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Find video protocols related to scientific articles indexed in Pubmed.
Chinese Herbal Medicine for Obesity: A Randomized, Double-Blinded, Multicenter, Prospective Trial.
Am. J. Chin. Med.
PUBLISHED: 11-20-2014
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Obesity is a serious medical problem worldwide. As a holistic therapy, traditional Chinese medicine (TCM) may have a potential in obesity management. In this controlled trial, we evaluated the safety and effectiveness of Xin-Ju-Xiao-Gao-Fang (XJXGF), a TCM herbal formulation, in 140 obese subjects over a 24-week period. The XJXGF formula mainly consists of rhubarb, coptis, semen cassia, and citrus aurantium. Subjects with body mass index (BMI) 28-40 kg/m(2) were recruited at 5 centers in China. We assessed the changes in subjects' body weight, its related parameters, and the reduction of insulin resistance (IR) after administration of XJXGF formula or low-dose XJXGF (10% of the XJXGF formula, as control). After 24-week treatment, among participants in the XJXGF formula group and low-dose XJXGF group, the mean ± SE changes in the body weight were -3.58±0.48 and -1.91±0.38 kg, respectively (p < 0.01). The changes in the IR-index of two groups were -2.65±1.04 and -1.58±1.3, respectively (p < 0.05). There were no serious adverse events reported during the 24-week trial. Participants reported 7 minor adverse events, 4 in the XJXGF formula group and 3 in the low-dose XJXGF group (p = 0.578). Future studies are needed to investigate the clinical utility of this TCM formulation in the treatment of obese subjects.
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Development of monoclonal antibody-based sandwich ELISA for detection of dextran.
Monoclon Antib Immunodiagn Immunother
PUBLISHED: 10-31-2014
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Dextran as anti-nutritional factor is usually a result of bacteria activity and has associated serial problems during the process stream in the sugar industry and in medical therapy. A sensitive method is expected to detect dextran quantitatively. Here we generated four monoclonal antibodies (MAbs) against dextran using dextran T40 conjugated with bovine serum albumin (BSA) as immunogen in our lab following hybridoma protocol. Through pairwise, an MAb named D24 was determined to be conjugated with horseradish peroxidase (HRP) and was used in the establishment of a sensitive sandwich enzyme-linked immunosorbent assay (ELISA) method for determination of dextran, in which MAb D9 was chosen as a capture antibody. The detection limit and working scope of the developed sandwich ELISA method were 3.9?ng/mL and 7.8-500?ng/mL with a correlation coefficient of 0.9909. In addition, the cross-reaction assay demonstrated that the method possessed high specificity with no significant cross-reaction with dextran-related substances, and the recovery rate ranged from 96.35 to 102.00%, with coefficient of variation ranging from 1.58 to 6.94%. These results indicated that we developed a detection system of MAb-based sandwich ELISA to measure dextran and this system should be a potential tool to determine dextran levels.
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Human Sex Hormone Binding Globulin Binding Affinities of 125 Structurally Diverse Chemicals and Comparison with Their Binding to Androgen Receptor, Estrogen Receptor and ?-Fetoprotein.
Toxicol. Sci.
PUBLISHED: 10-27-2014
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One endocrine disruption mechanism is through binding to nuclear receptors such as the androgen receptor (AR) and estrogen receptor (ER) in target cells. The concentration of a chemical in serum is important for its entry into the target cells to bind the receptors, which is regulated by the serum proteins. Human sex hormone binding globulin (SHBG) is the major transport protein in serum that can bind androgens and estrogens and thus change a chemical's availability to enter the target cells. Sequestration of an androgen or estrogen in the serum can alter the chemical elicited AR- and ER-mediated responses. To better understand chemical induced endocrine activity, we developed a competitive binding assay using human pregnancy plasma and measured the binding to the human SHBG for 125 structurally diverse chemicals, most of which were known to bind AR and ER. Eighty seven chemicals were able to bind the human SHBG in the assay, while 38 chemicals were non-binders. Binding data for human SHBG are compared with that for rat ?-fetoprotein, ER and AR. Knowing the binding profiles between serum and nuclear receptors will improve assessment of a chemical's potential for endocrine disruption. The SHBG binding data reported here represent the largest data set of structurally diverse chemicals tested for human SHBG binding. Utilization of the SHBG binding data with AR and ER binding data could enable better evaluation of endocrine disrupting potential of chemicals through AR- and ER-mediated responses since sequestration in serum could be considered.
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Value of Whole-Tumor Dual-Input Perfusion CT in Predicting the Effect of Multiarterial Infusion Chemotherapy on Advanced Non-Small Cell Lung Cancer.
AJR Am J Roentgenol
PUBLISHED: 10-24-2014
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OBJECTIVE. The purposes of this study were to prospectively evaluate tumor perfusion using whole-tumor dual-input perfusion CT in advanced non-small cell lung cancer treated with multiarterial infusion chemotherapy and to determine whether treatment effect can be predicted in light of perfusion parameters. SUBJECTS AND METHODS. Forty-two patients with advanced non-small cell lung cancer were enrolled in this study. Whole-tumor dual-input perfusion CT was performed for all these patients, who subsequently received multiarterial infusion chemotherapy. The patients were divided into responders and nonresponders according to response to treatment. The relation between baseline perfusion parameters and prognosis after therapy was analyzed. RESULTS. The responder group had higher bronchial flow than the nonresponder group (p = 0.02). The AUC for bronchial flow was 0.83; pulmonary flow, 0.71; and perfusion index, 0.66. The higher bronchial flow group (? 65.34 mL/min/100 mL) and lower pulmonary flow group (< 23.05 mL/min/100 mL) had longer median progression-free survival periods (p = 0.01, p = 0.03) and overall survival periods (p = 0.04, p = 0.04). Multivariate analysis showed that bronchial flow was a significant prognostic factor for progression-free survival and overall survival (p = 0.01, p = 0.02) and that pulmonary flow may be helpful for predicting progression-free survival (p = 0.04) and overall survival (p = 0.03). CONCLUSION. Whole-tumor dual-input perfusion CT can provide information on the dual blood supply of tumors, which is helpful for predicting the treatment effect of multiarterial infusion chemotherapy for advanced non-small cell lung cancer.
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[Effects of algae and kaolinite particles on the survival of bacteriophage MS2].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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In this study, Bacteriophage MS2, Kaolinite and Microcystis aeruginosa were selected as model materials for human enteric viruses, inorganic and organic particles, respectively. The influence of the inorganic (Kaolinite) or organic (Microcystis aeruginosa) particles on the survival of MS2 at different conditions, such as particles concentration, pH, ion concentration and natural organic matter (NOM) were studied. The results showed that Kaolinite had no effect on the survival of phage MS2 except that apparent survival of MS2 increased 1 logarithm in higher hardness water. Microcystis aeruginosa addition reduced 1 logarithm of MS2 survival. However, when the pH value was greater than 4.0 or the concentration of Microcystis aeruginosa was less than 1.0 x 10(6) cells x L(-1), Microcystis aeruginosa addition had no influence on the survival of MS2. In higher hardness water, Microcystis aeruginosa protected MS2 viruses and then increased the survival of MS2. In drinking water, resource containing higher concentration of particles, the survival ability of virus would be enhanced with the increase of the hardness and then elevated the risks of drinking water safety.
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Cardiovascular dysfunction in offspring of ovarian hyperstimulated women and effects of estradiol and progesterone: a retrospective cohort study and proteomics analysis.
J. Clin. Endocrinol. Metab.
PUBLISHED: 10-01-2014
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Context: The cardiovascular dysfunction in children born with assisted reproductive technologies has been widely concerned. However, the association of ovarian hyperstimulation syndrome (OHSS), a complication of assisted reproductive technologies, with worse cardiovascular functions and underlying mechanism remain unknown. Objectives: To assess the cardiovascular functions of children born to mothers with OHSS and investigate the underlying regulator(s). Design and Setting: This was a retrospective cohort recruited in a university hospital. Participants and Methods: We assessed cardiovascular functions by Doppler echography in 42 children born to OHSS women, 34 children of mothers with non- OHSS In Vitro Fertilization (IVF) and 48 spontaneously conceived (SC) children (mean age about 4.5 years). Groups were matched for gestational age at delivery and birth weight. An iTRAQ labeled proteomics analysis was performed with another set of umbilical arteries from OHSS and SC pregnancies (n=3 for both groups). Results: Children of OHSS mothers showed a significantly decreased mitral E/A ratio, reduced systolic and diastolic diameters of common carotid arteries and impaired flow-mediated dilation compared with non-OHSS IVF and SC children. Intima-media thickness and arterial stiffness indices were similar in three groups. In proteomics study, 1640 proteins were identified from OHSS and SC umbilical arteries, and, 40 differentially expressed proteins were selected for further analysis. Estradiol and progesterone were identified as activated upstream regulators. Conclusions: Children born to ovarian hyperstimulated women displayed cardiovascular dysfunctions. The underlying mechanisms may involve the effects of supraphysiological estradiol and progesterone levels.
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Metal-Free Oxidative C(sp(3))-H Bond Functionalization of Alkanes and Conjugate Addition to Chromones.
Org. Lett.
PUBLISHED: 09-25-2014
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A metal-free oxidative C(sp(3))-H bond functionalization and subsequent conjugate addition reaction using di-tert-butyl peroxide (DTBP) as the oxidant was established, which tolerates a wide range of simple alkane substrates to react with different substituted chromones for direct preparation of 2-alkylchromanones.
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[Identification of herbal tea ingredient Plumeria rubra and its adulterants using DNA barcoding].
Zhongguo Zhong Yao Za Zhi
PUBLISHED: 09-24-2014
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ITS2 sequence was used as a barcode to identify herbal tea ingredient Plumeria rubra and its adulterants. Genomic DNAs from forty eight samples were extracted, the ITS2 sequences were amplified and sequenced bi-direstionlly, and then assembled and obtained using CodonCode Aligner. The sequences were aligned using ClustalW, the genetic distances were computed by kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic trees were constructed using MEGA5.0. Results showed that the length of ITS2 sequence of P. rubra were 244 bp. The intra-specific genetic distances (0-0. 016 6) were much smaller than inter-specific ones between P. rubra and its adulterants(0.320 8-0.650 4). The NJ tree indicated that P. rubra and its adulterants could be distinguished clearly. Therefore, Using ITS2 barcode can accurately andeffectively distinguish herbal tea ingredient P. rubra from its adulterants, which providesa new molecular method to identify P. rubra and ensure its safety in use.
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An integrated extrapolation of long-term outcomes in systemic lupus erythematosus: analysis and simulation of the Hopkins Lupus Cohort.
Rheumatology (Oxford)
PUBLISHED: 09-20-2014
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The aim of this study was to develop an SLE disease model that simulates long-term outcomes of SLE to estimate the long-term effectiveness and cost-effectiveness of SLE treatments.
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The complete mitochondrial genome of Chinese pond mussel Sinanodonta woodiana (Unionoida: Unionidae).
Mitochondrial DNA
PUBLISHED: 09-11-2014
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Abstract The complete mitochondrial genome of Sinanodonta woodiana is a circular molecule of 16256?bp in length, containing 14 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and 2 control regions. The A?+?T content of the overall base composition of H-strand is 65.9% (T: 28.0%; C: 22.3%; A: 37.9%; G: 11.8%). F ORF (Female-specific open reading frame) begins with ATA, Cyt b begins with ATC, ATP6, ATP8, COII, COIII, ND1, ND2, ND3 and ND5 begin with ATG, ND4L begins with GTG, COI begins with TTG, and other two protein-coding genes begin with ATT as start codon. COII, COIII, F ORF, ND1, ND3, ND5 and ND6 genes are terminated with TAA as stop codon, ATP6, ATP8, COI, Cyt b, ND4 and ND4L end with TAG, and ND2 gene ends with T.
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The complete mitochondrial genome of the leopard spider Pardosa laura (Araneae: Lycosidae).
Mitochondrial DNA
PUBLISHED: 09-11-2014
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Abstract The complete mitochondrial genome of Pardosa laura is a circular molecule of 14,513?bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. The A?+?T content of the overall base composition of H-strand is 77.4% (T: 42.9%; C: 8.1%; A: 34.5%; G: 14.5%). ATP6, COII and COIII genes begin with TTG as start codon; ND4 and ND6 genes begin with ATA as start codon, while other eight protein-coding genes start with ATT. COII, COIII, ND2 and ND6 genes are terminated with TAG as stop codon, COI and ND4L end with T, ND4 ends with TA, ATP6, ATP8, Cyt b, ND1, ND3and ND5 end with TAA.
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The complete mitochondrial genome of striped lynx spider Oxyopes sertatus (Araneae: Oxyopidae).
Mitochondrial DNA
PUBLISHED: 09-11-2014
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Abstract The complete mitochondrial genome of Oxyopes sertatus is a circular molecule of 14,442?bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 22 transfer RNAs, and a control region. The A?+?T content of the overall base composition of H-strand is 75.9% (T: 42.9%; C: 8.2%; A: 33.0%; G: 15.9%). COII, COIII and ND4 genes begin with TTG as start codon; ATP6, COI, ND1 and ND5 genes begin with ATA as start codon, ATP8, Cyt b, ND2 and ND3 genes begin with ATT as start codon, ND6 gene begins with GTG as start codon, while ND4L gene start with a typical ATG initiation codon. ND2 gene is terminated with TAG as stop codon, Cyt b and ND5 end with TA, COI, ND1 and ND4L end with T, ATP6, ATP8, COII, COIII, ND3, ND4 and ND6 end with TAA.
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Identification of Eight Novel Mutations and Transcript Analysis of Two Splicing Mutations in Chinese newborns with MCC Deficiency.
Clin. Genet.
PUBLISHED: 09-06-2014
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3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive inborn error of leucine metabolism, caused by mutations in either MCCC1 or MCCC2 gene. We identified eight novel mutations of MCCC1 or MCCC2 in six Chinese newborns screened by tandem mass spectrometry. Transcript analysis revealed that the novel splice mutation c.639?+?5?G?>?T produced a normal transcript and a transcript of exon 6 skipping which led to truncated MCCC1 protein. The remaining seven novel mutations may cause structure damage and dysfunction of MCC as predicted by in silico analysis. In conclusion, our study expands the spectrum of mutations found in MCCC1 and MCCC2 and provides a rough prevalence of 1/68,333 in Chinese population. Although the affected patients remained asymptomatic during follow-up, we hold the view that early detection through newborn screening, early intervention and follow-up may provide an important guidance to prevent subsequent metabolic disorders and deal with crisis later in life.
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Syndrome in question.
An Bras Dermatol
PUBLISHED: 09-04-2014
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Vulvovaginal-gingival syndrome is characterized by erosions and desquamation of the vulva, vagina, and gingiva. We reported a case of a 32-year-old woman presenting with an 8-year history of damage to the vulval and perianal anatomy and limitation of mouth opening. The patient's symptoms were relieved after treatment with topical tacrolimus cream.
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Apolipoprotein-containing lipoprotein subclasses and subclinical atherosclerosis In systemic lupus erythematosus (SLE).
Arthritis Care Res (Hoboken)
PUBLISHED: 08-25-2014
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Objectives: Traditional classification of hyperlipidemia using HDL, LDL and VLDL does not provide information on lipoprotein function. Apolipoproteins, (which are protein components of plasma lipoproteins including A, B, C, D, E) with their different composition, metabolic and atherogenic properties, provide insight on lipoprotein functioning. In particular, the ApoB/A-1 ratio is associated with atherogenic LDL and development of cardiovascular disease. We explored the baseline association between these non-traditional risk factors with subclinical measures of atherosclerosis (coronary artery calcium and carotid intima-media thickness) in SLE. Methods: 58 SLE patients (97% female, 58% Caucasian, 40% African-American, 2% other, mean age 44±11 yrs) had measurement of apolipoprotein and lipoproteins by immunoturbidimetric procedures, electroimmunoassays and immunoprecipitation. Coronary artery calcium was measured by helical CT and carotid intima-media thickness by carotid duplex. This study was based on the baseline assessment of subclinical atherosclerosis in the LAPS study. The measurement of the lipoproteins was made on sera collected at the same time. Results: There was no association between cardioprotective apoliporoteins (apoA-I, LpA-I, LpA-I:AII) and coronary artery calcium (p<0.15,0.41,0.39) or carotid intima-media thickness (p<0.97,0.53,0.76). Coronary artery calcium and carotid intima-media thickness did not associate with atherogenic apolipoproteins either, including LpB:E+LpB:C:E, apoB, LpB, LpB:C, apoC-III, apoC-III-HS, apoC-III-HP, CIII-R, LpA-II:B:C:D:E and apoB/apoA-I. Measures of disease activity, including physician's global assessment and SLEDAI, were not associated with coronary artery calcium or carotid intima-media thickness. Conclusion: Neither cardioprotective nor atherogenic lipoproteins were associated with measures of subclinical atherosclerosis in this series of SLE patients. Further studies with larger sample size are warranted to confirm our findings. © 2014 American College of Rheumatology.
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The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance.
Nat. Biotechnol.
PUBLISHED: 08-24-2014
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The concordance of RNA-sequencing (RNA-seq) with microarrays for genome-wide analysis of differential gene expression has not been rigorously assessed using a range of chemical treatment conditions. Here we use a comprehensive study design to generate Illumina RNA-seq and Affymetrix microarray data from the same liver samples of rats exposed in triplicate to varying degrees of perturbation by 27 chemicals representing multiple modes of action (MOAs). The cross-platform concordance in terms of differentially expressed genes (DEGs) or enriched pathways is linearly correlated with treatment effect size (R(2)?0.8). Furthermore, the concordance is also affected by transcript abundance and biological complexity of the MOA. RNA-seq outperforms microarray (93% versus 75%) in DEG verification as assessed by quantitative PCR, with the gain mainly due to its improved accuracy for low-abundance transcripts. Nonetheless, classifiers to predict MOAs perform similarly when developed using data from either platform. Therefore, the endpoint studied and its biological complexity, transcript abundance and the genomic application are important factors in transcriptomic research and for clinical and regulatory decision making.
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Downregulation of microRNA-100 enhances the ICMT-Rac1 signaling and promotes metastasis of hepatocellular carcinoma cells.
Oncotarget
PUBLISHED: 08-20-2014
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Metastasis is responsible for rapid recurrence of hepatocellular carcinoma (HCC) and poor survival of HCC patients. Here we showed that miR-100 downregulation in HCC tissues was significantly associated with venous invasion, advanced TNM stage, tumor nodule without complete capsule, poorer cell differentiation, and shorter recurrence-free survival. Both gain- and loss-of-function studies showed that miR-100 dramatically suppressed the ability of HCC cells to migrate and to invade through Matrigel in vitro. Analyses using mouse orthotopic xenograft model further revealed that xenografts of miR-100-stable-expressing HCC cells displayed a significant reduction in pulmonary metastasis, compared with control group. Subsequent investigations revealed that miR-100 directly inhibited the expression of isoprenylcysteine carboxyl methyltransferase (ICMT) and ras-related C3 botulinum toxin substrate 1 (Rac1) by binding to their 3'-UTRs, and in turn suppressed lamellipodia formation and matrix metallopeptidase 2 (MMP2) activation. Furthermore, knockdown of ICMT and Rac1 phenocopied the anti-metastasis effect of miR-100, whereas overexpression of the constitutively active Rac1 (Q61L) antagonized the function of miR-100. Taken together, miR-100 represses metastasis of HCC cells by abrogating the ICMT-Rac1 signaling. Downregulation of miR-100 contributes to HCC metastasis and the restoration of miR-100 is a potential strategy for cancer therapy.
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A phenome-guided drug repositioning through a latent variable model.
BMC Bioinformatics
PUBLISHED: 08-08-2014
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The phenome represents a distinct set of information in the human population. It has been explored particularly in its relationship with the genome to identify correlations for diseases. The phenome has been also explored for drug repositioning with efforts focusing on the search space for the most similar candidate drugs. For a comprehensive analysis of the phenome, we assumed that all phenotypes (indications and side effects) were inter-connected with a probabilistic distribution and this characteristic may offer an opportunity to identify new therapeutic indications for a given drug. Correspondingly, we employed Latent Dirichlet Allocation (LDA), which introduces latent variables (topics) to govern the phenome distribution.
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Self-assembly of Au nanoparticles on PMMA template as flexible, transparent, and highly active SERS substrates.
Anal. Chem.
PUBLISHED: 06-11-2014
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We report a simple and rapid method for fabricating a surface-enhanced Raman scattering (SERS) substrate, which offers good flexibility, excellent optical transparency, and high SERS activity. Specifically, the SERS substrate (AuNPs/PMMA film) was obtained through self-assembly of gold nanoparticles (AuNPs) on newborn poly(methyl methacrylate) (PMMA) template. The UV-vis spectroscopy analysis and scanning electron microscopy observation revealed that the gold nanoparticles were closely assembled on the flexible and transparent PMMA template. The fabricated AuNPs/PMMA film SERS substrate allowed detection of model molecule, malachite green isothiocyanate, at a concentration as low as 0.1 nM, and exhibited good reproducibility in the SERS measurement. The Raman enhancement factor (EF) of the AuNPs/PMMA film was found to be as high as (2.4 ± 0.3) × 10(7). In addition, measure of residual malachite green on fish surface was carried out, and the result indicated that the AuNPs/PMMA film had great potential in the in situ ultrasensitive detection of analyte on irregular objects.
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Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro.
Mol Med Rep
PUBLISHED: 05-23-2014
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Berberine is a well?known component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC?3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a dose?and time?dependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostate?specific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway.
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Monodispersed Ag nanoparticles as catalyst: preparation based on crystalline supramolecular hybrid of decamethylcucurbit[5]uril and silver ions.
Inorg Chem
PUBLISHED: 05-12-2014
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Monodispersed silver nanoparticles (Ag(0) NPs) have been first prepared on the basis of a postsynthesis via mild reduction from a new crystalline supramolecular hybrid solid assembled from Ag(+) ions and decamethylcucurbit[5]uril (Me10CB[5]). Uniform growth of nearly spherical Ag(0) NPs with an average size of ca. 4.4 nm was observed on the organic Me10CB[5] support to form Ag@Me10CB[5] composite material. The as-synthesized composite material was characterized by a range of physical measurements (PXRD, TGA, XPS, ICP, TEM, etc.) and was further exploited as a heterogeneous catalyst for the reduction of various nitrophenols in the presence of NaBH4. The kinetics of the reduction process was monitored under various experimental conditions. The Ag@Me10CB[5] composite material showed excellent catalytic performance over the reduction reactions and remained active after several consecutive cycles.
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Interface strain-induced multiferroicity in a SmFeO3 film.
ACS Appl Mater Interfaces
PUBLISHED: 05-08-2014
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An epitaxial pseudocubic SmFeO3 thin film on (100) Nb-SrTiO3 was studied based on ferroelectric (FE) characterization and magnetic measurements. High-resolution transmission electron microscopy images clarify the nature of the epitaxial growth, the stress-induced structural distortion at the film/substrate interface, and the existence of two different orientation lattices. Clear grain boundaries can be seen, which could introduce an extra local distortion. Rectangular FE loops can be observed at room temperature, even by just applying a small voltage ranging from -1 to +1 V, indicative of the presence of FE polarization. Piezoelectric force microscopy images confirm the existence of FE domains and the switchable polarization. A strong ferromagnetic-like transition occurs around 185 K, which is much lower than the transition observed in the bulk sample. It is believed that the pseudocubic structure enhances FE polarization and decreases the magnetic ordering temperature, which is confirmed by the first-principles theoretical calculations. Meanwhile, the ferroelectricity in this thin film should originate from distortion and modification in the structural modules rather than from the exchange striction interaction that is found in the bulk SmFeO3.
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Cu-catalyzed C(sp³)-H bond activation reaction for direct preparation of cycloallyl esters from cycloalkanes and aromatic aldehydes.
Org. Lett.
PUBLISHED: 04-23-2014
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Cu-catalyzed dehydrogenation-olefination and esterification of C(sp(3))-H bonds of cycloalkanes with TBHP as an oxidant has been developed. The reaction involves four C-H bond activations and gives cycloallyl ester products directly from cycloalkanes and aromatic aldehydes.
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Iron-catalyzed cross-dehydrogenative coupling esterification of unactive C(sp3)-H bonds with carboxylic acids for the synthesis of ?-acyloxy ethers.
J. Org. Chem.
PUBLISHED: 04-11-2014
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An iron-catalyzed oxidative esterification reaction between unactivated C(sp(3))-H bonds from symmetric and asymmetric ethers and carboxylic acids using di-tert-butyl peroxide (DTBP) as the oxidant via a cross dehydrogenative coupling (CDC) reaction was established, which tolerates a wide range of cyclic ether substrates to react with aromatic acids and phenylacetic acid, providing an efficient method for the preparation of ?-acyloxy ethers with good to excellent yields. Intermolecular competing kinetic isotope effect (KIE) experiments were also carried out, which indicate that C(sp(3))-H bond cleavage may be the rate-determining step of this CDC reaction.
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Modeling sustained treatment effects in tumor xenograft experiments.
J Biopharm Stat
PUBLISHED: 04-05-2014
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In cancer drug development, demonstrated efficacy in tumor xenograft models is an important step toward bringing a promising compound to human use. A key outcome variable is tumor volume measured over a period of time, while mice are treated with certain treatment regimens. A constrained parametric model has been proposed to account for special features, such as intrinsic tumor growth, or tumor volume truncations due to tumor size being either too large or too small to detect. However, since the drug concentration in the blood of a mouse or its tissues may be stabilized at a certain level and maintained during a period of time, the treatment may have sustained effects. This article extends the constrained parametric model to account for the sustained drug effects. The ECM algorithm for incomplete data is applied to estimating the dose-response relationship in the proposed model. The model selection based on likelihood functions is given and a simulation study is conducted to investigate the performance of the proposed estimator. A real xenograft study on the antitumor agent temozolomide combined with irinotecan against the rhabdomyosarcoma is analyzed using the proposed methods.
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Developmental toxicity, oxidative stress, and related gene expression induced by dioxin-like PCB 126 in zebrafish (Danio rerio).
Environ. Toxicol.
PUBLISHED: 03-31-2014
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3,3',4,4',5-Pentachlorobiphenyl (PCB126) cause multiple adverse effects in organisms including animals and humans. Although PCB toxicities are linked to oxidative damage in rodents, the mechanism in early life stages of zebrafish is not clear. To explore the developmental toxicity mechanism of PCB126, three paradigms (toxicological phenotypes, biochemical changes, and molecular changes) were studied in 3-h postfertilization (hpf) zebrafish (Danio rerio) embryos exposed to different PCB126 concentrations (0, 16, 32, 64, and 128 ?g/L) until 168 hpf. Developmental malformations, including pericardial and yolk sac edema, impaired lower jaw growth, spinal curvature, head edema and failure to inflate the swim bladder were observed, some as early as 72 hpf. Mortality was not apparent in early stages but significantly increased in a dose-dependent manner from 144 hpf onward. A dose-dependent significant increase in malformation rate was observed from 72 hpf onward with up to 100% at 132 hpf in embryos exposed to 128 ?g/L of PCB126. Higher doses of PCB126 significantly decreased the copper-zinc superoxide dismutase (CuZn-Sod), catalase (Cat), and glutathione peroxidase (Gpx) enzyme activities at 96, 132 hpf, but markedly declined from thereafter. PCB126 at 128 ?g/L significantly increased the malondialdehyde content at 72, 96, and 132 hpf. The transcriptional gene expression of antioxidant enzymes Cat and Gpx was upregulated in embryos exposed to 64 ?g/L of PCB126 at 24 and 96 hpf. Sod1 messenger RNA (mRNA) was low in embryos exposed to 32 ?g/L at 72 and 96 hpf but was induced in embryos exposed to 64 and 128 ?g/L doses at 132 hpf. Collectively, the results suggest oxidative stress as a major factor in the induction of multiple developmental abnormalities in early life stages of zebrafish exposed to PCB126. However, the relationship between the antioxidant enzyme activity and the mRNA expression was not clear and the potential reasons for this are discussed. © 2014 Wiley Periodicals, Inc. Environ Toxicol, 2014.
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The efficacy and safety of arotinolol combined with a different calcium channel blocker in the treatment of Chinese patients with essential hypertension: a one-year follow-up study.
Clin. Exp. Hypertens.
PUBLISHED: 03-28-2014
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Abstract Background: Combined treatment of a calcium antagonist and ?/?-adrenoreceptor blocker is expected to offer some advantages in the management of hypertension; however, their antihypertensive efficacy and safety remain relatively under-explored.
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Risk factors of Clostridium difficile infections among patients in a university hospital in Shanghai, China.
Anaerobe
PUBLISHED: 03-12-2014
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Clostridium difficile infection (CDI) is an increasing concern in China. However, the risk factors of CDI are rarely reported in the Chinese population. A prospective observational study was therefore conducted among patients with hospital-acquired C. difficile diarrhoea and the risk factors of CDI in a retrospective case-control study. The CDI patients were compared with the non-CDI diarrhoeal patients and those without diarrhoea, respectively. The recurrent CDI patients were compared with the corresponding non-recurrent CDI patients and those without diarrhoea, respectively. Overall, of the 240 patients with hospital-acquired diarrhoea 90 (37.5%) were diagnosed as CDI, and 12 (13.3%) of the 90 CDI patients experienced recurrence. Multivariate analysis indicated that renal disease, malignancy, hypoalbuminemia, prior antibiotic treatment, chemotherapy, nasogastric tube use, length of stay >14 days and intra-abdominal surgery, defined daily dose of antimicrobial agents ?19, prior use of more than three antimicrobial agents, and use of carbapenems were independent risk factors for the first episode of CDI. Use of laxatives, the first- and second-generation narrow-spectrum cephalosporins or metronidazole was identified as protective factors. It is necessary to make testing of C. difficile available as a routine practice and control these risk factors in Chinese hospitals to avoid CDI outbreaks.
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Joint longitudinal and survival-cure models in tumour xenograft experiments.
Stat Med
PUBLISHED: 03-04-2014
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In tumour xenograft experiments, treatment regimens are administered, and the tumour volume of each individual is measured repeatedly over time. Survival data are recorded because of the death of some individuals during the observation period. Also, cure data are observed because of a portion of individuals who are completely cured in the experiments. When modelling these data, certain constraints have to be imposed on the parameters in the models to account for the intrinsic growth of the tumour in the absence of treatment. Also, the likely inherent association of longitudinal and survival-cure data has to be taken into account in order to obtain unbiased estimators of parameters. In this paper, we propose such models for the joint modelling of longitudinal and survival-cure data arising in xenograft experiments. Estimators of parameters in the joint models are obtained using a Markov chain Monte Carlo approach. Real data analysis of a xenograft experiment is carried out, and simulation studies are also conducted, showing that the proposed joint modelling approach outperforms the separate modelling methods in the sense of mean squared errors.
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A phenomenological expression to describe the temperature dependence of pressure-induced softening in negative thermal expansion materials.
J Phys Condens Matter
PUBLISHED: 03-03-2014
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By exploring a simple model of a negative thermal expansion (NTE) system, we introduce a phenomenological expression to describe the temperature dependence of the pressure-induced softening in NTE structures.
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Survival analysis with functional covariates for partial follow-up studies.
Stat Methods Med Res
PUBLISHED: 02-26-2014
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Predictive or prognostic analysis plays an increasingly important role in the era of personalized medicine to identify subsets of patients whom the treatment may benefit the most. Although various time-dependent covariate models are available, such models require that covariates be followed in the whole follow-up period. This article studies a new class of functional survival models where the covariates are only monitored in a time interval that is shorter than the whole follow-up period. This paper is motivated by the analysis of a longitudinal study on advanced myeloma patients who received stem cell transplants and T cell infusions after the transplants. The absolute lymphocyte cell counts were collected serially during hospitalization. Those patients are still followed up if they are alive after hospitalization, while their absolute lymphocyte cell counts cannot be measured after that. Another complication is that absolute lymphocyte cell counts are sparsely and irregularly measured. The conventional method using Cox model with time-varying covariates is not applicable because of the different lengths of observation periods. Analysis based on each single observation obviously underutilizes available information and, more seriously, may yield misleading results. This so-called partial follow-up study design represents increasingly common predictive modeling problem where we have serial multiple biomarkers up to a certain time point, which is shorter than the total length of follow-up. We therefore propose a solution to the partial follow-up design. The new method combines functional principal components analysis and survival analysis with selection of those functional covariates. It also has the advantage of handling sparse and irregularly measured longitudinal observations of covariates and measurement errors. Our analysis based on functional principal components reveals that it is the patterns of the trajectories of absolute lymphocyte cell counts, instead of the actual counts, that affect patient's disease-free survival time.
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Developmental toxicity, EROD, and CYP1A mRNA expression in zebrafish embryos exposed to dioxin-like PCB126.
Environ. Toxicol.
PUBLISHED: 02-18-2014
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Dioxin-like PCB126 is a persistent organic pollutant that causes a range of syndromes including developmental toxicity. Dioxins have a high affinity for aryl hydrocarbon receptor (AhR) and induce cytochrome P4501A (CYP1A). However, the role of CYP1A activity in developmental toxicity is less clear. To better understand dioxin induced developmental toxicity, we exposed zebrafish (Danio rerio) embryos to PCB126 at concentrations of 0, 16, 32, 64, and 128 ?g L(-1) from 3-h post-fertilization (hpf) to 168 hpf. The embryonic survival rate decreased at 144 and 168 hpf. The fry at 96 hpf displayed gross developmental malformations, including pericardial and yolk sac edema, spinal curvature, abnormal lower jaw growth, and non-inflated swim bladder. The pericardial and yolk sac edema rate significantly increased and the heart rate declined from 96 hpf compared with the controls. PCB126 did not alter the hatching rate. To elucidate the mechanism of PCB126-induced developmental toxicity, we conducted ethoxyresorufin-O-deethylase (EROD) in vivo assay to determine CYP1A enzyme activity, and real-time PCR to study the induction of CYP1A mRNA gene expression in embryo/larval zebrafish at 24, 72, 96, and 132 hpf. In vivo EROD activity was induced by PCB126 at 16 ?g L(-1) concentration as early as 72 hpf but significant increases were observed only in zebrafish exposed to 64 and 128 ?g L(-1) doses (p?
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Toward predictive models for drug-induced liver injury in humans: are we there yet?
Biomark Med
PUBLISHED: 02-14-2014
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Drug-induced liver injury (DILI) is a frequent cause for the termination of drug development programs and a leading reason of drug withdrawal from the marketplace. Unfortunately, the current preclinical testing strategies, including the regulatory-required animal toxicity studies or simple in vitro tests, are insufficiently powered to predict DILI in patients reliably. Notably, the limited predictive power of such testing strategies is mostly attributed to the complex nature of DILI, a poor understanding of its mechanism, a scarcity of human hepatotoxicity data and inadequate bioinformatics capabilities. With the advent of high-content screening assays, toxicogenomics and bioinformatics, multiple end points can be studied simultaneously to improve prediction of clinically relevant DILIs. This review focuses on the current state of efforts in developing predictive models from diverse data sources for potential use in detecting human hepatotoxicity, and also aims to provide perspectives on how to further improve DILI prediction.
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Combination immunotherapy after ASCT for multiple myeloma using MAGE-A3/Poly-ICLC immunizations followed by adoptive transfer of vaccine-primed and costimulated autologous T cells.
Clin. Cancer Res.
PUBLISHED: 02-11-2014
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Myeloma-directed cellular immune responses after autologous stem cell transplantation (ASCT) may reduce relapse rates. We studied whether coinjecting the TLR-3 agonist and vaccine adjuvant Poly-ICLC with a MAGE-A3 peptide vaccine was safe and would elicit a high frequency of vaccine-directed immune responses when combined with vaccine-primed and costimulated autologous T cells.
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Intake of fruit and vegetables and risk of bladder cancer: a dose-response meta-analysis of observational studies.
Cancer Causes Control
PUBLISHED: 02-02-2014
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Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial.
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A testing strategy to predict risk for drug-induced liver injury in humans using high-content screen assays and the 'rule-of-two' model.
Arch. Toxicol.
PUBLISHED: 01-28-2014
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Drug-induced liver injury (DILI) is a major cause of drug failures in both the preclinical and clinical phase. Consequently, improving prediction of DILI at an early stage of drug discovery will reduce the potential failures in the subsequent drug development program. In this regard, high-content screening (HCS) assays are considered as a promising strategy for the study of DILI; however, the predictive performance of HCS assays is frequently insufficient. In the present study, a new testing strategy was developed to improve DILI prediction by employing in vitro assays that was combined with the RO2 model (i.e., 'rule-of-two' defined by daily dose ?100 mg/day & logP ?3). The RO2 model was derived from the observation that high daily doses and lipophilicity of an oral medication were associated with significant DILI risk in humans. In the developed testing strategy, the RO2 model was used for the rational selection of candidates for HCS assays, and only the negatives predicted by the RO2 model were further investigated by HCS. Subsequently, the effects of drug treatment on cell loss, nuclear size, DNA damage/fragmentation, apoptosis, lysosomal mass, mitochondrial membrane potential, and steatosis were studied in cultures of primary rat hepatocytes. Using a set of 70 drugs with clear evidence of clinically relevant DILI, the testing strategy improved the accuracies by 10 % and reduced the number of drugs requiring experimental assessment by approximately 20 %, as compared to the HCS assay alone. Moreover, the testing strategy was further validated by including published data (Cosgrove et al. in Toxicol Appl Pharmacol 237:317-330, 2009) on drug-cytokine-induced hepatotoxicity, which improved the accuracies by 7 %. Taken collectively, the proposed testing strategy can significantly improve the prediction of in vitro assays for detecting DILI liability in an early drug discovery phase.
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Molecular mechanisms associated with Angiotensin-converting enzyme-inhibitory peptide activity on vascular extracellular matrix remodeling.
Cardiology
PUBLISHED: 01-24-2014
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This paper aimed to investigate the molecular mechanisms associated with angiotensin-converting enzyme (ACE)-inhibitory peptide activity involved in vascular extracellular matrix (ECM) remodeling. Therefore, changes in collagen fibers, elastic fibers and laminin were assessed in the left common carotid artery (LCCA).
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Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease.
Neural Regen Res
PUBLISHED: 01-18-2014
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Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson's disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson's disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of ?-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson's disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease by modulating neurotransmitter signaling in the corpus striatum.
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Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms.
World J. Gastroenterol.
PUBLISHED: 01-07-2014
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To investigate the effects and underlying mechanisms of resveratrol and genistein on contractile responses of rat gastrointestinal smooth muscle.
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Dietary fiber intake and risk of type 2 diabetes: a dose-response analysis of prospective studies.
Eur. J. Epidemiol.
PUBLISHED: 01-05-2014
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Observational studies suggest an association between dietary fiber intake and risk of type 2 diabetes, but the results are inconclusive. We conducted a meta-analysis of prospective studies evaluating the associations of dietary fiber intake and risk of type 2 diabetes. Relevant studies were identified by searching EMBASE (from 1974 to April 2013) and PubMed (from 1966 to April 2013). The fixed or random-effect model was selected based on the homogeneity test among studies. In addition, a 2-stage random-effects dose-response meta-analysis was performed. We identified 17 prospective cohort studies of dietary fiber intake and risk of type 2 diabetes involving 19,033 cases and 488,293 participants. The combined RR (95 % CI) of type 2 diabetes for intake of total dietary fiber, cereal fiber, fruit fiber and insoluble fiber was 0.81 (0.73-0.90), 0.77 (0.69-0.85), 0.94 (0.88-0.99) and 0.75 (0.63-0.89), respectively. A nonlinear relationship was found of total dietary fiber intake with risk of type 2 diabetes (P for nonlinearity < 0.01), and the RRs (95 % CI) of type 2 diabetes were 0.98 (0.90-1.06), 0.97 (0.87-1.07), 0.89 (0.80-0.99), 0.76 (0.65-0.88), and 0.66 (0.53-0.82) for 15, 20, 25, 30, and 35 g/day. The departure from nonlinear relationship was not significant (P for nonlinearity = 0.72), and the risk of type 2 diabetes decreased by 6 % (RR 0.94, 95 % CI 0.93-0.96) for 2 g/day increment in cereal fiber intake. Findings from this meta-analysis indicate that the intakes of dietary fiber may be inversely associated with risk of type 2 diabetes.
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Diagnostic value of endobronchial ultrasound guided transbronchial needle aspiration in superior vena cava syndrome.
Chin. Med. J.
PUBLISHED: 11-30-2013
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The pathological diagnosis is of critical importance to the subsequent treatment for the pathients with superior vena cava syndrome (SVCS). The aim of this study is to report our experience in the diagnosis of SVCS by endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA).
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Effect of "yang-warming and kidney essence-replenishing" herbal paste on cold-related asthma exacerbation.
J Tradit Chin Med
PUBLISHED: 11-06-2013
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To observe the effect of "Yang-warming and kidney essence-replenishing" herbal paste on cold-related asthma exacerbation.
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Diabetes mellitus increases the risk of bladder cancer: an updated meta-analysis of observational studies.
Diabetes Technol. Ther.
PUBLISHED: 11-05-2013
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Increasing evidence suggests that diabetes mellitus (DM) may be associated with an increased risk of bladder cancer. We performed an updated meta-analysis to examine the association between DM and risk of bladder cancer.
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[Inhibitory effects of 17beta-estradiol on spontaneous and activated contraction of rat uterus smooth muscle].
Zhongguo Ying Yong Sheng Li Xue Za Zhi
PUBLISHED: 11-02-2013
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To observe and compare the effects of 17beta-estradiol (EST) on the phasic and tonic contractile activities of the uterine smooth muscles of SD rats in vitro.
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In vitro antifungal activity of farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida.
Ann. Clin. Microbiol. Antimicrob.
PUBLISHED: 10-30-2013
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Protein farnesylation is an important tosttranslational modification in fungi. We evaluated the antifungal activity of two farnesyltransferase inhibitors against clinical isolates of Aspergillus and Candida. Unfortunately, the MICs were vastly higher than the concentrations that inhibit the proliferation and viability of mammalian cells.
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Data mining tools for Salmonella characterization: application to gel-based fingerprinting analysis.
BMC Bioinformatics
PUBLISHED: 10-09-2013
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Pulsed field gel electrophoresis (PFGE) is currently the most widely and routinely used method by the Centers for Disease Control and Prevention (CDC) and state health labs in the United States for Salmonella surveillance and outbreak tracking. Major drawbacks of commercially available PFGE analysis programs have been their difficulty in dealing with large datasets and the limited availability of analysis tools. There exists a need to develop new analytical tools for PFGE data mining in order to make full use of valuable data in large surveillance databases.
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A systems approach for analysis of high content screening assay data with topic modeling.
BMC Bioinformatics
PUBLISHED: 10-09-2013
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High Content Screening (HCS) has become an important tool for toxicity assessment, partly due to its advantage of handling multiple measurements simultaneously. This approach has provided insight and contributed to the understanding of systems biology at cellular level. To fully realize this potential, the simultaneously measured multiple endpoints from a live cell should be considered in a probabilistic relationship to assess the cells condition to response stress from a treatment, which poses a great challenge to extract hidden knowledge and relationships from these measurements.
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Homology modeling, molecular docking, and molecular dynamics simulations elucidated ?-fetoprotein binding modes.
BMC Bioinformatics
PUBLISHED: 10-09-2013
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An important mechanism of endocrine activity is chemicals entering target cells via transport proteins and then interacting with hormone receptors such as the estrogen receptor (ER). ?-Fetoprotein (AFP) is a major transport protein in rodent serum that can bind and sequester estrogens, thus preventing entry to the target cell and where they could otherwise induce ER-mediated endocrine activity. Recently, we reported rat AFP binding affinities for a large set of structurally diverse chemicals, including 53 binders and 72 non-binders. However, the lack of three-dimensional (3D) structures of rat AFP hinders further understanding of the structural dependence for binding. Therefore, a 3D structure of rat AFP was built using homology modeling in order to elucidate rat AFP-ligand binding modes through docking analyses and molecular dynamics (MD) simulations.
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Association of serum resistin with peripheral arterial disease.
Pol. Arch. Med. Wewn.
PUBLISHED: 09-26-2013
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 Resistin is an inflammatory mediator and a potential biomarker in cardiovascular diseases.
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Quantitative structure-activity relationship models for predicting drug-induced liver injury based on FDA-approved drug labeling annotation and using a large collection of drugs.
Toxicol. Sci.
PUBLISHED: 08-31-2013
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Drug-induced liver injury (DILI) is one of the leading causes of the termination of drug development programs. Consequently, identifying the risk of DILI in humans for drug candidates during the early stages of the development process would greatly reduce the drug attrition rate in the pharmaceutical industry but would require the implementation of new research and development strategies. In this regard, several in silico models have been proposed as alternative means in prioritizing drug candidates. Because the accuracy and utility of a predictive model rests largely on how to annotate the potential of a drug to cause DILI in a reliable and consistent way, the Food and Drug Administration-approved drug labeling was given prominence. Out of 387 drugs annotated, 197 drugs were used to develop a quantitative structure-activity relationship (QSAR) model and the model was subsequently challenged by the left of drugs serving as an external validation set with an overall prediction accuracy of 68.9%. The performance of the model was further assessed by the use of 2 additional independent validation sets, and the 3 validation data sets have a total of 483 unique drugs. We observed that the QSAR models performance varied for drugs with different therapeutic uses; however, it achieved a better estimated accuracy (73.6%) as well as negative predictive value (77.0%) when focusing only on these therapeutic categories with high prediction confidence. Thus, the models applicability domain was defined. Taken collectively, the developed QSAR model has the potential utility to prioritize compounds risk for DILI in humans, particularly for the high-confidence therapeutic subgroups like analgesics, antibacterial agents, and antihistamines.
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Convergent and Divergent Pathways Decoding Hierarchical Additive Mechanisms in Treating Cerebral Ischemia-Reperfusion Injury.
CNS Neurosci Ther
PUBLISHED: 08-25-2013
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Cerebral ischemia is considered to be a highly complex disease resulting from the complicated interplay of multiple pathways. Disappointedly, most of the previous studies were limited to a single gene or a single pathway. The extent to which all involved pathways are translated into fusing mechanisms of a combination therapy is of fundamental importance.
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Vitamin D deficiency does not predict progression of coronary artery calcium, carotid intima-media thickness or high-sensitivity C-reactive protein in systemic lupus erythematosus.
Rheumatology (Oxford)
PUBLISHED: 08-16-2013
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Vitamin D deficiency is common in SLE. Cardioprotective effects of vitamin D have been postulated due to modulation of inflammatory cytokines. However, the effects of vitamin D supplementation on inflammatory cytokines in trials have been inconsistent. We determined whether levels of vitamin D at baseline were associated with subclinical measures of atherosclerosis, or with changes in subclinical measures over 2 years.
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Value of Isolated IgA Anti-?2 -Glycoprotein I Positivity in the Diagnosis of the Antiphospholipid Syndrome.
Arthritis Rheum.
PUBLISHED: 08-06-2013
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To examine the prevalence of isolated IgA anti-?2 -glycoprotein I (anti-?2 GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of ?2 GPI, with clinical manifestations of the antiphospholipid syndrome (APS) in 3 patient groups and to evaluate the pathogenicity of IgA anti-?2 GPI in a mouse model of thrombosis.
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EADB: an estrogenic activity database for assessing potential endocrine activity.
Toxicol. Sci.
PUBLISHED: 07-28-2013
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Endocrine-active chemicals can potentially have adverse effects on both humans and wildlife. They can interfere with the bodys endocrine system through direct or indirect interactions with many protein targets. Estrogen receptors (ERs) are one of the major targets, and many endocrine disruptors are estrogenic and affect the normal estrogen signaling pathways. However, ERs can also serve as therapeutic targets for various medical conditions, such as menopausal symptoms, osteoporosis, and ER-positive breast cancer. Because of the decades-long interest in the safety and therapeutic utility of estrogenic chemicals, a large number of chemicals have been assayed for estrogenic activity, but these data exist in various sources and different formats that restrict the ability of regulatory and industry scientists to utilize them fully for assessing risk-benefit. To address this issue, we have developed an Estrogenic Activity Database (EADB; http://www.fda.gov/ScienceResearch/BioinformaticsTools/EstrogenicActivityDatabaseEADB/default.htm) and made it freely available to the public. EADB contains 18,114 estrogenic activity data points collected for 8212 chemicals tested in 1284 binding, reporter gene, cell proliferation, and in vivo assays in 11 different species. The chemicals cover a broad chemical structure space and the data span a wide range of activities. A set of tools allow users to access EADB and evaluate potential endocrine activity of chemicals. As a case study, a classification model was developed using EADB for predicting ER binding of chemicals.
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Complementation of HYPONASTIC LEAVES1 by double-strand RNA-binding domains of DICER-LIKE1 in nuclear dicing bodies.
Plant Physiol.
PUBLISHED: 07-25-2013
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MicroRNAs (miRNAs) are a class of small regulatory RNAs that are found in almost all of the eukaryotes. Arabidopsis (Arabidopsis thaliana) miRNAs are processed from primary miRNAs (pri-miRNAs), mainly by the ribonuclease III-like enzyme DICER-LIKE1 (DCL1) and its specific partner, HYPONASTIC LEAVES1 (HYL1), a double-strand RNA-binding protein, both of which contain two double-strand RNA-binding domains (dsRBDs). These dsRBDs are essential for miRNA processing, but the functions of them are not clear. Here, we report that the two dsRBDs of DCL1 (DCL1-D1D2), and to some extent the second dsRBD (DCL1-D2), complement the hyl1 mutant, but not the first dsRBD of DCL1 (DCL1-D1). DCL1-D1 is diffusely distributed throughout the nucleoplasm, whereas DCL1-D2 and DCL1-D1D2 concentrate in nuclear dicing bodies in which DCL1 and HYL1 colocalize. We show further that protein-protein interaction is mainly mediated by DCL1-D2, while DCL1-D1 plays a major role in binding of pri-miRNAs. These results suggest parallel roles between C-terminal dsRBDs of DCL1 and N-terminal dsRBDs of HYL1 and support a model in which Arabidopsis pri-miRNAs are recruited to dicing bodies through functionally divergent dsRBDs of microprocessor for accurate processing of plant pri-miRNAs.
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Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.
Ann. Hematol.
PUBLISHED: 05-16-2013
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We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n?=?14), ALL (n?=?10), NHL (n?=?18), and other refractory hematologic malignancies (n?=?6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (<80,000/mL) and lactic dehydrogenase (>500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.
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Predictors of self-reported health-related quality of life in systemic lupus erythematosus.
Rheumatology (Oxford)
PUBLISHED: 05-16-2013
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The Medical Outcomes Short Form-36 Survey (SF-36) has been widely used as a measure of health-related quality of life (HRQOL) in different populations. SLE patients have consistently reported lower scores compared with the general population. The objective of our study was to identify predictors of HRQOL using SF-36 among patients with SLE enrolled in a 2-year randomized controlled trial (RCT).
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Platelet glycoprotein Ib? ectodomain shedding and non-surgical bleeding in heart failure patients supported by continuous-flow left ventricular assist devices.
J. Heart Lung Transplant.
PUBLISHED: 04-10-2013
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Non-surgical bleeding (NSB) is a major complication among heart failure (HF) patients supported by continuous-flow left ventricular assist devices (CF-LVADs). Understanding the hemostatic defects contributing to NSB after CF-LVAD implantation is crucial for prevention of this adverse event. The aim of this study was to examine the link between platelet glycoprotein Ib? (GPIb?) ectodomain shedding and NSB in CF-LVAD recipients and to identify a potential biomarker of NSB.
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The Beneficial Effect of Total Glucosides of Paeony on Psoriatic Arthritis Links to Circulating Tregs and Th1 Cell Function.
Phytother Res
PUBLISHED: 03-21-2013
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Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-? and TNF-?), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ?25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA. Copyright © 2013 John Wiley & Sons, Ltd.
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Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio.
Arthritis Rheum.
PUBLISHED: 03-21-2013
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To investigate whether an increase in vitamin D levels in patients with systemic lupus erythematosus (SLE) was associated with improvement in disease activity.
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[Construction of a lentiviral RNA interference system targeting heparanase based on miR30 and its silencing effect].
Zhejiang Da Xue Xue Bao Yi Xue Ban
PUBLISHED: 03-19-2013
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To construct a lentiviral RNA interference system targeting heparanase (HPSE) based on miR30 and to test its silencing effect.
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Effects of estrogen and phytoestrogens on endometrial leakage in ovariectomized rats and the related mechanisms.
Sheng Li Xue Bao
PUBLISHED: 02-22-2013
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Phytoestrogens, a group of plant-derived non-steroidal compounds that can behave as estrogens by binding to estrogen receptors, have drawn great attention for their potentially beneficial effects on human health. However, there are few studies investigating the potential side effects of phytoestrogens on the reproductive system. The present study was to elucidate the effects of 17?-estradiol (E2), progesterone (P4), and phytoestrogens genistein (Gen), resveratrol (Res), and phloretin (Phl) on eosinophilic infiltration of the ovariectomized rat uterus and endometrial vascular permeability, and to analyze the underlying mechanisms. The ovariectomized rats received daily subcutaneous injections of E2, E2+P4, P4, Gen, Res, Phl, or an equivalent volume of vehicle for 21 days, and sham-operated animals (Sham rats) were used as the controls. Hematoxylin-eosin staining revealed a marked increase in uterine eosinophilic infiltrations in ovariectomized rats treated with E2, E2+P4 or P4, which was associated with increased expression of vascular endothelial growth factor (VEGF), nuclear factor-?B (NF-?B), and tumor necrosis factor-? (TNF-?) proteins as determined by immunohistochemical and Western blot analysis. However, all three phytoestrogens had no markedly effect on the uterine eosinophilic infiltration and the expressions of VEGF, NF-?B, and TNF-? in the uterus of ovariectomized rats. Our data demonstrate that E2 alone or in combination with P4 increases uterine eosinophilic infiltration which is related with vascular hyperpermeability caused by VEGF, NF-?B and TNF-?, whereas phytoestrogens Gen, Res, and Phl, have no such an effect.
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Hierarchical profiles of signaling pathways and networks reveal two complementary pharmacological mechanisms.
CNS Neurol Disord Drug Targets
PUBLISHED: 02-20-2013
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Until now the overlapping and diverse pharmacological protective mechanisms of different compounds in the treatment of cerebral ischemia, both on the signaling pathway and network levels have not been revealed. In order to find differential pathway networks from gene expression profiles of hippocampus of ischemic mice treated with baicalin (BA), ursodeoxycholic acid (UA) and jasminoidin (JA), a microarray comprising 16,463 genes, FDA Arraytrack software and Ingenuity Pathway Analysis, was employed. A total of 5, 8, 11, 9 networks and 6, 7, 40, 16 pathways were found in vehicle (vs sham), BA, UA and JA (vs vehicle), respectively. Only 4 and 7 overlapping pathways were shared between BA and UA, UA and JA, accounting for 9.3% and 14.3% of the total number of all pathways, respectively. BA, UA and JA all acted on Ca(2+)-dependent signaling cascades in diverse links. BA intervened in arachidonic acid metabolism. UA affected eicosanoid, cyclin-dependent kinase 5, nuclear factor-kB, and T-helper 1 cell cytokine production. It was found that JA might decrease oxidative damage via nuclear factor erythroid 2-related factor 2-mediated antioxidant response. Compared to vehicle, no overlapping pathways were found among three groups. However, the total of 60 (71.4%) overlapping functions could be approximately divided into diseases and disorders, molecular and cellular functions, physiological system development and function as categories with ratio of 1:1:1. Analysis of network functions and known pathways may be two complementary paradigms for revealing potential pharmacological mechanisms based on the same phenotype variation.
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Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus.
Rheumatol. Int.
PUBLISHED: 02-19-2013
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Accelerated atherosclerosis remains a major cause of death in late systemic lupus erythematosus (SLE). Omega-3 has been reported to have benefit for endothelial dysfunction, one of the earliest stages of atherosclerosis, and to reduce disease activity in SLE. We performed a randomized, double-blind placebo-controlled trial to examine the effect of Omega-3 on endothelial function, disease activity, inflammatory markers and lipids in SLE. SLE patients (n = 85, mean age 47, 55% Caucasian, 38% African-American, 94% female) were randomly assigned to 3 g of Omega-3 (Lovaza, GSK) versus placebo for 12 weeks. Endothelial function was measured at baseline and at 12 weeks using flow-mediated dilation, calculated using high-resolution B-mode ultrasound of the brachial artery diameter in response to vasoactive stimuli (hyperemia). Disease activity was measured using the physician global assessment and SELENA-SLEDAI score. Inflammatory markers (sICAM-1, sVCAM-1, IL-6) and fasting lipid profile were done at baseline and 12-week follow-up. There was no difference between the treatment groups with respect to changes in flow-mediated dilation parameters or disease activity. An average increase in LDL cholesterol of 3.11 mg/dL (±21.99) was found with Omega-3 versus a decrease of 1.87 mg/dL (±18.29) with placebo (p = 0.0266). In this trial, Omega-3 did not improve endothelial function, disease activity, nor reduce inflammatory markers in SLE. Longer trials might be required if there are delayed clinical effects. There was evidence that Omega-3 may increase LDL cholesterol, but not the LDL/HDL ratio.
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Meta-analysis of pulsed-field gel electrophoresis fingerprints based on a constructed Salmonella database.
PLoS ONE
PUBLISHED: 02-13-2013
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A database was constructed consisting of 45,923 Salmonella pulsed-field gel electrophoresis (PFGE) patterns. The patterns, randomly selected from all submissions to CDC PulseNet during 2005 to 2010, included the 20 most frequent serotypes and 12 less frequent serotypes. Meta-analysis was applied to all of the PFGE patterns in the database. In the range of 20 to 1100 kb, serotype Enteritidis averaged the fewest bands at 12 bands and Paratyphi A the most with 19, with most serotypes in the 13-15 range among the 32 serptypes. The 10 most frequent bands for each of the 32 serotypes were sorted and distinguished, and the results were in concordance with those from distance matrix and two-way hierarchical cluster analyses of the patterns in the database. The hierarchical cluster analysis divided the 32 serotypes into three major groups according to dissimilarity measures, and revealed for the first time the similarities among the PFGE patterns of serotype Saintpaul to serotypes Typhimurium, Typhimurium var. 5-, and I 4,[5],12:i:-; of serotype Hadar to serotype Infantis; and of serotype Muenchen to serotype Newport. The results of the meta-analysis indicated that the pattern similarities/dissimilarities determined the serotype discrimination of PFGE method, and that the possible PFGE markers may have utility for serotype identification. The presence of distinct, serotype specific patterns may provide useful information to aid in the distribution of serotypes in the population and potentially reduce the need for laborious analyses, such as traditional serotyping.
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Translational phase I trial of vorinostat (suberoylanilide hydroxamic acid) combined with cytarabine and etoposide in patients with relapsed, refractory, or high-risk acute myeloid leukemia.
Clin. Cancer Res.
PUBLISHED: 02-12-2013
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To determine the maximum-tolerated dose (MTD) of the histone deacetylase inhibitor vorinostat combined with fixed doses of cytarabine (ara-C or cytosine arabinoside) and etoposide in patients with poor-risk or advanced acute leukemia, to obtain preliminary efficacy data, describe pharmacokinetics, and in vivo pharmacodynamic effects of vorinostat in leukemia blasts.
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MicroRNA-195 suppresses angiogenesis and metastasis of hepatocellular carcinoma by inhibiting the expression of VEGF, VAV2, and CDC42.
Hepatology
PUBLISHED: 02-07-2013
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Hepatocellular carcinoma (HCC) is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. There is frequent down-regulation of miR-195 expression in HCC tissues. In this study, the role of miR-195 in HCC angiogenesis and metastasis was investigated with in vitro capillary tube formation and transwell assays, in vivo orthotopic xenograft mouse models, and human HCC specimens. Reduction of miR-195 in HCC tissues was significantly associated with increased angiogenesis, metastasis, and worse recurrence-free survival. Both gain-of-function and loss-of-function studies of in vitro models revealed that miR-195 not only suppressed the ability of HCC cells to promote the migration and capillary tube formation of endothelial cells but also directly repressed the abilities of HCC cells to migrate and invade extracellular matrix gel. Based on mouse models, we found that the induced expression of miR-195 dramatically reduced microvessel densities in xenograft tumors and repressed both intrahepatic and pulmonary metastasis. Subsequent investigations disclosed that miR-195 directly inhibited the expression of the proangiogenic factor vascular endothelial growth factor (VEGF) and the prometastatic factors VAV2 and CDC42. Knockdown of these target molecules of miR-195 phenocopied the effects of miR-195 restoration, whereas overexpression of these targets antagonized the function of miR-195. Furthermore, we revealed that miR-195 down-regulation resulted in enhanced VEGF levels in the tumor microenvironment, which subsequently activated VEGF receptor 2 signaling in endothelial cells and thereby promoted angiogenesis. Additionally, miR-195 down-regulation led to increases in VAV2 and CDC42 expression, which stimulated VAV2/Rac1/CDC42 signaling and lamellipodia formation and thereby facilitated the metastasis of HCC cells. Conclusion: miR-195 deregulation contributes to angiogenesis and metastasis in HCC. The restoration of miR-195 expression may be a promising strategy for HCC therapy.
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Optimal treatment opportunity for mTHPC-mediated photodynamic therapy of liver cancer.
Lasers Med Sci
PUBLISHED: 02-03-2013
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Photodynamic therapy (PDT) has been clinically used for liver cancer. The pharmacokinetics of a photosensitizer needs to be monitored so that PDT can be performed at the most favorable time and with the proper dose to increase the cure rate. As mTHPC is a fluorescent compound, we investigate its pharmacokinetics, distribution, and elimination in the rat orthotropic liver cancer model in order to confirm an optimal treatment opportunity of liver cancer PDT. After intravenous administration at a single dose of 300 ?g/kg, mTHPC was extracted from tissue homogenates or plasma. Then, mTHPC concentrations were assessed by fluorescence spectroscopy and the data were processed with PK-GRAPH pharmacokinetic procedure. The plasma concentration-time profile of mTHPC showed a short distribution half-life (T½? = 0.082 h) and a relatively longer elimination half-life (T½? = 28.23 h), which quite fitted with a two-compartment model. The results of mTHPC tissue distributions showed that the highest drug accumulation was in tumor tissue, and successively decreased in liver, heart, spleen, muscle, and skin tissues. The drug distribution ratio of tumor to normal tissue reached the peak at 24 h after mTHPC administration. mTHPC was eliminated at a suitable rate in rat orthotropic liver cancer model, and there was no long-term accumulation of mTHPC in rat tissues. For PDT of orthotropic liver cancer, 24 h after mTHPC intravenous injection may be the optimal treatment time point, which might provide higher clinical efficacy and reduce side effects.
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Comparison of MALDI-TOF MS and VITEK 2 system for laboratory diagnosis of Granulicatella and Abiotrophia species causing invasive infections.
Diagn. Microbiol. Infect. Dis.
PUBLISHED: 02-01-2013
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Granulicatella and Abiotrophia spp. were known as nutritionally variant streptococci (NVS). Such strains have caused major diagnostic difficulties due to fastidious culturing and unspecific colony morphology. The present study is aimed at comparing the performance of laboratory available diagnostic methods for NVS isolates and determining the antimicrobial susceptibility of these isolates. Fourteen clinical invasive isolates, consisting of 10 Granulicatella adiacens, 1 Granulicatella elegans, and 3 Abiotrophia defectiva were in parallel analyzed by 2 matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems, i.e., Bruker MS and Vitek MS, as well as Vitek 2 for the species determination. 16S rRNA gene sequencing was applied as a reference method. The Vitek MS gave correct identification for all 14 isolates. The Bruker MS could correctly identify 8/10 G. adiacens, 0/1 G. elegans, and 3/3 A. defectiva isolates at the first analysis occasion, and all 14 isolates became identifiable after repeated tests. The Vitek 2 system could identify 6/10 G. adiacens, 1/1 G. elegans, and 2/3 A. defectiva isolates at the species level. Antimicrobial susceptibilities of 11 antibiotics were determined by Etest. Resistance against ciprofloxacin, ceftriaxone, rifampicin, and tetracycline were observed in 4, 10, 4, and 1 isolates, respectively. In conclusion, MALDI-TOF MS is a useful tool for the rapid diagnosis of NVS. Phenotypic testing by Vitek 2 is only partially effective for the accurate identification of such strains. The emergence of resistant NVS isolates indicates the necessity of monitoring antimicrobial susceptibilities of such uncommon pathogens.
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