Lack of association between AQP4 polymorphisms and risk of inflammatory demyelinating disease in a Korean population

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating autoimmune inflammatory diseases that affect the central nervous system (CNS). Previous genome-wide or candidate gene studies have suggested that genetic variants might be associated with the risk of MS or NMO. Aquaporin 4 (AQP4) is a commonly distributed water channel in astrocytes of the CNS, and its expression is decreased in NMO lesions due to astrocyte cytotoxicity. Previous studies have suggested the associations of AQP4 single nucleotide polymorphisms (SNPs) with MS and/or NMO. However, there have been few replication studies in various ethnic populations. This study, as the first of its kind performed in an Asian population, investigated associations of AQP4 SNPs with the risk of inflammatory demyelinating disease (IDD), including MS and NMO, in a Korean population. A total of seven common AQP4 SNPs were selected based on status of linkage disequilibrium (LD), and then genotyped in 178 IDD cases (79 MS and 99 NMO patients) and 237 normal controls. Statistical analyses showed no significant associations between AQP4 SNPs/haplotypes and development of IDD, including MS and NMO (P > 0.05). Further replications in larger cohorts and other ethnic groups are needed.     

An efficient algorithm for DNA fragment assembly in MapReduce

Fragment assembly is one of the most important problems of sequence assembly. Algorithms for DNA fragment assembly using de Bruijn graph have been widely used. These algorithms require a large amount of memory and running time to build the de Bruijn graph. Another drawback of the conventional de Bruijn approach is the loss of information. To overcome these shortcomings, this paper proposes a parallel strategy to construct de Bruijin graph. Its main characteristic is to avoid the division of de Bruijin graph. A novel fragment assembly algorithm based on our parallel strategy is implemented in the MapReduce framework. The experimental results show that the parallel strategy can effectively improve the computational efficiency and remove the memory limitations of the assembly algorithm based on Euler superpath. This paper provides a useful attempt to the assembly of large-scale genome sequence using Cloud Computing.     

The Utility of Thoracic Ultrasound in Patients with Acute Eosinophilic Pneumonia

Thoracic ultrasound (TUS) is an easy-to-use imaging modality that aids physicians in the differential diagnosis of respiratory diseases. However, no data exist on the TUS findings of acute eosinophilic pneumonia (AEP) or their clinical utility in patients with AEP. Thus, we performed an observational study on TUS findings and their clinical utility for follow-up in patients with AEP. We prospectively screened patients who visited the emergency department for acute respiratory symptoms at the Armed Forces Capital Hospital in South Korea between February 2014 and July 2014. Of them, patients suspected to have AEP underwent an etiological investigation, including flexible bronchoscopy with bronchoalveolar lavage and TUS, and we evaluated TUS findings and serial changes on TUS during the treatment course compared with those from chest radiographs. In total, 22 patients with AEP were identified. The TUS examinations reveled that all patients exhibited multiple diffuse bilateral B-lines and lung sliding, with (n = 5) or without pleural effusion, which was consistent with alveolar-interstitial syndrome. B-line numbers fell during the course of treatment, as the lines became thinner and fainter. A-lines were evident in 19 patients on day 7 of hospitalization, when B-lines had disappeared in 13 patients, and all pleural effusion had resolved. All patients exhibited complete ultrasonic resolution by day 14, along with clinicoradiological improvement. Chest radiographs of five patients taken on day 7 seemed to show complete resolution, but several abnormal B-lines were evident on TUS performed the same day. As a result, our data show common TUS findings of AEP and suggest that AEP may be included as a differential diagnosis when multiple diffuse bilateral B-lines with preserved lung sliding are identified on a TUS examination in patients with acute symptoms, and that TUS is a useful modality for evaluating the treatment response in patients with AEP.     

The EPSPS gene flow from glyphosate-resistant Brassica napus to untransgene B. napus and wild relative species Orychophragmus violaceus

Gene flow from transgenic plants to compatible wild relatives is one of the major impediments to the development of the culture of genetically engineered crop plants. In this work, the flow of EPSPS (conferring resistance to glyphosate) gene of transgene Brassica napus toward the untransgene B. napus and wild relative species Orychophragmus violaceus in an open field (1 ha) was studied. The data related to only the 2004 and 2005 autumn season on one location of southwest of China. Pollen dispersal and fertilization of the target plants were favored and a detailed analysis of the hybrid offspring was performed. In field, the data studied show that the gene flow frequency was 0.16% between GM and non-GM B. napus at a distance of 1 m from the transgenic donor area. The crosspollination frequency was 0.05% between GM and non-GM B. napus at a distance of 5 m from the transgenic donor area. At a distance of 10 m, no crosspollination was observed. According to the results of this study, B. napus transgene flow was low. However, the wild relative species O. violaceus could not be fertilized by the transgenic pollen of B. napus, no matter what the distance was.     

Nosocomial Infection in Adult Admissions with Hematological Malignancies Originating from Different Lineages: A Prospective Observational Study

Background

Nosocomial infection (NI) causes prolonged hospital stays, increased healthcare costs, and higher mortality among patients with hematological malignancies (HM). However, few studies have compared the incidence of NI according to the HM lineage.

Objective

To compare the incidence of NI according to the type of HM lineage, and identify the risk factors for NI.

Methods

This prospective observational study monitored adult patients with HM admitted for >48 hours to the General Hospital of the People''s Liberation Army during 2010–2013. Attack rates and incidences of NI were compared, and multivariable logistic regression was used to control for confounding effects.

Results

This study included 6,613 admissions from 1,922 patients. During these admissions, 1,023 acquired 1,136 NI episodes, with an attack rate of 15.47% and incidence of 9.6‰ (95% CI: 9.1–10.2). Higher rates and densities of NIs were observed among myeloid neoplasm (MN) admissions, compared to lymphoid neoplasm (LN) admissions (28.42% vs. 11.00%, P<0.001 and 11.4% vs. 8.4‰, P<0.001). NI attack rates in acute myeloid leukemia (AML) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) were higher than those in MDS (30.69% vs. 20.19%, P<0.001; 38.89% vs. 20.19%, P = 0.003). Attack rates in T/NK-cell neoplasm and B-cell neoplasm were higher than those in Hodgkin lymphoma (15.04% vs. 3.65%; 10.94% vs. 3.65%, P<0.001). Multivariable regression analysis indicated prolonged hospitalization, presence of central venous catheterization, neutropenia, current stem cell transplant, infection on admission, and old age were independently associated with higher NI incidence. After adjusting for these factors, MN admissions still had a higher risk of infection (odds ratio 1.34, 95% CI: 1.13–1.59, P<0.001).

Conclusion

Different NI attack rates were observed for HM from different lineages, with MN lineages having a higher attack rate and incidence than LN lineages. Special attention should be paid to MN admissions, especially AML and MDS/MPN admissions, to control NI incidence.     

Design and synthesis of diarylamines and diarylethers as cytotoxic antitumor agents

Based on a shared structural core of diarylamine in several known anticancer drugs as well as a new cytotoxic hit 6-chloro-2-(4-cyanophenyl)amino-3-nitropyridine (7), 30 diarylamines and diarylethers were designed, synthesized, and evaluated for cytotoxic activity against A549, KB, KB-vin, and DU145 human tumor cell lines (HTCL). Four new leads 11e, 12, 13a, and 13b were discovered with GI(50) values ranging from 0.33 to 3.45μM. Preliminary SAR results revealed that a diarylamine or diarylether could serve as an active structural core, meta-chloro and ortho-nitro groups on the A-ring (either pyridine or phenyl ring) were necessary and crucial for cytotoxic activity, and the para-substituents on the other phenyl ring (B-ring) were related to inhibitory selectivity for different tumor cells. In an investigation of potential biological targets of the new leads, high thoughput kinase screening discovered that new leads 11e, 12 and 13b especially inhibit Mer tyrosine kinase, a proto-oncogene associated with munerous tumor types, with IC(50) values of 2.2-3.0μM. Therefore, these findings provide a good starting point to optimize a new class of compounds as potential anticancer agents, particularly targeting Mer tyrosine kinase.