Hemangioblastomas with leptomeningeal dissemination: case series and review of the literature.

BACKGROUND: Leptomeningeal dissemination of hemangioblastomas (HB) of the central nervous system (CNS) is extremely rare. Few studies have reported leptomeningeal involvement in sporadic HB or in HB associated with von Hippel-Lindau syndrome. The clinical and radiological features of leptomeningeal involvement in HB after surgery have not been described in detail. MATERIALS AND METHODS: This retrospective case review involved patients from three different tertiary referral centers with leptomeningeal dissemination of HB after surgery for the primary mass. A literature review was also performed to describe the clinical and radiological characteristics and long-term outcomes of patients who developed leptomeningeal dissemination after initial surgical resection. RESULTS: This study included seven patients, five males and two females, ranging in age from 36 to 54 years. Incidence of leptomeningeal dissemination in patients with HB was about 4.3 % (3/69). It appeared at a mean 94.9 months (range, 39-204 months) after gross total resection of CNS HBs. Three of the seven patients died 5, 38, and 79 months, respectively, after diagnosis of leptomeningeal dissemination. Review of the literature identified 21 patients with characteristics of leptomeningeal dissemination similar to those in our series. CONCLUSIONS: Leptomeningeal dissemination of HB is a rare pattern of long-term recurrence. Long-term outcomes may be fatal. The long developmental period suggests that early detection and aggressive management may improve prognosis in patients with CNS leptomeningeal dissemination of HB.

First report: Robotic pelvic exenteration for locally advanced rectal cancer.

AIM: The aim of this study was to present the feasibility and surgical outcome of robotic en bloc resection of the rectum and with prostate and seminal vesicle invaded by rectal cancer. METHOD: The details of three consecutive cases involving male patients in their forties, with locally invasive low rectal cancers are presented. The da Vinci robotic system was used by experienced colorectal and urological surgeons to perform en bloc resection of the rectum, prostate and seminal vesicles. RESULTS: In the first case, coloanal and vesico-urethral anastomoses were performed, and the second included an end colostomy and vesico-urethral anastomosis. The bladder and bulbar urethra were also removed en bloc in the third case, with robotic intracorporeal ileal conduit formation and end colostomy. There was no major complication postoperatively. In the second patient there was a minor leakage at the vesico-urethral anastomosis. The third was readmitted the following week with a urinary infection which settled with intravenous antibiotics. In the first case, the circumferential resection margin was microscopically positive but the patient is currently free of recurrence after 14 months. In the second and third cases, all margins were clear. CONCLUSION: This the first report of the use of the da Vinci robotic system for pelvic exenteration in patients with locally advanced rectal cancer invading the prostate and seminal vesicles. The robot may have a potential role in selected patients requiring exenterative pelvic surgery particularly in men.

Role of the superior turbinate when performing endoscopic endonasal transsphenoidal approach.

BACKGROUND: This study examined the relationship between the superior turbinate and natural ostium of the sphenoid sinus, as seen during the endoscopic endonasal transsphenoidal approach (EETSA) for sellar lesions and described how to enter the sphenoethmoid cell safely for complete exposure of the sellar floor, including adjacent vital structures such as the prominence of the optic nerve and carotid artery. MATERIALS AND METHODS: This study retrospectively reviewed the medical records and operative findings of 154 patients, who underwent EETSA between February 2009 and February 2011. We evaluated the location of the natural ostium of the sphenoid sinus relative to the superior turbinate and revealed the clinical significance of the superior turbinate as a surgical guide to enter into the sphenoethmoid cell during EETSA. RESULTS: The natural ostium of the sphenoid sinus was located medially to the posteroinferior end of the superior turbinate in 151 (98%) patients. In 1 patient, the natural ostia of the sphenoid sinus were located lateral to the superior turbinate bilaterally. Sphenoethmoid cell was encountered in 53 (34%) patients. We could easily enter the sphenoethmoid cell at the point where the superior turbinate was attached to the anterior wall of the sphenoid sinus. CONCLUSIONS: The superior turbinate is a good surgical landmark for identifying the natural ostium of the sphenoid sinus and as a guide for the surgical entrance to the sphenoethmoid cell extending to the sphenoid sinus during EETSA.

The relaxant effect of ginseng saponin on the bladder and prostatic urethra: an in vitro and in vivo study.

AIM: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. MATERIALS AND METHODS: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10(-6)-10(-2)M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (P(ves)) and urethral perfusion pressure (UPP). RESULTS: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10(-3)M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10(-2)M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline P(ves) than the PBOO group. CONCLUSIONS: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.

Pilot study of the Korean national breast implant registry: Experiences and lessons learned.

BACKGROUND: To improve the safety and early detection of unexpected breast implant-related complications, the Korean Breast Implant Registry (K-BIR) was launched in 2020 in cooperation with the Korean Society of Plastic and Reconstructive Surgeons and the Korean Ministry of Food and Drug Safety, and a pilot study was conducted. OBJECTIVE: This article provides an overview of our pilot study and experiences of the K-BIR. METHODS: The dataset to be used in the pilot form of K-BIR was constructed by holding online surveys and meetings focusing on the global breast device registry's minimum dataset. A pilot study was implemented from April 1, 2020, to July 31, 2020, with six university teaching hospitals and four private clinics. RESULTS: During the pilot study period, 325 patients, 451 procedures, and 366 implants were entered into the K-BIR. The most common procedure registered was augmentation mammaplasty (30%) for cosmetic indications, followed by direct-to-implant breast reconstruction (27%). Smooth silicone implant was the most common type (73%) of implant used. A feedback survey after the pilot study included questions about the registration rate compared with an actual procedure, entry time, reasons for difficulty in entry, and additional data needed. CONCLUSIONS: The continuous maintenance and development of K-BIR will require an effective dataset, a strengthened legal system for an opt-out registry and personal data protection, various incentives for increasing participation rates, and an electronic platform that patients, manufacturers, and clinicians can easily access. K-BIR has the potential to provide quality assurance and outcomes for research and post-market surveillance systems for breast implants as well as methods for enhancing patient safety.

Expression of RUNX3 in skin cancers.

BACKGROUND: Expression of Runt-related transcription factor 3 (RUNX3) is reduced in a large number of cancers. However, a few studies have reported higher expression of RUNX3 in several cancers, including basal cell carcinoma (BCC). In light of this, we explored the expression of RUNX3 in skin cancers generally, to determine whether it acts as an oncogene or a tumour-suppressor gene in skin tumours. AIM: To investigate the expression of RUNX3 in normal skin and malignant skin tumours. METHODS: RUNX3 expression was evaluated by western blotting in 24 specimens, comprising 6 malignant melanoma (MM), 6 squamous cell carcinoma (SCC), 6 BCC and 6 normal skin specimens. Immunohistochemical staining was carried out to analyse RUNX3 expression in 16 MM, 16 SCC and 16 BCC specimens. To identify where the protein was expressed, the cytoplasmic and nuclear protein expression of RUNX3 in skin cancer tissues was determined. A cell-proliferation study was performed on an MM line (G361) by small interfering (si)RNA transfection. RESULTS: The western blotting experiments showed that RUNX3 was not expressed in normal skin tissues, but it was overexpressed in all MM and SCC samples, and in five of the six BCC samples. Using immunochemistry, RUNX3 was found to be overexpressed in all cancer tissues analysed. Subcellular fraction analysis revealed that RUNX3 was expressed in the nuclei but not the cytoplasm of all the skin cancer tissues analysed, and RUNX3 silencing by siRNA in G361 cells resulted in a decrease in proliferation. CONCLUSIONS: Based on these results, we suggest that RUNX3 has an oncogenic potential and does not act as a tumour suppressor in skin cancers.

Long-term outcome of tamsulosin for patients with lower urinary tract symptoms according to the treatment response defined by lower urinary tract symptom outcomes score.

UNLABELLED: IMS: To evaluate long-term outcome of tamsuolsin 0.2 mg for benign prostatic hyperplasia (BPH) patients using a new subjective assessment of patient-reported outcomes and the lower urinary tract symptoms (LUTS) outcome score (LOS) over a 48-week period. METHODS: This study investigated the long-term outcomes of either well-responded or poorly responded patient group as defined by LOS at the period of 12 weeks after BPH treatment. Outcome parameters used in this study were the most bothersome symptoms, BPH K1-short form as well as International Prostate Symptom Score (IPSS), maximum flow rate (Qmax) and postvoiding residual urine volume at 24-, 36- and 48-week follow-up. RESULTS: Of the 414 patients recruited initially, 310 (75.2%) were defined as the responders and 39 (9.5%) as the non-responders to the treatment at 12 weeks, which was stratified by LOS. In this long-term study, the differences in improvement rates of clinical parameters between responder and non-responder groups at 12 weeks of treatment were maintained over the period of 48 weeks. Among the responder patients, most (75.6%) chose continuous administrations of tamsulosin. Improvements in clinical parameters were maintained in this subgroup. It is noteworthy that the improvements in clinical parameters of the non-responder group were dismal despite switching to the other treatment modalities. CONCLUSIONS: Long-term tamsulosin 0.2 mg for BPH patients is an effective treatment, both subjectively and objectively. Considering its integrative nature, LOS seemed to be one of the useful tools to predict the outcome after the management of LUTS.

Sports therapy for attention, cognitions and sociality.

The aim of the present study was to understand if sport improves attention symptoms, social competency, and cognitive functions in children with attention deficit and hyperactivity disorder (ADHD). The present study was designed as a 6-week, prospective trial, including 12 sessions of education/sports therapy. 13 ADHD children participated in a 90-min athletic activity (sports-cADHD) twice a week, while 15 ADHD children received education on behavior control (edu-cADHD). During the 6-week treatment period, the sports-cADHD group showed greater improvements in DuPaul's ADHD Rating Scale scores, parent and teacher version (K-ARS-PT), compared to those of the edu-sADHD group. The cognitive functions assessed with the digit symbol and Trail-Making Test part B (TMT B) were improved in the sports-cADHD group, while the cognitive functions observed in the edu-sADHD group were not significantly changed. The cooperativeness scores in the sports-cADHD group were greatly increased compared to those of the edu-sADHD group. The results demonstrated a positive correlation with sports and improvement in attention symptoms, cognitive symptoms and social skills. The results of the present study suggest that therapy in the form of athletic activity may increase social competency in children with ADHD, as demonstrated by improved cognitive functions.

Lack of association between the -759C/T polymorphism of the 5-HT2C receptor gene and olanzapine-induced weight gain among Korean schizophrenic patients.

BACKGROUND: Weight gain can be an adverse effect of antipsychotics that significantly affects long-term health and treatment compliance. Many reports have suggested that the 5-HT2C receptor gene (HTR2C) is related to appetite and eating behaviours associated with body weight change. We hypothesized that there was a relationship between the HTR2C -759C/T polymorphism and olanzapine-induced weight gain. METHOD: Seventy-nine Korean schizophrenic patients were examined. Their weight was measured before starting olanzapine and after long-term treatment for at least 3 months. We controlled the use of drugs other than olanzapine except benzodiazepines and anticholinergics. Genotyping for the HTR2C -759C/T polymorphism was performed on all participants. RESULT: We found that long-term treatment with olanzapine resulted in mean gains in weight and BMI of 5.2 kg and 1.93 kg/m(2), respectively. However, body weight changes from baseline to the study endpoint were not significantly associated with genotypes. The frequency of the T allele did not differ significantly between subjects with weight gains below and above a clinically significant cutoff, defined as 7% relative to baseline (chi(2) = 0.213, P = 0.445), indicating that the T allele had no protective effect against olanzapine-induced weight gain. DISCUSSION AND CONCLUSION: The findings from this study do not support the presence of a relationship between the -759C/T polymorphism of the HTR2C gene and weight gain in Korean schizophrenic patients receiving olanzapine treatment.

Clinical and radiographic results of unilateral transpedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures.

INTRODUCTION: Most previous reports indicate that traditional bilateral kyphoplasty improves patient function and restores height of collapsed vertebral bodies, but limited data about the effects of unilateral kyphoplasty on clinical and radiological outcome are available. MATERIAL AND METHODS: One hundred five patients were treated by unilateral kyphoplasty between January 2004 and December 2006. These patients underwent 105 operations to treat 132 vertebral compression fractures between T8 and L5. Sagittal alignment was analyzed from standing radiographs. Clinical outcomes were determined by comparison of preoperative and postoperative data from patient-reported index (visual analogue pain scale score). Radiographs were assessed as to percent vertebral collapse, vertebral height restoration and local kyphosis correction. RESULTS: Mean length of follow-up was 15.3 months (range 3-36 months); improved height 2.3 and 4.0 mm in the anterior and medial columns, respectively (P > 0.05); Cobb angle increased 3.0 degrees (P < 0.05), visual analogue pain scale score improved from 8.7 +/- 1.4 before surgery to 2.3 +/- 0.9 (P < 0.05); no adverse medical or procedural complications; 6.8% (9/132) cement leakage rate. CONCLUSION: Unilateral transpedicular kyphoplasty improves physical function, reduces pain, and may correct kyphotic deformity associated with vertebral compression fractures. This result shows comparable to traditional bilateral kyphoplasty procedure.

The Effects of N-terminal Mutations on ß-amyloid Peptide Aggregation and Toxicity.

Human amyloid ß1-42 (hAß1-42) peptides are known to self-aggregate into oligomers that contribute to the degeneration of neurons and development of Alzheimer's disease (AD) pathology. Unlike humans, rodents do not develop AD, possibly due to differences in three amino acids (R5G, Y10F and H13R) within the hydrophilic N-terminal domain of Aß1-42. This is partly supported by evidence that hAß1-42 is more prone to fibrillization and has a higher cellular toxicity than rodent Aß1-42 (rAß1-42). Mutagenesis studies, however, have shown that correlation between fibrillization potential and toxicity is not always direct. Thus, to understand better how N-terminal mutations can affect hAß1-42 toxicity through oligomerization, we evaluated fibrillization kinetics, oligomer sizes and toxicity profiles of double mutant (human toward rodent) Aß1-42. Additionally, we tested the mutant peptides in combination with hAß1-42, to assess effects on hAß1-42 aggregation/toxicity. Our results clearly show that double mutations to humanize rAß1-42 result in a significantly reduced efficiency of fibril formation, as determined by Thioflavin-T aggregation assays and confirmed with electron micrographic studies. Interestingly, the mutants are still able to aggregate into oligomers, which are predominantly larger than those comprised of hAß1-42. Our cell viability experiments further showed a rank order of oligomer toxicity of hAß1-42 > rAß1-42 ≫ mutant Aß1-42, suggesting that toxicity can be influenced by N-terminal Aß1-42 mutations via reduction of fibril formation and/or alteration of oligomer size. These results, taken together, confirm that N-terminal mutations can affect Aß fibril and oligomer formation with reduced toxicity despite lying outside the core amyloid region of Aß peptide.

Whole-Tumor Histogram and Texture Analyses of DTI for Evaluation of IDH1-Mutation and 1p/19q-Codeletion Status in World Health Organization Grade II Gliomas.

BACKGROUND AND PURPOSE: Prediction of the isocitrate dehydrogenase 1 (IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas. MATERIALS AND METHODS: Ninety-three patients with World Health Organization grade II gliomas with known IDH1-mutation and 1p/19q-codeletion status (18 IDH1 wild-type, 45 IDH1 mutant and no 1p/19q codeletion, 30 IDH1-mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the IDH1-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for IDH1 wild-type tumors and 1p/19q-codeletion status in IDH1-mutant subgroups were evaluated using the least absolute shrinkage and selection operator. RESULTS: Various histogram and texture parameters differed significantly according to IDH1-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an IDH1 wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in IDH1-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807. CONCLUSIONS: Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the IDH1-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.

Prediction of IDH1-Mutation and 1p/19q-Codeletion Status Using Preoperative MR Imaging Phenotypes in Lower Grade Gliomas.

BACKGROUND AND PURPOSE: WHO grade II gliomas are divided into three classes: isocitrate dehydrogenase (IDH)-wildtype, IDH-mutant and no 1p/19q codeletion, and IDH-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas. MATERIALS AND METHODS: MR imaging scans of 175 patients with lower grade gliomas with known IDH1 mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set. MR imaging features were reviewed by using Visually AcceSAble Rembrandt Images (VASARI); their associations with molecular markers were assessed. The predictive power of imaging features for IDH1-wild type tumors was evaluated using the Least Absolute Shrinkage and Selection Operator. We tested the model in a validation set (40 subjects). RESULTS: Various imaging features were significantly different according to IDH1 mutation. Nonlobar location, larger proportion of enhancing tumors, multifocal/multicentric distribution, and poor definition of nonenhancing margins were independent predictors of an IDH1 wild type according to the Least Absolute Shrinkage and Selection Operator. The areas under the curve for the prediction model were 0.859 and 0.778 in the discovery and validation sets, respectively. The IDH1-mutant, 1p/19q-codeleted group frequently had mixed/restricted diffusion characteristics and showed more pial invasion compared with the IDH1-mutant, no codeletion group. CONCLUSIONS: Preoperative MR imaging phenotypes are different according to the molecular markers of lower grade gliomas, and they may be helpful in predicting the IDH1-mutation status.

Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells.

OBJECTIVES: To characterize mesenchymal stem cell-like cells isolated from human amniotic fluid for a new source of therapeutic cells. MATERIALS: Fibroblastoid-type cells obtained from amniotic fluid at the time of birth. METHODS: The ability of ex vivo expansion was investigated until senescence, and stem cell-like characteristics were analyzed by examining differentiation potential, messenger RNA expression and immunophenotypes. RESULTS AND CONCLUSIONS: A morphologically homogenous population of fibroblastoid-type (HAFFTs) cells, similar to mesenchymal stem cells from bone marrow (BM-MSCs), was obtained at the third passage. The cells became senescent after 27 passages over a period of 8 months while undergoing 66 population doublings. Under appropriate culture conditions, by the 8th passage they differentiated into adipocytes, osteocytes, chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue and anti-NeuN antibody staining, respectively. Immunophenotype analyses at the 17th passage demonstrated the presence of TRA-1-60; SSEA-3 and-4; collagen types I, II, III, IV and XII; fibronectin; alpha-SMA; vimentin; desmin; CK18; CD44; CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase-polymerase chain reaction analysis of the HAFFTs from passages 6-20 showed consistent expression of Rex-1, SCF, GATA-4, vimentin, CK18, FGF-5 and HLA ABC genes. Oct-4 gene expression was observed up to the 19th passage but not at the 20th passage. HAFFTs showed telomerase activity at the 5th passage with a decreased level by the 21st passage. Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed differential gene expression during ex vivo expansion. Taken together, these observations suggest that HAFFTs are pluripotent stem cells that are less differentiated than BM-MSCs, and that their gene expression profiles vary with passage number during ex vivo expansion.

A dual-design expandable colorectal stent for malignant colorectal obstruction: results of a multicenter study.

BACKGROUND AND STUDY AIMS: It is known that metal stent placement is safe, easy, and effective for the treatment of malignant colorectal obstruction, but these stents are associated with delayed complications of tumor ingrowth and stent migration. The aim of this study was to prospectively investigate the technical feasibility, clinical effectiveness, and safety of a dual-design colorectal stent (consisting of an outer stent and an inner bare nitinol stent) in patients with malignant colorectal obstruction. PATIENTS AND METHODS: Placement of the dual stent using a 4.5-mm stent delivery system was attempted in 151 patients with malignant colorectal obstruction, either before surgery (n = 50) or for palliation (n = 101). Multivariate logistic regression analysis was used to identify risk factors associated with complications. RESULTS: Stent placement was technically successful in 145/151 patients (96%). Of the patients who had a technically successful placement, bowel obstruction resolved within 2 days after stent placement in 48/50 (96%) of the patients in the bridge-to-surgery group and in 87/95 (92%) of the patients in the palliative group. Perforation occurred in 16 patients, incomplete stent expansion in eight patients, stent migration in four patients, tumor overgrowth in five patients, severe rectal pain in five patients, and bleeding in eight patients. Complete obstruction was the only significant risk factor for perforation (odds ratio 6.88, 95% CI 2.04-23.17, P = 0.002). In the palliative group, the median survival was 152.0 days and the mean survival was 263.8 days. CONCLUSIONS: The dual stent with a 4.5-mm stent delivery system is easy to insert, safe, and reasonably effective for the palliative treatment of malignant colorectal obstruction. However, a great deal of care is needed in its deployment because of the high rate of perforation.

Characterization of a dUTPase from the hyperthermophilic archaeon Thermococcus onnurineus NA1 and its application in polymerase chain reaction amplification.

Genomic analysis of the hyperthermophilic archaeon Thermococcus onnurineus NA1 (TNA1) revealed the presence of a 471-bp open reading frame with 93% similarity to the dUTPase from Pyrococcus furiosus. The dUTPase-encoding gene was cloned and expressed in Escherichia coli. The purified protein hydrolyzed dUTP at about a 10-fold higher rate than dCTP. The protein behaved as a dimer in gel filtration chromatography, even though it contains five motifs that are conserved in all homotrimeric dUTPases. The dUTPase showed optimum activity at 80 degrees C and pH 8.0, and it was highly thermostable with a half-life (t (1/2)) of 170 min at 95 degrees C. The enzymatic activity of the dUTPase was largely unaffected by variations in MgCl(2), KCl, (NH(4))(2)SO(4), and Triton X-100 concentrations, although it was reduced by bovine serum albumin. Addition of the dUTPase to polymerase chain reactions (PCRs) run with TNA1 DNA polymerase significantly increased product yield, overcoming the inhibitory effect of dUTP. Further, addition of the dUTPase allowed PCR amplification of targets up to 15 kb in length using TNA1 DNA polymerase. This enzyme also improved the PCR efficiency of other archaeal family B type DNA polymerases, including Pfu and KOD.

The Initial Area Under the Curve Derived from Dynamic Contrast-Enhanced MRI Improves Prognosis Prediction in Glioblastoma with Unmethylated MGMT Promoter.

BACKGROUND AND PURPOSE: Although perfusion and permeability MR parameters have known to have prognostic value, they have reproducibility issues. Our aim was to evaluate whether the initial area under the time-to-signal intensity curve (IAUC) derived from dynamic contrast-enhanced MR imaging can improve prognosis prediction in patients with glioblastoma with known MGMT status. MATERIALS AND METHODS: We retrospectively examined 88 patients with glioblastoma who underwent preoperative dynamic contrast-enhanced MR imaging. The means of IAUC values at 30 and 60 seconds (IAUC30mean and IAUC60mean) were extracted from enhancing tumors. The prognostic values of IAUC parameters for overall survival and progression-free survival were assessed with log-rank tests, according to the MGMT status. Multivariate overall survival and progression-free survival models before and after adding the IAUC parameters as covariates were explored by net reclassification improvement after receiver operating characteristic analysis for 1.5-year overall survival and 1-year progression-free survival and by random survival forest. RESULTS: High IAUC parameters were associated with worse overall survival and progression-free survival in the unmethylated MGMT group, but not in the methylated group. In the unmethylated MGMT group, 1.5-year overall survival and 1-year progression-free survival prediction improved significantly after adding IAUC parameters (overall survival area under the receiver operating characteristic curve, 0.86; progression-free survival area under the receiver operating characteristic curve, 0.74-0.76) to the model with other prognostic factors (overall survival area under the receiver operating characteristic curve, 0.81; progression-free survival area under the receiver operating characteristic curve, 0.69; P < .05 for all) except in the case of IAUC60mean for 1-year progression-free survival prediction (P = .059). Random survival forest models indicated that the IAUC parameters were the second or most important predictors in the unmethylated MGMT group, except in the case of the IAUC60mean for progression-free survival. CONCLUSIONS: IAUC can be a useful prognostic imaging biomarker in patients with glioblastoma with known MGMT status, improving prediction of glioblastoma prognosis with the unmethylated MGMT promoter status.

Acute toxicity of organic antifouling biocides to phytoplankton Nitzschia pungens and zooplankton Artemia larvae.

The toxicity of the antifouling biocides Irgarol 1051, Diuron, Chlorothalonil, Dichlofluanid, Sea-nine 211, Copper pyrithione, Zinc pyrithione, Ziram and Zineb were evaluated on Nitzschia pungens and Artemia larvae. Results showed that EC50 for Irgarol 1051 was 0.586µgl-1 was the strongest effect on N. pungens following by Copper pyrithione (4.908µgl-1), Ziram (5.421µgl-1), Zinc pyrithione (5.513µgl-1), Diuron (6.640µgl-1), Zineb (232.249µgl-1), Sea-nine 211(267.368µgl-1), Chlorothalonil (360.963µgl-1) and Dichlofluanid (377.010µgl-1) in 96h. In Artemia larvae, the biocides were evaluated the LC50 for larval survivals at 48h. Sea-nine 211 and Copper pyrithione were 0.318 and 0.319mgl-1. Chlorothalonil, Zinc pyrithione and Ziram were 2.683, 3.147 and 4.778mgl-1. Irgarol 1051, Diuron, Zineb and Dichlofluanid were 9.734, 30.573, 41.170 and 154.944mgl-1. These results provide baseline data concerning the toxicity of antifouling biocides against marine environment.

Cloning, expression, and characterization of a methionyl aminopeptidase from a hyperthermophilic archaeon Thermococcus sp. NA1.

Genomic analysis of a hyperthermophilic archaeon Thermococcus sp. NA1 revealed the presence of an 885-bp open reading frame encoding a protein of 295 amino acids with a calculated molecular mass of 32,981 Da. Analysis of the deduced amino acid sequence showed that amino acid residues important for catalytic activity and the metal binding ligands conserved in all of methionyl aminopeptidases (MetAP) were also conserved and belonged to type IIa MetAP. The protein, designated TNA1_MetAP (Thermococcus sp. NA1 MetAP), was cloned and expressed in Escherichia coli. The recombinant enzyme was a Mn(2+)-, Ni(2+)-, Fe(2+)-, or Co(2+)-dependent metallopeptidase. Optimal MetAP activity against L: -methionine p-nitroanilide (Met-pNA) (K (m) = 0.68 mM) occurred at pH 7.0 and 80 to 90 degrees C. The MetAP was very unstable compared to Pyrococcus furiosus MetAP, which was completely inactivated by heating at 80 degrees C for 5 min. It seemed likely that the cysteine residue (Cys53) played a critical role in regulating the thermostability of TNA1_MetAP.

Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway.

Microbial metabolites, such as short-chain fatty acids (SCFAs), are highly produced in the intestine and potentially regulate the immune system. We studied the function of SCFAs in the regulation of T-cell differentiation into effector and regulatory T cells. We report that SCFAs can directly promote T-cell differentiation into T cells producing interleukin-17 (IL-17), interferon-γ, and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is independent of GPR41 or GPR43, but dependent on direct histone deacetylase (HDAC) inhibitor activity. Inhibition of HDACs in T cells by SCFAs increased the acetylation of p70 S6 kinase and phosphorylation rS6, regulating the mTOR pathway required for generation of Th17 (T helper type 17), Th1, and IL-10(+) T cells. Acetate (C2) administration enhanced the induction of Th1 and Th17 cells during Citrobacter rodentium infection, but decreased anti-CD3-induced inflammation in an IL-10-dependent manner. Our results indicate that SCFAs promote T-cell differentiation into both effector and regulatory T cells to promote either immunity or immune tolerance depending on immunological milieu.