Rate-dependent inhomogeneous-to-homogeneous transition of plastic flows during nanoindentation of bulk metallic glasses: Fact or artifact?

There has been considerable controversy over the "apparent" rate-dependent transition from inhomogeneous-to-homogeneous flow during nanoindentation of bulk metallic glasses (BMGs) at room temperature: whether it arises from the existence of homogeneous-flow regime in BMG deformation map or is an artifact due to the instrumental blurring at high rates. To provide a clue to address this dispute, the authors performed nanoindentation experiments on a Zr-based BMG with two geometrically self-similar indenters. The results are discussed in terms of the discrete plasticity ratio, which is a useful parameter in analyzing the contribution of inhomogeneous plasticity to the total plastic deformation.open232

Complete genome of streamlined marine actinobacterium Pontimonas salivibrio strain CL-TW6T adapted to coastal planktonic lifestyle

Background Pontimonas salivibrio strain CL-TW6T (=KCCM 90105 = JCM18206) was characterized as the type strain of a new genus within the Actinobacterial family Microbacteriaceae. It was isolated from a coastal marine environment in which members of Microbactericeae have not been previously characterized. Results The genome of P. salivibrio CL-TW6T was a single chromosome of 1,760,810 bp. Genomes of this small size are typically found in bacteria growing slowly in oligotrophic zones and said to be streamlined. Phylogenetic analysis showed it to represent a lineage originating in the Microbacteriaceae radiation occurring before the snowball Earth glaciations, and to have a closer relationship with some streamlined bacteria known through metagenomic data. Several genomic characteristics typical of streamlined bacteria are found: %G + C is lower than non-streamlined members of the phylum; there are a minimal number of rRNA and tRNA genes, fewer paralogs in most gene families, and only two sigma factors; there is a noticeable absence of some nonessential metabolic pathways, including polyketide synthesis and catabolism of some amino acids. There was no indication of any phage genes or plasmids, however, a system of active insertion elements was present. P. salivibrio appears to be unusual in having polyrhamnose-based cell wall oligosaccharides instead of mycolic acid or teichoic acid-based oligosaccharides. Oddly, it conducts sulfate assimilation apparently for sulfating cell wall components, but not for synthesizing amino acids. One gene family it has more of, rather than fewer of, are toxin/antitoxin systems, which are thought to down-regulate growth during nutrient deprivation or other stressful conditions. Conclusions Because of the relatively small number of paralogs and its relationship to the heavily characterized Mycobacterium tuberculosis, we were able to heavily annotate the genome of P. salivibrio CL-TW6T. Its streamlined status and relationship to streamlined metagenomic constructs makes it an important reference genome for study of the streamlining concept. The final evolutionary trajectory of CL-TW6 T was to adapt to growth in a non-oligotrophic coastal zone. To understand that adaptive process, we give a thorough accounting of gene content, contrasting with both oligotrophic streamlined bacteria and large genome bacteria, and distinguishing between genes derived by vertical and horizontal descent.This research was supported by the project BK 21+ of the Korean government, and the KOPRI project (20140410). The funding bodies had no role in the design of the study or the collection, analysis, interpretation of data or in writing the manuscript

Altered expression of thioredoxin reductase-1 in dysplastic bile ducts and cholangiocarcinoma in a hamster model

Thioredoxin reductase 1 (TrxR) is a homodimeric selenoenzyme catalyzing thioredoxin (Trx) in an NADPHdependent manner. With regard to carcinogenesis, these redox proteins have been implicated in cell proliferation, transformation and anti-apoptosis. In the present study, using a hamster cholangiocarcinoma (ChC) model, we evaluated the immunohistochemical expression pattern of TrxR in precancerous lesions and ChCs as well as in normal bile ducts. The goal of this study was to determine the potential role and importance of TrxR in cholangiocarcinogenesis. For the ChC model, we obtained liver tissue specimens with dysplastic bile ducts prior to the development of ChC 8 weeks after initiation of the experiment and ChC samples at 27 weeks. The immunohistochemical analysis showed diffuse cytoplasmic overexpression of TrxR in the dysplastic bile duct epithelial cells as well as in cholangiocarcinoma; this was comparable to the negative or weakly positive in normal and type 1 hyperplastic bile ducts. However, TrxR appeared to be considerably down-regulated in the ChCs when compared to the higher expression observed in the dysplastic bile ducts. Therefore, these results suggest that TrxR overexpression followed by down-regulation might be an important event in cholangiocarcinogenesis, especially at early stages including the cellular transformation of candidate bile ducts. Further studies are however required to determine whether TrxR may be a potential target molecule for chemoprevention against cholangiocarcinogenesis. In addition, the molecular mechanism as well as the importance of the loss of TrxR in the development of cholangiocarcinoma, following dysplastic transformation of bile duct cells, also remains to be clarified.This study was supported by Kangwon National University and Korea Research Foundation Grant (KRF-2004-041- E00324). The authors wish to thank Dr. Min-Ho Choi, College of Medicine, Seoul National University, for providing Clonorchis sinensis

Whole genomic approach in mutation discovery of infantile spasms patients

Infantile spasms (IS) are a clinically and genetically heterogeneous group of epilepsy disorders in early infancy. The genetic backgrounds of IS have been gradually unraveled along with the increased application of next-generation sequencing (NGS). However, to date, only selected genomic regions have been sequenced using a targeted approach in most cases of IS, and the genetic etiologies of the majority of patients remain unknown. We conducted a proof-of-concept study using whole-genome sequencing (WGS) for the genetic diagnosis of IS. We included 16 patients with IS for this study, and WGS was applied as a first-tier test for genetic diagnosis. In total, we sequenced the whole genomes of 28 participants, including the genomes of six patients, which were sequenced with those of their parents. Among variants identified, we focused on those located in epilepsy or seizure-associated genes. We used two different methods to call relevant large deletions from WGS results. We found pathogenic or likely pathogenic variants in four patients (25.0%); a de novo variant in HDAC4, compound heterozygous variants in GRM7, and heterozygous variants in CACNA1E and KMT2E. We also selected two more candidate variants in SOX5 and SHROOM4 intronic regions. Although there are currently several difficulties in applying WGS for genetic diagnosis, especially in clinical interpretation of non-coding variants, we believe that developing sequencing technologies would overcome these hurdles in the near future. Considering the vast genetic heterogeneity and the substantial portion of patients with unknown etiologies, further studies using whole genomic approaches are necessary for patients with IS

A childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy

Tuberculosis is primarily a pulmonary disease, but extra-pulmonary manifestations are not uncommon, especially in children and adolescents. Ten percent of extra pulmonary tuberculosis localizes to the bones and joints, and 56% of such cases affect the spine. We treated a childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy in a patient without specific constitutional symptoms. We report this case because the patient had an unusual presentation of spinal tuberculosis

Choice of recipient vessels in muscle-sparing transverse rectus abdominis myocutaneous flap breast reconstruction: A comparative study

Background Thoracodorsal vessels (TDVs) and internal mammary vessels (IMVs) have both been widely employed as recipient vessels for use in free muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps. However, whether TDVs or IMVs are preferable as recipient vessels for autologous breast reconstruction with a free MS-TRAM flap remains controversial. The purpose of this study was to compare the clinical outcomes when TDVs were used as recipient vessels to those obtained when IMVs were used as recipient vessels for autologous breast reconstruction with a free MS-TRAM flap. Methods A retrospective matched-cohort study was performed. We retrospectively reviewed data collected from patients who underwent a free MS-TRAM flap for autologous breast reconstructions after mastectomy between March 2003 and June 2013. After a one-to-one matching using age, 100 autologous breast reconstructions were selected in this study. Of the 100 breast reconstructions, 50 flaps were anastomosed to TDVs and 50 to IMVs. Patient demographics and clinical outcomes including operation time, length of hospital stay, postoperative complications, and aesthetic score were compared between the two groups. Results No statistically significant differences were found between the two groups in patient demographics and clinical outcomes, including the complication rates and aesthetic scores. There were no major complications such as total or partial flap loss in either group. Conclusions The results of our study demonstrate that both TDVs and IMVs were safe and efficient as recipient vessels in terms of the complication rates and aesthetic outcomes

Altered expression of thioredoxin reductase-1 in dysplastic bile ducts and cholangiocarcinoma in a hamster model

Thioredoxin reductase 1 (TrxR) is a homodimeric selenoenzyme catalyzing thioredoxin (Trx) in an NADPH-dependent manner. With regard to carcinogenesis, these redox proteins have been implicated in cell proliferation, transformation and anti-apoptosis. In the present study, using a hamster cholangiocarcinoma (ChC) model, we evaluated the immunohistochemical expression pattern of TrxR in precancerous lesions and ChCs as well as in normal bile ducts. The goal of this study was to determine the potential role and importance of TrxR in cholangiocarcinogenesis. For the ChC model, we obtained liver tissue specimens with dysplastic bile ducts prior to the development of ChC 8 weeks after initiation of the experiment and ChC samples at 27 weeks. The immunohistochemical analysis showed diffuse cytoplasmic overexpression of TrxR in the dysplastic bile duct epithelial cells as well as in cholangiocarcinoma; this was comparable to the negative or weakly positive in normal and type 1 hyperplastic bile ducts. However, TrxR appeared to be considerably down-regulated in the ChCs when compared to the higher expression observed in the dysplastic bile ducts. Therefore, these results suggest that TrxR overexpression followed by down-regulation might be an important event in cholangiocarcinogenesis, especially at early stages including the cellular transformation of candidate bile ducts. Further studies are however required to determine whether TrxR may be a potential target molecule for chemoprevention against cholangiocarcinogenesis. In addition, the molecular mechanism as well as the importance of the loss of TrxR in the development of cholangiocarcinoma, following dysplastic transformation of bile duct cells, also remains to be clarified

Role of age and sex in determining antibiotic resistance in febrile urinary tract infections

SummaryObjectivesTo identify the age- and sex-specific antimicrobial susceptibility patterns of Gram-negative bacteria (GNB) in outpatient febrile urinary tract infections (UTIs) in Korea.MethodsA total 2262 consecutive samples collected from patients aged 1–101 years with febrile UTIs, during the period January 2012 to December 2014, were analyzed in this multicentre, retrospective cohort study.ResultsThe sensitivities to cefotaxime and cefoxitin were over 85% for females but under 75% for males. Sex played an important role in the susceptibility of GNB to cefotaxime (p<0.001) and cefoxitin (p<0.001). The sensitivity to ciprofloxacin (age >20 years) was under 75% in both sexes, and was not influenced by sex (p=0.204). Age distributions of the incidences of resistance to cefotaxime, cefoxitin, and ciprofloxacin (age >20 years) were similar to the age distribution of the incidence of GNB, which indicates that the resistance patterns to these drugs were not affected by age (Kolmogorov–Smirnov test, female/male: p=0.927/p=0.509, p=0.193/p=0.911, and p=0.077/p=0.999, respectively).ConclusionsAge is not a considerable factor in determining the antibiotic resistance in febrile UTIs. Ciprofloxacin should be withheld from both sexes until culture results indicate its use. Second- or third-generation cephalosporins such as cefoxitin and cefotaxime can be used empirically only in females

A Case of Santorinicele without Pancreas Divisum: Diagnosis with Multi-detector Row Computed Tomography

A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla. Most cases reported previously were associated with pancreas divisum and a santorinicele without pancreas divisum is known to be rare. We recently experienced a typical case of a santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain and hematochezia, subsequently proven to be the result of an ischemic colitis. The santorinicele was diagnosed incidentally with multi-detector row computed tomography using a minimum intensity projection technique, which clearly showed a cystic dilatation of the terminal portion of the dorsal pancreatic duct and a communication between the ventral and dorsal pancreatic ducts. This finding was also confirmed by a magnetic resonance cholangiopancreatography

Extrahepatic Biliary Schwannomas: A Case Report

Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature