurance admission data between 2002 and 2011 was performed. The incidence of traffic-accidents-related hospitalization was between 9.17% and 11.54% and the average mortality rate of the inpatients admitted due to traffic accidents was 0.68%. Of all inpatients due to road traffic accidents in Taiwan, orthopedic fractures were the most common injuries that accounted for 29.36% of them. There were a total of 391,197 cases of three orthopedic fracture groups that were divided into (1) fracture of upper limb, (2) fracture of lower limb, and (3) fracture of spine and trunk. An increase in national medical cost used for inpatients with orthopedic fractures was noted and ranged from US$ 45.6 million to US$ 86 million annually. These orthopedic fracture patterns were frequently associated with other injuries especially head injuries (ranged from 14% to 26%). A significant relation to male gender, older age, low income, and admission to high-level hospital to the observed fracture patterns was observed.

Five weekly intra-articular injections of Artz provide pain relief and functional improvements in patients with Kellgren-Lawrence grades I and II ankle OA. The clinical effect was rapid at 1 week and may last for 6 months or more.

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Significant improvement in pain, physical function and balance tests was demonstrated after five weekly Artzal injections in geriatric patients with knee OA. The effect had rapid onset at 1 week and may last for 6 months.

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.

BackgroundLower extremity (LE) peripheral artery disease (PAD), which is associated with a reduced quality of life and increased mortality from atherosclerotic cardio-/cerebro-vascular occlusion, is a significant public health problem, especial for an aging society such as that of Taiwan.MethodsSpecific datasets of the 2000–2011 nationwide inpatient databases were analyzed. Two inclusion criteria, including one of the major diagnosis codes of PAD and one of three categorical invasive treatments of LE PAD, were used consecutively to select cases diagnosed as LE PAD and receiving invasive treatment. The epidemiology of invasively-treated PAD in Taiwan was estimated, and the influences of potential confounders on these invasively-treated methods were evaluated.ResultsIn general, the invasively-treated incidence of PAD in Taiwan doubled, from 3.73/10,000 (in 2000) to 7.48/10,000 (in 2011). On average, the total direct medical cost of one hospitalized and invasively-treated PAD case ranged from $US 4,600 to $US 5,900. The annual cases of bypass surgery for the PAD cases averaged 1,000 and the cases for limb amputation ranged from 4,100 to 5,100 annually. However, the number of percutaneous transluminal angioplasty (PTA) procedures remarkably increased by 15 times, from 600/year to 9,100/year, from 2000 to 2011. 51.3% of all the enrolled cases were treated with limb amputations, and female, young and middle-aged people (30–65 years of age), DM patients and those on a low income had a tendency to undergo amputation due to PAD. 37.6% of all the enrolled cases were treated with PTAs related to hypertension, cardiovascular disease, hyperlipidemia and catastrophic Illness. 2-year PTA failure rates of 22.13%, 11.91% and 10.61% were noted among the first (2000–2001), second (2004–2005) and the third (2008–2009) cohort groups, respectively.ConclusionsIn Taiwan, a gender difference and age and period effects on the invasively-treated incidence of LE PAD were observed. Female, young and middle-aged people (30–50 and 50–65 years of age), DM patients and those on a low income had a tendency to undergo amputation. The number of PTA procedures remarkably increased, but the 2-year failure rate of PTAs reduced from 2000 to 2011.