Retrospective Analysis of Peripheral Blood Stem Cell Transplantation for the Treatment of High-Risk Neuroblastoma

Disease relapse after autologous peripheral blood stem cell transplantation (APBSCT) is the main cause of treatment failure in high-risk neuroblastoma (NBL). To reduce relapse, various efforts have been made such as CD34+ selection and double APBSCT. Here the authors reviewed the clinical features and outcomes of high-risk NBL patients and analyzed their survival. The medical records of 36 patients with stage III or IV NBL who underwent APBSCT at Seoul National University Children's Hospital between May 1996 and May 2004 were reviewed. Total 46 APBSCTs were performed in 36 patients. Disease free survival (DFS) and overall survival of all patients were 47.7% and 68.8%, respectively. The patients were allocated to three groups according to the APBSCT type. The DFS of CD34+ non-selected single APBSCT patients (N=13), CD34+ selected single APBSCT patients (N=14), and CD34+ selected double APBSCT patients (N=9) were 55.6%, 40.6%, and 50.0%, respectively, which were not significantly different. Thus the survival was not found to be affected by CD34+ selection or transplantation number. To improve long-term survival, various efforts should be made such as chemotherapy dose intensification, more effective tumor purging, and control of minimal residual disease via the use of differentiating and immune-modulating agents

Precision genome engineering with programmable DNA-nicking enzymes

Zinc finger nucleases (ZFNs) are powerful tools of genome engineering but are limited by their inevitable reliance on error-prone nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs), which gives rise to randomly generated, unwanted small insertions or deletions (indels) at both on-target and off-target sites. Here, we present programmable DNA-nicking enzymes (nickases) that produce single-strand breaks (SSBs) or nicks, instead of DSBs, which are repaired by error-free homologous recombination (HR) rather than mutagenic NHEJ. Unlike their corresponding nucleases, zinc finger nickases allow site-specific genome modifications only at the on-target site, without the induction of unwanted indels. We propose that programmable nickases will be of broad utility in research, medicine, and biotechnology, enabling precision genome engineering in any cell or organism.

Replication of the genetic effects of IFN regulatory factor 5 (IRF5) on systemic lupus erythematosus in a Korean population

Recently, two studies provided convincing evidence that IFN regulatory factor 5 (IRF5) gene polymorphisms are significantly associated with systemic lupus erythematosus (SLE) in several white populations. To replicate the association with SLE in an Asian population, we examined the genetic effects in our SLE cohort from a Korean population. A total of 1,565 subjects, composed of 593 cases and 972 controls, were genotyped using the TaqMan® (Applied Biosystems, Foster City, CA, USA) method. The genetic effects of polymorphisms on the risk of SLE were evaluated using χ2 tests and a Mantel–Haenszel meta-analysis. Statistical analysis revealed results in the Korean population were similar to the previous reports from white populations. The rs2004640 T allele had a higher frequency in SLE cases (0.385) than controls (0.321; odds ratio (OR) = 1.32, P = 0.0003). In combined analysis, including all seven independent cohorts from the three studies so far, robust and consistent associations of the rs2004640 T allele with SLE were observed. The estimate of risk was OR = 1.44 (range, 1.34–1.55), with an overall P = 1.85 × 10-23 for the rs2004640 T allele. The haplotype (rs2004640T–rs2280714T) involved in both the alternative splice donor site and the elevated expression of IRF5 also had a highly significant association with SLE (pooled, P = 2.11 × 10-16). Our results indicate that the genetic effect on the risk of SLE mediated by IRF5 variants can be generally accepted in both white and Asian populations

Level of Contamination of Positive Airway Pressure Devices Used in Obstructive Sleep Apnea

Objectives. No study has yet evaluated the degree of contamination after the total disassembly of continuous positive airway pressure (CPAP) devices. We investigated the extent of contamination of CPAP devices used daily by patients with obstructive sleep apnea (OSA) by disassembling the systems and identifying the factors that influenced the degree of CPAP contamination. Methods. We conducted a chart review of the medical records of patients with OSA for whom the CPAP devices were disassembled and cleaned. Two skilled technicians photographed the levels of contamination of each component and scored them using a visual analog scale. Patients’ clinical characteristics and records of CPAP device usage were statistically analyzed to identify characteristics that were significantly associated with the degree of CPAP device contamination. Results. Among the 55 participants, both the external components, including the mask and tube, and the internal components, such as the humidifier and the interior of the main body, showed a substantial degree of contamination. The total and average daily duration of usage of the CPAP device did not show significant associations with the degree of contamination. Age was most consistently associated with the degree of contamination, such as in masks, humidifiers, and interior and exterior main parts. The degree of contamination of the internal components of the device was significantly correlated with the degree of contamination of the external components. Conclusion. Age-specific guidelines for managing the hygiene of external and internal CPAP components should be prepared

A DNA barcode library of the beetle reference collection (Insecta: Coleoptera) in the National Science Museum, Korea

AbstractColeoptera is a group of insects that are most diverse among insect resources. Although used as indicator species and applied in developing new drugs, it is difficult to identify them quickly. Since the development of a method using mitochondrial DNA information for identification, studies have been conducted in Korea to swiftly and accurately identify species. The National Science Museum of Korea (NSMK) has been collecting and morphologically identifying domestic reference insects since 2013, and building a database of DNA barcodes with digital images. The NSMK completed construction of a database of digital images and DNA barcodes of 60 beetle species in the Korean National Research Information System. A total of 179 specimens and 60 species were used for the analysis, and the averages of intraspecific and interspecific variations were 0.70±0.45% and 26.34±6.01%, respectively, with variation rates ranging from 0% to 1.45% and 9.83% to 56.23%, respectively

Microstructure and Mechanical Properties of High-Entropy Alloy Co20Cr26Fe20Mn20Ni14 Processed by High-Pressure Torsion at 77 K and 300 K

In this work, the mechanical characteristics of high-entropy alloy Co20Cr26Fe20Mn20Ni14 with low-stacking fault energy processed by cryogenic and room temperature high-pressure torsion (HPT) were studied. X-ray diffraction, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) analyses were performed to identify the phase and microstructure variation and the mechanical properties characterized by Vickers hardness measurements and tensile testing. Cryogenic HPT was found to result in a lower mechanical strength of alloy Co20Cr26Fe20Mn20Ni14 than room temperature HPT. Microstructure analysis by SEM and TEM was conducted to shed light on the microstructural changes in the alloy Co20Cr26Fe20Mn20Ni14 caused by HPT processing. Electron microscopy data provided evidence of a deformation-induced phase transformation in the alloy processed by cryogenic HPT. Unusual softening phenomena induced by cryogenic HPT were characterized by analyzing the dislocation density as determined from X-Ray diffraction peak broadening.11Ysciescopu

Dexrazoxane for Preventing Anthracycline Cardiotoxicity in Children with Solid Tumors

This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8±83.4 mg/m2 in the dexrazoxane group and 266.1±75.0 mg/m2 in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors

Surgical Resection of Recurrent Lung Cancer in Patients Following Curative Resection

We reviewed our experience with resection of recurrent lung cancer to evaluate the benefit and risk of the procedure. From December 1994 to December 2003, 29 consecutive patients underwent pulmonary resections for recurrent lung cancer. The mean duration from the first resection to second surgery was 25.4±15.1 months for the definite 2nd primary lung cancer (n=20) and 8.9±5.7 months for metastatic lung cancer (n=9). The procedures at the second operations were completion-pneumonectomy in 11 patients, lobectomy in 5 patients, wedge resection in 12 patients and resection and anastomosis of trachea in 1 patient. Morbidity was observed in 6 (21%) of the patients and the in-hospital mortality was two patients (7%) after the repeated lung resection. Tumor recurrence after reoperation was observed in 14 patients (48%). The actuarial 5-yr survival rate was 69% and the 5-yr disease free rate following reoperation was 44%. No significant difference was found in overall survival and disease free survival between the 2nd primary lung cancer group and the metastatic lung cancer group. The recurrence rate following reoperation was significantly different between the wedge resection group and lobectomy/completion pneumonectomy group (p=0.008), but the survival rate was not significantly different (p=0.41). Surgical intervention for recurrent lung cancers can be performed with acceptable mortality and morbidity. If tolerable, completion pneumonectomy or lobectomy is recommended for resection of recurrent lung cancer