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1.  Science, Technology, Engineering, and Mathematics (STEM) Participation Among College Students with an Autism Spectrum Disorder 
Little research has examined the popular belief that individuals with an autism spectrum disorder (ASD) are more likely than the general population to gravitate toward science, technology, engineering, and mathematics (STEM) fields. This study analyzed data from the National Longitudinal Transition Study-2, a nationally representative sample of students with an ASD in special education. Findings suggest that students with an ASD had the highest STEM participation rates although their college enrollment rate was the third lowest among 11 disability categories and students in the general population. Disproportionate postsecondary enrollment and STEM participation by gender, family income, and mental functioning skills were found for young adults with an ASD. Educational policy implications are discussed.
doi:10.1007/s10803-012-1700-z
PMCID: PMC3620841  PMID: 23114569
autism spectrum disorder; postsecondary enrollment; college; major; science; technology; engineering; and mathematics (STEM); college; young adult
2.  Reactive oxygen species contribute to simulated ischemia/reperfusion-induced autophagic cell death in human umbilical vein endothelial cells 
Background
Autophagy is important for cells to degrade protein aggregates and organelles. Our preliminary study suggests that ischemia/reperfusion in rabbit hearts promoted autophagic myocardial injury, resulting in no-reflow phenomenon. In this study, we sought to further understand the mechanism and outcome of the upregulation of autophagy in ischemia/reperfusion.
Material/Methods
We employed a simulated ischemia/reperfusion (sI/R) model in human umbilical vein endothelial cells (HUVECs) in vitro, in the presence or absence of antioxidants.
Results
Our study confirms that sI/R induces autophagy in HUVECs as measured by increased expression of Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3), electron microscopic analysis, and special biofluorescent staining with monodansylcadaverine. This sI/R-induced autophagy was also accompanied by increased levels of p65 protein expression and cell death. In addition, we detected the accumulation of reactive oxygen species (ROS) after sI/R. Moreover, with the application of ROS scavengers that block the release of ROS, we were able to demonstrate that inhibition of autophagy increases cell survival.
Conclusions
The study suggests that ROS accumulation is involved in the sI/R-induced autophagic cell death in HUVECs.
doi:10.12659/MSM.890897
PMCID: PMC4074109  PMID: 24943908
Autophagy; Reactive Oxygen Species; Reperfusion Injury
3.  Application of activated nucleoside analogs for the treatment of drug-resistant tumors by oral delivery of nanogel-drug conjugates 
A majority of nanoencapsulated drugs that have shown promise in cancer chemotherapy are administered intravenously. Development of effective oral nanoformulations presents a very challenging medical goal. Here, we describe successful applications of innovative polymeric nanogels in the form of conjugates with activated nucleoside analogs for oral administration in cancer chemotherapy. Previously, we reported the synthesis of amphiphilic polyvinyl alcohol and dextrin-based nanogel conjugates with the phosphorylated 5-FU nucleoside Floxuridine and demonstrated their enhanced activity against regular and drug-resistant cancers[1]. In this study, we synthesized and evaluated oral applications of nanogel conjugates of a protected Gemcitabine, the drug never used in oral therapies. These conjugates were able to quickly release an active form of the drug (Gemcitabine 5′-mono-, di- and triphosphates) by specific enzymatic activities, or slowly during hydrolysis. Gemcitabine conjugates demonstrated up to 127 times higher in vitro efficacy than the free drug against various cancer cells, including the lines resistant to nucleoside analogs. Surprisingly, these nanogel-drug conjugates were relatively stable in gastric conditions and able to actively penetrate through the gastrointestinal barrier based on permeability studies in Caco-2 cell model. In tumor xenograft models of several drug-resistant human cancers, we observed an efficient inhibition of tumor growth and extended the life-span of the animals by 4 times that of the control with orally treated Gemcitabine- or Floxuridine-nanogel conjugates. Thus, we have demonstrated a potential of therapeutic nanogel conjugates with the activated and stabilized Gemcitabine as a successful oral drug form against Gemcitabine-resistant and other drug-resistant tumors.
doi:10.1016/j.jconrel.2013.01.020
PMCID: PMC3612132  PMID: 23385032
Nanogel-drug conjugates; Gemcitabine; phosphorylated nucleoside analogs; oral drug administration; drug-resistant animal tumor xenografts
4.  Hyaluronic acid-based nanogel-drug conjugates with enhanced anticancer activity designed for targeting of CD44-positive and drug-resistant tumors 
Bioconjugate chemistry  2013;24(4):658-668.
Many drug-resistant tumors and cancer stem cells (CSC) express elevated levels of CD44 receptor, a cellular glycoprotein binding hyaluronic acid (HA). Here, we report the synthesis of nanogel-drug conjugates based on membranotropic cholesteryl-HA (CHA) for efficient targeting and suppression of drug-resistant tumors. These conjugates significantly increased the bioavailability of poorly soluble drugs with previously reported activity against CSC, such as etoposide, salinomycin, and curcumin. The small nanogel particles (diam. 20–40 nm) with a hydrophobic core and high drug loads (up to 20%) formed after ultrasonication and demonstrated a sustained drug release following the hydrolysis of biodegradable ester linkage. Importantly, CHA-drug nanogels demonstrated 2–7 times higher cytotoxicity in CD44-expressing drug-resistant human breast and pancreatic adenocarcinoma cells compared to free drugs and non-modified HA-drug conjugates. These nanogels were efficiently internalized via CD44 receptor-mediated endocytosis and simultaneous interaction with the cancer cell membrane. Anchoring by cholesterol moieties in the cellular membrane after nanogel unfolding evidently caused more efficient drug accumulation in cancer cells compared to non-modified HA-drug conjugates. CHA-drug nanogels were able to penetrate multicellular cancer spheroids and displayed higher cytotoxic effect in the system modeling tumor environment than both free drugs and HA-drug conjugates. In conclusion, the proposed design of nanogel-drug conjugates allowed us to significantly enhance drug bioavailability, cancer cell targeting, and the treatment efficacy against drug-resistant cancer cells and multicellular spheroids.
doi:10.1021/bc300632w
PMCID: PMC3677708  PMID: 23547842
nanogel; hyaluronic acid; CD44; drug conjugate; cancer spheroids; drug-resistant cancer cells
5.  Effect of Different rhBMP-2 and TG-VEGF Ratios on the Formation of Heterotopic Bone and Neovessels 
BioMed Research International  2014;2014:571510.
Bioengineered bone substitutes might represent alternatives to autologous bone grafts in medically compromised patients due to reduced operation time and comorbidity. Due to the lack of an inherent vascular system their dimension is limited to the size of critical bone size defect. To overcome this shortcoming, the experiment tried to create heterotopic bone around vessels. In vivo, a two-component fibrin and thrombin gel containing recombinant bone morphogenic protein (rhBMP-2) and transglutamate vascular endothelial growth factor (TG-VEGF) in different ratios, respectively, was injected into a dimensionally stable membrane tube, wrapped around the femoral vessel bundle in twelve New Zealand white rabbits. Sacrifice occurred eight weeks postoperatively. Microcomputed tomography of the specimens showed significantly increased bone volume in the rhBMP-2 to TG-VEGF ratio of 10 to 1 group. Histology showed new bone formation in close proximity to the vessel bundle. Immunohistochemistry detected increased angiogenesis within the newly formed bone in the rhBMP-2 to TG-VEGF ratios of 3 to 1 and 5 to 1. Heterotopic bone was engineered in vivo around vessels using different rhBMP-2 and TG-VEGF ratios in a fibrin matrix injected into a dimensionally stable membrane tube which prevented direct contact with skeletal muscles.
doi:10.1155/2014/571510
PMCID: PMC3982283  PMID: 24783213
6.  Clinical Evaluation of a Low Cost, In-House Developed Real-Time RT-PCR Human Immunodeficiency Virus Type 1 (HIV-1) Quantitation Assay for HIV-1 Infected Patients 
PLoS ONE  2014;9(3):e89826.
Objectives
HIV-1 viral quantitation is essential for treatment monitoring. An in-house assay would decrease financial barriers to access.
Materials and Methods
A real-time competitive RT-PCR in house assay (Sing-IH) was developed in Singapore. Using HXB2 as reference, the assay's primers and probes were designed to generate a 183-bp product that overlaps a portion of the LTR region and gag region. A competitive internal control (IC) was included in each assay to monitor false negative results due to inhibition or human error. Clinical evaluation was performed on 249 HIV-1 positive patient samples in comparison with the commercially available Generic HIV Viral Load assay. Correlation and agreement of results were assessed for plasma HIV-1 quantification with both assays.
Results
The assay has a lower limit of detection equivalent to 126 copies/mL of HIV-1 RNA and a linear range of detection from 100–1000000 copies/mL. Comparative analysis with reference to the Generic assay demonstrated good agreement between both assays with a mean difference of 0.22 log10 copies/mL and 98.8% of values within 1 log10 copies/mL range. Furthermore, the Sing-IH assay can quantify HIV-1 group M subtypes A–H and group N isolates adequately, making it highly suitable for our region, where subtype B and CRF01_AE predominate.
Conclusions
With a significantly lower running cost compared to commercially available assays, the broadly sensitive Sing-IH assay could help to overcome the cost barriers and serve as a useful addition to the currently limited HIV viral load assay options for resource-limited settings.
doi:10.1371/journal.pone.0089826
PMCID: PMC3945479  PMID: 24603460
7.  Single Nucleotide Polymorphisms of Toll-Like Receptor 7 and Toll-Like Receptor 9 in Hepatitis C Virus Infection Patients from Central China 
Yonsei Medical Journal  2014;55(2):428-434.
Purpose
To analyze the correlation of polymorphisms of toll-like receptor 7 (TLR7) (rs179009) and toll-like receptor 9 (TLR9) (rs187084) in hepatitis C virus (HCV) infections in the Han population.
Materials and Methods
The genotypes of TLR7IVS2-151 in HCV infection were detected by Sanger sequencing using polymerase chain reaction-restriction fragment length polymorphism to determine the TLR9 T-1486C single nucleotide polymorphisms (SNP) for all enrolled patients.
Results
We found no significant difference between males with spontaneous clearance of HCV versus those chronically infected [χ2=2.71, p=0.10, odd ratios (OR)=0.58, 95% confidence interval (CI) 0.31-1.11]. However, significant differences were found for the distribution of TLR7 (rs179009) in females (χ2=9.46, p=0.01). In females, a significant difference was also found between chronic hepatitis C and those with spontaneous clearance of HCV in terms of TLR7 IVS2-151G/A allele frequencies (χ2=9.50, p=0.00, OR=0.46, 95% CI 0.28-0.75). In HCV-infected patients, no significant association was found between the frequency of TLR9 genotypes and alleles.
Conclusion
The site of TLR7 IVS2-151 (rs179009) G/A may be a factor for susceptibility of chronic HCV in the female Han population. TLR9T-1486C (rs18084) SNP may not play a major role in HCV infection. However, individual risk profiles for HCV infection did vary by sex and this relationship should be further investigated.
doi:10.3349/ymj.2014.55.2.428
PMCID: PMC3936647  PMID: 24532514
Hepatitis C virus; single nucleotide polymorphism; TLR7; TLR9
8.  Unstable Jefferson fractures: Results of transoral osteosynthesis 
Indian Journal of Orthopaedics  2014;48(2):145-151.
Background:
Majority of C1 fractures can be effectively treated conservatively by immobilization or traction unless there is an injury to the transverse ligament. Conservative treatment usually involves a long period of immobilization in a halo-vest. Surgical intervention generally involves fusion, eliminating the motion of the upper cervical spine. We describe the treatment of unstable Jefferson fractures designed to avoid these problems of both conservative and invasive methods.
Materials and Methods:
A retrospective review of 12 patients with unstable Jefferson fractures treated with transoral osteosynthesis of C1 between July 2008 and December 2011 was performed. A steel plate and C1 lateral mass screw fixation were used to repair the unstable Jefferson fractures. Our study group included eight males and four females with an average age of 33 years (range 23-62 years).
Results:
Patients were followed up for an average of 16 months after surgery. Range of motion of the cervical spine was by and large physiologic: Average flexion 35° (range 28-40°), average extension 42° (range 30-48°). Lateral bending to the right and left averaged 30° and 28° respectively (range 12-36° and 14-32° respectively). The average postoperative rotation of the atlantoaxial joint, evaluated by functional computed tomography scan was 60° (range 35-72°). Total average lateral displacement of the lateral masses was 7.0 mm before surgery (range 5-12 mm), which improved to 3.5 mm after surgery (range 1-6.5 mm). The total average difference of the atlanto-dens interval in flexion and extension after surgery was 1.0 mm (range 1-3 mm).
Conclusions:
Transoral osteosynthesis of the anterior ring using C1 lateral mass screws is a viable option for treating unstable Jefferson fractures, which allows maintenance of rotation at the C1-C2 joint and restoration of congruency of the atlanto-occipital and atlantoaxial joints.
doi:10.4103/0019-5413.128750
PMCID: PMC3977369  PMID: 24741135
Jefferson fractures; osteosynthesis; transoral approach
9.  Disability Identification and Self-Efficacy among College Students on the Autism Spectrum 
Autism Research and Treatment  2014;2014:924182.
The number of youth on the autism spectrum approaching young adulthood and attending college is growing. Very little is known about the subjective experience of these college students. Disability identification and self-efficacy are two subjective factors that are critical for the developmental and logistical tasks associated with emerging adulthood. This study uses data from the National Longitudinal Transition Study 2 to examine the prevalence and correlates of disability identification and self-efficacy among college students on the autism spectrum. Results indicate nearly one-third of these students do not report seeing themselves as disabled or having a special need. Black race was associated with lower likelihood of both disability identification and self-efficacy.
doi:10.1155/2014/924182
PMCID: PMC3953486  PMID: 24707401
10.  Heat-killed VSL#3 Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Experimental Colitis in Rats 
To determine the effects of heat-killed VSL#3 (B. breve, B. longum and B. infantis; L. plantarum, L. bulgaricus, L. casei and L. acidophilus; S. salivarius subsp. thermophilus) therapy in the dextran sulfate sodium (DSS)-induced acute experimental colitis in rats. Acute experimental colitis was induced in rats by 5% DSS and freely drink for seven days. Beginning on Day 8, rats underwent gavage once daily for seven days with heat-killed probiotic VSL#3 (0.6 g/kg/day), colonic damage was evaluated histologically and biochemically seven days after gavage. Expression of inflammatory related mediators (STAT3, P-STAT3) and cytokines (IL-6, IL-23, TGFβ) in colonic tissue were detected. The results revealed that heat-killed and live VSL#3 have identical anti-inflammatory properties by the assessed DAI (disease activity index), colon length, histological tissue and MPO activity. Heat-killed and live VSL#3 results in reduced IL-6, IL-23, TGFβ, STAT3 and P-STAT3 expression in colonic tissue. Heat-killed and live VSL#3 have showed the similar anti-inflammatory activity by inhibiting IL-6/STAT3 pathway in the DSS-induced acute experimental colitis in rats.
doi:10.3390/ijms15010015
PMCID: PMC3907795  PMID: 24451125
probiotic; ulcerative colitis; inflammatory bowel disease; experimental colitis; IL-6/STAT3
11.  Draft Genome Sequence of a Multidrug-Resistant New Delhi Metallo-β-Lactamase-1 (NDM-1)-Producing Escherichia coli Isolate Obtained in Singapore 
Genome Announcements  2013;1(6):e01020-13.
We report the draft genome sequence of a New Delhi metallo-β-lactamase-1 (NDM-1)-positive Escherichia coli isolate obtained from a surgical patient. The assembled data indicate the presence of 3 multidrug resistance plasmids, 1 of which shares 100% identity with an NDM-1 plasmid isolated previously from a nearby hospital, suggesting possible local transmission.
doi:10.1128/genomeA.01020-13
PMCID: PMC3868851  PMID: 24356827
12.  Phylodynamic Profile of HIV-1 Subtype B, CRF01_AE and the Recently Emerging CRF51_01B among Men Who Have Sex with Men (MSM) in Singapore 
PLoS ONE  2013;8(12):e80884.
HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 – 2629), gp120 (HXB2: 6942 – 7577) and gp41 (HXB2: 7803 – 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 – 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
doi:10.1371/journal.pone.0080884
PMCID: PMC3846621  PMID: 24312505
13.  Development of PLGA-based itraconazole injectable nanospheres for sustained release 
Purpose
Itraconazole (ITZ) is a synthetic triazole antifungal agent, which is widely used for treatment and prevention of fungal infections. The purpose of this study is to develop ITZ-loaded poly(lactic-co-glycolic acid) (PLGA) nanospheres (PLGA-ITZ-NS) as a new sustained-release formulation for intravenous ITZ administration.
Materials and methods
PLGA-ITZ-NS were prepared by a nanoprecipitation method and optimized by modifying the surfactant poloxamer 188 concentration and PLGA:ITZ ratio. Their physicochemical properties, including size, zeta potential, external morphology and encapsulation efficiency, were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM) and high performance liquid chromatography (HPLC). The effect of the different selected lyoprotectants with various concentrations on NS particles size and surface charge were also assessed. Rapid and sensitive HPLC and liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were developed to determine ITZ concentrations in formulation and in rat plasma, respectively. Pharmacokinetics of the optimum PLGA-ITZ-NS formulation was compared with the former commercial Sporanox® injection formulation using rats as the animal model. Noncompartmental pharmacokinetic parameters were obtained by WinNonlin® software.
Results
Optimal PLGA-ITZ-NS had a mean particle size of about 200 nm with a high homogeneity (polydispersity index ≈0.2), favorable zeta potential (approximately −20 to −30 mV) and encapsulation efficiency (72%). In addition, 2% w/v sucrose was selected as a lyoprotectant for NS freeze-drying. The newly developed LC-MS/MS assay was validated and found to be accurate and precise. The in vivo study showed that the NS formulation has a similar systemic bioavailability to Sporanox® while providing a sustained plasma level (> 100 ng/mL) for up to 24 hours after intravenous administration.
Conclusion
Our newly developed PLGA-ITZ-NS has shown great sustained release and comparable bioavailability with Sporanox®, therefore having the potential to be an alternative injectable formulation of ITZ.
doi:10.2147/IJN.S54040
PMCID: PMC3839800  PMID: 24311942
itraconazole; poly(lactic-co-glycolic acid); PLGA; nanoparticle; sustained release; pharmacokinetics; intravenous injection
14.  Efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis: A phase II trial 
Background
This study aimed to determine the efficacy and safety of recombinant Mycobacterium tuberculosis ESAT-6 protein for diagnosis of pulmonary tuberculosis (TB).
Material/Methods
A phase II trial was performed in 158 patients with pulmonary TB (145 initially-treated and 13 re-treated) and 133 healthy subjects. Skin testing was carried out by injecting purified protein derivative (PPD) (on left forearm) or recombinant ESAT-6 protein at a dosage of 2, 5, or 10 μg/mL (on the right forearm) in each subject. Reaction activity and adverse events were monitored at 24, 48, and 72 h following the injection. Receiver operating characteristic curves were plotted to determine the areas under the curves (AUCs) and the cut-off induration diameters for the optimal diagnostic performance.
Results
The reaction activity was significantly increased upon recombinant ESAT-6 injection in pulmonary TB patients compared with healthy subjects. In pulmonary TB patients, the reaction was dose-dependent, and at 48 h, 10 μg/mL recombinant ESAT-6 produced a reaction similar to that produced by PPD. The AUCs for a 10 μg/mL dosage were 0.9823, 0.9552, and 0.9266 for 24 h, 48 h, and 72 h, respectively, and the induration diameters of 4.5–5.5 mm were the optimal trade-off values between true positive rates and false positive rates. No serious adverse events occurred in any subjects.
Conclusions
Recombinant ESAT-6 protein is efficacious and safe for diagnosing pulmonary TB. Based on the reaction, performance, safety, and practicability, we recommend that 10 μg/mL at 48 h with an induration cut-off value of 5.0 mm be used.
doi:10.12659/MSM.889425
PMCID: PMC3836599  PMID: 24217560
pulmonary tuberculosis; recombinant ESAT-6 protein; skin testing; phase II trial
15.  A Microtus fortis protein, serum albumin, is a novel inhibitor of Schistosoma japonicum schistosomula 
Memórias do Instituto Oswaldo Cruz  2013;108(7):865-872.
Schistosomiasis is an endemic parasite disease and praziquantel is the only drug currently in use to control this disease. Experimental and epidemiological evidence strongly suggests that Microtus fortis ( Mf ) is a naturally resistant vertebrate host of Schistosoma japonicum . In the present study, we found that Mf serum albumin ( Mf -albumin) and the conditioned medium of pcDNA3.1- Mf -albumin caused 46.2% and 38.7% schistosomula death rates in 96 h, respectively, which were significantly higher than that of the negative control (p < 0.05). We also found that mice injected with Mf -albumin had a 43.5% reduction in worm burden and a 48.1% reduction in liver eggs per gram (p < 0.05) in comparison to the control animals. To characterise the mechanisms involved in clearance, schistosomula were incubated with fluorescein isothiocyanate-labelled Mf -albumin and fluorescent enrichment effects were found in the gut lumen of schistosomula after 48 h of incubation. Next, digestive tract excretions from schistosomula were collected and the sensitivity of Mf -albumin to digestive tract excretions was evaluated. The results indicated that schistosomula digestive tract excretions showed indigestibility of Mf -albumin. The death of schistosomula could be partially attributed to the lack of digestion of Mf -albumin by digestive tract excretions during the development of the schistosomula stage. Therefore, these data indicate the potential of Mf -albumin as one of the major selective forces for schistosomiasis.
doi:10.1590/0074-0276130659
PMCID: PMC3970633  PMID: 24271043
Schistosoma japonicum; Microtus fortis; serum albumin
16.  Chronic psychosocial stressors and salivary biomarkers in emerging adults 
Psychoneuroendocrinology  2011;37(8):1158-1170.
Summary
We investigated whole saliva as a source of biomarkers to distinguish individuals who have, and who have not, been chronically exposed to severe and threatening life difficulties. We evaluated RNA and DNA metrics, expression of 37 candidate genes, and cortisol release in response to the Trier Social Stress Test, as well as clinical characteristics, from 48 individuals stratified on chronic exposure to psychosocial stressors within the last year as measured by the Life Events and Difficulties Schedule. Candidate genes were selected based on their differential gene expression ratio in circulating monocytes from a published genome-wide analysis of adults experiencing different levels of exposure to a chronic stressor.
In univariate analyses, we observed significantly decreased RNA integrity (RIN) score (P = 0.04), and reduced expression of glucocorticoid receptor-regulated genes (Ps < 0.05) in whole saliva RNA from individuals exposed to chronic stressors, as compared to those with no exposure. In those exposed, we observed significantly decreased BMI (P < 0.001), increased ever-smoking and increased lifetime alcohol abuse or dependence (P ≤ 0.03), and a reduction of cortisol release. In post hoc multivariate analyses including clinical and biospecimen-derived variables, we consistently observed significantly decreased expression of IL8 (Ps < 0.05) in individuals exposed, with no significant association to RIN score. Alcohol use disorders, tobacco use, a reduced acute stress response and decreased salivary IL8 gene expression characterize emerging adults chronically exposed to severe and threatening psychosocial stressors.
doi:10.1016/j.psyneuen.2011.11.010
PMCID: PMC3774595  PMID: 22172638
Human; Saliva; Gene expression; IL8; qPCR
17.  A Vesicular Stomatitis Virus-Based Therapeutic Vaccine Generates a Functional CD8 T Cell Response to Hepatitis B Virus in Transgenic Mice 
Journal of Virology  2013;87(5):2969-2973.
Recombinant vesicular stomatitis virus (VSV) is a promising therapeutic vaccine platform. Using a transgenic mouse model of chronic hepatitis B virus (HBV) infection, we evaluated the therapeutic potential of a VSV vector expressing the HBV middle surface envelope glycoprotein (MS). VSV-MS immunization generated HBV-specific CD8 T cell and antibody responses in transgenic mice that express low HBV antigen levels. These findings support the further development of VSV as a therapeutic vaccine vector for chronic HBV.
doi:10.1128/JVI.02111-12
PMCID: PMC3571382  PMID: 23269785
18.  The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis 
BioMed Research International  2013;2013:275805.
Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR) and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS) and overall survival (OS) which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 (P = 0.11) and 3.99 (P = 0.46), respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P = 0.39) and 6.75 (P = 0.92), respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 (P = 0.79) and 5.1 (P = 0.51), respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL) and mantle cell lymphoma (MCL), it would be necessary to perform F-PET for predictive purposes.
doi:10.1155/2013/275805
PMCID: PMC3830841  PMID: 24288671
19.  Heterotopic Bone Formation Around Vessels: Pilot Study of a New Animal Model 
BioResearch Open Access  2013;2(4):266-272.
Abstract
To achieve an easily established, safe, and reproducible animal model for the study of heterotopic bone formation around vessels, a small animal series using New Zealand White rabbits was performed. Three different dosages of recombinant human bone morphogenic protein (rhBMP-2) carried by fibrin matrix were tested. A guided tissue regeneration (GTR) membrane sheet was formed into a tube and allowed to harden; it served both to maintain the space around the vessel bundle and to separate the fibrin matrix with rhBMP-2 from skeletal muscle. Wrapped around the femoral vessel bundle and fixed in place, the tube was filled with the fibrin matrix containing rhBMP-2. The surgical site was closed in layers, and the postoperative healing was uneventful. All animals resumed their full preoperative daily activities 3–4 days after the operation. No adverse events such as wound dehiscence or infection occurred, and all animals could be sacrified at the scheduled date. Micro–computed tomography and histological investigations showed heterotopic bone formation around the vessel bundle in the medium- and high-dosage rhBMP-2 groups. An easy, safe, and reproducible animal model that allows the study of heterotopic bone formation around vessels was successfully established.
doi:10.1089/biores.2013.0025
PMCID: PMC3731688  PMID: 23914333
biomaterials; growth factor; tissue engineering
20.  Systemic Blockade of Dopamine D2-Like Receptors Increases High-Voltage Spindles in the Globus Pallidus and Motor Cortex of Freely Moving Rats 
PLoS ONE  2013;8(6):e64637.
High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical–basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D1-like receptors or D2-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D2-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D2-like receptor antagonists. On the contrary, the selective dopamine D1-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D2-like receptors, but not D1-like receptors, were involved in HVS regulation. This supports the important role of dopamine D2-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.
doi:10.1371/journal.pone.0064637
PMCID: PMC3674001  PMID: 23755132
21.  Quality of life in women with female pattern hair loss and the impact of topical minoxidil treatment on quality of life in these patients 
Female pattern hair loss (FPHL) is the most common hair loss disorder in women and it may impact on the psychological and social activities of patients, thereby reducing their quality of life (QoL). Topical minoxidil has been shown to be effective and safe in the treatment of patients with FPHL. The aim of this study was to assess the QoL of patients with FPHL and investigate whether topical minoxidil solution treatment improves the QoL of these patients. In this study, we enrolled 125 female patients aged 16–72 years to answer visual analog scale (VAS) and dermatology life quality index (DLQI) questionnaires. Of these patients, 31 were recruited for the follow-up study after 12 months of treatment with 2% minoxidil. Each index and the change in QoL prior to and following treatment were statistically analyzed. There was identified to be a correlation between clinical severity and the values of the indices in all patients. There was a statistically significant difference between the VAS and DLQI scores prior to and following treatment with 2% minoxidil. A comparison between the good responders (n=23) and the poor responders (n=8) revealed no significant difference in the improvement of VAS and DLQI scores. The QoL of the patients was severely impaired by FPHL. The DLQI and VAS used in this study were validated as useful indices for the evaluation of QoL due to their high reliability, sensitivity and simplicity. This evaluation is recommended for the management of FPHL treatment. The results of the study demonstrated that topical minoxidil improved the QoL of the patients.
doi:10.3892/etm.2013.1126
PMCID: PMC3786879  PMID: 24137223
China; dermatology life quality index; visual analog scale
22.  Preclinical study and phase I clinical safety evaluation of recombinant Mycobacterium tuberculosis ESAT6 protein 
Background
To investigate the ability of rESAT6 to identify different mycobacteria-sensitized guinea pigs and its safety in preclinical and phase I clinical study.
Material/Methods
Guinea pigs were sensitized with different Mycobacteria. After sensitization, all animals were intradermally injected with rESAT6 and either PPD or PPD-B. At 24 h after the injection, the erythema of the injection sites were measured using a double-blind method. For the preclinical safety study, different doses of rESAT6 and BSA were given 3 times intramuscularly to guinea pigs. On day 14 after the final immunization, the guinea pigs were intravenously injected with the same reagents in the hind legs and the allergic reactions were observed. A single-center, randomized, open phase I clinical trial was employed. The skin test was conducted in 32 healthy volunteers aged 19–65 years with 0.1 μg, 0.5 μg, and 1 μg rESAT6. Physical examination and laboratory tests were performed before and after the skin test and adverse reactions were monitored. The volunteers’ local and systemic adverse reactions and adverse events were recorded for 7 days.
Results
Positive PPD or PPD-B skin tests were observed in all Mycobacteria-sensitized guinea pigs; the diameters of erythema were all >10 mm. The rESAT6 protein induced a positive skin test result in the guinea pigs sensitized with MTB, M. bovis, M. africanum and M. kansasii; the diameters of erythema were 14.7±2.0, 9.3±3.8, 18.7±2.4, and 14.8±4.2 mm, respectively. A negative skin test result was detected in BCG-vaccinated and other NTM-sensitized guinea pigs. The rESAT6 caused no allergic symptoms, but many allergic reactions, such as cough, dyspnea, and even death, were observed in the guinea pigs who were administered BSA. During the phase I clinical trial, no adverse reactions were found in the 0.1 μg rESAT6 group, but in the 0.5 μg rESAT6 group 2 volunteers reported pain and 1 reported itching, and in the 1 μg rESAT6 group there was 1 case of pain, 1 case of itching, and 1 case of blister. No other local or systemic adverse reactions or events were reported.
Conclusions
The rESAT6 can differentiate effectively among MTB infection, BCG vaccination, and NTM infection and is safe in healthy volunteers.
doi:10.12659/MSMBR.883912
PMCID: PMC3659126  PMID: 23676766
phase I clinical trial; recombinant protein; skin test; latent M. tuberculosis infection
23.  A Survey of Body Sensor Networks 
Sensors (Basel, Switzerland)  2013;13(5):5406-5447.
The technology of sensor, pervasive computing, and intelligent information processing is widely used in Body Sensor Networks (BSNs), which are a branch of wireless sensor networks (WSNs). BSNs are playing an increasingly important role in the fields of medical treatment, social welfare and sports, and are changing the way humans use computers. Existing surveys have placed emphasis on the concept and architecture of BSNs, signal acquisition, context-aware sensing, and system technology, while this paper will focus on sensor, data fusion, and network communication. And we will introduce the research status of BSNs, the analysis of hotspots, and future development trends, the discussion of major challenges and technical problems facing currently. The typical research projects and practical application of BSNs are introduced as well. BSNs are progressing along the direction of multi-technology integration and intelligence. Although there are still many problems, the future of BSNs is fundamentally promising, profoundly changing the human-machine relationships and improving the quality of people's lives.
doi:10.3390/s130505406
PMCID: PMC3690007  PMID: 23615581
body sensor network; sensor; data fusion; network communication; practical application of BSNs
24.  Differentiation of Central Lung Cancer from Atelectasis: Comparison of Diffusion-Weighted MRI with PET/CT 
PLoS ONE  2013;8(4):e60279.
Objective
Prospectively assess the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) for differentiation of central lung cancer from atelectasis.
Materials and Methods
38 consecutive lung cancer patients (26 males, 12 females; age range: 28–71 years; mean age: 49 years) who were referred for thoracic MR imaging examinations were enrolled. MR examinations were performed using a 1.5-T clinical scanner and scanning sequences of T1WI, T2WI, and DWI. Cancers and atelectasis were measured by mapping of the apparent diffusion coefficients (ADCs) obtained with a b-value of 500 s/mm2.
Results
PET/CT and DW-MR allowed differentiation of tumor and atelectasis in all 38 cases, but T2WI did not allow differentiation in 9 cases. Comparison of conventional T2WI and DW-MRI indicated a higher contrast noise ratio of the central lung carcinoma than the atelectasis by DW-MRI. ADC maps indicated significantly lower mean ADC in the central lung carcinoma than in the atelectasis (1.83±0.58 vs. 2.90±0.26 mm2/s, p<0.0001). ADC values of small cell lung carcinoma were significantly greater than those from squamous cell carcinoma and adenocarcinoma (p<0.0001 for both).
Conclusions
DW-MR imaging provides valuable information not obtained by conventional MR and may be useful for differentiation of central lung carcinoma from atelectasis. Future developments may allow DW-MR imaging to be used as an alternative to PET-CT in imaging of patients with lung cancer.
doi:10.1371/journal.pone.0060279
PMCID: PMC3617228  PMID: 23593186
25.  Gene Cloning, Expression and Characterization of a Novel Xylanase from the Marine Bacterium, Glaciecola mesophila KMM241 
Marine Drugs  2013;11(4):1173-1187.
Marine xylanases are rather less studied compared to terrestrial xylanases. In this study, a new xylanase gene, xynB, was cloned from the marine bacterium, Glaciecola mesophila KMM241, and expressed in Escherichia coli. xynB encodes a multi-domain xylanase XynB of glycoside hydrolase (GH) family 8. The recombinant XynB comprises an N-terminal domain (NTD) with unknown function and a catalytic domain, which is structurally novel among the characterized xylanases of GH family 8. XynB has the highest identity (38%) to rXyn8 among the characterized xylanases. The recombinant XynB showed maximal activity at pH 6–7 and 35 °C. It is thermolabile and salt-tolerant. XynB is an endo-xylanase that demands at least five sugar moieties for effective cleavage and to hydrolyze xylohexaose and xylopentaose into xylotetraose, xylotriose and xylobiose. NTD was expressed in Escherichia coli to analyze its function. The recombinant NTD exhibited a high binding ability to insoluble xylan and avicel and little binding ability to chitosan and chitin. Since the NTD shows no obvious homology to any known carbohydrate-binding module (CBM) sequence in public databases, XynB may contain a new type of CBM.
doi:10.3390/md11041173
PMCID: PMC3705397  PMID: 23567318
xylanase; XynB; cold-active; Glaciecola mesophila KMM241; carbohydrate-binding module

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