JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Amino acid modified Ni catalyst exhibits reversible H2 oxidation/production over a broad pH range at elevated temperatures.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-03-2014
Show Abstract
Hide Abstract
Hydrogenases interconvert H2 and protons at high rates and with high energy efficiencies, providing inspiration for the development of molecular catalysts. Studies designed to determine how the protein scaffold can influence a catalytically active site have led to the synthesis of amino acid derivatives of [Formula: see text] complexes, [Formula: see text] (CyAA). It is shown that these CyAA derivatives can catalyze fully reversible H2 production/oxidation at rates approaching those of hydrogenase enzymes. The reversibility is achieved in acidic aqueous solutions (pH = 0-6), 1 atm 25% H2/Ar, and elevated temperatures (tested from 298 to 348 K) for the glycine (CyGly), arginine (CyArg), and arginine methyl ester (CyArgOMe) derivatives. As expected for a reversible process, the catalytic activity is dependent upon H2 and proton concentrations. CyArg is significantly faster in both directions (?300 s(-1) H2 production and 20 s(-1) H2 oxidation; pH = 1, 348 K, 1 atm 25% H2/Ar) than the other two derivatives. The slower turnover frequencies for CyArgOMe (35 s(-1) production and 7 s(-1) oxidation under the same conditions) compared with CyArg suggests an important role for the COOH group during catalysis. That CyArg is faster than CyGly (3 s(-1) production and 4 s(-1) oxidation) suggests that the additional structural features imparted by the guanidinium groups facilitate fast and reversible H2 addition/release. These observations demonstrate that outer coordination sphere amino acids work in synergy with the active site and can play an important role for synthetic molecular electrocatalysts, as has been observed for the protein scaffold of redox active enzymes.
Related JoVE Video
Primary bladder amyloidosis.
Intern. Med.
PUBLISHED: 11-01-2014
Show Abstract
Hide Abstract
Primary bladder amyloidosis is a rare disease, with only 200 cases reported worldwide. This condition is clinically important since it masquerades as a malignancy. We herein present a case of primary bladder amyloidosis presenting as painless hematuria and dysuria. Computed tomography and ultrasound showed thickening of the posterior bladder wall. Cystoscopy revealed abnormal bladder tissue suspicious of malignancy. However, transurethral resection of a bladder tumor showed no evidence of malignant cells. Amyloid was identified on Congo red staining. Therefore, the possibility of secondary amyloidosis was ruled out and a diagnosis of primary bladder amyloidosis was made. Nine months after undergoing primary resection, the patient's amyloidosis recurred at the initial site.
Related JoVE Video
Phase I Trial of Bortezomib (PS-341; NSC 681239) and "Nonhybrid" (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms.
Clin. Cancer Res.
PUBLISHED: 09-23-2014
Show Abstract
Hide Abstract
This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).
Related JoVE Video
Evaluating the validity of MELD exception points for HCC patients with multiple nodules <2cm.
Clin Transplant
PUBLISHED: 09-18-2014
Show Abstract
Hide Abstract
Liver transplant allocation policy does not give MELD exception points for patients with a single hepatocellular carcinoma (HCC) less than 2cm in size, but does give points to patients with multiple small nodules. Because standard-of-care imaging for HCC struggles to differentiate HCC from other nodules, it is possible that a subset of patients receiving liver transplant for multiple nodules <2cm in size do not have HCC. We evaluate risk of post-transplant HCC recurrence and waitlist dropout for patients with multiple small nodules using competing risks regression based on the Fine and Gray model. We identified 5002 adult HCC patients in the OPTN/UNOS dataset diagnosed and transplanted between January 2006 and September 2010. Compared to patients with >1 tumor <2cm, risk of developing recurrence was significantly higher in patients with 1 or more tumors with only 1 tumor ?2cm (SHR 1.63, p=0.009), as well as in patients with 2-3 tumors ?2cm (SHR 1.84, p=0.02). Dropout risk was not significantly different among size categories. HCC recurrence risk was significantly lower in patients with multiple nodules <2cm in size than in those with larger tumors, supporting the possibility that some patients received unnecessary transplants. The priority given to these patients must be re-examined. This article is protected by copyright. All rights reserved.
Related JoVE Video
Periorbital Mohs reconstruction: characterization of tumor histology, anatomic location, and factors influencing postoperative complications.
Dermatol Surg
PUBLISHED: 09-18-2014
Show Abstract
Hide Abstract
When addressing skin malignancies of the periorbita, it is important to limit the excision of healthy tissue and preserve normal anatomic features while minimizing complications.
Related JoVE Video
The Potential Role of the Donor in Hepatocellular Carcinoma Recurrence Following Liver Transplantation.
Liver Transpl.
PUBLISHED: 06-09-2014
Show Abstract
Hide Abstract
A subset of liver transplant (LT) recipients who undergo transplant for hepatocellular carcinoma (HCC) will develop post-operative recurrence. There has yet to be a thorough investigation of donor factors influencing recurrence. Data regarding adult, primary LT recipients with HCC (n=5002) transplanted between January 1, 2006 and September 30, 2010 were extracted from United Network for Organ Sharing (UNOS) database, with subsequent estimation of the cumulative incidence of post-LT recurrence by donor factors. Of the HCC LT recipients, 324 (6.5%) developed recurrence. Analysis of donor characteristics demonstrated a higher cumulative incidence of recurrence within 4 years of transplant among recipients of donors ?60 years old (versus donors <60 years old) (11.8% versus 7.3%, respectively; p<0.001), and donors from non-local share distribution (versus local share distribution) (10.6% versus 7.4%, respectively; p=0.004). The latter two findings held true on multivariable analysis with HCC recurrence risk increased by 70% for recipients of donor livers ?60 years old (SHR=1.70, 95% CI 1.31-2.20, p<0.001) and by 42% for recipients of non-local share distribution (SHR=1.42, 95% CI 1.09-1.84, p=0.009) after adjusting for clinical characteristics. In conclusion, consideration of certain donor factors may reduce the cumulative incidence of post-transplant HCC recurrence, and thus improve long-term survival following LT. Liver Transpl , 2014. © 2014 AASLD.
Related JoVE Video
A hydrogen-evolving Ni(P2N2)2 electrocatalyst covalently attached to a glassy carbon electrode: preparation, characterization, and catalysis. comparisons with the homogeneous analogue.
Inorg Chem
PUBLISHED: 06-07-2014
Show Abstract
Hide Abstract
A hydrogen-evolving homogeneous Ni(P2N2)2 electrocatalyst with peripheral ester groups has been covalently attached to a 1,2,3-triazolyllithium-terminated planar glassy carbon electrode surface. Coupling proceeds with both the Ni(0) and the Ni(II) complexes. X-ray photoemission spectra show excellent agreement between the Ni(0) coupling product and its parent complex, and voltammetry of the surface-confined system shows that a single species predominates with a surface density of 1.3 × 10(-10) mol cm(-2), approaching the value estimated for a densely packed monolayer. With the Ni(II) system, both photoemission and voltammetric data show speciation to unidentified products on coupling, and the surface density is 6.7 × 10(-11) mol cm(-2). The surface-confined Ni(0) complex is an electroctalyst for hydrogen evolution, showing the onset of catalytic current at the same potential as the soluble parent complex. Decomposition of the surface-confined species is observed in acidic acetonitrile. This is interpreted to reflect the lability of the Ni(II)-phosphine interaction and the basicity of the free phosphine and bears on concurrent efforts to implement surface-confined Ni(P2N2)2 complexes in electrochemical or photoelectrochemical devices.
Related JoVE Video
Lower plasma Apolipoprotein A1 levels are found in Parkinson's disease and associate with apolipoprotein A1 genotype.
Mov. Disord.
PUBLISHED: 05-13-2014
Show Abstract
Hide Abstract
The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P?
Related JoVE Video
Recognition of an important water quality issue at zoos: prevalence and potential threat of toxic cyanobacteria.
J. Zoo Wildl. Med.
PUBLISHED: 04-10-2014
Show Abstract
Hide Abstract
Zoo animals may be particularly vulnerable to water sources contaminated with cyanobacterial toxins given their nonvoluntary close association with this resource. However, the prevalence and potential threat of toxic cyanobacteria in this setting are unknown. Several otherwise unexplained yellow-bellied slider (Trachemys scripta scripta) deaths were documented in a zoo moat with recurring blooms of toxic Microcystis aeruginosa. Furthermore, an extremely high and potentially lethal concentration of the hepatotoxin microcystin (166 ng/g) was found in the liver of a necropsied turtle that died in this moat. A subsequent monthly survey of water quality revealed detectable concentrations of microcystin in all moats (0.0001 to 7.5 microg/L), with moats higher than 1 microg/L being significantly higher than the threshold for safe drinking water recommended by the World Health Organization. These results demonstrate that cyanobacterial blooms are an important water quality issue in zoos, and future research is necessary to identify potential associations among water quality, zoo animal health, and moat management strategies.
Related JoVE Video
Indicators for detection of septic arthritis in the acutely swollen joint cohort of those without joint prostheses.
Orthopedics
PUBLISHED: 04-01-2014
Show Abstract
Hide Abstract
Differentiating septic arthritis from culture-negative, acute atraumatic joint effusion is difficult. Studies have attempted to elucidate factors that herald infection, but, due to overlap, most conclude that the diagnosis ultimately relies on clinical judgment. Furthermore, studies are limited by broad inclusion criteria. The current retrospective case study sought to examine (1) which markers differentiate a culture-positive septic joint from culture-negative effusion in patients suspicious for infection despite no growth on Gram stain and without previous surgery in the affected joint and (2) whether threshold values of these markers exist that predict septic arthritis. The study was performed by reviewing records of those who underwent operative irrigation and debridement involving the shoulder, elbow, wrist, hip, knee, and ankle. Patients were included if they were older than 18 years and had an acutely swollen/painful joint and no organisms on initial Gram stain. Exclusion criteria were lack of serum markers or synovial fluid aspirate, antibiotics within 1 week, adjacent wound or skin infection, recent trauma to the joint, and previous joint infection or surgery to the joint. Several clinical, serological, and synovial parameters were collected and analyzed using paired t test with Bonferonni correction. Serum C-reactive protein was the only significantly different variable between groups. Serum C-reactive protein greater than 10.5 mg/dL was predictive of infection. In those suspicious for infection despite no growth on Gram stain and without previous surgery in the affected joint, C-reactive protein greater than 10.5 mg/dL is suspicious for joint sepsis and should warrant consideration for urgent irrigation and debridement.
Related JoVE Video
Time to transplantation as a predictor of hepatocellular carcinoma recurrence after liver transplantation.
Liver Transpl.
PUBLISHED: 03-12-2014
Show Abstract
Hide Abstract
In the United States, there are significant geographic disparities in the time to transplantation for patients with hepatocellular carcinoma (HCC); it is possible that rapid transplantation contributes to higher rates of posttransplant HCC recurrence because there is insufficient time for the tumor biology to manifest. In this study, we compared HCC recurrence in rapid transplant patients and their slower transplant counterparts. We identified adult liver transplantation (LT) candidates in the Organ Procurement and Transplantation Network/United Network for Organ Sharing (UNOS) data set who were granted an initial exception for an HCC diagnosis between January 1, 2006 and September 30, 2010 and underwent transplantation in the same time window. Patients were followed until HCC recurrence, non-HCC-related death, or last follow-up. The cumulative incidence of HCC recurrence was compared for patients waiting ? 120 days and patients waiting >120 days from an HCC exception to LT. The association between the risk of posttransplant recurrence and the wait time was further evaluated via competing risks regression with the Fine and Gray model. For 5002 LT recipients with HCC, the median wait time from an exception to LT was 77 days, and it varied from 30 to 169 days by UNOS region. The cumulative incidence of posttransplant HCC recurrence was 3.3% [95% confidence interval (CI) = 2.8%-3.8%] and 5.6% (95% CI = 5.0%-6.3%) within 1 and 2 years, respectively. The rate of observed recurrence within 1 year of transplantation was significantly lower for patients waiting >120 days versus patients waiting ? 120 days (2.2% versus 3.9%, P = 0.002); however, the difference did not persist at 2 years (5.0% versus 5.9%, P = 0.09). After we accounted for clinical factors, the HCC recurrence risk was reduced by 40% for patients waiting >120 days (subhazard ratio = 0.6, P = 0.005). In conclusion, the risk of HCC recurrence within the first year after transplantation may be lessened by the institution of a mandatory waiting time after an exception is granted.
Related JoVE Video
Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization.
Liver Transpl.
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down-stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no-TACE group and 7.9% in the TACE group (P?=?0.22). All HA stenosis complications (n?=?14) occurred in the TACE group (P?=?0.018 versus the no-TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no-TACE group according to an adjusted analysis (odds ratio?=?2.02, 95% confidence interval?=?0.79-5.16, P?=?0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE group and 19.8% in the TACE group (P?=?0.40). In conclusion, a lower pre-LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis.
Related JoVE Video
Conformational preferences of N,N-dimethylsuccinamate as a function of alkali and alkaline earth metal salts: experimental studies in DMSO and water as determined by 1H NMR spectroscopy.
J Phys Chem A
PUBLISHED: 03-10-2014
Show Abstract
Hide Abstract
The fraction of gauche conformers of N,N-dimethylsuccinamic acid (1) and its Li(+), Na(+), K(+), Mg(2+), Ca(2+), and N(Bu)4(+) salts were estimated in DMSO and D2O solution by comparing the experimental vicinal proton-proton couplings determined by (1)H NMR spectroscopy with those calculated using the Haasnoot, de Leeuw, and Altona (HLA) equation. In DMSO, the gauche preferences were found to increase with decreasing Ahrens ionic radius of the metal counterion. The same trend was not seen in D2O, where the gauche fraction for all of the metallic salts were estimated to be approximately statistical or less. This highlights the importance of metal chelation on the conformation of organic molecules in polar aprotic media, which has implications for protein folding.
Related JoVE Video
Alpha-fetoprotein level > 1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria.
Liver Transpl.
PUBLISHED: 02-26-2014
Show Abstract
Hide Abstract
Serum alpha-fetoprotein (AFP) has been increasingly recognized as a marker for a poor prognosis after liver transplantation (LT) for hepatocellular carcinoma (HCC). Many published reports, however, have included a large proportion of patients with HCC beyond the Milan criteria, and the effects of incorporating AFP as an exclusion criterion for LT remain unclear. We studied 211 consecutive patients undergoing LT for HCC within the Milan criteria according to imaging under the Model for End-Stage Liver Disease organ allocation system between June 2002 and January 2009. The majority (93.4%) had locoregional therapy before LT. The median follow-up was 4.5 years (minimum = 2 years). The Kaplan-Meier 1- and 5-year patient survival rates were 94.3% and 83.4%, respectively. In a univariate analysis, significant predictors of HCC recurrence included vascular invasion [hazard ratio (HR) = 10, 95% confidence interval (CI) = 3.9-26, P < 0.001], a pathological tumor stage beyond the University of California San Francisco criteria (HR = 4.1, 95% CI = 1.36-12.6, P = 0.01), an AFP level > 1000 ng/mL (HR = 4.5, 95% CI = 1.3-15.3, P = 0.02), and an AFP level > 500 ng/mL (HR = 3.1, 95% CI = 1.04-9.4, P = 0.04). In a multivariate analysis, vascular invasion was the only significant predictor of tumor recurrence (HR = 5.6, 95% CI = 1.9-19, P = 0.02). An AFP level > 1000 ng/mL was the strongest pretransplant variable predicting vascular invasion (odds ratio = 6.8, 95% CI = 1.6-19.1, P = 0.006). The 1- and 5-year rates of survival without recurrence were 90% and 52.7%, respectively, for patients with an AFP level > 1000 ng/mL and 95% and 80.3%, respectively, for patients with an AFP level ? 1000 ng/mL (P = 0.026). Applying an AFP level > 1000 ng/mL as a cutoff would have resulted in the exclusion of 4.7% of the patients fr m LT and a 20% reduction in HCC recurrence. In conclusion, an AFP level > 1000 ng/mL may be a surrogate for vascular invasion and may be used to predict posttransplant HCC recurrence. Incorporating an AFP level > 1000 ng/mL as an exclusion criterion for LT within the Milan criteria may further improve posttransplant outcomes.
Related JoVE Video
The lived experiences of nurses in one hyper-acute stroke unit.
Br J Nurs
PUBLISHED: 02-15-2014
Show Abstract
Hide Abstract
Hyper-acute stroke units (HASUs) admit all stroke patients across London. As a novel London stroke model, the integration of thrombolysis in acute ischaemic stroke is an important element of hyper-acute stroke care for patients. In this model, nurses working in a hyper-acute stroke unit are involved in the delivery of thrombolysis treatment. By use of a phenomenological approach, the study investigates the 'lived experiences' of nurses' preparation for their role and explores any factors that affect nurses' participation in thrombolysis treatment. The nurses' roles-which facilitate, support, monitor, anticipate and result in prevention-are central to effective thrombolysis treatment. However, factors such as communication, teamwork, clinical decision, training, staffing and safety affect their thrombolysis roles. Addressing factors that affect nurses' thrombolysis roles could lead to improved communication, collaborative teamwork and better patient outcomes.
Related JoVE Video
Arginine-containing ligands enhance H? oxidation catalyst performance.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
Hydrogenase enzymes use Ni and Fe to oxidize H2 at high turnover frequencies (TOF) (up to 10,000?s(-1)) and low overpotentials (<100?mV). In comparison, the fastest reported synthetic electrocatalyst, [Ni(II)(P(Cy)2N(tBu)2)2](2+), oxidizes H2 at 60?s(-1) in MeCN under 1 atm H2 with an unoptimized overpotential of ca. 500?mV using triethylamine as a base. Here we show that a structured outer coordination sphere in a Ni electrocatalyst enhances H2 oxidation activity: [Ni(II)(P(Cy)2N(Arg)2)2](8+) (Arg=arginine) has a TOF of 210?s(-1) in water with high energy efficiency (180?mV overpotential) under 1?atm H2 , and 144,000?s(-1) (460?mV overpotential) under 133?atm H2. The complex is active from pH?0-14 and is faster at low pH, the most relevant condition for fuel cells. The arginine substituents increase TOF and may engage in an intramolecular guanidinium interaction that assists in H2 activation, while the COOH groups facilitate rapid proton movement. These results emphasize the critical role of features beyond the active site in achieving fast, efficient catalysis.
Related JoVE Video
Multiple listings as a reflection of geographic disparity in liver transplantation.
J. Am. Coll. Surg.
PUBLISHED: 02-07-2014
Show Abstract
Hide Abstract
Geographic disparity in access to liver transplantation (LT) exists. This study sought to examine Model for End-Stage Liver Disease-era multiply listed (ML) LT candidate (ie, candidates who list at 2 or more LT centers to receive a liver transplant).
Related JoVE Video
Enzyme design from the bottom up: an active nickel electrocatalyst with a structured peptide outer coordination sphere.
Chemistry
PUBLISHED: 01-17-2014
Show Abstract
Hide Abstract
Catalytic, peptide-containing metal complexes with a well-defined peptide structure have the potential to enhance molecular catalysts through an enzyme-like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide-based metal complex built upon the well-characterized hydrogen production catalyst [Ni(P(Ph)2N(Ph))2](2+) (P(Ph)2N(Ph)=1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane). The incorporated peptide maintains its ?-hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide-based metal complex (?100,000?s(-1)) is enhanced compared to the parent complex ([Ni(P(Ph)2N(APPA))2](2+); ?50,500 s(-1)). The combination of an active molecular catalyst with a structured peptide provides a scaffold that permits the incorporation of features of an enzyme-like outer-coordination sphere necessary to create molecular electrocatalysts with enhanced functionality.
Related JoVE Video
Trans-radial versus trans-femoral access in patients with end-stage liver disease undergoing cardiac catheterization.
Am J Cardiovasc Dis
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Cardiac catheterization has been increasingly utilized to evaluate coronary artery disease in patients with end stage liver disease (ESLD). It is known in other populations that radial access reduces access site complications;however, there is a paucity of data in ESLD patients. We investigated vascular and bleeding complications rates between trans-femoral and trans-radial cardiac catheterizations in this high risk population. In this retrospective cohort study, three hundred and thirty four ESLD patients were identified between August 2004 and December 2012 who had undergone trans-femoral (femoral group) or trans-radial (radial group) cardiac catheterizations at our institution. The radial group was not significantly different from the femoral group in age (p = 0.056), proportions of genders (p = 0.85), and weight (p = 0.19); however, compared to the femoral group, the radial group had significantly lower blood pressure (p < 0.0001), hemoglobin (10.4 ± 1.9 vs 11.1 ± 2.02 g/dL, p = 0.001), and hematocrit (30.3 ± 5.7% vs 32.6 ± 6.0%, p < 0.0006), and had a significantly higher INR (1.94 ± 1.16 vs 1.59 ± 0.62, p = 0.0001). In terms of vascular complications, the radial group had a significantly lower rate of pseudoaneurysms (0% vs 3.7%, p = 0.019) than the femoral group. While there were no bleeding complications in either group or differences in transfusion requirements, there was a significantly lower percentage drop in hematocrit in the radial group compared to the femoral group (5.4% vs 7.8%, p = 0.039). In conclusion, trans-radial catheterization is associated with lower rates of vascular access site complications compared to trans-femoral catheterization.
Related JoVE Video
Comparative neuronal morphology of the cerebellar cortex in afrotherians, carnivores, cetartiodactyls, and primates.
Front Neuroanat
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Although the basic morphological characteristics of neurons in the cerebellar cortex have been documented in several species, virtually nothing is known about the quantitative morphological characteristics of these neurons across different taxa. To that end, the present study investigated cerebellar neuronal morphology among eight different, large-brained mammalian species comprising a broad phylogenetic range: afrotherians (African elephant, Florida manatee), carnivores (Siberian tiger, clouded leopard), cetartiodactyls (humpback whale, giraffe) and primates (human, common chimpanzee). Specifically, several neuron types (e.g., stellate, basket, Lugaro, Golgi, and granule neurons; N = 317) of the cerebellar cortex were stained with a modified rapid Golgi technique and quantified on a computer-assisted microscopy system. There was a 64-fold variation in brain mass across species in our sample (from clouded leopard to the elephant) and a 103-fold variation in cerebellar volume. Most dendritic measures tended to increase with cerebellar volume. The cerebellar cortex in these species exhibited the trilaminate pattern common to all mammals. Morphologically, neuron types in the cerebellar cortex were generally consistent with those described in primates (Fox et al., 1967) and rodents (Palay and Chan-Palay, 1974), although there was substantial quantitative variation across species. In particular, Lugaro neurons in the elephant appeared to be disproportionately larger than those in other species. To explore potential quantitative differences in dendritic measures across species, MARSplines analyses were used to evaluate whether species could be differentiated from each other based on dendritic characteristics alone. Results of these analyses indicated that there were significant differences among all species in dendritic measures.
Related JoVE Video
Minimal proton channel enables h2 oxidation and production with a water-soluble nickel-based catalyst.
J. Am. Chem. Soc.
PUBLISHED: 11-27-2013
Show Abstract
Hide Abstract
Hydrogenase enzymes use first-row transition metals to interconvert H2 with protons and electrons, reactions that are important for the storage and recovery of energy from intermittent sources such as solar, hydroelectric, and wind. Here we present Ni(P(Cy)2N(Gly)2)2, a water-soluble molecular electrocatalyst with the amino acid glycine built into the diphosphine ligand framework. Proton transfer between the outer coordination sphere carboxylates and the second coordination sphere pendant amines is rapid, as observed by cyclic voltammetry and FTIR spectroscopy, indicating that the carboxylate groups may participate in proton transfer during catalysis. This complex oxidizes H2 (1-33 s(-1)) at low overpotentials (150-365 mV) over a range of pH values (0.1-9.0) and produces H2 under identical solution conditions (>2400 s(-1) at pH 0.5). Enzymes employ proton channels for the controlled movement of protons over long distances-the results presented here demonstrate the effects of a simple two-component proton channel in a synthetic molecular electrocatalyst.
Related JoVE Video
Substituent effects on energetics of Peptide-carboxylate hydrogen bonds as studied by (1)h NMR spectroscopy: implications for enzyme catalysis.
J. Org. Chem.
PUBLISHED: 11-18-2013
Show Abstract
Hide Abstract
Substituent effects in N-H···O hydrogen bonds were estimated by comparing the acidities of two series of model compounds: N-benzoylanthranilic acids (A) and 4-benzoylamidobenzoic acids (B). Intramolecular N-H···O hydrogen bonds were found to be present in the A series of compounds, while B acids were used as control models. The respective pKa values for A and B acids were determined experimentally in DMSO solution using proton NMR spectroscopy. With X = H, the pKa for A and B acids were observed to be 7.6 and 11.6, respectively, a difference of 4.0 units (?pKa). However, with X = p-NO2, the ?pKa value between A and B acids increased to 4.7 units: the pKa values for A and B acids were determined as 6.7 and 11.4, respectively. The ?pKa values between A and B acids as a function of the X substituents were studied in 10 other examples. The effects of X substituents in A acids could be predicted on the basis of the observed linear Hammett correlations, and the sensitivity of each substituent effect was found to be comparable to those observed for the ionization of substituted benzoic acids (? = 1.04 for A acids, and ? = 1.00 for benzoic acids).
Related JoVE Video
The electrode as organolithium reagent: catalyst-free covalent attachment of electrochemically active species to an azide-terminated glassy carbon electrode surface.
Inorg Chem
PUBLISHED: 11-14-2013
Show Abstract
Hide Abstract
The reaction of a lithium acetylide-ethylenediamine complex with azide-terminated glassy carbon surfaces affords 1,2,3-triazolyllithium surface groups that are active toward covalent C-C coupling reactions, including salt metathesis with an aliphatic halide and nucleophilic addition at an aldehyde. Surface ferrocenyl groups were introduced by reaction with (6-iodohexyl)ferrocene; the voltammetry of electrode samples shows narrow, symmetric peaks indicating uniform attachment. X-ray photoelectron and reflectance infrared spectroscopic data provide further support for the surface-attached products. Formation of the 1,2,3-triazolyllithium linkage requires neither a catalyst nor a strained alkyne. Coverages obtained by this route are similar to those obtained by the more common Cu(I)-catalyzed alkyne-azide coupling (CuAAC) of ethynylferrocene with surface azides. Preconditioning of the glassy carbon disk electrodes at ambient temperature under nitrogen affords coverages comparable to those reported with preconditioning at 1000 °C under hydrogen/nitrogen.
Related JoVE Video
Synthesis and electrochemical studies of cobalt(III) monohydride complexes containing pendant amines.
Inorg Chem
PUBLISHED: 08-14-2013
Show Abstract
Hide Abstract
Two new tetraphosphine ligands, P(nC-PPh2)2N(Ph)2 (1,5-diphenyl-3,7-bis((diphenylphosphino)alkyl)-1,5-diaza-3,7-diphosphacyclooctane; alkyl = (CH2)2, n = 2 (L2); (CH2)3, n = 3 (L3)), have been synthesized. Coordination of these ligands to cobalt affords the complexes [Co(II)(L2)(CH3CN)](2+) and [Co(II)(L3)(CH3CN)](2+), which are reduced by KC8 to afford [Co(I)(L2)(CH3CN)](+) and [Co(I)(L3)(CH3CN)](+). Protonation of the Co(I) complexes affords [HCo(III)(L2)(CH3CN)](2+) and [HCo(III)(L3)(CH3CN)](2+). The cyclic voltammetry of [HCo(III)(L2)(CH3CN)](2+), analyzed using digital simulation, is consistent with an ErCrEr reduction mechanism involving reversible acetonitrile dissociation from [HCo(II)(L2)(CH3CN)](+) and resulting in formation of HCo(I)(L2). Reduction of HCo(III) also results in cleavage of the H-Co bond from HCo(II) or HCo(I), leading to formation of the Co(I) complex [Co(I)(L2)(CH3CN)](+). Under voltammetric conditions, the reduced cobalt hydride reacts with a protic solvent impurity to generate H2 in a monometallic process involving two electrons per cobalt. In contrast, under bulk electrolysis conditions, H2 formation requires only one reducing equivalent per [HCo(III)(L2)(CH3CN)](2+), indicating a bimetallic route wherein two cobalt hydride complexes react to form 2 equiv of [Co(I)(L2)(CH3CN)](+) and 1 equiv of H2. These results indicate that both HCo(II) and HCo(I) can be formed under electrocatalytic conditions and should be considered as potential catalytic intermediates.
Related JoVE Video
Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man.
Br J Clin Pharmacol
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
SRT2104 is a novel, first-in-class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SRT2104 was dosed to healthy male and female volunteers in a series of phase 1 clinical studies that were designed to elucidate tolerability and pharmacokinetics associated with oral dosing to aid in dose selection for subsequent clinical trials.
Related JoVE Video
Center competition and outcomes following liver transplantation.
Liver Transpl.
PUBLISHED: 08-03-2013
Show Abstract
Hide Abstract
In the United States, livers for transplantation are distributed within donation service areas (DSAs). In DSAs with multiple transplant centers, competition among centers for organs and recipients may affect recipient selection and outcomes in comparison with DSAs with only 1 center. The objective of this study was to determine whether competition within a DSA is associated with posttransplant outcomes and variations in patients wait-listed within the DSA. United Network for Organ Sharing data for 38,385 adult cadaveric liver transplant recipients undergoing transplantation between January 1, 2003 and December 31, 2009 were analyzed to assess differences in liver recipients and donors and in posttransplant survival by competition among centers. The main outcome measures that were studied were patient characteristics, actual and risk-adjusted graft and patient survival rates after transplantation, organ quality as quantified by the donor risk index (DRI), wait-listed patients per million population by DSA, and competition as quantified by the Hirschman-Herfindahl index (HHI). Centers were stratified by HHI levels as no competition or as low, medium (or mid), or high competition. In comparison with DSAs without competition, the low-, mid-, and high-competition DSAs (1) performed transplantation for patients with a higher risk of graft failure [hazard ratio (HR) = 1.24, HR = 1.26, and HR = 1.34 (P < 0.001 for each)] and a higher risk of death [HR = 1.21, HR = 1.23, and HR = 1.34 (P < 0.001 for each)] and for a higher proportion of sicker patients as quantified by the Model for End-Stage Liver Disease (MELD) score [10.0% versus 14.8%, 20.1%, and 28.2% with a match MELD score of 31-40 (P < 0.001 for each comparison)], (2) were more likely to use organs in the highest risk quartile as quantified by the DRI [18.3% versus 27.6%, 20.4%, and 31.7% (P ? 0.001 for each)], and (3) listed more patients per million population [18 (median) versus 34 (P = not significant), 37 (P = 0.005), and 45 (P = 0.0075)]. Significant variability in patient selection for transplantation is associated with market variables characterizing competition among centers. These findings suggest both positive and negative effects of competition among health care providers.
Related JoVE Video
Pediatric liver transplantation for urea cycle disorders and organic acidemias: United Network for Organ Sharing data for 2002-2012.
Liver Transpl.
PUBLISHED: 07-11-2013
Show Abstract
Hide Abstract
Decision making concerning liver transplantation is unique for children with urea cycle disorders (UCDs) and organic acidemias (OAs) because of their immediate high priority on the waiting list, which is not related to the severity of their disease. There are limited national outcome data on which recommendations about liver transplantation for UCDs or OAs can be based. This study was a retrospective analysis of United Network for Organ Sharing data for liver recipients who underwent transplantation at an age?
Related JoVE Video
Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.
Transplantation
PUBLISHED: 07-05-2013
Show Abstract
Hide Abstract
In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified.
Related JoVE Video
Validating posttransplant hepatocellular carcinoma recurrence data in the united network for organ sharing database.
Liver Transpl.
PUBLISHED: 07-04-2013
Show Abstract
Hide Abstract
The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database is the most comprehensive collection of liver transplantation data, but the quality of these data with respect to hepatocellular carcinoma (HCC) recurrence has not been well assessed. In this study, we compared observed HCC recurrence rates in the UNOS database to expected rates calculated with a hierarchical model for recurrence adjusted for recipient and tumor characteristics. We used the UNOS Standard Transplant Analysis and Research data set for adult transplant patients with an initial exception for an HCC diagnosis granted between January 1, 2006 and September 30, 2010 who underwent transplantation within the same time window. We developed a risk-adjusted Poisson model with patients as the unit of analysis, random effects for transplant centers, and years of follow-up as an offset to predict expected recurrences for each center. To further investigate the possibility of underreporting, we imputed expected recurrences for non-HCC deaths. In all, 5034 HCC liver transplant recipients were identified, and 6.8% experienced recurrence at a median of 1 year after transplantation. The covariate-adjusted shrinkage estimates of the observed/expected HCC recurrence ratios by transplant center ranged from 0.6 to 1.76 (median = 0.97). The 95% confidence intervals for the shrinkage ratios included unity for every center, and this indicated that none could be unambiguously identified as having lower or higher than expected HCC recurrence rates. Imputing outcomes for patients potentially experiencing unreported recurrence changed the center-specific shrinkage ratios to 0.72 to 1.39 (median = 0.98), with no centers having a shrinkage ratio significantly different from 1. The observed HCC recurrence rate was not significantly lower than the expected rate at any center, and this suggests that no systematic underreporting has occurred. This study validates the OPTN HCC recurrence data and supports their potential for further analysis. Liver Transpl 19:1318-1323, 2013. © 2013 AASLD.
Related JoVE Video
Association mapping of the PARK10 region for Parkinsons disease susceptibility genes.
Parkinsonism Relat. Disord.
PUBLISHED: 07-02-2013
Show Abstract
Hide Abstract
Previous studies indicate that as many as six genes within the PARK10 region (RNF11, UQCRH, HIVEP3, EIF2B3, USP24, ELAVL4) might modify susceptibility or age at onset in Parkinsons disease (PD).
Related JoVE Video
p38 mitogen-activated protein kinase interacts with vinculin at focal adhesions during fatty acid-stimulated cell adhesion.
Biochem. Cell Biol.
PUBLISHED: 06-24-2013
Show Abstract
Hide Abstract
Arachidonic acid stimulates cell adhesion by activating ?2?1 integrins in a process that depends on protein kinases, including p38 mitogen activated protein kinase. Here, we describe the interaction of cytoskeletal components with key signaling molecules that contribute to the spreading of, and morphological changes in, arachidonic acid-treated MDA-MB-435 human breast carcinoma cells. Arachidonic acid-treated cells showed increased attachment and spreading on collagen type IV, as measured by electric cell-substrate impedance sensing. Fatty acid-treated cells displayed short cortical actin filaments associated with an increased number of ?1 integrin-containing pseudopodia, whereas untreated cells displayed elongated stress fibers and fewer clusters of ?1 integrins. Confocal microscopy of arachidonic acid-treated cells showed that vinculin and phospho-p38 both appeared enriched in pseudopodia and at the tips of actin filaments, and fluorescence ratio imaging indicated the increase was specific for the phospho-(active) form of p38. Immunoprecipitates of phospho-p38 from extracts of arachidonic acid-treated cells contained vinculin, and GST-vinculin fusion proteins carrying the central region of vinculin bound phospho-p38, whereas fusion proteins expressing the terminal portions of vinculin did not. These data suggest that phospho-p38 associates with particular domains on critical focal adhesion proteins that are involved in tumor cell adhesion and spreading, and that this association can be regulated by factors in the tumor microenvironment.
Related JoVE Video
Production of H2 at fast rates using a nickel electrocatalyst in water-acetonitrile solutions.
Chem. Commun. (Camb.)
PUBLISHED: 06-08-2013
Show Abstract
Hide Abstract
We report a synthetic nickel complex containing proton relays, [Ni(P(Ph)2N(C6H4OH)2)2](BF4)2 (P(Ph)2N(C6H4OH)2 = 1,5-bis(p-hydroxyphenyl)-3,7-diphenyl-1,5-diaza-3,7-diphosphacyclo-octane), that catalyzes the production of H2 in aqueous acetonitrile with turnover frequencies of 750-170,000 s(-1) at experimentally determined overpotentials of 310-470 mV.
Related JoVE Video
Identification of liver transplant candidates with hepatocellular carcinoma and a very low dropout risk: Implications for the current organ allocation policy.
Liver Transpl.
PUBLISHED: 05-26-2013
Show Abstract
Hide Abstract
It has been shown that patients with hepatocellular carcinoma (HCC) meeting the United Network for Organ Sharing T2 (Milan) criteria have an advantage in comparison with patients without HCC under the current organ allocation system for liver transplantation (LT). We hypothesized that within the T2 HCC group, there is a subgroup with a low risk of wait-list dropout that should not receive the same listing priority. This study evaluated 398 consecutive patients with T2 HCC listed for LT with a Model for End-Stage Liver Disease exception from March 2005 to January 2011 at our center. Competing risk (CR) regression was used to determine predictors of dropout. The probabilities of dropout due to tumor progression or death without LT according to the CR analysis were 9.4% at 6 months and 19.6% at 12 months. The median time from listing to LT was 8.8 months, and the median time from listing to dropout or death without LT was 7.2 months. Significant predictors of dropout or death without LT according to a multivariate CR regression included 1 tumor of 3.1 to 5 cm (versus 1 tumor of 3 cm or less), 2 or 3 tumors, a lack of a complete response to the first locoregional therapy (LRT), and a high alpha-fetoprotein (AFP) level after the first LRT. A subgroup (19.9%) that met certain criteria (1 tumor of 2 to 3 cm, a complete response after the first LRT, and an AFP level ? 20 ng/mL after the first LRT) had 1- and 2-year probabilities of dropout of 1.3% and 1.6%, respectively, whereas the probabilities were 21.6% and 26.5% for all other patients (P = 0.004). In conclusion, a combination of tumor characteristics and a complete response to the first LRT define a subgroup of patients with a very low risk of wait-list dropout who do not require the same listing priority. Our results may have important implications for the organ allocation policy for HCC. Liver Transpl 19:1343-1353, 2013. © 2013 AASLD.
Related JoVE Video
Determinants of second-order bile duct visualization at CT cholangiography in potential living liver donors.
AJR Am J Roentgenol
PUBLISHED: 04-27-2013
Show Abstract
Hide Abstract
The purpose of this article is to investigate the determinants of second-order bile duct visualization at CT cholangiography in living potential liver donors.
Related JoVE Video
In vivo packaging of triacylglycerols enhances Arabidopsis leaf biomass and energy density.
Plant Physiol.
PUBLISHED: 04-24-2013
Show Abstract
Hide Abstract
Our dependency on reduced carbon for energy has led to a rapid increase in the search for sustainable alternatives and a call to focus on energy densification and increasing biomass yields. In this study, we generated a uniquely stabilized plant structural protein (cysteine [Cys]-oleosin) that encapsulates triacylglycerol (TAG). When coexpressed with diacylglycerol O-acyltransferase (DGAT1) in Arabidopsis (Arabidopsis thaliana), we observed a 24% increase in the carbon dioxide (CO2) assimilation rate per unit of leaf area and a 50% increase in leaf biomass as well as approximately 2-, 3-, and 5-fold increases in the fatty acid content of the mature leaves, senescing leaves, and roots, respectively. We propose that the coexpression led to the formation of enduring lipid droplets that prevented the futile cycle of TAG biosynthesis/lipolysis and instead created a sustained demand for de novo lipid biosynthesis, which in turn elevated CO2 recycling in the chloroplast. Fatty acid profile analysis indicated that the formation of TAG involved acyl cycling in Arabidopsis leaves and roots. We also demonstrate that the combination of Cys-oleosin and DGAT1 resulted in the highest accumulation of fatty acids in the model single-cell eukaryote, Saccharomyces cerevisiae. Our results support the notion that the prevention of lipolysis is vital to enabling TAG accumulation in vegetative tissues and confirm the earlier speculation that elevating fatty acid biosynthesis in the leaf would lead to an increase in CO2 assimilation. The Cys-oleosins have applications in biofuels, animal feed, and human nutrition as well as in providing a tool for investigating fatty acid biosynthesis and catabolism.
Related JoVE Video
Calcineurin inhibitor-free mycophenolate mofetil/sirolimus maintenance in liver transplantation: the randomized spare-the-nephron trial.
Liver Transpl.
PUBLISHED: 04-08-2013
Show Abstract
Hide Abstract
Mycophenolate mofetil (MMF) and sirolimus (SRL) have been used for calcineurin inhibitor (CNI) minimization to reduce nephrotoxicity following liver transplantation. In this prospective, open-label, multicenter study, patients undergoing transplantation from July 2005 to June 2007 who were maintained on MMF/CNI were randomized 4 to 12 weeks after transplantation to receive MMF/SRL (n?=?148) or continue MMF/CNI (n?=?145) and included in the intent-to-treat population. The primary efficacy endpoints were the mean percentage change in the calculated glomerular filtration rate (GFR) and a composite of biopsy-proven acute rejection (BPAR), graft lost, death, and lost to follow-up 12 months after transplantation. Patients were followed for a median of 519 days after randomization. MMF/SRL was associated with a significantly greater renal function improvement from baseline with a mean percentage change in GFR of 19.7?±?40.6 (versus 1.2?±?39.9 for MMF/CNI, P?=?0.0012). The composite endpoint demonstrated the noninferiority of MMF/SRL versus MMF/CNI (16.4% versus 15.4%, 90% confidence interval?=?-7.1% to 9.0%). The incidence of BPAR was significantly greater with MMF/SRL (12.2%) versus MMF/CNI (4.1%, P?=?0.02). Graft loss (including death) occurred in 3.4% of the MMF/SRL-treated patients and in 8.3% of the MMF/CNI-treated patients (P?=?0.04). Malignancy-related deaths were less frequent with MMF/SRL. Adverse events caused withdrawal for 34.2% of the MMF/SRL-treated patients and for 24.1% of the MMF/CNI-treated patients (P?=?0.06). The use of MMF/SRL is an option for liver transplant recipients who can benefit from improved renal function but is associated with an increased risk of rejection (but not graft loss).
Related JoVE Video
Evaluation of the test of significant toxicity for determining the toxicity of effluents and ambient water samples.
Environ. Toxicol. Chem.
PUBLISHED: 03-29-2013
Show Abstract
Hide Abstract
The test of significant toxicity (TST) is a hypothesis-testing approach based on bioequivalence developed by the U.S. Environmental Protection Agency (U.S. EPA) for analyzing whole-effluent toxicity (WET) and ambient toxicity data. The present study compares results of acute and chronic toxicity tests of effluent, storm-water, and ambient (i.e., receiving-water) samples using both the TST and the standard no-observed-effect concentration (NOEC) approach. Valid WET data were analyzed from 890 tests provided by more than 25 dischargers in California and Washington, USA, representing the majority of test methods used in the U.S. WET program. An additional 3,201 freshwater chronic toxicity tests, obtained from ambient monitoring programs in California, were also analyzed. The TST and NOEC approaches both declared a low number (<6.5%) of tests toxic if effects were below the unacceptable toxicity regulatory management decision (RMD) of 25% effect in chronic tests or 20% effect in acute tests. However, those test methods having generally lower within-test variability and greater test power (e.g., urchin fertilization test) had a much lower percentage of tests declared toxic than the NOEC approach when effects were below the unacceptable toxicity RMD. In addition, the TST showed fewer tests to be nontoxic than NOEC if the test exhibited effects greater than the toxicity RMD (0.1 and 9.6% for TST and NOEC, respectively, for effluents and 0 and 9.5%, respectively, for ambient samples). Our results demonstrate that the TST is more likely to identify a toxic sample when effects are fairly substantial (? 25% effect in chronic testing and ? 20% effect in acute tests) and less likely to identify a sample as toxic when effects are negligible (? 10% effect). Furthermore, these results demonstrate that appropriate WET data interpretation benefits from having well-designed test methods with sufficient power to identify significant toxicity or biologically insignificant effects when they occur.
Related JoVE Video
Transformation of social networks in the late pre-Hispanic US Southwest.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-25-2013
Show Abstract
Hide Abstract
The late pre-Hispanic period in the US Southwest (A.D. 1200-1450) was characterized by large-scale demographic changes, including long-distance migration and population aggregation. To reconstruct how these processes reshaped social networks, we compiled a comprehensive artifact database from major sites dating to this interval in the western Southwest. We combine social network analysis with geographic information systems approaches to reconstruct network dynamics over 250 y. We show how social networks were transformed across the region at previously undocumented spatial, temporal, and social scales. Using well-dated decorated ceramics, we track changes in network topology at 50-y intervals to show a dramatic shift in network density and settlement centrality from the northern to the southern Southwest after A.D. 1300. Both obsidian sourcing and ceramic data demonstrate that long-distance network relationships also shifted from north to south after migration. Surprisingly, social distance does not always correlate with spatial distance because of the presence of network relationships spanning long geographic distances. Our research shows how a large network in the southern Southwest grew and then collapsed, whereas networks became more fragmented in the northern Southwest but persisted. The study also illustrates how formal social network analysis may be applied to large-scale databases of material culture to illustrate multigenerational changes in network structure.
Related JoVE Video
A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.
Clin. Cancer Res.
PUBLISHED: 03-20-2013
Show Abstract
Hide Abstract
This phase I study was conducted to identify the maximum-tolerated dose (MTD) of alvocidib when combined with vorinostat in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2. Secondary objectives included investigating the pharmacokinetic and pharmacodynamic effects of the combination.
Related JoVE Video
Ex vivo split-liver transplantation: the true right/left split.
HPB (Oxford)
PUBLISHED: 03-18-2013
Show Abstract
Hide Abstract
BACKGROUND: Successful left lateral segment (sectionectomy) and right trisegmentectomy (trisectionectomy) split-liver transplantation (SLT) have been achieved. However, there are few reports of the use of true right/left splitting in SLT. METHODS: A single-centre retrospective review of true right/left ex vivo split-liver transplants performed during the period 1993-2010 was conducted. Nine cadaveric liver grafts underwent splitting and the resultant 18 allografts were used in transplants performed at the study centre. RESULTS: In the nine right lobe recipients, 10-year patient and graft survival rates were both 74%. There were no vascular complications, one biliary complication and one re-exploration. In the nine left lobe recipients, 10-year patient and graft survival rates were 78% and 66%, respectively. Postoperative complications included six biliary complications, four of which required surgical revision and all of which occurred within 5 months of transplantation, and two vascular complications, including one early hepatic artery thrombosis (HAT) and one late HAT, one of which required retransplantation. Five left lobe recipients required re-exploration, and one patient developed small-for-size syndrome following SLT, which resolved with conservative measures. CONCLUSIONS: True right/left ex vivo?SLT remains a viable option for facilitating the expansion of the adult cadaver donor pool and allows for excellent patient and graft survival. Postoperative morbidity remains high, especially in recipients of the left lobe graft, and must be balanced with the benefits to be derived from transplant.
Related JoVE Video
Offer patterns of nationally placed livers by donation service area.
Liver Transpl.
PUBLISHED: 03-17-2013
Show Abstract
Hide Abstract
We previously reported that national liver distribution is highly concentrated in 6 US centers, and this raises the possibility of expedited placement. Therefore, we evaluated all national offers of nationally placed livers (n=1625) to adult wait-list candidates from February 2005 to January 2010. We developed a model to predict national utilization pathways; pathways exceeding the best-fit linear unbiased predictions by ?3 standard errors were defined as preferred. All 51 donation service areas (DSAs) placed 1 or more livers nationally, but the percentage per DSA ranged from 1% to 36%. Of 2830 possible national DSA-center pathways, 87% were used. Five hundred eighty livers (36%) were accepted on the first national offer. Four DSAs accounted for 47% of first-national-offer livers, and 44% of these were accepted by a single center. In comparison with first-offer livers using nonpreferred pathways, first offers along a preferred pathway were offered to fewer status 1 candidates (19% versus 61%) and had lower median model for end-stage liver disease (MELD) scores (22 versus 36, P<0.001). In conclusion, DSA placement patterns of national livers vary widely, with 4 DSAs exporting a high proportion of national livers on the first national offer to non-status 1 candidates with MELD scores less than their local transplant MELD scores. Although this practice may facilitate liver placement, it raises the possibility of expedience trumping patient need. Here we propose changes to the national liver distribution system that will help to balance equity, efficiency, and transparency.
Related JoVE Video
Direct determination of equilibrium potentials for hydrogen oxidation/production by open circuit potential measurements in acetonitrile.
Inorg Chem
PUBLISHED: 03-14-2013
Show Abstract
Hide Abstract
Open circuit potentials were measured for acetonitrile solutions of a variety of acids and their conjugate bases under 1 atm H2. Acids examined were triethylammonium, dimethylformamidium, 2,6-dichloroanilinium, 4-cyanoanilinium, 4-bromoanilinium, and 4-anisidinium salts. These potentials, along with the pKa values of the acids, establish the value of the standard hydrogen electrode (SHE) potential in acetonitrile as -0.028(4) V vs the ferrocenium/ferrocene couple. Dimethylformamidium forms homoconjugates and other aggregates with dimethylformamide; open circuit potentials (OCPs) were used to quantify the extent of these reactions. Overpotentials for electrocatalytic hydrogen production and oxidation were determined from open circuit potentials and voltammograms of acidic or basic catalyst solutions under H2. For these solutions, agreement between OCP values and potentials calculated using the Nernst equation is within 12 mV. Use of the measured equilibrium potential allows direct comparison of catalytic systems in different media; it requires neither pKa values, homoconjugation constants, nor the SHE potential.
Related JoVE Video
Decadal analysis of deceased organ donation in Spain and the United States linking an increased donation rate and the utilization of older donors.
Liver Transpl.
PUBLISHED: 02-26-2013
Show Abstract
Hide Abstract
After the foundation of the National Transplant Organization, Spanish rates of deceased donor donation rapidly outpaced US growth over the decade from 1989 to 1999. An analysis of the following decade, 1999-2009, demonstrated a markedly flattened growth curve for Spanish deceased donor organ procurement, which increased only 2.4% from 33.6 to 34.4 donors per million population (pmp). In comparison, over the same decade in the United States, the rate of deceased donation increased from 20.9 to 26.3 donors pmp (25.8%). An age group comparison demonstrated a much higher donation rate among older donors in Spain. For example, the number of donors older than 70 years increased from 3.8 to 8.8 pmp (a 132% increase), and they now constitute 25.4% of all Spanish organ donors. In contrast, the number of US donors older than 70 years increased from 1.0 to 1.3 pmp, and they constitute only 4.4% of total deceased donors. Over the same decade, the number of younger donors (15-30 years old) decreased from 6.6 to 2.5 pmp (a 62% decrease) in Spain, and this contrasted with a slightly increased US donation rate for the same age subgroup (a 15.5% increase from 5.8 to 6.7 pmp). Although older donors were more rarely used in the United States, growth in donation over the 2 decades (1989-2009) was strongly associated with the utilization of donors aged 65 or older (P?
Related JoVE Video
Ratios of biliary glutathione disulfide (GSSG) to glutathione (GSH): a potential index to screen drug-induced hepatic oxidative stress in rats and mice.
Anal Bioanal Chem
PUBLISHED: 02-03-2013
Show Abstract
Hide Abstract
Hepatotoxicity of drug candidates is one of the major concerns in drug screening in early drug discovery. Detection of hepatic oxidative stress can be an early indicator of hepatotoxicity and benefits drug selection. The glutathione (GSH) and glutathione disulfide (GSSG) pair, as one of the major intracellular redox regulating couples, plays an important role in protecting cells from oxidative stress that is caused by imbalance between prooxidants and antioxidants. The quantitative determination of the GSSG/GSH ratios and the concentrations of GSH and GSSG have been used to indicate oxidative stress in cells and tissues. In this study, we tested the possibility of using the biliary GSSG/GSH ratios as a biomarker to reflect hepatic oxidative stress and drug toxicity. Four compounds that are known to alter GSH and GSSG levels were tested in this study. Diquat (diquat dibromide monohydrate) and acetaminophen were administered to rats. Paraquat and tert-butyl hydroperoxide were administered to mice to induce changes of biliary GSH and GSSG. The biliary GSH and GSSG were quantified using calibration curves prepared with artificial bile to account for any bile matrix effect in the LC-MS analysis and to avoid the interference of endogenous GSH and GSSG. With four examples (in rats and mice) of drug-induced changes in the kinetics of the biliary GSSG/GSH ratios, this study showed the potential for developing an exposure response index based on biliary GSSG/GSH ratios for predicting hepatic oxidative stress.
Related JoVE Video
Conformational equilibria of N,N-dimethylsuccinamic acid and its lithium salt as a function of solvent.
Org. Lett.
PUBLISHED: 01-30-2013
Show Abstract
Hide Abstract
The conformational preferences of N,N-dimethylsuccinamic acid and its Li(+) salt were estimated by comparing the respective experimental NMR vicinal proton-proton coupling constants to semiempirical coupling constants for each staggered conformer as derived by the Haasnoot-De Leeuw-Altona method. The strong gauche preferences for the Li(+) salts clearly depended more on the solvents hydrogen-bond donating strength (?) than on their hydrogen-bond accepting (?) counterpart, where ? and ? are the corresponding Kamlet-Taft parameters.
Related JoVE Video
Use of rifabutin for the treatment of a latent tuberculosis infection in a patient after solid organ transplantation.
Liver Transpl.
PUBLISHED: 01-26-2013
Show Abstract
Hide Abstract
Latent tuberculosis infection is an important problem for solid organ transplant recipients because of the frequency of its occurrence and its potential for reactivation. Because of the high mortality rate associated with active tuberculosis infections in transplant recipients, guidelines from the American Thoracic Society recommend treatment for latent tuberculosis in this population. However, the choice of treatments is often difficult because liver transplant recipients may be more sensitive to isoniazid hepatotoxicity, and rifampin has significant drug interactions with the calcineurin inhibitors used for immunosuppression. Two prior case reports described success with the use of rifabutin, a rifampin alternative, as part of a multidrug treatment regimen for active tuberculosis in posttransplant patients; however, there is no prior literature describing any experience with rifabutin for the treatment of latent tuberculosis in the posttransplant setting. We present a summary of tacrolimus drug levels and corresponding dose requirements for a single posttransplant patient during the administration of 3 different latent tuberculosis drug regimens: rifampin alone, rifampin plus ketoconazole, and rifabutin. In this patients case, rifabutin allowed the maintenance of adequate tacrolimus levels, although an approximate 2.5-fold increase in the dose was required. Rifampin alone was associated with inadequate immunosuppressant levels, and rifampin plus ketoconazole was associated with a problematically prolonged QT interval and concerns about inadequate tuberculosis treatment.
Related JoVE Video
Conformational preferences of cis-1,3-cyclopentanedicarboxylic acid and its salts by 1H NMR spectroscopy: energetics of intramolecular hydrogen bonds in DMSO.
J. Org. Chem.
PUBLISHED: 01-14-2013
Show Abstract
Hide Abstract
The conformational populations of cis-1,3-cyclopentanedicarboxylic acid (1) and its mono- and dianion were established in DMSO solution by comparing the vicinal proton–proton coupling constants (3J(HH)) obtained in solution to their theoretical counterparts. Geometries used for 3J(HH) theoretical estimation (using Karplus-type equations) were obtained from optimized structures at the B3LYP/6-31G(2d,2p) level. The diacid (1) adopted many conformations, whereas the ionized species (1A mono- and 1B dianion) assumed single conformations. A downfield chemical shift of 19.45 ppm (??(H) = 7.43 ppm) observed at ?60 °C was indicative of intramolecular hydrogen bonding in 1A, which was later corroborated by determining the ratio of the first (K1) to the second (K2) ionization constants. K1/K2 in DMSO (1.3 × 10(7)) was significantly larger than the value in water (2 × 10). In addition, K1/K(E) = 200 (where K(E) is the acidity constant of the monomethylester of 1) was greater than the intramolecular hydrogen bonding threshold value of 2. The calculated intramolecular hydrogen bond strength of 1A was ~3.1 kcal mol(–1), which is ~2.7 kcal mol(–1) more stable than the values for cis-1,3-cyclohexanedicarboxylic acid (2A). Thus, the relative energies of intramolecular hydrogen bonding in the monoanions 1A and 2A suggests that 1,3-diaxial conformers are more favored for cyclopentane than for cyclohexane rings.
Related JoVE Video
Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.
Invest New Drugs
PUBLISHED: 01-13-2013
Show Abstract
Hide Abstract
Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination.
Related JoVE Video
Left hepatectomy versus right hepatectomy for living donor liver transplantation: shifting the risk from the donor to the recipient.
Liver Transpl.
PUBLISHED: 01-09-2013
Show Abstract
Hide Abstract
Living donor liver transplantation (LDLT), originally used in children with left lateral segment grafts, has been expanded to adults who require larger grafts to support liver function. Most adult LDLT procedures have been performed with right lobe grafts, and this means a significant risk of morbidity for the donors. To minimize the donor risk for adults, there is renewed interest in smaller left lobe grafts. The smaller graft size increases the recipient risk in the form of small-for-size syndrome (SFSS) and essentially transfers the risk from the donor to the recipient. We review the donor and recipient risks of LDLT and pay particular attention to the different types of liver grafts and the use of graft inflow modification to ameliorate the risk of SFSS. Finally, a new metric is proposed for quantifying the recipient benefit in exchange for a specific donor risk.
Related JoVE Video
Visual cues given by humans are not sufficient for Asian elephants (Elephas maximus) to find hidden food.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Recent research suggests that domesticated species--due to artificial selection by humans for specific, preferred behavioral traits--are better than wild animals at responding to visual cues given by humans about the location of hidden food. Although this seems to be supported by studies on a range of domesticated (including dogs, goats and horses) and wild (including wolves and chimpanzees) animals, there is also evidence that exposure to humans positively influences the ability of both wild and domesticated animals to follow these same cues. Here, we test the performance of Asian elephants (Elephas maximus) on an object choice task that provides them with visual-only cues given by humans about the location of hidden food. Captive elephants are interesting candidates for investigating how both domestication and human exposure may impact cue-following as they represent a non-domesticated species with almost constant human interaction. As a group, the elephants (n = 7) in our study were unable to follow pointing, body orientation or a combination of both as honest signals of food location. They were, however, able to follow vocal commands with which they were already familiar in a novel context, suggesting the elephants are able to follow cues if they are sufficiently salient. Although the elephants inability to follow the visual cues provides partial support for the domestication hypothesis, an alternative explanation is that elephants may rely more heavily on other sensory modalities, specifically olfaction and audition. Further research will be needed to rule out this alternative explanation.
Related JoVE Video
Druggability assessment of protein-protein interfaces.
Future Med Chem
PUBLISHED: 11-22-2011
Show Abstract
Hide Abstract
Recent success stories concerning the targeting of protein-protein interactions (PPIs) have led to an increased focus on this challenging target class for drug discovery. This article explores various avenues to assess the druggability of PPIs and describes a druggability decision flow chart, which can be applied to any PPI target. This flow chart not only covers small molecules but also peptidomimetics, peptides and conformationally restricted peptides as potential modalities for targeting PPIs. Additionally, a retrospective analysis of PPI druggability using various computational tools is summarized. The application of a systematic approach as presented in this paper will increase confidence that modulators (e.g., small organic molecules or peptides) can ultimately be identified for a particular target before a decision is made to commit significant discovery resources.
Related JoVE Video
Overweight and obesity in pediatric liver transplant recipients: prevalence and predictors before and after transplant, United Network for Organ Sharing Data, 1987-2010.
Pediatr Transplant
PUBLISHED: 11-17-2011
Show Abstract
Hide Abstract
Obesity is extremely common in adult liver transplant recipients and healthy U.S. children. Little is known about the prevalence or risk factors for post-transplant obesity in pediatric liver transplant recipients. UNOS data on all U.S. liver transplants 1987-2010 in children 6?months-20?yr at transplant were analyzed. Subjects were categorized as underweight, normal weight, overweight, or obese by CDC guidelines. Predictors of weight status at and after transplant were identified using multivariate logistic regression. Of 3043 children 6-24?months at transplant, 14% were overweight. Of 4658 subjects 2-20?yr at transplant, 16% were overweight and 13% obese. Children overweight/obese at transplant were more likely to be overweight/obese at one, two, and five?yr after transplant in all age groups after adjusting for age, ethnicity, primary diagnosis, year of transplant, and transplant type. Weight status at transplant was not associated with overweight/obesity by 10?yr after transplant. The prevalence of post-transplant obesity remained high in long-term follow-up, from 20% to 50% depending on age and weight status at transplant. Weight status at transplant is the strongest predictor of post-transplant overweight/obesity. To optimize long-term outcomes in pediatric liver transplant recipients, monitoring for obesity and its comorbidities is important.
Related JoVE Video
Living kidney donor follow-up: state-of-the-art and future directions, conference summary and recommendations.
Am. J. Transplant.
PUBLISHED: 11-04-2011
Show Abstract
Hide Abstract
In light of continued uncertainty regarding postkidney donation medical, psychosocial and socioeconomic outcomes for traditional living donors and especially for donors meeting more relaxed acceptance criteria, a meeting was held in September 2010 to (1) review limitations of existing data on outcomes of living kidney donors; (2) assess and define the need for long-term follow-up of living kidney donors; (3) identify the potential system requirements, infrastructure and costs of long-term follow-up for living kidney donor outcomes in the United States and (4) explore practical options for future development and funding of United States living kidney donor data collection, metrics and endpoints. Conference participants included prior kidney donors, physicians, surgeons, medical ethicists, social scientists, donor coordinators, social workers, independent donor advocates and representatives of payer organizations and the federal government. The findings and recommendations generated at this meeting are presented.
Related JoVE Video
Is it homogeneous or heterogeneous catalysis derived from [RhCp*Cl2]2? In operando XAFS, kinetic, and crucial kinetic poisoning evidence for subnanometer Rh4 cluster-based benzene hydrogenation catalysis.
J. Am. Chem. Soc.
PUBLISHED: 10-28-2011
Show Abstract
Hide Abstract
Determining the true, kinetically dominant catalytically active species, in the classic benzene hydrogenation system pioneered by Maitlis and co-workers 34 years ago starting with [RhCp*Cl(2)](2) (Cp* = [?(5)-C(5)(CH(3))(5)]), has proven to be one of the most challenging case studies in the quest to distinguish single-metal-based "homogeneous" from polymetallic, "heterogeneous" catalysis. The reason, this study will show, is the previous failure to use the proper combination of: (i) in operando spectroscopy to determine the dominant form(s) of the precatalysts mass under catalysis (i.e., operating) conditions, and then crucially also (ii) the previous lack of the necessary kinetic studies, catalysis being a "wholly kinetic phenomenon" as J. Halpern long ago noted. An important contribution from this study will be to reveal the power of quantitiative kinetic poisoning experiments for distinguishing single-metal, or in the present case subnanometer Rh(4) cluster-based catalysis, from larger, polymetallic Rh(0)(n) nanoparticle catalysis, at least under favorable conditions. The combined in operando X-ray absorption fine structure (XAFS) spectroscopy and kinetic evidence provide a compelling case for Rh(4)-based, with average stoichiometry "Rh(4)Cp*(2.4)Cl(4)H(c)", benzene hydrogenation catalysis in 2-propanol with added Et(3)N and at 100 °C and 50 atm initial H(2) pressure. The results also reveal, however, that if even ca. 1.4% of the total soluble Rh(0)(n) had formed nanoparticles, then those Rh(0)(n) nanoparticles would have been able to account for all the observed benzene hydrogenation catalytic rate (using commercial, ca. 2 nm, polyethyleneglycol-dodecylether hydrosol stabilized Rh(0)(n) nanoparticles as a model system). The results--especially the poisoning methodology developed and employed--are of significant, broader interest since determining the nature of the true catalyst continues to be a central, often vexing issue in any and all catalytic reactions. The results are also of fundamental interest in that they add to a growing body of evidence indicating that certain, appropriately ligated, coordinatively unsaturated, subnanometer M(4) transition-metal clusters can be relatively robust catalysts. Also demonstrated herein is that Rh(4) clusters are poisoned by Hg(0), demonstrating for the first time that the classic Hg(0) poisoning test of "homogeneous" vs "heterogeneous" catalysts cannot distinguish Rh(4)-based subnanometer catalysts from Rh(0)(n) nanoparticle catalysts, at least for the present examples of these two specific, Rh-based catalysts.
Related JoVE Video
Medical record and imaging evaluation to identify arterial tortuosity phenotype in populations at risk for intracranial aneurysms.
AMIA Annu Symp Proc
PUBLISHED: 10-22-2011
Show Abstract
Hide Abstract
High arterial tortuosity may signify early arterial pathology which may precede development of intracranial aneurysms. We measured arterial tortuosity of intracranial vessels and reviewed the medical records of three groups of patients: with intracranial aneurysms, without aneurysms but at increased clinical risk, and controls without aneurysms or associated risk factors. There was significant but inconsistent evidence of increased arterial tortuosity in aneurysm cases and high-risk cases across different arteries. Medical records review identified that a subset of aneurysm cases carried a diagnosis of Loeys-Dietz syndrome that is often misdiagnosed as Marfan syndrome. We found increased arterial tortuosity in the Loeys-Dietz syndrome cases. A combination of medical record screening for Marfan syndrome or Loeys-Dietz symptoms such as aneurysms and evaluation of arterial tortuosity by a curve of scores from medical images may identify previously undiagnosed cases of Loeys-Dietz syndrome.
Related JoVE Video
Validation of an arterial tortuosity measure with application to hypertension collection of clinical hypertensive patients.
BMC Bioinformatics
PUBLISHED: 10-18-2011
Show Abstract
Hide Abstract
Hypertension may increase tortuosity or twistedness of arteries. We applied a centerline extraction algorithm and tortuosity metric to magnetic resonance angiography (MRA) brain images to quantitatively measure the tortuosity of arterial vessel centerlines. The most commonly used arterial tortuosity measure is the distance factor metric (DFM). This study tested a DFM based measurements ability to detect increases in arterial tortuosity of hypertensives using existing images. Existing images presented challenges such as different resolutions which may affect the tortuosity measurement, different depths of the area imaged, and different artifacts of imaging that require filtering.
Related JoVE Video
Outcomes with split liver transplantation in 106 recipients: the University of California, San Francisco, experience from 1993 to 2010.
Arch Surg
PUBLISHED: 09-21-2011
Show Abstract
Hide Abstract
Split liver transplantation (SLT) allows for expansion of the deceased donor pool.
Related JoVE Video
Occlusion of the thoracic duct using ultrasonically activated shears in six dogs.
Vet Surg
PUBLISHED: 09-16-2011
Show Abstract
Hide Abstract
To assess the feasibility of sealing the thoracic duct (TD) in dogs using ultrasonically activated shears via thoracoscopy.
Related JoVE Video
Management of coronary artery disease in end-stage renal disease.
Semin Dial
PUBLISHED: 09-09-2011
Show Abstract
Hide Abstract
Despite a substantial number of patients with end-stage renal disease who have coronary artery disease, the comparative effectiveness of revascularization procedures such as coronary artery bypass grafting and percutaneous coronary intervention remain unclear. Innovations in the field of coronary artery revascularization and concomitant changes in the standard of practice have improved outcomes in general. However, meaningful clinical decision-making remains difficult because it requires clinicians to extrapolate evidence derived from studies in the general population to patients with kidney disease for whom there is limited information from intervention trials. In non-randomized studies, this high-risk population for cardiovascular morbidity and mortality appear to derive substantial benefits from coronary revascularization. However, specific treatment decisions are often made based upon individual circumstances and contexts that are not well captured in these studies. This article reviews the available evidence, and its limitations, for deciding between various revascularization strategies for patients with end-stage renal disease. Several considerations that arise while making such decisions are discussed.
Related JoVE Video
Computerized adaptive assessment of personality disorder: introducing the CAT-PD project.
J Pers Assess
PUBLISHED: 09-07-2011
Show Abstract
Hide Abstract
Assessment of personality disorders (PD) has been hindered by reliance on the problematic categorical model embodied in the most recent Diagnostic and Statistical Model of Mental Disorders (DSM), lack of consensus among alternative dimensional models, and inefficient measurement methods. This article describes the rationale for and early results from a multiyear study funded by the National Institute of Mental Health that was designed to develop an integrative and comprehensive model and efficient measure of PD trait dimensions. To accomplish these goals, we are in the midst of a 5-phase project to develop and validate the model and measure. The results of Phase 1 of the project--which was focused on developing the PD traits to be assessed and the initial item pool--resulted in a candidate list of 59 PD traits and an initial item pool of 2,589 items. Data collection and structural analyses in community and patient samples will inform the ultimate structure of the measure, and computerized adaptive testing will permit efficient measurement of the resultant traits. The resultant Computerized Adaptive Test of Personality Disorder (CAT-PD) will be well positioned as a measure of the proposed DSM-5 PD traits. Implications for both applied and basic personality research are discussed.
Related JoVE Video
Comproportionation of cationic and anionic tungsten complexes having an N-heterocyclic carbene ligand to give the isolable 17-electron tungsten radical CpW(CO)2(IMes)(•).
J. Am. Chem. Soc.
PUBLISHED: 08-29-2011
Show Abstract
Hide Abstract
A series consisting of a tungsten anion, radical, and cation, supported by the N-heterocyclic carbene 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and spanning formal oxidation states W(0), W(I), and W(II), has been synthesized, isolated, and characterized. Reaction of the hydride CpW(CO)(2)(IMes)H with KH and 18-crown-6 gives the tungsten anion [CpW(CO)(2)(IMes)](-)[K(18-crown-6)](+). Electrochemical oxidation of [CpW(CO)(2)(IMes)](-) in MeCN (0.2 M (n)Bu(4)N(+)PF(6)(-)) is fully reversible (E(1/2) = -1.65 V vs Cp(2)Fe(+•/0)) at all scan rates, indicating that CpW(CO)(2)(IMes)(•) is a persistent radical. Hydride transfer from CpW(CO)(2)(IMes)H to Ph(3)C(+)PF(6)(-) in MeCN affords [cis-CpW(CO)(2)(IMes)(MeCN)](+)PF(6)(-). Comproportionation of [CpW(CO)(2)(IMes)](-) with [CpW(CO)(2)(IMes)(MeCN)](+) gives the 17-electron tungsten radical CpW(CO)(2)(IMes)(•). This complex shows paramagnetically shifted resonances in the (1)H NMR spectrum and has been characterized by IR spectroscopy, low-temperature EPR spectroscopy, and X-ray diffraction. CpW(CO)(2)(IMes)(•) is stable with respect to disproportionation and dimerization. NMR studies of degenerate electron transfer between CpW(CO)(2)(IMes)(•) and [CpW(CO)(2)(IMes)](-) are reported. DFT calculations were carried out on CpW(CO)(2)(IMes)H, as well as on related complexes bearing NHC ligands with N,N substituents Me (CpW(CO)(2)(IMe)H) or H (CpW(CO)(2)(IH)H) to compare to the experimentally studied IMes complexes with mesityl substituents. These calculations reveal that W-H homolytic bond dissociation energies (BDEs) decrease with increasing steric bulk of the NHC ligand, from 67 to 64 to 63 kcal mol(-1) for CpW(CO)(2)(IH)H, CpW(CO)(2)(IMe)H, and CpW(CO)(2)(IMes)H, respectively. The calculated spin density at W for CpW(CO)(2)(IMes)(•) is 0.63. The W radicals CpW(CO)(2)(IMe)(•) and CpW(CO)(2)(IH)(•) are calculated to form weak W-W bonds. The weakly bonded complexes [CpW(CO)(2)(IMe)](2) and [CpW(CO)(2)(IH)](2) are predicted to have W-W BDEs of 6 and 18 kcal mol(-1), respectively, and to dissociate readily to the W-centered radicals CpW(CO)(2)(IMe)(•) and CpW(CO)(2)(IH)(•).
Related JoVE Video
Comprehensive thermochemistry of W-H bonding in the metal hydrides CpW(CO)2(IMes)H, [CpW(CO)2(IMes)H](•+), and [CpW(CO)2(IMes)(H)2]+. Influence of an N-heterocyclic carbene ligand on metal hydride bond energies.
J. Am. Chem. Soc.
PUBLISHED: 08-29-2011
Show Abstract
Hide Abstract
The free energies interconnecting nine tungsten complexes have been determined from chemical equilibria and electrochemical data in MeCN solution (T = 22 °C). Homolytic W-H bond dissociation free energies are 59.3(3) kcal mol(-1) for CpW(CO)(2)(IMes)H and 59(1) kcal mol(-1) for the dihydride [CpW(CO)(2)(IMes)(H)(2)](+) (where IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene), indicating that the bonds are the same within experimental uncertainty for the neutral hydride and the cationic dihydride. For the radical cation, [CpW(CO)(2)(IMes)H](•+), W-H bond homolysis to generate the 16-electron cation [CpW(CO)(2)(IMes)](+) is followed by MeCN uptake, with free energies for these steps being 51(1) and -16.9(5) kcal mol(-1), respectively. Based on these two steps, the free energy change for the net conversion of [CpW(CO)(2)(IMes)H](•+) to [CpW(CO)(2)(IMes)(MeCN)](+) in MeCN is 34(1) kcal mol(-1), indicating a much lower bond strength for the 17-electron radical cation of the metal hydride compared to the 18-electron hydride or dihydride. The pK(a) of CpW(CO)(2)(IMes)H in MeCN was determined to be 31.9(1), significantly higher than the 26.6 reported for the related phosphine complex, CpW(CO)(2)(PMe(3))H. This difference is attributed to the electron donor strength of IMes greatly exceeding that of PMe(3). The pK(a) values for [CpW(CO)(2)(IMes)H](•+) and [CpW(CO)(2)(IMes)(H)(2)](+) were determined to be 6.3(5) and 6.3(8), much closer to the pK(a) values reported for the PMe(3) analogues. The free energy of hydride abstraction from CpW(CO)(2)(IMes)H is 74(1) kcal mol(-1), and the resultant [CpW(CO)(2)(IMes)](+) cation is significantly stabilized by binding MeCN to form [CpW(CO)(2)(IMes)(MeCN)](+), giving an effective hydride donor ability of 57(1) kcal mol(-1) in MeCN. Electrochemical oxidation of [CpW(CO)(2)(IMes)](-) is fully reversible at all observed scan rates in cyclic voltammetry experiments (E° = -1.65 V vs Cp(2)Fe(+/0) in MeCN), whereas CpW(CO)(2)(IMes)H is reversibly oxidized (E° = -0.13(3) V) only at high scan rates (800 V s(-1)). For [CpW(CO)(2)(IMes)(MeCN)](+), high-pressure NMR experiments provide an estimate of ?G° = 10.3(4) kcal mol(-1) for the displacement of MeCN by H(2) to give [CpW(CO)(2)(IMes)(H)(2)](+).
Related JoVE Video
Elderly recipients of hepatitis C positive renal allografts can quickly develop liver disease.
J. Surg. Res.
PUBLISHED: 08-22-2011
Show Abstract
Hide Abstract
Our institution explored using allografts from donors with Hepatitis C virus (HCV) for elderly renal transplantation (RT). Thirteen HCV- elderly recipients were transplanted with HCV+ allografts (eD+/R-) between January 2003 and April 2009. Ninety HCV- elderly recipients of HCV- allografts (eD-/R-), eight HCV+ recipients of HCV+ allografts (D+/R+) and thirteen HCV+ recipients of HCV- allografts (D-/R+) were also transplanted. Median follow-up was 1.5 (range 0.8-5) years. Seven eD+/R- developed a positive HCV viral load and six had elevated liver transaminases with evidence of hepatitis on biopsy. Overall, eD+/R- survival was 46% while the eD-/R- survival was 85% (P = 0.003). Seven eD+/R- died during follow-up. Causes included multi-organ failure and sepsis (n = 4), cancer (n = 1), failure-to-thrive (n = 1) and surgical complications (n = 1). One eD+/R- died from causes directly related to HCV infection. In conclusion, multiple eD+/R- quickly developed HCV-related liver disease and infections were a frequent cause of morbidity and mortality.
Related JoVE Video
A randomized, multicenter study comparing steroid-free immunosuppression and standard immunosuppression for liver transplant recipients with chronic hepatitis C.
Liver Transpl.
PUBLISHED: 08-19-2011
Show Abstract
Hide Abstract
This randomized, prospective, multicenter trial compared the safety and efficacy of steroid-free immunosuppression (IS) to the safety and efficacy of 2 standard IS regimens in patients undergoing transplantation for hepatitis C virus (HCV) infection. The outcome measures were acute cellular rejection (ACR), severe HCV recurrence, and survival. The patients were randomized (1:1:2) to tacrolimus (TAC) and corticosteroids (arm 1; n = 77), mycophenolate mofetil (MMF), TAC, and corticosteroids (arm 2; n = 72), or MMF, TAC, and daclizumab induction with no corticosteroids (arm 3; n = 146). In all, 295 HCV RNA-positive subjects were enrolled. At 2 years, there were no differences in ACR, HCV recurrence (biochemical evidence), patient survival, or graft survival rates. The side effects of IS did not differ, although there was a trend toward less diabetes in the steroid-free group. Liver biopsy samples revealed no significant differences in the proportions of patients in arms 1, 2, and 3 with advanced HCV recurrence (ie, an inflammation grade ? 3 and/or a fibrosis stage ? 2) in years 1 (48.2%, 50.4%, and 43.0%, respectively) and 2 (69.5%, 75.9%, and 68.1%, respectively). Although we have found that steroid-free IS is safe and effective for liver transplant recipients with chronic HCV, steroid sparing has no clear advantage in comparison with traditional IS.
Related JoVE Video
Electrocatalytic oxidation of formate by [Ni(P(R)2N(R)2)2(CH3CN)]2+ complexes.
J. Am. Chem. Soc.
PUBLISHED: 07-22-2011
Show Abstract
Hide Abstract
[Ni(P(R)(2)N(R)(2))(2)(CH(3)CN)](2+) complexes with R = Ph, R = 4-MeOPh or R = Cy, R = Ph , and a mixed-ligand [Ni(P(R)(2)N(R)(2))(P(R(2))N(R(2)))(CH(3)CN)](2+) with R = Cy, R = Ph, R = Ph, have been synthesized and characterized by single-crystal X-ray crystallography. These and previously reported complexes are shown to be electrocatalysts for the oxidation of formate in solution to produce CO(2), protons, and electrons, with rates that are first-order in catalyst and formate at formate concentrations below ?0.04 M (34 equiv). At concentrations above ?0.06 M formate (52 equiv), catalytic rates become nearly independent of formate concentration. For the catalysts studied, maximum observed turnover frequencies vary from <1.1 to 15.8 s(-1) at room temperature, which are the highest rates yet reported for formate oxidation by homogeneous catalysts. These catalysts are the only base-metal electrocatalysts as well as the only homogeneous electrocatalysts reported to date for the oxidation of formate. An acetate complex demonstrating an ?(1)-OC(O)CH(3) binding mode to nickel has also been synthesized and characterized by single-crystal X-ray crystallography. Based on this structure and the electrochemical and spectroscopic data, a mechanistic scheme for electrocatalytic formate oxidation is proposed which involves formate binding followed by a rate-limiting proton and two-electron transfer step accompanied by CO(2) liberation. The pendant amines have been demonstrated to be essential for electrocatalysis, as no activity toward formate oxidation was observed for the similar [Ni(depe)(2)](2+) (depe = 1,2-bis(diethylphosphino)ethane) complex.
Related JoVE Video
Hepatic steatosis at 1 year is an additional predictor of subsequent fibrosis severity in liver transplant recipients with recurrent hepatitis C virus.
Liver Transpl.
PUBLISHED: 07-20-2011
Show Abstract
Hide Abstract
Recurrent hepatitis C virus (HCV) is the most common cause of graft loss for HCV-infected recipients of liver transplantation (LT). Diabetes mellitus (DM) has been associated with increased rates of fibrosis progression, but whether steatosis affects post-LT outcomes independently of DM is unclear. Using a retrospective cohort of HCV-infected LT recipients, we determined the prevalence of hepatic steatosis and evaluated the relationship between steatosis on index biopsy 1 year after LT (± 6 months) and the severity of the subsequent fibrosis. One hundred fifty-two LT recipients with HCV were followed up for a median of 2.09 years (range = 0.13-6.17 years) after index biopsy; the median number of biopsy procedures per patient after index biopsy was 2 (range = 1-6). Steatosis (? 5%) was present in 45 individuals (29.6%) according to index biopsy samples taken 1 year after LT; the steatosis was mild (grade 1) in 80% of the patients. In the multivariate analysis, the presence of steatosis 1 year after LT was positively associated with HCV genotype 3 [odds ratio (OR) = 3.60, P = 0.02], older donor age (OR = 1.03, P = 0.04), and pre-LT hypertension (OR = 3.29, P = 0.009). Two years after index biopsy, the cumulative rate of significant fibrosis (F2-F4 on the Ludwig-Batts scale) was 49% in the patients with steatosis at 1 year and 24% in the patients without steatosis (P = 0.003). In the multivariate analysis, steatosis at 1 year was an independent predictor of subsequent F2 to F4 fibrosis (HR = 2.63, 95% CI = 1.49-4.63). Steatosis was a stronger predictor of fibrosis in the setting of sirolimus use (hazard ratio = 9.38, 95% confidence interval = 1.37-64.16, P = 0.02). In conclusion, steatosis is frequent in the early post-LT period, and steatosis within the first year after LT is a marker of a higher risk of fibrosis progression in HCV-infected patients.
Related JoVE Video
Experience with laparoscopic donor nephrectomy among more than 1000 cases: low complication rates, despite more challenging cases.
Arch Surg
PUBLISHED: 07-20-2011
Show Abstract
Hide Abstract
Despite the overall acceptance of laparoscopic donor nephrectomy (LDNX), concern remains about the application of this technique in certain complex situations, such as right-sided nephrectomies and in donors with complex kidney anatomy and obese donors. This study was designed to determine if complication rates have remained stable as we have offered LDNX to all medically acceptable donors and to analyze the results of cases in each of the complex categories. We hypothesized that complication rates in the 3 complex categories would be equivalent to those among more straightforward cases.
Related JoVE Video
In vivo and ex vivo measurements of the mean ADC values of lipid necrotic core and hemorrhage obtained from diffusion weighted imaging in human atherosclerotic plaques.
J Magn Reson Imaging
PUBLISHED: 07-15-2011
Show Abstract
Hide Abstract
To determine the apparent diffusion coefficient (ADC) values of lipid and hemorrhage in atherosclerotic plaque in human carotid arteries in vivo and compare the values obtained from ex vivo carotid endarterectomy specimens.
Related JoVE Video
Botulinum toxin for subacute/chronic neck pain.
Cochrane Database Syst Rev
PUBLISHED: 07-08-2011
Show Abstract
Hide Abstract
Neck disorders are common, disabling and costly. Botulinum toxin (BoNT) intramuscular injections are often used with the intention of treating neck pain.
Related JoVE Video
simple hit counter

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.