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Find video protocols related to scientific articles indexed in Pubmed.
Stability analysis of electrical powered wheelchair-mounted robotic-assisted transfer device.
J Rehabil Res Dev
PUBLISHED: 11-07-2014
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The ability of people with disabilities to live in their homes and communities with maximal independence often hinges, at least in part, on their ability to transfer or be transferred by an assistant. Because of limited resources and the expense of personal care, robotic transfer assistance devices will likely be in great demand. An easy-to-use system for assisting with transfers, attachable to electrical powered wheelchairs (EPWs) and readily transportable, could have a significant positive effect on the quality of life of people with disabilities. We investigated the stability of our newly developed Strong Arm, which is attached and integrated with an EPW to assist with transfers. The stability of the system was analyzed and verified by experiments applying different loads and using different system configurations. The model predicted the distributions of the system's center of mass very well compared with the experimental results. When real transfers were conducted with 50 and 75 kg loads and an 83.25 kg dummy, the current Strong Arm could transfer all weights safely without tip-over. Our modeling accurately predicts the stability of the system and is suitable for developing better control algorithms to enhance the safety of the device.
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The coagulation characteristics of humic acid by using acid-soluble chitosan, water-soluble chitosan, and chitosan coagulant mixtures.
Environ Technol
PUBLISHED: 11-04-2014
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Abstract Chitosan is a potential substitute for traditional aluminum salts in water treatment systems. This study compared the characteristics of humic acid (HA) removal by using acid-soluble chitosan, water-soluble chitosan, and coagulant mixtures of chitosan with aluminum sulfate (alum) or polyaluminum chloride (PACl). In addition, we evaluated their respective coagulation efficiencies at various coagulant concentrations, pH values, turbidities, and hardness levels. Furthermore, we determined the size and settling velocity of flocs formed by these coagulants to identify the major factors affecting HA coagulation. The coagulation efficiency of acid- and water-soluble chitosan for 15?mg/l of HA was 74.4% and 87.5%, respectively. The optimal coagulation range of water-soluble chitosan (9-20?mg/l) was broader than that of acid-soluble chitosan (4-8?mg/l). Notably, acid-soluble chitosan/PACl and water-soluble chitosan/alum coagulant mixtures exhibited a higher coagulation efficiency for HA than for PACl or alum alone. Furthermore, these coagulant mixtures yielded an acceptable floc settling velocity and savings in both installation and operational expenses. Based on these results, we confidently assert that coagulant mixtures with a 1:1 mass ratio of acid-soluble chitosan/PACl and water-soluble chitosan/alum provide a substantially more cost-effective alternative to using chitosan alone for removing HA from water. Supplementary material.
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Rhenium and technetium tricarbonyl complexes of N-heterocyclic carbene ligands.
Inorg Chem
PUBLISHED: 10-03-2014
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A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(?N)] (?N is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl(-), RCO2(-)) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by (1)H and (13)C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. (1)H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[(99m)Tc(OH2)3(CO)3](+). To confirm the structure of the (99m)Tc-labeled complex, the equivalent (99)Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [(99m/99)Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)](+) with an acetonitrile molecule coordinated to the metal center.
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Relationship of lifestyle and body stature growth with the development of myopia and axial length elongation in Taiwanese elementary school children.
Indian J Ophthalmol
PUBLISHED: 09-19-2014
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The development of myopia and growth of the eye, occur at a time when body stature is increasing.
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Identification of a Novel Lysosomal Trafficking Peptide using Phage Display Biopanning Coupled with Endocytic Selection Pressure.
Bioconjug. Chem.
PUBLISHED: 09-15-2014
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Methods to select ligands that accumulate specifically in cancer cells and traffic through a defined endocytic pathway may facilitate rapid pairing of ligands with linkers suitable for drug conjugate therapies. We performed phage display biopanning on cancer cells that are treated with selective inhibitors of a given mechanism of endocytosis. Using chlorpromazine to inhibit clathrin-mediated endocytosis in H1299 nonsmall cell lung cancer cells, we identified two clones, ATEPRKQYATPRVFWTDAPG (15.1) and a novel peptide LQWRRDDNVHNFGVWARYRL (H1299.3). The peptides segregate by mechanism of endocytosis and subsequent location of subcellular accumulation. The H1299.3 peptide primarily utilizes clathrin-mediated endocytosis and colocalizes with Lamp1, a lysosomal marker. Conversely, the 15.1 peptide is clathrin-independent and localizes to a perinuclear region. Thus, this novel phage display scheme allows for selection of peptides that selectively internalize into cells via a known mechanism of endocytosis. These types of selections may allow for better matching of linker with targeting ligand by selecting ligands that internalize and traffic to known subcellular locations.
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Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin's lymphomas.
Oncotarget
PUBLISHED: 09-12-2014
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Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma (NHL). In cancers, tumor suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling of representative EBV-negative MCL cell lines before and after demethylation treatment, miR-155-3p was found significantly restored. Methylation-specific PCR, verified by pyrosequencing, showed complete methylation of miR-155-3p in one MCL cell line (REC-1). 5-aza-2'-deoxycytidine treatment of REC-1 led to demethylation and re-expression of miR-155-3p. Over-expression of miR-155-3p led to increased sub-G1 apoptotic cells and reduced cellular viability, demonstrating its tumor suppressive properties. By luciferase assay, lymphotoxin-beta (LT-?) was validated as a miR-155-3p target. In 31 primary MCL, miR-155-3p was found hypermethylated in 6(19%) cases. To test if methylation of miR-155-3p was MCL-specific, miR-155-3p methylation was tested in an additional 191 B-cell, T-cell and NK-cell NHLs, yielding miR-155-3p methylation in 66(34.6%) including 36(27%) non-MCL B-cell, 24(53%) T-cell and 6(46%) of NK-cell lymphoma. Moreover, in 72 primary NHL samples with RNA, miR-155-3p methylation correlated with miR-155-3p downregulation (p=0.024), and LT-? upregulation (p=0.043). Collectively, miR-155-3p is a potential tumor suppressive microRNA hypermethylated in MCL and other NHL subtypes. As miR-155-3p targets LT-?, which is an upstream activator of the non-canonical NF-kB signaling, miR-155-3p methylation is potentially important in lymphomagenesis.
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Measurement of biochemical oxygen demand from different wastewater samples using a mediator-less microbial fuel cell biosensor.
Environ Technol
PUBLISHED: 08-23-2014
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Microbial fuel cells (MFCs) have attracted considerable attention as potential biosensors. A MFC biosensor for rapid measurement of biochemical oxygen demand (BOD) has been recently studied. However, a standardized bacterial mixture inoculated in the MFC biosensor for BOD measurement is unavailable. Thus, the commercial application of a MFC biosensor is limited. In this study, a mediator-less MFC biosensor inoculated with known mixed cultures to quickly determine BOD concentration was tested. Optimal external resistance, operating temperature and measurement time for the MFC biosensor were determined to be 5000 omega, 35 degrees C and 12h, respectively. A good relationship between BOD concentration and voltage output, high reproducibility and long-term stability for the MFC biosensor was observed. The newly developed MFC biosensor was inoculated with a mixture of six bacterial strains (Thermincola carboxydiphila, Pseudomonas aeruginosa, Ochrobactrum intermedium, Shewanella frigidimarina, Citrobacter freundii and Clostridium acetobutylicum) capable of degrading complex organic compounds and surviving toxic conditions. The described MFC biosensor was able to successfully measure BOD concentrations below 240 mg L(-1) in real wastewater samples.
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A simple improved-throughput xylem protoplast system for studying wood formation.
Nat Protoc
PUBLISHED: 08-21-2014
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Isolated protoplasts serve as a transient expression system that is highly representative of stable transgenics in terms of transcriptome responses. They can also be used as a cellular system to study gene transactivation and nucleocytoplasmic protein trafficking. They are particularly useful for systems studies in which stable transgenics and mutants are unavailable. We present a protocol for the isolation and transfection of protoplasts from wood-forming tissue, the stem-differentiating xylem (SDX), in the model woody plant Populus trichocarpa. The method involves tissue preparation, digestion of SDX cell walls, protoplast isolation and DNA transfection. Our approach is markedly faster and provides better yields than previous protocols; small (milligrams)- to large (20 g)-scale SDX preparations can be achieved in ~60 s, with isolation of protoplasts and their subsequent transfection taking ~50 min. Up to ten different samples can be processed simultaneously in this time scale. Our protocol gives a high yield (~2.5 × 10(7) protoplasts per g of SDX) of protoplasts sharing 96% transcriptome identity with intact SDX.
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A robust chromatin immunoprecipitation protocol for studying transcription factor-DNA interactions and histone modifications in wood-forming tissue.
Nat Protoc
PUBLISHED: 08-21-2014
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Woody cells and tissues are recalcitrant to standard chromatin immunoprecipitation (ChIP) procedures. However, we recently successfully implemented ChIP in wood-forming tissue of the model woody plant Populus trichocarpa. Here we provide the detailed ChIP protocol optimized for wood-forming tissue that we used in those studies. By using stem-differentiating xylem (SDX; a wood-forming tissue), we identified all steps that were ineffective in standard ChIP protocols and systematically modified them to develop and optimize a robust ChIP protocol. The protocol includes tissue collection, cross-linking, nuclear isolation, chromatin extraction, DNA fragmentation, immunoprecipitation, DNA purification and sequence analysis. The protocol takes 2.5 d to complete and allows a robust 8-10-fold enrichment of transcription factor (TF)-bound genomic fragments (~150 ng/g of SDX) over nonspecific DNAs. The enriched DNAs are of high quality and can be used for subsequent PCR and DNA-seq analyses. We used this protocol to identify genome-wide specific TF-DNA interactions during wood formation and histone modifications associated with regulation of wood formation. Our protocol, which may be suitable for many tissue types, is so far the only working ChIP system for wood-forming tissue.
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The relationship between independent transfer skills and upper limb kinetics in wheelchair users.
Biomed Res Int
PUBLISHED: 08-05-2014
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Transfers are one of the most physically demanding wheelchair activities. The purpose of this study was to determine if using proper transfer skills as measured by the Transfer Assessment Instrument (TAI) is associated with reduced loading on the upper extremities. Twenty-three wheelchair users performed transfers to a level-height bench while a series of forces plates, load cells, and a motion capture system recorded the biomechanics of their natural transferring techniques. Their transfer skills were simultaneously evaluated by two study clinicians using the TAI. Logistic regression and multiple linear regression models were used to determine the relationships between TAI scores and the kinetic variables on both arms across all joints. The results showed that the TAI measured transfer skills were closely associated with the magnitude and timing of joint moments (P < .02, model R(2) values ranged from 0.27 to 0.79). Proper completion of the skills which targeted the trailing arm was associated with lower average resultant moments and rates of rise of resultant moments at the trailing shoulder and/or elbow. Some skills involving the leading side had the effect of increasing the magnitude or rate loading on the leading side. Knowledge of the kinetic outcomes associated with each skill may help users to achieve the best load-relieving effects for their upper extremities.
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Mast cell leukemia: an extremely rare disease.
J Chin Med Assoc
PUBLISHED: 07-12-2014
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Systemic mastocytosis is characterized by pathologic proliferation and accumulation of mast cells in at least one extracutaneous organ such as liver, spleen, bone marrow, or lymph nodes. The clinical features are highly variable depending on impairment of the involved organ systems. It often raises diagnostic challenges. Here we report a case of a 78-year-old patient with mast cell leukemia. The literature is reviewed regarding the diagnosis and updated management of this rare disease.
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Randomized Phase II Study of the X-linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC).
Am. J. Clin. Oncol.
PUBLISHED: 07-01-2014
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This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone.
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Prompt bone marrow-derived mesenchymal stem cell therapy enables early porcine heart function recovery from acute myocardial infarction.
Int Heart J
PUBLISHED: 06-25-2014
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Impact of early bone marrow-derived mesenchymal stem cell (BMDMSC) implantation on left ventricular (LV) function after AMI was studied.Twelve mini-pigs were equally divided into placebo (AMI through left coronary artery ligation) and cell-treated groups [BMDMSCs (3.0 × 10(7)) implanted into infarct area (IA)] with myocardium harvested by post-AMI day 90. Six healthy animals served as controls.On post-AMI day 90, magnetic resonance imaging showed a lower LV ejection fraction but higher LV dimensions in the placebo group (P < 0.003) that also had increased IAs but reduced wall thickness (P < 0.005). Pro-apoptotic gene expressions (Bax, caspase-3) and apoptotic nucleus number in IAs and peri-IAs were highest in the placebo group (P < 0.001). Inflammatory biomarker expressions (MMP-9, oxidized protein, CD40+ cells) were highest, whereas those of angiogenesis (VEGF, CD31+ cells, SDF-1?, CXCR4) and myocardium-preservation (connexin43, troponin-I, cytochrome-C) were lowest in the placebo group (P < 0.01).BMDMSC implantation preserved LV function and alleviated remodeling at post-AMI day 90.
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Thyroid hormone enhanced human hepatoma cell motility involves brain-specific serine protease 4 activation via ERK signaling.
Mol. Cancer
PUBLISHED: 06-19-2014
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The thyroid hormone, 3, 3', 5-triiodo-L-thyronine (T3), has been shown to modulate cellular processes via interactions with thyroid hormone receptors (TRs), but the secretory proteins that are regulated to exert these effects remain to be characterized. Brain-specific serine protease 4 (BSSP4), a member of the human serine protease family, participates in extracellular matrix remodeling. However, the physiological role and underlying mechanism of T3-mediated regulation of BSSP4 in hepatocellular carcinogenesis are yet to be established.
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Allicin protects rat cardiomyoblasts (H9c2 cells) from hydrogen peroxide-induced oxidative injury through inhibiting the generation of intracellular reactive oxygen species.
Int J Food Sci Nutr
PUBLISHED: 06-19-2014
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Abstract Oxidative stress is considered an important factor that promotes cell death in response to a variety of pathophysiological conditions. This study investigated the antioxidant properties of allicin, the principle ingredient of garlic, on preventing oxidative stress-induced injury. The antioxidant capacities of allicin were measured by using 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay and hydrogen peroxide (H2O2)-induced cell damage on H9c2 cardiomyoblasts. Allicin (0.3-10??M) pre-incubation could concentration-dependently attenuate the intracellular reactive oxygen species (ROS) increase induced by H2O2 on H9c2 cells. It could also protect H9c2 cells against H2O2-induced cell damage. However, the DPPH free radical scavenging activity of allicin was shown to be low. Therefore, it is believed that the protective effect of allicin on H9c2 cells could inhibit intracellular ROS production instead of scavenging extracellular H2O2 or free radicals. For the observed protective effect on H9c2 cells, allicin might also be effective in reducing free radical-induced myocardial cell death in ischemic condition.
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Psychometric evaluation, using Rasch analysis, of the WHOQOL-BREF in heroin-dependent people undergoing methadone maintenance treatment: further item validation.
Health Qual Life Outcomes
PUBLISHED: 05-30-2014
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The brief version of World Health Organization Quality of Life assessment (WHOQOL-BREF), a useful outcome measure for clinical decision making, has been evaluated using classical test theory (CTT) for psychometric properties on heroin-dependent patients. However, CTT has a major disadvantage of invalid summated score, and using Rasch models can overcome the shortcoming. The purpose of this study was using Rasch models to evaluate the psychometric properties of the WHOQOL-BREF for heroin-dependent patients, and the hypothesis was that each WHOQOL-BREF domain is unidimensional.
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Risk and impact of tuberculosis in patients with chronic myeloid leukemia: A nationwide population-based study in Taiwan.
Int. J. Cancer
PUBLISHED: 05-06-2014
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The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p?=?0.001) for both pulmonary (aHR 3.23, p?
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Psychometric evaluation of the Short Form 36 Health Survey (SF-36) and the World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF) for patients with schizophrenia.
Psychol Assess
PUBLISHED: 05-05-2014
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Quality-of-life (QoL) instruments measure the overall health status of people with schizophrenia, for whom the activities of daily life are often difficult. However, information on the psychometric properties of scores from the Short Form 36 Health Survey (SF-36) and the World Health Organization Quality of Life Scale Brief Version (WHOQOL-BREF), 2 commonly used generic QoL instruments in this population, is limited. Thus, we used a multitrait-multimethod analysis plus confirmatory factor analysis (CFA) to examine their psychometric properties. To test the reliability of their scores, we used methods of absolute reliability (standard error of measurement [SEM] and smallest real difference [SRD]) and relative reliability (i.e., intraclass correlation coefficient [ICC]). We recruited 100 patients with schizophrenia from a psychiatric hospital in southern Taiwan. All participants filled out the SF-36 and the WHOQOL-BREF at baseline and 2 weeks later. The participants' QoL scores were lower than those of the Taiwan general population (ps < .01), and CFA indicated that the constructs of QoL scores for the SF-36 (comparative fit index [CFI] = .918; incremental fit index [IFI] = .919; Tucker-Lewis index [TLI] = .885) and the WHOQOL-BREF (CFI = .967; IFI = .967; TLI = .900) were acceptable. The SEM and SRD analyses suggested that the total scores of the SF-36 (SEM% = 10.03%; SRD% = 27.80%) and of the WHOQOL-BREF (SEM% = 5.55%; SRD% = 15.40%) were reliable. Also, our results demonstrated that the WHOQOL-BREF scores were more reliable and valid than the SF-36 scores for assessing people with schizophrenia. The scores of both questionnaires were valid and reliable and detected different aspects of QOL in the population with schizophrenia.
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Combination of photoreactor and packed bed bioreactor for the removal of ethyl violet from wastewater.
Chemosphere
PUBLISHED: 04-26-2014
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An efficient treatment system that combines a photoreactor and packed bed bioreactor (PBR) was developed and evaluated for treating ethyl violet (EV)-containing wastewater. Initial experiments demonstrated that the optimal operating parameters for the photoreactor in treating EV-containing wastewater were 2h reaction time, pH of 7, and 2min liquid retention time. Under these conditions, the photocatalytic reaction achieved a 61% EV removal efficiency and resulted in a significant BOD/COD increase in the solution. The results displayed by the coupled photobiological system achieved a removal efficiency of 85% and EC50 of the solution increased by 19 times in a semi-continuous mode when the EV concentration was <150mgL(-)(1). The effect of shock loading on the EV removal was temporary but coexisting substrate (glucose and crystal violet) at specific levels would affect the EV removal efficiency of the PBR. Phylogenetic analysis in the PBR indicated that the major bacteria species were Bdellovibrio bacteriovorus, Ralstonia pickettii, Stenotrophomonas maltophilia, and Comamonas sp. Furthermore, the possible degrading mechanisms of this coupled system were demethylation, deethylation, aromatic ring opening, nitrification, and carbon oxidation. The intermediates were characterized using gas chromatography-mass spectrometry analysis. These results indicated that the coupled photobiological system provides an effective method of EV removal.
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Minimizing door-to-balloon time is not the most critical factor in improving clinical outcome of ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.
Crit. Care Med.
PUBLISHED: 04-11-2014
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We tested the hypothesis that, as compared with conventional door-to-balloon, shortened door-to-balloon time would further improve 30-day outcome in ST-elevation myocardial infarction patients undergoing primary stenting.
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Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy.
J Transl Med
PUBLISHED: 03-31-2014
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We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA).
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RevErb? preferentially deforms DNA by induced fit.
Chembiochem
PUBLISHED: 03-29-2014
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Using free-energy simulations, we have shown that RevErb?-induced DNA deformation preferentially occurs by induced fit rather than by conformational selection, even though the DNA is only slightly distorted in the complex. Our study shows that information on the sequence of binding events is needed to establish whether conformational selection or induced fit is operative, and that the presence of multiple apo-state structures might not be enough to distinguish between these binding models
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Measurement properties of streamlined wolf motor function test in patients at subacute to chronic stages after stroke.
Neurorehabil Neural Repair
PUBLISHED: 03-13-2014
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Background. Previous research using the streamlined Wolf Motor Function Test (SWMFT) has focused either on the 3- to 9-month period or on the >12-month period after stroke and lacked the information for those at 9 to 12 months. Whether SWMFT scores reflect motor deficit and recovery from early to late stages after stroke remains unclear. Objective. A retrospective study using the Functional Ability Scale (FAS) was conducted to evaluate whether all SWMFTs items measure the poststroke recovery of upper extremity (UE) motor function and if they could be used for patients within 9 to 12 months after a stroke. Methods. Rasch analysis was conducted, and data were drawn from patients 3 months to years after a stroke. Results. The continuum of UE motor function in SWMFT-FAS was supported. Subacute patients had the best motor function, followed by the 9- to 12-month group, and then chronic patients. Variation in UE motor function was large (2.35-2.72 logits), and motor abilities of these 3 groups overlapped. The 8 SWMFT items could target a broad range of UE motor function, from -8.28 to 7.80 logits. The average difficulty of these 8 items also matched the UE motor ability of the subgroup at 9 to 12 months after stroke, and individual versions of the SWMFT performed well to assess the motor ability of this group. Conclusions. The SWMFTs had sound hierarchical properties. The SWMFT-Chronic or the SWMFT-Subacute could be used to evaluate UE function of this subgroup at 9 to 12 months after stroke.
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Systems Biology of Lignin Biosynthesis in Populus trichocarpa: Heteromeric 4-Coumaric Acid:Coenzyme A Ligase Protein Complex Formation, Regulation, and Numerical Modeling.
Plant Cell
PUBLISHED: 03-11-2014
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As a step toward predictive modeling of flux through the pathway of monolignol biosynthesis in stem differentiating xylem of Populus trichocarpa, we discovered that the two 4-coumaric acid:CoA ligase (4CL) isoforms, 4CL3 and 4CL5, interact in vivo and in vitro to form a heterotetrameric protein complex. This conclusion is based on laser microdissection, coimmunoprecipitation, chemical cross-linking, bimolecular fluorescence complementation, and mass spectrometry. The tetramer is composed of three subunits of 4CL3 and one of 4CL5. 4CL5 appears to have a regulatory role. This protein-protein interaction affects the direction and rate of metabolic flux for monolignol biosynthesis in P. trichocarpa. A mathematical model was developed for the behavior of 4CL3 and 4CL5 individually and in mixtures that form the enzyme complex. The model incorporates effects of mixtures of multiple hydroxycinnamic acid substrates, competitive inhibition, uncompetitive inhibition, and self-inhibition, along with characteristic of the substrates, the enzyme isoforms, and the tetrameric complex. Kinetic analysis of different ratios of the enzyme isoforms shows both inhibition and activation components, which are explained by the mathematical model and provide insight into the regulation of metabolic flux for monolignol biosynthesis by protein complex formation.
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A comparison of bioelectricity in microbial fuel cells with aerobic and anaerobic anodes.
Environ Technol
PUBLISHED: 03-08-2014
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Microbial fuel cells (MFCs) can, besides running on wastewater, also derive energy directly from certain aquatic plants. However, few studies have focussed on electricity generation using aerobic anodes. This study presents a comparison of the MFC performances of an anaerobic-anode MFC (ana-MFC) and an aerobic-anode MFC (aa-MFC), and shows their individual conditions for optimal operation. Results show that the maximum power density of 7.07 +/- 0.45 mW/m2 for the ana-MFC occurred at 500 omega, whereas the aa-MFC had a maximum power density of 2.34 +/- 0.16 mW/m2 at 2200 omega. The ana-MFC generally achieved high electricity generation, and the aa-MFC achieved relatively high electricity generation when fed with a diluted substrate. In the ana-MFC, the optimal substrate for electricity generation was glucose (fermentable substrate); however, glucose and acetic acid (non-fermentable substrate) were both suitable substrates for the aa-MFC. The optimal gas retention times of the ana-MFC and the aa-MFC were 9 and 120 s, respectively. This retention time is an important limiting factor of electricity generation for the ana-MFC. The aa-MFCs fed with different substrates exhibited non-significant differences between bacterial communities. We observed the relative diversities of bacterial communities in the ana-MFC fed with various substrates. The results of denaturing gradient gel electrophoresis analysis suggest that Ochrobactrum intermedium, Delftia acidovorans, and Citrobacterfreundii may be potential electrogenic bacteria. To our knowledge, this is the first study comparing the MFC performances of anaerobic and aerobic anodes.
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Interleukin-32 increases human gastric cancer cell invasion associated with tumor progression and metastasis.
Clin. Cancer Res.
PUBLISHED: 03-06-2014
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The proinflammatory cytokine interleukin-32 (IL-32) is a novel tumor marker highly expressed in various human carcinomas, including gastric cancer. However, its effects on prognosis of patients with gastric cancer and cancer metastasis are virtually unknown at present. The main aim of this study was to explore the clinical significance of IL-32 in gastric cancer and further elucidate the molecular mechanisms underlying IL-32-mediated migration and invasion.
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Durable expression of minicircle DNA-liposome-delivered androgen receptor cDNA in mice with hepatocellular carcinoma.
Biomed Res Int
PUBLISHED: 03-06-2014
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The most common gene-based cancer therapies involve the suppression of oncogenic molecules and enhancement of the expression of tumor-suppressor genes. Studies in noncancer disease animal models have shown that minicircle (MC) DNA vectors are easy to deliver and that the proteins from said MC-carrying DNA vectors are expressed over a long period of time. However, delivery of therapeutic genes via a liposome-mediated, MC DNA complex has never been tested in vascular-rich hepatocellular carcinoma (HCC). Liposome-mediated DNA delivery exhibits high in vivo transfection efficiency and minimal systemic immune response, thereby allowing for repetitive interventions. In this study, we evaluated the efficacy of delivering an MC-liposome vector containing a 3.2?kb androgen receptor (AR; HCC metastasis suppressor) cDNA into Hepatitis B Virus- (HBV-) induced HCC mouse livers.
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Potential prognostic, diagnostic and therapeutic markers for human gastric cancer.
World J. Gastroenterol.
PUBLISHED: 02-28-2014
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The high incidence of gastric cancer (GC) and its consequent mortality rate severely threaten human health. GC is frequently not diagnosed until a relatively advanced stage. Surgery is the only potentially curative treatment. Thus, early screening and diagnosis are critical for improving prognoses in patients with GC. Gastroscopy with biopsy is an appropriate method capable of aiding the diagnosis of specific early GC tumor types; however, the stress caused by this method together with it being excessively expensive makes it difficult to use it as a routine method for screening for GC on a population basis. The currently used tumor marker assays for detecting GC are simple and rapid, but their use is limited by their low sensitivity and specificity. In recent years, several markers have been identi?ed and tested for their clinical relevance in the management of GC. Here, we review the serum-based tumor markers for GC and their clinical significance, focusing on discoveries from microarray/proteomics research. We also review tissue-based GC tumor markers and their clinical application, focusing on discoveries from immunohistochemical research. This review provides a brief description of various tumor markers for the purposes of diagnosis, prognosis and therapeutics, and we include markers already in clinical practice and various forthcoming biomarkers.
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Additional benefit of combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cell against sepsis-induced kidney injury.
J. Pineal Res.
PUBLISHED: 02-23-2014
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This study tested whether combined therapy with melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSCs) offered additional benefit in ameliorating sepsis-induced acute kidney injury. Adult male Sprague-Dawley rats (n = 65) were randomized equally into five groups: Sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating TNF-? level at post-CLP 6 hr was highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups (all P < 0.001). Immune reactivity as reflected in the number of splenic helper-, cytoxic-, and regulatory-T cells at post-CLP 72 hr exhibited the same pattern as that of circulating TNF-? among all groups (P < 0.001). The histological scoring of kidney injury and the number of F4/80+ and CD14+ cells in kidney were highest in CLP and lowest in SC groups, higher in CLP-melatonin than in CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, and higher in CLP-A-ADMSC than in CLP-melatonin-A-ADMSC groups (all P < 0.001). Changes in protein expressions of inflammatory (RANTES, TNF-1?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers, reactive-oxygen-species (NOX-1, NOX-2), and oxidative stress displayed a pattern identical to that of kidney injury score among the five groups (all P < 0.001). Expressions of antioxidants (GR+, GPx+, HO-1, NQO-1+) were lowest in SC group and highest in CLP-melatonin-A-ADMSC group, lower in CLP than in CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin- than in CLP-A-ADMSC-tretaed animals (all P < 0.001). In conclusion, combined treatment with melatonin and A-ADMSC was superior to A-ADMSC alone in protecting the kidneys from sepsis-induced injury.
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iPSC-derived human mesenchymal stem cells improve myocardial strain of infarcted myocardium.
J. Cell. Mol. Med.
PUBLISHED: 02-19-2014
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We investigated global and regional effects of myocardial transplantation of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) in infarcted myocardium. Acute myocardial infarction (MI) was induced by ligation of left coronary artery of severe combined immunodeficient mice before 2 × 10(5) iMSCs or cell-free saline were injected into peri-infarcted anterior free wall. Sham-operated animals received no injection. Global and regional myocardial function was assessed serially at 1-week and 8-week by segmental strain analysis by using two dimensional (2D) speckle tracking echocardiography. Early myocardial remodelling was observed at 1-week and persisted to 8-week with global contractility of ejection fraction and fractional area change in saline- (32.96 ± 14.23%; 21.50 ± 10.07%) and iMSC-injected (32.95 ± 10.31%; 21.00 ± 7.11%) groups significantly depressed as compared to sham control (51.17 ± 11.69%, P < 0.05; 34.86 ± 9.82%, P < 0.05). However, myocardial dilatation was observed in saline-injected animals (4.40 ± 0.62 mm, P < 0.05), but not iMSCs (4.29 ± 0.57 mm), when compared to sham control (3.74 ± 0.32 mm). Furthermore, strain analysis showed significant improved basal anterior wall strain (28.86 ± 8.16%, P < 0.05) in the iMSC group, but not saline-injected (15.81 ± 13.92%), when compared to sham control (22.18 ± 4.13%). This was corroborated by multi-segments deterioration of radial strain only in saline-injected (21.50 ± 5.31%, P < 0.05), but not iMSC (25.67 ± 12.53%), when compared to sham control (34.88 ± 5.77%). Improvements of the myocardial strain coincided with the presence of interconnecting telocytes in interstitial space of the infarcted anterior segment of the heart. Our results show that localized injection of iMSCs alleviates ventricular remodelling, sustains global and regional myocardial strain by paracrine-driven effect on neoangiogenesis and myocardial deformation/compliance via parenchymal and interstitial cell interactions in the infarcted myocardium.
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Health risk assessments of DEHP released from chemical protective gloves.
J. Hazard. Mater.
PUBLISHED: 02-06-2014
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The substance di-2-ethylhexyl phthalate (DEHP) is widely used as a plasticizer in chemical protective gloves to improve their flexibility and workability. However, it is possible that workers using protective gloves to handle various solvents may be exposed to DEHP leached by the solvents. Using an ASTM F739 permeation cell, it was found that BTEX solvents permeating through the glove samples dissolved DEHP from the gloves. Even without continuously contacting the permeant, DEHP was released from the contaminated glove samples during the desorption experiments. The DEHP leaching amounts were found to be inversely correlated to the permeability coefficients of BTEX in the glove samples. This result implied that the larger the amount of DEHP released from the glove samples, the higher the permeation resistance of gloves. Although chemical protective gloves provide adequate skin exposure protection to workers, the dermal exposure model developed herein indicates that leaching of DEHP from the glove samples may pose a potential health risk to the workers who handle BTEX. This study suggests that the selection of protective gloves should not only be concerned with the chemical resistance of the gloves but also the health risk associated with leaching of chemicals, such as DEHP, used in the manufacturing of the gloves.
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Inflammatory Myofibroblastic Tumours of the Urinary Bladder: Multi-Centre 18-Year Experience.
Urol. Int.
PUBLISHED: 01-15-2014
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Objective: To review a series of inflammatory myofibroblastic tumours (IMTs) of the urinary bladder in 10 hospitals in Hong Kong. Methods: A database search in the pathology archives of 10 hospitals in Hong Kong from 1995 to 2013 was performed using the key words 'inflammatory myofibroblastic tumour', 'inflammatory pseudotumour' and 'spindle cell lesion'. Patient characteristics, clinical features, histological features, immunohistochemical staining results and treatment outcomes were reviewed. Results: Nine cases of IMT of the urinary bladder were retrieved. The mean age was 45.4 ± 22.8 years (range 11-78). Eight patients (88.9%) presented with haematuria and 5 patients (55.6%) had anaemia with a mean haemoglobin level of 6.8 ± 1.3 g/dl. Histologically, the majority of patients (77.8%) had a compact spindle cell pattern. Anaplastic lymphoma kinase staining was positive in 75% of cases. During a mean follow-up period of 43.4 months (range 8-94), none of them developed any local recurrence or distant metastasis. Conclusions: A high index of suspicion of IMT should be maintained for young patients presenting with bleeding bladder tumours and significant anaemia. IMTs of the urinary bladder run a benign disease course, and good prognosis can be achieved after surgical resection. © 2014 S. Karger AG, Basel.
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MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in human gastric cancer.
Cancer Lett.
PUBLISHED: 01-13-2014
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MicroRNAs (miRNAs) play an important role to contribute carcinogenesis. The aim of the current study was to identify useful biomarkers from miRNAs. Differential miRNA profiles were analyzed using the miRNA qRT-PCR-based assay. Two of the most upregulated miRNAs were selected and validated. The miR-196a/-196b levels were significantly increased in gastric cancer (GC) tissues (n=109). Overexpression of miR-196a/-196b was significantly associated with tumor progression and poorer 5-year survival outcomes. Overexpression of miR-196a/-196b enhances GC cell migration and invasion. Further, radixin was identified as a target gene of miR-196a/-196b. Elevated miR-196a/-196b expression in GC cells led to reduced radixin protein levels and vice versa. Notably, an inverse correlation between miR-196a/-196b and radixin mRNA and protein expression was observed in GC tissues with in situ hybridization and immunohistochemistry analyses. Together, miR-196a/-196b inhibitory oligonucleotides or overexpression of the radixin may thus have therapeutic potential in suppressing GC metastasis.
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Pulmonary pleomorphic carcinoma with multiple metastases to the right posterior knee complicated by paraneoplastic hypercalcemia.
Oncol Lett
PUBLISHED: 01-08-2014
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In this report, we describe the case of a 46-year-old male who presented with a three-month history of progressive intermittent pain over the right posterior knee. Magnetic resonance imaging showed soft tissue masses over the right popliteal fossa. Surgery was performed, and histological examination revealed the mass to be a sarcomatoid carcinoma of poor differentiation. Fluorodeoxyglucose (FDG)-positron emission tomography showed FDG uptake in the lungs and in the right para-aortic and popliteal regions. On the basis of the morphological and immunohistochemical features of the specimens, the patient's condition was diagnosed as a pulmonary pleomorphic carcinoma with multiple metastases. Systemic chemotherapy was initiated with paclitaxel and cisplatin. The patient then developed paraneoplastic hypercalcemia and ultimately succumbed to healthcare-acquired pneumonia. The results of this rare case indicate that pulmonary pleomorphic carcinomas respond poorly to combination chemotherapy with paclitaxel and cisplatin. The firm mass in the popliteal fossa that was situated behind the knee was considered to be a Baker cyst; however, the possibility of malignant metastatic sarcomas, such as pulmonary sarcomatoid carcinoma, should be considered in the differential diagnosis. In conclusion, we emphasize that pretherapeutic examinations should be the basis for the diagnosis of a mass lesion at either an unusual or usual site.
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Melatonin augments apoptotic adipose-derived mesenchymal stem cell treatment against sepsis-induced acute lung injury.
Am J Transl Res
PUBLISHED: 01-01-2014
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This study investigated whether combining melatonin and apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) was superior to ADMSC alone in ameliorating sepsis-induced acute lung injury. Adult male Sprague-Dawley rats (n=50) were randomized equally into five groups: sham controls (SC), sepsis induced by cecal-ligation and puncture (CLP), CLP-melatonin, CLP-A-ADMSC, and CLP-melatonin-A-ADMSC. Circulating interleukin (IL)-6 at 6, 18, and 72 hrs, were highest in CLP and lowest in SC groups, higher in CLP-melatonin than CLP-A-ADMSC and CLP-melatonin-A-ADMSC groups, higher in CLP-A-ADMSC than CLP-melatonin-A-ADMSC groups (all p<0.001). Immune reactivity (indicated by circulating cytotoxic-, and regulatory-T cells) and WBC count at 72 h exhibited the same pattern as that of circulating IL-6 (all p<0.001). Changes in histological scoring of lung parenchyma and the number of CD68+ and CD14+ cells showed a similar pattern compared to that of IL-6 level in all groups (all p<0.001). Changes in protein expressions of inflammatory (oxidative stress, RANTES, TNF-?, NF-?B, MMP-9, MIP-1, IL-1?), apoptotic (cleaved caspase 3 and PARP, mitochondrial Bax), fibrotic (Smad3, TGF-?) markers and those of reactive-oxygen-species (NOX-1, NOX-2) displayed an identical pattern compared to that of circulating IL-6 in all groups (all p<0.001). Anti-oxidative capacities (GR+, GPx+, HO-1, NQO-1+) and angiogenesis marker (CXCR4+ cells) were lowest in SC group but highest in CLP-melatonin-A-ADMSC group, lower in CLP than CLP-melatonin and CLP-A-ADMSC groups, and lower in CLP-melatonin than CLP-A-ADMSC groups (all p<0.001). In conclusion, combined melatonin and A-ADMSC were superior to A-ADMSC alone in protecting the lung from sepsis-induced injury.
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Enhanced Cytotoxicity of Natural Killer Cells following the Acquisition of Chimeric Antigen Receptors through Trogocytosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. However, use of viral transduction methods raises the safety concern of viral integration into the NK cell genome. In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. Immunofluorescence analysis confirmed the localization of the anti-CD19 CARs on the NK cell surface. Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary B-ALL cells derived from patients. To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors.
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Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.
PLoS ONE
PUBLISHED: 01-01-2014
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To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1?. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1?, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.
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Psychometric evaluation of the internalized stigma of mental illness scale for patients with mental illnesses: measurement invariance across time.
PLoS ONE
PUBLISHED: 01-01-2014
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The current investigation examined the psychometric properties of the Internalized Stigma of Mental Illness (ISMI) scale in a sample of patients with mental illness. In addition to the internal consistency, test-retest reliability, and concurrent validity that previous studies have tested for the ISMI, we extended the evaluation to its construct validity and measurement invariance using confirmatory factor analysis (CFA).
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Surface scattering mechanisms of tantalum nitride thin film resistor.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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In this letter, we utilize an electrical analysis method to develop a TaN thin film resistor with a stricter spec and near-zero temperature coefficient of resistance (TCR) for car-used electronic applications. Simultaneously, we also propose a physical mechanism mode to explain the origin of near-zero TCR for the TaN thin film resistor (TFR). Through current fitting, the carrier conduction mechanism of the TaN TFR changes from hopping to surface scattering and finally to ohmic conduction for different TaN TFRs with different TaN microstructures. Experimental data of current-voltage measurement under successive increasing temperature confirm the conduction mechanism transition. A model of TaN grain boundary isolation ability is eventually proposed to influence the carrier transport in the TaN thin film resistor, which causes different current conduction mechanisms.
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Insulin and LiCl synergistically rescue myogenic differentiation of FoxO1 over-expressed myoblasts.
PLoS ONE
PUBLISHED: 01-01-2014
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Most recent studies reported that FoxO1 transcription factor was a negative regulator of myogenesis under serum withdrawal condition, a situation not actually found in vivo. Therefore, the role of FoxO1 in myogenesis should be re-examined under more physiologically relevant conditions. Here we found that FoxO1 was preferentially localized to nucleus in proliferating (PMB) and confluent myoblasts (CMB) and its nuclear exclusion was a prerequisite for formation of multinucleated myotubes (MT). The nuclear shuttling of FoxO1 in PMB could be prevented by leptomycin B and we further found that cytoplasmic accumulation of FoxO1 in myotubes was caused by the blockade of its nuclear import. Although over-expression of wildtype FoxO1 in C2C12 myoblasts significantly blocked their myogenic differentiation under serum withdrawal condition, application of insulin and LiCl, an activator of Wnt signaling pathway, to these cells successfully rescued their myogenic differentiation and generated myotubes with larger diameters. Interestingly, insulin treatment significantly reduced FoxO1 level and also delayed nuclear re-accumulation of FoxO1 triggered by mitogen deprivation. We further found that FoxO1 directly repressed the promoter activity of myogenic genes and this repression can be relieved by insulin and LiCl treatment. These results suggest that FoxO1 inhibits myogenesis in serum withdrawal condition but turns into a hypertrophy potentiator when other myogenic signals, such as Wnt and insulin, are available.
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Variant GADL1 and Response to Lithium Therapy in Bipolar I Disorder.
N. Engl. J. Med.
PUBLISHED: 12-25-2013
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Background Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. Methods We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. Results Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. Conclusions Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).
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SND1 Transcription Factor-Directed Quantitative Functional Hierarchical Genetic Regulatory Network in Wood Formation in Populus trichocarpa.
Plant Cell
PUBLISHED: 11-26-2013
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Wood is an essential renewable raw material for industrial products and energy. However, knowledge of the genetic regulation of wood formation is limited. We developed a genome-wide high-throughput system for the discovery and validation of specific transcription factor (TF)-directed hierarchical gene regulatory networks (hGRNs) in wood formation. This system depends on a new robust procedure for isolation and transfection of Populus trichocarpa stem differentiating xylem protoplasts. We overexpressed Secondary Wall-Associated NAC Domain 1s (Ptr-SND1-B1), a TF gene affecting wood formation, in these protoplasts and identified differentially expressed genes by RNA sequencing. Direct Ptr-SND1-B1-DNA interactions were then inferred by integration of time-course RNA sequencing data and top-down Graphical Gaussian Modeling-based algorithms. These Ptr-SND1-B1-DNA interactions were verified to function in differentiating xylem by anti-PtrSND1-B1 antibody-based chromatin immunoprecipitation (97% accuracy) and in stable transgenic P. trichocarpa (90% accuracy). In this way, we established a Ptr-SND1-B1-directed quantitative hGRN involving 76 direct targets, including eight TF and 61 enzyme-coding genes previously unidentified as targets. The network can be extended to the third layer from the second-layer TFs by computation or by overexpression of a second-layer TF to identify a new group of direct targets (third layer). This approach would allow the sequential establishment, one two-layered hGRN at a time, of all layers involved in a more comprehensive hGRN. Our approach may be particularly useful to study hGRNs in complex processes in plant species resistant to stable genetic transformation and where mutants are unavailable.
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Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism.
Autophagy
PUBLISHED: 11-11-2013
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The thyroid hormone, T 3, regulates cell growth, differentiation and development through binding to the nuclear thyroid hormone receptor (THR), a member of the steroid/TR superfamily of ligand-dependent transcriptional factors. T 3 modulates lipid metabolism in liver, although the detailed molecular mechanisms are unclear at present. Here, by a microarray analysis, we identified a novel chromosome 19 open reading frame 80 (C19orf80) which was activated by T 3. T 3 stimulation led to upregulation of both mRNA and protein levels of C19orf80. Immunofluorescence analysis revealed a vesicle-like pattern of C19orf80 around lipid droplets or within the lysosome-associated compartment in cells. Furthermore, T 3 treatment as well as C19orf80 overexpression specifically activated the autophagic response and lipid metabolism, as observed from lipidated LC3 (LC3-II) and levels of oxygen consumption rate, respectively. Reciprocally, knockdown of C19orf80 obstructed T 3-activated autophagy and lipolysis. Moreover, treatment with autolysosome maturation inhibitors, ammonium chloride and chloroquine, not only suppressed the T 3-activated autophagic process but also lipid metabolism. Our results collectively suggested that T 3 regulates lipid metabolism through a C19orf80-activated autophagic process.
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Choroidal thickness in patients with a history of retinopathy of prematurity.
JAMA Ophthalmol
PUBLISHED: 10-01-2013
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The cause of reduced vision in patients with a history of retinopathy of prematurity (ROP) is not yet fully understood. The role of the choroid in ROP remains unknown and existing studies of choroidal thickness in patients with a history of ROP are limited. It might be helpful to understand the association of the choroid with ROP by measuring the choroidal thickness in patients with a history of ROP and correlating these findings with the visual outcome of these patients.
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Impact of chronic obstructive pulmonary disease on patient with acute myocardial infarction undergoing primary percutaneous coronary intervention.
Biomed J
PUBLISHED: 08-29-2013
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Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD) patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7%) with diagnosis of COPD and 1430 (90.3%) without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726). However, the hospitalization duration was notably longer (p = 0.003), the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02). Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO) (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012), multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI.
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Measurement equivalence across child self-reports and parent-proxy reports in the Chinese version of the pediatric quality of life inventory version 4.0.
Child Psychiatry Hum Dev
PUBLISHED: 08-24-2013
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An important assumption for comparing childrens quality of life (QoL) between childrens and parents perceptions is that measurement equivalence/invariance (ME/I) exists. The ME/I across the child- and parent-reported Chinese PedsQL was examined, and the latent means between child self-reports and parent-proxy reports were compared. Third-grade to sixth-grade children (n = 519) and their parents (n = 270) respectively completed the child- and parent-reported PedsQL. Seventy-eight parents completed parent-proxy reports twice. Full ME/I across child and parent reports was found in first- and second-order factor loadings. Partial ME/I was supported in item intercepts and item residual variances. The latent means of child self-reports and of parent-proxy reports were not significantly different, which suggested interchangeability between child- and parent-reported PedsQL. The ME/I results support the use of PedsQL scores to compare childrens and parents perceptions of childrens QoL.
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Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4.
Biochem. Biophys. Res. Commun.
PUBLISHED: 08-06-2013
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Triiodothyronine (T3) is a potent form of thyroid hormone mediates several physiological processes including cellular growth, development, and differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent studies have demonstrated critical roles of T3/TR in tumor progression. Moreover, long-term hypothyroidism appears to be associated with the incidence of human hepatocellular carcinoma (HCC), independent of other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein that antagonizes the canonical Wnt signaling pathway, is induced by T3 at both mRNA and protein levels in HCC cell lines. However, the mechanism underlying T3-mediated regulation of DKK4 remains unknown. In the present study, the 5 promoter region of DKK4 was serially deleted, and the reporter assay performed to localize the T3 response element (TRE). Consequently, we identified an atypical direct repeat TRE between nucleotides -1645 and -1629 conferring T3 responsiveness to the DKK4 gene. This region was further validated using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells suppressed cell invasion and metastatic potential, both in vivo andin vitro, via reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings collectively suggest that DKK4 upregulated by T3/TR antagonizes the Wnt signal pathway to suppress tumor cell progression, thus providing new insights into the molecular mechanism underlying thyroid hormone activity in HCC.
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Cardiovascular disease risk reduction in rural China: a clustered randomized controlled trial in Zhejiang.
Trials
PUBLISHED: 07-24-2013
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Cardiovascular disease (CVD) is a major cause of death in China. Despite government efforts, the majority of hypertensive and diabetic patients in China do not receive proper treatment. Reducing CVD events requires long-term care that is proactive, patient-centred, community-based, and sustainable. We have designed a package of interventions for patients at high risk of CVD to be implemented by family doctors based in township hospitals (providers of primary care) in rural Zhejiang, China. This trial aims to determine whether the systematic CVD risk reduction package results in reduced CVD events among patients at risk of CVD compared with usual care, and whether the package is cost-effective and suitable for routine implementation and scale-up.
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Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan: A prospective cohort study.
Drug Alcohol Rev
PUBLISHED: 06-30-2013
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Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines.
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Child-rated versus parent-rated quality of life of community-based obese children across gender and grade.
Health Qual Life Outcomes
PUBLISHED: 06-23-2013
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Quality of life (QoL), which can be examined using self-reports or parental reports, might help healthcare providers understand obese childrens subjective well-being in several domains of life. Community-based obese children report their QoL lower than their parents do. However, the differences between child- and parent-reported QoL have neither been tested across gender and grade nor analyzed by item. This study probed the relationship between obesity and QoL item scores in children, and compared child-reported with parent-reported QoL stratified by gender and grade.
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Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B.
J. Clin. Oncol.
PUBLISHED: 06-17-2013
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The role of antiviral prophylaxis in preventing hepatitis B virus (HBV) reactivation before rituximab-based chemotherapy in patients with lymphoma and resolved hepatitis B is unclear.
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Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-04-2013
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Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ?15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)--a bicyclic diterpenoid lactone isolated from Andrographis paniculata--and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP-GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP-GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras.
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Comparison of prognostic models for patients with diffuse large B-cell lymphoma in the rituximab era.
Ann. Hematol.
PUBLISHED: 05-25-2013
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Several revisions of International Prognostic Index (IPI) have been proposed for patients with diffuse large B-cell lymphoma (DLBCL) after the introduction of rituximab. Expanding evidence suggests that baseline absolute lymphocyte count (ALC) is also an independent factor for outcome prediction. We investigated the optimal prognostic model for these patients in the rituximab era. The study enrolled 274 consecutive patients with DLBCL receiving first-line cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapy with rituximab between 2003 and 2009. Five factors within IPI and ALC were entered for Cox regression analysis. Overall survival (OS) and progression-free survival were calculated for different risk groups of models. Efficacy of models was compared by the value of Akaike information criterion (AIC). Revised IPI (R-IPI) and ALC/R-IPI, but not IPI, were informative to discriminate between different risk groups. In multivariate analysis for individual factors of the prognostic models, performance status >1 [odds ratio (OR) 3.59], Ann Arbor stage III or IV (OR 2.24), and ALC <1?×?10?/L (OR, 2.75) remained significant. Another modified score based on the three factors divided patients into four risk groups and the 3-year OS rate was 93, 77, 39, and 13 %, respectively. By comparing AIC values in the Cox proportional hazards model, the modified three-factor model was the superior prognostic model followed by established ALC/R-IPI, R-IPI, and standard IPI. In conclusion, the addition of the novel factor, ALC, interacts with other established factors in outcome prediction for DLBCL. Development of a new score is needed for a better risk stratification in the rituximab era and would be helpful in the design of future clinical trials. The proposed three-factor model should be validated in large-scale studies.
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Objective measurement of weekly physical activity and sensory modulation problems in children with attention deficit hyperactivity disorder.
Res Dev Disabil
PUBLISHED: 05-21-2013
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This study aimed to objectively compare the daily physical activity (PA), as indicated by moderate-to-vigorous physical activity (MVPA) during a week and metabolic equivalents (METs) per minute, between children with attention deficit hyperactivity disorder (ADHD) and typically developing children. Moreover, sensory modulation problems were examined using behavioral and physiological measures. Twenty boys with ADHD (mean age 8.64 ± 2.57 years), and 20 matched typically developing boys (mean age 9.10 ± 1.79 years) participated in our study. Each child wore a PA monitor for 14 h a day, seven days a week. All participants parents were asked to fill out daily activity logs for their children. The problems of sensory modulation were detected using sensory profile (SP) questionnaires and Sensory Challenge Protocol that measured electrodermal response (EDR) to repeated sensory stimulation. Compared with the controls, the children with ADHD had a generally higher level of PA (1.48 ± 0.10 vs. 1.60 ± 0.12 METs/min; p=001), and tended to spend more time in MVPA on weekdays (35.71%) and the weekend (57.14%). However, when analyzing hourly recorded PA, the group differences were obvious only for certain hours. Our data suggested that children with ADHD were more hyperactive in structure-free than structured settings. The ADHD group showed their sensory modulation problems on the SP but not on the EDR. We found some correlations between sensory modulation problems and hyperactivity in children with ADHD.
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Predictors for changes in various developmental outcomes of children with cerebral palsy--a longitudinal study.
Res Dev Disabil
PUBLISHED: 05-11-2013
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We aimed to identify predictors for the changes of various developmental outcomes in preschool children with cerebral palsy (CP). Participants were 78 children (49 boys, 29 girls) with CP (mean age: 3 years, 8 months; SD: 1 year, 7 months; range: 1 year to 5 years, 6 months). We examined eight potential predictors: age, sex, CP subtype, Gross Motor Function Classification System (GMFCS) level, selective motor control, Modified Ashworth Scale, and the spinal alignment (SA) and range of motion subscales of the Spinal Alignment and Range of Motion Measure (SAROMM). Developmental outcomes for cognition, language, self-help, and social and motor functions were measured at baseline and a 6-month follow-up with the Comprehensive Developmental Inventory for Infants and Toddlers. Regression model showed GMFCS level was a negative predictor for change of language (adjusted r(2)=0.30, p<.001), motor function (adjusted r(2)=0.26, p<.001), social function (adjusted r(2)=0.07, p=0.014), and self-help (adjusted r(2)=0.26, p<.001). Age was a negative predictor for change of cognition (adjusted r(2)=0.21, p<.001) and language functions (adjusted r(2)=0.26, p<.001). SAROMM-SA was a negative predictor for cognitive change (adjusted r(2)=0.30, p<.001). The GMFCS levels and age are robust negative predictors for change of most developmental domains in these children.
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Elimination of high concentration hydrogen sulfide and biogas purification by chemical-biological process.
Chemosphere
PUBLISHED: 05-03-2013
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A chemical-biological process was performed to remove a high concentration of H2S in biogas. The high iron concentration tolerance (20gL(-1)) of Acidithiobacillus ferrooxidans CP9 provided sufficient ferric iron level for stable and efficient H2S elimination. A laboratory-scale apparatus was setup for a 45 d operation to analyze the optimal conditions. The results reveal that the H2S removal efficiency reached 98% for 1500ppm H2S. The optimal ferric iron concentration was kept between 9 and 11gL(-1) with a cell density of 10(8)CFUg(-1) granular activated carbon and a loading of 15gSm(-3)h(-1). In pilot-scale studies for biogas purification, the average inlet H2S concentration was 1645ppm with a removal efficiency of up to 97% for a 311d operation and an inlet loading 40.8gSm(-3)h(-1). When 0.1% glucose was added, the cell density increased twofold under the loading of 65.1gSm(-3)h(-1) with an H2S removal efficiency still above 96%. The analysis results of the distribution of microorganisms in the biological reactor by DGGE show that microorganism populations of 96.7% and 62.7% were identical to the original strain at day 200 and day 311, respectively. These results clearly demonstrate that ferric iron reduction by H2S and ferrous iron oxidation by A. ferrooxidans CP9 are feasible processes for the removal of H2S from biogas.
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Prevalence, correlates, and risk perception of HIV infection among heroin users in Central Taiwan.
Kaohsiung J. Med. Sci.
PUBLISHED: 04-25-2013
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We investigated the prevalence and correlated factors of human immunodeficiency virus (HIV) among heroin users attending methadone maintenance treatment (MMT) programs in Central Taiwan, and explored the degree of risk perception of HIV infection among the participants. Our study participants were 781 heroin users seeking treatment at the MMT program at Tsaotun Psychiatric Center in Taiwan. The presence of HIV antibodies was identified by microparticle enzyme immunoassay and confirmed by western blot. Multivariate logistic regression was used to identify the independent correlates of HIV infection. The mean age of the sample was 36.1 years [standard deviation (SD) = 7.6]; of the patients, 710 (90.9%) were men. The prevalence of HIV infection among our study population was 20.7%. Multivariate logistic regression analysis revealed that HIV infection was independently associated with the age of the patients of initial heroin use, heroin injection use, nondrug-related criminal convictions, needle-sharing behaviors, and sharing injection paraphernalia. A strong agreement existed between self-reported HIV serostatus and the results of laboratory analyses, with 88.8% of patients reporting their condition correctly. We found a high rate of HIV infection among patients in the MMT program. Factors associated with HIV infection were mostly related to drug-use behaviors. These findings stress the importance of education regarding drug-risk behaviors.
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Basic psychometric properties of the transfer assessment instrument (version 3.0).
Arch Phys Med Rehabil
PUBLISHED: 04-19-2013
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To refine the Transfer Assessment Instrument (TAI 2.0), develop a training program for the TAI, and analyze the basic psychometric properties of the TAI 3.0, including reliability, standard error of measurement (SEM), minimal detectable change (MDC), and construct validity.
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Sitagliptin therapy enhances the number of circulating angiogenic cells and angiogenesis-evaluations in vitro and in the rat critical limb ischemia model.
Cytotherapy
PUBLISHED: 04-10-2013
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We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis.
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Effect of matured compost as an inoculating agent on odour removal and maturation of vegetable and fruit waste compost.
Environ Technol
PUBLISHED: 03-28-2013
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The use of matured compost as an inoculation agent to improve the composting of vegetable and fruit wastes in a laboratory-scale composter was evaluated, and the commercial feasibility of this approach in a pilot-scale (1.8 x 10(4) L) composter was subsequently confirmed. The effect of aeration rate on the physico-chemical and biological properties of compost was also studied. Aeration rate affected the fermentation temperature, moisture content, pH, O2 consumption rate, CO2 production rate and the formation of odour. The optimal aeration rate was 2.5 L air/kg dry solid/min. The CO2 production rate approached the theoretical value during composting and was linearly dependent on temperature, indicating that the compost system had good operating characteristics. The inoculation of cellulolytic bacteria and deodorizing bacteria to compost in the pilot-scale composter led to an 18.2% volatile solids loss and a 64.3% volume reduction ratio in 52 h; only 1.5 ppm(v) odour was detected. This is the first study to focus on both operating performance and odour removal in a pilot-scale composter.
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The removal of kaolinite suspensions by acid-soluble and water-soluble chitosans.
Environ Technol
PUBLISHED: 03-28-2013
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Chitosan is a potential substitute for traditional aluminium salts in water treatment systems. This research compared the coagulant performance of acid-soluble chitosan with water-soluble chitosan and with coagulant mixtures of chitosan and aluminium sulfate (alum). We also assessed the coagulant performance of chitosan and poly-aluminium chloride (PAC) to remove kaolinite from turbid water. In addition, we evaluated their respective coagulation efficiencies under different coagulant concentrations, degrees of turbidity (NTU) and pH levels. Furthermore, we determined the size and settling velocity of flocs formed by these coagulants in order to illustrate major factors affecting kaolinite coagulation. The optimal concentrations of acid- versus water- soluble chitosan required to remove kaolinite from a 300 NTU suspension were 4.0 and 10.0 mg/l, respectively-with individual efficiencies of 79.3 and 92.4%, in that order. Optimum concentrations ofwater-soluble chitosan demonstrated a broader range than that of acid-soluble chitosan. In addition, it is of note that chitosan/alum and chitosan/PAC water-soluble coagulant mixtures demonstrated much wider ranges of optimal concentrations for turbidity reduction than either alum or PAC alone. Moreover, our water-soluble chitosan coagulant mixtures produced denser floc with elevated settling velocities that favour cost savings relevant to both installation and operational expenses. Based on our observations of these noteworthy performances, we confidently propose that a coagulant mixture with a 1:1 mass ratio of chitosan and alum presents a remarkably more cost-effective alternative to the use of chitosan alone in water treatment systems.
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Impact of extracorporeal membrane oxygenation support on clinical outcome of pediatric patients with acute cardiopulmonary failure: a single-center experience.
Biomed J
PUBLISHED: 03-22-2013
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Conventional therapy against acute pediatric cardiopulmonary failure (APCPF) caused by a variety of disease entities remains unsatisfactory with extremely high morbidity and mortality. For refractory APCPF, extracorporeal membrane oxygenation (ECMO) is one of the last resorts.
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Simvastatin attenuates the additive effects of TNF-? and IL-18 on the connexin 43 up-regulation and over-proliferation of cultured aortic smooth muscle cells.
Cytokine
PUBLISHED: 03-11-2013
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Statin therapy is known to down-regulate inflammatory activities in atheromatous tissues of animals. The aims of this study were to examine the regulatory role of interleukin-18 (IL-18) in the connexin 43 (Cx43) and the proliferation of cultured aortic smooth muscle cells (SMCs) as well as to elucidate the underlying therapeutic mechanism of simvastatin. Vytorin therapy significantly alleviated high-cholesterol diet-induced hypercholesterolemia, suppressed neointimal hyperplasia, macrophage infiltration, and Cx43 and IL-18 expression in rabbit aortic walls. In vitro study using an aortic SMC line showed that IL-18 up-regulated constitutive Cx43 expression and potentiated tumor necrosis factor-? (TNF-?)-triggered Akt and MAPK signaling pathways. Simvastatin treatment alone reduced constitutive Cx43 levels and prevented the TNF-?-induced IL-18 up-regulation. Mechanistic investigation using kinase-specific inhibitors showed that simvastatin pretreatment attenuated TNF-?-elicited Akt and ERK1/2 phosphorylation, whereas PI3K and all MAPK activities were also implied in the additive effect of TNF-? and IL-18 on Cx43 up-regulation. Proliferation assay indicated that IL-18 stimulated SMC proliferation and synergized the TNF-?-stimulated cell proliferation. Likewise, simvastatin treatment suppressed the SMC over-proliferation induced not only by TNF-? alone, but also by simultaneous treatment with TNF-? and IL-18. The suppression of simvastatin in SMC proliferation was not mediated through mitochondrial related pro-apoptogenesis under both scenarios. In conclusion, simvastatin attenuates the additive effects of TNF-? and IL-18 on Cx43 up-regulation and over-proliferation of aortic SMCs, mainly through the blockade of Akt signaling pathway. These findings may fortify the rationale underlying the atheroprotective mechanism of statin therapy.
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Benefit of combined therapy with nicorandil and colchicine in preventing monocrotaline-induced rat pulmonary arterial hypertension.
Eur J Pharm Sci
PUBLISHED: 02-28-2013
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This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p<0.001). Pulmonary damage severity (thickened alveolar septum and pulmonary arteriolar wall, decreased alveolar-sac numbers), number of CD3+ cells, and protein expressions of inflammatory (MMP-9, NF-?B, VCAM-1, angiotensin II-receptor), apoptotic (Bax, caspase 3, cleaved PARP), and fibrotic (TGF-?, Smad3) biomarkers showed an identical pattern compared to that of RVSBP, whereas pulmonary expressions of anti-apoptotic (Bcl-2) and anti-fibrotic (BMP-2, Smad1/5) biomarkers displayed a reverse pattern (all p<0.01). The protein expressions of RV damage markers (BNP, caspase 3) were increased, whereas expression of biomarker for RV functional preservation (Cx43) was reduced in group 2 compared with group 1, elevated in groups 3 and 4 compared to group 2, and further increased in group 5 (all p<0.01). Combined therapy with nicorandil and colchicine is superior to either alone in attenuating MCT-induced PAH in rats.
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Thyroid hormone regulation of miR-21 enhances migration and invasion of hepatoma.
Cancer Res.
PUBLISHED: 02-26-2013
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Thyroid hormone (T(3)) signaling through the thyroid hormone receptor (TR?1) regulates hepatoma cell growth and pathophysiology, but the underlying mechanisms are unclear at present. Here, we have shown that the oncomir microRNA-21 (miR-21) is activated by T(3) through a native T(3) response element in the primary miR-21 promoter. Overexpression of miR-21 promoted hepatoma cell migration and invasion, similar to that observed with T(3) stimulation in hepatoma cells. In addition, anti-miR-21-induced suppression of cell migration was rescued by T(3). The Rac-controlled regulator of invasion and metastasis, T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally downregulated by T(3). Attenuation and overexpression of miR-21 induced upregulation and downregulation of TIAM1, respectively. TIAM1 attenuation, in turn, enhanced migration and invasion via the upregulation of ?-catenin, vimentin, and matrix metalloproteinase-2 in hepatoma cells. Notably, correlations between TR?1, miR-21, and TIAM1 expression patterns in animal models paralleled those observed in vitro. In the clinic, we observed a positive correlation (P = 0.005) between the tumor/nontumor ratios of TR?1 and miR-21 expression, whereas a negative correlation (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma. Our findings collectively indicate that miR-21 stimulation by T(3) and subsequent TIAM1 suppression promotes hepatoma cell migration and invasion.
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Effects of peptide concentration on remineralization of eroded enamel.
J Mech Behav Biomed Mater
PUBLISHED: 02-14-2013
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Promoting remineralization to repair eroded enamel is a promising therapy in clinics. In this study, biocompatible asparagine-serine-serine (NSS) peptide chelates free ions from artificial saliva through charged functional groups, and subsequently form nano-hydroxyapatite crystals to partially repair erosive lesions. The nanomechanical properties, cross-sectional microstructure, types of deposited minerals, and subsurface microstructure of enamel at various treatment stages were characterized by nanoindentation, scanning electron microscopy (SEM), X-ray diffraction (XRD), and transmission electron microscopy (TEM), respectively. The results revealed that the nanohardness and elastic modulus of eroded enamel increase with peptide concentration, particularly for the 3NSS peptide system. In contrast, the structure of the 5NSS peptide is larger and longer, leading to increasing difficulty in penetrating to the deep acid-eroded regions; therefore, the remineralization effect was restricted to the top enamel surface. The 3NSS peptide with high concentration promoted the formation of smaller, finer, and staggered nanohydroxyapatite crystals. The enamel remineralized with a 100?M 3NSS exhibited the highest degree of nanohardness recovery (34%), resulting from subsurface crystalline regrowth.
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Necrotizing scleritis after strabismus surgery in thyroid eye disease.
J AAPOS
PUBLISHED: 02-06-2013
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Surgically induced necrotizing scleritis, which can lead to potentially devastating consequences, is a rare sequela to many types of ocular surgeries. We describe a 58-year-old woman who developed necrotizing scleritis following strabismus surgery for thyroid ophthalmopathy. Tectonic corneal patch grafting resulted in a favorable outcome.
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Molecular functions of thyroid hormones and their clinical significance in liver-related diseases.
Biomed Res Int
PUBLISHED: 02-04-2013
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Thyroid hormones (THs) are potent mediators of several physiological processes, including embryonic development, cellular differentiation, metabolism, and cell growth. Triiodothyronine (T3) is the most biologically active TH form. Thyroid hormone receptors (TRs) belong to the nuclear receptor superfamily and mediate the biological functions of T3 via transcriptional regulation. TRs generally form heterodimers with the retinoid X receptor (RXR) and regulate target genes upon T3 stimulation. Research over the past few decades has revealed that disruption of cellular TH signaling triggers chronic liver diseases, including alcoholic or nonalcoholic fatty liver disease and hepatocellular carcinoma (HCC). Animal model experiments and epidemiologic studies to date imply close associations between high TH levels and prevention of liver disease. Moreover, several investigations spanning four decades have reported the therapeutic potential of T3 analogs in lowering lipids, preventing chronic liver disease, and as anticancer agents. Thus, elucidating downstream genes/signaling pathways and molecular mechanisms of TH actions is critical for the treatment of significant public health issues. Here, we have reviewed recent studies focusing on the roles of THs and TRs in several disorders, in particular, liver diseases. We also discuss the potential therapeutic applications of THs and underlying molecular mechanisms.
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Paradoxical impairment of angiogenesis, endothelial function and circulating number of endothelial progenitor cells in DPP4-deficient rat after critical limb ischemia.
Stem Cell Res Ther
PUBLISHED: 02-04-2013
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INTRODUCTION: We hypothesized that dipeptidyl peptidase-IV (DPP4) may impair angiogenesis, endothelial function, and the circulating number of endothelial progenitor cells (EPC) in a model of critical limb ischemia (CLI) through ligating the left femoral artery using DPP4-deficient rats. METHODS: Adult male DPP4-deficient (DPP4D) rats (n = 18) were equally divided into CLI only (DPP4D-CLI) and CLI treated by granulocyte colony-stimulating factor (GCSF) (DPP4D-CLI-GCSF). For comparison, age-matched wild-type (WT) Fischer 344 rats (n = 18) were randomized into two groups receiving identical treatment compared to their DPP4-deficient counterparts and labeled as WT-CLI (n = 9) and WT-CLI-GCSF (n = 9), respectively. RESULTS: The circulating number of EPCs (CD31+, CD34+, CD133, C-kit+) was significantly lower in DPP4-deficient than in WT rats on post-CLI days 1 and 4 (all P < 0.01). The ratio of ischemia/normal blood flow was remarkably lower in DPP4D-CLI-GCSF rats than in WT-CLI-GCSF animals on post-CLI Day 14 (all P < 0.01). Protein expressions of pro-angiogenic factors (endothelial nitric oxide synthase (eNOS), CXCR4, SDF-1?, vascular endothelial growth factor (VEGF)) were remarkably higher in WT-CLI than in DPP4D-CLI rats, and higher in WT-CLI-GCSF than in DPP4D-CLI-GCSF animals (all P < 0.01). Moreover, the numbers of small vessel in the ischemic area were substantially higher in WT-CLI-GCSF than in DPP4D-CLI-GCSF rats (P < 0.001). Furthermore, vasorelaxation and nitric oxide production of the normal femoral artery were significantly reduced in DPP4-deficient than in WT Fischer rats (all P < 0.01). CONCLUSIONS: Contrary to our hypothesis, DPP4-deficient rats were inferior to age-matched WT Fischer rats in terms of angiogenesis, endothelial function, circulating EPC number and response to GCSF, suggesting a positive role of DPP4 in maintaining vascular function and tissue perfusion in this experimental setting.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.