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Articles by Justin Tong in JoVE

 JoVE Bioengineering

Microfluidic-based Electrotaxis for On-demand Quantitative Analysis of Caenorhabditis elegans' Locomotion

1Department of Biology, McMaster University, 2Department of Mechanical Engineering, McMaster University


JoVE 50226

A semi-automated micro-electro-fluidic method to induce on-demand locomotion in Caenorhabditis elegans is described. This method is based on the neurophysiologic phenomenon of worms responding to mild electric fields (“electrotaxis”) inside microfluidic channels. Microfluidic electrotaxis serves as a rapid, sensitive, low-cost, and scalable technique to screen for factors affecting neuronal health.

Other articles by Justin Tong on PubMed

[Genotype of Hantavirus in Zhejiang Province]

To identify the genotype and clades of hantavirus (HV) in Zhejiang province.

[Progress in the Structure and Function of Human Carboxylesterase 1]

Human carboxylesterase 1 (HCE1), belonging to a multigene serine hydrolase family, is a major liver carboxylesterase responsible for the hydrolysis and metabolism of various xenobiotics. It also plays an important role in the transportation and metabolism of endogenous cholesterol ester and free fatty acid, and is closely associated with the pathogenesis of hepatocellular carcinoma. This review describes current developments in the molecular structure, the roles in drug, toxins and lipid metabolism, and the early diagnosis for hepatocellular carcinoma of human carboxylesterase 1.

[Construction and Identification of a Recombinant PRRSV Expressing Protective Antigens of Type O Foot-and-mouth Disease Virus]

Using mutation PCR, we cloned the target gene containing 421-480nt (141-160aa) and 598-639nt (200-213aa) of VP1 gene of foot and mouth disease virus (FMDV) into the deleted region (508-532aa) of Nsp2 gene of a highly pathogenic porcine reproductive and respiratory syndrome virus derived vaccine strain (HuN4-F112) that was used as vector. The recombinant cDNA was in vitro transcribed followed by transfection of BHK-21 cells for 36 h. Then, the supernatant of the cell culture was continuously seeded to monolayer of MARC-145 cells for recovery of the recombinant virus. CPE was obviously visible after a couple of passages in the seeded MARC-145, and the rescued virus (designated as rPRRSV-F112-O/VP1ep) was identified by Mlu I digestion, sequencing and immunofluorescence assay. Meanwhile, expression of inserted FMDV epitopes was also detected by indirect immunofluorescence assay with polyclonal antibodies against VP1 protein of FMDV. The analysis of biological characteristics shows that the titer of the rescued recombinant PRRSV (TCID50 = -log10(-6.75)/0.1 mL) was similar to its direct parental virus rHuN4-F112-delta508-532, but higher than rHuN4-F112.

[Etiological Analysis of Influenza Surveillance Data in Xuzhou from 2005 to 2011]

To investigate the prevalence and subtypes of influenza viruses in Xuzhou city from 2005 to 2011 and to provide the scientific supports for influenza prevention and control in this religion.

[Analysis on Pathogen Detection for 53 Influenza Outbreaks]

In order to provide a scientific basis for influenza prevention and control, analyzing the epidemic characteristics and laws of influenza outbreaks in Xuzhou area during 2005-2011.

[Experimental Study on Yougui Recipe in Preventing Osteolysis Surrounding Artificial Prosthesis]

To explore effects of Yougui recipe (see text) and salmon calcitonin acetate in preventing osteolysis surrounding artificial prosthesis.

Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg Proteins

We report the solution structures of the VPg proteins from feline calicivirus (FCV) and murine norovirus (MNV), which have been determined by nuclear magnetic resonance spectroscopy. In both cases, the core of the protein adopts a compact helical structure flanked by flexible N and C termini. Remarkably, while the core of FCV VPg contains a well-defined three-helix bundle, the MNV VPg core has just the first two of these secondary structure elements. In both cases, the VPg cores are stabilized by networks of hydrophobic and salt bridge interactions. The Tyr residue in VPg that is nucleotidylated by the viral NS7 polymerase (Y24 in FCV, Y26 in MNV) occurs in a conserved position within the first helix of the core. Intriguingly, given its structure, VPg would appear to be unable to bind to the viral polymerase so as to place this Tyr in the active site without a major conformation change to VPg or the polymerase. However, mutations that destabilized the VPg core either had no effect on or reduced both the ability of the protein to be nucleotidylated and virus infectivity and did not reveal a clear structure-activity relationship. The precise role of the calicivirus VPg core in virus replication remains to be determined, but knowledge of its structure will facilitate future investigations.

A Mutated Glucagon-like Peptide-1 with Improved Glucose-lowering Activity in Diabetic Mice

The aim of this study was to characterize the conformation and potency of a mutated glucagon-like peptide-1 (mGLP-1), and evaluate its glucose-lowering activity in diabetic mice.

Improvement in Liver Histology Among Asian Patients with Chronic Hepatitis B After Long-term Treatment with Entecavir

Clinical Utility of Serum Tumor Markers and Cytokines in Cervical Cancer and Neoplasia

Study of an Elevated Carbohydrate Antigen 19-9 Concentration in a Large Health Check-up Cohort in China

Abstract Background: Carbohydrate antigen 19-9 (CA19-9) is frequently tested in cancer patients. However, elevated CA19-9 can be found in many benign diseases. We investigated the relationship between elevated CA19-9 and diseases, and presented suggestions for its utility in a health check-up cohort. Methods: From June 2008 to December 2008, we enrolled consecutive health check-up individuals with elevated CA19-9 (>37 U/mL). They were divided into three groups: group A (malignant diseases), group B (decreasing concentrations), and group C (increasing concentrations) according to the following criteria: (i) CA19-9 was rechecked monthly in the first 3 months; (ii) follow-up was completed if malignancy was found or if CA19-9 concentration dropped to normal; (iii) if CA19-9 kept increasing, it was monitored every 3 months; (4) total duration was 1 year. Results: Among 33,867 individuals, 572 (1.7%) individuals showed elevated CA19-9 concentration. A total of 509 (90.0%) individuals finished at 1-year follow-up. In total, nine (1.8%) individuals were diagnosed with malignancies. For 336 (66.0%) individuals CA19-9 concentrations dropped to normal, whereas for 164 (32.2%) individuals it kept rising. Interestingly, we did not find any differences in concentration levels between group A and group C. The main associated benign diseases included fatty liver (25.3%), cholecystolithiasis (13.9%), and chronic hepatitis B (13.9%). Conclusions: Dynamic monitoring of CA19-9 is recommended in asymptomatic populations with elevated CA19-9 concentrations.

Is the Prediction of Prognosis Not Improved by the Seventh Edition of the TNM Classification for Colorectal Cancer? Analysis of the Surveilla006Ece, Epidemiology, and End Results (SEER) Database

BACKGROUND: Whether the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system (AJCC-7) is a successful revision remains debatable. We aimed to compare the predictive capacity of the AJCC-7 for colorectal cancer with the 6th edition of the AJCC TNM staging system (AJCC-6). METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) dataset consisting of 158,483 records was used in this study. We evaluated the predictive capacity of the two editions of the staging system using Harrell's C index and Bayesian Information Criterion (BIC). RESULTS: There was a significant prognostic difference between patients at stage IIB and IIC (P < 0.001). Stage III patients with similar prognoses were adequately sub-grouped in the same stage according to AJCC-7. The Harrell's C index revealed a value of 0.7692 for AJCC-7, which was significantly better than 0.7663 for AJCC-6 (P < 0.001). BIC analysis provided consistent results (P < 0.001). CONCLUSIONS: This study demonstrates that AJCC-7 is superior to the AJCC-6 staging system in predictive capacity.

The Prognostic Value of Estrogen Receptor Beta and Proline-, Glutamic Acid- and Leucine-rich Protein 1 (PELP1) Expression in Ovarian Cancer

Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of the estrogen receptors (ERs) alpha and beta, is a potential proto-oncogene in hormone dependent gynecological malignancies. To better understand the role of PELP1 in epithelial ovarian cancer (EOC), the protein expression and prognostic significance of PELP1 was evaluated together with ERalpha and ERbeta in EOC tissues.

Promoting Colorectal Cancer Screening Discussion: a Randomized Controlled Trial

Provider recommendation is a predictor of colorectal cancer (CRC) screening.

Immune Tolerance of Skin Allograft Transplantation Induced by Immature Dendritic Cells of a Third Party Carrying Donor Antigens in Mice

Dendritic cells (DCs) are the most powerful antigen-presenting cells in the body. Immature DCs (imDCs) can induce transplantation tolerance. In this study, using a mouse model of skin transplantation. We explored the antigen uptake by imDCs, changes in phenotype and function after antigen loading, as well as survival of skin grafts.

Nitric Oxide Bioavailability and Adiponectin Production in Chronic Systolic Heart Failure: Relation to Severity Of cardiac Dysfunction

Adiponectin is an anti-inflammatory, antiatherogenic adipokine elevated in heart failure (HF) that may protect against endothelial dysfunction by influencing underlying nitric oxide bioavailability. In this study, we examine the relationship between plasma adiponectin levels and measures of nitric oxide bioavailability and myocardial performance in patients with chronic systolic HF. In 139 ambulatory patients with stable, chronic systolic HF (left ventricular [LV] ejection fraction ≤40%, New York Heart Association class I to IV), we measured plasma levels of adiponectin, asymmetric dimethylarginine (ADMA), and global arginine bioavailability (GABR), and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse events (all-cause mortality or cardiac transplantation) were prospectively tracked for a median of 39 months. Plasma adiponectin levels directly correlated with plasma ADMA levels (Spearman's r = 0.41, P < 0.001) and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) levels (r = 0.55, P < 0.001), inversely correlated with GABR (r = -0.39, P < 0.001), and were not associated with high-sensitivity C-reactive protein (P = 0.81) or myeloperoxidase (P = 0.07). Interestingly, increased plasma adiponectin levels remained positively correlated with plasma ADMA levels only in patients with elevated NT-proBNP levels (r = 0.33, P = 0.009). Higher plasma adiponectin levels were associated with worse LV diastolic dysfunction (rank sums P = 0.002), right ventricular (RV) systolic dysfunction (rank sums P = 0.002), and RV diastolic dysfunction (rank sums P = 0.011), but not after adjustment for plasma ADMA and NT-proBNP levels. Plasma adiponectin levels predicted increased risk of adverse clinical events (hazard ratio, 95% confidence interval 1.45 [1.02-2.07], P = 0.038) but not after adjustment for plasma ADMA and NT-proBNP levels, or echocardiographic indices of diastolic or RV systolic dysfunction. In patients with chronic systolic HF, adiponectin production is more closely linked with nitric oxide bioavailability than inflammation, and appears to be more robust in the setting of cardiac dysfunction or elevated natriuretic peptide levels.

Inspiratory Muscle Warm-up Attenuates Muscle Deoxygenation During Cycling Exercise in Women Athletes

This study examines the effects of inspiratory muscle warm-up (IMW) on performance and muscle oxygenation during cycling exercise. In a randomized crossover study of 10 female soccer players, the IMW, placebo (IMWP) and control (CON) trials were conducted before two 6-min submaximal cycling exercises (100 and 150W) followed by intermittent high-intensity sprint (IHIS, 6×10s with 60s recovery). The reduction in tissue saturation index (TSI) in legs in the IMW were significantly less than those in IMWP and CON (P<0.01) during submaximal cycling exercises. The average reduction in TSI during the IHIS test with IMW was significantly less than those in the IMWP and CON (P=0.023). Nevertheless, the IHIS performance with IMW did not differ from that in other trials. In conclusion, the leg TSI during continuous submaximal cycling exercise followed by intermittent sprinting was likely improved by specific IMW (40% maximal inspiratory mouth pressure), which did not enhance IHIS performance.

Spatial Patterns and Climate Drivers of Carbon Fluxes in Terrestrial Ecosystems of China

Understanding the dynamics and underlying mechanism of carbon exchange between terrestrial ecosystems and the atmosphere is one of the key issues in global change research. In this study, we quantified the carbon fluxes in different terrestrial ecosystems in China, and analyzed their spatial variation and environmental drivers based on the long-term observation data of ChinaFLUX sites and the published data from other flux sites in China. The results indicate that gross ecosystem productivity (GEP), ecosystem respiration (ER), and net ecosystem productivity (NEP) of terrestrial ecosystems in China showed a significantly latitudinal pattern, declining linearly with the increase of latitude. However, GEP, ER, and NEP did not present a clear longitudinal pattern. The carbon sink functional areas of terrestrial ecosystems in China were mainly located in the subtropical and temperate forests, coastal wetlands in eastern China, the temperate meadow steppe in the northeast China, and the alpine meadow in eastern edge of Qinghai-Tibetan Plateau. The forest ecosystems had stronger carbon sink than grassland ecosystems. The spatial patterns of GEP and ER in China were mainly determined by mean annual precipitation (MAP) and mean annual temperature (MAT), whereas the spatial variation in NEP was largely explained by MAT. The combined effects of MAT and MAP explained 79%, 62%, and 66% of the spatial variations in GEP, ER, and NEP, respectively. The GEP, ER, and NEP in different ecosystems in China exhibited 'positive coupling correlation' in their spatial patterns. Both ER and NEP were significantly correlated with GEP, with 68% of the per-unit GEP contributed to ER and 29% to NEP. MAT and MAP affected the spatial patterns of ER and NEP mainly by their direct effects on the spatial pattern of GEP.

Heart Rate Decrease During Crizotinib Treatment and Potential Correlation to Clinical Response

BACKGROUND: Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) is a side effect listed in its package insert. We investigated the frequency and timing of SB, patient characteristics associated with SB during crizotinib treatment, and potential correlation between heart rate (HR) changes and clinical response to crizotinib. METHODS: A retrospective chart review was conducted of the timing and frequency of SB, patient characteristics, and clinical response of patients to crizotinib treatment. RESULTS: Forty-twp patients who had ALK-rearranged or mesenchymal epithelial transition (MET)-amplified NSCLC and received treatment with oral crizotinib 250 mg twice daily who were enrolled in 2 crizotinib trials (PROFILE 1001 and PROFILE 1005) were analyzed. There was an average decrease of 26.1 beats per minute (bpm) from the pretreatment HR among all patients during crizotinib treatment. Twenty-nine patients (69%) experienced at least 1 episode of SB (HR, <60 bpm). The average time to the lowest HR recorded was 18.6 weeks (range, 5-72 weeks). Patients who experienced SB were significantly older (aged 55.8 years vs 47.8 years; P = .0336), had a lower pretreatment HR (mean, 77.9 bpm vs 100.6 bpm; P = .002), and were on crizotinib longer (52.9 weeks vs 24.6 weeks; P = .0050) than patients who did not experience SB. The overall response rate (P = .0195) and the maximum tumor shrinkage (P = .0205) were significantly greater in patients who experienced SB. CONCLUSIONS: HR decrease is common during crizotinib treatment. It remains to be determined whether the correlation between HR decrease and clinical response to crizotinib reflects a biomarker of drug efficacy or a time/cumulative dose-dependent phenomenon. Cancer 2013;. © 2013 American Cancer Society.

Resilin-Like Polypeptide Hydrogels Engineered for Versatile Biological Functions

Natural resilin, the rubber-like protein that exists in specialized compartments of most arthropods, possesses excellent mechanical properties such as low stiffness, high resilience and effective energy storage. Recombinantly-engineered resilin-like polypeptides (RLPs) that possess the favorable attributes of native resilin would be attractive candidates for the modular design of biomaterials for engineering mechanically active tissues. Based on our previous success in creating a novel RLP-based hydrogel and demonstrating useful mechanical and cell-adhesive properties, we have produced a suite of new RLP-based constructs, each equipped with 12 repeats of the putative resilin consensus sequence and a single, distinct biologically active domain. This approach allows independent control over the concentrations of cell-binding, MMP-sensitive, and polysaccharide-sequestration domains in hydrogels comprising mixtures of the various RLPs. The high purity, molecular weight and correct compositions of each new polypeptide have been confirmed via high performance liquid chromatography (HPLC), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), and amino acid analysis. These RLP-based polypeptides exhibit largely random-coil conformation, both in solution and in the cross-linked hydrogels, as indicated by circular dichroic and infrared spectroscopic analyses. Hydrogels of various compositions, with a range of elastic moduli (1kPa to 25kPa) can be produced from these polypeptides, and the activity of the cell-binding and matrix metalloproteinase (MMP) sensitive domains was confirmed. Tris(hydroxymethyl phosphine) cross-linked RLP hydrogels were able to maintain their mechanical integrity as well as the viability of encapsulated primary human mesenchymal stem cells (MSCs). These results validate the promising properties of these RLP-based elastomeric biomaterials.

α-Lipoic Acid Reduces Infarct Size and Preserves Cardiac Function in Rat Myocardial Ischemia/reperfusion Injury Through Activation of PI3K/Akt/Nrf2 Pathway

The present study investigates the effects and mechanisms of α-Lipoic acid (LA) on myocardial infarct size, cardiac function and cardiomyocyte apoptosis in rat hearts subjected to in vivo myocardial ischemia/reperfusion (MI/R) injury.

Green Tea Supplementation Increases Glutathione and Plasma Antioxidant Capacity in Adults with the Metabolic Syndrome

Green tea, a popular polyphenol-containing beverage, has been shown to alleviate clinical features of the metabolic syndrome. However, its effects in endogenous antioxidant biomarkers are not clearly understood. Thus, we tested the hypothesis that green tea supplementation will upregulate antioxidant parameters (enzymatic and nonenzymatic) in adults with the metabolic syndrome. Thirty-five obese participants with the metabolic syndrome were randomly assigned to receive one of the following for 8 weeks: green tea (4 cups per day), control (4 cups water per day), or green tea extract (2 capsules and 4 cups water per day). Blood samples and dietary information were collected at baseline (0 week) and 8 weeks of the study. Circulating carotenoids (α-carotene, β-carotene, lycopene) and tocopherols (α-tocopherol, γ-tocopherol) and trace elements were measured using high-performance liquid chromatography and inductively coupled plasma mass spectroscopy, respectively. Serum antioxidant enzymes (glutathione peroxidase, glutathione, catalase) and plasma antioxidant capacity were measured spectrophotometrically. Green tea beverage and green tea extract significantly increased plasma antioxidant capacity (1.5 to 2.3 μmol/L and 1.2 to 2.5 μmol/L, respectively; P < .05) and whole blood glutathione (1783 to 2395 μg/g hemoglobin and 1905 to 2751 μg/g hemoglobin, respectively; P < .05) vs controls at 8 weeks. No effects were noted in serum levels of carotenoids and tocopherols and glutathione peroxidase and catalase activities. Green tea extract significantly reduced plasma iron vs baseline (128 to 92 μg/dL, P < .02), whereas copper, zinc, and selenium were not affected. These results support the hypothesis that green tea may provide antioxidant protection in the metabolic syndrome.

Reply to the Letter by Xing-Ru Zhang and Zhen-Yong Zhang: Comments on "Inverse Relationship Between Macular Pigment Optical Density and Axial Length in Chinese Subjects with Myopia"

A Cluster of Primary Pneumonic Plague Transmitted in a Truck Cab in a New Enzootic Focus in China

We investigated a cluster of five cases of severe pneumonia from one village in Yunnan Province, China. We searched for severe pneumonia in the village and hospitals. We interviewed patients and family members about exposures. We tested acute and convalescent sera for antigen and antibody of severe acute respiratory syndrome, avian influenza, and plague. The only common exposure of the five patients was riding together in the enclosed cab of a truck for 1.5 hours while taking the first patient to the hospital. Seroconversion to plague F1 antigen confirmed plague in three survivors. Unfamiliarity of clinicians with plague and lack of sputum examination, blood culture, or postmortem examination delayed the diagnosis. No plague cases occurred among family and village contacts and health care workers. High infectivity in this cluster was limited to a crowded, poorly ventilated truck.

Reply to "Susceptibility of Streptococcus Pyogenes to Trimethoprim-sulfamethoxazole"

Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2-Overexpressing Metastatic Breast Cancer

PURPOSELapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC).Patients And methodsThis phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety.ResultsThe addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. CONCLUSIONThis trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.

The Importance of Timing of Decompression in Severe Acute Pancreatitis Combined with Abdominal Compartment Syndrome

Surgical decompression is widely considered as an important treatment in patients with severe acute pancreatitis (SAP) and abdominal compartment syndrome (ACS). Until now, the indication and optimal time of decompression remain unknown, and no experimental data exist, although extremely high mortality has been repeatedly reported in these patients. The aim of this study was to evaluate the effects of three different time points for decompression in a 24-hour lasting porcine model.

Ammonia Formation by a Thiolate-bridged Diiron Amide Complex As a Nitrogenase Mimic

Although nitrogenase enzymes routinely convert molecular nitrogen into ammonia under ambient temperature and pressure, this reaction is currently carried out industrially using the Haber-Bosch process, which requires extreme temperatures and pressures to activate dinitrogen. Biological fixation occurs through dinitrogen and reduced NxHy species at multi-iron centres of compounds bearing sulfur ligands, but it is difficult to elucidate the mechanistic details and to obtain stable model intermediate complexes for further investigation. Metal-based synthetic models have been applied to reveal partial details, although most models involve a mononuclear system. Here, we report a diiron complex bridged by a bidentate thiolate ligand that can accommodate HN=NH. Following reductions and protonations, HN=NH is converted to NH3 through pivotal intermediate complexes bridged by N2H3(-) and NH2(-) species. Notably, the final ammonia release was effected with water as the proton source. Density functional theory calculations were carried out, and a pathway of biological nitrogen fixation is proposed.

AIB1 Predicts Bladder Cancer Outcome and Promotes Bladder Cancer Cell Proliferation Through AKT and E2F1

Background:We previously demonstrated that AIB1 overexpression is an independent molecular marker for shortened survival of bladder cancer (BC) patients. In this study, we characterised the role and molecular mechanisms of AIB1 in BC tumorigenicity.Methods:AIB1 expression was measured by immunohistochemistry in non-muscle-invasive BC tissue and adjacent normal bladder tissue. In addition, the tumorigenicity of AIB1 was assessed with in vitro and in vivo functional assays.Results:Overexpression of AIB1 was observed in tissues from 46 out of 146 patients with non-muscle-invasive BC and was an independent predictor for poor progression-free survival. Lentivirus-mediated AIB1 knockdown inhibited cell proliferation both in vitro and in vivo, whereas AIB1 overexpression promoted cell proliferation in vitro. The growth-inhibitory effect induced by AIB1 knockdown was mediated by G1 arrest, which was caused by reduced expression of key cell-cycle regulatory proteins through the AKT pathway and E2F1.Conclusion:Our results suggest that AIB1 promotes BC cell proliferation through the AKT pathway and E2F1. Furthermore, AIB1 overexpression predicts tumour progression in patients with non-muscle-invasive BC.

PEGylation-aided Refolding of Globular Adiponectin

Globular adiponectin (GAD) as the active domain of adiponectin is a promising candidate for anti-diabetic drug development. The recombinant production of GAD in Escherichia coli, however, is difficult because it is mainly expressed as inclusion bodies which need to be refolded to regain function. In this study we developed a novel method for refolding of GAD with a high efficiency by using polyethylene glycol (PEG) conjugation. An artificially designed DNA sequence encoding for GAD was synthesized and inserted into the pET28a vector to construct an expression plasmid which was thereafter transformed into E. coli BL21 (DE3) host cells for heterologous expression. After bacterial cell culture employing auto-induction medium, the inclusion bodies were collected, washed and dissolved in guanidine hydrochloride before PEG conjugation. Then the PEG-conjugated GAD was refolded by dialysis and purified by two steps of chromatography. The refolded conjugate showed a marked glucose-lowering activity in mice, demonstrating that it had been successfully refolded. As a convenient method, PEGylation-aided refolding could also be tested on other proteins to explore its suitability.

Conserved Nucleotides in the Terminus of the 3' UTR Region Are Important for the Replication and Infectivity of Porcine Reproductive and Respiratory Syndrome Virus

The 3' untranslated region (3' UTR), including the poly (A) tail, reportedly plays an important role in arterivirus replication, but the roles of the cis-acting elements present in the 3' UTR of porcine reproductive and respiratory syndrome virus (PRRSV) remain largely unknown. In the present study, PCR-based mutagenic analysis was conducted on the 3' UTR of PRRSV infectious full-length cDNA clone pAPRRS to investigate the structure and function of the conserved terminal nucleotides between the poly (A) tail and the 3' UTR region. Our findings indicated that the conservation of the primary sequence of the 3' terminal nucleotides, rather than the surrounding secondary structure, was vital for viral replication and infectivity. Four nucleotides (nt) (5'-(15517)AAUU(15520)-3') at the 3' proximal end of the 3' UTR and the dinucleotide 5'-AU-3' exerted an important regulatory effect on viral viability. Of the five 3'-terminal nucleotides of the 3' UTR (5'-(15503)AACCA(15507)-3'), at least three, including the last dinucleotide (5'-CA-3'), were essential for maintaining viral infectivity. Taken together, the 3'-terminal conserved sequence plays a critical role in PRRSV replication and may function as a contact site for specific assembly of the replication complex.

Neural Correlates of Motor Impairment During Motor Imagery and Motor Execution in Sub-cortical Stroke

Objective: This study aims at identifying the neural substrates for motor execution (ME) and motor imagery (MI) in patients after stroke and their correlations with functional outcomes. Methods: 10 chronic stroke patients with left sub-cortical lesions and 10 unimpaired subjects were recruited. Their cortical processes were studied when they were asked to perform ME and MI unimanually using their unaffected and affected wrists during fMRI. Results: From correlation results, the supplementary motor area (SMA), its activation volume and congruence in functional neuroanatomy associated with ME and MI using affected wrist positively correlated with motor performance. During ME of the affected wrist, the precuneus, its activation volume and congruence in functional neuroanatomy between patient and unimpaired groups showed a negative correlation, while, in non-primary motor areas, the hemispheric balance of premotor cortex and the congruence in functional neuroanatomy of contralesional inferior parietal lobule between patient and unimpaired groups showed a positive correlation with motor performance. Conclusions: The non-primary motor-related areas were revealed to play a critical role in determining motor outcomes after left sub-cortical stroke, which was demonstrated in the stroke patients. In particular, SMA might be the key neural substrate associated with motor recovery.

Distinct Binding Affinities of Mac-1 and LFA-1 in Neutrophil Activation

Macrophage-1 Ag (Mac-1) and lymphocyte function-associated Ag-1 (LFA-1), two β2 integrins expressed on neutrophils (PMNs), mediate PMN recruitment cascade by binding to intercellular adhesive molecule 1. Distinct functions of LFA-1-initiating PMN slow rolling and firm adhesion but Mac-1-mediating cell crawling are assumed to be governed by the differences in their binding affinities and kinetic rates. In this study, we applied an adhesion frequency approach to compare their kinetics in the quiescent and activated states using three molecular systems, constitutively expressed receptors on PMNs, wild-type and high-affinity (HA) full-length constructs transfected on 293T cells, and wild-type and HA recombinant extracellular constructs. Data indicate that the difference in binding affinity between Mac-1 and LFA-1 is on-rate dominated with slightly or moderately varied off-rate. This finding was further confirmed when both β2 integrins were activated by chemokines (fMLF or IL-8), divalent cations (Mg(2+) or Mn(2+)), or disulfide bond lockage on an HA state. Structural analyses reveal that such the kinetics difference is likely attributed to the distinct conformations at the interface of Mac-1 or LFA-1 and intercellular adhesive molecule 1. This work furthers the understandings in the kinetic differences between Mac-1 and LFA-1 and in their biological correlations with molecular activation and structural bases.

Identification of the Immunogenic Spore and Vegetative Proteins of Bacillus Anthracis Vaccine Strain A16R

Immunoproteomics was used to screen the immunogenic spore and vegetative proteins of Bacillus anthracis vaccine strain A16R. The spore and vegetative proteins were separated by 2D gel electrophoresis and transferred to polyvinylidene difluoride membranes, and then western blotting was performed with rabbit immune serum against B.anthracis live spores. Immunogenic spots were cut and digested by trypsin. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed to identify the proteins. As a result, 11 and 45 immunogenic proteins were identified in the spores and vegetative cells, respectively; 26 of which have not been reported previously. To verify their immunogenicity, 12 of the identified proteins were selected to be expressed, and the immune sera from the mice vaccinated by the 12 expressed proteins, except BA0887, had a specific western blot band with the A16R whole cellular lytic proteins. Some of these immunogenic proteins might be used as novel vaccine candidates themselves or for enhancing the protective efficacy of a protective-antigen-based vaccine.

The Protective Effect of Intrasplenic Transplantation of Ad-IL-18BP/IL-4 Gene-modified Fetal Hepatocytes on ConA-induced Hepatitis in Mice

Concanavalin A (ConA)-induced hepatitis is an experimental murine model mirroring the pathology of human autoimmune hepatitis.

Lysine-specific Demethylase 1 in Breast Cancer Cells Contributes to the Production of Endogenous Formaldehyde in the Metastatic Bone Cancer Pain Model of Rats

Bone cancer pain seriously affects the quality of life of cancer patients. Our previous study found that endogenous formaldehyde was produced by cancer cells metastasized into bone marrows and played an important role in bone cancer pain. However, the mechanism of production of this endogenous formaldehyde by metastatic cancer cells was unknown in bone cancer pain rats. Lysine-specific demethylase 1 (LSD1) is one of the major enzymes catalyzing the production of formaldehyde. The expression of LSD1 and the concentration of formaldehyde were up-regulated in many high-risk tumors.

Modulating the Behaviors of Mesenchymal Stem Cells Via the Combination of High-Frequency Vibratory Stimulations and Fibrous Scaffolds

We are interested in the in vitro engineering of artificial vocal fold tissues via the strategic combination of multipotent mesenchymal stem cells (MSCs), physiologically relevant mechanical stimulations, and biomimetic artificial matrices. We have constructed a vocal fold bioreactor that is capable of imposing vibratory stimulations on the cultured cells at human phonation frequencies. Separately, fibrous poly (ɛ-caprolactone) (PCL) scaffolds emulating the ligamentous structure of the vocal fold were prepared by electrospinning, were incorporated in the vocal fold bioreactor, and were driven into a wave-like motion in an axisymmetrical fashion by the oscillating air. MSC-laden PCL scaffolds were subjected to vibrations at 200 Hz with a normal center displacement of ∼40 μm for a total of 7 days. A continuous (CT) or a 1 h-on-1 h-off (OF) regime with a total dynamic culture time of 12 h per day was applied. The dynamic loading did not cause any physiological trauma to the cells. Immunohistotochemical staining revealed the reinforcement of the actin filament and the enhancement of α5β1 integrin expression under selected dynamic culture conditions. Cellular expression of essential vocal fold extracellular matrix components, such as elastin, hyaluronic acid, and matrix metalloproteinase-1, was significantly elevated as compared with the static controls, and the OF regime is more conducive to matrix production than the CT vibration mode. Analyses of genes of typical fibroblast hallmarks (tenascin-C, collagen III, and procollagen I) as well as markers for MSC differentiation into nonfibroblastic lineages confirmed MSCs' adaptation of fibroblastic behaviors. Overall, the high-frequency vibratory stimulation, when combined with a synthetic fibrous scaffold, serves as a potent modulator of MSC functions. The novel bioreactor system presented here, as a versatile, yet well-controlled model, offers an in vitro platform for understanding vibration-induced mechanotransduction and for engineering of functional vocal fold tissues.

Improved Axonal Regeneration After Spinal Cord Injury in Mice with Conditional Deletion of Ephrin B2 Under the GFAP Promoter

Spinal cord injury (SCI) initiates a cascade of processes that ultimately form a nonpermissive environment for axonal regeneration. Emerging evidence suggests that regenerative failure may be due in part to inhibitory factors expressed by reactive spinal cord glial cells and meningeal fibroblasts, such as the Eph receptor protein-tyrosine kinases and their corresponding ligands (ephrins). Here we sought to assess the role of ephrin B2, an inhibitory axonal guidance molecule, as an inhibitor of the recovery process following SCI. To determine the extent of ephrin B2 involvement in axonal regenerative failure, a SCI model was performed on a conditional ephrin B2 knockout mouse strain (ephrin B2(-/-)), in which the ephrin B2 gene was deleted under the GFAP promoter . The expression of ephrin B2 was significantly decreased in astrocytes of injured and uninjured ephrin B2(-/-) mice compared to wild-type mice. Notably, in the ephrin B2(-/-) mice, the deletion of ephrin B2 reduced astrogliosis, and accelerated motor function recovery after SCI. Anterograde axonal tracing on a hemisection model of SCI further showed that ephrin B2(-/-) mice exhibited increased regeneration of injured corticospinal axons and a reduced glial scar, when compared to littermate controls exposed to similar injury. These results were confirmed by an in vitro neurite outgrowth assay and ephrin B2 functional blockage, which showed that ephrin B2 expressed on astrocytes inhibited axonal growth. Combined these findings suggest that ephrin B2 ligands expressed by reactive astrocytes impede the recovery process following SCI.

Rapid Diagnosis of Goose Viral Infections by Multiplex PCR

Goose parvovirus (GPV), newcastle disease virus (NDV), goose herpesvirus (GHV) and goose adenovirus (GAV) are considered collectively to be four of the most important and widespread viruses of geese. Because all of these viruses cause similar pathological changes, histological differentiation among these viruses is difficult. A reliable, specific and sensitive multiplex PCR (mPCR) assay was developed for the combined detection of GPV, NDV, GHV and GAV in clinical samples of geese. Using the mPCR technique, single infections with GPV (28/76; 36.8%), NDV (9/76; 11.8%), GHV (3/76; 3.9%) and GAV (12/76; 15.8%) were identified in the samples; co-infections with GAV and either GPV or NDV (31.6%; 24/76) were also identified with this approach. The results for all of the samples tested were the same in both the uPCR and mPCR systems. The mPCR approach is considered to be useful for routine molecular diagnosis and epidemiological applications in geese.

DAR2 Acts As an Important Node Connecting Cytokinin, Auxin, SHY2 and PLT1/2 in Root Meristem Size Control

Cytokinin and auxin antagonistically affect cell proliferation and differentiation and thus regulate root meristem size by influencing the abundance of SHORT HYPOCOTYL2 (SHY2/IAA3). SHY2 affects auxin distribution in the root meristem by repressing the auxin-inducible expression of PIN-FORMED (PIN) auxin transport genes. The PLETHORA (PLT1/2) genes influence root meristem growth by promoting stem cells and transit-amplifying cells. However, the factors connecting cytokinin, auxin, SHY2 and PLT1/2 are largely unknown. In a recent study, we have shown that the DA1-related protein 2 (DAR2) acts downstream of cytokinin and SHY2 but upstream of PLT1/2 to affect root meristem size. Here, we discuss the possible molecular mechanisms by which Arabidopsis DAR2 controls root meristem size.

Determination of Tumor-infiltrating CD8+ Lymphocytes in Human Ovarian Cancer

Tumor-infiltrating immune cells and their prognostic value have been analyzed in various malignancies. Although tissue microarray (TMA) has been used in some of these studies, it is still questionable whether this technique can represent the results of infiltrating CD8 cells obtained from whole-tissue sections (WTS). The aim of this study was to assess and compare the density of tumor-infiltrating CD8 cells in ovarian cancer using TMA and WTS. CD8 lymphocytes were immunohistochemically stained on WTS and TMA cores from 37 ovarian cancer patients and quantified using the image analysis software HistoQuest. Four different areas were selected on the WTS, namely (i) tumor; (ii) stroma; (iii) mixed; and (iv) dense, whereby dense represented areas of most abundant CD8 cells. On the TMA, (i) the whole TMA cores and (ii) areas containing only epithelial tumor tissue were analyzed. The Pearson correlation and principal component analysis was used to estimate the correlation of results from different techniques. CD8 lymphocytes showed highly correlated measurements between tumor, mixed, and dense areas. Moderate correlations were found between each of these 3 measurements and stroma. CD8 cell counts from WTS showed moderate correlation with TMA cell counts. Consistently, principal component analysis showed 3 clusters (i) tumor, dense, mixed; (ii) stroma; and (iii) TMA areas. Taken together, when the prognostic impact of tumor-infiltrating CD8 cells in ovarian cancer is investigated with TMA technique, a moderate correlation with WTS results has to be considered.

Carbon Quantum Dots Enhance the Photocatalytic Performance of BiVO4 with Different Exposed Facets

Carbon quantum dots (CQDs) were demonstrated to have the ability to enhance the photocatalytic performance of monoclinic BiVO4 with different exposed facets under visible light.

Nox4-dependent ROS Modulation by Amino Endoperoxides to Induce Apoptosis in Cancer Cells

Tumor metastasis is the main cause of death in cancer patients. Anoikis resistance is one critical malefactor of metastatic cancer cells to resist current clinical chemotherapeutic treatments. Although endoperoxide-containing compounds have long been suggested as anticancer drugs, few have been clinically employed due to their instability, complex synthesis procedure or low tumor cell selectivity. Herein, we describe a one-pot strategy to synthesize novel amino endoperoxides and their derivatives with good yields and stabilities. In vitro cell-based assays revealed that 4 out of the 14 amino endoperoxides selectively induce metastatic breast carcinoma cells but not normal breast cells to undergo apoptosis, in a dose-dependent manner. Mechanistic studies showed that the most potent amino endoperoxide, 4-Me, is selective for cancer cells expressing a high level of Nox4. The anticancer effects are further shown to be associated with reduced O2(-):H2O2 ratio and increased ·OH level in the cancerous cells. Animal study showed that 4-Me impairs orthotopic breast tumor growth as well as tumor cell metastasis to lymph nodes. Altogether, our study suggests that anticancer strategies that focus on redox-based apoptosis induction in tumors are clinically viable.

Does Warmer China Land Attract More Super Typhoons?

Accurate prediction of where and when typhoons (or named hurricanes which form over the North Atlantic Ocean) will make landfall is critical to protecting human lives and properties. Although the traditional method of typhoon track prediction based on the steering flow theory has been proven to be an effective way in most situations, it slipped up in some cases. Our analysis of the long-term Chinese typhoon records reveals that typhoons, especially super typhoons (those with maximum sustained surface winds of greater than 51 ms(-1)), have a trend to make landfalls toward warmer land in China over the past 50 years (1960-2009). Numerical sensitivity experiments using an advanced atmospheric model further confirm this finding. Our finding suggests an alternative approach to predict the landfall tracks of the most devastating typhoons in the southeastern China.

Microdevices for Nanomedicine

This review surveys selected methods of manufacture and applications of microdevices-miniaturized functional devices capable of handling cell and tissue cultures or producing particles-and discusses their potential relevance to nanomedicine. Many characteristics of microdevices such as miniaturization, increased throughput, and the ability to mimic organ-specific microenvironments are promising for the rapid, low-cost evaluation of the efficacy and toxicity of nanomaterials. Their potential to accurately reproduce the physiological environments that occur in vivo could reduce dependence on animal models in pharmacological testing. Technologies in microfabrications and microfluidics are widely applicable for nanomaterial synthesis and for the development of diagnostic devices. Although the use of microdevices in nanomedicine is still in its infancy, these technologies show promise for enhancing fundamental and applied research in nanomedicine.

Addition of Artificial Salt Bridge by Ile646Lys Mutation in Gp41 Coiled-coil Domain Regulates 6-helical Bundle Formation

HIV entry is mediated by the envelope glycoproteins gp120 and gp41. The gp41 subunit contains several functional domains: the N-terminal heptad repeat (NHR) domains fold a triple stranded coiled-coil forming a meta-stable prefusion intermediate. C-terminal heptad repeat (CHR) subsequently folds onto the hydrophobic grooves of the NHR coiled-coil to form a stable 6-helix bundle, which juxtaposes the viral and cellular membranes for fusion. The C34 which has 34 amino acid residues is known as the core structure in CHR. A highly anti-HIV peptide inhibitor derived from C34 was designed. An artificial salt bridge was added in the 6-helical bundle by substitution of lysine for Ile646. With a cholesterol modification at C-terminal, the inhibitor containing I646K mutation represented higher anti-viral activity than C34-cholesterol combination without mutation.

A Mammalian Pre-mRNA 5' End Capping Quality Control Mechanism and an Unexpected Link of Capping to Pre-mRNA Processing

Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5Å provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing.

Segmentation of MR Images Via Discriminative Dictionary Learning and Sparse Coding: Application to Hippocampus Labeling

We propose a novel method for the automatic segmentation of brain MRI images by using discriminative dictionary learning and sparse coding techniques. In the proposed method, dictionaries and classifiers are learned simultaneously from a set of brain atlases, which can then be used for the reconstruction and segmentation of an unseen target image. The proposed segmentation strategy is based on image reconstruction, which is in contrast to most existing atlas-based labeling approaches that rely on comparing image similarities between atlases and target images. In addition, we propose a Fixed Discriminative Dictionary Learning for Segmentation (F-DDLS) strategy, which can learn dictionaries offline and perform segmentations online, enabling a significant speed-up in the segmentation stage. The proposed method has been evaluated for the hippocampus segmentation of 80 healthy ICBM subjects and 202 ADNI images. The robustness of the proposed method, especially of our F-DDLS strategy, was validated by training and testing on different subject groups in the ADNI database. The influence of different parameters was studied and the performance of the proposed method was also compared with that of the nonlocal patch-based approach. The proposed method achieved a median Dice coefficient of 0.879 on 202 ADNI images and 0.890 on 80 ICBM subjects, which is competitive compared with state-of-the-art methods.

Evaluating the Effects of Systemic Low Frequency Oscillations Measured in the Periphery on the Independent Component Analysis Results of Resting State Networks

Independent component analysis (ICA) is widely used in resting state functional connectivity studies. ICA is a data-driven method, which uses no a priori anatomical or functional assumptions. However, as a result, it still relies on the user to distinguish the independent components (ICs) corresponding to neuronal activation, peripherally originating signals (without directly attributable neuronal origin, such as respiration, cardiac pulsation and Mayer wave), and acquisition artifacts. In this concurrent near infrared spectroscopy (NIRS)/functional MRI (fMRI) resting state study, we developed a method to systematically and quantitatively identify the ICs that show strong contributions from signals originating in the periphery. We applied group ICA (MELODIC from FSL) to the resting state data of 10 healthy participants. The systemic low frequency oscillation (LFO) detected simultaneously at each participant's fingertip by NIRS was used as a regressor to correlate with every subject-specific IC time course. The ICs that had high correlation with the systemic LFO were those closely associated with previously described sensorimotor, visual, and auditory networks. The ICs associated with the default mode and frontoparietal networks were less affected by the peripheral signals. The consistency and reproducibility of the results were evaluated using bootstrapping. This result demonstrates that systemic, low frequency oscillations in hemodynamic properties overlay the time courses of many spatial patterns identified in ICA analyses, which complicates the detection and interpretation of connectivity in these regions of the brain.

Cytotoxic Effect of Novel Flammulina Velutipes Sterols and Its Oral Bioavailability Via Mixed Micellar Nanoformulation

The aim of this study was to investigate the anti-tumor effect of sterols initially separated from Flammulina velutipes and the pharmacokinetics and tissue distribution after oral administration of F. velutipes sterol nanomicelles (FVSNs). F. velutipes sterol (FVS) consisted of mainly ergosterol (54.78%), 22,23-dihydroergosterol (27.94%) and ergost-8(14)-ene-3β-ol (discovered for the first time in F. velutipes). In vitro cytotoxicity assay of FVS against U251 cells and HeLa cells showed that at 72h treatment, the FVS (IC50=23.42μg/mL) exhibited strong inhibitory effect against U251 cells, even overwhelmed the standard anti-tumor drug (5-fluorouracil) to an extent, while the HeLa cells were not significantly susceptible to the FVS. To improve the solubility and bioavailability of FVS, a model for insoluble anti-tumor drugs, FVSNs were prepared. In vitro characterization of FVSNs revealed satisfactory size distribution, loading capacity and encapsulation efficiency. Pharmacokinetic study in SD rats demonstrated that the mixed micellar nanoformulation significantly enhanced the bioavailability of FVS than free drug. Additionly, tissue distribution in mice manifested that the biodistribution of FVSNs as compared to the free FVS suspension were significantly improved. In conclusion, the nanomicelles developed in our study provided a promising delivery system for enhancing the oral bioavailability and selective biodistribution of FVS, a potential anti-tumor agent.

EEG Patterns from Acute to Chronic Stroke Phases in Focal Cerebral Ischemic Rats: Correlations with Functional Recovery

Monitoring the neural activities from the ischemic penumbra provides critical information on neurological recovery after stroke. The purpose of this study is to evaluate the temporal alterations of neural activities using electroencephalography (EEG) from the acute phase to the chronic phase, and to compare EEG with the degree of post-stroke motor function recovery in a rat model of focal ischemic stroke. Male Sprague-Dawley rats were subjected to 90 min transient middle cerebral artery occlusion surgery followed by reperfusion for seven days (n = 58). The EEG signals were recorded at the pre-stroke phase (0 h), acute phase (3, 6 h), subacute phase (12, 24, 48, 72 h) and chronic phase (96, 120, 144, 168 h) (n = 8). This study analyzed post-stroke seizures and polymorphic delta activities (PDAs) and calculated quantitative EEG parameters such as the alpha-to-delta ratio (ADR). The ADR represented the ratio between alpha power and delta power, which indicated how fast the EEG activities were. Forelimb and hindlimb motor functions were measured by De Ryck's test and the beam walking test, respectively. In the acute phase, delta power increased fourfold with the occurrence of PDAs, and the histological staining showed that the infarct was limited to the striatum and secondary sensory cortex. In the subacute phase, the alpha power reduced to 50% of the baseline, and the infarct progressed to the forelimb cortical region. ADRs reduced from 0.23 ± 0.09 to 0.04 ± 0.01 at 3 h in the acute phase and gradually recovered to 0.22 ± 0.08 at 168 h in the chronic phase. In the comparison of correlations between the EEG parameters and the limb motor function from the acute phase to the chronic phase, ADRs were found to have the highest correlation coefficients with the beam walking test (r = 0.9524, p < 0.05) and De Ryck's test (r = 0.8077, p < 0.05). This study measured EEG activities after focal cerebral ischemia and showed that functional recovery was closely correlated with the neural activities in the penumbra. Longitudinal EEG monitoring at different phases after a stroke can provide information on the neural activities, which are well correlated with the motor function recovery.

Autologous Fat Grafting in Lip Reconstruction Following Hemangioma Treatment

Autologous fat grafting has been successfully used in lip cosmetic surgery. However, little supportive evidence exists for its use in lip reconstruction following hemangioma treatment.

Motivators and Barriers to Incorporating Climate Change-related Health Risks in Environmental Health Impact Assessment

Climate change presents risks to health that must be addressed by both decision-makers and public health researchers. Within the application of Environmental Health Impact Assessment (EHIA), there have been few attempts to incorporate climate change-related health risks as an input to the framework. This study used a focus group design to examine the perceptions of government, industry and academic specialists about the suitability of assessing the health consequences of climate change within an EHIA framework. Practitioners expressed concern over a number of factors relating to the current EHIA methodology and the inclusion of climate change-related health risks. These concerns related to the broad scope of issues that would need to be considered, problems with identifying appropriate health indicators, the lack of relevant qualitative information that is currently incorporated in assessment and persistent issues surrounding stakeholder participation. It was suggested that improvements are needed in data collection processes, particularly in terms of adequate communication between environmental and health practitioners. Concerns were raised surrounding data privacy and usage, and how these could impact on the assessment process. These findings may provide guidance for government and industry bodies to improve the assessment of climate change-related health risks.

The Impact of Heat Waves on Children's Health: a Systematic Review

Young children are thought to be particularly sensitive to heat waves, but relatively less research attention has been paid to this field to date. A systematic review was conducted to elucidate the relationship between heat waves and children's health. Literature published up to August 2012 were identified using the following MeSH terms and keywords: "heatwave", "heat wave", "child health", "morbidity", "hospital admission", "emergency department visit", "family practice", "primary health care", "death" and "mortality". Of the 628 publications identified, 12 met the selection criteria. The existing literature does not consistently suggest that mortality among children increases significantly during heat waves, even though infants were associated with more heat-related deaths. Exposure to heat waves in the perinatal period may pose a threat to children's health. Pediatric diseases or conditions associated with heat waves include renal disease, respiratory disease, electrolyte imbalance and fever. Future research should focus on how to develop a consistent definition of a heat wave from a children's health perspective, identifying the best measure of children's exposure to heat waves, exploring sensitive outcome measures to quantify the impact of heat waves on children, evaluating the possible impacts of heat waves on children's birth outcomes, and understanding the differences in vulnerability to heat waves among children of different ages and from different income countries. Projection of the children's disease burden caused by heat waves under climate change scenarios, and development of effective heat wave mitigation and adaptation strategies that incorporate other child protective health measures, are also strongly recommended.

A Versatile Triphenylamine/Fluoranthene-Based Derivative As a Nondoped Green-Emitting, Hole-Transporting Interlayer for Electroluminescent Devices

A new triphenylamine-bridged fluoranthene derivative, 4-(7,10-diphenylfluoranthen-8-yl)-N-[4-(7,10-diphenylfluoranthen-8-yl)phenyl]-N-phenylaniline (BDPFPA), with a high glass transition temperature of 220 °C has been synthesized and characterized. BDPFPA is a highly fluorescent and versatile material that can be used as a nondoped green emitter and as a hole transporter. BDPFPA was used in a standard trilayer device as the emitting layer, which showed a low turn-on voltage (<3 V) and a high efficiency of 11.6 cd A(-1) . The device also shows little efficiency roll-off at high brightness. For example, the efficiency can still be maintained at 11.4 cd A(-1) (5.4 lm W(-1) ) at a brightness of 10 000 cd m(-2) . These results are among the best reported for nondoped fluorescent green organic light-emitting diodes. A simple bilayer device, in which BDPFPA serves as a hole-transporting layer, has a maximum power efficiency of 3.3 lm W(-1) and the performance is nearly 40 % higher than that of an N,N'-bis(1-naphthyl)-N,N'- diphenyl-1,1'-biphenyl-4,4'-diamine (NPB)-based standard device.

Efficacy of Early Treatment on 52 Patients with Preneoplastic Hepatitis B Virus-associated Hepatocellular Carcinoma by Compound Phyllanthus Urinaria L

OBJECTIVE: To observe the change in the number of antibodies of preneoplastic hepatocellular carcinoma (HCC) using early treatment by Compound Phyllanthus Urinaria L. (CPUL) on patients with preneoplastic hepatitis B virus (HBV)-associated HCC. METHODS: A total of 102 cirrhosis patients with regenerative or dysplastic nodules whose sera were tested positive for at least one of these six proteins (five up-regulated genes URG4, URG7, URG11, URG12 and URG19, and one down-regulated gene DRG2) were assigned randomly to two groups using continual random codes by SPSS software. Fifty-two patients were in the treatment group and 50 patients were in the control group. CPUL was used in the treatment group for 3 years, while the control group did not receive any treatment. The changes in HBV-DNA level, number of antibodies, and hepatocarcinogenesis occurred were observed. Patients who did not develop HCC were followed up for another 2 years. RESULTS: HBV-DNA levels decreased [Symbol: see text]2log in 22.2% (10/45) of patients in the treatment group in contrast to only 5.0% (2/40) of patients in the control group (P=0.0228). The number of antibodies that were tested positive in the treatment group (1.08±1.01) was significantly lower compared with the control group (2.11±1.12) after 24 months of drug treatment (P<0.01). Both the positive rates of anti-URG11 (33/52) and anti-URG19 (31/52) were over 60% at baseline in the two groups, and were decreased to 48.1% (25/52) and 46.2% (24/52) respectively at 36 months of drug treatment, while the rates increased to 68.0% (34/50) and 66.0% (33/50) respectively (P=0.0417, P=0.0436) in the control group. The positive rate of anti-DRG2 was increased to 55.8% (29/52) at 36 months of drug treatment, while in the control group was decreased to 36.0% (18/50, P=0.0452). Among the 102 patients who developed HCC, 2 were in the treatment group and 9 were in the control group, meaning that a significant difference between the two groups (P=0.0212). In 11 patients who developed HCC, anti-URG11 and anti-URG19 were always positive, while anti-DRG2 was negative. Patients newly developing HCC were 6 (20.0%) in the control group, and only one (2.5%) in the treatment group (P=0.0441) during 2-year follow-up after the end of the treatment. CONCLUSIONS: Anti-URG11, anti-URG19 and anti-DRG2 could be used as early markers in the prediction of the therapeutic efficacy of CPUL in treating preneoplastic HCC. CPUL is useful in preventing or delaying the development of HBV-associated cirrhosis to HCC.

Pre- and Postsynaptic Inhibitory Control in the Spinal Cord Dorsal Horn

Sensory information transmitted to the spinal cord dorsal horn is modulated by a complex network of excitatory and inhibitory interneurons. The two main inhibitory transmitters, GABA and glycine, control the flow of sensory information mainly by regulating the excitability of dorsal horn neurons. A presynaptic action of GABA has also been proposed as an important modulatory mechanism of transmitter release from sensory primary afferent terminals. By inhibiting the release of glutamate from primary afferent terminals, activation of presynaptic GABA receptors could play an important role in nociceptive and tactile sensory coding, while changes in their expression or function could be involved in pathological pain conditions, such as allodynia.

A Selective Turn-on Fluorescent Probe for Cd(2+) Based on a Boron Difluoride β-dibenzoyl Dye and Its Application in Living Cells

Herein we report the first example of a difluoroboron dibenzoyl based fluorescent probe for Cd(2+) detection. The probe displays high selectivity and sensitivity toward Cd(2+) over Zn(2+) in aqueous solution under physiological conditions. Fluorescence imaging experiments demonstrate its potential application for detecting Cd(2+) in living cells.

Fetal Hypoxia Results in Programming of Aberrant Angiotensin II Receptor Expression Patterns and Kidney Development

AIMS: The present study tested the hypothesis that fetal hypoxia adversely affects kidney development in fetal and offspring rats and alter the expression patterns of angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. METHODS: Time-dated pregnant rats were divided between normoxic and hypoxic (10.5% O2 last period of gestation) groups. Protein expression, in the offspring, was determined using western blot. RESULTS: Hypoxic treatment significantly decreased body and kidney weight in 21-day fetuses (E21) and 7-day neonates (P7). In 3-month-old offspring there were no significant differences in body and kidney weight between hypoxic and control animals. Fetal hypoxia had no effect on kidney AT1R density in E21 or P7, but significantly decreased kidney AT1R protein and mRNA abundance in both male and female adults. In contrast, kidney AT2R density was not affected by fetal hypoxia throughout the developmental stages studied. The hypoxia-mediated reduction of nephron numbers was progressively from P7 worsened into the adulthood with females affected more than males. CONCLUSION: The results suggest that fetal hypoxia causes programming of aberrant kidney development and accelerates the aging process of the kidney during the postnatal development, which may contribute to an increased risk of cardiovascular disease.

Construction and in Vitro/in Vivo Targeting of PSMA-targeted Nanoscale Microbubbles in Prostate Cancer

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a highly specific biological marker and treatment target for prostate cancer. So ultrasound molecular imaging using PSMA antibody-loaded targeted nanoscale microbubbles (MBs) may contribute to the early diagnosis of prostate cancer. METHODS: PSMA monoclonal antibody-loaded targeted nanoscale MBs were prepared using biotin-avidin technology. Antibody binding was evaluated with immunofluorescence. Using MKN45 gastric cancer cells as controls, the targeting capability of the targeted MBs was observed in prostate cancer cells (LNCaP and C4-2) under optical microscope. Contrast enhancement was monitored by an ultrasound system in C4-2, LNCaP, and MKN45 transplanted tumors in nude mice. The arrival time, time to peak, peak intensity, and duration of contrast enhancement of targeted and blank nanoscale MBs were compared and analyzed. RESULTS: Targeted PSMA monoclonal antibody-loaded nanoscale MBs were successfully synthesized. These MBs were stable and could specifically bind to LNCaP and C4-2 cells in vitro but did not bind to MKN45 cells. There were significant differences in peak intensity and duration of contrast enhancement between targeted and blank nanoscale MBs in both transplanted prostate tumors (P < 0.05). Among the three types of transplanted tumors with targeted nanoscale MBs, the peak intensity was significantly higher in prostate tumors (LNCaP and C4-2) than in gastric tumors (MKN45) (P < 0.05). CONCLUSIONS: PSMA monoclonal antibody-loaded targeted nanoscale MBs can target and bind to prostate cancer cells specifically and allow for obvious contrast enhancement in vivo. Therefore, this study lays a foundation for early diagnosis and targeted therapy for prostate cancer. Prostate © 2013 Wiley Periodicals, Inc.

The Diagnostic Significance of Coapplying a Rabeprazole Test with the SF-36 for Gastroesophageal Reflux Disease

Gastroesophageal reflux disease is a diversity disease that affects life quality of people in the world. Due to the complicated pathogenesis and variations in clinical manifestations, there is still no true gold standard for GERD diagnosis, and it is still difficult to diagnose this disease in some patients. The proton pump inhibitor's diagnostic test (the PPI test) is noninvasive, of low cost, tied to treatment, and widely accepted. Our aim is to evaluate the diagnostic significance of coapplying a rabeprazole test with the SF-36 for GERD in this study. Our study shows that the SF-36 in combination with the rabeprazole test can screen GERD patients and increase the sensitivity and specificity of GERD diagnosis through reference to the change in SF-36 score before and after the treatment (65 in the trial).

Adipocytokines As Features of the Metabolic Syndrome Determined Using Confirmatory Factor Analysis

PURPOSE: Confirmatory factor analysis (CFA) was used to test the hypothesis whether adipocytokines are associated with the risk factor cluster that characterizes the metabolic syndrome (MetS). METHODS: Data from 134 nondiabetic subjects were analyzed using CFA. Insulin sensitivity (SI) was quantified using intravenous glucose tolerance tests, visceral fat area by computed tomography and fasting high-density lipoprotein, triglycerides, monocyte chemoattractant protein-1 (MCP-1), serum amyloid A (SAA), tumor necrosis factor (TNF)-α, adiponectin, resistin, leptin, interleukin (IL)-6, C-reactive protein (CRP), and plasminogen activator inhibitor (PAI)-1 were measured. RESULTS: The basic model representing the MetS included six indicators comprising obesity, SI, lipids, and hypertension, and demonstrated excellent goodness of fit. Using multivariate analysis, MCP-1, SAA, and TNF-α were not independently associated with any of the MetS variables. Adiponectin, resistin, leptin, CRP, and IL-6 were associated with at least one of the risk factors, but when added to the basic model decreased all goodness-of-fit parameters. PAI-1 was associated with all cardiometabolic factors and improved goodness-of-fit compared with the basic model. CONCLUSIONS: Addition of PAI-1 increased the CFA model goodness of fit compared with the basic model, suggesting that this protein may represent an added feature of the MetS.

Succinate is an Inflammatory Signal That Induces IL-1β Through HIF-1α

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation.

Draft Genome of the Wheat A-genome Progenitor Triticum Urartu

Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.

Congenital Fibrosis of Extraocular Muscle Type 1A Due to KIF21A Mutation: First Case Report from Hong Kong

With the advancement of ophthalmological genetics, the molecular basis for more and more eye diseases can be elucidated. Congenital fibrosis of extraocular muscle (CFEOM) is an example. It is characterised by a congenital non-progressive restrictive ophthalmoplegia and ptosis. It is an autosomal dominant disease, caused by mutations of the KIF21A gene. With positive family history and typical ophthalmological findings, mutational analysis of KIF21A gene should be performed, not only to confirming the diagnosis, but also to offer a prognosis, for genetic counselling, and the possibility of prenatal diagnosis. Here we report the first KIF21A mutation associated with CFEOM1A in Hong Kong.

Engineered Deafness Reveals That Mouse Courtship Vocalizations Do Not Require Auditory Experience

Auditory experience during development is necessary for normal language acquisition in humans. Although songbirds, some cetaceans, and maybe bats may also be vocal learners, vocal learning has yet to be well established for a laboratory mammal. Mice are potentially an excellent model organism for studying mechanisms underlying vocal communication. Mice vocalize in different social contexts, yet whether they learn their vocalizations remains unresolved. To address this question, we compared ultrasonic courtship vocalizations emitted by chronically deaf and normal hearing adult male mice. We deafened CBA/CaJ male mice, engineered to express diphtheria toxin (DT) receptors in hair cells, by systemic injection of DT at postnatal day 2 (P2). By P9, almost all inner hair cells were absent and by P16 all inner and outer hair cells were absent in DTR mice. These mice did not show any auditory brainstem responses as adults. Wild-type littermates, also treated with DT at P2, had normal hair cells and normal auditory brainstem responses. We compared the temporal structure of vocalization bouts, the types of vocalizations, the patterns of syllables, and the acoustic features of each syllable type emitted by hearing and deaf males in the presence of a female. We found that almost all of the vocalization features we examined were similar in hearing and deaf animals. These findings indicate that mice do not need auditory experience during development to produce normal ultrasonic vocalizations in adulthood. We conclude that mouse courtship vocalizations are not acquired through auditory feedback-dependent learning.

Blood Pressure Control Among Hypertensive Patients With and Without Diabetes Mellitus in Six Public Primary Care Clinics in Malaysia

Hypertension is a common comorbidity among diabetic patients. This study aimed to determine blood pressure (BP) control among hypertensive patients with and without diabetes. This was a cross-sectional study in 6 public primary care clinics in Wilayah Persekutuan, Malaysia. Hypertensive patients aged ≥18 years and attending the clinics were selected via systematic random sampling. The BP control target was defined as <130/80 mm Hg for diabetic patients and <140/90 mm Hg for nondiabetic patients. A total of 1107 hypertensive patients participated in this study and 540 (48.7%) had diabetes. About one fourth (24.3%) of the hypertensive patients with diabetes achieved BP control target, compared with 60.1% patients without diabetes (P < .001). Being diabetic and on ≥2 antihypertensive treatments were associated with poor BP control. Attention needs to be given to these groups of patients when managing patients with hypertension.

[Expression of DOG-1 in Gastrointestinal Stromal Tumors and Its Significance]

To identify the expression of DOG-1 in gastrointestinal stromal tumors(GIST) and to explore its potential association with clinicopathological features of GIST.

Novel Insights into the Composition, Variation, Organization, and Expression of the Low-molecular-weight Glutenin Subunit Gene Family in Common Wheat

Low-molecular-weight glutenin subunits (LMW-GS), encoded by a complex multigene family, play an important role in the processing quality of wheat flour. Although members of this gene family have been identified in several wheat varieties, the allelic variation and composition of LMW-GS genes in common wheat are not well understood. In the present study, using the LMW-GS gene molecular marker system and the full-length gene cloning method, a comprehensive molecular analysis of LMW-GS genes was conducted in a representative population, the micro-core collections (MCC) of Chinese wheat germplasm. Generally, >15 LMW-GS genes were identified from individual MCC accessions, of which 4-6 were located at the Glu-A3 locus, 3-5 at the Glu-B3 locus, and eight at the Glu-D3 locus. LMW-GS genes at the Glu-A3 locus showed the highest allelic diversity, followed by the Glu-B3 genes, while the Glu-D3 genes were extremely conserved among MCC accessions. Expression and sequence analysis showed that 9-13 active LMW-GS genes were present in each accession. Sequence identity analysis showed that all i-type genes present at the Glu-A3 locus formed a single group, the s-type genes located at Glu-B3 and Glu-D3 loci comprised a unique group, while high-diversity m-type genes were classified into four groups and detected in all Glu-3 loci. These results contribute to the functional analysis of LMW-GS genes and facilitate improvement of bread-making quality by wheat molecular breeding programmes.

Expression and Regulation of Nampt in Human Islets

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme in the mammalian NAD+ biosynthesis of a salvage pathway and exists in 2 known forms, intracellular Nampt (iNampt) and a secreted form, extracellular Nampt (eNampt). eNampt can generate an intermediate product, nicotinamide mononucleotide (NMN), which has been reported to support insulin secretion in pancreatic islets. Nampt has been reported to be expressed in the pancreas but islet specific expression has not been adequately defined. The aim of this study was to characterize Nampt expression, secretion and regulation by glucose in human islets. Gene and protein expression of Nampt was assessed in human pancreatic tissue and isolated islets by qRT-PCR and immunofluorescence/confocal imaging respectively. Variable amounts of Nampt mRNA were detected in pancreatic tissue and isolated islets. Immunofluorescence staining for Nampt was found in the exocrine and endocrine tissue of fetal pancreas. However, in adulthood, Nampt expression was localized predominantly in beta cells. Isolated human islets secreted increasing amounts of eNampt in response to high glucose (20 mM) in a static glucose-stimulated insulin secretion assay (GSIS). In addition to an increase in eNampt secretion, exposure to 20 mM glucose also increased Nampt mRNA levels but not protein content. The secretion of eNampt was attenuated by the addition of membrane depolarization inhibitors, diazoxide and nifedipine. Islet-secreted eNampt showed enzymatic activity in a reaction with increasing production of NAD+/NADH over time. In summary, we show that Nampt is expressed in both exocrine and endocrine tissue early in life but in adulthood expression is localized to endocrine tissue. Enzymatically active eNampt is secreted by human islets, is regulated by glucose and requires membrane depolarization.

Norisoboldine Suppresses Osteoclast Differentiation Through Preventing the Accumulation of TRAF6-TAK1 Complexes and Activation of MAPKs/NF-κB/c-Fos/NFATc1 Pathways

Norisoboldine (NOR) is the main alkaloid constituent in the dry root of Lindera aggregata (Sims) Kosterm. (L. strychnifolia Vill.). As reported previously, orally administered NOR displayed a robust inhibition of joint bone destruction present in both mouse collagen-induced arthritis and rat adjuvant-induced arthritis with lower efficacious doses than that required for ameliorating systemic inflammation. This attracted us to assess the effects of NOR on differentiation and function of osteoclasts, primary effector cells for inflammatory bone destruction, to get insight into its anti-rheumatoid arthritis mechanisms. Both RAW264.7 cells and mouse bone marrow-derived macrophages (BMMs) were stimulated with RANKL (100 ng/mL) to establish osteoclast differentiation models. ELISA, RT-PCR, gelatin zymography, western blotting, immunoprecipitation and EMSA were used to reveal related signalling pathways. NOR (10 and 30 µM), without significant cytotoxicity, showed significant reduction of the number of osteoclasts and the resorption pit areas, and it targeted osteoclast differentiation at the early stage. In conjunction with the anti-resorption effect of NOR, mRNA levels of cathepsin K and MMP-9 were decreased, and the activity of MMP-9 was attenuated. Furthermore, our mechanistic studies indicated that NOR obviously suppressed the ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of ERK and p38 MAPK, and reduced the nuclear translocation of NF-κB-p65 and DNA-binding activity of NF-κB. However, NOR had little effect on expressions of TRAF6 or the phosphorylation and degradation of IκBα. Moreover, NOR markedly inhibited expressions of transcription factor NFATc1, but not c-Fos. Intriguingly, the subsequent nuclear translocations of c-Fos and NFATc1 were substantially down-regulated. Hence, we demonstrated for the first time that preventing the differentiation and function of osteoclasts at the early stage was an important anti-bone destruction mechanism of NOR, which might be attributed to inhibition of ubiquitination of TRAF6, the accumulation of TRAF6-TAK1 complexes and the activation of MAPKs/NF-κB/c-Fos/NFATc1 pathways.

Redox-Responsive, Core Cross-Linked Polyester Micelles

Monomethoxy poly(ethylene glycol)-b-poly(Tyr(alkynyl)-OCA), a biodegradable amphiphilic block copolymer, was synthesized by means of ring-opening polymerization of 5-(4-(prop-2-yn-1-yloxy)benzyl)-1,3-dioxolane-2,4-dione (Tyr(alkynyl)-OCA) and used to prepare core cross-linked polyester micelles via click chemistry. Core cross-linking not only improved the structural stability of the micelles but also allowed controlled release of cargo molecules in response to the reducing reagent. This new class of core cross-linked micelles can potentially be used in controlled release and drug delivery applications.

[B-type Natriuretic Peptide and Weaning from Mechanical Ventilation]

Minimal Change Disease Caused by Exposure to Mercury-containing Skin Lightening Cream: a Report of 4 Cases

Mercury is a known cause of nephrotic syndrome and the underlying renal pathology in most of the reported cases was membranous nephropathy. We describe here 4 cases of minimal change disease following exposure to mercury-containing skin lightening cream for 2 - 6 months. The mercury content of the facial creams was very high (7,420 - 30,000 parts per million). All patients were female and presented with nephrotic syndrome and heavy proteinuria (8.35 - 20.69 g/d). The blood and urine mercury levels were 26 - 129 nmol/l and 316 - 2,521 nmol/d, respectively. Renal biopsy revealed minimal change disease (MCD) in all patients. The use of cosmetic cream was stopped and chelation therapy with D-penicillamine was given. Two patients were also given steroids. The time for blood mercury level to normalize was 1 - 7 months, whereas it took longer for urine mercury level to normalize (9 - 16 months). All patients had complete remission of proteinuria and the time to normalization of proteinuria was 1 - 9 months. Mercury-containing skin lightening cream is hazardous because skin absorption of mercury can cause minimal change disease. The public should be warned of the danger of using such products. In patients presenting with nephrotic syndrome, a detailed history should be taken, including the use of skin lightening cream. With regard to renal pathology, apart from membranous nephropathy, minimal change disease should be included as another pathological entity caused by mercury exposure or intoxication.

Complement Activation in Pediatric Patients with Recurrent Acute Otitis Media

OBJECTIVE: Otitis media (OM) is one of the most common childhood diseases. The relative contribution of complement activation in protection and pathogenesis during OM remains largely unknown. The purpose of this study was to investigate the beneficial and pathogenic contributions of complement activation in the middle ear of pediatric patients with recurrent acute otitis media (rAOM), and therefore to provide a rational approach to prevent sequelae of OM such as hearing loss. METHODS: Twenty children undergoing pressure equalization tube placement with or without adenoidectomy for rAOM were enrolled in the study. Bacterial cultures, enzyme-linked immunosorbent assay (ELISA) for complement components and cytokines and western blot for complement activation were performed on middle ear effusion (MEE) and serum samples. The levels of complement C3a, C5a and sC5-b9 in MEEs and serum samples were compared. The levels of these factors were also examined in regards to length of episode. Pearson's correlation coefficients were calculated on variables between C5a and IL-6 or IL-8. Complement gene expression in human middle ear epithelial (HMEE) cells induced by otopathogens was evaluated. Data were analyzed with Student's t test or the Mann-Whitney rank sum test. In all cases, a P value of <0.05 was set as the measure of significance. RESULTS: Our data demonstrated that the complement classical/lectin, alternative and terminal pathways were activated in the middle ear of children with rAOM. Increased complement components of C3a, C5a and sC5-b9 in MEEs were detected in patients with the episode lasting more than six weeks. There was a strong correlation between C5a and IL-6 or IL-8 in the MEEs. Additionally, otopathogens induced enhanced gene expression of factor B and C3 in HMEE cells, which is beneficial for host defense against invading pathogens. CONCLUSION: Our studies provided important new insights on how complement activation contributes to inflammatory process during rAOM. Knowledge of the activity of the complement pathway in patients with rAOM may stimulate the development of new strategies to prevent middle ear inflammatory tissue destruction by directing treatment to specific pathways within the complement cascade.

Clinical Outcomes and Cost Implications of Routine Early PCI After Fibrinolysis: One-year Follow-up of the Trial of Routine Angioplasty and Stenting After Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI) Study

In patients with ST-elevation myocardial infarction treated with fibrinolysis, routine early percutaneous coronary intervention (r-PCI) improves clinical outcomes at 30 days compared with a more standard approach of performing early PCI only for failed fibrinolysis (s-PCI).

Primary Research on Unrelated Double Umbilical Cord Blood Transplantation and Implantation Kinetics

OBJECTIVE: This study sought to examine implantation and implantation kinetics in double umbilical cord blood transplantation (DUCBT). METHODS: Twenty-nine patients who underwent a two-unit unrelated donor cord blood transplantation were included in this study. After transplantation, hematopoietic chimerism of the peripheral blood was evaluated based on the results of short tandem repeat polymerase chain reaction. Using these results, we were able to judge whether the transplanted cells implanted, determine which donor's cells implanted, and further examine the kinetics of implantation in DUCBT. The numbers of total nucleated cells (TNCs), CD34(+) cells, colony forming units (CFUs), colony forming unit-granulocytes and macrophages (CFU-GMs), and CD3(+) cells were compared between the dominant units and the non-dominant units in an attempt to understand the discipline and implantation kinetics of DUCBT. RESULTS: Neither the TNC counts nor the counts of CD34(+) cells, CFU, CFU-GM, or CD3(+) cells were significantly different between the dominant units and the non-dominant units (P values of 0.584, 0.322, 0.842, 0.534, and 0.082, respectively). CONCLUSIONS: We were able to determine the engraftment status at 14 days after DUCBT, although the implantation kinetics of DUCBT remain uncharacterized and require further research.

A Classification System for Fat Necrosis in Autologous Breast Reconstruction

Fat necrosis (FN) is a common complication of autologous breast reconstruction, yet no classification system exists to describe it. We sought to develop and validate a tool for meaningful reporting, comparison of techniques, and treatment planning. Our hypothesis was that a valid classification system would demonstrate higher grades of FN for pedicled transverse rectus abdominus myocutaneous (pTRAM) flaps as compared to free flaps (FF).

An Allometric Model for Mapping Seed Development in Plants

Despite a tremendous effort to map quantitative trait loci (QTLs) responsible for agriculturally and biologically important traits in plants, our understanding of how a QTL governs the developmental process of plant seeds remains elusive. In this article, we address this issue by describing a model for functional mapping of seed development through the incorporation of the relationship between vegetative and reproductive growth. The time difference of reproductive from vegetative growth is described by Reeve and Huxley's allometric equation. Thus, the implementation of this equation into the framework of functional mapping allows dynamic QTLs for seed development to be identified more precisely. By estimating and testing mathematical parameters that define Reeve and Huxley's allometric equations of seed growth, the dynamic pattern of the genetic effects of the QTLs identified can be analyzed. We used the model to analyze a soybean data, leading to the detection of QTLs that control the growth of seed dry weight. Three dynamic QTLs, located in two different linkage groups, were detected to affect growth curves of seed dry weight. The QTLs detected may be used to improve seed yield with marker-assisted selection by altering the pattern of seed development in a hope to achieve a maximum size of seeds at a harvest time.

Nickel and Cobalt-Catalyzed Coupling of Alkyl Halides with Alkenes Via Heck Reactions and Radical Conjugate Addition

Cross-coupling of alkyl halides with alkenes leading to Heck-type and addition products is summarized. The development of Heck reaction with aliphatic halides although has made significant progress in the past decade and particularly recently, it was much less explored in comparison with the aryl halides. The use of Ni- and Co-catalyzed protocols allowed efficient Heck coupling of activated and unactivated alkenes with 1(o), 2(o) and 3(o) alkyl halides. In addition, radical conjugate addition to activated alkenes has become a well-established method that has led to efficient construction of many natural products. The utilization of Ni- and Co-catalyzed strategies would avoid toxic tin reagents, and therefore worth exploring. The recent development of Ni- and Co-catalyzed addition of alkyl halides to alkenes displays much improved reactivity and functional group tolerance. In this mini-review, we also attempt to overview the mechanisms that are proposed in the reactions, aiming at providing insight into the nickel and cobalt-catalyzed coupling of alkyl halides with alkenes.

Evidence for Different Patterns of Natural Inter-genotype Recombination Between Two PCV2 Parental Strains in the Field

Co-infection with different virus strains is a precondition for genome recombination, which give rise to continuous evolution of porcine circovirus type 2 (PCV2). In the present study, 32 PCV2 positive clinical samples from the diseased and dead pigs were identified by classic PCR. 15 of 32 (46.8%) clinical samples were identified as infection with both PCV2a and PCV2b using genotype-specific PCR. 13/15 of PCV2 strains were identified as recombinants using sequencing analysis, phylogenetic analysis, recombination detection program and base-by-base comparison. Further analyses of the full-length sequences of these strains suggest that the natural recombination events occurred between strains DQ104423 (PCV2a) and AY579893 (PCV2b), yield two new recombinant clusters through different recombination patterns with crossover regions located in ORF2. Recombinant cluster 1 included 3 strains, and recombinant cluster 2 included 10 strains. These results demonstrate that recombination between PCV2a and PCV2b strains can occur in cap protein coding region through different patterns and yield different recombinants. Our study not only provided new evidences that PCV2 strains can undergo recombination through a variety of patterns, but also suggests that recombination events easily occur in the co-existence of different strains of PCV2.

Electrical Stimulation Enhances Peripheral Nerve Regeneration After Crush Injury in Rats

Injured peripheral nerves have the ability to regenerate; however, there is conflicting evidence with regard to whether electrical stimulation (ES) accelerates or hinders neural regeneration. To study the effect of ES on peripheral nerve regeneration following nerve crush injury, 54 Wistar rats were randomly divided into three groups (n=18/group); the control, crush and crush + ES group. Four weeks after surgery, the sciatic functional index (SFI), compound muscle action potential (CMAP) conduction velocity and amplitude in the regenerated nerve, nerve histomorphometry, and levels of myelin protein zero (P0) mRNA and protein at the crush site were assessed. The rats exposed to crush + ES had a significantly increased CMAP conduction velocity, enhanced myelin sheath thickness and increased P0 mRNA and protein levels compared with the rats exposed to crush alone. However, the CMAP amplitude and axonal diameter were similar in the crush and crush + ES rats. Findings of this study demonstrated that the application of ES (3 V, 0.1 ms, 20 Hz, 1 h) immediately after nerve injury accelerates remyelination and may provide a therapeutic clinical strategy.

[3-dimensional Speckle Tracking Echocardiography for Left Ventricular Rotation and Twist in Patients with Hypertension]

Objective: To analyze the characteristics of left ventricular rotation and twist in patients with essential hypertension (EH) of different left ventricular configurations by 3-dimensional speckle tracking echocardiography (3D-STE). Methods: A total of 106 EH patients were divided into 4 groups: a left ventricular normal configuration (LVN) group (n=30), a concentric remodeling (CCR) group (n=31), a concentric hypertrophy (CCH) group (n=29), an eccentric hypertrophy (ECH) group (n=16), and a control group of 30 healthy subjects. The parameters of LVEF, peak basal rotation (Prot-B), peak apical rotation (Prot-A), left ventricular peak apical rotation (LV-rot), and left ventricular peak apical twist (LV-tw) were compared. Results: The left ventricular mass index in the EH groups, which kept increasing, was higher than that in the normal control group (P<0.05). Compared with the normal control group, LVN and ECH group, the left ventricular posterior wall thickness, interventricular septum at end-diastole, and relative wall thickness significantly increased in the CCH and CCR group (P<0.05). LVEF showed no significant difference among the normal control, LVN, CCR and CCH group (P>0.05), but LVEF was lower in the ECH group than in other groups (P<0.05). Compared with the normal control group, Prot-B, Prot-A, LVrot and LVtw were significantly higher in the LVN, CCR and CCH group (P<0.05), but decreased in the ECH group (P<0.05). Conclusion: 3D-STE can evaluate the left ventricular rotation and twist in EH patients with different configurations, and reflect changes in the left ventricular systolic function in EH of different configurations.

Adaptive Centroid-finding Algorithm for Freeform Surface Measurements

Wavefront sensing systems measure the slope or curvature of a surface by calculating the centroid displacement of two focal spot images. Accurately finding the centroid of each focal spot determines the measurement results. This paper studied several widely used centroid-finding techniques and observed that thresholding is the most critical factor affecting the centroid-finding accuracy. Since the focal spot image of a freeform surface usually suffers from various types of image degradation, it is difficult and sometimes impossible to set a best threshold value for the whole image. We propose an adaptive centroid-finding algorithm to tackle this problem and have experimentally proven its effectiveness in measuring freeform surfaces.

Enhanced Performance of InGaN/GaN Based Solar Cells with an In0.05Ga0.95N Ultra-thin Inserting Layer Between GaN Barrier and In0.2Ga0.8N Well

The effect of ultra-thin inserting layer (UIL) on the photovoltaic performances of InGaN/GaN solar cells is investigated. With UIL implemented, the open-circuit voltage was increased from 1.4 V to 1.7 V, short-circuit current density was increased by 65% and external quantum efficiency was increased by 59%, compared to its counterparts at room temperature under 1-sun AM1.5G illumination. The improvements in electrical and photovoltaic properties are mainly attributed to the UIL which can boost the crystal quality and alleviate strain. Moreover, it can act as a transition layer for higher indium incorporation and an effective light sub-absorption layer in multiple quantum wells.

Electron-beam-activated Light-emitting Polymer Nanofibers

We demonstrate a simple approach to high-stability light-emitting polymer nanofibers. We show that nonluminescent polyacrylamide (PAM) nanofibers, when being irradiated by electron beams, can be locally activated into light-emitting nanofibers with high resistance to photobleaching, precise emission patterns, spectrally tunable emission, high repeatability, and great mechanical flexibility. Compared to unirradiated nanofibers, the electron-beam-activated PAM nanofibers show an obvious increase in refractive index of about 0.1. Due to its high versatility, the electron-beam-activated nanofiber demonstrated here represents a promising nanometer-scale integratable light source for functional nanophotonic circuits or devices.

[Study on Using NSP2 Protein of Porcine Reproductive and Respiratory Syndrome Virus (HuN4-F112) to Express E2 Neutralizing Epitope of Classical Swine Fever Virus]

Establishment of recombinant porcine reproductive and respiratory syndrome virus (PRRSV) with co-expression E2 Epitope of Classical Swine Fever virus (CSFV) is a crucial step to develop a genetic engineered vaccine against PRRSV and CSFV. Reverse genetic manipulation could be adopted as a com monly used technique. In this study, we focus on using nonessential regions of NSP2 (aa480-532 and aa508-532) as viral vector to express E2 Epitope of CSFV. A neutralizing epitope of classical swine fever virus (CSFV) E2 protein was inserted into the two nonessential region of nsp2 by the method of mutant PCR, basing on the infectious clone of HuN4-F112 vaccine strain. The co-expressed full-length cDNA clones (psk-HuN4-F112-delta508-532 + E2 and psk-HuN4-F112-delta480-532 + E2) were assembled by cloning and splice of the gene fragments. The completely assembled full-length cDNA clones were confirmed by sequence and Swa I enzyme digestion. Capped RNAs were transcribed in vitro from a full-length cDNA clone of the viral genome and transfected into BHK-21 cells by liposome to acquire the rescued virus. The rescued recombinant viruses were passaged on MARC-145 cells. The successfully rescued viruses were tested by RT-PCR, digestion, and genome sequence. The results showed that these rescued viruses could be distinguished from the parental virus (HuN4-F112) with the mutant genetic marker (Mlu I enzyme site of virual genome at 14 667nt was created by synonymous mutation) and the inserted nsp2 gene region. The results of IFA showed that the inserted E2 epitope could be expressed by the recombinant viruses and the E2 epitope gene was stable during the viral serial passage. The results of plaque assay and viral growth curve showed that the recovery viruses possessed similar characterses of viral growth to those of the parental virus. In summary, the full-length infectious cDNA clones containing the marker gene were constructed and the marker recombinant viruses were rescued. The results suggested that these stable infectious clones could be used as an important tool for development of novel vaccine against PRRSV.

[Utility of High Throughput Sequencing Technology in Analyzing the Terminal Sequence of Caudovirales Bacteriophage Genome]

To confirm the hypothesis that the high frequency sequences of high throughput sequencing are the terminal sequences of the bacteriophage genome. An adaptor of specific sequence was linked to the end of the bacteriophage T3 genomic DNA, which was then subject to high throughput sequencing; as a control, the same T3 genomic DNA without adaptor was also analyzed by high throughput sequencing. The sequencing results were examined with bioinformatics software. Similar high throughput sequencing technique was applied to analyze the genomic sequence of N4-like bacteriophage IME11. Bioinformatics study showed that the sequences tagged with adaptors were consistent with the high frequency sequences without adaptor labeling. Our analysis also indicated that the end of the T4-like phage genome had specific sequences instead of random sequences, disagreeing with the previous assertion. Evidences were provided that N4-like bacteriophage had a particular terminal sequence: the left end of the genome was unique while the right end was permuted. The high throughput sequencing technique was convenient and practical to be used to simultaneously detect the terminal sequence and the complete sequence of bacteriophage genome.

Temperature Sensitivity in Indigenous Australians

Upregulation of SIRT1 by 17β-estradiol Depends on Ubiquitin-proteasome Degradation of PPAR-γ Mediated by NEDD4-1

17β-estradiol (E2) treatment of cells results in an upregulation of SIRT1 and a down-regulation of PPARγ. The decrease in PPARγ expression is mediated by increased degradation of PPARγ. Here we report that PPARγ is ubiquitinated by HECT E3 ubiquitin ligase NEDD4-1 and degraded, along with PPARγ, in response to E2 stimulation. The PPARγ interacts with ubiquitin ligase NEDD4-1 through a conserved PPXY-WW binding motif. The WW3 domain in NEDD4-1 is critical for binding to PPARΓ. NEDD4-1 overexpression leads to PPARγ ubiquitination and reduced expression of PPARγ. Conversely, knockdown of NEDD4-1 by specific siRNAs abolishes PPARΓ ubiquitination. These data indicate that NEDD4-1 is the E3 ubiquitin ligase responsible for PPARγ ubiquitination. Here, we show that NEDD4-1 delays cellular senescence by degrading PPARΓ expression. Taken together, our data show that E2 could upregulate SIRT1 expression via promoting the PPARΓ ubiquitination-proteasome degradation pathway to delay the process of cell senescence.

Hepatitis D is Rare or Non-existent in Hepatitis B Virus-infected Indigenous Australians in the Northern Territory

Post-esophagectomy Gastric Conduit Cancers: Treatment Experiences and Literature Review

Esophagectomy remains the mainstay of treatment for esophageal cancer. The stomach is the commonest organ used to restore intestinal continuity after esophagectomy. Metachronous gastric cancer in the gastric conduit after esophagectomy is rare; the etiology remains unclear. Possible risk factors include Helicobacter pylori infection, biliary or pancreatic reflux and prior radiotherapy. Prognosis of these patients remains poor. Treatment of this particular entity poses unique challenges to the surgeon and oncologist. Early diagnosis by endoscopy may allow endoscopic excision such as endoscopic mucosal resection or endoscopic submucosal dissection. In more advanced cancers, surgery is difficult, reconstruction is complicated, and further radiation may not be feasible because of previous neoadjuvant therapy. In this report, four patients who developed gastric conduit cancers are presented. They were treated with either surgery alone or combined with chemoradiotherapy. All four patients were still alive after at least 21 months, with three patients currently still alive (21-48 months). The literature is also reviewed, in particular addressing the incidence, possible underlying causes, prognosis and options of treatment for this specific clinical scenario.

A Combined Blood Based Gene Expression and Plasma Protein Abundance Signature for Diagnosis of Epithelial Ovarian Cancer - a Study of the OVCAD Consortium

The immune system is a key player in fighting cancer. Thus, we sought to identify a molecular 'immune response signature' indicating the presence of epithelial ovarian cancer (EOC) and to combine this with a serum protein biomarker panel to increase the specificity and sensitivity for earlier detection of EOC.

Adsorption Removal of Tetracycline from Aqueous Solution by Anaerobic Granular Sludge: Equilibrium and Kinetic Studies

High concentration animal wastewater is often contaminated by tetracycline and an upflow anaerobic sludge bioreactor (UASB) with granular sludge is often used to treat the wastewater. The investigation of the adsorption process of tetracycline on anaerobic granular sludge during anaerobic digestion of animal wastewater will increase the understanding of antibiotics behavior in the UASB reactor. In this study, the effects of initial pH, humic acid concentration, and temperature on the removal of tetracycline by anaerobic granular sludge from aqueous solution were investigated using the batch adsorption technique in 100 mL flasks with 75 mL of work volume. The results show that the highest removal efficiency of 93.0% was achieved around pH 3.0 and the removal efficiency at the neutral pH range (pH 6.0-8.0) is about 91.5%. The thermodynamic analysis indicates that the adsorption is a spontaneous and endothermic process. The adsorption kinetics followed the pseudo-second-order equation. The adsorption isotherms analysis indicates that the Langmuir model is better than the Freundlich model for the description of the adsorption process and confirms the result of thermodynamics analysis. The maximum adsorption capacities were 2.984, 4.108 and 4.618 mg/g at 25, 35 and 45 °C, respectively. These results provide useful information for understanding the fate and transformation of tetracycline in a UASB digestion system and improving the management of tetracycline contaminated animal wastewater.

[The Role of Occlusal Factors in the Occurrence of Vertical Root Fracture]

To investigate the occlusal characteristics and the condition of tooth abrasion in patients with vertical root fracture and to discuss the etiology of the vertical root fracture and the relationships between occlusal disorder, tooth abrasion and vertical root fracture of molars.

Incidence and Bone Biopsy Findings of Atypical Femoral Fractures

Bisphosphonates are widely used in the treatment of osteoporosis. It has been suggested that bisphosphonate treatment may be associated with atypical femoral fractures (AFFs), severely suppressed bone turnover rate, and decreased mineralization. We studied bone properties using bone quantitative histomorphometry and Fourier transform infrared spectroscopic imaging (FTIRI) on patients with AFFs. Further, the incidence of AFFs was estimated. Patient records of Kuopio University Hospital, Finland from January 2007 to June 2009 were reviewed to identify all patients who had sustained and had been operated for AFF (n = 8). The incidence of AFFs among patients on bisphosphonates was 0.61 fractures/1,000 patients per year, compared to 0.0067/1,000 per year among untreated patients. The patients that underwent bone biopsy (n = 4) were postmenopausal women (aged 55.5-81.1 years) who had been treated with bisphosphonates for over 4 years. Histomorphometry revealed low trabecular bone volume. Bone formation and resorption parameters tended to be low. Trabecular bone single labels were detected in one patient in the region of interest. In the extended label search, trabecular bone double labels were found in two patients. Based on FTIRI results, higher phosphate-to-amide I ratio and collagen maturity were found compared to normal samples. The heterogeneity of phosphate-to-amide I ratio was low. Overall incidence of atypical femoral fractures is low. The poor fracture resistance in some patients on long-term bisphosphonate-therapy could be explained by low bone formation, and changes in bone composition, i.e., higher degree of mineralization, increased collagen maturity, and decreased heterogeneity of the degree of mineralization.

Synergistic Effects of Ultrashort Wave and Bone Marrow Stromal Cells on Nerve Regeneration with Acellular Nerve Allografts

Acellular nerve allografts (ANA) possess bioactivity and neurite promoting factors in nerve tissue engineering. Previously we reported that low dose ultrashort wave (USW) radiation could enhance the rate and quality of peripheral nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA implanted with bone marrow stromal cells (BMSCs) exhibited a similar result. Thus, it is interesting to know whether it might yield a synergistic effect when USW radiation is combined with BMSCs-laden ANA. Here we investigated the effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing peripheral nerve injuries. Adult male Wistar rats were randomly divided into four groups: Dulbecco's Modified Eagle's Medium (DMEM) control group, BMSCs-laden group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves were assayed morphologically and functionally, and growth-promoting factors in the regenerated tissues following USW administration or BMSCs integration were also detected. The results indicated that the combination therapy caused much better beneficial effects evidenced by increased myelinated nerve fiber number, myelin sheath thickness, axon diameter, sciatic function index, nerve conduction velocity and restoration rate of tibialis anterior wet weight. Moreover, the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the spinal cord and muscles were elevated significantly. In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment on peripheral nerve regeneration, which may help establish novel strategies for repairing peripheral nerve defects. Synapse, 2013. © 2013 Wiley Periodicals, Inc.

DEPRESSIVE DISORDERS AMONG CHILDREN IN THE TRANSFORMING CHINA: AN EPIDEMIOLOGICAL SURVEY OF PREVALENCE, CORRELATES, AND SERVICE USE

BACKGROUND: To date, no one-phase survey of childhood depression has been performed in China that involves both urban and rural community children. The objective of this study was to determine the prevalence, correlates, and mental health service utilization of depressive disorders (DDs) in a community-based sample of 6-14-year-old children in south-central China. METHODS: Children (3,582) were approached through multistage sampling and interviewed using a Chinese version of the Mini International Neuropsychiatric Interview for Children and Adolescents 5.0, which is a structured interview that is administered by trained psychiatrists to obtain information from children and their guardians. RESULTS: The overall prevalence of all current DDs was found to be 2.8% (95%CI: 1.5-3.9). The risk factors for depression included being 9-14-year old, not attending school, having unmarried parents, living in a nonnuclear family (single parent or parentless family), being taken care of by people other than two parents (single parent, grandparent(s), other relatives, or others) during the past year, and not being breastfed prior to 1 year of age. Only 5.8% of the depressed children had received professional help prior to the interview. CONCLUSIONS: The prevalence of DDs among children in this part of China is relatively high compared with most figures reported in other countries. Depression in this age group has been a major public health concern, but it is often underrecognized. There is an urgent need to develop efficacious interventions aimed at the prevention and early recognition of childhood depression.

Prevalence and Trends of Aminoglycoside Resistance in Shigella Worldwide, 1999-2010

Shigellosis causes diarrheal disease in humans in both developed and developing countries, and multi-drug resistance in Shigella is an emerging problem. Understanding changing resistance patterns is important in determining appropriate antibiotic treatments. This meta-analysis systematically evaluated aminoglycoside resistance in Shigella. A systematic review was constructed based on MEDLINE and EMBASE databases. Random-effect models or fixed-effect models were used based on P value considering the possibility of heterogeneity between studies for meta-analysis. Data manipulation and statistical analyses were performed using software STATA 11.0. By means of meta-analysis, we found a lower resistance to three kinds of aminoglycosides in the Europe-America areas during the 12 year study period than that of the Asia-Africa areas. Kanamycin resistance was observed to be the most common drug resistance among Shigella isolates with a prevalence of 6.88% (95%CI: 6.36%-7.43%). Comparison of data from Europe-America and Asia-Africa areas revealed that Shigella flexneri resistance was greater than the resistance calculated for Shigella sonnei. Importantly, Shigella sonnei has played a significant role in aminoglycoside-resistance in recent years. Similarly, data showed that resistance to these drugs in children was higher than the corresponding data of adults. In conclusion, aminoglycoside-resistant Shigella is not an unusual phenomenon worldwide. Distribution in Shigella resistance differs sharply based on geographic areas, periods of time and subtypes. The results from the present study highlight the need for continuous surveillance of resistance and control of antibiotic usage.

Genetic Variant Rs7758229 in 6q26-q27 Is Not Associated with Colorectal Cancer Risk in a Chinese Population

A recent genome-wide association study has identified a new genetic variant rs7758229 in SLC22A3 for colorectal cancer susceptibility in a Japanese population, but it is unknown whether this newly identified variant is associated with colorectal cancer in other populations, including the Chinese population.

White-Opaque Switching in Natural MTLa/α Isolates of Candida Albicans: Evolutionary Implications for Roles in Host Adaptation, Pathogenesis, and Sex

Phenotypic transitions play critical roles in host adaptation, virulence, and sexual reproduction in pathogenic fungi. A minority of natural isolates of Candida albicans, which are homozygous at the mating type locus (MTL, a/a or α/α), are known to be able to switch between two distinct cell types: white and opaque. It is puzzling that white-opaque switching has never been observed in the majority of natural C. albicans strains that have heterozygous MTL genotypes (a/α), given that they contain all of the opaque-specific genes essential for switching. Here we report the discovery of white-opaque switching in a number of natural a/α strains of C. albicans under a condition mimicking aspects of the host environment. The optimal condition for white-to-opaque switching in a/α strains of C. albicans is to use N-acetylglucosamine (GlcNAc) as the sole carbon source and to incubate the cells in 5% CO2. Although the induction of white-to-opaque switching in a/α strains of C. albicans is not as robust as in MTL homozygotes in response to GlcNAc and CO2, opaque cells of a/α strains exhibit similar features of cellular and colony morphology to their MTL homozygous counterparts. Like MTL homozygotes, white and opaque cells of a/α strains differ in their behavior in different mouse infection models. We have further demonstrated that the transcriptional regulators Rfg1, Brg1, and Efg1 are involved in the regulation of white-to-opaque switching in a/α strains. We propose that the integration of multiple environmental cues and the activation and inactivation of a set of transcriptional regulators controls the expression of the master switching regulator WOR1, which determines the final fate of the cell type in C. albicans. Our discovery of white-opaque switching in the majority of natural a/α strains of C. albicans emphasizes its widespread nature and importance in host adaptation, pathogenesis, and parasexual reproduction.

Association Among Polymorphisms in EGFR Gene Exons, Lifestyle and Risk of Gastric Cancer with Gender Differences in Chinese Han Subjects

BACKGROUND: The epidermal growth factor receptor (EGFR) gene plays a key role in tumor survival, invasion, angiogenesis, and metastatic spread. Recent studies showed that gastric cancer (GC) was associated with polymorphisms of the EGFR gene and environmental influences, such as lifestyle factors. In this study, seven known SNPs in EGFR exons were investigated in a high-risk Chinese population in Jiangsu province to test whether genetic variants of EGFR exons and lifestyle are associated with an increased risk of GC. METHODOLOGYPRINCIPAL FINDINGS: A hospital-based case-control study was performed in Jiangsu province. The results showed that smoking, drinking and preference for salty food were significantly associated with the risk of GC. The differences of lifestyle between males and females might be as the reason of higher incidence rates in males than those in females. Seven exon SNPs were genotyped rs2227983,rs2072454,rs17337023,rs1050171,rs1140475, rs2293347, and rs28384375. It was noted that the variant rs2072454 T allele and TT genotype were significantly associated with an increased risk of GC. Interestingly, our result suggested the ACAGCA haplotype might be associated with decreased risk of GC. However, no significant association was examined between the other six SNPs and the risk of GC both in the total population and the age-matching population even with gender differences. CONCLUSIONS: Smoking, drinking and preference for salty food were significantly associated with the risk of GC in Jiangsu province with gender differences. Although only one SNP (rs2072454) was significantly associated with an increased risk of GC, combined the six EGFR exon SNPs together may be useful for predicting the risk of GC.

Experimental Evaluations of the Accuracy of 3D and 4D Planning in Robotic Tracking Stereotactic Body Radiotherapy for Lung Cancers

Purpose: Due to the complexity of 4D target tracking radiotherapy, the accuracy of this treatment strategy should be experimentally validated against established standard 3D technique. This work compared the accuracy of 3D and 4D dose calculations in respiration tracking stereotactic body radiotherapy (SBRT).Methods: Using the 4D planning module of the CyberKnife treatment planning system, treatment plans for a moving target and a static off-target cord structure were created on different four-dimensional computed tomography (4D-CT) datasets of a thorax phantom moving in different ranges. The 4D planning system used B-splines deformable image registrations (DIR) to accumulate dose distributions calculated on different breathing geometries, each corresponding to a static 3D-CT image of the 4D-CT dataset, onto a reference image to compose a 4D dose distribution. For each motion, 4D optimization was performed to generate a 4D treatment plan of the moving target. For comparison with standard 3D planning, each 4D plan was copied to the reference end-exhale images and a standard 3D dose calculation was followed. Treatment plans of the off-target structure were first obtained by standard 3D optimization on the end-exhale images. Subsequently, they were applied to recalculate the 4D dose distributions using DIRs. All dose distributions that were initially obtained using the ray-tracing algorithm with equivalent path-length heterogeneity correction (3DEPL and 4DEPL) were recalculated by a Monte Carlo algorithm (3DMC and 4DMC) to further investigate the effects of dose calculation algorithms. The calculated 3DEPL, 3DMC, 4DEPL, and 4DMC dose distributions were compared to measurements by Gafchromic EBT2 films in the axial and coronal planes of the moving target object, and the coronal plane for the static off-target object based on the γ metric at 5%∕3mm criteria (γ5%∕3mm). Treatment plans were considered acceptable if the percentage of pixels passing γ5%∕3mm (Pγ<1) ≥ 90%.Results: The averaged Pγ<1 values of the 3DEPL, 3DMC, 4DEPL, and 4DMC dose calculation methods for the moving target plans are 95%, 95%, 94%, and 95% for reproducible motion, and 95%, 96%, 94%, and 93% for nonreproducible motion during actual treatment delivery. The overall measured target dose distributions are in better agreement with the 3DMC dose distributions than the 4DMC dose distributions. Conversely, measured dose distributions agree much better with the 4DEPL∕MC than the 3DEPL∕MC dose distributions in the static off-target structure, resulting in higher Pγ<1 values with 4DEPL∕MC (91%) vs 3DEPL (24%) and 3DMC (25%). Systematic changes of target motion reduced the averaged Pγ<1 to 47% and 53% for 4DEPL and 4DMC dose calculations, and 22% for 3DEPL∕MC dose calculations in the off-target films.Conclusions: In robotic tracking SBRT, 4D treatment planning was found to yield better prediction of the dose distributions in the off-target structure, but not necessarily in the moving target, compared to standard 3D treatment planning, for reproducible and nonreproducible target motion. It is important to ensure on a patient-by-patient basis that the cumulative uncertainty associated with the 4D-CT artifacts, deformable image registration, and motion variability is significantly smaller than the cumulati.

A Solitary Fibrous Tumor in the Pancreas

Partial Protective of Chickens Against Eimeria Tenella Challenge with Recombinant EtMIC-1 Antigen

Eimeria tenella microneme protein 1 (EtMIC-1) is highly conserved with TgMIC-2, which is involved in parasite binding specifically to host cells. Little is known about the immune responses and protective efficacy against E. tenella infection with EtMIC-1 antigen. In the present study, the recombinant proteins of E. tenella mature MIC-1 and adhesive domain (von Willebrand factor type A domain, EtMIC-1-VD) were obtained, protective efficacy against E.tenella infection and the mucosal immune response, which is induced in broilers was evaluated. The antibody levels and the transcription profiles of cytokine of chickens, such as interleukin-12 (IL-12) and interferon-γ (IFN-γ), were detected after being immunized three times with the recombinant EtMIC-1 and EtMIC-1-VD by ELISA assay and quantitative real-time PCR, respectively. The results showed that both groups of chickens, after being immunized with 100 μg EtMIC-1 or EtMIC-1-VD antigen, induced about tenfold higher IgG levels compared to the nonimmune groups. The transcription profiles of IL-12 and IFN-γ of the immunized groups were significantly higher than the control groups as well. The anticoccidial index of the group immunized with 100 μg EtMIC-1 and the group immunized with 100 μg EtMIC-1-VD were 167.2 and 165.5, respectively, which are significantly higher than low-dose immunized groups and challenged control groups. Our data suggests that VD domain is the key functional structure of EtMIC-1 that could trigger a significant humoral and cellular response against E. tenella infection, and EtMIC-1 had the potential in imparting partial protection in chickens against homologous challenge.

Enhancing Specific-Antibody Production to the RagB Vaccine with GITRL That Expand Tfh, IFN-γ(+) T Cells and Attenuates Porphyromonas Gingivalis Infection in Mice

The outer membrane protein RagB is one of the major virulence factors of the periodontal pathogen Porphyromonas gingivalis (P. gingivalis). In order to induce protective immune response against P. gingivalis infection, an mGITRL gene-linked ragB DNA vaccine (pIRES-ragB-mGITRL ) was constructed. Six-week-old female BALB/c mice were immunized with pIRES-ragB-mGITRL through intramuscular injection and then challenged by subcutaneous injection in the abdomen with P. gingivalis. RagB-specific antibody-forming cells were evaluated by an Enzyme-linked immunosorbent spot, and specific antibody was determined by enzyme-linked immunosorbent assay. In addition, the frequencies of Tfh and IFN-γ(+) T cells in spleen were measured using flow cytometer, and the levels of IL-21 and IFN-γ mRNA or proteins were detected by real time RT-PCR or ELISA. The data showed that the mGITRL-linked ragB DNA vaccine induced higher levels of RagB-specific IgG in serum and RagB-specific antibody-forming cells in spleen. The frequencies of Tfh and IFN-γ(+) T cells were obviously expanded in mice immunized by pIRES-ragB-mGITRL compared with other groups (pIRES or pIRES-ragB ). The levels of Tfh and IFN-γ(+) T cells associated cytokines were also significantly increased in pIRES-ragB-mGITRL group. Therefore, the mice immunized with ragB plus mGITRL showed the stronger resistant to P. gingivalis infection and a significant reduction of the lesion size caused by P. gingivalis infection comparing with other groups. Taken together, our findings demonstrated that intramuscular injection of DNA vaccine ragB together with mGITRL induced protective immune response dramatically by increasing Tfh and IFN-γ(+) T cells and antibody production to P. gingivalis.

Temperature-Induced Emission Enhancement of Star Conjugated Copolymers with Poly(2-(dimethylamino)ethyl Methacrylate) Coronas for Detection of Bacteria

A facile strategy for temperature-induced emission enhancement of star conjugated copolymers has been developed for biodetection. The star copolymers (HCP-star-PDMAEMAs) with different poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) chain lengths were synthesized from the hyperbranched conjugated polymer (HCP) macroinitiator by atom transfer radical polymerization (ATRP). The star conjugated copolymers exhibited interesting thermoresponsive phase transitions with adjustable lower critical solution temperature (LCST) depending on the pH of copolymer solution. Above the LCST, the emission of HCP-star-PDMAEMAs was enhanced greatly through restriction of intermolecular aggregation of conjugated polymer cores by the collapse of PDMAEMA arms. By changing the PDMAEMA length, the emission performance of HCP-star-PDMAEMAs could be readily adjusted. Correspondingly, this temperature-dependent emission enhancement of HCP-star-PDMAEMAs was successfully applied in the highly sensitive detection of bacteria. Due to the existence of a hyperbranched conjugated core and many thermo-responsive PDMAEMA arms, the detection limit of E. coli could reach 10(2) cfu mL(-1).

Enhancing the Biological Performance of Osteoconductive Nanocomposite Scaffolds Through Negative Voltage Electrospinning

Aim: To investigate negative voltage electrospinning of fibrous nanocomposite scaffolds bearing negative electric charges (N-poled), and determine whether and how retained negative charges could influence the biological performance of scaffolds for bone tissue engineering. Materials & methods: Poly(D,L-lactic acid) was used as the polymer matrix and carbonated hydroxyapatite nanospheres were the osteoconductive phase in the electrospun nanocomposite scaffolds. N-poled nanocomposite scaffolds were formed using negative voltage electrospinning, while conventional positive voltage electrospinning produced fibrous nanocomposite scaffolds bearing positive electric charges (P-poled). N-poled and P-poled scaffolds were systematically characterized and their biological performance was investigated through in vitro cell culture experiments. Results & conclusion: N-poled and P-poled scaffolds retained charges for different periods of time after electrospinning. Both types of scaffolds supported cell spreading and promoted filopodia formation. Compared with P-poled scaffolds, N-poled scaffolds enhanced cell proliferation, alkaline phosphatase activity and mineralization. N-poled scaffolds offer distinct advantages for bone tissue engineering.

Are Heat Warning Systems Effective?

Heatwaves are associated with significant health risks particularly among vulnerable groups. To minimize these risks, heat warning systems have been implemented. The question therefore is how effective these systems are in saving lives and reducing heat-related harm. We systematically searched and reviewed 15 studies which examined this. Six studies asserted that fewer people died of excessive heat after the implementation of heat warning systems. Demand for ambulance decreased following the implementation of these systems. One study also estimated the costs of running heat warning systems at US$210,000 compared to the US$468 million benefits of saving 117 lives. The remaining eight studies investigated people's response to heat warning systems and taking appropriate actions against heat harms. Perceived threat of heat dangers emerged as the main factor related to heeding the warnings and taking proper actions. However, barriers, such as costs of running air-conditioners, were of significant concern, particularly to the poor. The weight of the evidence suggests that heat warning systems are effective in reducing mortality and, potentially, morbidity. However, their effectiveness may be mediated by cognitive, emotive and socio-demographic characteristics. More research is urgently required into the cost-effectiveness of heat warning systems' measures and improving the utilization of the services.

Porcine Epidemic Diarrhea Virus N Protein Prolongs S-phase Cell Cycle, Induces Endoplasmic Reticulum Stress, and Up-regulates Interleukin-8 Expression

Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV). The porcine intestinal epithelial cell is the PEDV target cell. In this study, we established a porcine intestinal epithelial cell (IEC) line which can stably express PEDV N protein. We also investigate the subcellular localization and function of PEDV N protein by examining its effects on cell growth, cycle progression, interleukin-8 (IL-8) expression, and survival. The results show that the PEDV N protein localizes in the endoplasmic reticulum (ER), inhibits the IEC growth and prolongs S-phase cell cycle. The S-phase is prolonged which is associated with a decrease of cyclin A transcription level and an increase of cyclin A degradation. The IEC expressing PEDV N protein can express higher levels of IL-8 than control cells. Further studies show that PEDV N protein induces ER stress and activates NF-κB, which is responsible for the up-regulation of IL-8 and Bcl-2 expression. This is the first report to demonstrate that PEDV N protein can induce cell cycle prolongation at the S-phase, ER stress and up-regulation interleukin-8 expression. These findings provide novel information on the function of the PEDV N protein and are likely to be very useful in understanding the molecular mechanisms responsible for PEDV pathogenesis.

Osteoprotegerin Influences the Bone Resorption Activity of Osteoclasts

The aim of the present study was to determine whether osteoprotegerin (OPG) influences the bone resorption activity of osteoclasts. RAW264.7 cells were induced by macrophage colony-stimulating factor (M-CSF) + receptor activator of nuclear factor-κB ligand (RANKL) and 0, 10, 20, 50 and 100 ng/ml OPG were added into various groups in the presence of the two cytokines. The OPG treatment was continued for 24 h. Osteoclast differentiation and activation were estimated via TRAP staining assay, TRITC-conjugated phalloidin staining, resorption activity analysis. Furthermore, the expression levels of the osteoclastic bone resorption-related genes MMP-9, cathepsin K and carbonic anhydrase II (CA II) were examined using real-time polymerase chain reaction (PCR). The data demonstrated that high concentrations of OPG could inhibit the differentiation and activation of osteoclasts. Furthermore, real-time PCR analysis illustrated that OPG decreased the expression of MMP-9 and cathepsin K in different concentrations of OPG and it decreased the expression of CA II genes at 10 and 20 ng/ml concentrations of OPG. For the time gradient study, OPG decreased the expression of MMP-9 and CA II genes but not that of the cathepsin K gene. In summary, the resorption activity of osteoclasts was suppressed by high concentrations of OPG and, at the molecular level, OPG decreased the expression of osteoclastic bone resorption-related genes.

A Mechanistic Study into the Catalytic Effect of Ni(OH)2 on Hematite for Photoelectrochemical Water Oxidation

We report a mechanistic study of the catalytic effect of Ni(OH)2 on hematite nanowires for photoelectrochemical water oxidation. Ni compounds have been shown to be good catalysts for electrochemical and photoelectrochemical water oxidation. While we also observed improved photocurrents for Ni-catalyst decorated hematite photoanodes, we found that the photocurrents decay rapidly, indicating the photocurrents were not stable. Importantly, we revealed that the enhanced photocurrent was due to water oxidation as well as the photo-induced charging effect. In addition to oxidizing water, the photoexcited holes generated in hematite efficiently oxidize Ni(2+) to Ni(3+) (0.35 V vs. Ag/AgCl). The instability of photocurrent was due to the depletion of Ni(2+). We proposed that the catalytic mechanism of the Ni(ii) catalyst for water oxidation is a two-step process that involves the fast initial oxidation of Ni(2+) to Ni(3+), and followed by the slow oxidation of Ni(3+) to Ni(4+), which is believed to be the active catalytic species for water oxidation. The catalytic effect of the Ni(ii) catalyst was limited by the slow formation of Ni(4+). Finally, we elucidated the real catalytic performance of Ni(OH)2 on hematite for photoelectrochemical water oxidation by suppressing the photo-induced charging effect. This work could provide important insights for future studies on Ni based catalyst modified photoelectrodes for water oxidation.

Evaluating the Effectiveness of Heat Warning Systems: Systematic Review of Epidemiological Evidence

OBJECTIVES: To review the existing research on the effectiveness of heat warning systems (HWSs) in saving lives and reducing harm. METHODS: A systematic search of major databases was conducted, using "heat, heatwave, high temperature, hot temperature, OR hot climate" AND "warning system". RESULTS: Fifteen articles were retrieved. Six studies asserted that fewer people died of excessive heat after HWS implementation. HWS was associated with reduction in ambulance use. One study estimated the benefits of HWS to be $468 million for saving 117 lives compared to $210,000 costs of running the system. Eight studies showed that mere availability of HWS did not lead to behavioral changes. Perceived threat of heat dangers to self/others was the main factor related to heeding warnings and taking proper actions. However, costs and barriers associated with taking protective actions, such as costs of running air conditioners, were of significant concern particularly to the poor. CONCLUSIONS: Research in this area is limited. Prospective designs applying health behavior theories should establish whether HWS can produce the health benefits they are purported to achieve by identifying the target vulnerable groups.

Fabrication of Tunable Janus Microspheres with Dual Anisotropy of Porosity and Magnetism

This work presents a facile approach to produce a novel type of Janus microspheres with dual anisotropy of porosity and magnetism based on Pickering-type double emulsion templates. A stable aqueous Fe3O4 dispersion-in-oil-in-water (WF/O/W) double Pickering emulsion is first generated by using hydrophobic silica and hydrophilic mesoporous silica particles as stabilizers. Janus microspheres with multi-hollow structure possessing magnetite nanoparticles concentrated on one side of the microspheres are obtained after polymerization of the middle oil phase of the double emulsion under a magnetic field. The resultant Janus microspheres are characterized by optical microscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray analysis (EDX). Moreover, we have systematically investigated the influences of Fe3O4 particle concentration, hydrophobic silica particle content, and volume ratio of the inner water phase to middle oil phase (WF/O) on the double emulsion formation and consequently on the structure of the resulting Janus microspheres. Our results show that the distribution of the multi-hollow structures within the prepared microspheres can be accurately tailored by adjusting the ratio of WF/O. In addition, the obtained Janus microsphere can be fairly orientated under a magnetic field, making them a potential candidate for synthesizing Janus membrane.

Visual Impairment and Spectacle Coverage Rate in Baoshan District, China: Population-based Study

To investigate the prevalence and risk factors of visual impairment associated with refractive error and the unmet need for spectacles in a special suburban senior population in Baoshan District of Shanghai, one of several rural areas undergoing a transition from rural to urban area, where data of visual impairment are limited.

4-Azolylphenyl Isoxazoline Insecticides Acting at the GABA Gated Chloride Channel

Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides.

Brain Edema in Acute Liver Failure: Role of Neurosteroids

Brain edema is a major neurological complication of acute liver failure (ALF) and swelling of astrocytes (cytotoxic brain edema) is the most prominent neuropathological abnormality in this condition. Elevated brain ammonia level has been strongly implicated as an important factor in the mechanism of astrocyte swelling/brain edema in ALF. Recent studies, however, have suggested the possibility of a vasogenic component in the mechanism in ALF. We therefore examined the effect of ammonia on blood-brain barrier (BBB) integrity in an in vitro co-culture model of the BBB (consisting of primary cultures of rat brain endothelial cells and astrocytes). We found a minor degree of endothelial permeability to dextran fluorescein (16.2%) when the co-culture BBB model was exposed to a pathophysiological concentration of ammonia (5mM). By contrast, lipopolysaccharide (LPS), a molecule well-known to disrupt the BBB, resulted in an 87% increase in permeability. Since increased neurosteroid biosynthesis has been reported to occur in brain in ALF, and since neurosteroids are known to protect against BBB breakdown, we examined whether neurosteroids exerted any protective effect on the slight permeability of the BBB after exposure to ammonia. We found that a nanomolar concentration (10nM) of the neurosteroids allopregnanolone (THP) and tetrahydrodeoxycorticosterone (THDOC) significantly reduced the ammonia-induced increase in BBB permeability (69.13 and 58.64%, respectively). On the other hand, we found a marked disruption of the BBB when the co-culture model was exposed to the hepatotoxin azoxymethane (218.4%), but not with other liver toxins commonly used as models of ALF (thioacetamide and galactosamine, showed a 29.3 and 30.67% increase in permeability, respectively). Additionally, THP and THDOC reduced the effect of TAA and galactosamine on BBB permeability, while no BBB protective effect was observed following treatment with azoxymethane. These findings suggest that ammonia does not cause a significant BBB disruption, and that the BBB is intact in the TAA or galactosamine-induced animal models of ALF, likely due to the protective effect of neurosteroids that are synthesized in brain in the setting of ALF. However, caution should be exercised when using azoxymethane as an experimental model of ALF as it caused a severe breakdown of the BBB, and neurosteriods failed to protect against this.

Bi-layer Collagen/microporous Electrospun Nanofiber Scaffold Improves the Osteochondral Regeneration

An optimal scaffold is crucial for osteochondral regeneration. Collagen and electrospun nanofibers have been demonstrated to facilitate cartilage and bone regeneration, respectively. However, the effect of combining collagen and electrospun nanofibers on osteochondral regeneration has yet to be evaluated. Here, we report that the combination of collagen and electrospun poly-l-lactic acid nanofibers synergistically promotes osteochondral regeneration. We first fabricated bi-layer microporous scaffold with collagen and electrospun poly-l-lactic acid nanofibers (COL-nanofiber). Mesenchymal stem cells were cultured on the bi-layer scaffold and their adhesion, proliferation and differentiation were examined. Moreover, osteochondral defects were created in rabbits and implanted with COL-nanofiber scaffold. Cartilage and subchondral bone regeneration were evaluated at 6 and 12weeks after surgery. Compared with COL scaffold, cells on COL-nanofiber scaffold exhibited more robust osteogenic differentiation, indicated by higher expression levels of OCN and runx2 genes as well as the accumulation of calcium nodules. Furthermore, implantation of COL-nanofiber scaffold seeded with cells induced more rapid subchondral bone emergence, and better cartilage formation, which led to better functional repair of osteochondral defects as manifested by histological staining, biomechanical test and micro-computed tomography data. Our study underscores the potential of using the bi-layer microporous COL-nanofiber scaffold for the treatment of deep osteochondral defects.

A Probabilistic Patch-Based Label Fusion Model for Multi-Atlas Segmentation with Registration Refinement: Application to Cardiac MR Images

The evaluation of ventricular function is important for the diagnosis of cardiovascular diseases. It typically involves measurement of the left ventricular (LV) mass and LV cavity volume. Manual delineation of the myocardial contours is timeconsuming and dependent on the subjective experience of the expert observer. In this paper, a multi-atlas method is proposed for cardiac MR image segmentation. The proposed method is novel in two aspects. First, it formulates a patch-based label fusion model in a Bayesian framework. Second, it improves image registration accuracy by utilising label information, which leads to improvement of segmentation accuracy. The proposed method was evaluated on a cardiac MR image set of 28 subjects. The average Dice overlap metric of our segmentation is 0.92 for the LV cavity, 0.89 for the RV cavity and 0.82 for the myocardium. The results show that the proposed method is able to provide accurate information for clinical diagnosis.

Enantioseparation of Chiral Aromatic Acids by Multiple Dual Mode Counter-current Chromatography Using Hydroxypropyl-β-cyclodextrin As Chiral Selector

This work concentrates on extending the utilization of multiple dual mode counter-current chromatography in chiral separations. Two aromatic acids, 2-(6-methoxy-2-naphthyl) propionic acid and 2-phenylpropionic acid, were enantioseparated by multiple dual mode counter-current chromatography using hydroxypropyl-β-cyclodextrin as chiral selector. The two-phase solvent systems consisting of n-hexane-ethyl acetate-0.1 mol L(-1) phosphate buffer pH2.67 containing 0.1 mol L(-1) hydroxypropyl-β-cyclodextrin (7.5:2.5:10 for 2-(6-methoxy-2-naphthyl) propionic acid and 7:3:10 for 2-phenylpropionic acid, v/v/v) were used. Conventional multiple dual mode and modified multiple dual mode were compared according to peak resolution under current separation mechanism. The influence of elution time after the first phase inversion and number of cycles for multiple dual mode were investigated. Peak resolution of 2-(6-methoxy-2-naphthyl) propionic acid and 2-phenylpropionic acid increased from 0.62 to 1.05 and 0.72 to 0.84 respectively using optimized multiple dual mode conditions. Being an alternative elution method for counter-current chromatography, multiple dual mode elution greatly improved peak resolution in chiral separations.

Controlled Fabrication and Optoelectrical Properties of Metallosupramolecular Films Based on Ruthenium(II) Phthalocyanines and 4,4'-Bipyridine Covalently Anchored on Inorganic Substrates

Fully conjugated metallosupramolecular self-assembled multilayer films were controllably fabricated based on bibenzonitril-phthalocyaninato ruthenium(II) (BBPR) and 4,4'-bipyridine (BP) via axially coordination interaction between ruthenium ions and the pyridine groups on the modified substrates. The substrates were first functionalized by 4-(pyridine-4-ylethynyl)benzenic diazonium salt (PBD) through photodecomposition of diazonium group under UV irradiation. As a result, the pyridine-containing functional groups were vertically and covalently anchored onto the surface of substrate and got a stable monolayer. Soluble ruthenium phthalocyanine, axially coordinated by labile benzonitrile groups, was used to fabricate the layer-by-layer self-assembled films with BP through ligand-exchanging reaction between benzonitrile and pyridine in each self-assembled cycle. The UV-vis analysis results demonstrated the successful fabrication of bi(4,4'-bipyridine)phthalocyaninato ruthenium(II) (BPPR) metallosupramolecular ultrathin films with definite structures on PBD-modified substrate. Under illumination, the BPPR self-assembled multilayer films displayed a quick response to light. The maximum current density reached 120 nA/cm(2) at six bilayers. The Eg, HOMO, and LUMO of the six-bilayer were quantitatively measured to be 1.68, -5.29, and -3.61 eV, respectively. This strategy supplies a facile method to get full-conjugated metallosupramolecules and a platform for developing higher performance solar cell from the point of adjusting dye aggregate state structure.

GABAB Receptors Resist Acute Desensitization in Both Postsynaptic and Presynaptic Compartments of Periaqueductal Gray Neurons

The ventrolateral midbrain periaqueductal gray (PAG) neurons have been intensively studied because of their pivotal role in the descending pain modulation system. Activation of GABAB receptors, one type of inhibitory G-protein-coupled receptors (GPCRs), in PAG neurons results in both presynaptic and postsynaptic inhibition. Acute desensitization is defined as rapid attenuation of receptor-mediated signaling. Recent studies report that multiple inhibitory GPCRs, including GABAB receptors, resist acute desensitization in the presynaptic but not postsynaptic compartments of certain neurons in mammal brains. In the present study, employing whole-cell voltage-clamp recordings on acute PAG slices from adult rats, we found that GABAB receptors resist acute desensitization to prolonged administration of baclofen (GABAB receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABAB receptors was independent of presynaptic alteration and vice versa. The GABAB receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABAB receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons.

Performance Improvement of GaN-based LEDs with Step Stage InGaN/GaN Strain Relief Layers in GaN-based Blue LEDs

The performance of nitride-based LEDs was improved by inserting dual stage and step stage InGaN/GaN strain relief layer (SRL) between the active layer and n-GaN template. The influences of step stage InGaN/GaN SRL on the structure, electrical and optical characteristics of GaN-based LEDs were investigated. The analysis of strain effect on recombination rate based kâ‹…p method indicated 12.5% reduction of strain in InGaN/GaN MQWs by inserting SRL with step stage InGaN/GaN structures. The surface morphology was improved and a smaller blue shift in the electroluminescence (EL) spectral with increasing injection current was observed for LEDs with step stage SRL compared with conventional LEDs. The output power of LEDs operating at 20mA was about 15.3mW, increased by more than 108% by using step stage InGaN/GaN SRL, which shows great potential of such InGaN/GaN SRL in modulating InGaN/GaN MQWs optical properties based on its strain relief function.

Comprehensively Identifying and Characterizing the Missing Gene Sequences in Human Reference Genome with Integrated Analytic Approaches

The human reference genome is still incomplete and a number of gene sequences are missing from it. The approaches to uncover them, the reasons causing their absence and their functions are less explored. Here, we comprehensively identified and characterized the missing genes of human reference genome with RNA-Seq data from 16 different human tissues. By using a combined approach of genome-guided transcriptome reconstruction coupled with genome-wide comparison, we uncovered 3.78 and 2.37 Mb transcribed regions in the human genome assemblies of Celera and HuRef either missed from their homologous chromosomes of NCBI human reference genome build 37.2 or partially or entirely absent from the reference. We further identified a significant number of novel transcript contigs in each tissue from de novo transcriptome assembly that are unalignable to NCBI build 37.2 but can be aligned to at least one of the genomes from Celera, HuRef, chimpanzee, macaca or mouse. Our analyses indicate that the missing genes could result from genome misassembly, transposition, copy number variation, translocation and other structural variations. Moreover, our results further suggest that a large portion of these missing genes are conserved between human and other mammals, implying their important biological functions. Totally, 1,233 functional protein domains were detected in these missing genes. Collectively, our study not only provides approaches for uncovering the missing genes of a genome, but also proposes the potential reasons causing genes missed from the genome and highlights the importance of uncovering the missing genes of incomplete genomes.

Dance, Drama and Laughter: the Best Medicine

A Population Genetic Model to Infer Allotetraploid Speciation and Long-term Evolution Applied to Two Yarrow Species

Allotetraploid speciation, that is, the generation of a hybrid tetraploid species from two diploid species, and the long-term evolution of tetraploid populations and species are important in plants. We developed a population genetic model to infer population genetic parameters of tetraploid populations from data of the progenitor and descendant species. Two yarrow species, Achillea alpina-4x and A. wilsoniana-4x, arose by allotetraploidization from the diploid progenitors, A. acuminata-2x and A. asiatica-2x. Yet, the population genetic process has not been studied in detail. We applied the model to sequences of three nuclear genes in populations of the four yarrow species and compared their pattern of variability with that in four plastid regions. The plastid data indicated that the two tetraploid species probably originated from multiple independent allopolyploidization events and have accumulated many mutations since. With the nuclear data, we found a low rate of homeologous recombination or gene conversion and a reduction in diversity relative to the level of both diploid species combined. The present analysis with a novel probabilistic model suggests a genetic bottleneck during tetraploid speciation, that the two tetraploid species have a long evolutionary history, and that they have a small amount of genetic exchange between the homeologous genomes.

Subsegmental Bowel Enteral Nutrition Infusion and Succus Entericus Reinfusion in Patients with Severe Acute Pancreatitis Complicated with Multiple Enteric Fistulae: a Successful Experience

Direct Methanol Steam Reforming to Hydrogen over CuZnGaOx Catalysts Without CO Post-treatment: Mechanistic Considerations

Utilization of hydrogen gas (and carbon dioxide) from methanol steam reforming reaction directly without CO post-treatment to supply proton exchange membrane fuel cells for mobile applications is an attractive option. CuZnGaOx based mixed oxides prepared by co-precipitation are found to be active as catalysts for the reforming reaction. It is also found that the use of lower temperature and a faster substrate flow rate with a shorter contact time with the catalyst bed can significantly reduce the CO level in the product gas stream. At 150 °C this class of oxides gives a decent methanol conversion but can also totally suppress the CO production at a short contact time, which is in a sharp contrast with conventional CuZnOx based catalysts that give a significant degree of CO formation. Characterization using Diffuse Reflectance Infrared Fourier Transform (DRIFT) analysis presented in this work clearly suggests the importance of the interface between copper metal-defective oxides for the catalysis. Mechanistic aspects of this reaction are therefore discussed in this paper.

Amine-Promoted Asymmetric (4+2) Annulations for the Enantioselective Synthesis of Tetrahydropyridines: A Traceless and Recoverable Auxiliary Strategy

Gone, without a trace: The in situ reaction of 2-(acetoxymethyl)buta-2,3-dienoate and a secondary amine produces a 2-methylene-3-oxobutanoate equivalent that can be used in asymmetric [4+2] annulations with N-tosylimines to provide tetrahydropyridines in good to excellent yields and enantioselectivities. The amine is easily recovered and acts as a traceless auxiliary.

Medium Chain Triglycerides Dose-dependently Prevent Liver Pathology in a Rat Model of Non-alcoholic Fatty Liver Disease

Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by non-alcoholic fatty liver disease (NAFLD) leading to non-alcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been shown to protect against steatosis and alcoholic liver injury. The current study was designed to determine if a similar beneficial effect of MCT occurs in a rat model of NAFLD. Groups of male rats were isocalorically overfed diets containing 10%, 35% or 70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20% to 65% for 21 days using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum alanine amino transferases were elevated (P < 0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P < 0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P < 0.05). Keeping the total dietary fat at 70%, but increasing the proportion of MCT-enriched saturated fat resulted in a dose-dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8-C10 FAs into liver lipids, but increasing the ratio of MCT to corn oil: reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA β- and ω-oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)α, and appeared to increase mitochondrial respiration through complex III. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.

Comparison of Corneal Sensitivity, Tear Function and Corneal Staining Following Laser in Situ Keratomileusis with Two Femtosecond Laser Platforms

To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers.

Studies on Culture and Osteogenic Induction of Human Mesenchymal Stem Cells Under CO2-Independent Conditions

Abstract Human mesenchymal stem cells (hMSCs) are one of the important factors that regulate bone anabolism. Osteoporosis resulting from microgravity during spaceflight may possibly be due to a decrease in osteogenesis mediated by hMSCs. This speculation should be verified through culture and osteogenic induction of hMSCs in a microgravity environment during spaceflight. Control of CO2 is a key component in current experimental protocols for growth, survival, and proliferation of in vitro cultured cells. However, carrying CO2 tanks on a spaceflight and devoting space/mass allowances for classical CO2 control protocols make experimentation on culture and osteogenesis difficult during most missions. Therefore, an experimental culture and osteogenic medium was developed through modifying the components of buffer salts in conventional culture medium. This experimental medium was used to culture and induce hMSCs under CO2-independent conditions. The results showed that culture and induction of hMSCs with conventional culture medium and conventional osteogenic medium under CO2-independent conditions resulted in an increase of pH in medium. The proliferation of hMSCs was also inhibited. hMSCs cultured with experimental culture medium under CO2-independent conditions showed a proliferation potential that was the same as those cultured with conventional culture medium under CO2-dependent conditions. The experimental osteogenic medium could promote hMSCs to differentiate into osteoblast-like cells under CO2-independent conditions. Cells induced by this induction system showed high alkaline phosphatase activity. The expression levels of osteogenic genes in cells induced with experimental osteogenic medium under CO2-independent conditions were not significantly different from those cells induced with conventional osteogenic medium under CO2-dependent conditions. These results suggest that the experimental culture and induction system could be used to culture hMSCs and induce the osteogenesis of hMSCs in the atmospheric conditions common to spaceflights without additional CO2. Key Words: hMSCs-CO2-independent culture-Osteogenic differentiation-Proliferation. Astrobiology 13, xxx-xxx.

Cognitive Parallels Between Moral Judgment and Modal Judgment

A central question in the study of moral psychology is how immediate intuition interacts with more thoughtful deliberation in the generation of moral judgments. The present study sheds additional light on this question by comparing adults' judgments of moral permissibility with their judgments of physical possibility-a form of judgment that also involves the coordination of intuition and deliberation (Shtulman, Cognitive Development 24:293-309, 2009). Participants (N = 146) were asked to judge the permissibility of 16 extraordinary actions (e.g., Is it ever morally permissible for an 80-year-old woman to have sex with a 20-year-old man?) and the possibility of 16 extraordinary events (e.g., Will it ever be physically possible for humans to bring an extinct species back to life?). Their tendency to judge the extraordinary events as possible was predictive of their tendency to judge the extraordinary actions as permissible, even when controlling for disgust sensitivity. Moreover, participants' justification and response latency patterns were correlated across domains. Taken together, these findings suggest that modal judgment and moral judgment may be linked by a common inference strategy, with some individuals focusing on why actions/events that do not occur cannot occur, and others focusing on how those same actions/events could occur.

Modeling Methods for Identifying Critical Source Areas of Bacteria: Recent Developments and Future Perspectives

Identification of critical source areas of bacteria in a watershed is essential to environmental management and restoration. As a result of the nonpoint and distributed nature of bacterial pollution in watersheds, it is often difficult to identify specific source areas of bacteria for remediation because bacteria collected from different sampling sites might display similar fingerprints. Over the past decade, extensive efforts have been made to identify microbial pollution sources, especially in watersheds. The primary objective of this study was to identify effective methods that can be applied to tracking critical source areas of bacteria in a watershed by a review of recent developments in several modeling methods. Comparisons of the models and their applications revealed that comprehensive watershed-scale source area tracking primarily involves two steps-geographical tracking and mathematical tracking. In terms of geographical tracking, bacterial source locations must be identified to prepare structural best management practices or low impact development for site treatments. For mathematical tracking, the quantity (strength) or release history of bacterial sources must be computed to develop total maximum daily loads (TMDLs) for bacterial load reduction and water quality restoration. Mathematically, source tracking is essentially an inverse modeling issue under uncertainty, requiring inverse modeling combined with a geostatistical method or an optimization algorithm. Consequently, combining biological methods, mathematical models, and sensor technologies (including remote sensing and in-situ sensing) provides an effective approach to identifying critical source locations of bacteria at the watershed-scale.

Apolipoprotein (a) Impairs Endothelial Progenitor Cell-Mediated Angiogenesis

Improvement of blood flow and promotion of angiogenesis are important therapeutic measures for the treatment of ischemic peripheral vascular diseases. Since apolipoprotein (a) (apo (a)) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen (Plg), apo (a) may also have a negative effect on endothelial progenitor cell (EPC)-induced angiogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration, and angiogenesis. To evaluate the effect of apo (a) on EPCs-induced angiogenesis, EPCs were isolated from the bone marrow of apo (a) transgenic mice, wild-type litter mates, and normal mice. These cells were cultured without or with apo (a) before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenous injection of 3×10(5) EPCs. At 3, 7, and 14 days post EPC transplantation, the adhesion, migration abilities, and capillary density in calf muscles were assessed. Results indicate that apo (a) significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In vivo experiments showed the homing of EPCs to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in apo(a) transgenic mice. This study demonstrated that apo (a) could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the angiogenesis ability of EPCs.

Antithrombin is Protective Against Myocardial Ischemia and Reperfusion Injury

BACKGROUND: Antithrombin (AT) is a plasma serpin inhibitor that regulates the proteolytic activity of procoagulant proteases of the clotting cascade. In addition to its anticoagulant activity, AT also possesses potent antiinflammatory properties. OBJECTIVES: The objective of this study is to investigate the antiinflammatory activity of wild-type AT (AT-WT) and a reactive center loop mutant of AT (AT-RCL) which is not capable of inhibiting thrombin. Methods Cardioprotective activities of AT-WT and AT-RCL were monitored in a mouse model of ischemia/reperfusion injury in which the left anterior descending coronary artery was occluded and then released. RESULTS: We demonstrate that AT markedly reduces myocardial infarct size by a mechanism that is independent of its anticoagulant activity. Thus, AT-RCL attenuated myocardial infarct size to the same extent as AT-WT in this acute injury model. Further studies revealed that AT binds to vascular heparan sulfate proteoglycans via its heparin-binding domain to exert its protective activity as evidenced by the therapeutic AT-binding pentasaccharide (fondaparinux) abrogating the cardioprotective activity of AT and a heparin-site mutant of AT exhibiting no cardioprotective property. We further demonstrate that AT up-regulates production of prostacyclin in myocardial tissues and inhibits expression of proinflammatory cytokines TNF-α and IL-6 in vivo by attenuating ischemia/reperfusion-induced JNK and NF-κB signaling pathways. CONCLUSIONS: Our results suggest that both AT and the non-anticoagulant AT-RCL, through their antiinflammatory signaling effects, elicit potent cardioprotective responses. Thus, AT may have therapeutic potential for treating cardiac ischemia/reperfusion injury. This article is protected by copyright. All rights reserved.

Quantifying MRNA Coding Growth Genes in the Maternal Circulation to Detect Fetal Growth Restriction

OBJECTIVE: To examine whether mRNA circulating in maternal blood coding genes regulating fetal growth are differentially expressed in 1) severe preterm FGR and 2) at 28 weeks' gestation in pregnancies destined to develop FGR at term. STUDY DESIGN: mRNA coding growth genes were measured in two independent cohorts. The first was women diagnosed with severe preterm FGR (<34 weeks gestation; n=20) and gestation matched controls (n=15), where the mRNA was measured in both maternal blood and placenta. The second cohort was a prospective longitudinal study (n=52) of women whom had serial ultrasound assessments of fetal growth. mRNA coding growth genes in maternal blood was measured at 28 and 36 weeks in pregnancies with declining growth trajectories (ending up with term FGR; n=10 among the 52 recruited) and controls who maintained normal growth trajectory (n=15). RESULTS: In women with severe preterm FGR there was increased expression of PGH (6.3 fold), IGFs (IGF1 3.4 fold, IGF2 5.0 fold), IGF receptors (2.1 fold) and IGF binding proteins (3.0 fold), and reduced expression of ADAM12 (0.5 fold) in maternal blood (and similar trends in placenta) compared to controls (p<0.05). Notably, at 28 weeks gestation there was increased IGF2 (3.9 fold), PGH (2.7 fold) and IGFBP2 (2.1 fold) expression in maternal blood in women destined to develop FGR at term (p<0.05). CONCLUSION: Measuring mRNA coding growth genes in maternal blood may detect unsuspected severe preterm FGR already present in utero, and predict term FGR when measured at 28 weeks' gestation.

Control of IgG LC:HC Ratio in Stably Transfected CHO Cells and Study of the Impact on Expression, Aggregation, Glycosylation and Conformational Stability

Immunoglobulin G (IgG), the most common class of commercial monoclonal antibodies (mAbs), exists as multimers of two identical light chains (LC) and two identical heavy chains (HC) assembled together by disulfide bridges. Due to the kinetics of mAb assembly, it is suggested that expression of LC and HC in equal amounts is not optimal for IgG production. We designed a set of vectors using internal ribosome entry site (IRES) elements to control LC and HC expression. The intracellular LC:HC ratio of stable IgG expressing Chinese hamster ovary (CHO) cell pools can be controlled effectively at four different ratios of 3.43, 1.24, 1.12, and 0.32. The stable pools were used to study the impact of LC:HC ratio on mAb expression and quality. Gene amplification was most effective for pools with excess LC and generated the highest mAb titers among the transfected pools. When LC:HC ratio was greater than one, more than 97% of the secreted products were IgG monomers. The products also have similar N-glycosylation profiles and conformational stabilities at those ratios. For pools presented a lower LC:HC ratio of 0.32, monomers only constituted half of the product with the other half being aggregates and mAb fragments. High mannose-type N-glycans increased while fucosylated and galactosylated glycans decreased significantly at the lowest LC:HC ratio. Product stability was also adversely affected. The results obtained provide insights to the impact of different LC:HC ratios on stable mAb production and useful information for vector design during generation of mAb producing cell lines.

Electrochemical Synthesis of Nanostructured Materials for Electrochemical Energy Conversion and Storage

Electrochemical synthesis represents a highly efficient method for the fabrication of nanostructured energy materials, and various nanostructures, such as nanorods, nanowires, nanotubes, nanosheets, dendritic nanostructures, and composite nanostructures, can be easily fabricated with advantages of low cost, low synthetic temperature, high purity, simplicity, and environmental friendliness. The electrochemical synthesis, characterization, and application of electrochemical energy nanomaterials have advanced greatly in the past few decades, allowing an increasing understanding of nanostructure-property-performance relationships. Herein, we highlight some recent progress in the electrochemical synthesis of electrochemical energy materials with the assistance of additives and templates in solution or grafted onto metal or conductive polymer supports, with special attention to the effects on surface morphologies, structures and, more importantly, electrochemical performance. The methodology for preparing novel electrochemical energy nanomaterials and their potential applications has been summarized. Finally, we outline our personal perspectives on the electrochemical synthesis and applications of electrochemical energy nanomaterials.

[Calculation and Simulation on Infrared Radiation of Hot Jet from Engine]

Spectral distribution of infrared radiation from plume by the method to calculate infrared radiance of the gaze direction in small sight field was calculated. Based on numerical value and form of radiative transfer equation, infrared radiant intensity of the gaze direction was calculated using the Malkmus statistical narrow-band model and CG approach. Flow field and mole fraction distribution were simulated using a FLUENT computational fluid dynamic (CFD) software. Infrared imaging simulation model of hot jet was established. The hot jet's infrared images of liquid rocket engine were generated. The results demonstrate that the method can detect well-resolved fine structure of flow field. And the model is also applicable to calculation and simulation on infrared radiation of hot jet from engine.

Interpretation of Chinese Society of Endocrinology Consensus Statement on Hyperglycemia Management Target in Adult Inpatients in China

Hyperglycemia of inpatients will increase the incidence of complications, mortality and medical cost, meanwhile prolong the hospitalized course. A consensus on hyperglycemia management target in adult inpatients is proposed by experts of Chinese Society of Endocrinology in order to control hyperglycemia of inpatients safely and effectively. Individualization is emphasized in this consensus. Different stratified glycemic targets should be established according to different patients and conditions. Target blood glucose control is unnecessary for diabetic patients during hospital stay. Glycemic decrement should generally not be quick. Hypoglycemia should be avoided as much as possible, and for overweight and obesity individuals weight gain should be avoided as much as possible also. At the same time, the risks of infection and hyperglycemic crisis must also be avoided due to loose glycemic control.

Efficient Removal of Trace Arsenite Through Oxidation and Adsorption by Magnetic Nanoparticles Modified with Fe-Mn Binary Oxide

Magnetic nanoparticles (MNPs) modified simultaneously with amorphous Fe and Mn oxides (Mag-Fe-Mn) were synthesized to remove arsenite [As(III)] from water. Mag-Fe-Mn particles were fabricated through heterogeneous nucleation technique by employing the maghemite as the magnetic core and Fe-Mn binary oxide (FMBO) as the coating materials. Powder X-ray diffraction, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and transmission electron microscopy were utilized to characterize the hybrid material. With a saturation magnetization of 23.2 emu/g, Mag-Fe-Mn particles with size of 20-50 nm could be easily separated from solutions with a simple magnetic process in short time (within 5 min). At pH 7.0, 200 μg/L of As(III) could be easily decreased to below 10 μg/L by Mag-Fe-Mn particles (0.1 g/L) within 20 min. As(III) could be effectively removed by Mag-Fe-Mn particles at initial pH range from 4 to 8 and the residual As was completely oxidized to less toxic arsenate [As(V)]. The co-occurring redox reactions between Mn oxide and As(III) was confirmed by XPS analysis. Chloride, sulfate, bicarbonate, and nitrate at common concentration range had negligible influence on As(III) removal, whereas, silicate and phosphate reduced the As(III) removal by competing with arsenic species for adsorption sites. As(III) removal was not obviously affected by natural organic matter (up to 8 mg/L as TOC). Mag-Fe-Mn could be regenerated with ternary solution of NaOH, NaCl, and NaClO. Throughout five consecutive cycles, the adsorption and desorption efficiencies maintained above 98% and 87%, respectively. Mag-Fe-Mn had a larger adsorption capacity for As(III) (47.76 mg/g) and could remove trace As(III) more thoroughly than MNPs modified solely with either Fe or Mn oxide due to the synergistic effect of the coating Fe and Mn oxides. This research extended the potential applicability of FMBO to a great extent and provided a convenient approach to efficiently remove trace As(III) from water.

The Role of Homer 1a in Increasing Locomotor Activity and Non-selective Attention, and Impairing Learning and Memory Abilities

The current study aimed to investigate the possible role of Homer 1a in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD). We divided 32 rats into four groups. The rats in the RNAi-MPH group were given the lentiviral vector containing Homer 1a-specific miRNA (Homer 1a-RNAi-LV) by intracerebroventricular injection, and 7 days later they were given three daily doses of methylphenidate (MPH) by intragastric gavage. The RNAi-SAL group was given Homer 1a-RNAi-LV and saline later. The NC-MPH group was given the negative control lentiviral vector (NC-LV) and MPH later. The NC-SAL group was given NC-LV and saline later. Rats that were given Homer 1a RNAi exhibited increased locomotor activity and non-selective attention, and impaired learning and memory abilities, which is in line with the behavioral findings of animal models of ADHD. However, MPH ameliorated these abnormal behaviors. All findings indicated that Homer 1a may play an important role in the etiology and pathogenesis of ADHD.

Physiologic Concentrations of Exogenously Infused Ghrelin Reduces Insulin Secretion Without Affecting Insulin Sensitivity in Healthy Humans

Infusion of ghrelin to supraphysiologic levels inhibits glucose-stimulated insulin secretion, reduces insulin sensitivity and worsens glucose tolerance in humans.Objective:To determine the effects of lower doses of ghrelin on insulin secretion and insulin sensitivity in healthy men and women.Methods:Acyl ghrelin (0.2 and 0.6 nmol kg(-1) hr(-1)) or saline was infused for 225 min in 16 healthy subjects on 3 separate occasions in randomized order. An IV glucose tolerance test was performed and the insulin sensitivity index (SI) derived from the minimal model. Insulin secretion was measured as the acute insulin response to glucose (AIRg) and the disposition index (DI) computed as AIRg x SI.Results:Ghrelin infusions at 0.2 and 0.6 nmol kg(-1) hr(-1) raised steady-state plasma total ghrelin levels 2.2 and 6.1-fold above fasting concentrations. Neither dose of ghrelin altered fasting plasma insulin, glucose, or SI, but both doses reduced insulin secretion compared to the saline control, computed either as AIRg (384 ± 75 and 354 ± 65 vs. 520 ± 110 pM·min, respectively, mean ± SEM; p < 0.01 for both low-and high-dose vs. saline) or DI (2238 ± 421 and 2067 ± 396 vs. 3339 ± 705, respectively; p < 0.02 for both comparisons). The high-dose ghrelin infusion also decreased glucose tolerance.Conclusions:Ghrelin infused to levels occurring in physiologic states such as starvation decreases insulin secretion without affecting insulin sensitivity. These findings are consistent with a role for endogenous ghrelin in the regulation of insulin secretion, and suggest that ghrelin antagonism could improve β-cell function.

Imaging Calcium Microdomains Within Entire Astrocyte Territories and Endfeet with GCaMPs Expressed Using Adeno-associated Viruses

Intracellular Ca(2+) transients are considered a primary signal by which astrocytes interact with neurons and blood vessels. With existing commonly used methods, Ca(2+) has been studied only within astrocyte somata and thick branches, leaving the distal fine branchlets and endfeet that are most proximate to neuronal synapses and blood vessels largely unexplored. Here, using cytosolic and membrane-tethered forms of genetically encoded Ca(2+) indicators (GECIs; cyto-GCaMP3 and Lck-GCaMP3), we report well-characterized approaches that overcome these limitations. We used in vivo microinjections of adeno-associated viruses to express GECIs in astrocytes and studied Ca(2+) signals in acute hippocampal slices in vitro from adult mice (aged ∼P80) two weeks after infection. Our data reveal a sparkling panorama of unexpectedly numerous, frequent, equivalently scaled, and highly localized Ca(2+) microdomains within entire astrocyte territories in situ within acute hippocampal slices, consistent with the distribution of perisynaptic branchlets described using electron microscopy. Signals from endfeet were revealed with particular clarity. The tools and experimental approaches we describe in detail allow for the systematic study of Ca(2+) signals within entire astrocytes, including within fine perisynaptic branchlets and vessel-associated endfeet, permitting rigorous evaluation of how astrocytes contribute to brain function.

A Wheat Phosphate Starvation Response Regulator Ta-PHR1 is Involved in Phosphate Signalling and Increases Grain Yield in Wheat

Background and AimsPhosphorus deficiency is a major limiting factor for crop yield worldwide. Previous studies revealed that PHR1 and it homologues play a key role in regulating the phosphate starvation response in plants. However, the function of PHR homologues in common wheat (Triticum aestivum) is still not fully understood. The aim of the study was to characterize the function of PHR1 genes in regulating phosphate signalling and plant growth in wheat.MethodsWheat transgenic lines over-expressing a wheat PHR1 gene were generated and evaluated under phosphorus-deficient and -sufficient conditions in hydroponic culture, a soil pot trial and two field experiments.Key ResultsThree PHR1 homologous genes Ta-PHR1-A1, B1 and D1 were isolated from wheat, and the function of Ta-PHR1-A1 was analysed. The results showed that Ta-PHR1-A1 transcriptionally activated the expression of Ta-PHT1.2 in yeast cells. Over-expressing Ta-PHR1-A1 in wheat upregulated a subset of phosphate starvation response genes, stimulated lateral branching and improved phosphorus uptake when the plants were grown in soil and in nutrient solution. The data from two field trials demonstrated that over-expressing Ta-PHR1-A1 increased grain yield by increasing grain number per spike.ConclusionsTaPHR1 is involved in phosphate signalling in wheat, and was valuable in molecular breeding of crops, with improved phosphorus use efficiency and yield performance.

Common Variants in Adiponectin Gene Are Associated with Coronary Artery Disease and Angiographical Severity of Coronary Atherosclerosis in Type 2 Diabetes

BACKGROUND: Adiponectin, an adipokine facilitating insulin action, has antiatherogenic effects. This study investigated whether common single nucleotide polymorphisms (SNPs) in the adiponectin gene influenced plasma adiponectin level and whether they were associated with the risk of coronary artery disease (CAD) and its angiographical severity in type 2 diabetes in Chinese population. METHODS: 11 tagging SNPs were genotyped in 1110 subjects with or without CAD in type 2 diabetes. Variants of adiponectin gene were determined by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by sandwich enzyme-linked immunosorbent assay. The severity and extent of coronary atherosclerosis were assessed using the angiographic Gensini score and Sullivan Extent score. RESULTS: Among the 11 SNPs, the minor G allele of SNP rs266729 was significantly associated with higher odds of CAD (odds ratio (95% CI) = 1.49 (1.10 - 2.16), P = 0.022) after adjusting for covariates. In stepwise multivariate logistic regression, SNP rs266729 was a significant independent factor of CAD. Multivariate linear regression analysis revealed that rs266729 (beta = -0.101, P < 0.0001), rs182052 (beta = -0.044, P = 0.0035), and rs1501299 (beta = 0.073, P < 0.0001) were significantly associated with adiponectin level, and also indicated that the minor G allele of SNP rs266729 had higher Gensini score (beta = 0.139, P < 0.001) and Sullivan Extent score (beta = 0.107, P < 0.001). Haplotypes analysis revealed different haplotype distributions in case and control subjects (P = 0.0003), with two common haplotypes GGG and GAG of the rs266729, rs182052, and rs1501299 being associated in heterozygotes with a greater than threefold increase in cardiovascular risk (odds ratio (95% CI)=3.39 (1.83 - 6.30), P = 0.0001). CONCLUSIONS: In our population, genetic variants in the adiponectin gene influence plasma adiponectin levels, and one of them is a strong determinant of CAD susceptibility and its angiographical severity in type 2 diabetes. This study has provided further evidence for a role of adiponectin in the development of CAD.

[Comparison of Southern Blotting and Real-time PCR in Measuring Telomere Shortening]

To analyze and compare the performances of two telomere measurement methods (digoxigenin-labeled Southern blot and Real-time PCR) in cellular senescence research.

Antihypertensive Prescriptions Over a 10-Year Period in a Large Chinese Population

BACKGROUND: International guidelines recommending antihypertensive prescriptions for the management of hypertension have been published in the past decade. Beta-blocker use was discouraged by a significant body of evidence and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) were found more effective among younger patients. This study aims to evaluate the trends in prescription profiles in a large Chinese population because patterns of antihypertensive agent dispensation represent important information for physicians and policymakers. METHODS: From clinical databases consisting of all patient records in the public health-care system of Hong Kong, we examined all antihypertensive prescriptions according to the drug classes (thiazide diuretics, alpha-blockers, beta-blockers, calcium channel blockers (CCBs), ACEIs, ARBs, fixed-dose combinations, and polytherapy (2, ≥3)) between 2001 and 2010. We retrieved >6.3 million prescription episodes for 223,287 patients. RESULTS: The average age of the patients was 59.9 years (SD = 17.6), and 54.8% were women. According to prescription episodes, the most commonly prescribed medications were beta-blockers (31.7%) and CCBs (29.2%), followed by ACEIs (13.9%), thiazide diuretics (5.0%), and alpha-blockers (4.5%). Between 2001 and 2010, the prescription proportions of beta-blockers decreased from 41.5% to 21.5%, whereas that of ARBs increased from 0.5% to 1.0% (P < 0.001, χ(2) test for trend). It was found that the decline of beta-blockers (71.0% to 35.4%) and increase in ARB prescriptions (0.4% to 1.0%) were particularly marked among younger subjects aged <55 years. CONCLUSIONS: These findings provided information on the prescription patterns of antihypertensive agents in a large Chinese population. It sets a future research direction to study the various reasons influencing these drug class-specific trends.

Identification of Impurities in Methotrexate Drug Substances Using High-performance Liquid Chromatography Coupled with a Photodiode Array Detector and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

Methotrexate (MTX) is an antineoplastic therapeutic medicine that acts as an antimetabolite of folic acid. In this study we identified the impurities in MTX drug substances produced by different manufacturers and in different batches using high-performance liquid chromatography coupled with a photodiode array detector and Fourier transform ion cyclotron resonance mass spectrometry (HPLC-PDA/FTICR-MS).

Rhodium-Catalyzed Asymmetric Arylative Cyclization of Meso-1,6-Dienynes Leading to Enantioenriched Cis-Hydrobenzofurans

In tandem: The title reaction of cyclohexadienone-containing meso-1,6-dienynes with arylboronic acids through a tandem arylrhodation/conjugate addition sequence has been realized, and provides a novel approach to the enantioenriched cis-hydrobenzofurans with both excellent yields and enantioselectivities. binap=2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl, Boc=tert-butoxycarbonyl.

DNA Methylation Mediated Repression of MiR-886-3p Predicts Poor Outcome of Human Small Cell Lung Cancer

Small-cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the pathological mechanisms underlying its devastating clinic outcome remain elusive. In this report, we surveyed 924 microRNA (miR) for their expressions in the formalin-fixed paraffin-embedded (FFPE) specimens from 42 SCLC patients, and found that the down-regulated miR-886-3p is closely correlated with the shorter survival of SCLC. This correlation was validated with another 40 cases. It was further discovered that loss of miR-886-3p expression was mediated by DNA hypermethylation of its promoter in both cultured SCLC cells and tumor samples. Moreover, miR-886-3p potently repressed cell proliferation, migration and invasion of NCI-H446 cell in cell culture via suppression of the expression of its target genes: PLK1 and TGF-β1 at post-transcription levels. Forced upregulation of miR-886-3p greatly inhibited in vivo tumor growth, bone/muscle invasion and lung metastasis of NCI-H446 cells. This newly identified miR-886-3p-PLK1 /TGF-β1 nexus that modulates SCLC aggression suggests that both loss of miR-886-3p expression and hypermethylation of the miR-886 promoter are the promising indicators for poor outcome of as well as new therapeutic targets for SCLC.

Highly Enantio- and Diastereoselective Allylic Alkylation of Morita-Baylis-Hillman Carbonates with Allyl Ketones

The asymmetric allylic alkylation of Morita-Baylis-Hillman (MBH) carbonates with allyl ketones has been developed. The α-regioselective alkylation adducts, containing a hexa-1,5-diene framework with important synthetic value, were achieved in up to 83% yield, >99% ee, and 50:1 dr by using a commercially available Cinchona alkaloid as the catalyst. From the allylic alkylation adduct, a cyclohexene bearing two adjacent chiral centers was readily prepared.

Metadherin Confers Chemoresistance of Cervical Cancer Cells by Inducing Autophagy and Activating ERK/NF-κB Pathway

Overexpression of metadherin (MTDH) has been reported in many solid tumors and implicated in chemoresistance. This study aimed to examine MTDH expression in cervical cancer tissues and explore its role in chemoresistance of cervical cancer. MTDH expression in cervical cancer biopsies and several cervical cancer cell lines was detected by immunoblotting and immunohistochemisty. MTDH expression level was experimentally modulated in HeLa cells to determine the effects on chemoresistance to cisplatin. The results showed that MTDH expression was higher in tissues from both cervical squamous carcinoma and cervical adenocarcinoma, compared to normal cervical tissues. MTDH expression was not correlated to patient age or cervical cancer grade, although nuclear MTDH expression was correlated with poor differentiation of cervical cancer. In SiHa, HeLa, CasKi, and C33A cells, MTDH expression level was positively correlated with chemoresistance to cisplatin. MTDH increased autophagy in HeLa cells, which was associated with decreased cleavage of Caspase-3 and the activation of EER/NF-κB pathway. In conclusion, MTDH expression is high in cervical cancer, and it contributes to chemoresistance of cervical cancer. MTDH could be utilized as a therapeutic target to overcome chemoresistance of cervical cancer.

Homoharringtonine in Combination with Cytarabine and Aclarubicin in the Treatment of Refractory/relapsed Acute Myeloid Leukemia: a Single-center Experience

To assess the efficacy and toxicity of HAA regimen (Homoharringtonine 4 mg/m(2)/day, days 1-3; cytarabine 150 mg/m(2)/day, days 1-7; aclarubicin 12 mg/m(2)/day, days 1-7) as a salvage therapy in the treatment of refractory and/or relapsed acute myeloid leukemia (AML), 46 patients with refractory and/or relapsed AML, median age 37 (16-65) years, participated in this clinical study. The median follow-up was 41 (10-86) months. Eighty percent of patients achieved complete remission (CR), and the first single course of re-induction HAA regimen resulted in CR rate of 76.1 %. The study protocol allowed two courses of induction. The CR rates of patients with favorable, intermediate and unfavorable cytogenetics were 90 %, 88.9 %, and 37.5 %, respectively. For all patients, the estimated 3-year overall survival (OS) rate was 42 %, and the estimated relapse free survival (RFS) at 3 years for the 36 CR cases was 49 %. The toxicities associated with HAA regimen were acceptable. HAA is a good choice in cases with refractory/relapsing AML for salvage chemotherapy, preferably with a high-efficacy and low-toxicity profile.

Essential Factors of Sui Zheng Shi Liang Strategy in Type 2 Diabetes Treatment Assessed by Questionnaire

Sui Zheng Shi Liang strategy (regulating prescription dosage with different syndromes) is an important part of syndrome differentiation and treatment in Traditional Chinese Medicine (TCM). Questionnaires were given to doctors and patients to study the essential factors (indicators and timing) of Sui Zheng Shi Liang strategy in the treatment process of type 2 diabetes (T2DM).

An Online Field-amplification Sample Stacking Method for the Determination of β2-agonists in Human Urine by CE-ESI/MS

Field amplified sample stacking (FASS) was combined with a simple, rapid, sensitive CE-ESI-MS method to achieve the on-line enrichment and simultaneous determination of Clenbuterol (CLE), Salbutamol (SAL), Terbutaline (TER) and Formoterol (FOR). Samples were diluted in deionized water, and electrokinetic injection (10kV×50s) was employed to carry out FASS. With FASS, the four β2-agonists had simultaneously baseline enhancement as much as 319, 332, 297 and 115 fold, respectively. Consequently, satisfactory LODs (S/N=3) of 0.08, 0.1, 0.1 and 0.5ng/mL for CLE, SAL, TER and FOR were obtained. The separation of the four analytes was performed at 22kV in ammonium acetate/ammonia (20mmol/L, pH 9.0), using 7.5mmol/L acetic acid in isopropanol/water 50/50% (v/v) as sheath liquid. In addition, an excellent linear response was obtained with RSD less than 1.3% for migration times and less than 6.7% for peak areas (n=5). The recoveries of spiked urine samples were in the range of 82.7-101% with RSD lower than 9.8%. The proposed method has been applied to analyze human urine samples successfully.

Poly(N-isopropylacrylamide-co-N,N'-methylene Bisacrylamide) Monolithic Column Embedded with γ-alumina Nanoparticles Microextraction Coupled with High-performance Liquid Chromatography for the Determination of Synthetic Food Dyes in Soft Drink Samples

The present work proposes a study of the synthesis of poly(N-isopropylacrylamide-co-N,N'-methylene bisacrylamide) monolithic column embedded with γ-alumina nanoparticles and its applications to the extraction of synthetic food dyes in soft drink samples. The monolithic column was synthesized inside fused silica capillaries using thermally initiated free-radical polymerization with N-isopropylacrylamide (NIPAAm) as the monomer, N,N'-methylene bisacrylamide (MBAAm) as the cross-linker, dimethylsulfoxide (DMSO) and dodecanol as the porogen. γ-Alumina nanoparticles were introduced to prevent the swelling of the organic polymer and enhance the loading capacity. In order to obtain optimum experimental conditions, sample pH, sample flow rate, sample volume, eluent flow rate were investigated. Under the optimum conditions, we obtained acceptable linearities, low limits of detection, and good intra-day/inter-day relative standard deviations. When applied to the determination of four synthetic food dyes (Tartrazine, Sunset Yellow, Allura Red, and Azorubine) in soft drink samples, satisfactory recoveries were obtained in the range of 90.4-109.2%.

Outbreak of Microsporidial Keratoconjunctivitis with Rugby Sport Due to Soil Exposure

AimsTo investigate a cluster of microsporidial keratoconjunctivitis in 33 eyes of 25 previously healthy paediatric and teenage individuals after a rugby match.MethodsAn observational case series was reported. Analysis of medical record of patients with microsporidial keratoconjunctivitis, who presented within May 2012, was performed. All patients were treated by a single ophthalmologist with a standardized topical regime, including a fluoroquinolone (moxifloxacin) and an antiseptic (Brolene or Desomedine). Five eyes received corneal scrapings.ResultsThe mean age was 13.36 years (range 5-16). All patients have participated in a rugby match on 21-22 April 2012. The onset of symptoms ranged from 10 to 30 days post exposure. All eyes had multiple superficial coarse punctate keratitis. Four (12%) eyes presented with keratic precipitates. One (3%) eye had intraocular pressure of 27 mm Hg. Microscopic examination of corneal scrapings with modified trichrome or calcofluor white (CFW) fluorescent staining was unremarkable but subsequent PCR test was positive for the small subunit rRNA gene of Vittaforma corneae in three out of five eyes. Sequencing of the PCR product of 1150 bp showed 96-100% identity with the Indian or Singaporean strains of V. corneae. After treatment, all eyes healed without sequel.ConclusionsThe first outbreak of microsporidial keratoconjunctivitis in paediatric and teenage individuals with a rugby match is reported. A standardized topical regime, including a fluoroquinolone (moxifloxacin) and an antiseptic (Brolene or Desomedine), seems to be safe and effective, and requires validation in future treatment trials.Eye advance online publication, 19 April 2013; doi:10.1038/eye.2013.55.

Virulence of Endemic Non-Pigmented Northern Australian Staphylococcus Aureus Clone (Clonal Complex 75 - S. Argenteus) is Not Augmented by Staphyloxanthin

Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus), lacks the carotenoid pigment operon, crtOPQMN, responsible for production of the putative virulence factor, staphyloxanthin. Although a common cause of community-onset skin infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with either bacteremic or non-bacteremic infections. We hypothesized that S. argenteus would have attenuated virulence compared to other S. aureus strains due to its staphyloxanthin 'deficiency'. Compared to prototypical S. aureus strains, S. argenteus was more susceptible to oxidative stress and neutrophil killing in vitro, and had reduced virulence in murine sepsis and skin infection models. Transformation with pTX-crtOPQMN resulted in staphyloxanthin expression and increased resistance to oxidative stress in vitro. However, neither resistance to neutrophil killing nor in vivo virulence were increased. Thus, reduced virulence of S. argenteus in these models is due to mechanisms unrelated to lack of staphyloxanthin production.

Case Study. Whose Bed? Commentary

Intestinal Absorption and Bioavailability of Traditional Chinese Medicines: a Review of Recent Experimental Progress and Implication for Quality Control

Experimental studies on the pharmacokinetics of traditional Chinese medicines (TCMs) have achieved great progress in recent years. This review aims to summarize the progress made on intestinal absorption and bioavailability of TCMs, and proposes the application of intestinal absorption assays as new tools for the quality and safety control of these medicines.

Synergistic Effects Between SO2 and HCOOH on α-Fe2O3

The heterogeneous reactions on mineral aerosol remains an important subject in the atmospheric chemistry due to its role in altering the properties of particles and the budget of trace gases. Yet, the role of co-adsorption of trace gases onto mineral aerosol and potential synergistic effect is largely uncertain, especially, synergistic effect between inorganic and organic gas-phase pollutants. In this study, the synergistic effects between HCOOH and SO2 was investigated for the first time using in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS). It is found that the heterogeneous reaction of HCOOH was hindered significantly by coexisting SO2. The total amount of formate decreased while the one of sulfate did not affect during the co-adsorption on the surface of α-Fe2O3. Futhermore, a part of formate on the surface was catalytic decomposed to CO2 by α-Fe2O3 with the help of SO2. These results suggest a possible mechanism for observed correlations between sulfate and carboxylate in the atmosphere.

Increased Dickkopf-1 Expression in Patients with Unexplained Recurrent Spontaneous Miscarriage

Wnt pathways play an important role in pre-implantation embryo development, blastocyst implantation, and post-implantation uterine decidualisation. However, little is known about the potential role that Wnt signaling plays in patients with unexplained recurrent spontaneous miscarriage (URSM), and no single biomarker with a high predictive value of maternally caused URSM has been identified. We aim to study the molecular mechanisms by which the Wnt pathway controls the progression of early pregnancy by investigating the expression of Dickkopf-1 (DKK1), one of the Wnt agonists, in URSM patients. Plasma and fresh decidual tissues samples were collected from 59 subjects (29 patients with URSM and 30 patients with normal, early pregnancy). Time-resolved immunofluorometric assay system and quantitative real-time RT-PCR were used to determine the serum levels of DKK1 and DKK1 mRNA in the deciduas, respectively. Western blot and immunohistochemistry were used to measure DKK1 protein levels in the deciduas. Serum DKK1 levels were significantly higher in URSM patients compared to the control group (P < 0·001); the expression of DKK1 mRNA and protein in URSM patients were higher relative to healthy controls (P = 0·013). Glandular epithelium from decidual tissues demonstrated cytoplasmic signals for DKK1 in URSM patients, and DKK1 did not stain in healthy controls. Furthermore, serum DKK1 levels significantly correlated with those in the decidual tissues. Our study suggests that DKK1 may be a valuable biomarker of URSM; it can be reliably and conveniently detected in serum, thus obviating the need for decidual tissue analysis.

A "turn-on" Fluorescent Chemosensor for Zinc Ion with Facile Synthesis and Application in Live Cell Imaging

Compound 1 was facilely synthesized through a one step reaction from commercially available materials. As a sensitive and selective "turn-on" fluorescent chemosensor for Zn(II), 1 exhibits a 40-fold fluorescence enhancement response to Zn(II) over other physiological relevant metal ions in aqueous solution at neutral pH. Furthermore, 1 could be efficiently delivered to live cells for bioimaging of Zn(II).

Comparison of Ultrasound Versus Fluorcoscopic Guided Rotator Cuff Interval Approach for MR Arthrography

Our purpose is to compare ultrasound and fluoroscopic-guided approaches to the glenohumeral joint at the rotator cuff interval for magnetic resonance (MR) arthrography of the shoulder. Forty consecutive patients were prospectively studied. 20 patients underwent ultrasound-guided and 20 patients underwent fluoroscopic guided injection. Successful rate of ultrasound guidance is 95%. No significant difference in pain score and duration of injection between two methods (P>.05). Ultrasound-guided rotator cuff interval injection of the glenohumeral joint for MR arthrography is comparable with fluoroscopic-guided injection. Ultrasound is the preferred method as there is no ionizing radiation.

Comparison of the Hypoglycemic Effect of Acarbose Monotherapy in Patients With Type 2 Diabetes Mellitus Consuming an Eastern or Western Diet: A Systematic Meta-analysis

BACKGROUND: Because of its mechanism of action, the starch content of a diet might alter the hypoglycemic effect of acarbose. OBJECTIVE: We aimed to determine whether differences in this hypoglycemic effect existed between individuals consuming Eastern and Western diets with significantly different starch contents, a systematic meta-analysis of studies comparing acarbose with placebo or other hypoglycemic agents in patients with type 2 diabetes mellitus (T2DM) was performed. METHODS: Records were retrieved from the Cochrane clinical controlled trials, MEDLINE, EMBASE, Wanfang, Chinese Technical Periodicals, and ongoing trials databases, and full texts and reference lists were screened. Because no study has directly compared patients consuming different types of diet, fixed- and random-effect models were used to indirectly compare the hypoglycemic effect of acarbose monotherapy with that of placebo and/or comparator drugs in patients with T2DM consuming an Eastern (Eastern Asia) or Western (including Europe and North America) diet. RESULTS: A total of 46 studies were included in the meta-analysis. The results revealed that, compared with placebo, hemoglobin A1c (HbA1c) levels were reduced to a significantly greater extent (1.02%) in the Eastern diet (mean [SD], 1.54% [2.00%]) than in the Western diet (mean [SD], 0.52% [1.20%]) P < 0.00001). The ability of acarbose to reduce HbA1c levels in the Eastern (P = 0.20) and Western (P = 0.10) diet groups was similar to that of sulfonylureas, and HbA1c levels were reduced significantly more (0.39%; P < 0.00001) in the Eastern than in the Western diet group. The ability of acarbose to reduce HbA1c levels was similar to those of metformin and nateglinide/repaglinide, but a comparison of its efficacy with different diets was difficult because of the inclusion of few studies in these categories. Analysis of all included studies revealed that acarbose achieved a greater absolute reduction of HbA1c levels in the Eastern diet (mean [SD], 1.26% [1.20%]) than in the Western diet (mean [SD], 0.62% [1.28%]; P < 0.00001) group. However, the poor quality of Eastern diet trials may have affected the outcomes of the meta-analysis. CONCLUSION: The hypoglycemic effect of acarbose is superior in patients with T2DM consuming an Eastern diet than in those consuming a Western diet and is similar to that of sulfonylureas, metformin, and glinide drugs.

The Discovery of Colchicine-SAHA Hybrids As a New Class of Antitumor Agents

A novel class of colchicine-SAHA hybrids were designed and synthesised based on the synergistic antitumor effect of tubulin inhibitors and histone deacetylases (HDAC) inhibitors. To the best of our knowledge, this is the first design of molecules that are dual inhibitors of tubulin and HDAC. Biological evaluations of these compounds included the inhibitory activity of HDAC, in vitro cell cycle analysis in BEL-7402 cells as well as cytotoxicity in five cancer cell lines.

Chronic Oxidative Stress Modulates TRPC3 and TRPM2 Channel Expression and Function in Rat Primary Cortical Neurons: Relevance to the Pathophysiology of Bipolar Disorder

Recent findings implicate the calcium-permeable transient receptor potential (TRP) melastatin subtype 2 (TRPM2) and canonical subtype 3 (TRPC3) channels in the pathogenesis of bipolar disorder (BD). As both channels are involved in calcium and oxidative stress signaling, thought to be disrupted in BD, we sought to determine the effects of elevated oxidative stress on their expression and function. Primary rat cortical neurons and astrocytes were treated with oxidative stressors for 1 (acute) and 4 days (chronic). Expression of TRPC3 and TRPM2 were determined by immunoblotting and real-time PCR. Channel functionality was assessed using a TRPC3 activator, 1-oleoyl-2-acetyl-sn-glycerol (OAG), and live cell, ratiometric fluorometry with the calcium sensitive dye, Fura-2. Neurons treated with rotenone (15-30nM) for 4 days but not 24h showed significant dose-dependent decreases in TRPC3 mRNA (31%, p<0.001) and protein levels (60%, p<0.001). Similar dose-dependent attenuation of TRPC3-mediated calcium fluxes was demonstrated upon chronic rotenone exposure relative to vehicle controls. In contrast, TRPM2 mRNA but not protein levels increased (47%, p=0.017) after acute and chronic rotenone treatment. Chronic exposure of neurons to paraquat (1-2µM), an alternate oxidative stressor, similarly decreased TRPC3 expression (mRNA: 41%; protein: 61%). Unlike neurons, rotenone treatment incurred no changes in astrocyte TRPC3 levels. These findings demonstrate that TRPC3 and TRPM2 channel expression and/or function is sensitive to the redox status of rat primary neurons and that these changes are time dependent. This provides a critical mechanistic link between altered oxidative stress markers, dysfunction of these TRP channels and calcium dyshomeostasis in BD.

Structural Determinants for Phosphatidylinositol Recognition by Sfh3 and Substrate-induced Dimer-monomer Transition During Lipid Transfer Cycles

Sec14 family homologs are the major yeast phosphatidylinositol/phosphatidylcholine transfer proteins regulating lipid metabolism and vesicle trafficking. The structure of Saccharomyces cerevisiae Sfh3 displays a conserved Sec14 scaffold and reveals determinants for the specific recognition of phosphatidylinositol ligand. Apo-Sfh3 forms a dimer through the hydrophobic interaction of gating helices. Binding of phosphatidylinositol leads to dissociation of the dimer into monomers in a reversible manner. This study suggests that the substrate induced dimer-monomer transformation is an essential part of lipid transfer cycles by Sfh3.

The Motivations, Experiences, and Perspectives of Bone Marrow and Peripheral Blood Stem Cell Donors: Thematic Synthesis of Qualitative Studies

BACKGROUND: Hematopoietic stem cell (HSC) transplantation using bone marrow and peripheral blood stem cells is a lifesaving treatment for patients with leukemia or other blood disorders. However, donors face the risk of physical and psychosocial complications. We aimed to synthesize qualitative studies on the experiences and perspectives of HSC donors. METHODS: We searched MEDLINE, Embase, PsycINFO, CINAHL, Google Scholar, and reference lists of relevant articles to 13th November 2012. Thematic synthesis was used to analyze the findings. RESULTS: Thirty studies involving 1552 donors were included. The decision to donate included themes of: saving life, family loyalty, building a positive identity, religious conviction, fear of invasive procedures, and social pressure and obligation. Five themes about the donation experience were identified: mental preparedness (pervasive pain, intense disappointment over recipient death, exceeding expectations and valuing positive recipient gains); burden of responsibility (striving to be a quality donor, unresolved guilt, and exacerbated grief); feeling neglected (medical dismissiveness and family inattention); strengthened relationships (stronger family ties, establishing blood bonds); and personal sense of achievement (satisfaction and pride, personal development, hero status and social recognition). CONCLUSIONS: Although HSC donation was appreciated as an opportunity to save life, some donors felt anxious and unduly compelled to donate. HSC donors became emotionally invested and felt responsible for their recipient's outcomes, and were profoundly grieved and disappointed if the transplant was unsuccessful. To maximize donor satisfaction and mitigate the psychosocial risks for HSC donors, strategies to address the emotional challenges of anxiety, sense of coercion, guilt, and grief in donors are warranted.

Cutaneous Immunosurveillance and Regulation of Inflammation by Group 2 Innate Lymphoid Cells

Type 2 immunity is critical for defense against cutaneous infections but also underlies the development of allergic skin diseases. We report the identification in normal mouse dermis of an abundant, phenotypically unique group 2 innate lymphoid cell (ILC2) subset that depended on interleukin 7 (IL-7) and constitutively produced IL-13. Intravital multiphoton microscopy showed that dermal ILC2 cells specifically interacted with mast cells, whose function was suppressed by IL-13. Treatment of mice deficient in recombination-activating gene 1 (Rag1(-/-)) with IL-2 resulted in the population expansion of activated, IL-5-producing dermal ILC2 cells, which led to spontaneous dermatitis characterized by eosinophil infiltrates and activated mast cells. Our data show that ILC2 cells have both pro- and anti-inflammatory properties and identify a previously unknown interactive pathway between two innate populations of cells of the immune system linked to type 2 immunity and allergic diseases.

Association of Three Polymorphisms in ARID5B, IKZF1and CEBPE with the Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

Recent genome-wide association studies (GWAS) that focus on childhood acute lymphoblastic leukemia (ALL), the most common malignancy in children younger than 15years old, have found evidence that single nucleotide polymorphisms (SNPs) in IKZF1 (7p12.2), ARID5B (10q21.2) and CEBPE (14q11.2) are strongly related to the risk of childhood ALL. These polymorphisms may lead to abnormal expression and dysfunction of the corresponding transcription factors and are likely to increase the risk of ALL. To validate the relationship between these SNPs and the risk of childhood ALL in Chinese population, we conducted a case-control study of 570 ALL cases and 673 controls. We determined that the SNP rs10821936 in ARID5B was statistically significantly associated with the risk of childhood ALL (P<0.0001). The results were also significant for the subgroup analysis of high-risk, medium-risk and low-risk ALL as well as B-lineage ALL. Statistically significant differences were not found in the SNPs for IKZF1 and CEBPE. In conclusion, ARID5B rs10821936 could serve as a potential biomarker for assessing the risk of childhood ALL in Chinese children.

The LIM Homeobox Gene Ceh-14 is Required for Phasmid Function and Neurite Outgrowth

Transcription factors play key roles in cell fate specification and cell differentiation. Previously, we showed that the LIM homeodomain factor CEH-14 is expressed in the AFD neurons where it is required for thermotaxis behavior in Caenorhabditis elegans. Here, we show that ceh-14 is expressed in the phasmid sensory neurons, PHA and PHB, a number of neurons in the tail, i.e., PHC, DVC, PVC, PVN, PVQ, PVT, PVW and PVR, as well as the touch neurons. Analysis of the promoter region shows that important regulatory elements for the expression in most neurons reside from -4kb to -1.65kb upstream of the start codon. Further, within the first introns are elements for expression in the hypodermis. Phylogenetic footprinting revealed numerous conserved motifs in these regions. In addition to the existing deletion mutation ceh-14(ch3), we isolated a new allele, ceh-14(ch2), in which only one LIM domain is disrupted. The latter mutant allele is partially defective for thermosensation. Analysis of both mutant alleles showed that they are defective in phasmid dye-filling. However, the cell body, dendritic outgrowth and ciliated endings of PHA and PHB appear normal, indicating that ceh-14 is not required for growth. The loss of a LIM domain in the ceh-14(ch2) allele causes a partial loss-of-function phenotype. Examination of the neurites of ALA and tail neurons using a ceh-14::GFP reporter shows abnormal axonal outgrowth and pathfinding.

Real Time Monitoring of Junction Ribonuclease Activity of RNase H Using Chimeric Molecular Beacons

As a highly conserved damage repair protein, except for hydrolysis of DNA-RNA heteroduplex endonucleolytically, RNase H can cleave RNA-DNA junctions in Okazaki fragment processing through its junction ribonuclease (JRNase) activity. We report here a real time fluorescence method for detecting JRNase activity of RNase H with high accuracy by applying chimeric molecular beacons as substrates. The detection limit of E. coli RNase H is 0.5 U ml(-1). The Km and kcat are 20 nM and 0.6 s(-1), respectively. In addition, we used the method to investigate the effect of chemical drugs on the enzyme and found that both penicillin and streptomycin sulfate inhibit its activity with the IC50 values of 0.2 and 0.07 mM, respectively. Finally, we applied the method to reliably detect the JRNase level in tumor cells. In summary, these data indicate that the simple, rapid and sensitive method can be hopefully applied for high-throughput detection of samples and drug screening in vitro.

Tailor-made Au@Ag Core-shell Nanoparticle 2D Arrays on Protein-coated Graphene Oxide with Assembly Enhanced Antibacterial Activity

Water-dispersible two-dimensional (2D) assemblies of Au@Ag core-shell nanoparticles are obtained through a highly selective electroless silver deposition on pre-assembled gold nanoparticles on bovine serum albumin (BSA)-coated graphene oxide (BSA-GO). While neither BSA-GO nor AuNP-decorated BSA-GO shows any antibacterial ability, the silver-coated GO@Au nanosheets (namely GO@Au@Ag) exhibit an enhanced antibacterial activity against Gram-negative Escherichia coli (E. coli) bacteria, superior to unassembled Au@Ag nanoparticles and even ionic Ag. Such an improvement may be attributed to the increased local concentration of silver nanoparticles around a bacterium and a polyvalent interaction with the bacterial surface. In addition, the colloidal stability of this novel nano-antimicrobial against the formation of random nanoparticle aggregates guarantees a minimized activity loss of the Au@Ag nanoparticles. The antibacterial efficacy of GO@Au@Ag is less sensitive to the existence of Cl(-), in comparison with silver ions, providing another advantage for wound dressing applications. Our research unambiguously reveals a strong and very specific interaction between the GO@Au@Ag nanoassembly and E. coli, which could be an important clue toward a rational design, synthesis and assembly of innovative and highly active antibacterial nanomaterials.

Sanpodo Controls Sensory Organ Precursor Fate by Directing Notch Trafficking and Binding γ-secretase

In Drosophila peripheral neurogenesis, Notch controls cell fates in sensory organ precursor (SOP) cells. SOPs undergo asymmetric cell division by segregating Numb, which inhibits Notch signaling, into the pIIb daughter cell after cytokinesis. In contrast, in the pIIa daughter cell, Notch is activated and requires Sanpodo, but its mechanism of action has not been elucidated. As Sanpodo is present in both pIIa and pIIb cells, a second role for Sanpodo in regulating Notch signaling in the low-Notch pIIb cell has been proposed. Here we demonstrate that Sanpodo regulates Notch signaling levels in both pIIa and pIIb cells via distinct mechanisms. The interaction of Sanpodo with Presenilin, a component of the γ-secretase complex, was required for Notch activation and pIIa cell fate. In contrast, Sanpodo suppresses Notch signaling in the pIIb cell by driving Notch receptor internalization. Together, these results demonstrate that a single protein can regulate Notch signaling through distinct mechanisms to either promote or suppress signaling depending on the local cellular context.

The Experiences and Perspectives of Adults Living with Systemic Lupus Erythematosus (SLE): Thematic Synthesis of Qualitative Studies

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that significantly impairs patients' quality of life and can be life-threatening. This study aimstodescribe the experiences and perspectivesof adults living with SLE. METHODS: We conducted a systematic review andthematic synthesis ofqualitative studies that explored the experiences of adults living with SLE. We searched MEDLINE, Embase, PsycINFO, CINAHL(to November week 1 2012), Google Scholar, a thesis database and reference lists of relevant articles. RESULTS: Forty-six studies involving 1385 participants were included. Five themes were identified: restricted lifestyle (including subthemes of pervasive pain, debilitating fatigue, mental deterioration, disruptive episodic symptoms, and postponing parenthood); disrupted identity (gaining diagnostic closure, prognostic uncertainty, being a burden, hopelessness, heightened self-consciousness, fearing rejection, and guilt and punishment); societal stigma and indifference (illness trivialisation, socially ostracised, and averse to differential treatment); gaining resilience (optimism, control and empowerment, being informed and involved, and valuing mutual understanding); and treatment adherence (preserving health, rapport with clinicians, negotiating medication regimens, and financial burden). CONCLUSION: SLE has a severe and pervasive impact on patients'self-esteem and independence. Their physical and social functioning is limited and they feel anxious about their future. Patients perceive that SLE is trivialised, misunderstood and stigmatised by theirfamily, friends and physicians, which intensifies their sense of isolation. Educational, psychosocial and self-care interventions are needed to promote mental resilience, positive coping strategies, self-advocacy and capacities for social participation; and thereby achieve better treatment and health outcomes in patients with SLE. © 2013 by the American College of Rheumatology.

Computed Tomography Enterography Versus Balloon-assisted Enteroscopy for Evaluation of Small Bowel Lesions in Crohn's Disease

OBJECTIVE: We aimed to assess the correlation between CT enterography (CTE) and balloon-assisted enteroscopy (BAE) on severity of small bowel lesions, and evaluated the accuracy of CTE parameters in assessing small intestine lesions in patients with Crohn's disease (CD). METHODS: We performed an observational study of a single-centre cohort. Data were retrieved from our inpatient databases starting from October 2007. Correlations between CT parameters (bowel wall thickness, mural enhancement, comb sign, extramural findings and stricture), endoscopic and histological severity scores, CDAI, and CRP were assessed using Spearman's rank correlation. RESULTS: Seventy patients were included in this study. 157 segments were examined. Bowel wall thickness (r=0.6334, P<0.0001), mural enhancement (r=0.5477, P<0.0001), comb sign (r=0.5898, P<0.0001) and extramural findings (r=0.4754, P<0.0001) were moderately correlated with the segmental capsule endoscopy Crohn's disease activity index (CECDAI-S). The segmental CTE score (CTE-S) also moderately correlated with the CECDAI-S (r=0.6714, P<0.0001), while the total CTE score (CTE-T) strongly correlated with the total capsule endoscopy Crohn's disease activity index (CECDAI-T) (r=0.7252, P<0.0001). Both CTE-T (r= 0.5937, P<0.0001) and CECDAI-T (r=0.6364, P<0.0001) correlated significantly with the Harvey-Bradshaw index. Of five CT parameters, bowel wall thickness have the best accuracy to detect small intestine lesions with an AUROC of 0.811 (p<0.0001), with a sensitivity and specificity of 81.82% and 74.14%, respectively. CONCLUSION: CTE is a reliable technique for detecting small intestine lesions in patients with Crohn's disease, also provides accurate information on small bowel CD severity and activity, with close agreement to inflammatory markers, CDAI, and histopathology.

The Effect of MTADN on 10 Enterococcus Faecalis Isolates and Biofilm: An In Vitro Study

Enterococcus faecalis is frequently isolated from both secondary and persistent root canal infections. MTAD is an effective intracanal irrigant, but its bactericidal activity requires improvement. The goal of this study was to investigate whether nisin, an antibacterial peptide, improves the antibacterial and antibiofilm activities of MTAD against E. faecalis clinical isolates.

Expression Profiling of Abundant Genes in Pulmonary and Cardiac Muscle Tissues of Tibetan Antelope (Pantholops Hodgsonii)

The Tibetan Antelope (TA), which has lived at high altitude for millions of years, was selected as the model species of high hypoxia-tolerant adaptation. Here we constructed two cDNA libraries from lung and cardiac muscle tissues, obtained EST sequences from the libraries, and acquired extensive expression data related energy metabolism genes. Comparative analyses of synonymous (Ks) and nonsynonymous (Ka) substitution rates of nucleus-encoded mitochondrial unigenes among different species revealed that many antelope genes have undergone rapid evolution. Surfactant-associated protein A (SP-A) and surfactant-associated protein B (SP-B) genes in the AT lineage experienced accelerated evolution compared to goat and sheep, and these two genes are highly expressed in the lung tissue. This study suggests that many specific genes of lung and cardiac muscle tissues showed unique expression profiles and may undergo fast adaptive evolution in TA. These data provide useful information for studying on molecular adaptation to high-altitude in humans as well as other mammals.

Comparison of Three Methods for the Recovery of Skin Pathogens from Impetigo Swabs Collected in a Remote Community of Northern Territory, Australia

BACKGROUND: Impetigo is a common infection in children living in remote areas. Immediate plating of impetigo swabs is the gold standard for bacterial recovery but is rarely feasible in remote regions. Bacterial culture increases our understanding of antibiotic resistance and strain diversity, which guides treatment protocols and epidemiological monitoring. METHODS: We investigated three practical alternatives for recovering Streptococcus pyogenes and Staphylococcus aureus from transported swabs: dry swabs transported at 4°C with desiccant and plated within 48 h; swabs inoculated into skim milk tryptone glucose glycerol broth (STGGB), transported at 4°C, stored at - 70°C and plated within 61 days; and ESwabs inoculated into Amies broth, transported at 4°C and plated within 48 h. Detection of Strep. pyogenes and Staph. aureus from simultaneously collected swabs was compared for the dry vs STGGB (36 sores) and the STGGB vs Amies (39 sores) methods. Swabs were collected from 43 children (75 sores sampled) in a remote community of Northern Territory, Australia in November 2011. The children had impetigo and were participating in the Skin Sore Trial [Australian Clinical Trials Registry ACTRN12609000858291]. RESULTS: Recovery of Strep. pyogenes for dry vs STGGB was 72% (26/36) and 92% (33/36) and for STGGB vs Amies was 92% (36/39) for both methods. Staphylococcus aureus recovery for dry vs STGGB was 69% (25/36) and 72% 26/36) and for STGGB vs Amies was 74% (29/39) and 85% (33/39). CONCLUSION: STGGB and Amies media provided higher recovery of Strep. pyogenes than dry swabs. These results and the opportunity to batch and store specimens for molecular studies support the use of STGGB transport media for future impetigo research.

Predictive and Prognostic Role of BRAF Mutation in Metastatic Colorectal Cancer Patients Treated with Anti- Epidermal Growth Factor Receptor Monoclonal Antibodies: A Meta-analysis

OBJECTIVE: This study aimed to evaluate the relationship between BRAF mutation and its predictive and prognostic role on the patients with metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies. METHODS: Computerized researches on BRAF mutation in mCRC patients were performed. Studies with objective response rate (ORR) to anti-EGFR monoclonal antibodies and/or overall survival (OS) and progression-free survival (PFS) with different BRAF gene expression in mCRC patients were eligible. RESULTS: A total of 19 studies including 2825 patients were enrolled in the meta-analysis. BRAF mutation was detected in 246 primary tumors. The ORR reported by 17 studies was 18.4% (40/217) in BRAF mutation group and 41.7% (831/1993) in BRAF wild-type group. The overall risk ratio (RR) for ORR of BRAF mutation patients over BRAF wild-type patients was 0.58 (95% confidence intervals [CI] 0.35-0.94, P = 0.027). The median PFS of BRAF mutation patients was significantly shorter than that of BRAF wild-type patients (hazard ratio [HR] 2.98, 95% CI 2.07-4.27, P <0.001), and the median OS of BRAF mutation was also significantly shorter than that of BRAF wild-type patients (HR 2.85, 95% CI 2.31-3.52, P <0.001). CONCLUSION: BRAF mutation is associated with poor response to the anti-EGFR monoclonal antibodies, and it is an adverse prognostic biomarker of the survival of patients with mCRC.

Clinical Spectrum of Neurosyphilis Among HIV-Negative Patients in the Modern Era

Background: The clinical spectrum of neurosyphilis (NS) has changed over time. Objective: To describe the clinical spectrum and characteristics of NS in HIV-negative patients. Methods: A retrospective chart review was performed for 149 in patients with NS. Result: All patients were >25 years old, including 16.8% asymptomatic for NS, 15.4% with syphilitic meningitis, 24.2% with meningovascular NS, 38.9% with general paresis, 4.0% with tabes dorsalis and 0.7% with gummatous NS. The original misdiagnosis rate was 84.6%. All 149 patients had positive serum Treponema pallidum particle agglutination (TPPA) and rapid plasma reagin (RPR). The overall positive rates of cerebrospinal fluid RPR (CSF-RPR) and CSF-TPPA were 57.0 and 89.9%, respectively. CSF pleocytosis and elevated CSF protein were found in 40.3% of patients. Nonspecific abnormal brain magnetic resonance imaging and electroencephalography findings were present in 60.4 and 54.8% of NS patients, respectively. Conclusions: NS has various clinical manifestations, laboratory findings and magnetic resonance imaging and electroencephalography findings, but all studies lack specificity. Every patient with neurological or psychiatric symptoms that are without unambiguous causes should have blood tests for syphilis. When serology proves positive, patients should undergo CSF examination.

Topical Drug Formulations for Prolonged Corneal Anesthesia

PURPOSE:: Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied. METHODS:: Solutions of TTX, PPC, and OTAB, singly or in combination, were applied topically to the rat cornea. The blink response, an indirect measure of corneal sensitivity, was recorded using a Cochet-Bonnet esthesiometer, and the duration of corneal anesthesia was calculated. The effect of test compounds on the rate of corneal epithelialization was studied in vivo after corneal debridement. RESULTS:: Combination of TTX and PPC resulted in corneal anesthesia that was 8 to 10 times longer in duration than that from either drug administered alone, whereas OTAB did not prolong anesthesia. The rate of corneal healing was moderately delayed after coadministration of TTX and PPC. CONCLUSIONS:: Coadministration of TTX and PPC significantly prolonged corneal anesthesia, but in view of delayed corneal reepithelialization, caution is suggested in the use of the drug combination.

Splicing Kinetics and Transcript Release from the Chromatin Compartment Limit the Rate of Lipid A-induced Gene Expression

The expression of eukaryotic mRNAs is achieved though an intricate series of molecular processes that provide many steps for regulating the production of a final gene product. However, the relationships between individual steps in mRNA biosynthesis and the rates at which they occur are poorly understood. By applying RNA-seq to chromatin-associated and soluble nucleoplasmic fractions of RNA from Lipid A-stimulated macrophages, we examined the timing of exon ligation and transcript release from chromatin relative to the induction of transcription. We find that for a subset of genes in the Lipid A response, the ligation of certain exon pairs is delayed relative to the synthesis of the complete transcript. In contrast, 3' end cleavage and polyadenylation occur rapidly once transcription extends through the cleavage site. Our data indicate that these transcripts with delayed splicing are not released from the chromatin fraction until all the introns have been excised. These unusual kinetics result in a chromatin-associated pool of completely transcribed and 3'-processed transcripts that are not yet fully spliced. We also find that long introns containing repressed exons that will be excluded from the final mRNA are excised particularly slowly relative to other introns in a transcript. These results indicate that the kinetics of splicing and transcript release contribute to the timing of expression for multiple genes of the inflammatory response.

[Effects of Yougui Recipe on the Behavioral Changes in Rat of Steroid-induced Avascular Necrosis of the Femoral Head]

To explore the effect of Yougui Recipe, a kidney-supplementing and yang-activating formula which on the behavioral changes of rat of steroid-induced avascular necrosis of the femoral head (SANFH).

Aggregation-Mediated Macromolecular Uptake by a Molecular Transporter

Endocytosis is a key process in cellular delivery of macromolecules by molecular transporters, although the mechanism of internalization remains unclear. Here, we probe the cellular uptake of streptavidin using biotinylated guanidinoneomycin (biotinGNeo), a low molecular weight guanidinium-rich molecular transporter. Two distinct modes were explored: (i) incubation of cells with a preformed tetravalent streptavidin-(biotinGNeo)4 conjugate and (ii) preincubation of cells with the biotinGNeo before exposure to streptavidin. A significant enhancement in uptake was observed after preincubation with biotinGNeo. FRET studies showed that the enhanced uptake was accompanied by extensive aggregation of streptavidin on the cell surface. Because guanidinylated neomycin was previously found to exclusively bind to heparan sulfate, our observations suggest that heparan sulfate proteoglycan aggregation is a pivotal step for endocytic entry into cells by guanidinoglycosides. These observations put forward a practical and general pathway for the cellular delivery of diverse macromolecules.

The Histone Mark H3K36me3 Regulates Human DNA Mismatch Repair Through Its Interaction with MutSα

DNA mismatch repair (MMR) ensures replication fidelity by correcting mismatches generated during DNA replication. Although human MMR has been reconstituted in vitro, how MMR occurs in vivo is unknown. Here, we show that an epigenetic histone mark, H3K36me3, is required in vivo to recruit the mismatch recognition protein hMutSα (hMSH2-hMSH6) onto chromatin through direct interactions with the hMSH6 PWWP domain. The abundance of H3K36me3 in G1 and early S phases ensures that hMutSα is enriched on chromatin before mispairs are introduced during DNA replication. Cells lacking the H3K36 trimethyltransferase SETD2 display microsatellite instability (MSI) and an elevated spontaneous mutation frequency, characteristic of MMR-deficient cells. This work reveals that a histone mark regulates MMR in human cells and explains the long-standing puzzle of MSI-positive cancer cells that lack detectable mutations in known MMR genes.

Novel Polymer Linkers for Single Molecule AFM Force Spectroscopy

Flexible polymer linkers play an important role in various imaging and probing techniques that require surface immobilization, including atomic force microscopy (AFM). In AFM force spectroscopy, polymer linkers are necessary for the covalent attachment of molecules of interest to the AFM tip and the surface. The polymer linkers tether the molecules and provide their proper orientation in probing experiments. Additionally, the linkers separate specific interactions from nonspecific short-range adhesion and serve as a reference point for the quantitative analysis of single molecule probing events. In this report, we present our results on the synthesis and testing of a novel polymer linker and the identification of a number of potential applications for its use in AFM force spectroscopy experiments. The synthesis of the linker is based on the well-developed phosphoramidate (PA) chemistry that allows the routine synthesis of linkers with predetermined lengths and PA composition. These linkers are homogeneous in length and can be terminated with various functional groups. PA linkers with different functional groups were synthesized and tested in experimental systems utilizing different immobilization chemistries. We probed interactions between complementary DNA oligonucleotides; DNA and protein complexes formed by the site-specific binding protein SfiI; and interactions between amyloid peptide (Aβ42). The results of the AFM force spectroscopy experiments validated the feasibility of the proposed approach for the linker design and synthesis. Furthermore, the properties of the tether (length, functional groups) can be adjusted to meet the specific requirements for different force spectroscopy experiments and system characteristics, suggesting that it could be used for a large number of various applications.

Correlation of TP53 Mutations with HCV Positivity in Hepatocarcinogenesis: Identification of a Novel TP53 Microindel in Hepatocellular Carcinoma with HCV Infection

Although it is known that chronic hepatitis C virus (HCV) infection may contribute to tumor initiation and development, the molecular processes causing hepatocellular carcinoma (HCC) remain unclear. Microindels are unique, infrequent mutations that result in inserted and deleted sequences at the same nucleotide position, and are important contributors to cancer. To date, microindels in the p53 tumor suppressor gene (TP53) have not been fully examined in tumors. In the present study, 116 cases of HCC were screened for mutations in the TP53 gene (exon 5-8) by single-stranded conformational polymorphism analysis followed by direct sequencing. A special type of complex TP53 mutation, 616ins14del1 (14-1 microindel), was identified in a case of HCC with HCV infection. This rare TP53 microindel led to the generation of a truncated protein of 211 amino acids that lacked the DNA-binding domain and tetramerization domain. Immunohistochemistry showed loss of p53 protein expression and downregulation of p21WAF/CIP, Mdm2 and Bax in the tumor cells, indicating an impaired p53 signaling pathway. Nineteen of the 116 (16.4%) HCCs carried a total of 19 TP53 mutations. Notably, 5 of the 13 HCV-positive (38.5%) cases contained a TP53 mutation, and there was a significant association between TP53 mutations and HCV positivity (P=0.0379). No correlation of TP53 mutations with hepatitis B virus (HBV) positivity was observed. In summary, we identified a novel TP53 microindel in HCC, and provided evidence of HCC characterized by HCV infections typically associated with mutational inactivation of the TP53 gene.

Extended Lymphadenectomy in Esophageal Cancer is Crucial

Surgery with lymphadenectomy remains the mainstay of treatment for esophageal cancer. The optimal extent of nodal dissection is controversial. Evidence is accumulating, however, that could demonstrate the benefits of extended lymphadenectomy, which include more accurate disease staging, better locoregional disease control, and improved survival. Except in very early disease where nodal metastases are rare, extended lymphadenectomy is indicated. Data from a randomized controlled trial comparing transhiatal and transthoracic resection have shown better survival in patients with limited nodal burden. Other investigations on en bloc resection, three-field lymphadenectomy, and large-scale international collaborative studies have all provided evidence for the more extensive approach to enhance cure for esophageal cancer. The more extended surgery does lead to potentially higher morbidity rates, and thus surgeons should be versatile in applying such techniques in carefully selected patients, so that postoperative survival and quality of life of patients are not compromised. The challenge in the future is how to tailor surgical strategies for individual patients in order to achieve the best outcome.

Detection of ALK Rearrangement by Immunohistochemistry in Lung Adenocarcinoma and the Identification of a Novel EML4-ALK Variant

INTRODUCTION:: The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as a potent oncogenic driver in non-small-cell lung cancer, in particular adenocarcinoma (ADC). It defines a unique subgroup of lung ADC, which may be responsive to ALK inhibitors. Detection of ALK rearrangement by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the standard procedure, but each with its own limitation. We evaluated the practical usefulness of immunohistochemistry (IHC) to detect ALK expression as a reliable detection method of ALK rearrangement in lung ADC. METHODS:: We tested 373 lung ADCs for ALK rearrangement by IHC and FISH. Multiplex RT-PCR was performed to confirm the fusion variants. RESULTS:: Twenty-two of 373 lung ACs (5.9%) were positive for ALK immunoreactivity. ALK-positive tumor cells demonstrated strong and diffused granular staining in the cytoplasm. All the ALK IHC-positive cases were confirmed to harbor ALK rearrangement, either by FISH, or RT-PCR. Two cases with positive ALK protein expression, but negative for breakapart FISH signal were shown to harbor EML4-ALK variant 1 by RT-PCR. None of the ALK IHC-negative cases were FISH-positive. In addition, we identified a novel EML4-ALK fusion variant (E3:ins53A20), and its potent transformation potential has been confirmed by in vivo tumorigenicity assay. CONCLUSION:: IHC can effectively detect ALK rearrangement in lung cancer. It might provide a reliable and cost-effective diagnostic approach in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy.

Development of GMDR-GPU for Gene-Gene Interaction Analysis and Its Application to WTCCC GWAS Data for Type 2 Diabetes

Although genome-wide association studies (GWAS) have identified a significant number of single-nucleotide polymorphisms (SNPs) associated with many complex human traits, the susceptibility loci identified so far can explain only a small fraction of the genetic risk. Among other possible explanations, the lack of a comprehensive examination of gene-gene interaction (G×G) is often considered a source of the missing heritability. Previously, we reported a model-free Generalized Multifactor Dimensionality Reduction (GMDR) approach for detecting G×G in both dichotomous and quantitative phenotypes. However, the computational burden and less efficient implementation of the original programs make them impossible to use for GWAS. In this study, we developed a graphics processing unit (GPU)-based GMDR program (named GWAS-GPU), which is able not only to analyze GWAS data but also to run much faster than the earlier version of the GMDR program. As a demonstration of the program, we used the GMDR-GPU software to analyze a publicly available GWAS dataset on type 2 diabetes (T2D) from the Wellcome Trust Case Control Consortium. Through an exhaustive search of pair-wise interactions and a selected search of three- to five-way interactions conditioned on significant pair-wise results, we identified 24 core SNPs in six genes (FTO: rs9939973, rs9940128, rs9922047, rs1121980, rs9939609, rs9930506; TSPAN8: rs1495377; TCF7L2: rs4074720, rs7901695, rs4506565, rs4132670, rs10787472, rs11196205, rs10885409, rs11196208; L3MBTL3: rs10485400, rs4897366; CELF4: rs2852373, rs608489; RUNX1: rs445984, rs1040328, rs990074, rs2223046, rs2834970) that appear to be important for T2D. Of these core SNPs, 11 in FTO, TSPAN8, and TCF7L2 have been reported to be associated with T2D, obesity, or both, providing an independent replication of previously reported SNPs. Importantly, we identified three new susceptibility genes; i.e., L3MBTL3, CELF4, and RUNX1, for T2D, a finding that warrants further investigation with independent samples.

Fabrication and Bioproperties of Raspberry-type Hybrid Nanoparticles of Au-thioethyl Pendant Ligand@chitosan

Synthesis of nanoparticles with desired size/morphology has enormous importance, especially in the compelling field of nanotechnology. In this case, a novel kind of raspberry-type hybrid nanoparticles was prepared by hybridization of chitosan (CS) with thioethyl pendant ligand (TPL) modified Au nanoparticles (Au-TPL@CS NPs). Such method was based on ionic gelation using sodium tripolyphosphate as a counterion. The blood compatibility of Au-TPL@CS NPs was characterized by coagulation tests, plasma recalcification time, hemolysis assay, morphological changes of red blood cells (RBCs) and complement activation in vitro. The results showed that Au-TPL@CS NPs exhibited good blood compatibility. The possible underlying mechanism was also present. Finally, the direct electron transfer reactivity of the Hemoglobin/Au-TPL@CS NPs/multi-walled carbon nanotubes/glassy carbon electrode was investigated with cyclic voltammetry measurements. The biosensor exhibited a good electrocatalytic activity to the reduction of H2O2. Such new type of Au-TPL@CS NPs provides a promising platform of biological system for early illness detection and treatment in future.

The Association Between Glycogen Synthase Kinase 3 Beta (GSK3-β) Polymorphisms and Parkinson's Disease Susceptibility: A Meta-analysis

Previous studies on the association between glycogen synthase kinase 3 beta (GSK3-β) polymorphisms (rs334558 and rs6438552) and Parkinson's disease (PD) susceptibility remained inconsistent. Thus, the goal of this study was to re-examine their exact association by a meta-analysis. All eligible studies were identified by a systematic literature search of multiple databases. Six studies (3,105 cases and 4,387 controls) on rs334558 and six studies (2,579 cases and 4,091 controls) on rs6438552 were included. The quality of these studies was generally good according to the Newcastle-Ottawa Scale (NOS). The meta-analysis showed null association between the two variants and PD susceptibility in all genetic models from the overall or Caucasian population. However, the analysis of rs334558 revealed that the risk of PD decreased in heterozygote, dominant or additive models (OR=0.60, 95% CI: 0.48, 0.74; OR=0.63, 95% CI: 0.51, 0.78; OR=0.82, 95% CI: 0.71, 0.94, respectively) from the Eastern Asian population. Moreover, the analysis on the homozygote, heterozygote, dominant or additive models suggested that rs6438552 also reduced the PD risk (OR=0.45, 95% CI: 0.24, 0.84; OR=0.62, 95% CI: 0.39, 0.97; OR=0.57, 95% CI: 0.37, 0.87; OR=0.66, 95% CI: 0.49, 0.88, respectively) in the Eastern Asian population. Together, the findings suggest that the two variants both reduced the risk of PD in the Eastern Asian subgroup but not in the overall and Caucasian population, which should be cautiously interpreted because of limited number of included studies.

Identification of PTC725: An Orally Bioavailable Small Molecule That Selectively Targets the Hepatitis C Virus NS4B Protein

While new direct-acting antiviral agents for the treatment of chronic hepatitis C virus (HCV) infection have been approved, there is a continued need for novel antiviral agents that act on new targets and can be used in combination with current therapies to enhance efficacy and to restrict emergence of drug resistant viral variants. To this end, we have identified a novel class of small molecules, exemplified by PTC725, that target the nonstructural protein 4B (NS4B). PTC725 inhibited HCV 1b (Con 1) replicon with an EC50 of 1.7 nM and an EC90 of 9.6 nM and demonstrated a >1000-fold selectivity window with respect to cytotoxicity. The compounds were fully active against HCV replicon mutants that are resistant to inhibitors of NS3 protease and NS5B polymerase. Replicons selected for resistance to PTC725 harbored amino acid substitutions F98L/C and V105M in NS4B. Anti-replicon activity of PTC725 was additive to synergistic in combination with alpha interferon or with inhibitors of HCV protease and polymerase. Immunofluorescence microscopy demonstrated that neither the HCV inhibitors nor the F98C substitution altered the subcellular localization of NS4B or NS5A in replicon cells. Oral dosing of PTC725 showed a favorable pharmacokinetic profile with high liver and plasma exposure in mice and rats. Modeling of dosing regimens in humans indicates that a once-per-day or twice-per-day oral dosing regimen is feasible. Overall, the preclinical data support the development of PTC725 for use in the treatment of chronic HCV infection.

The Improvement of Pelvic Floor Muscle Function in POP Patients After the Prolift Procedure: Results from Surface Electromyography

INTRODUCTION AND HYPOTHESIS: Patients with pelvic organ prolapse (POP) have lower pelvic floor muscle (PFM) function. We hypothesized that pelvic reconstructive surgery could improve PFM function and strength. METHODS: The controlled, nonrandomized study recruited 37 POP patients in the Prolift group and 30 non-POP patients in the control group. Two urogynecologists performed the Prolift procedure. One experienced physiotherapist who was blinded to the grouping conducted the surface electromyography (SEMG) evaluation using an intravaginal probe. The patient was considered objectively cured if she had stage 0 or I according to the Pelvic Organ Prolapse Quantification system (POP-Q) at the 3rd month postoperatively. Two types of contractions, namely maximum voluntary contraction (MVC) and short, fast contractions (SFC) in 6 s were performed at each SEMG measurement. The SEMG data were collected once in the control group on admission and twice in the Prolift group (on admission and at the 3rd month postoperatively). The t test, Mann-Whitney U test, and Wilcoxon test were used for statistical analysis. RESULTS: A total of 36 POP patients were cured by the Prolift procedure. At the 3-month follow-up, the voltage and duration of MVC as well as the numbers and voltage of SFC increased significantly in the Prolift group. These variables were lower in POP patients compared to women without POP. CONCLUSIONS: The restoration of pelvic anatomy may account for the improved PFM function with increased electrical activity in POP patients verified by SEMG. Evaluation of PFM function may be used as a clinical tool in the overall assessment of pelvic reconstructive surgeries.

Distal-Less Regulates Eyespot Patterns and Melanization in Bicyclus Butterflies

Butterfly eyespots represent novel complex traits that display substantial diversity in number and size within and across species. Correlative gene expression studies have implicated a large suite of transcription factors, including Distal-less (Dll), Engrailed (En), and Spalt (Sal), in eyespot development in butterflies, but direct evidence testing the function of any of these proteins is still missing. Here we show that the characteristic two-eyespot pattern of wildtype Bicyclus anynana forewings is correlated with dynamic progression of Dll, En, and Sal expression in larval wings from four spots to two spots, whereas no such decline in gene expression ensues in a four-eyespot mutant. We then conduct transgenic experiments testing whether over-expression of any of these genes in a wild-type genetic background is sufficient to induce eyespot differentiation in these pre-patterned wing compartments. We also produce a Dll-RNAi transgenic line to test how Dll down-regulation affects eyespot development. Finally we test how ectopic expression of these genes during the pupal stages of development alters adults color patters. We show that over-expressing Dll in larvae is sufficient to induce the differentiation of additional eyespots and increase the size of eyespots, whereas down-regulating Dll leads to a decrease in eyespot size. Furthermore, ectopic expression of Dll in the early pupal wing led to the appearance of ectopic patches of black scales. We conclude that Dll is a positive regulator of focal differentiation and eyespot signaling and that this gene is also a possible selector gene for scale melanization in butterflies. J. Exp. Zool. (Mol. Dev. Evol.) 9999B: XX-XX, 2013. © 2013 Wiley Periodicals, Inc.

Estimates of Smoking Before and During Pregnancy, and Smoking Cessation During Pregnancy: Comparing Two Population-based Data Sources

We compared three measures of maternal smoking status--prepregnancy, during pregnancy, and smoking cessation during pregnancy-between the Pregnancy Risk Assessment Monitoring System (PRAMS) questionnaire and the 2003 revised birth certificate (BC).

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