Postpartum haemorrhage requiring transfusion and risk of cardiovascular disease later in life: a retrospective cohort study.

OBJECTIVE: To determine whether postpartum haemorrhage (PPH) is associated with cardiovascular disease (CVD), including cerebrovascular and ischaemic heart disease beyond the peripartum period. DESIGN: Population-based cohort study. SETTING: Merged databases of the Korea National Health Insurance (KNHI) claims, National Health Screening Examination and National Health Screening Program for Infants and Children. POPULATION: Women who gave birth in 2007 in the Republic of Korea and who were tracked through to 2015 for the occurrence of CVD. METHODS: Patients were identified and the occurrences of PPH and transfusion were determined using the KNHI claims database. The occurrence of CVD was tracked through 2015 using codes from the International Classification of Diseases, tenth revision (ICD-10). MAIN OUTCOME MEASURES: The risk of CVD after PPH. RESULTS: Among 150 381 women who gave birth during the study period, 9107 were diagnosed with PPH and 899 were treated with transfusion. The risk of CVD in women with PPH was no different than in women without PPH, after adjustment (HR 1.03, 95% CI 0.93-1.13). The risk of CVD in women with PPH requiring transfusion was significantly increased compared with women without PPH, after adjustment (HR 1.60, 95% CI 1.25-2.06). The risk of CVD in women with PPH without transfusion was not significantly different compared with women without PPH (HR 0.96, 95% CI 0.86-1.07). CONCLUSIONS: Postpartum haemorrhage (PPH) requiring transfusion is associated with an increased risk of CVD. Guidelines for management should be established, and further studies on the mechanisms involved should be conducted. TWEETABLE ABSTRACT: PPH requiring transfusion is associated with an increased risk of CVD.

Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression.

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.

Therapeutic advantage of genetically engineered Salmonella typhimurium carrying short hairpin RNA against inhibin alpha subunit in cancer treatment.

Background: In contrast to its well-known endocrine function, the role of inhibin in cancer development and therapeutic response is unclear. Salmonella, particularly less toxic attenuated Salmonella strains, are used to treat cancer in two ways. First, Salmonella accumulate around tumors, penetrate the cell barrier, and replicate inside the tumors. Second, Salmonella can act as a vehicle for delivering anticancer agents or proapoptotic genes to attack tumors. In this study, we aimed to develop a suitable cancer therapeutic strategy by genetically modifying attenuated Salmonella typhimurium to harbor short hairpin RNA (shRNA) expression plasmids targeting alpha subunit of inhibin (sh-INHA). Methods: We analyzed the expression of human INHA in normal and cancer cells and tissues. We developed genetically engineered attenuated S. typhimurium harboring sh-INHA (S. typhimurium/sh-INHA) and assessed its cancer therapeutic effects by using cell culture models and syngeneic mouse tumor models. Results: INHA expression levels were markedly higher in colon cancer and melanoma cells and tissues than in their normal counterparts. Suppression of INHA expression mildly reduced cancer cell survival and induced caspase activation and downregulation of anti-apoptotic Bcl-2 and Bcl-xL expressions. Although the genetically engineered S. typhimurium mildly interfered with the invasion of S. typhimurium into host colon cancer and melanoma cells, S. typhimurium/sh-INHA caused remarkable cytotoxicity in cancer compared with unmodified S. typhimurium or S. typhimurium expressing a control scrambled shRNA (S. typhimurium/sh-Cont). Salmonella typhimurium/sh-INHA-treated mice also showed a significantly inhibited growth of colon cancers and melanomas, with a survival advantage. Conclusion: Our results suggest that tumor-targeted therapy using S. typhimurium/sh-INHA may provide a novel cancer treatment option.

Release of TGF-ß1 into root canals with various final irrigants in regenerative endodontics: an in vitro analysis.

AIM: To investigate the release of growth factors into the root canal space after various final irrigants during regenerative endodontic procedures. The residual cytotoxic effect of final irrigants on stem cells from the apical papilla (SCAP) was also examined. METHODOLOGY: To measure the release of TGF-ß1, root segments (8 mm long) were irrigated with 1.5% NaOCl followed by 20 mL of final irrigants; Saline, 17% EDTA, 10% citric acid, 10% or 37% phosphoric acid. Specimens were then immersed into culture medium for 24 h and the supernatants were collected to measure TGF-ß1 by ELISA. For the cytotoxicity of residual final irrigants, dentine chips (5 × 5 × 1 mm) treated with irrigants as above were placed in the upper chamber of transwell system. Stem cells from the apical papilla were incubated indirectly in the lower chamber for 24 h and MTS assay was performed after 24 h. The surfaces of irrigated root canals were examined for smear layer with a scanning electron microscope (SEM). Log transformation was performed for ELISA data to compare different groups (one-way ANOVA, α = 0.05). RESULTS: Ten percent citric acid released the greatest amount of TGF-ß1 amongst all groups, which was significantly different to 17% EDTA (P < 0.01). All dentine chips irrigated with the irrigants showed no significant difference of cytotoxicity on SCAP compared to nonirrigated dentine (P > 0.05). SEM revealed completely open dentinal tubules in 10% citric acid, whereas 17% EDTA was associated with partially open dentinal tubules. CONCLUSIONS: Ten percent citric acid was effective as a final irrigant for releasing TGF-ß1 with good biocompatibility in regenerative endodontics.

Developmental therapeutics for patients with breast cancer and central nervous system metastasis: current landscape and future perspectives.

Breast cancer is the second-leading cause of metastatic disease in the central nervous system (CNS). Recent advances in the biological understanding of breast cancer have facilitated an unprecedented increase of survival in a subset of patients presenting with metastatic breast cancer. Patients with HER2 positive (HER2+) or triple negative breast cancer are at highest risk of developing CNS metastasis, and typically experience a poor prognosis despite treatment with local and systemic therapies. Among the obstacles ahead in the realm of developmental therapeutics for breast cancer CNS metastasis is the improvement of our knowledge on its biological nuances and on the interaction of the blood­brain barrier with new compounds. This article reviews recent discoveries related to the underlying biology of breast cancer brain metastases, clinical progress to date and suggests rational approaches for investigational therapies.

Comparison of the paediatric blade of the Pentax-AWS and Ovassapian airway in fibreoptic tracheal intubation in patients with limited mouth opening and cervical spine immobilization by a semi-rigid neck collar: a randomized controlled trial.

BACKGROUND: We compared the performances of the paediatric blade of a Pentax Airway Scope and an Ovassapian airway in fibreoptic tracheal intubation in patients whose necks were stabilized by semi-rigid neck collars. METHODS: Ninety patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated to one of two groups (Group OVA-FOB and Group AWS-FOB). The time to tracheal intubation, success rate of tracheal intubation, number of optimization manoeuvres (jaw thrust), and difficulty of manipulation of the fibreoptic bronchoscope were compared between the groups. RESULTS: The time to tracheal intubation was significantly shorter (32 vs 50 s; median difference 19 s; 95% confidence interval 14-25 s; P<0.001) and manipulation of the fibreoptic bronchoscope was significantly easier for Group AWS-FOB. Optimization manoeuvres were rarely required to facilitate fibreoptic tracheal intubation in Group AWS-FOB [jaw thrust, 0 (0%); jaw thrust with anterior neck collar removal, 1 (2%)] compared with that required in Group OVA-FOB [jaw thrust, 39 (87%); jaw thrust with anterior neck collar removal, 2 (4%)]. There was no significant difference in the success rate of tracheal intubation on the first attempt between groups [Group AWS-FOB, 45 (100%); Group OVA-FOB, 44 (98%)]. CONCLUSIONS: Combined use of the paediatric blade of a Pentax Airway Scope and a fibreoptic bronchoscope enabled rapid tracheal intubation, minimizing the use of external manoeuvres of the airway, in patients with limited mouth opening and cervical spine immobilization by semi-rigid neck collars, compared with use of the Ovassapian airway and the fibreoptic bronchoscope. CLINICAL TRIAL REGISTRATION: NCT02827110.

S100A9 and EGFR gene signatures predict disease progression in muscle invasive bladder cancer patients after chemotherapy.

BACKGROUND: In our previous gene expression profile analysis, IL1B, S100A8, S100A9, and EGFR were shown to be important mediators of muscle invasive bladder cancer (MIBC) progression. The aim of the present study was to investigate the ability of these gene signatures to predict disease progression after chemotherapy in patients with locally recurrent or metastatic MIBC. PATIENTS AND METHODS: Patients with locally advanced MIBC who received chemotherapy were enrolled. The expression signatures of four genes were measured and carried out further functional analysis to confirm our findings. RESULTS: Two of the four genes, S100A9 and EGFR, were determined to significantly influence disease progression (P = 0.023, 0.045, respectively). Based on a receiver operating characteristic curve, a cut-off value for disease progression was determined. Patients with the good-prognostic signature group had a significantly longer time to progression and cancer-specific survival time than those with the poor-prognostic signature group (P < 0.001, 0.042, respectively). In the multivariate Cox regression analysis, gene signature was the only factor that significantly influenced disease progression [hazard ratio: 4.726, confidence interval: 1.623-13.763, P = 0.004]. In immunohistochemical analysis, S100A9 and EGFR positivity were associated with disease progression after chemotherapy. Protein expression of S100A9/EGFR showed modest correlation with gene expression of S100A9/EGFR (r = 0.395, P = 0.014 and r = 0.453, P = 0.004). Our functional analysis provided the evidence demonstrating that expression of S100A9 and EGFR closely associated chemoresistance, and that inhibition of S100A9 and EGFR may sensitize bladder tumor cells to the cisplatin-based chemotherapy. CONCLUSIONS: The S100A9/EGFR level is a novel prognostic marker to predict the chemoresponsiveness of patients with locally recurrent or metastatic MIBC.

Do newly built homes affect rhinitis in children? The ISAAC phase III study in Korea.

BACKGROUND: As Korea has experienced rapid economic development, the lifestyles of Koreans have become more Westernized, in terms of urbanization and dietary habits. Also, the prevalences of allergic diseases, such as rhinitis, asthma, and dermatitis, have increased rapidly. This study aimed to identify the factors influencing the symptoms of rhinitis conditions, including rhinitis, allergic rhinitis, overlapped rhinitis, and overlapped allergic rhinitis, among Korean children aged 6-7 years. METHODS: The study subjects were drawn from participants in the International Study of Asthma and Allergies in Childhood (ISAAC) study in 2010 and were aged 6-7 years. We analysed data for a total of 3804 children. RESULTS: The prevalences of symptoms suggestive of rhinitis and allergic rhinitis in the previous 12 months were 43.4% and 22.1%, respectively. For overlapped rhinitis and overlapped allergic rhinitis, only 2.5% and 1.9% of the children had overlapping symptoms, having rhinitis with asthma and eczema simultaneously. Gender, a parental history of allergic disease, mould or dampness at home, and the risk factors for 'sick building syndrome' (SBS) were risk factors influencing rhinitis diseases. In particular, a history of moving to a newly built home in the child's infancy was strongly associated with symptoms of all the rhinitis diseases examined. CONCLUSIONS: This study identified patterns of the prevalence of rhinitis conditions among Korean children that were similar to those reported in Western countries. We confirmed that a history of moving to a newly built home during infancy was associated with a considerable risk of rhinitis conditions.

The hOGG1 mutant genotype is associated with prostate cancer susceptibility and aggressive clinicopathological characteristics in the Korean population.

BACKGROUND: The gene encoding human 8-oxoguanine glycosylase 1 (hOGG1) is involved in DNA base excision repair from oxidatively damaged DNA. A case-control study was conducted to evaluate the correlation between the susceptibility and clinicopathological outcomes of prostate cancer (CaP) and hOGG1 genotype. PATIENTS AND METHODS: Subjects were recruited from 266 CaP patients and 266 age-matched benign prostatic hyperplasia patients. The hOGG1 codon 326 genotype was determined by peptide nucleic acid-mediated PCR clamping and compared with Gleason score and tumor stage. RESULTS: The Cys allele at codon 326 of hOGG1 was associated with an increased risk of CaP in comparison with the Ser allele (P = 0.005). Gleason scores of 8 or higher were observed more often in patients with the mutant genotypes Ser/Cys and Cys/Cys than in those with a wild-type genotype (P = 0.045), and the Cys/Cys homozygous genotype was associated with a significantly higher risk of metastatic disease in comparison with the Ser/Ser genotype (P = 0.017). CONCLUSIONS: These results suggest that hOGG1 is associated with the susceptibility to CaP and its aggressive clinicopathological characteristics.

Remifentanil requirement for acceptable intubation conditions with two different doses of ketamine without a neuromuscular blocking agent in pediatric patients.

OBJECTIVE: The optimal remifentanil concentration for improving intubation conditions when intubation is performed without neuromuscular blocking agents (NMBAs) but with ketamine as an induction agent remains unknown. Here, we aimed to identify the effective bolus doses of remifentanil required to achieve acceptable intubation conditions upon anesthesia induction with 1 or 2 mg/kg ketamine without NMBAs. PATIENTS AND METHODS: In this prospective, double-blinded, randomized up-down sequential allocation study, we enrolled pediatric patients aged 3-12 years undergoing general anesthesia for inguinal hernia surgery. The patients were randomly allocated to one of two groups to receive either ketamine 1.0 mg/kg (K1 group) or 2.0 mg/kg (K2 group) intravenously until seven success-failure pairs were achieved. The remifentanil dose for each patient was determined using the modified Dixon's up-and-down method with an initial dose of 2.5 µg/kg and a step size of 0.5 µg/kg. RESULTS: In total, 51 patients (22 in the K1 group and 29 in the K2 group) were enrolled. The effective dose (ED)50s of remifentanil for obtaining clinically acceptable intubation conditions under anesthesia induction with ketamine but without NMBAs was 3.2 µg/kg in the K1 group and 1.6 µg/kg in the K2 group. High-dose remifentanil with 1 mg/kg ketamine was associated with more severe chest wall rigidity and lower mean blood pressure and heart rate than was low-dose remifentanil with 2 mg/kg ketamine. CONCLUSIONS: The ED50 of remifentanil required for clinically acceptable intubation conditions with anesthesia induction using 1 mg/kg ketamine without NMBAs in pediatric patients was twice that when using 2 mg/kg ketamine. The combination of 2 mg/kg ketamine and remifentanil was better at preventing chest wall rigidity.

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure.

INTRODUCTION/OBJECTIVES: It has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility. ANIMALS, MATERIALS AND METHODS: Forty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared. RESULTS: At the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83-155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not. CONCLUSIONS: VLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.

Correlations between skeletal maturity and dental calcification stages in Korean children.

AIM: To evaluate the relationship between dental calcification and skeletal maturity and to identify the tooth with the highest correlation with skeletal maturity index in Korean children. MATERIALS: For 447 children (205 boys and 242 girls) aged between 5 and 13 years, hand-wrist and lateral cephalometric radiographs were taken to assess skeletal maturity by Fishman's skeletal maturity indicators (SMI) and Baccetti's cervical vertebrae maturation (CVM) stages. Dental panoramic radiographs were taken to assess dental maturity of the permanent mandibular canine, first and second premolar, and second molar using the method devised by Dermirjian. CONCLUSION: Dental calcification stages determined by panoramic radiographs can be clinically used as useful indices to predict skeletal maturity in Korean children.

Suspected human intravenous immunoglobulin-induced acute haemolytic anaemia in a dog.

A 2-year-old mixed breed dog presented with a 1-year history of crust and erosion on the nasal planum. Because histopathological examination revealed ruptured intraepidermal pustules and superficial dermal inflammation, the dog was diagnosed with pemphigus foliaceus. Human intravenous immunoglobulin was administered in two consecutive doses of 0.5 g/kg/day due to poor therapeutic response to previous immunosuppressive therapy. From Day 3 after the first dose of human intravenous immunoglobulin, tachypnoea, pale mucous membrane, haemoglobinuria and haemoglobinemia were observed, thus confirming haemolytic anaemia. Other drug-induced haemolytic anaemias were excluded because no additional drugs had been administered before the haemolysis occurred. Immune-mediated haemolytic anaemia was also excluded because the direct antiglobulin test was negative. Two transfusions were performed, and haemolysis was not observed from Day 4 of haemolytic anaemia onset. In conclusion, human intravenous immunoglobulin-induced haemolytic anaemia should be considered in dogs that develop haemolysis following the administration of human intravenous immunoglobulin.

Ulnar nerve morphology on magnetic resonance imaging predicts nerve recovery after surgery for cubital tunnel syndrome.

Magnetic resonance imaging (MRI) can evaluate nerve morphology in cubital tunnel syndrome (CuTS), but its value in predicting surgical outcome is unclear. The purpose of this study was to determine whether ulnar nerve morphology on MRI correlated with outcome after CuTS surgery. We reviewed 40 patients who had preoperative MRI and electrodiagnostic (EDX) examinations for CuTS and outcome evaluation 6 months and 2 years postoperatively. Using MRI, ulnar nerve cross-sectional area (UNCSA), changes in signal intensity, and any space-occupying lesion were evaluated. Other factors assessed were age, symptom duration and severity, type-2 diabetes and EDX parameters. Factors associated with unfavorable surgical outcome were identified. At 6 months postoperatively, 12 patients (30%) had excellent, 19 (47.5%) good, 8 (20%) fair and 1 (2.5%) poor results on modified Wilson-Krout criteria. On univariate analysis, unfavorable outcomes were associated with increased UNCSA, space-occupying lesion, and decreased motor nerve conduction velocity (mNCV), and on multivariate analysis with increased UNCSA 1 cm distal from the epicondyle only (model 1) or increased UNCSA 1 cm proximal from the epicondyle and decreased mNCV (model 2). At 2 years, 15 patients (37.5%) had excellent, 21 (52.5%) good, 3 (7.5%) fair and 1 (2.5%) poor results, and no factors correlated with unfavorable outcome. Increased UNCSA on MRI was associated with unfavorable outcome at 6 months but not at 2 years. This study suggests that morphologic ulnar nerve changes can predict delayed nerve recovery after surgery for CuTS.

A Blood-Based Metabolite Panel for Distinguishing Ovarian Cancer from Benign Pelvic Masses.

PURPOSE: To assess the contributions of circulating metabolites for improving upon the performance of the risk of ovarian malignancy algorithm (ROMA) for risk prediction of ovarian cancer among women with ovarian cysts. EXPERIMENTAL DESIGN: Metabolomic profiling was performed on an initial set of sera from 101 serous and nonserous ovarian cancer cases and 134 individuals with benign pelvic masses (BPM). Using a deep learning model, a panel consisting of seven cancer-related metabolites [diacetylspermine, diacetylspermidine, N-(3-acetamidopropyl)pyrrolidin-2-one, N-acetylneuraminate, N-acetyl-mannosamine, N-acetyl-lactosamine, and hydroxyisobutyric acid] was developed for distinguishing early-stage ovarian cancer from BPM. The performance of the metabolite panel was evaluated in an independent set of sera from 118 ovarian cancer cases and 56 subjects with BPM. The contributions of the panel for improving upon the performance of ROMA were further assessed. RESULTS: A 7-marker metabolite panel (7MetP) developed in the training set yielded an AUC of 0.86 [95% confidence interval (CI): 0.76-0.95] for early-stage ovarian cancer in the independent test set. The 7MetP+ROMA model had an AUC of 0.93 (95% CI: 0.84-0.98) for early-stage ovarian cancer in the test set, which was improved compared with ROMA alone [0.91 (95% CI: 0.84-0.98); likelihood ratio test P: 0.03]. In the entire specimen set, the combined 7MetP+ROMA model yielded a higher positive predictive value (0.68 vs. 0.52; one-sided P < 0.001) with improved specificity (0.89 vs. 0.78; one-sided P < 0.001) for early-stage ovarian cancer compared with ROMA alone. CONCLUSIONS: A blood-based metabolite panel was developed that demonstrates independent predictive ability and complements ROMA for distinguishing early-stage ovarian cancer from benign disease to better inform clinical decision making.

Predictive factors for long-term survival in patients with clinically significant portal hypertension following resection of hepatocellular carcinoma.

BACKGROUND: Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. AIM: To clarify the post-operative prognostic relevance of clinically significant PHT in Child-Pugh A cirrhotic patients. METHODS: A total of 100 Child-Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). RESULTS: Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P<0.001). The proportion of patients who died because of complications of cirrhosis was significantly higher in the PHT group (P=0.001). Multivariate analysis indicated that the presence of clinically significant PHT was the most powerful adverse prognostic factor for overall survival. Multivariate analysis of the 47 patients with clinically significant PHT indicated that gross vascular invasion and non-single nodular type were poor prognostic factors. The 5-year survival rate of patients with single nodular type and without gross vascular invasion (n=17) was 78.4%. CONCLUSIONS: In Child-Pugh A cirrhotic patients, the presence of clinically significant PHT was significantly associated with post-operative hepatic decompensation and poor prognosis after resection of HCC. However, in patients with clinically significant PHT, those with single nodular tumours lacking gross vascular invasion may be good surgical candidates.

Observation of room temperature negative differential resistance in multi-layer heterostructures of quantum dots and conducting polymers.

Multi-layer heterostructure negative differential resistance devices based on poly-[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4-phenylenevinylene] (MEH-PPV) conducting polymer and CdSe quantum dots is reported. The conducting polymer MEH-PPV acts as a barrier while CdSe quantum dots form the well layer. The devices exhibit negative differential resistance (NDR) at low voltages. For these devices, strong negative differential resistance is observed at room temperature. A maximum value of 51 for the peak-to-valley ratio of current is reported. Tunneling of electrons through the discrete quantum confined states in the CdSe quantum dots is believed to be responsible for the multiple peaks observed in the I-V measurement. Depending on the observed NDR signature, operating mechanisms are explored based on resonant tunneling and Coulomb blockade effects.

Detection and characterization of enterovirus associated with herpangina and hand, foot, and mouth disease in Seoul, Korea.

BACKGROUND: Human enteroviruses (HEVs) are a major cause of herpangina, HFMD (hand, foot, and mouth disease), and other neurological diseases in Seoul, Korea. METHODS: A total of 56 specimens from hospitalized patients collected from February to December 2009 (37 females and 19 males) in Seoul were tested for HEV from stool, throat swab, and vesicle swab samples taken from patients with herpangina or HFMD using cell culture and RT-PCR in 2009. By the 1D gene, encoding the VP1 capsid protein, seven different HEV genotypes were detected with Coxsackievirus A2, A4, A5, A9, A16 (CA), Coxsackievirus B1 (CB), and Enterovirus 71 (EV71). The most prevalent genotype was CA16 (6, 10.7%), followed by CA2 (4, 7.1%), CA5 (4, 7.1%), EV71 (2, 3.6%), CA4 (1, 1.8%), CA9 (1, 1.8%), and CB1 (1, 1.8%). The 1D gene sequences of two EV71 strains were closely related with one another (98.5% nucleotide similarity) and belonged to the C4 genotype. CONCLUSIONS: It is important to continuously survey the genetic characteristics of EV71 and CA16 from patients, which will provide useful data that aids in our understanding of HFMD infections in Seoul, Korea and may contribute to future control.

Customized surgical guide with a bite block and retraction arm for a deeply impacted odontoma; a technical note.

Odontomas can cause impaction of permanent teeth. During the removal of odontomas associated with an impacted tooth, minimally-invasive surgical approaches are necessary. We present a technical note highlighting easy extraction of a deeply impacted odontoma using a patient-specific computer-aided design/computer-aided manufacturing (CAD/CAM) surgical guide. Its use and advantages are described.

Potential role of CMPK1, SLC29A1, and TLE4 polymorphisms in gemcitabine-based chemotherapy in HER2-negative metastatic breast cancer patients: pharmacogenetic study results from the prospective randomized phase II study of eribulin plus gemcitabine versus paclitaxel plus gemcitabine (KCSG-BR-13-11).

BACKGROUND: In this study, we evaluated the association between genetic polymorphisms of 23 genes associated with gemcitabine metabolism and the clinical efficacy of gemcitabine in breast cancer patients. PATIENTS AND METHODS: This prospective, pharmacogenetic study was conducted in cooperation with a phase II clinical trial. A total of 103 genetic polymorphisms of the 23 genes involved in gemcitabine transport and metabolism were selected for genotyping. The associations of genetic polymorphisms with overall survival, progression-free survival (PFS), and 6-month PFS were analyzed. RESULTS: A total of 91 breast cancer patients were enrolled in this study. In terms of 6-month PFS, rs1044457 in CMPK1 was the most significant genetic polymorphism [55.9% for CT and TT and 78.9% for CC, P < 0.001, hazard ratio (HR): 4.444, 95% confidence interval (CI): 1.905-10.363]. For the rs693955 in SLC29A1, the median duration of PFS was 5.4 months for AA and 10.5 months for CA and CC (P = 0.002, HR: 3.704, 95% CI: 1.615-8.497). For the rs2807312 in TLE4, the median duration of PFS was 5.7 months for TT and 10.4 months for CT and CC (P = 0.005, HR: 4.948, 95% CI: 1.612-15.190). In survival analysis with a multi-gene model, the TT genotype of rs2807312 had the worst PFS regardless of other genetic polymorphisms, whereas the CA genotype of rs693955 or the CT genotype of rs2807312 without the AA genotype of rs693955 had the best PFS compared with those of other genetic groups (P < 0.001). CONCLUSIONS: Genetic polymorphisms of rs1044457 in CMPK1, rs693955 in SLC29A1, and rs2807312 in TLE4 were significantly associated with the 6-month PFS rate and/or the duration of PFS. Further studies with a larger sample size and expression study would be helpful to validate the association of genetic polymorphisms and clinical efficacy of gemcitabine.