The genetics behind the progression of myelodysplasia to secondary acute myeloid leukemia (sAML) is poorly understood. In this study, we profiled somatic mutations and their dynamics using next ...generation sequencing on serial samples from a total of 124 patients, consisting of a 31 patient discovery cohort and 93 patients from two validation cohorts. Whole-exome analysis on the discovery cohort revealed that 29 of 31 patients carry mutations related to at least one of eight commonly mutated pathways in AML. Mutations in genes related to DNA methylation and splicing machinery were found in T-cell samples, which expand at the initial diagnosis of the myelodysplasia, suggesting their importance as early disease events. On the other hand, somatic variants associated with signaling pathways arise or their allelic burdens expand significantly during progression. Our results indicate a strong association between mutations in activated signaling pathways and sAML progression. Overall, we demonstrate that distinct categories of genetic lesions play roles at different stages of sAML in a generally fixed order.
SETTING: Tertiary referral centre, Samsung Medical Center, South Korea.OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to ...Mycobacterium abscessus.DESIGN: A retrospective review of 48 patients
with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015.RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 μg/ml
was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic
in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047).CONCLUSION: Our results suggest that once-daily
AMK for 4 weeks with a target Cmax of 55-65 μg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.
Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, ...and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009–2013). One hundred and twenty‐six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA/l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.
The lifetime of the τ lepton is measured using the process e+ e- → τ+ τ- , where both τ leptons decay to 3πν(τ). The result for the mean lifetime, based on 711 fb(-1) of data collected with the ...Belle detector at the ϒ(4S) resonance and 60 MeV below, is τ=(290.17±0.53(stat)±0.33(syst))×10(-15) s. The first measurement of the lifetime difference between τ+ and τ- is performed. The upper limit on the relative lifetime difference between positive and negative τ leptons is |Δτ|/τ<7.0×10(-3) at 90% C.L.
We search for lepton-flavor-violating τ→ℓV0 decays, where ℓ is an electron or muon and V0 is one of the vector mesons ρ0, ϕ, ω, K⁎0 and K¯⁎0. We use 854 fb−1 of data collected with the Belle detector ...at the KEKB asymmetric-energy e+e− collider. No evidence for a signal is found in any decay mode, and we obtain 90% confidence level upper limits on the individual branching fractions in the range (1.2–8.4)×10−8.
Aims
To investigate the intracellular lipid accumulation inhibitory effect of spent culture medium extract and the cytoplasmic fraction of Weissella koreensis OK1‐6 cells isolated from kimchi in ...differentiating 3T3‐L1 cells.
Methods and Results
Differentiating 3T3‐L1 cells were treated with either cytoplasmic fraction of W. koreensis OK1‐6 cells or its spent media for 4 days. Both the spent culture medium extract and cytoplasmic fraction of W. koreensis OK1‐6 cells significantly decreased the triglyceride concentration and intracellular lipid accumulation in the treated groups compared with the control group. The mRNA expression levels of C/EBP‐α, one of the major transcriptional factors involved in adipocyte differentiation, were significantly less expressed in 3T3‐L1 cells treated with the spent medium and cytoplasmic fraction. The expressions of aP2, fatty acid synthase (FAS) and SREBP1 genes were also decreased significantly.
Conclusions
These results suggested that W. koreensis OK1‐6 could play a crucial role in preventing intracellular lipid accumulation by down‐regulating the expression of adipocyte‐specific genes C/EBPα, aP2, SREBP1 and FAS.
Significance and Impact of the Study
These results may contribute to nutraceutical and food industries in developing probiotic‐based therapies for the treatment and prevention of obesity.
The purpose of this study was to examine the association between bisphosphonate exposure and osteonecrosis of the jaw (ONJ) in Korean patients with osteoporosis. A nested case-control study was ...performed using the claims database during 2002 to 2010 provided by the National Health Insurance Service. We identified a cohort of individuals with diagnosis of osteoporosis during 2002 to 2010. Cases and controls were identified during 2004 to 2010, and the date of potential cases of ONJ was defined as the index date. Bisphosphonate exposure was evaluated during 2 y prior to the index date. The association between bisphosphonate exposure and ONJ was tested by performing a conditional logistic regression analysis for matched data, and odds ratios (ORs) with 95% confidence intervals (CIs) were presented. Subjects were classified as nonuser, recent user, past user, or continuous user, depending on the prescription of bisphosphonates in 2 periods (1 to 2 y and 0 to 1 y prior to the index date). Continuous users were defined as patients who were exposed to bisphosphonate in both periods. We also examined the impact of bisphosphonate medication compliance by measuring the cumulative duration of exposure (CDE) on the risk of ONJ. A total of 212 cases with ONJ and 2,120 controls matched by sex, age, income level, and insurance type were identified among 109,787 patients with osteoporosis out of 1,025,340 enrollees in the sample cohort. The odds of having ONJ after adjusting for patient comorbidities significantly increased in continuous users of bisphosphonates (OR, 3.9; 95% CI, 2.4 to 6.2) compared to nonusers. Increased odds of ONJ were observed as CDE increased. The adjusted OR in patients with 1.5 y < CDE ≤ 2 y prior to the index date was 7.8 (95% CI, 4.0 to 15.5) versus nonusers. Our study results support significantly increased occurrences of potential ONJ in patients with osteoporosis who were exposed to bisphosphonates compared to those without exposure.
We report the first observation of the decay Λ+c→pK+π- using a 980 fb-1 data sample collected by the Belle detector at the KEKB asymmetric-energy e+e- collider. This is the first observation of a ...doubly Cabibbo-suppressed decay of a charmed baryon. We measure the branching ratio of this decay with respect to its Cabibbo-favored counterpart to be B(Λ+c→pK+π-)/B(Λ+c→pK-π+)=(2.35±0.27±0.21)×10-3, where the uncertainties are statistical and systematic, respectively.
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