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Find video protocols related to scientific articles indexed in Pubmed.
Aromaticity Evaluations of Planar [6]Radialenes.
Org. Lett.
PUBLISHED: 11-20-2014
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The aromatic character of fused polycyclic systems varies with the nature of their annulated rings. Computed extra cyclic resonance energies (ECREs) reveal that the central six membered rings (6MRs) of the heterocyclic fused congeners 1-5 are "[6]radialene-like", but that the central 6MRs of triphenylene 9, coronene 10, and isocoronene 11 are "benzene-like." Comparisons with geometric (harmonic oscillator model of aromaticity, HOMA) and magnetic (nucleus independent chemical shifts, NICS) criteria illustrate the multifaceted nature of aromaticity in 1-11.
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Examining the Risks of Cardiac Arrhythmia and Mortality among New-Generation Macrolides, Fluoroquinolones, and Beta-Lactam/Beta-Lactamase Inhibitor: A Nationwide Study.
Clin. Infect. Dis.
PUBLISHED: 11-20-2014
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?Previous studies have demonstrated increased cardiovascular mortality related to azithromycin and levofloxacin. Risks associated with alternative drugs in the same class, including clarithromycin and moxifloxacin, were unknown. We used the Taiwan National Health Insurance Database to perform a nationwide, population-based study that compares the risks of ventricular arrhythmia and cardiovascular death among these antibiotics.
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In situ observation of facet-dependent oxidation of graphene on platinum in an environmental TEM.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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We performed a direct observation of a crystal facet-dependent oxidation of graphene layers on platinum nanocrystals at atomic resolution in an environmental transmission electron microscope. Combined with density functional theory calculations, our work provides a novel approach for the dynamical exploration of the facet-dependent reactions at the atomic level.
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Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Gut
PUBLISHED: 11-20-2014
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Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population.
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Arabidopsis DOK1 encodes a functional dolichol kinase involved in reproduction.
Plant J.
PUBLISHED: 11-06-2014
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Dolichol phosphate (Dol-P) serves as a carrier of complex polysaccharides during protein glycosylation. Dol-P is synthesized by the phosphorylation of dolichol or the monodephosphorylation of dolichol pyrophosphate (Dol-PP); however, the enzymes that catalyze these reactions remain unidentified in Arabidopsis thaliana. We performed a genome-wide search for cytidylyltransferase motif-containing proteins in Arabidopsis and found that At3g45040 encodes a protein homologous with Sec59p, a dolichol kinase (DOK) in Saccharomyces cerevisiae. At3g45040, designated AtDOK1, complemented defects in the growth and N-linked glycosylation of the S. cerevisiae sec59 mutant, suggesting that AtDOK1 encodes a functional DOK. To characterize the physiological roles of AtDOK1 in planta, we isolated two independent lines of T-DNA-tagged AtDOK1 mutants, dok1-1 and dok1-2. The heterozygous plants showed developmental defects in male and female gametophytes, including an aberrant pollen structure, low pollen viability, and short siliques. Additionally, the mutations had incomplete penetrance. These results suggest that AtDOK1 is a functional DOK required for reproductive processes in Arabidopsis. This article is protected by copyright. All rights reserved.
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The 9-homocubyl cation rearrangement revisited.
Chem. Commun. (Camb.)
PUBLISHED: 11-06-2014
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Complexity of the potential energy surface of the 9-homocubyl cation is revealed by Born-Oppenheimer molecular dynamics simulations and high ab initio levels. The stereospecific automerizations observed experimentally involve bridged ions, which have either an aromatic or an anti-aromatic character. New pathways leading to more stable isomers are unveiled.
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Method Validation of a Tricyclic Antidepressant Drug Panel in Urine by UPLC-MS/MS.
Ann. Clin. Lab. Sci.
PUBLISHED: 11-02-2014
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Tricyclic antidepressant (TCA) drugs are also used as adjunctive therapy to treat chronic pain. To monitor patient compliance to therapy, urine specimens may be preferred since collection is non-invasive, and the specimen can provide a longer detection window. TCA drugs are frequently monitored by immunoassay; however, poor antibody specificity may compromise results. The purpose for this study was to develop a confirmation method for determining TCA in urine specimens by ultra-pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Our method can quantify 9 TCA drugs in less than 5 min. Method validation experiments were performed, and the coefficient variation for inter- and intra-day precision was within 12% for each analyte at five different concentrations. Accuracy studies had good agreement with another laboratory that performs testing by GC/MS.
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Structural Studies and Anticancer Activity of a Novel Class of ?-Peptides.
Chem Asian J
PUBLISHED: 10-11-2014
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Functionalized oligomeric organic compounds with well-defined ?-proline scaffold have been synthesized by a cycloadditive oligomerization approach in racemic and enantiopure forms. The structure of the novel ?-peptides was investigated by NMR spectroscopic and X-ray methods determining the conformational shapes of the ?-proline oligomers in solution and solid states. The main structural elements subject to conformational switches are ?-peptide bonds between 5-arylpyrrolidine-2-carboxylic acid units existing in Z/E configurations. The whole library of short ?-peptides and intermediate acrylamides has been tested on antiproliferative activity towards the hormone-refractory prostate cancer cell line PC-3 revealing several oligomeric compounds with low micromolar and submicromolar activities. Bromine-substituted dimeric and trimeric acrylamides induced caspase-dependent apoptosis of PC-3 cells through cell-cycle arrest and mitochondrial damage.
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Evaluation of a new pediatric positive airway pressure mask.
J Clin Sleep Med
PUBLISHED: 09-15-2014
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The choice and variety of pediatric masks for continuous positive airway pressure (CPAP) is limited in the US. Therefore, clinicians often prescribe modified adult masks. Until recently a mask for children aged < 7 years was not available. This study evaluated apnea-hypopnea index (AHI) equivalence and acceptability of a new pediatric CPAP mask for children aged 2-7 years (Pixi; ResMed Ltd, Sydney, Australia).
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Electrochemically induced surface metal migration in well-defined core-shell nanoparticles and its general influence on electrocatalytic reactions.
ACS Nano
PUBLISHED: 09-05-2014
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Bimetallic nanoparticle catalysts provide enhanced activity, as combining metals allows tuning of electronic and geometric structure, but the enhancement may vary during the reaction because the nanoparticles can undergo metal migration under catalytic reaction conditions. Using cyclic voltammetry to track the surface composition over time, we carried out a detailed study of metal migration in a well-defined model Au-Pd core-shell nanocatalyst. When subjected to electrochemical conditions, Au migration from the core to the shell was observed. The effect of Pd shell thickness and electrolyte identity on the extent of migration was studied. Migration of metals during catalytic ethanol oxidation was found to alter the particle's surface composition and electronic structure, enhancing the core-shell particles' activity. We show that metal migration in core-shell nanoparticles is a phenomenon common to numerous electrochemical systems and must be considered when studying electrochemical catalysis.
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Protonation states of the tryptophan synthase internal aldimine active site from solid-state NMR spectroscopy: direct observation of the protonated Schiff base linkage to pyridoxal-5'-phosphate.
J. Am. Chem. Soc.
PUBLISHED: 09-03-2014
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The acid-base chemistry that drives catalysis in pyridoxal-5'-phosphate (PLP)-dependent enzymes has been the subject of intense interest and investigation since the initial identification of PLP's role as a coenzyme in this extensive class of enzymes. It was first proposed over 50 years ago that the initial step in the catalytic cycle is facilitated by a protonated Schiff base form of the holoenzyme in which the linking lysine ?-imine nitrogen, which covalently binds the coenzyme, is protonated. Here we provide the first (15)N NMR chemical shift measurements of such a Schiff base linkage in the resting holoenzyme form, the internal aldimine state of tryptophan synthase. Double-resonance experiments confirm the assignment of the Schiff base nitrogen, and additional (13)C, (15)N, and (31)P chemical shift measurements of sites on the PLP coenzyme allow a detailed model of coenzyme protonation states to be established.
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Molecular encapsulation beyond the aperture size limit through dissociative linker exchange in metal-organic framework crystals.
J. Am. Chem. Soc.
PUBLISHED: 08-29-2014
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Under linker exchange conditions, large guests with molecular diameters 3-4 times the framework aperture size have been encapsulated into preformed nanocrystals of the metal-organic framework ZIF-8. Guest encapsulation is facilitated by the formation of short-lived "open" states of the pores upon linker dissociation. Kinetic studies suggested that linker exchange reactions in ZIF-8 proceed via a competition between dissociative and associative exchange mechanisms, and guest encapsulation was enhanced under conditions where the dissociative pathway predominates.
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Comparing HbA1c, fasting and 2-h plasma glucose for screening for abnormal glucose regulation in patients undergoing coronary angiography.
Clin. Chem. Lab. Med.
PUBLISHED: 08-27-2014
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Abstract Background: We aimed to investigate the prevalence of undiagnosed abnormal glucose regulation (AGR, including diabetes and prediabetes) in patients undergoing coronary angiography (CAG) by using both glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to screen, and to compare the performance of fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), and HbA1c for screening for AGR. Methods: Eligible patients were adults without known diabetes who were admitted for CAG. Patients' glucose regulation status was defined by conducting HbA1c and OGTT 2-4 weeks after hospital discharge. The performance of FPG, 2hPG, and HbA1c for detecting AGR was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 689 subjects were included. According to OGTT, the prevalence rates of diabetes and prediabetes were 19.9% and 41.7%, respectively. The corresponding values were 28.0% and 60.4%, respectively, when HbA1c was adopted as a diagnostic criterion in addition to OGTT. For detecting diabetes, the area under the ROC curve (AUC) was higher for HbA1c than for FPG (0.87 vs. 0.80, p=0.005), but was not significantly different from that for 2hPG (0.87 vs. 0.88, p=0.58). For detecting AGR, the AUC was higher for HbA1c than for either FPG (0.94 vs. 0.74, p<0.001) or 2hPG (0.94 vs. 0.83, p<0.001). Conclusions: Using HbA1c and OGTT to screen, we reported an extremely high prevalence of previously undiagnosed AGR (28.0% diabetes and 60.4% prediabetes) in patients admitted for CAG. HbA1c may be adopted as an alternative to OGTT for screening for AGR in patients undergoing CAG.
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Terfenadine induces anti-proliferative and apoptotic activities in human hormone-refractory prostate cancer through histamine receptor-independent Mcl-1 cleavage and Bak up-regulation.
Naunyn Schmiedebergs Arch. Pharmacol.
PUBLISHED: 08-26-2014
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Although the results of several studies have underscored the regulatory effect of H1-histamine receptors in cell proliferation of some cancer cell types, its effect in prostate cancers remains unclear. We have therefore studied the effect of terfenadine (an H1-histamine receptor antagonist) in prostate cancer cell lines. Our data demonstrate that terfenadine was effective against PC-3 and DU-145 cells (two prostate cancer cell lines). In contrast, based on the sulforhodamine B assay, loratadine had less potency while fexofenadine and diphenhydramine had little effect. Terfenadine induced the cleavage of Mcl-1 cleavage into a pro-apoptotic 28-kDa fragment and up-regulation of Bak, resulting in the loss of mitochondrial membrane potential (??m) and the release of cytochrome c and apoptosis-inducing factor into the cytosol. The activation of caspase cascades was detected to be linked to terfenadine action. Bak up-regulation was also examined at both the transcriptional and translational levels, and Bak activation was validated based on conformational change to expose the N terminus. Terfenadine also induced an indirect-but not direct-DNA damage response through the cleavage and activation of caspase-2, phosphorylation and activation of Chk1 and Chk2 kinases, phosphorylation of RPA32 and acetylation of Histone H3; these processes were highly correlated to severe mitochondrial dysfunction and the activation of caspase cascades. In conclusion, terfenadine induced apoptotic signaling cascades against HRPCs in a sequential manner. The exposure of cells to terfenadine caused the up-regulation and activation of Bak and the cleavage of Mcl-1, leading to the loss of ??m and activation of caspase cascades which further resulted in DNA damage response and cell apoptosis.
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Diatomological investigation in sphenoid sinus fluid and lung tissue from cases of suspected drowning.
Forensic Sci. Int.
PUBLISHED: 08-20-2014
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We report on the presence, distribution and numbers of diatoms within specific organs as a result of drowning in fresh, treated and seawater. Specimens of sphenoid sinus fluid and lung tissue from 100 cases of suspected drowning and 20 cases where death was by natural causes, to act as a control, were examined for the presence of diatoms. In the 100 cases where the deceased was suspected to have drowned, 94 were confirmed as a death by drowning after autopsy with the other six being reported as death by another cause. No diatoms were found in cases confirmed as death by causes unrelated to drowning, with the exception of possible contamination via open wounds and through decomposition. In 94 cases, where all fatalities were confirmed as death by drowning, there were 81 cases in which diatoms were detected in samples taken from the sphenoid sinus fluid and/or lung tissue. No, or only few, diatoms were observed from the samples where the deceased drowned in treated waters such as spa or swimming pools. A significantly higher number of diatoms were detected in the sphenoid sinus fluid and lung tissue of confirmed drowning cases in fresh water compared to seawater. More diatoms were observed in sphenoid sinus fluid compared to lung tissue regardless of the water in which the deceased drowned. This study illustrates the potential use of diatom screening using both sphenoid sinus fluid and lung tissue to determine the cause of death in suspected cases of drowning. This report also highlights specific variables that need to be considered prior to such as conclusion being reached.
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A novel adaptive servoventilation (ASVAuto) for the treatment of central sleep apnea associated with chronic use of opioids.
J Clin Sleep Med
PUBLISHED: 08-15-2014
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To compare the efficacy and patient comfort of a new mode of minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto-titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA) associated with chronic use of opioid medications.
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Long-term outcomes after dialysis-requiring acute kidney injury.
Biomed Res Int
PUBLISHED: 08-12-2014
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AKI-dialysis patients had a higher incidence of long-term ESRD and mortality than the patients without AKI. The patients who recovered from dialysis were associated with a lower incidence of long-term ESRD and mortality than in the patients who still required dialysis.
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The pathological effects of CCR2+ inflammatory monocytes are amplified by an IFNAR1-triggered chemokine feedback loop in highly pathogenic influenza infection.
J. Biomed. Sci.
PUBLISHED: 07-28-2014
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BackgroundHighly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1¿+¿CD11b¿+¿myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection.ResultsWe established H1N1 IAV-infected mouse models using three viruses of varying pathogenicity and noted the accumulation of a defined Gr1¿+¿CD11b¿+¿myeloid population correlating with the pathogenicity. Herein, we reported that CCR2+ inflammatory monocytes are the major cell compartments in this population. Of note, impaired clearance of the high pathogenicity virus prolonged IFN expression, leading to CCR2+ inflammatory monocytes amplifying their own recruitment via an interferon-¿/ß receptor 1 (IFNAR1)-triggered chemokine loop. Blockage of IFNAR1-triggered signaling or inhibition of viral replication by Oseltamivir significantly suppresses the expression of CCR2 ligands and reduced the influx of CCR2+ inflammatory monocytes. Furthermore, trafficking of CCR2+ inflammatory monocytes from the bone marrow to the lung was evidenced by a CCR2-dependent chemotaxis. Importantly, leukocyte infiltration, cytokine storm and expression of iNOS were significantly reduced in CCR2¿/¿ mice lacking infiltrating CCR2+ inflammatory monocytes, enhancing the survival of the infected mice.ConclusionsOur results indicated that uncontrolled viral replication leads to excessive production of inflammatory innate immune responses by accumulating CCR2+ inflammatory monocytes, which contribute to the fatal outcomes of high pathogenicity virus infections.
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Surfactant-directed atomic to mesoscale alignment: metal nanocrystals encased individually in single-crystalline porous nanostructures.
J. Am. Chem. Soc.
PUBLISHED: 07-23-2014
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Composite nanomaterials are attractive for a diverse range of applications in catalysis, plasmonics, sensing, imaging, and biology. In such composite nanomaterials, it is desired, yet still challenging to create a controlled alignment between components with lattices in disparate scales. To address this challenge, we report a new concept of colloidal synthesis, in which self-assembled molecular layers control the alignment between materials during the synthesis. To illustrate this concept, self-assembled cetyltrimethylammonium bromide (CTAB) molecules are used to control interfaces in a core-shell nanocomposite with a well-defined metal nanocrystal core and a metal-organic-framework (MOF) shell, which differ in structural dimensions by orders of magnitude. We show that single metal nanocrystals are captured individually in single-crystalline MOFs, and an alignment between the {100} planes of the metal and {110} planes of the MOFs is observed. By utilizing the same concept, a layer of mesostructured silica is formed over MOF crystals. These multilayered core-shell structures demonstrate a controlled alignment across a wide range of materials, from the metal nanocrystals, extending to nanoporous MOFs and mesostructured silica.
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Risk of Parkinson's disease following severe constipation: A nationwide population-based cohort study.
Parkinsonism Relat. Disord.
PUBLISHED: 07-18-2014
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Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample.
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The impact of acute kidney injury on the long-term risk of stroke.
J Am Heart Assoc
PUBLISHED: 07-17-2014
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The incidence of acute kidney injury (AKI) requiring dialysis in hospitalized patients is increasing; however, information on the long-term incidence of stroke in patients surviving to discharge after recovering from AKI after dialysis has not been reported.
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Hyperplastic polyps identified during screening endoscopy: reevaluated by histological examinations and genetic alterations.
J. Formos. Med. Assoc.
PUBLISHED: 06-26-2014
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Screening colonoscopy is one of the most effective methods to detect and prevent colorectal cancer by removing neoplastic polyps. The recent discovery of serrated polyps with neoplastic potential has reclassified these polyps into hyperplastic polyps (HPs), sessile serrated adenoma (SSA), and traditional serrated adenoma (TSA) on the basis of macroscopic morphology and microscopic histology. In this study, we aimed to revisit HPs identified during screening endoscopy by histological reevaluation and genetic alterations.
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Selective deposition of Ru nanoparticles on TiSi? nanonet and its utilization for Li?O? formation and decomposition.
J. Am. Chem. Soc.
PUBLISHED: 06-16-2014
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The Li-O2 battery promises high capacity to meet the need for electrochemical energy storage applications. Successful development of the technology hinges on the availability of stable cathodes. The reactivity exhibited by a carbon support compromises the cyclability of Li-O2 operation. A noncarbon cathode support has therefore become a necessity. Using a TiSi2 nanonet as a high surface area, conductive support, we obtained a new noncarbon cathode material that corrects the deficiency. To enable oxygen reduction and evolution, Ru nanoparticles were deposited by atomic layer deposition onto TiSi2 nanonets. A surprising site-selective growth whereupon Ru nanoparticles only deposit onto the b planes of TiSi2 was observed. DFT calculations show that the selectivity is a result of different interface energetics. The resulting heteronanostructure proves to be a highly effective cathode material. It enables Li-O2 test cells that can be recharged more than 100 cycles with average round-trip efficiencies >70%.
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Shaped Pd-Ni-Pt core-sandwich-shell nanoparticles: influence of Ni sandwich layers on catalytic electrooxidations.
ACS Nano
PUBLISHED: 06-11-2014
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Shape-controlled metal nanoparticles (NPs) interfacing Pt and nonprecious metals (M) are highly active energy conversion electrocatalysts; however, there are still few routes to shaped M-Pt core-shell NPs and fewer studies on the geometric effects of shape and strain on catalysis by such structures. Here, well-defined cubic multilayered Pd-Ni-Pt sandwich NPs are synthesized as a model platform to study the effects of the nonprecious metal below the shaped Pt surface. The combination of shaped Pd substrates and mild reduction conditions directs the Ni and Pt overgrowth in an oriented, layer-by-layer fashion. Exposing a majority of Pt(100) facets, the catalytic performance in formic acid and methanol electro-oxidations (FOR and MOR) is assessed for two different Ni layer thicknesses and two different particle sizes of the ternary sandwich NPs. The strain imparted to the Pt shell layer by the introduction of the Ni sandwich layer (Ni-Pt lattice mismatch of ?11%) results in higher specific initial activities compared to core-shell Pd-Pt bimetallic NPs in alkaline MOR. The trends in activity are the same for FOR and MOR electrocatalysis in acidic electrolyte. However, restructuring in acidic conditions suggests a more complex catalytic behavior from changes in composition. Notably, we also show that cubic quaternary Au-Pd-Ni-Pt multishelled NPs, and Pd-Ni-Pt nanooctahedra can be generated by the method, the latter of which hold promise as potentially highly active oxygen reduction catalysts.
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Neoadjuvant bevacizumab and chemoradiotherapy in locally advanced rectal cancer: early outcome and technical impact on toxicity.
World J Surg Oncol
PUBLISHED: 06-05-2014
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We aimed to evaluate early clinical and pathological results for treating locally advanced rectal cancer with bevacizumab and neoadjuvant concurrent chemoradiotherapy using the technique of prone-position volumetric modulated arc therapy and to compare the toxicity of volumetric modulated arc therapy with that of supine-position four-field box radiotherapy.
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Severe Hepatic Injury Associated with Different Statins in Patients with Chronic Liver Disease: A Nationwide Population-based Cohort Study.
J. Gastroenterol. Hepatol.
PUBLISHED: 06-03-2014
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The hepatotoxicity of statins in patients with chronic liver diseases remains unclear. In this study, we aimed to estimate the risk of severe hepatic injury associated with different statins in patients with chronic liver disease.
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Fast Track Ultrasound Protocol to Detect Acute Complications After Totally Implantable Venous Access Device Placement.
Ann. Surg. Oncol.
PUBLISHED: 06-02-2014
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The role of ultrasound examination in detection of postprocedure complications from totally implantable venous access devices (TIVAD) placement is still uncertain. In a cohort of 665 cancer outpatients, we assessed a quick ultrasound examination protocol in early detection of mechanical complications of catheterization.
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Evaluation of endoscopic salpingectomy for sterilization of female Formosan macaques (Macaca cyclopis).
Am. J. Primatol.
PUBLISHED: 05-16-2014
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We evaluated the safety and postsurgical outcomes of endoscopic salpingectomy for sterilization of female Formosan macaques (Macaca cyclopis) as a method of population control. Nineteen adult female Formosan macaques were included in our study. The fallopian tubes of each anesthetized macaque were cauterized and excised endoscopically using a 2.7-mm rigid endoscope system. We recorded the complications encountered, and objectively scored the amount of hemorrhage throughout the procedure. Postoperative ovarian function was evaluated by monitoring the serum levels of sex hormones in ten of the macaques for two ovarian cycles following the salpingectomy. Two to 13 months later, eight of the 19 macaques underwent laparoscopy for the objective evaluation of inflammation at the surgical sites on the fallopian tubes. No major anesthetic- or surgical-associated complications were observed in any of the macaques. The hormonal evaluation showed cyclic ovarian function after salpingectomy in all of the ten macaques examined, and the parameters were comparable to those of other macaque species. The long-term postoperative level of inflammation at the surgical site was minimal to low, and was lower than that reported for other tubal occlusion techniques used in macaques. The use of a 2.7-mm rigid endoscope for salpingectomy in macaques is safe and efficient, with fewer postoperative complications than comparable sterilization techniques. Am. J. Primatol. © 2014 Wiley Periodicals, Inc.
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Amino acid networks in a (?/?)? barrel enzyme change during catalytic turnover.
J. Am. Chem. Soc.
PUBLISHED: 05-02-2014
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Proteins can be viewed as small-world networks of amino acid residues connected through noncovalent interactions. Nuclear magnetic resonance chemical shift covariance analyses were used to identify long-range amino acid networks in the ? subunit of tryptophan synthase both for the resting state (in the absence of substrate and product) and for the working state (during catalytic turnover). The amino acid networks observed stretch from the surface of the protein into the active site and are different between the resting and working states. Modification of surface residues on the network alters the structural dynamics of active-site residues over 25 Å away and leads to changes in catalytic rates. These findings demonstrate that amino acid networks, similar to those studied here, are likely important for coordinating structural changes necessary for enzyme function and regulation.
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Weight loss reduces serum monocyte chemoattractant protein-1 concentrations in association with improvements in renal injury in obese men with metabolic syndrome.
Clin. Chem. Lab. Med.
PUBLISHED: 05-01-2014
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Abstract Background: Monocyte chemoattractant protein-1 (MCP-1) is involved in obesity-related renal injury. The aim of the present study was to examine the effects of weight loss on changes in MCP-1 and markers of renal injury, specifically serum cystatin C (S-CysC) and urinary N-acetyl glucosaminidase (UNAG), in obese people. Methods: In this prospective study, 40 obese men with metabolic syndrome (MetS) participated in a 3-month dietary and exercise intervention. Twenty-eight subjects completed the study with a ?5% weight loss. Circulating MCP-1, S-CysC and UNAG to creatinine ratio (UNCR) were determined before and after the weight loss program. Results: Obesity-associated components of MetS demonstrated significant improvements after the weight loss program. In addition, at baseline, circulating MCP-1 concentrations were positively correlated with UNCR and S-CysC levels. After weight loss, blood MCP-1 and UNCR levels were significantly decreased, but S-CysC was not affected. Using multiple linear regression analysis, there was a significant relationship between changes in UNCR and MCP-1 after adjusting for other potential confounding factors. Conclusions: Weight loss may improve renal tubular injury by ameliorating obesity-related inflammation in obese men with MetS.
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Formyl Peptide receptor 1 expression is associated with tumor progression and survival in gastric cancer.
Anticancer Res.
PUBLISHED: 04-30-2014
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Formyl peptide receptor 1 (FPR1) as a regulator of innate inflammatory response has been implicated in tumor progression of gliomas. The purpose of the present study was to evaluate the prognostic significance and the ligand-receptor interaction of FPR1 in gastric cancer (GC).
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ARGONAUTE PIWI domain and microRNA duplex structure regulate small RNA sorting in Arabidopsis.
Nat Commun
PUBLISHED: 04-19-2014
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Small RNAs (sRNAs) are loaded into ARGONAUTE (AGO) proteins to induce gene silencing. In plants, the 5'-terminal nucleotide is important for sRNA sorting into different AGOs. Here we show that microRNA (miRNA) duplex structure also contributes to miRNA sorting. Base pairing at the 15th nucleotide of a miRNA duplex is important for miRNA sorting in both Arabidopsis AGO1 and AGO2. AGO2 favours miRNA duplexes with no middle mismatches, whereas AGO1 tolerates, or prefers, duplexes with central mismatches. AGO structure modelling and mutational analyses reveal that the QF-V motif within the conserved PIWI domain contributes to recognition of base pairing at the 15th nucleotide of a duplex, while the DDDE catalytic core of AtAGO2 is important for recognition of the central nucleotides. Finally, we rescued the adaxialized phenotype of ago1-12, which is largely due to miR165 loss-of-function, by changing miR165 duplex structure which we predict redirects it to AGO2.
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Fatal falls from height in Taiwan.
J. Forensic Sci.
PUBLISHED: 04-16-2014
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This study conducts an investigation of fatal falls from height, examines gender differences, and compares our findings with those of Western countries. We review deaths in Taiwan caused by falls from height that underwent forensic autopsy from 1994 to 2010. Among the examined cases, 182 were suicide, 156 were accidents, and 18 were homicides. Men who fell from greater heights had a lower probability of fatal head trauma (p = 0.045), and women exhibited a lower fatal head trauma rate when falling from heights of between 10 and 25 m in accident group (p = 0.003). There was no significant difference between cases of falling from greater and lower heights within the suicide group (p = 0.834). Psychiatric illness was only reported in 20.3% and 28.8% cases in suicide and accident groups. Only in male cases was the use of psychotropic substances higher in the suicide groups than in the accident groups (p = 0.047).
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A novel small molecule hybrid of vorinostat and DACA displays anticancer activity against human hormone-refractory metastatic prostate cancer through dual inhibition of histone deacetylase and topoisomerase I.
Biochem. Pharmacol.
PUBLISHED: 04-06-2014
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Vorinostat, which is an extensively studied inhibitor against histone deacetylase (HDAC), shows limited clinical activity to solid tumors. WJ35435, a new hybrid of vorinostat and DACA (a topoisomerase inhibitor) potently inhibited HDAC activity (in particular HDAC1 and HDAC6) in kinase assay and cell-based examination. The anti-HDAC effect was confirmed by the induction of histone H3 acetylation and phosphorylation, ?-tubulin acetylation and ?-H2AX formation. WJ35435 showed better potency than vorinostat and DACA against PC-3 and DU-145, two human hormone-refractory metastatic prostate cancer (HRMPC) cell lines, but not benign prostate cells. WJ35435 at differential concentrations induced G1- or G2-phase arrest of the cell cycle in HRMPCs but not in benign prostate cells. WJ35435 induced the formation of topoisomerase I-DNA cleavable complexes but not type-II? or -II?. Topoisomerase activity assay confirmed the selective inhibition of topoisomerase I. WJ35435 induced profound DNA damage using comet tailing assay. WJ35435 was less effective than camptothecin and etoposide in inducing the phosphorylation and activation of Chk1, Chk2 and RPA32 which were crucial coordinators in DNA repair pathway, indicating a low DNA repair activity to WJ35435 action. Furthermore, WJ35435 showed an in vivo antitumor activity. A synergistic apoptosis (combination index=0.55) was obtained in combination between WJ35435 and MG-132 (a proteasome inhibitor). In summary, WJ35435 is a dual-targeted anticancer hybrid induces anti-HDAC and anti-topoisomerase I activities that cause DNA damage associated with a low DNA repair capability, and induce cell cycle arrest at G1- and G2-phase. Ultimately, WJ35435 inhibits cell proliferation and induces apoptosis of HRMPCs.
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Effectiveness and safety of extracranial carotid stent placement: A nationwide self-controlled case-series study.
J. Formos. Med. Assoc.
PUBLISHED: 04-03-2014
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Carotid angioplasty and stent (CAS) placement has emerged as an attractive revascularization strategy for patients with internal carotid artery stenosis. However, the effectiveness and safety of CAS were not fully evaluated, mainly because of methodological difficulties in finding an appropriate comparison group.
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Different angiotensin receptor blockers and incidence of diabetes: a nationwide population-based cohort study.
Cardiovasc Diabetol
PUBLISHED: 03-31-2014
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Angiotensin receptor blockers (ARBs) have been shown to exert various peroxisome proliferator-activated receptor gamma (PPAR?) binding activities and insulin-sensitizing effects. The objective of this study was to investigate the association of different ARBs with new-onset diabetes mellitus.
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Optimized metal-organic-framework nanospheres for drug delivery: evaluation of small-molecule encapsulation.
ACS Nano
PUBLISHED: 02-14-2014
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We have developed a general synthetic route to encapsulate small molecules in monodisperse zeolitic imid-azolate framework-8 (ZIF-8) nanospheres for drug delivery. Electron microscopy, powder X-ray diffraction, and elemental analysis show that the small-molecule-encapsulated ZIF-8 nanospheres are uniform 70 nm particles with single-crystalline structure. Several small molecules, including fluorescein and the anticancer drug camptothecin, were encapsulated inside of the ZIF-8 framework. Evaluation of fluorescein-encapsulated ZIF-8 nanospheres in the MCF-7 breast cancer cell line demonstrated cell internalization and minimal cytotoxicity. The 70 nm particle size facilitates cellular uptake, and the pH-responsive dissociation of the ZIF-8 framework likely results in endosomal release of the small-molecule cargo, thereby rendering the ZIF-8 scaffold an ideal drug delivery vehicle. To confirm this, we demonstrate that camptothecin encapsulated ZIF-8 particles show enhanced cell death, indicative of internalization and intracellular release of the drug. To demonstrate the versatility of this ZIF-8 system, iron oxide nanoparticles were also encapsulated into the ZIF-8 nanospheres, thereby endowing magnetic features to these nanospheres.
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Do ?-conjugative effects facilitate SN2 reactions?
J. Am. Chem. Soc.
PUBLISHED: 02-13-2014
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Rigorous quantum chemical investigations of the SN2 identity exchange reactions of methyl, ethyl, propyl, allyl, benzyl, propargyl, and acetonitrile halides (X = F(-), Cl(-)) refute the traditional view that the acceleration of SN2 reactions for substrates with a multiple bond at C? (carbon adjacent to the reacting C? center) is primarily due to ?-conjugation in the SN2 transition state (TS). Instead, substrate-nucleophile electrostatic interactions dictate SN2 reaction rate trends. Regardless of the presence or absence of a C? multiple bond in the SN2 reactant in a series of analogues, attractive C?(?(+))···X(?(-)) interactions in the SN2 TS lower net activation barriers (E(b)) and enhance reaction rates, whereas repulsive C?(?(-))···X(?(-)) interactions increase E(b) barriers and retard SN2 rates. Block-localized wave function (BLW) computations confirm that ?-conjugation lowers the net activation barriers of SN2 allyl (1t, coplanar), benzyl, propargyl, and acetonitrile halide identity exchange reactions, but does so to nearly the same extent. Therefore, such orbital interactions cannot account for the large range of E(b) values in these systems.
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Brain-derived neurotrophic factor, but not body weight, correlated with a reduction in depression scale scores in men with metabolic syndrome: a prospective weight-reduction study.
Diabetol Metab Syndr
PUBLISHED: 02-11-2014
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Obesity, a critical component of metabolic syndrome (MetS), is associated with depression. Deficiency of brain-derived neurotrophic factor (BDNF) is involved in the mechanism of depression. We hypothesized that weight reduction would improve depressive symptoms via increasing BDNF levels in obese men.
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Switches of hydrogen bonds during ligand-protein association processes determine binding kinetics.
J. Mol. Recognit.
PUBLISHED: 02-10-2014
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Revealing the processes of ligand-protein associations deepens our understanding of molecular recognition and binding kinetics. Hydrogen bonds (H-bonds) play a crucial role in optimizing ligand-protein interactions and ligand specificity. In addition to the formation of stable H-bonds in the final bound state, the formation of transient H-bonds during binding processes contributes binding kinetics that define a ligand as a fast or slow binder, which also affects drug action. However, the effect of forming the transient H-bonds on the kinetic properties is little understood. Guided by results from coarse-grained Brownian dynamics simulations, we used classical molecular dynamics simulations in an implicit solvent model and accelerated molecular dynamics simulations in explicit waters to show that the position and distribution of the H-bond donor or acceptor of a drug result in switching intermolecular and intramolecular H-bond pairs during ligand recognition processes. We studied two major types of HIV-1 protease ligands: a fast binder, xk263, and a slow binder, ritonavir. The slow association rate in ritonavir can be attributed to increased flexibility of ritonavir, which yields multistep transitions and stepwise entering patterns and the formation and breaking of complex H-bond pairs during the binding process. This model suggests the importance of conversions of spatiotemporal H-bonds during the association of ligands and proteins, which helps in designing inhibitors with preferred binding kinetics.
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Examining the association of olmesartan and other angiotensin receptor blockers with overall and cause-specific mortality.
Hypertension
PUBLISHED: 02-10-2014
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Concerns about an increased cardiovascular risk with the angiotensin receptor blocker, olmesartan, prompted the current study to examine associations between olmesartan and other angiotensin receptor blockers with overall and cause-specific mortalities. We collected patients who started to use losartan, valsartan, irbesartan, candesartan, telmisartan, and olmesartan between January 1, 2004, and December 31, 2009, from Taiwan's National Health Insurance claims database. Prescribed drug types, dosage, and other clinical information were collected. Overall mortality and cause-specific mortality were ascertained through linkages with Taiwan's National Death Registry. Two follow-up analyses, labeled intention-to-treat and as-treated, were conducted. A Cox proportional hazard regression model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI) using losartan as the reference group. A total of 690 463 subjects were included, with a mean follow-up ranging from a low of 2.8 years for olmesartan to a high of 4.1 years for irbesartan. Subjects who began with valsartan had a modest but significantly increased risk of overall mortality (HR, 1.04; 95% CI, 1.02-1.06) compared with losartan. Irbesartan (HR, 0.96; 95% CI, 0.94-0.99), candesartan (HR, 0.95; 95% CI, 0.92-0.99), telmisartan (HR, 0.93; 95% CI, 0.90-0.96), and olmesartan (HR, 0.93; 95% CI, 0.88-0.97) were associated with a slightly lower overall mortality risk than losartan. The analysis indicates that the differences in mortality risk among individual angiotensin receptor blockers were only marginal and thus less likely to be clinically important. Although uncontrolled confounding might still exist, olmesartan does not seem to increase cardiovascular risk compared with losartan.
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Use of inhaled corticosteroids in patients with COPD and the risk of TB and influenza: A systematic review and meta-analysis of randomized controlled trials. a systematic review and meta-analysis of randomized controlled trials.
Chest
PUBLISHED: 02-08-2014
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Background: The use of inhaled corticosteroids (ICSs) is associated with an increased risk of pneumonia in patients with COPD. However, the risks of other respiratory infections, such as TB and influenza, remain unclear.Methods: Through a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and ClinicalTrials.gov from inception to July 2013, we identified randomized controlled trials of ICS therapy lasting at least 6 months. We conducted meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate summary estimates comparing ICS with non-ICS treatment on the risk of TB and influenza.Results: Twenty-fi ve trials (22,898 subjects) for TB and 26 trials (23,616 subjects) for influenza were included. Compared with non-ICS treatment, ICS treatment was associated with a significantly higher risk of TB (Peto OR, 2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24;95% CI, 0.94-1.63). Results were similar with each meta-analytic approach. Furthermore, the number needed to harm to cause one additional TB event was lower for patients with COPD treated with ICSs in endemic areas than for those in nonendemic areas (909 vs 1,667, respectively).Conclusions: This study raises safety concerns about the risk of TB and influenza associated with ICS use in patients with COPD, which deserve further investigation.
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Outcome of early-treated type III Gaucher disease patients.
Blood Cells Mol. Dis.
PUBLISHED: 02-06-2014
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Recombinant human acid ?-glucosidase GBA (rhGBA) infusion is an effective therapy for non-neuropathic (type I) Gaucher disease (GD), but its effect on subacute neuropathic (type III) GD is still controversial. The most common genotype for type III GD is homozygous c.1448T>C (p.L444P) mutation, and in this study, we treated seven such patients starting from an early age (median 2.1 years; range 1-2.9 years). Before the start of treatment, all patients presented hepatosplenomegaly, anemia, and thrombocytopenia, but with no neurological signs. Normalization of hemoglobin levels and platelet numbers was achieved in all patients in one year. However, after a median treatment period of 7.6 years (2.2-12.0 years), two patients developed horizontal gaze palsy, one had seizures, four demonstrated mental retardation, and five showed kyphosis. Moreover, lymphadenopathy in the neck, thorax, or abdomen was observed in four patients. Therefore, the progression of neurological symptoms in these patients probably reflected the neurologic natural history of type III GD. Residual somatic symptoms, including kyphosis and lymphadenopathy, may be more common than what we thought. An additional treatment will be necessary to improve the outcome of type III GD.
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Protein binding for detection of small changes on a nanoparticle surface.
Analyst
PUBLISHED: 02-01-2014
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Protein adsorption on nanoparticles is closely associated with the physicochemical properties of particles, in particular, their surface properties. We synthesized two batches of polyacrylic acid-coated nanoparticles under almost identical conditions except for the heating duration and found differences in the head-group structure of the polyacrylic acid. The structure change was confirmed by NMR and MS. The two batches of particles had varied binding affinities to a selected group of proteins. Computational work confirmed that the head group of the polymer on the surface of a nanoparticle could directly interact with a protein, and small structural changes in the head group were sufficient to result in a significant difference in the free energy of binding. Our results demonstrate that protein adsorption is so sensitive to the surface properties of particles that it can reveal even small variations in the structure of a nanoparticle surface ligand, and should be useful for quick assessment of nanoparticle properties.
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Metabolic syndrome and smoking may justify earlier colorectal cancer screening in men.
Gastrointest. Endosc.
PUBLISHED: 01-25-2014
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Gender, smoking, and metabolic syndrome (MetS) are important risk factors of colorectal neoplasm. Whether presence of these factors may warrant earlier screening remains unclear.
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On the large ?-hyperconjugation in alkanes and alkenes.
J Mol Model
PUBLISHED: 01-22-2014
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The conventional view that the ?CC and ?CH bonds in alkanes and unsaturated hydrocarbons are so highly localized that their non-steric interactions are negligible is scrutinized by the block-localized wavefunction (BLW) method. Even molecules considered conventionally to be "strain free" and "unperturbed" have surprisingly large and quite significant total ?-BLW-delocalization energies (DEs) due to their geminal and vicinal hyperconjugative interactions. Thus, the computed BLW-DEs (in kcal mol(-1)) for the antiperiplanar conformations of the n-alkanes (C(N)H(2N+2), N = 1-10) range from 11.6 for ethane to 82.2 for?n-decane and are 50.9 for cyclohexane and 91.0 for adamantane. Although ?-electron delocalization in unsaturated hydrocarbons usually is ignored, the ?-BLW-DEs (in kcal mol(-1)) are substantial, as exemplified by D2h ethylene (9.0), triplet D2d ethylene (16.4), allene (19.3), butadiene (19.0), hexatriene (28.3), benzene (28.1), and cyclobutadiene (21.1). While each individual geminal and vicinal hyperconjugative interaction between hydrocarbon ?-bonding and ?-antibonding orbitals tends to be smaller than an individual ? conjugative interaction (e.g., 10.2 kcal mol(-1) in anti-1,3-butadiene, the presence of many ?-hyperconjugative interactions (e.g., a total of 12 in anti-1,3-butadiene, see text), result in substantial total ?-stabilization energies (e.g., 19.0 kcal mol(-1) for butadiene), which may surpass those from the ? interactions. Although large in magnitude, ?-electron delocalization energies often are obscured by cancellation when two hydrocarbons are compared. Rather than being strain-free, cyclohexane, adamantane, and diamantane suffer from their increasing number of intramolecular 1,4-C…C repulsions resulting in elongated C-C bond lengths and reduced ?-hyperconjugation, compared to the (skew-free) antiperiplanar n-alkane conformers. Instead of being inconsequential, ?-bond interactions are important and merit consideration.
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Infection, antibiotic therapy and risk of colorectal cancer: a nationwide nested case-control study in patients with Type 2 diabetes mellitus.
Int. J. Cancer
PUBLISHED: 01-20-2014
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Patients with Type 2 diabetes mellitus are at a higher risk of colorectal cancer (CRC). The objective of our study was to examine the inter-relationship among infection sites, systemic antibiotic use and risk of CRC among patients with Type 2 diabetes mellitus. From a diabetic cohort from the Taiwan's National Health Insurance claims database, we identified 3,593 incident colon cancer cases, 1,979 rectal cancer cases and 22,288 controls and conducted a nested case-control study to examine the association between antibiotic use and CRC incidence. Logistic regression models were applied to estimate the odds ratio (OR) and the 95% confidence interval (95% CI) between infection sites, antibiotic use and CRC incidence. Patients with intra-abdominal infection were significantly associated with increased risk for colon cancer (OR = 2.01, 95% CI = 1.73-2.35) and rectal cancer (OR = 1.59, 95% CI = 1.26-2.00). Any antianaerobic antibiotic use was associated with a higher risk of colon cancer (OR = 2.31, 95% CI = 2.12-2.52) and rectal cancer (OR = 1.69, 95% CI = 1.50-1.90) but without an obvious dose-response relationship for cumulative use. Antianaerobic antibiotics also increased the risks for those with nonintra-abdominal infection. No association was found between antiaerobic agent use and the CRC risk. The results suggest intra-abdominal infections and antianaerobic antibiotic use may be a marker for precancerous lesions or early CRC, although the possibility of antianaerobic antibiotics playing an additional role cannot be excluded. Further research examining the relationship between intra-abdominal infection, antianaerobic antibiotics use and possible change of microbiota leading to colorectal carcinogenesis is warranted.
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Effect of radiofrequency catheter ablation for atrial fibrillation on morbidity and mortality: a nationwide cohort study and propensity score analysis.
Circ Arrhythm Electrophysiol
PUBLISHED: 01-20-2014
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This study examined the effect of radiofrequency catheter ablation (RFA) on reducing morbidity and mortality among patients with atrial fibrillation (AF).
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Current management of diminutive colorectal polyps in Taiwan.
Dig Endosc
PUBLISHED: 01-17-2014
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The majority of polyps detected during colonoscopy are diminutive polyps, for which the cost of pathological analysis is substantial. In our analysis of a screening cohort of 10737 subjects undergoing screening colonoscopy, a total of 15877 neoplastic lesions were detected, of which 10816 (68.1%) were diminutive lesions. Of those diminutive lesions, 90 (0.83%) had a villous component, 14 (0.1%) had high-grade dysplasia, and none had invasive cancer. Only 1.3% of patients were advised to decrease their surveillance interval because of unfavorable histology. Laws regulating medical practice, uncertainty regarding the accuracy of endoscopic diagnosis of diminutive polyps outside of academic centers, and the relatively low cost of pathological analysis are among the barriers to adopting a 'resect and discard' practice in Taiwan.
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Planar Möbius aromatic pentalenes incorporating 16 and 18 valence electron osmiums.
Nat Commun
PUBLISHED: 01-15-2014
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Aromaticity, a highly stabilizing feature of molecules with delocalized electrons in closed circuits, is generally restricted to 'Hückel' systems with 4n+2 mobile electrons. Although the Möbius concept extends the principle of aromaticity to 4n mobile electron species, the rare known examples have complex, twisted topologies whose extension is unlikely. Here we report the realization of osmapentalenes, the first planar Möbius aromatic complexes with 16 and 18 valence electron transition metals. The Möbius aromaticity of these osmapentalenes, documented by X-ray structural, magnetic and theoretical analyses, demonstrates the basis of the aromaticity of the parent osmapentalynes. All these osmapentalenes are formed by both electrophilic and nucleophilic reactions of the in-plane ? component of the same carbyne carbon, illustrating ambiphilic carbyne reactivity, which is seldom observed in transition metal chemistry. Our results widen the scope of Möbius aromaticity dramatically and open prospects for the generalization of planar Möbius aromatic chemistry.
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Mediating effects of social support on depression and quality of life among patients with HIV infection in Taiwan.
AIDS Care
PUBLISHED: 01-15-2014
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Few empirical studies have evaluated the mediating effects of quality of life (QoL) among people living with HIV/AIDS (PLWHA). The purposes of this study were to identify the predictors of QoL and to test the mediating effects of social support on depression and QoL among patients enrolled in an HIV case-management program in Taiwan. A cross-sectional, descriptive correlation design collected data from 108 HIV-infected individuals. Individuals were assessed using the Beck Depression Inventory II, the short version of the World Health Organization Quality of Life Assessment (WHOQOL-BREF), and the Multidimensional Scale of Perceived Social Support between September 2007 and April 2010. After adjusting for sociodemographic characteristics (including age, gender, and mode of transmission) and clinical information (including CD4 count and time since diagnosis with HIV), the study findings showed that QoL was significantly and positively correlated with both social support and the initiation of highly active antiretroviral therapy (HAART), and was negatively correlated with depression and time since diagnosis with HIV. The strongest predictors for QoL were depression followed by the initiation of HAART and social support, with an R(2) of 0.40. Social support partially mediated the relationship between depression and QoL. Health professionals should enhance HIV-infected individuals' social support to alleviate the level of depression and further increase the QoL among PLWHA.
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Continuation of statin therapy and a decreased risk of atrial fibrillation/flutter in patients with and without chronic kidney disease.
Atherosclerosis
PUBLISHED: 01-10-2014
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To contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status.
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SMART DOCS: A New Patient-Centered Outcomes and Coordinated-Care Management Approach for the Future Practice of Sleep Medicine.
Sleep
PUBLISHED: 01-07-2014
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The practice of medicine is currently undergoing a transformation to become more efficient, cost-effective, and patient centered in its delivery of care. The aim of this article is to stimulate discussion within the sleep medicine community in addressing these needs by our approach as well as other approaches to sleep medicine care. The primary goals of the Sustainable Methods, Algorithms, and Research Tools for Delivering Optimal Care Study (SMART DOCS) are: (1) to introduce a new Patient-Centered Outcomes and Coordinated-Care Management (PCCM) approach for the future practice of sleep medicine, and (2) to test the PCCM approach against a Conventional Diagnostic and Treatment Outpatient Medical Care (CONV) approach in a randomized, two-arm, single-center, long-term, comparative effectiveness trial. The PCCM approach is integrated into a novel outpatient care delivery model for patients with sleep disorders that includes the latest technology, allowing providers to obtain more accurate and rapid diagnoses and to make evidence-based treatment recommendations, while simultaneously enabling patients to have access to personalized medical information and reports regarding their diagnosis and treatment so that they can make more informed health care decisions. Additionally, the PCCM approach facilitates better communication between patients, referring primary care physicians, sleep specialists, and allied health professionals so that providers can better assist patients in achieving their preferred outcomes. A total of 1,506 patients 18 y or older will be randomized to either the PCCM or CONV approach and will be followed for at least 1 y with endpoints of improved health care performance, better health, and cost control.
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Differential Regulation of Human Aortic Smooth Muscle Cell Proliferation by Monocyte-Derived Macrophages from Diabetic Patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Macrophage accumulation in the arterial wall and smooth muscle cell (SMC) proliferation are features of type 2 diabetes mellitus (DM) and its vascular complications. However, the effects of diabetic monocyte-derived macrophages on vascular SMC proliferation are not clearly understood. In the present study, we investigated the pro-proliferative effect of macrophages isolated from DM patients on vascular SMCs. Macrophage-conditioned media (MCM) were prepared from macrophages isolated from DM patients. DM-MCM treatment induced HASMC proliferation, decreased p21Cip1 and p27Kip1 expressions, and increased microRNA (miR)-17-5p and miR-221 expressions. Inhibition of either miR-17-5p or miR-221 inhibited DM-MCM-induced cell proliferation. Inhibition of miR-17-5p abolished DM-MCM-induced p21Cip1 down-regulation; and inhibition of miR-221 attenuated the DM-MCM-induced p27Kip1 down-regulation. Furthermore, blocking assays demonstrated that PDGF-CC in DM-MCM is the major mediators of cell proliferation in SMCs. In conclusion, our present data support the hypothesis that SMC proliferation stimulated by macrophages may play critical roles in vascular complications in DM patients and suggest a new mechanism by which arterial disease is accelerated in diabetes.
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Correlation between reduction of superior interventricular groove epicardial fat thickness and improvement of insulin resistance after weight loss in obese men.
Diabetol Metab Syndr
PUBLISHED: 01-01-2014
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It has been recognized that reduction of abdominal visceral fat and subcutaneous fat are associated with improvement in insulin-resistance (IR) after weight loss. However, few studies have investigated the correlation of reduction in epicardial adipose tissue (EAT) with improvement of IR index after weight loss in obese non-diabetic men with metabolic syndrome (MetS).
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SLCO3A1, a Novel Crohn's Disease-Associated Gene, Regulates NF-?B Activity and Associates with Intestinal Perforation.
PLoS ONE
PUBLISHED: 01-01-2014
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To date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.
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Antihypertensive agents and risk of Parkinson's disease: a nationwide cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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Hypertension has been associated with Parkinson's disease (PD), but data on antihypertensive drugs and PD are inconclusive. We aim to evaluate antihypertensive drugs for an association with PD in hypertensive patients.
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Achieving peptide binding specificity and promiscuity by loops: case of the forkhead-associated domain.
PLoS ONE
PUBLISHED: 01-01-2014
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The regulation of a series of cellular events requires specific protein-protein interactions, which are usually mediated by modular domains to precisely select a particular sequence from diverse partners. However, most signaling domains can bind to more than one peptide sequence. How do proteins create promiscuity from precision? Moreover, these complex interactions typically occur at the interface of a well-defined secondary structure, ? helix and ? sheet. However, the molecular recognition primarily controlled by loop architecture is not fully understood. To gain a deep understanding of binding selectivity and promiscuity by the conformation of loops, we chose the forkhead-associated (FHA) domain as our model system. The domain can bind to diverse peptides via various loops but only interact with sequences containing phosphothreonine (pThr). We applied molecular dynamics (MD) simulations for multiple free and bound FHA domains to study the changes in conformations and dynamics. Generally, FHA domains share a similar folding structure whereby the backbone holds the overall geometry and the variety of sidechain atoms of multiple loops creates a binding surface to target a specific partner. FHA domains determine the specificity of pThr by well-organized binding loops, which are rigid to define a phospho recognition site. The broad range of peptide recognition can be attributed to different arrangements of the loop interaction network. The moderate flexibility of the loop conformation can help access or exclude binding partners. Our work provides insights into molecular recognition in terms of binding specificity and promiscuity and helpful clues for further peptide design.
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Reevesioside A, a cardenolide glycoside, induces anticancer activity against human hormone-refractory prostate cancers through suppression of c-myc expression and induction of G1 arrest of the cell cycle.
PLoS ONE
PUBLISHED: 01-01-2014
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In the past decade, there has been a profound increase in the number of studies revealing that cardenolide glycosides display inhibitory activity on the growth of human cancer cells. The use of potential cardenolide glycosides may be a worthwhile approach in anticancer research. Reevesioside A, a cardenolide glycoside isolated from the root of Reevesia formosana, displayed potent anti-proliferative activity against human hormone-refractory prostate cancers. A good correlation (r²?=?0.98) between the expression of Na?/K?-ATPase ?? subunit and anti-proliferative activity suggested the critical role of the ?? subunit. Reevesioside A induced G1 arrest of the cell cycle and subsequent apoptosis in a thymidine block-mediated synchronization model. The data were supported by the down-regulation of several related cell cycle regulators, including cyclin D1, cyclin E and CDC25A. Reevesioside A also caused a profound decrease of RB phosphorylation, leading to an increased association between RB and E2F1 and the subsequent suppression of E2F1 activity. The protein and mRNA levels of c-myc, which can activate expression of many downstream cell cycle regulators, were dramatically inhibited by reevesioside A. Transient transfection of c-myc inhibited the down-regulation of both cyclin D1 and cyclin E protein expression to reevesioside A action, suggesting that c-myc functioned as an upstream regulator. Flow cytometric analysis of JC-1 staining demonstrated that reevesioside A also induced the significant loss of mitochondrial membrane potential. In summary, the data suggest that reevesioside A inhibits c-myc expression and down-regulates the expression of CDC25A, cyclin D1 and cyclin E, leading to a profound decrease of RB phosphorylation. G1 arrest is, therefore, induced through E2F1 suppression. Consequently, reevesioside A causes mitochondrial damage and an ultimate apoptosis in human hormone-refractory prostate cancer cells.
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Effects of selective serotonin reuptake inhibitors versus tricyclic antidepressants on cerebrovascular events: a nationwide population-based cohort study.
J Clin Psychopharmacol
PUBLISHED: 10-05-2013
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Depression is a common disorder worldwide and is strongly associated with stroke. Use of antidepressants could potentially decrease the risk of stroke in patients with depression. However, the role of selective serotonin reuptake inhibitors (SSRIs), the most frequently prescribed antidepressant in this era, in the risk of stroke showed inconsistent results. We aimed to assess the association between the use of different types of antidepressants, SSRIs and tricyclic antidepressants (TCAs), and the risk of cerebrovascular events in patients with depression or anxiety. A nationwide population-based cohort study was retrospectively conducted in patients with depression or anxiety who started to take SSRIs and TCAs identified from the Taiwan National Health Insurance claims database (2001-2009). We examined the association between the 2 types of antidepressants and incidence of stroke using a proportional hazard model adjusted for stroke risk factors. Among the 24,662 SSRI and 14,736 TCA initiators, the crude incidence rate for stroke was 10.03 and 13.77 per 100 person-years, respectively. Selective serotonin reuptake inhibitor use was not associated with risk of stroke as compared with TCAs in the time-fixed analysis. After adjusting for baseline propensity scores in the time-varying analysis, SSRI use significantly reduced risk of stroke as compared with TCAs with the adjusted hazard ratio of 0.67 (95% confidence interval, 0.47-0.96). The effect persisted even after considering the antidepressant dosage (hazard ratio, 0.65 [0.42 to 0.99]). In summary, use of SSRIs was associated with a reduced risk for stroke, as compared with TCAs, in this specific disease population.
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Nanoscale-phase-separated Pd-Rh boxes synthesized via metal migration: an archetype for studying lattice strain and composition effects in electrocatalysis.
J. Am. Chem. Soc.
PUBLISHED: 09-23-2013
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Developing syntheses of more sophisticated nanostructures comprising late transition metals broadens the tools to rationally design suitable heterogeneous catalysts for chemical transformations. Herein, we report a synthesis of Pd-Rh nanoboxes by controlling the migration of metals in a core-shell nanoparticle. The Pd-Rh nanobox structure is a grid-like arrangement of two distinct metal phases, and the surfaces of these boxes are {100} dominant Pd and Rh. The catalytic behaviors of the particles were examined in electrochemistry to investigate strain effects arising from this structure. It was found that the trends in activity of model fuel cell reactions cannot be explained solely by the surface composition. The lattice strain emerging from the nanoscale separation of metal phases at the surface also plays an important role.
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National antiviral treatment program and the incidence of hepatocellular carcinoma and associated mortality in Taiwan: a preliminary report.
Med Care
PUBLISHED: 08-24-2013
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Taiwans Bureau of National Health Insurance launched the National Antiviral Treatment Program (NATP) in 2003 to reimburse patients for antiviral drugs and interferons for chronic hepatitis B and C. The objective was to examine the impact of the NATP on the incidence and mortality due to hepatocellular carcinoma (HCC).
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Risk of severe dysglycemia among diabetic patients receiving levofloxacin, ciprofloxacin, or moxifloxacin in Taiwan.
Clin. Infect. Dis.
PUBLISHED: 08-14-2013
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Observational studies and fatal case reports raise concern about the safety of severe dysglycemia associated with fluoroquinolone use. The objective of this study was to assess the risk of severe dysglycemia among diabetic patients who received different fluoroquinolones.
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Pneumonia risk and use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers.
J Epidemiol
PUBLISHED: 08-03-2013
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Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan.
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Discontinuation of statin therapy associates with Parkinson disease: a population-based study.
Neurology
PUBLISHED: 07-24-2013
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To evaluate the effect of discontinuing statin therapy on incidence of Parkinson disease (PD) in statin users.
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Zebularine inhibits tumorigenesis and stemness of colorectal cancer via p53-dependent endoplasmic reticulum stress.
Sci Rep
PUBLISHED: 07-15-2013
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Aberrant DNA hypermethylation is frequently found in tumor cells and inhibition of DNA methylation is an effective anticancer strategy. In this study, the therapeutic effect of DNA methyltransferase (DNMT) inhibitor zebularine (Zeb) on colorectal cancer (CRC) was investigated. Zeb exhibited anticancer activity in cell cultures, tumor xenografts and mouse colitis-associated CRC model. It stabilizes p53 through ribosomal protein S7 (RPS7)/MDM2 pathways and DNA damage. Zeb-induced cell death was dependent on p53. Microarray analysis revealed that genes related to endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were affected by Zeb. Zeb induced p53-dependent ER stress and autophagy. Pro-survival markers of ER stress/UPR (GRP78) and autophagy (p62) were increased in tumor tissues of CRC patients, AOM/DSS-induced CRC mice and HCT116-derived colonospheres. Zeb downregulates GRP78 and p62, and upregulates a pro-apoptotic CHOP. Our results reveal a novel mechanism for the anticancer activity of Zeb.
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Elevated urine zinc concentration reduces the detection of methamphetamine, cocaine, THC and opiates in urine by EMIT.
J Anal Toxicol
PUBLISHED: 07-10-2013
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Methods for circumventing positive drug tests continue to evolve and are often spread through internet websites reporting on the proposed effectiveness of various adulteration methods. Recent claims of the use of zinc added directly to urine or ingested prior to urine collection have prompted investigation into the vulnerability of ELISA-based testing, providing interesting but inconclusive results. We investigated the potential interference of zinc used as a direct adulterant and after zinc self-administration for enzyme multiplied immunoassay technique (EMIT)-based drug abuse testing in urine. Negative urine samples and samples collected before and after zinc self-administration were fortified with d-methamphetamine, benzoylecgonine, morphine and 11-nor-9-carboxy-tetrahydrocannabinol prior to analysis by the EMIT. Our data indicate that zinc added directly to urine in concentrations 5,000 times higher than a typical random urine total zinc concentration is capable of producing false-negative results; however, self-administration of oral zinc was unable to generate random urine total zinc concentrations in the required range. Further, no evidence of a secondary interfering substance was observed as a result of oral zinc self-administration. Our results indicate that the total zinc concentrations required to directly interfere with EMIT-based testing are easily distinguishable from routine random urine total zinc concentrations, and that alleged oral ingestion of zinc does not produce total zinc concentrations capable of direct interference.
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Prostate
PUBLISHED: 06-28-2013
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Histone deacetylase (HDAC) inhibitors are successful for treatment of advanced cutaneous T-cell lymphoma but only show modest effect in solid tumors. Approaches for HDAC inhibitors to improve activity against solid tumors are necessary.
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Statin use and cataract surgery: a nationwide retrospective cohort study in elderly ethnic Chinese patients.
Drug Saf
PUBLISHED: 06-18-2013
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Since a report of lenticular opacities in dogs treated with high dosages of statins, the debate on the relationship between statin therapy and cataracts has not reached a conclusion.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.