Evaluation of the MolecuTech® REBA MTB-XMDR kit for detection of pre-extensively drug-resistant TB.

BACKGROUND: Rapid diagnosis of drug-resistant TB is critical for early initiation of effective therapy. YD Diagnostics in South Korea recently developed the MolecuTech® REBA MTB-XMDR test to rapidly detect multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and resistance to second-line injectable drugs (SLIDs) simultaneously using a fully automated test platform. This study aimed to evaluate the MolecuTech® test for the detection of MDR- and pre-XDR-TB, as well as SLID resistance.METHODS: A total of 151 clinical Mycobacterium tuberculosis isolates from South Korea were tested using the MolecuTech test, and the results were analysed by comparing these with phenotypic drug susceptibility testing (pDST) and sequencing.RESULTS: Compared to pDST, the MolecuTech test showed a sensitivity and specificity of respectively 97.7% and 100.0% for rifampicin (RIF), 82.4% and 100.0% for isoniazid (INH), 97.5% and 97.2% for fluoroquinolones (FQs), and 94.0% and 98.8% for SLIDs. Concordances with the sequencing results of each resistance determinant were 99.3% for RIF, 96.7% for INH, 98.7% for FQs and 99.3% for SLIDs.CONCLUSION: The MolecuTech test is an efficient and reliable rapid molecular diagnostic tool for the simultaneous screening of MDR- and pre-XDR-TB.

Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

Characterization of a Long-Acting Site-Specific PEGylated Murine GM-CSF Analog and Analysis of Its Hematopoietic Properties in Normal and Cyclophosphamide-Treated Neutropenic Rats.

Previously we reported that site-specific modification of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) A3C analog with polyethylene glycol (PEG) dramatically improved the pharmacokinetic properties of the protein in rats. However, we could not evaluate the hematological properties of the PEG-A3C protein in rats because human GM-CSF is inactive in rodents. To study the biological effects of PEGylated GM-CSF analogs in rodents we created a homologous site-specific PEGylated murine (mu) GM-CSF (T3C) protein. muGM-CSF and the T3C protein were expressed in Escherichia coli and purified by column chromatography. The purified T3C protein was covalently modified with a linear 20 kDa- or a branched 40 kDa-maleimide-PEG, and the monoPEGylated proteins purified by column chromatography. muGM-CSF, T3C and the two PEG-T3C proteins had comparable in vitro biological activities, as measured by stimulation of proliferation of the murine FDC-P1 cell line. The PEG-T3C proteins had 10- to 25-fold longer circulating half-lives than muGM-CSF and stimulated greater and longer lasting increases in neutrophils and white blood cells than muGM-CSF following a single intravenous or subcutaneous administration to rats. Treatment of rats made neutropenic with cyclophosphamide with the PEG-T3C proteins shortened the time for recovery of neutrophils to normal levels from 9 or 10 days to 5 or 6 days, whereas muGM-CSF showed no benefit versus vehicle solution. Acceleration of neutrophil recovery in cyclophosphamide-treated rats required a minimum of three PEG-T3C treatments over five days. The PEG-T3C proteins should prove useful for evaluating the potential therapeutic benefits of GM-CSF and long-acting GM-CSF proteins in rodent disease models.

Coculture With Ischemia/Reperfusion-Preconditioned Hepatocytes Improves Islet Function and Survival.

In clinical islet transplantation, hepatic ischemia and insufficient neovascularization of transplanted islets are barriers to islet survival and function. However, hepatocytes have a potency to protect themselves against ischemia. We hypothesized that ischemia/reperfusion preconditioning (IRP) of hepatocytes might beneficially affect islet cells in a coculture system. Primary islets were cocultured with primary hepatocytes, and hepatocyte IRP was conducted by subjecting cells to hypoxic conditions for single 15-minute/30-minute hypoxia, or 2 tandem 15-minute/30-minute hypoxic treatments (hypoxic-normoxic-hypoxic). We show that gene expression levels of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF), transforming growth factor-α (TGF-α), and TGF-ß1 in hepatocytes were increased by IRP. IRP hepatocytes secreted hepatocyte growth factor and insulin-like growth factor-1. Coculture of islets with IRP hepatocytes enhanced islet insulin secretion in glucose challenge test and expression of the survival-related gene Bcl-2 and the regenerating gene-1α (Reg-1α). Islets cocultured with the 30-minute double-IRP hepatocytes displayed significantly higher viability in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase dUTP nick end labeling stain compared with that of islets subjected to 30 minutes of hypoxia. These results suggest that islet coculture with IRP hepatocytes can improve islet survival and insulin secretion.

Supercooling Storage for the Transplantable Sources From the Rat and the Rabbit: A Preliminary Report.

BACKGROUND: It is necessary to store the transplantable sources for a certain period during the variety of manipulation processing steps. The method used to preserve (depending on conditions of solvent, temperature, periods, density, and physical impulse, etc.) can affect the safety and efficacy of the samples. Supercooling refers to a phenomenon of lowering the temperature below its freezing point without freezing. We investigated the possibility of supercooling for the preservation of cells and organs according to the limited conditions. METHOD: The viability of mesenchymal stem cells (MSCs) derived from the intra-abdominal fat of the New Zealand white rabbit were observed, and the neonatal rat kidneys were maintained in histidine-tryptophan-ketoglutarate solution and stored at various temperatures for 48 hours. The supercooling refrigerator was used for -2 °C and -5 °C in controlled preservation conditions. We observed and compared histopathological changes of samples at each temperature condition. RESULTS: As time passed, the number of rabbit MSCs decreased in each group with storage temperature. At room temperature, the number of viable MSCs decreased rapidly, but the number of MSCs tended to decrease slowly in the cooling and supercooling groups. The rat kidneys preserved on supercooling temperature at -2 °C tended to have the least damage on the cortex and medulla parenchyma. CONCLUSIONS: The difference in damage of transplantable sources by storage temperature conditions is the evidence that effectiveness may depend on the storage method. It is necessary to determine further optimal supercooling temperature of the preservation methods with various cells, tissues, and organs in the future.

Analysis of the number of enlarged pores according to site, age, and sex.

BACKGROUND: Increasing the number of enlarged pores causes cosmetic problems. The difference in the number of enlarged pores according to facial site, age, and sex is unclear. OBJECTIVE: To analyze the distribution of the number of enlarged pores according to facial site, age, and sex. METHODS AND MATERIALS: We analyzed the number of the enlarged pores and the percentage of wrinkles in the nose, forehead, and cheek from 434 polarized images. The measurement results were analyzed according to site, age, and sex. Relationship between enlarged pore counts and wrinkle severity was also analyzed. The study was conducted by using DermaVision,™ which can take cross-polarization, parallel polarization, and ultraviolet light images. RESULTS: The enlarged pores of the nose and forehead were more prominent than in the cheeks. Pore counts were increased with age, and the increment was significant between the 30's and 40's. There was no significant difference by gender. Enlarged pore counts were related to wrinkle severity. CONCLUSIONS: The number of enlarged pores differs depending on body site and increased with age. The enlarged pore counts correlate with wrinkle severity and the correlation varies depending on the body site.

Preoperative Computed Tomography-Determined Sarcopenia and Postoperative Outcome After Surgery for Non-Small Cell Lung Cancer.

BACKGROUND: Sarcopenia, reduced skeletal muscle mass, is associated with frailty, injuries, and mortality. The purpose of this study was to evaluate the impact of computed tomography-determined sarcopenia on surgical complications and outcomes after resection of non-small cell lung cancer. METHODS: For a total 272 non-small cell lung cancer patients that underwent surgery between 2011 and 2016, cross-sectional area of muscle at the third lumbar vertebra (L3) was retrospectively measured using preoperative chest computed tomography images. Sarcopenia was defined as an L3 muscle index of <55 cm2/m2 for men and of <39 cm2/m2 for women. Clinical characteristics, postoperative complications, disease-free survival, and overall survival of patients with or without sarcopenia were compared. RESULTS: A total of 60.3% ( n = 164) were male, and mean patient age was 62.9 ± 9.6 years. The prevalence of sarcopenia was 22.4% for all study subjects, 32.9% for men, and 6.5% for women. No significant difference was observed between patients with or without sarcopenia in terms of intensive care unit or hospital stay ( p = 0.502 and p = 0.378, respectively), and the presence of sarcopenia was not associated with postoperative complications. Furthermore, no significant difference was observed between the 3-year disease-free survival rate (74.3% vs 66.7%, p = 0.639) or 3-year overall survival rate (83.9% vs 87.7%, p = 0.563) of patients with or without sarcopenia. CONCLUSION: Sarcopenia as determined by preoperative computed tomography does not appear to have a negative impact on surgical outcome or overall survival for resected non-small cell lung cancer patients.

Multidirectional flexible force sensors based on confined, self-adjusting carbon nanotube arrays.

We demonstrate a highly sensitive force sensor based on self-adjusting carbon nanotube (CNT) arrays. Aligned CNT arrays are directly synthesized on silicon microstructures by a space-confined growth technique which enables a facile self-adjusting contact. To afford flexibility and softness, the patterned microstructures with the integrated CNTs are embedded in polydimethylsiloxane structures. The sensing mechanism is based on variations in the contact resistance between the facing CNT arrays under the applied force. By finite element analysis, proper dimensions and positions for each component are determined. Further, high sensitivities up to 15.05%/mN of the proposed sensors were confirmed experimentally. Multidirectional sensing capability could also be achieved by designing multiple sets of sensing elements in a single sensor. The sensors show long-term operational stability, owing to the unique properties of the constituent CNTs, such as outstanding mechanical durability and elasticity.

Surgical Techniques of Allogeneic Liver Transplantation in a Nonhuman Primate Model.

Herein, we report our experience of performing allogeneic orthotopic liver transplantation (LT) in nonhuman primates. We designed an allogeneic ABO-compatible orthotopic LT model in monkeys in a manner similar to that used in humans. We applied almost the same surgical procedures used for human conventional deceased donor LT. A total of 6 monkeys underwent allogeneic LT. One cynomolgus monkey aged 45 months (3.4 kg) and 5 rhesus macaque monkeys aged 50.2 ± 14.8 months (5.40 ± 0.33 kg) were used as recipients. In the donor surgery, the liver was perfused in situ through the aorta using cold histidine-tryptophan-ketoglutarate solution. The portal vein (diameter, 5-10 mm), supra- and infra-hepatic inferior vena cava (IVC) (diameter, 12-15 mm), and common bile duct (diameter, 1.5-3.0 mm) were dissected out. The hepatic artery was kept in continuity with the celiac trunk and abdominal aorta up to the iliac bifurcation (diameter, 5-6 mm). The mean graft weight was 102.0 g (94.8-111.0 g). Recipient surgery was conducted in parallel. After recipient hepatectomy, the graft was implanted. The suprahepatic IVC and portal vein were anastomosed to those of the graft. After reperfusion, the infrahepatic IVC was anastomosed. The aorta conduit of the graft was anastomosed to the infrarenal aorta of the recipient in a retrocolic end-to-side manner. Biliary reconstruction was performed in a duct-to-duct anastomosis with cholecystectomy. Mean operative time was 107.0 minutes for donor and 198.2 minutes for recipient. There was one operative death due to unknown cause. In conclusion, for allogeneic orthotopic LT in nonhuman primate model, we can apply almost the same procedure used for human conventional deceased donor LT in a similar manner.

Metastatic carcinoma of the oral region: An analysis of 21 cases.

BACKGROUND: Metastatic carcinoma to the jaws and oral region are very rare, representing less than 1% of all oral tumors. Unfortunately, oral metastasis is usually manifestation of an advanced stage of primary cancer, and indicates widespread disease and poor prognosis. MATERIAL AND METHODS: In this retrospective study, a total of 2039 patients with history of oral malignant tumor between 1980 and 2012 at Seoul National University Dental Hospital were evaluated. We analyzed the dental and medical records, and histopathological database of 2039 patients to assess the prevalence of oral metastasis of carcinoma in terms of sex and age, as well as, the most common origin of primary cancer, and prevalent site and histopathological type of metastatic carcinoma. RESULTS: Among 2039 patients, 21 (1.03%) were finally diagnosed with metastatic carcinoma of the jaws and oral region. Among the 21 patients, only 11 had a working diagnosis as oral metastasis upon clinical evaluation before performing a biopsy. The mean age at the time of diagnosis with a metastatic carcinoma was 56.86, and there was a male preponderance. Metastatic carcinoma was more frequent in the jaws than in the soft tissue, especially in the mandible compared to the maxilla. The most frequent primary site was the lungs, followed by the liver and breasts. The predominant histopathological types were hepatocellular carcinoma and adenocarcinoma. Patient outcomes indicated a poor prognosis with the time from the appearance of the metastasis to death was only 12 months. CONCLUSIONS: According to these cases, oral metastases of carcinoma were exceedingly rare in Koreans. It can allow the clinicians take into account the possible presence of metastases and lead to early diagnosis.

Prognostic Value of Labyrinthine 3D-FLAIR Abnormalities in Idiopathic Sudden Sensorineural Hearing Loss.

BACKGROUND AND PURPOSE: According to recent research, modern MR imaging can detect the presense of abnormalities on labyrinthine. Our aim was to report the patterns and prognostic role of abnormal findings on labyrinthine imaging in patients with sudden sensorineural hearing loss. MATERIALS AND METHODS: This study comprised 113 patients who were diagnosed with unilateral sudden sensorineural hearing loss and underwent 3T MR imaging, including pre-/postcontrast 3D fluid-attenuated inversion recovery and T1-weighted imaging. We analyzed abnormalities on MR imaging and correlated them with audiometric results. RESULTS: Thirty-one (27%) patients showed abnormal findings on labyrinthine MR imaging in the affected ear. The initial/final hearing levels of the MRI+ group (91 ± 25/73 ± 27 dB hearing loss) were significantly worse than those of the MRI- group (69 ± 30/48 ± 24 dB hearing loss). The incidence of abnormalities on labyrinthine MR imaging was significantly lower (3 of 40, 8%) in 40 patients with initial mild-to-moderate hearing loss than in those with profound hearing loss (16 of 34, 47%). Considering hearing improvement by the Siegel criteria, the rate of complete or partial recovery was significantly higher in the MRI- group (34%) than in the MRI+ group (10%). In patients with initial severe or profound hearing loss, the MRI- group showed greater hearing improvement (38 ± 21 dB) than the MRI+ group (23 ± 22 dB). CONCLUSIONS: Abnormalities on labyrinthine MR imaging were found in 27% of patients with sudden sensorineural hearing loss. The initial hearing loss was worse in the MRI+ group than in the MRI- group. In patients with initial severe and profound hearing loss, the presence of abnormalities on labyrinthine MR imaging indicated a poor prognosis.

Source identification and distribution reveals the potential of the geochemical Antarctic sea ice proxy IPSO25.

The presence of a di-unsaturated highly branched isoprenoid (HBI) lipid biomarker (diene II) in Southern Ocean sediments has previously been proposed as a proxy measure of palaeo Antarctic sea ice. Here we show that a source of diene II is the sympagic diatom Berkeleya adeliensis Medlin. Furthermore, the propensity for B. adeliensis to flourish in platelet ice is reflected by an offshore downward gradient in diene II concentration in >100 surface sediments from Antarctic coastal and near-coastal environments. Since platelet ice formation is strongly associated with super-cooled freshwater inflow, we further hypothesize that sedimentary diene II provides a potentially sensitive proxy indicator of landfast sea ice influenced by meltwater discharge from nearby glaciers and ice shelves, and re-examination of some previous diene II downcore records supports this hypothesis. The term IPSO25-Ice Proxy for the Southern Ocean with 25 carbon atoms-is proposed as a proxy name for diene II.

Multidetector-row computed tomography (MDCT) features of small bowel obstruction (SBO) caused by Meckel's diverticulum.

OBJECTIVES: To report the multidetector-row computed tomography (MDCT) findings of small bowel obstruction (SBO) caused by Meckel's diverticulum. MATERIALS AND METHODS: Ten patients (9 men and 1 woman; age range, 2-44 years; median age, 21years) with surgical proven Meckel's diverticulum who presented SBO on the preoperative MDCT were included in the study. RESULTS: On MDCT, all patients presented with SBO, either high-grade (n=6) or low-grade obstruction (n=4). Meckel's diverticulum was identified in five patients (n=5, 50%) on preoperative MDCT. In the five patients in whom a diverticulum was not seen on preoperative MDCT, MDCT showed a transition site on ileum with dilated proximal loops (n=3), pneumoperitoneum (n=1), jejuno-jejunal intussusception (n=1). Transition zone was located near midline in four patients (4/5, 80%). CONCLUSION: The diagnosis of Meckel's diverticulum complicated SBO can be made with certainty when the diverticulum is visualized on preoperative MDCT. However, the preoperative diagnosis is difficult if the Meckel's diverticulum is not noted on the MDCT. When the obstructive processes are visualized in the lower abdomen or pelvis, particularly near the midline, one should keep in mind that SBO may be caused by Meckel's diverticulum without prior surgical history.

Viability and functional assessment of murine pancreatic islets after transportation between Korea and Japan.

BACKGROUND: Organ donor scarcity remains a restricting factor for pancreatic islet transplantation. To date, limited information is available on the impact of long-distance transportation on transplantable pancreatic islets. The objective of this study was to assess the effects of transportation on the viability and function of murine pancreatic islet cells. METHODS: The isolated murine pancreatic islets were transported from Japan to Korea with the use of commercial modes of transportation: subway and commercial airplane. After transportation, the islets were assessed by performing a viability assay and by evaluating the islets' insulin secretion in response to glucose stimulation. A comparative study was performed for evaluating the insulin secretory responses of transported and control islets (not transported). RESULTS: There was no evidence of contamination in the transported pancreatic islets. No significant differences were observed in the viability and functionality of the transported and control islet cells. CONCLUSIONS: These findings show the feasibility of pancreatic islet transportation from Japan to Korea. Our data could be used not only for the inter-Asian but also for global advancement of animal and human islet transportation methods and transplantation research.

Natural cardiac extracellular matrix sheet as a biomaterial for cardiomyocyte transplantation.

Cardiovascular diseases associated with myocardial infarction are among the major causes of death worldwide due to the limited regenerative capacity of cardiac tissues. Although various approaches, such as biosynthetic biomaterials, have been developed to promote postinfarction cardiac regeneration, a number of limitations, including the immune complications caused by biodegradation of these scaffolds and insufficient cell migration, need to be overcome prior to their clinical application. Hence, the development of natural biomaterials to support myocardial regeneration is crucial. Here, we investigated the effects of a natural biomaterial, cardiac extracellular matrix (ECM) on the proliferation and maintenance of cardiomyocytes in order to assess its suitability for cardiomyocyte expansion. The ECM components not only provide mechanical support, but also induce and preserve the required phenotypic and functional characteristics of the cells. We prepared ECM sheets from decellularized cardiac sections. Cardiomyocytes were then cultured with and without these cardiac ECM sheets. We compared the proliferation rates and phenotypes, and cardiac gene and protein expression, of the cultured cardiomyocytes by automatic cell counting and the MTT assay, microscopy, and RT-PCR and western blotting, respectively. The cardiomyocytes cultured with the natural cardiac ECM sheets exhibited higher proliferation rates and cardiac gene and protein expression than those cultured without the ECM sheets. Our results demonstrate that the ECM sheets are suitable for use in cardiomyocyte transplantation and can provide a novel in vitro model for investigating cell and ECM interactions. We hypothesize that these ECM sheets can be used in the future to improve cardiac transplantation strategies.

Single incision laparoscopic totally extraperitoneal hernioplasty (SIL-TEP): experience of 512 procedures.

PURPOSE: Reports have been issued recently on single incision laparoscopic hernioplasty, but no large-scale study has been conducted as yet. This study aimed to assess the safety and feasibility of the single incision laparoscopic totally extraperitoneal hernioplasty (SIL-TEP) on a large number of cases. METHODS: 512 SIL-TEPs in 471 patients were performed from June 2010 to January 2014 at Incheon St. Mary's Hospital, The Catholic University of Korea. SIL-TEP was performed using a glove single port device and standard laparoscopic instruments. Short-term outcomes were reviewed. RESULTS: Of the 512 hernias, 329 (64.3 %) were indirect, 144 (28.1 %) were direct, 9 (1.8 %) were femoral, and 30 (5.9 %) were combined. There were 3 (0.6 %) conversions to single or three-port laparoscopic transabdominal preperitoneal hernioplasty. Mean operative time was 41.6 min for unilateral hernias and 65.3 min for bilateral hernias. Postoperative complications occurred in 45 cases (9.6 %); 21 were wound seromas, 5 were hematomas, and 18 were urinary retentions. All were successfully treated conservatively. Mean hospital stay was 1.8 days. CONCLUSION: The SIL-TEP is safe and technically feasible. Additional studies on long-term recurrence rates are needed to confirm the safety of SIL-TEP.