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Find video protocols related to scientific articles indexed in Pubmed.
International Federation of Gynecology and Obstetrics Staging Classification for Cancer of the Ovary, Fallopian Tube, and Peritoneum: Estimation of Survival in Patients With Node-Positive Epithelial Ovarian Cancer.
Int. J. Gynecol. Cancer
PUBLISHED: 11-19-2014
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The objective of this study was to determine the survival of patients with node-positive epithelial ovarian cancer according to the 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system.
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A phase I trial of AT9283 (a selective inhibitor of Aurora kinases) in children and adolescents with solid tumours: A Cancer Research UK study.
Clin. Cancer Res.
PUBLISHED: 11-06-2014
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Purpose: A phase I trial of AT9283 (a multi-targeted inhibitor of Aurora kinases A and B) was conducted in children and adolescents with solid tumours, to identify maximum-tolerated dose (MTD), safety, efficacy, pharmacokinetics and pharmacodynamic activity. Experimental Design: AT9283 was administered as a 72-hour continuous intravenous infusion every 3 weeks. A rolling-six design, explored six dose levels (7, 9, 11.5, 14.5, 18.5 and 23 mg/m2/day). Pharmacokinetic and pharmacodynamic assessments, included inhibition of phospho-histone 3 (pHH3) in paired skin punch biopsies. Results: Thirty three patients were evaluable for toxicity. There were six dose limiting toxicities and the MTD was 18.5 mg/m2/day. Most common drug-related toxicities were haematological (neutropaenia, anaemia and thrombocytopaenia in 36.4, 18.2 and 21.2% of patients), which were Grade ?3 in 30.3, 6.1 and 3% of patients. Non-haematological toxicities included fatigue, infections, febrile neutropaenia and ALT elevation. One patient with central nervous system primitive neuroectodermal tumour (CNS-PNET) achieved a Partial Response after 16 cycles and three cases were stable for 4 or more cycles. Plasma concentrations were comparable to those in adults at the same dose level, clearance was similar although half-life was shorter (4.9±1.5 hours, compared to 8.4±3.7 hours in adults). Inhibition of Aurora kinase B was shown by reduction in pHH3 in 17/18 patients treated at ?11.5 mg/m2/day. Conclusions: AT9283 was well tolerated in children and adolescents with solid tumours with manageable haematologic toxicity. Target inhibition was demonstrated. Disease stabilisation was documented in intra-cranial and extra-cranial paediatric solid tumours and a phase II dose determined.
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Active Food Packaging Based on Molecularly Imprinted Polymers: Study of the Release Kinetics of Ferulic Acid.
J. Agric. Food Chem.
PUBLISHED: 11-05-2014
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A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.
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Invited Commentary: Multiple Human Papillomavirus Infections and Type Replacement-Anticipating the Future After Human Papillomavirus Vaccination.
Am. J. Epidemiol.
PUBLISHED: 10-29-2014
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Prophylactic human papillomavirus (HPV) vaccination with 3 doses of either of 2 commercially available vaccines is highly efficacious in preventing infections with the most carcinogenic types of HPV (HPV 16 and HPV 18) at the cervix and other anatomical sites at which HPV-related cancers develop. Concern has been raised that eradicating the most virulent HPV types, 16 and 18, could result in 1 or more of the types that are not targeted by the vaccine occupying the ecological niche created by the elimination of these types, referred to as type replacement. In this issue of the Journal, Yang et al. (Am J Epidemiol. 2014;000(00):000-000) report on concurrent infections with multiple HPV types in unvaccinated women who underwent cervical screening in New Mexico (December 2007-April 2009) to identify possible interactions between HPV types, which if present could suggest the possibility of type replacement. Consistent with previous reports, they show minimal type-specific interactions among women with normal cytology, which they consider an indication that type replacement of HPV 16/18 is unlikely to be an issue in the general population postvaccination. Type replacement may be of less concern with the introduction of multivalent vaccines that include most of the carcinogenic HPV types; continued surveillance postvaccination should improve our understanding of the impact of HPV vaccination on type distribution and screening performance.
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Inhibition of HSP90 by AT13387 Delays the Emergence of Resistance to BRAF Inhibitors and Overcomes Resistance to dual BRAF and MEK Inhibition in Melanoma Models.
Mol. Cancer Ther.
PUBLISHED: 10-27-2014
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Emergence of clinical resistance to BRAF inhibitors, alone or in combination with MEK inhibitors, limits clinical responses in melanoma. Inhibiting HSP90 offers an approach to simultaneously interfere with multiple resistance mechanisms. Using the HSP90 inhibitor, AT13387, which is currently in clinical trials, we investigated the potential of HSP90 inhibition to overcome or delay the emergence of resistance to these kinase inhibitors in melanoma models. In vitro, treating vemurafenib-sensitive cells (A375 or SK-MEL-28) with a combination of AT13387 and vemurafenib prevented colony growth under conditions where vemurafenib treatment alone generated resistant colonies. In vivo, when AT13387 was combined with vemurafenib in a SK-MEL-28, vemurafenib-sensitive model, no regrowth of tumors was observed over 5 months, although 2 out of 7 tumors in the vemurafenib monotherapy group relapsed in this time. Together these data suggest that the combination of these agents can delay the emergence of resistance. Cell lines with acquired vemurafenib resistance, derived from these models (A375R, SK-MEL-28R) were also sensitive to HSP90 inhibitor treatment; key clients were depleted, apoptosis was induced and growth in 3D-culture was inhibited. Similar effects were observed in cell lines with acquired resistance to both BRAF and MEK inhibitors (SK-MEL-28RR, WM164RR, 1205LuRR). These data suggest that treatment with an HSP90 inhibitor, such as AT13387, is a potential approach for combatting resistance to BRAF and MEK inhibition in melanoma. Moreover, frontline combination of these agents with an HSP90 inhibitor could delay the emergence of resistance, providing a strong rationale for clinical investigation of such combinations in BRAF-mutated melanoma.
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Chelation assistance as a tool for the selective preparation of an imidazole-based mesoionic palladium carbene complex.
Chem. Commun. (Camb.)
PUBLISHED: 10-27-2014
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A C(4)-bound palladium-N-heterocyclic carbene (4) was selectively obtained from the C(2)-unsubstituted imidazolium salt 3. The higher stability of the C(4) versus the C(2)-bound carbene complex due to pyridine chelation assistance allowed this mesoionic compound to be obtained.
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Measurement of Endothelium-Dependent Vasodilation in Mice.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 10-23-2014
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Endothelium-dependent, flow-mediated vasodilation after an increase in shear stress at the endothelial lining of conduit arteries during reactive hyperemia after ischemia is a fundamental principle of vascular physiology adapting blood flow to demand of supplied tissue. Flow-mediated vasodilation measurements have been performed in human studies and are of diagnostic and prognostic importance, but have been impossible because of technical limitations in transgenic mice to date, although these represent the most frequently used animal model in cardiovascular research.
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CENTRAL ROLE OF ENOS IN THE MAINTENANCE OF ENDOTHELIAL HOMEOSTASIS.
Antioxid. Redox Signal.
PUBLISHED: 10-21-2014
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Significance: Disruption of endothelial function is considered as a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase is a central regulator of cellular function important to maintain endothelial homeostasis. Recent Advances: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue´s demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells and attraction of circulating angiogenic cells (CAC) both supporting repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Whereas flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of nitric oxide dependent vasodilation, EMP are up-coming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with nitric oxide representing a central signaling molecule. Critical Issues: Improvements of reproducibility and observer-independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research. Future Directions: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance.
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Rho Kinase and Dopaminergic Degeneration: A Promising Therapeutic Target for Parkinson's Disease.
Neuroscientist
PUBLISHED: 10-18-2014
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The small GTP-binding protein Rho plays an important role in several cellular functions. RhoA, which is a member of the Rho family, initiates cellular processes that act on its direct downstream effector Rho-associated kinase (ROCK). ROCK inhibition protects against dopaminergic cell death induced by dopaminergic neurotoxins. It has been suggested that ROCK inhibition activates neuroprotective survival cascades in dopaminergic neurons. Axon-stabilizing effects in damaged neurons may represent another mechanism of neuroprotection of dopaminergic neurons by ROCK inhibition. However, it has been shown that microglial cells play a crucial role in neuroprotection by ROCK inhibition and that activation of microglial ROCK mediates major components of the microglial inflammatory response. Additional mechanisms such as interaction with autophagy may also contribute to the neuroprotective effects of ROCK inhibition. Interestingly, ROCK interacts with several brain factors that play a major role in dopaminergic neuron vulnerability such as NADPH-oxidase, angiotensin, and estrogen. ROCK inhibition may provide a new neuroprotective strategy for Parkinson's disease. This is of particular interest because ROCK inhibitors are currently used against vascular diseases in clinical practice. However, it is necessary to develop more potent and selective ROCK inhibitors to reduce side effects and enhance the efficacy.
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Enantiopure N,N,O-scorpionate zinc amide and chloride complexes as efficient initiators for the heteroselective ROP of cyclic esters.
Dalton Trans
PUBLISHED: 10-14-2014
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The reaction of bpzbeH, bpzteH (racemic mixture) or (R,R)-bpzmmH (enantiopure) with the amide complexes Zn{N(SiMe3)2}2 or Zn{N(SiHMe2)2}2 in 1?:?1 molar ratio in toluene afforded the mononuclear amide zinc complexes [Zn(NR2)(?(3)-NNO)] () [?(3)-NNO = bpzbe, R = SiMe3, SiHMe2; bpzte, R = SiMe3, SiHMe2; (R,R)-bpzmm, SiMe3, SiHMe2]. These complexes were employed in a protonolysis reaction with HCl-Et2O in 2?:?1 molar ratio to yield the dinuclear amide/chloride zinc complexes [Zn(?(2)-NN-?-O)2{ZnCl(NR2)}] () [?(2)-NN-?-O = bpzbe, R = SiMe3, SiHMe2; bpzte, R = SiMe3, SiHMe2; (R,R)-bpzmm, SiMe3, SiHMe2]. The mononuclear complexes and and dinuclear complexes and are the first enantiopure-scorpionate zinc amide complexes to be synthesized. The single-crystal X-ray structure analysis of derivatives and confirmed a monomeric 4-coordinative structure in which the heteroscorpionate ligands are in a ?(3) coordination mode, while had a dimeric molecular disposition with two ?-bridging alkoxides of the heteroscorpionate ligands between the two six- and four-coordinate Zn(ii) centers. Interestingly, the chiral amide-containing zinc complexes and can act as single-component initiators for the ring-opening polymerization of ?-caprolactone and lactides under mild conditions, affording, in a few hours, medium/low molecular weight polymers with low polydispersity indices. MALDI-ToF mass spectra confirmed that the initiation occurred through a nucleophilic attack by the amide on the lactide monomer, and inspection of the kinetic parameters showed that propagations present the usual pseudo-first order dependence on monomer and catalyst concentrations. In addition, microstructural analysis of poly(rac-lactide)s revealed that the myrtenal substituent on the alkoxide fragment has a significant influence on the degree of stereoselectivity, producing enriched-heterotactic PLAs with a Ps value of up to 0.79 under mild conditions.
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Derivation of Structure-Activity Relationships from the Anticancer Properties of Ruthenium(II) Arene Complexes with 2-Aryldiazole Ligands.
Inorg Chem
PUBLISHED: 10-10-2014
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The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(?(6)-arene)RuCl(?(2)-N,N-HL)]Y [HL = HL(1), HL(2), or HL(3); Y = Cl or BF4; arene = 2-phenoxyethanol (phoxet), benzene (bz), or p-cymene (p-cym)]; (ii) dicationic aqua complexes of the formula [(?(6)-arene)Ru(OH2)(?(2)-N,N-HL(1))](Y)2 (Y = Cl or TfO; arene = phoxet, bz, or p-cym); (iii) the nucleobase derivative [(?(6)-arene)Ru(9-MeG)(?(2)-N,N-HL(1))](PF6)2 (9-MeG = 9-methylguanine); (iv) neutral complexes consistent with the formulation [(?(6)-arene)RuCl(?(2)-N,N-L(1))] (arene = bz or p-cym); (v) the neutral cyclometalated complex [(?(6)-p-cym)RuCl(?(2)-N,C-L(4))]. The cytototoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (MCR-5, MCF-7, A2780, and A2780cis) in order to establish structure-activity relationships. Three of the compounds with the general formula [(?(6)-arene)RuCl(?(2)-N,N-HL(1))]Cl differing in the arene moiety have been studied in depth in terms of thermodynamic dissociation constants, aquation kinetic constants, and DNA binding measurements. The biologically most active compound is the p-cym derivative, which strongly destabilizes the DNA double helix, whereas those with bz and phoxet have only a small effect on the stability of the DNA double helix. Moreover, the inhibitory activity of several compounds toward CDK1 has also been evaluated. The DNA binding ability of some of the studied compounds and their CDK1 inhibitory effect suggest a multitarget mechanism for their biological activity.
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IDENTIFICATION OF TARGETS FOR PREVENTION OF PERITONEAL CATHETER TUNNEL AND EXIT-SITE INFECTIONS IN LOW INCIDENCE SETTINGS.
Perit Dial Int
PUBLISHED: 10-09-2014
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? Background: Peritoneal catheter tunnel and exit-site infection (TESI) complicates the clinical course of peritoneal dialysis (PD) patients. Adherence to recommendations for catheter insertion, exit-site care, and management of Staphylococcus aureus (SAu) carriage reduces, but does not abrogate the risk of these infections. ? Objective: To reappraise the risk profile for TESI in an experienced center with a long-term focus on management of SAu carriage and a low incidence of these infections. ? Method: Following a retrospective, observational design, we investigated 665 patients incident on PD. The main study variable was survival to the first episode of TESI. We considered selected demographic, clinical, and technical variables, applying multivariate strategies of analysis. ? Main results: The overall incidence of TESI was 1 episode/68.5 patient-months. Staphylococcus aureus carriage disclosed at inception of PD (but not if observed sporadically during follow-up) (hazard ratio [HR] 1.53, p = 0.009), PD started shortly after catheter insertion (HR 0.98 per day, p = 0.011), PD after kidney transplant failure (HR 2.18, p= 0.017), lower hemoglobin levels (HR 0.88 per g/dL, p= 0.013) and fast peritoneal transport rates (HR 2.92, p = 0.03) portended an increased risk of TESI. Delaying PD ? 30 days after catheter insertion markedly improved the probability of TESI. Carriage of methicillin-resistant SAu since the start of PD was associated with a high incidence of TESI by these bacteria. On the contrary, resistance to mupirocin did not predict such a risk, probably due to the use of an alternative regime in affected patients. ? Conclusions: Adherence to current recommendations results in a low incidence of TESI in PD patients. Interventions on specific risk subsets have a potential to bring incidence close to negligible levels. Despite systematic screening and management, SAu carriage is still a predictor of TESI. Antibiotic susceptibility patterns may help to refine stratification of the risk of TESI by these bacteria. Early insertion of the peritoneal catheter should be considered whenever possible, to reduce the risk of later TESI.
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[The artistic heritage of the Mexican National Academy of Medicine: Two important pieces].
Gac Med Mex
PUBLISHED: 10-03-2014
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El trabajo que sigue fue presentado en el marco de los festejos del 150 aniversario de la Academia Nacional de Medicina de México (ANMM), el 24 de abril de 2013. Se refiere a dos importantes bienes que posee nuestra Academia: la estatua de Esculapio y El cuadro de los académicos en 1923.
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Interaction between the guanidinium cation and aromatic amino acids.
Phys Chem Chem Phys
PUBLISHED: 09-18-2014
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The interaction of the guanidinium cation with phenylalanine, tyrosine and tryptophan has been studied using a variety of computational methods. Benchmark values for the interaction have been estimated using the CCSD(T) method extrapolated to the complete basis set limit, indicating that the complexation energy amounts to -123.0, -124.4 and -134.2 kJ mol(-1) for Phe, Tyr and Trp, respectively. Most stable minima correspond to neutral folded amino acids, with the cation interacting simultaneously with the carboxyl oxygen, the amino nitrogen and the aromatic ring. However, complexes with the amino acids as zwitterions are as stable as neutral ones. The final relative stability of the different structures results from a complex balance among different contributions to the complexation energy. Extended neutral structures are favored by larger electrostatic and smaller repulsion contributions, as well as by smaller deformation costs for bringing the amino acid to its final geometry into the complex. Zwitterions show large electrostatic and induction contributions that cancel out the huge deformation cost needed to transfer the proton to the amino group. The presence of the cation···? contact in folded minima introduces larger contributions from induction and dispersion (also as a consequence of the bulky guanidinium cation) that are able to overcome other effects, making folded minima the most stable together with zwitterionic ones.
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Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update.
Arch. Toxicol.
PUBLISHED: 09-03-2014
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There is substantial interest in the role of plant secondary metabolites as protective dietary agents. In particular, the involvement of flavonoids and related compounds has become a major topic in human nutrition research. Evidence from epidemiological and human intervention studies is emerging regarding the protective effects of various (poly)phenol-rich foods against several chronic diseases, including neurodegeneration, cancer and cardiovascular diseases. In recent years, the use of HPLC-MS for the analysis of flavonoids and related compounds in foods and biological samples has significantly enhanced our understanding of (poly)phenol bioavailability. These advancements have also led to improvements in the available food composition and metabolomic databases, and consequently in the development of biomarkers of (poly)phenol intake to use in epidemiological studies. Efforts to create adequate standardised materials and well-matched controls to use in randomised controlled trials have also improved the quality of the available data. In vitro investigations using physiologically achievable concentrations of (poly)phenol metabolites and catabolites with appropriate model test systems have provided new and interesting insights on potential mechanisms of actions. This article will summarise recent findings on the bioavailability and biological activity of (poly)phenols, focusing on the epidemiological and clinical evidence of beneficial effects of flavonoids and related compounds on urinary tract infections, cognitive function and age-related cognitive decline, cancer and cardiovascular disease.
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Effect of different human papillomavirus serological and DNA criteria on vaccine efficacy estimates.
Am. J. Epidemiol.
PUBLISHED: 08-19-2014
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Two trials of clinically approved human papillomavirus (HPV) vaccines, Females United to Unilaterally Reduce Endo/Ectocervical Disease (FUTURE I/II) and the Papilloma Trial Against Cancer in Young Adults (PATRICIA), reported a 22% difference in vaccine efficacy (VE) against cervical intraepithelial neoplasia grade 2 or worse in HPV-naïve subcohorts; however, serological testing methods and the HPV DNA criteria used to define HPV-unexposed women differed between the studies. We applied previously described methods to simulate these HPV-naïve subcohorts within the Costa Rica HPV16/18 Vaccine Trial and assessed how these criteria affect the estimation of VE. We applied 2 enzyme-linked immunosorbent assay (ELISA) thresholds for HPV16 and HPV18 seropositivity (8 and 7 ELISA units/mL, respectively, for PATRICIA; 54 and 65 ELISA units/mL, respectively, for FUTURE I/II (to approximate the competitive Luminex immunoassay)) and 2 criteria for HPV DNA positivity (12 oncogenic HPV types, plus HPV66 and 68/73 for PATRICIA; or plus HPV6 and 11 for FUTURE I/II). VE was computed in the 2 naïve subcohorts. Using the FUTURE I/II and PATRICIA criteria, VE estimates against cervical intraepithelial neoplasia grade 2 or worse, regardless of HPV type, were 69.0% (95% confidence interval: 40.3%, 84.9%) and 80.8% (95% confidence interval: 52.6%, 93.5%), respectively (P = 0.1). Although the application of FUTURE I/II criteria to our cohort resulted in the inclusion of more sexually experienced women, methodological differences did not fully explain the VE differences.
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An updated natural history model of cervical cancer: derivation of model parameters.
Am. J. Epidemiol.
PUBLISHED: 07-31-2014
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Mathematical models of cervical cancer have been widely used to evaluate the comparative effectiveness and cost-effectiveness of preventive strategies. Major advances in the understanding of cervical carcinogenesis motivate the creation of a new disease paradigm in such models. To keep pace with the most recent evidence, we updated a previously developed microsimulation model of human papillomavirus (HPV) infection and cervical cancer to reflect 1) a shift towards health states based on HPV rather than poorly reproducible histological diagnoses and 2) HPV clearance and progression to precancer as a function of infection duration and genotype, as derived from the control arm of the Costa Rica Vaccine Trial (2004-2010). The model was calibrated leveraging empirical data from the New Mexico Surveillance, Epidemiology, and End Results Registry (1980-1999) and a state-of-the-art cervical cancer screening registry in New Mexico (2007-2009). The calibrated model had good correspondence with data on genotype- and age-specific HPV prevalence, genotype frequency in precancer and cancer, and age-specific cancer incidence. We present this model in response to a call for new natural history models of cervical cancer intended for decision analysis and economic evaluation at a time when global cervical cancer prevention policy continues to evolve and evidence of the long-term health effects of cervical interventions remains critical.
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Microglial TNF-? mediates enhancement of dopaminergic degeneration by brain angiotensin.
Glia
PUBLISHED: 07-17-2014
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In vitro and in vivo models of Parkinson's disease were used to investigate whether TNF-? plays a major role in the enhancement of the microglial response and dopaminergic degeneration induced by brain angiotensin hyperactivity. Treatment of primary mesencephalic cultures with low doses of the neurotoxin MPP(+) induced a significant loss of dopaminergic neurons, which was enhanced by cotreatment with angiotensin II and inhibited by TNF-? inhibitors. Treatment of primary cultures with angiotensin induced a marked increase in levels of TNF-?, which was inhibited by treatment with angiotensin type-1-receptor antagonists, NADPH-oxidase inhibitors and NFK-? inhibitors. However, TNF-? levels were not significantly affected by treatment with angiotensin in the absence of microglia. The microglial origin of the angiotensin-induced increase in TNF-? levels was confirmed using dopaminergic (MES 23.5) and microglial (N9) cell lines. Inhibition of the microglial Rho-kinase activity also blocked the AII-induced increase in TNF-? levels. Treatment of the dopaminergic cell line with TNF-? revealed that NFK-? activation mediates the deleterious effect of microglial TNF-? on dopaminergic neurons. Treatment of mice with MPTP also induced significant increases in striatal and nigral TNF-? levels, which were inhibited by angiotensin type-1-receptor antagonists or NFK-? inhibitors. The present results show that microglial TNF-? plays a major role in angiotensin-induced dopaminergic cell death and that the microglial release of TNF-? is mediated by activation of angiotensin type-1 receptors, NADPH-oxidase, Rho-kinase and NFK-?.
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Analysis of three strategies to increase screening coverage for cervical cancer in the general population of women aged 60 to 70 years: the CRICERVA study.
BMC Womens Health
PUBLISHED: 07-09-2014
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Cervical cancer is a frequently diagnosed cancer in women worldwide. Despite having easy preventive and therapeutic approaches, it is an important cause of mortality among women.
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Physiological and biochemical responses to severe drought stress of nine Eucalyptus globulus clones: a multivariate approach.
Tree Physiol.
PUBLISHED: 07-08-2014
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Seasonal drought, typical of temperate and Mediterranean environments, creates problems in establishing plantations and affects development and yield, and it has been widely studied in numerous species. Forestry fast-growing species such as Eucalyptus spp. are an important resource in such environments, selected clones being generally used for production purposes in plantations in these areas. However, use of mono-specific plantations increases risk of plant loss due to abiotic stresses, making it essential to understand differences in an individual clone's physiological responses to drought stress. In order to study clonal differences in drought responses, nine Eucalyptus globulus (Labill.) clones (C14, C46, C97, C120, C222, C371, C405, C491 and C601) were gradually subjected to severe drought stress (<14% of field capacity). A total of 31 parameters, physiological (e.g., photosynthesis, gas exchange), biochemical (e.g., chlorophyll content) and hormonal (abscisic acid [ABA] content), were analysed by classic and multivariate techniques. Relationships between parameters were established, allowing related measurements to be grouped into functional units (pigment, growth, water and ABA). Differences in these units showed that there were two distinct groups of E. globulus clones on the basis of their different strategies when faced with drought stress. The C14 group (C14, C120, C405, C491 and C601) clones behave as water savers, maintaining high water content and showing high stomatal adjustment, and reducing their aerial growth to a great extent. The C46 group (C46, C97, C222 and C371) clones behave as water spenders, reducing their water content drastically and presenting osmotic adjustment. The latter maintains the highest growth rate under the conditions tested. The method presented here can be used to identify appropriate E. globulus clones for drought environments, facilitating the selection of material for production and repopulation environments.
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Interaction between NADPH-oxidase and Rho-kinase in angiotensin II-induced microglial activation.
Glia
PUBLISHED: 07-01-2014
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Previous studies have shown that the brain renin-angiotensin system may play a major role, via angiotensin type 1 (AT1) receptors, in the regulation of neuroinflammation, oxidative stress and progression of dopaminergic degeneration. Angiotensin-induced activation of the microglial nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase complex and microglial Rho-kinase are particularly important in this respect. However, it is not known whether crosstalk between Rho-kinase and NADPH-oxidase leads to microglial activation. In the present study, we found that, in the substantia nigra of rats, NADPH-oxidase activation was involved in angiotensin-induced Rho-kinase activation, which, in turn, was involved in angiotensin-induced NADPH-oxidase activation. In N9 microglial cell line and primary microglial cultures, a crosstalk signaling between NADPH-oxidase and Rho-kinase occurred in a positive feedback fashion during angiotensin-induced microglial activation. Angiotensin-induced NADPH-oxidase activation and superoxide generation led to NF-?B translocation and Rho-kinase activation. Rho-kinase activation was involved in regulation of NADPH-oxidase activation via p38 mitogen-activated protein kinase. Moreover, Rho-kinase activation, via NF-?B, upregulated AT1 receptor expression in microglial cells through a feed-forward mechanism. NADPH-oxidase and Rho-kinase pathways are known to be responsible for major components of the microglial response, such as changes involving microglial motility and phagocytosis, generation of superoxide, and release of inflammatory cytokines. The present results show that both pathways are linked by a common mechanism that may constitute a basic means of coordinating the microglial response. GLIA 2014.
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Repurposing human Aurora kinase inhibitors as leads for anti-protozoan drug discovery.
Medchemcomm
PUBLISHED: 06-10-2014
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Hesperadin, an established human Aurora B inhibitor, was tested against cultures of Trypanosoma brucei, Leishmania major, and Plasmodium falciparum, and was identified to be a potent proliferation inhibitor. A series of analogs was designed and tested to establish the initial structure-activity relationships for each parasite. In this study, we identified multiple non-toxic compounds with high potency against T. brucei and P. falciparum with good selectivity. These compounds may represent an opportunity for continued optimization.
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Effect of a Mediterranean Diet Intervention on Dietary Glycemic Load and Dietary Glycemic Index: The PREDIMED Study.
J Nutr Metab
PUBLISHED: 05-27-2014
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Objective. To compare the one year effect of two dietary interventions with MeDiet on GL and GI in the PREDIMED trial. Methods. Participants were older subjects at high risk for cardiovascular disease. This analysis included 2866 nondiabetic subjects. Diet was assessed with a validated 137-item food frequency questionnaire (FFQ). The GI of each FFQ item was assigned by a 5-step methodology using the International Tables of GI and GL Values. Generalized linear models were fitted to assess the relationship between the intervention group and dietary GL and GI at one year of follow-up, using control group as reference. Results. Multivariate-adjusted models showed an inverse association between GL and MeDiet + extra virgin olive oil (EVOO) group: ? = -8.52 (95% CI: -10.83 to -6.20) and MeDiet + Nuts group: ? = -10.34 (95% CI: -12.69 to -8.00), when comparing with control group. Regarding GI, ? = -0.93 (95% CI: -1.38 to -0.49) for MeDiet + EVOO, ? = -1.06 (95% CI: -1.51 to -0.62) for MeDiet + Nuts when comparing with control group. Conclusion. Dietary intervention with MeDiet supplemented with EVOO or nuts lowers dietary GL and GI.
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Synthesis and structural characterization of amido scorpionate rare earth metals complexes.
Dalton Trans
PUBLISHED: 05-16-2014
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The reactivity of hybrid scorpionate/cyclopentadienyl ligands in the form of the protio derivatives as a mixture of two regioisomers, namely bpzcpH [1-{2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1-diphenylethyl}-1,3-cyclopentadiene and 2-{2,2-bis(3,5-dimethylpyrazol-1-yl)-1,1-diphenylethyl}-1,3-cyclopentadiene] and bpztcpH [1-{2,2-bis(3,5-dimethylpyrazol-1-yl)-1-tert-butylethyl}-1,3-cyclopentadiene and 2-{2,2-bis(3,5-dimethylpyrazol-1-yl)-1-tert-butylethyl}-1,3-cyclopentadiene], with the tris(silylamide) precursors [M{N(SiHMe2)2}3(thf)x] of rare earth metals (including the group 3 metals scandium and yttrium) is related to the atomic radii of the metal centres. The reaction with the precursor containing the smallest ion, [Sc{N(SiHMe2)2}3(thf)], did not proceed even heating at reflux temperature in toluene. The reaction with the precursors that contain a medium-sized metal ion, i.e., [M{N(SiHMe2)2}3(thf)2] (M = Y, Lu), proceeded only at high temperature and gave good yields of the silylenediamide-containing derivatives [M{?(2)-NN-Me2Si(NSiHMe2)2}(bpzcp)] (M = Y , Lu ) and [M{?(2)-NN-Me2Si(NSiHMe2)2}(bpztcp)] (M = Y , Lu ) by an double activation of Si-H and Si-N bonds. However, the reaction with the precursors that contained the largest metal ions, i.e., [M{N(SiHMe2)2}3(thf)2] (M = Nd, Sm), proceeded rapidly at room temperature to afford the bis(silylamide) complexes [M{N(SiHMe2)2}2(bpzcp)] (M = Nd , Sm ) and [M{N(SiHMe2)2}2(bpztcp)] (M = Nd , Sm ). Additionally, the alkyl heteroscorpionate yttrium and lutetium complexes [M(CH2SiMe3)2(NNCp)] (M = Y, Lu) reacted with an excess of HN(SiHMe2)2 to give the mixed alkyl/amide derivatives [M{N(SiHMe2)2}(CH2SiMe3)(bpzcp)] (M = Y , Lu ) and [M{N(SiHMe2)2}(CH2SiMe3)(bpztcp)] (M = Y , Lu ). The structures of the complexes were determined by spectroscopic methods and the X-ray crystal structures of , and were also established.
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Gonadal steroids negatively modulate oxidative stress in CBA/Ca female mice infected with P. berghei ANKA.
Biomed Res Int
PUBLISHED: 05-14-2014
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We decreased the level of gonadal steroids in female and male mice by gonadectomy. We infected these mice with P. berghei ANKA and observed the subsequent impact on the oxidative stress response. Intact females developed lower levels of parasitaemia and lost weight faster than intact males. Gonadectomised female mice displayed increased levels of parasitaemia, increased body mass, and increased anaemia compared with their male counterparts. In addition, gonadectomised females exhibited lower specific catalase, superoxide dismutase, and glutathione peroxidase activities in their blood and spleen tissues compared with gonadectomised males. To further study the oxidative stress response in P. berghei ANKA-infected gonadectomised mice, nitric oxide levels were assessed in the blood and spleen, and MDA levels were assessed in the spleen. Intact, sham-operated, and gonadectomised female mice exhibited higher levels of nitric oxide in the blood and spleen compared with male mice. MDA levels were higher in all of the female groups. Finally, gonadectomy significantly increased the oxidative stress levels in females but not in males. These data suggest that differential oxidative stress is influenced by oestrogens that may contribute to sexual dimorphism in malaria.
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Barriers to lose weight from the perspective of children with overweight/obesity and their parents: a sociocultural approach.
J Obes
PUBLISHED: 04-16-2014
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Introduction. There are not enough studies about the barriers to lose weight from the perspective of children and their parents. Methods. Children and adolescents diagnosed with overweight/obesity in the Department of Endocrinology and their parents were invited to participate in a series of focus group discussions (FGD). Twenty-nine children 10-16 years old and 22 parents participated in 7 focus groups; 2 mothers and 2 adolescents participated in depth interviews. All interviews were recorded, transcribed, and analyzed through grounded theory. Results. Parents went to the hospital only when their children presented any obesity complication; for them, overweight was not a health problem. Parents referred to lack of time to supervise about a healthy diet and exercise; besides, the same parents, relatives, friends, and the mass media encourage the consumption of junk food. Children accepted eating a lot, not doing exercise, skipping meals, and not understanding overweight consequences. Both, parents and children, demanded support to do the time recommended for exercise inside the schools. They also suggested getting information from schools and mass media (TV) about overweight consequences, exercise, and healthy food by health workers; they recommended prohibiting announcements about junk food and its sale. Conclusions. The barriers detected were lack of perception of being overweight, its identification as a disease and its consequences, lack of time to supervise a healthy lifestyle, and a big social influence to eat junk food.
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Removal of Anisakis simplex allergens from infected fish during the washing step of surimi production.
J. Sci. Food Agric.
PUBLISHED: 04-15-2014
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The washing operation of fish muscle is one of the key steps in the production of surimi. The aim of this study was to assess in parasitized minced fish the effect of the washing steps on the allergen removal of Anisakis simplex and on protein yield during surimi processing. Experimentally infected hake (Merluccius merluccius) (50 Anisakis simplex s.s L3 larvae per 100?g of muscle) underwent three successive washing steps with water, phosphate buffer (20 mM), sodium bicarbonate (60 mM), or sodium hypochlorite (0.27 mM) in the surimi processing (4?kg muscle, 1:4?w/v for each solution). Total protein concentration and A. simplex antigens and allergens were evaluated in each waste fraction.
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Impact of processing on the bioavailability and vascular effects of blueberry (poly)phenols.
Mol Nutr Food Res
PUBLISHED: 04-04-2014
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Blueberries are a rich source of flavonoids and phenolic acids. Currently, little information is available regarding the impact of processing on the bioavailability and the bioactivity of blueberry (poly)phenols.
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Cation···? interaction and microhydration effects in complexes formed by pyrrolidinium cation and aromatic species in amino acid side chains.
Org. Biomol. Chem.
PUBLISHED: 04-03-2014
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A computational study has been carried out in complexes formed by pyrrolidinium cation and aromatic units present in amino acid side chains. The interaction is stronger with indole (-21.9 kcal mol(-1) at the CCSD(T) complete basis set level) than with phenol (-17.4 kcal mol(-1)) or benzene (-16.1 kcal mol(-1)). Most stable structures show a N-H···? contact between pyrrolidinium cation and the phenyl ring of the three aromatic species, except in phenol complexes where the most stable minimum shows a N-HO hydrogen bond. In phenol and indole complexes, secondary contacts are established between the C-H groups of the carbon skeleton of pyrrolidinium and the aromatic rings or hydroxyl oxygen, being the main reason for the enhanced stability with respect to benzene, where these contacts are not possible. The interaction is mainly controlled by electrostatics, but contributions from induction and dispersion are also significant, especially the latter in indole complexes. These three attractive contributions increase their intensity when going from benzene to phenol and indole. Microhydration effects have been estimated by including up to three water molecules in the complexes. In monohydrated pyrrolidiniumbenzene complex the most stable structure shows the water molecule coordinated to the cation without interacting with the ring. In phenol and indole, otherwise, the water molecule interacts with both the cation and the aromatic species, forming a cyclic hydrogen bond pattern ?(phenyl)···H-N-H···O-H···X (X = ?, O). This pattern is also present among the most stable structures found for complexes with two and three water molecules, though a variety of almost isoenergetic minima showing different hydrogen bond patterns have been found. Water molecules remove the stability differences between phenol and indole complexes, which already with two water molecules show similar stabilities, though around 5 kcal mol(-1) larger than benzene ones.
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Inhibition of the microglial response is essential for the neuroprotective effects of Rho-kinase inhibitors on MPTP-induced dopaminergic cell death.
Neuropharmacology
PUBLISHED: 03-18-2014
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Several recent studies have shown that activation of the RhoA/Rho-associated kinase (ROCK) pathway is involved in the MPTP-induced dopaminergic cell degeneration and possibly in Parkinson's disease. ROCK inhibitors have been suggested as candidate neuroprotective drugs for Parkinson's disease. However, the mechanism responsible for the increased survival of dopaminergic neurons after treatment with ROCK inhibitors is not clear. We exposed primary (neuron-glia) mesencephalic cultures, cultures of the MES 23.5 dopaminergic neuron cell line and primary mesencephalic cultures lacking microglial cells to the dopaminergic neurotoxin MPP+ and the ROCK inhibitor Y-27632 in order to study the effects of ROCK inhibition on dopaminergic cell loss and the length of neurites of surviving dopaminergic neurons. In primary (neuron-glia) cultures, simultaneous treatment with MPP+ and the ROCK inhibitor significantly reduced the loss of dopaminergic neurons. In the absence of microglia, treatment with the ROCK inhibitor did not induce a significant reduction in the dopaminergic cell loss. Treatment with the ROCK inhibitor induced a significant decrease in axonal retraction in primary cultures with and without microglia and in cultures of the MES 23.5 neuron cell line. In conclusion, inhibition of microglial ROCK is essential for the neuroprotective effects of ROCK inhibitors against cell death induced by the dopaminergic neurotoxin MPP+. In addition, ROCK inhibition induced a direct effect against axonal retraction in surviving neurons. However, the latter effect was not sufficient to cause a significant increase in the survival of dopaminergic neurons after treatment with MPP+.
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Proteomic profiling and characterization of differential allergens in the nematodes Anisakis simplex sensu stricto and A. pegreffii.
Proteomics
PUBLISHED: 03-07-2014
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The parasite species complex Anisakis simplex sensu lato (Anisakis simplex sensu stricto; (A. simplex s.s.), A. pegreffii, A. simplex C) is the main cause of severe anisakiasis (allergy) worldwide and is now an important health matter. In this study, the relationship of this Anisakis species complex and their allergenic capacities is assessed by studying the differences between the two most frequent species (A. simplex s.s., A. pegreffii) and their hybrid haplotype by studying active L3 larvae parasiting Merluccius merluccius. They were compared by 2D gel electrophoresis and parallel Western blot (2DE gels were hybridized with pools of sera from Anisakis allergenic patients). Unambiguous spot differences were detected and protein assignation was made by MALDI-TOF/TOF analysis or de novo sequencing. Seventy-five gel spots were detected and the corresponding proteins were identified. Differentially expressed proteins for A. simplex s.s., A. pegreffii, and their hybrid are described and results are statistically supported. Twenty-eight different allergenic proteins are classified according to different families belonging to different biological functions. These proteins are described for the first time as antigenic and potentially new allergens in Anisakis. Comparative proteomic analyses of allergenic capacities are useful for diagnosis, epidemiological surveys, and clinical research. All MS data have been deposited in the ProteomeXchange with identifier PXD000662 (http://proteomecentral.proteomexchange.org/dataset/PXD000662).
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Definitions for the sonographic features of joints in healthy children.
Arthritis Care Res (Hoboken)
PUBLISHED: 03-06-2014
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Objectives Musculoskeletal ultrasonography (MSUS) has potential in the assessment of disease activity and structural damage in childhood arthritides. In order to assess pathology, the ultrasonographic characteristics of joints in healthy children need to be defined first. The aim of this study was to develop definitions for the various components of the normal pediatric joint. Methods Definitions were developed by an expert group and applicability was assessed on a collection of standardized scans of the knee and ankle joints by scoring them on a Likert scale. The definitions were then modified and the applicability was reassessed before sending them for approval to a larger panel of experts. A final scoring on stored images of all relevant joints at different ages followed. Results Five definitions were developed addressing articular bone, cartilage, the joint capsule, the epiphyseal ossification centre and the synovial membrane. 224 ultrasound images of knees and ankles were acquired of which 172 were selected for scoring. An 80 % agreement was not met for either definition but after modifications an 81-95% agreement was reached. This version of the definitions was approved by 15 ultrasound experts. In the final validation exercise all definitions reached an agreement of ? 80% for the shoulder, elbow, wrist, MCP, hip, knee, ankle and MTP. Conclusions Ultrasonographic definitions for the normal pediatric joint were successfully developed through a Delphi process and validated in a practical exercise. These results provide the basis to develop definitions for pathology and support the standardized use of ultrasonography in pediatric rheumatology. © 2014 American College of Rheumatology.
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External morphology explains the success of biological invasions.
Ecol. Lett.
PUBLISHED: 02-26-2014
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Biological invasions have become major players in the current biodiversity crisis, but realistic tools to predict which species will establish successful populations are still unavailable. Here we present a novel approach that requires only a morphometric characterisation of the species. Using fish invasions of the Mediterranean, we show that the abundance of non-indigenous fishes correlates with the location and relative size of occupied morphological space within the receiving pool of species. Those invaders that established abundant populations tended to be added outside or at the margins of the receiving morphospace, whereas non-indigenous species morphologically similar to resident ones failed to develop large populations or even to establish themselves, probably because the available ecological niches were already occupied. Accepting that morphology is a proxy for a species' ecological position in a community, our findings are consistent with ideas advanced since Darwin's naturalisation hypothesis and provide a new warning signal to identify invaders and to recognise vulnerable communities.
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Glutathione S-transferase L1 multiplex serology as a measure of cumulative infection with human papillomavirus.
BMC Infect. Dis.
PUBLISHED: 02-26-2014
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Several assays are used to measure type-specific serological responses to human papillomavirus (HPV), including the bead-based glutathione S-transferase (GST)-L1 multiplex serology assay and virus-like particle (VLP)-based ELISA. We evaluated the high-throughput GST-L1, which is increasingly used in epidemiologic research, as a measure of cumulative HPV infection and future immune protection among HPV-unvaccinated women.
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Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome.
Surg Res Pract
PUBLISHED: 02-20-2014
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Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1) and 2A (MEN-2A) syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome.
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Diversity-oriented synthesis yields a new drug lead for treatment of chagas disease.
ACS Med Chem Lett
PUBLISHED: 02-13-2014
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A phenotypic high-throughput screen using ?100,000 compounds prepared using Diversity-Oriented Synthesis yielded stereoisomeric compounds with nanomolar growth-inhibition activity against the parasite Trypanosoma cruzi, the etiological agent of Chagas disease. After evaluating stereochemical dependence on solubility, plasma protein binding and microsomal stability, the SSS analogue (5) was chosen for structure-activity relationship studies. The p-phenoxy benzyl group appended to the secondary amine could be replaced with halobenzyl groups without loss in potency. The exocyclic primary alcohol is not needed for activity but the isonicotinamide substructure is required for activity. Most importantly, these compounds are trypanocidal and hence are attractive as drug leads for both acute and chronic stages of Chagas disease. Analogue (5) was nominated as the molecular libraries probe ML341 and is available through the Molecular Libraries Probe Production Centers Network.
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Lenalidomide induces immunomodulation in chronic lymphocytic leukemia and enhances antitumor immune responses mediated by NK and CD4 T cells.
Biomed Res Int
PUBLISHED: 02-11-2014
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Lenalidomide is an immunomodulatory drug with therapeutic activity in chronic lymphocytic leukemia (CLL). However, it has pleiotropic effects, and the mechanism of action responsible for its therapeutic activity has not been well defined yet. Herein, we show that lenalidomide treatment does not have an effect on the proliferation of leukemia cells, but it increases the proliferation of B cells from healthy donors. Lenalidomide did not exert a direct effect on the apoptosis of leukemia cells obtained from CLL patients, although it indirectly induced their apoptosis through the activation of nonmalignant immune cells. Thus, lenalidomide markedly increased the proliferation of NK and CD4 T cells. The effect of lenalidomide on NK cells was secondary to the induction of IL-2 production by CD4 T cells. Accordingly, depletion of T cells or blockade of IL-2 activity completely abrogated the proliferation of NK cells. Additionally, lenalidomide enhanced NK and NKT-like cell-mediated natural cytotoxicity against leukemia cells from CLL patients. Lenalidomide also upregulated CD20 expression on leukemia cells and, accordingly, it had a synergistic effect with rituximab on promoting antibody-dependent cell-mediated cytotoxicity against primary leukemia cells. Overall, these observations provide a support for combining lenalidomide with rituximab as a treatment in CLL.
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Risk of colorectal cancer among long-term cervical cancer survivors.
Med. Oncol.
PUBLISHED: 02-01-2014
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Because advances in therapy have increased long-term survival for women with cervical cancer, it is important to study the risk of secondary primary malignancies in high-dose organ areas. From the 1973-2009 National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program, we studied the risk of developing cancer of the colon and rectum in 64,507 cervical cancer patients over 35 years after initial radiation treatment. We also assessed change in risk over time. Kaplan-Meier estimator for survival curve and Cox proportional hazards models was used. More than half (52.6%) of the cervical cancer patients received radiation treatment. In the analyses adjusted for race/ethnicity, age, marital status, surgery status, stage and grade, the risk of colon cancer between those both with and without XRT diverged beginning at approximately 8 years. After 8 years, the hazard ratio for developing colon cancer was 2.00 (95% CI 1.43-2.80) for women with radiation versus those without radiation treatment. The risk of rectal cancer diverged after 15 years of follow-up (HR 4.04, 95% CI 2.08-7.86). After 35 years of follow-up, the absolute risk of developing colon cancer was 6.5% for those who received radiation versus 2.5% for those without, and 3.7 versus 0.8% for rectum. The risk of colon and rectum cancer over 20 years of follow-up after radiation remained the same across three eras (1973-1980, 1981-1990, and 1991-2000). Radiation-induced second cancers of the colon and rectum may occur 8 years after radiation treatment for cervical cancer.
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Effect of stepwise microhydration on the guanidinium···? interaction.
J Mol Model
PUBLISHED: 01-30-2014
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The characteristics of the interaction of microhydrated guanidinium cation with the aromatic moieties present in the aromatic amino acids side chains have been studied by means of computational methods. The most stable minima found for non-hydrated complexes correspond in all cases to structures with guanidinium oriented toward the ring and interacting by means of N-H···? hydrogen bonds. The interaction becomes stronger when going from benzene (-14 kcal mol?¹) to phenol (-17 kcal mol?¹) to indole (-21 kcal mol?¹). These complexes are held together mainly by electrostatics, but with important contributions from induction and dispersion. The presence of a small number of water molecules significantly affects the characteristics of the complexes. Hydrogen bonds formed by water with the cation, another water molecule, or the aromatic units become more and more similar in intensity as water molecules are included in the complex, leading to a great variety of minima with similar stability but showing very different structural patterns. The behavior is similar with the three aromatic units, the differences in stability mainly being a consequence of the different strength of the cation···? contact.
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[Results of the cooperative study of Spanish peritoneal dialysis registries: analysis of 12 years of follow-up].
Nefrologia
PUBLISHED: 01-28-2014
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There is currently no registry that gives a complete and overall view of the peritoneal dialysis (PD) situation in Spain. However, a report on PD in Spain was developed for various conferences and meetings over several years from data provided by each registry in the autonomous communities and regions. The main objective of this study is to analyse this data in aggregate and comparatively to obtain a representative sample of the Spanish population on PD in recent years, in order that analysis and results in terms of demographic data, penetration of the technique, geographical differences, incidence and prevalence, technical aspects, intermediate indicators, comorbidity, and outcomes such as patient and technique survival may be extrapolated to the whole country. DESIGN, MATERIAL AND METHOD: Observational cohort study of autonomous PD registries, covering the largest possible percentage of the adult Spanish population (over 14 years of age) on PD, at least in the last decade (1999-2010), and in the largest possible geographical area in which we were able to recruit. A precise data collection strategy was followed for each regional registry. Once the information was received and clarified, they were added as aggregate data for statistical study.
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Uptake and metabolism of (-)-epicatechin in endothelial cells.
Arch. Biochem. Biophys.
PUBLISHED: 01-19-2014
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Accumulating evidence suggest that diets rich in cocoa flavanols may have beneficial effects on cardiovascular health. The major cocoa flavanol monomer, (-)-epicatechin (EC), is readily absorbed and circulates primarily as glucuronidated, sulfated, and O-methylated metabolites in human plasma. However, cellular metabolism, for example in endothelial cells, is less well defined. In the present study we detail the uptake and cellular metabolism of EC and its major in vivo metabolites, (-)-epicatechin-3'-?-D-glucuronide (E3G), (-)-epicatechin-3'-sulfate (E3S), 3'-O-methyl-(-)-epicatechin-5-sulfate (3ME5S), and 3'-O-methyl-(-)-epicatechin-7-sulfate (3ME7S) in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that EC associates with HUVECs, leading to its intracellular metabolism to 3ME7G and 3ME7S. In contrast, none of the metabolites were taken up by the cells. The metabolic rate and pattern of metabolism in HUVECs was similar to that observed in HepG2 cells, whilst in Caco-2 cells EC was metabolized to E3G, 3ME5G, 3ME7G, 4ME5G, 4ME7G and 3ME7S. Our data support the notion that endothelial cells may contribute significantly to EC metabolism. However, major human circulating metabolites are not accounted for in these model systems underscoring that caution should be taken when drawing conclusions on in vivo flavanol metabolism from in vitro experiments.
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Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways.
Mol Nutr Food Res
PUBLISHED: 01-15-2014
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Consumption of flavanol-rich foods is associated with an improvement in endothelial function. However, the specific biologically active flavanol metabolites involved in this benefit, as well as their molecular mechanisms of action have not been identified. The aim of this work was to examine the effect of plasma flavanol metabolites on adhesion of monocytes to TNF-?-activated endothelial cells and identify potential underlying mechanisms.
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Trends in the national distribution of laparoscopic hysterectomies from 2003 to 2010.
J Minim Invasive Gynecol
PUBLISHED: 01-13-2014
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The purpose of this analysis was to compare the trends in undergoing laparoscopic hysterectomy (versus abdominal or vaginal hysterectomy) based on patient age, race, median income and insurance type, from 2003 to 2010.
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Comparison of antibody responses to human papillomavirus vaccination as measured by three assays.
Front Oncol
PUBLISHED: 01-13-2014
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Different assays, including the competitive Luminex immunoassay (cLIA), secreted alkaline phosphatase neutralization assay (SEAP-NA), and virus-like particle-based ELISA, are commonly used to measure antibody responses after human papillomavirus (HPV) vaccination. Direct assay comparisons aid interpretation of immunogenicity data evaluated by different assays.
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Soluble Factors from Lactobacillus reuteri CRL1098 Have Anti-Inflammatory Effects in Acute Lung Injury Induced by Lipopolysaccharide in Mice.
PLoS ONE
PUBLISHED: 01-01-2014
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We have previously demonstrated that Lactobacillus reuteri CRL1098 soluble factors were able to reduce TNF-? production by human peripheral blood mononuclear cells. The aims of this study were to determine whether L. reuteri CRL1098 soluble factors were able to modulate in vitro the inflammatory response triggered by LPS in murine macrophages, to gain insight into the molecular mechanisms involved in the immunoregulatory effect, and to evaluate in vivo its capacity to exert anti-inflammatory actions in acute lung injury induced by LPS in mice. In vitro assays demonstrated that L. reuteri CRL1098 soluble factors significantly reduced the production of pro-inflammatory mediators (NO, COX-2, and Hsp70) and pro-inflammatory cytokines (TNF-?, and IL-6) caused by the stimulation of macrophages with LPS. NF-kB and PI3K inhibition by L. reuteri CRL1098 soluble factors contributed to these inhibitory effects. Inhibition of PI3K/Akt pathway and the diminished expression of CD14 could be involved in the immunoregulatory effect. In addition, our in vivo data proved that the LPS-induced secretion of the pro-inflammatory cytokines, inflammatory cells recruitment to the airways and inflammatory lung tissue damage were reduced in L. reuteri CRL1098 soluble factors treated mice, providing a new way to reduce excessive pulmonary inflammation.
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Expansion of NK Cells and Reduction of NKG2D Expression in Chronic Lymphocytic Leukemia. Correlation with Progressive Disease.
PLoS ONE
PUBLISHED: 01-01-2014
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The immune system may mediate anti-tumor responses in chronic lymphocytic leukemia (CLL) which may affect disease progression and survival. In this study, we analyzed the immune characteristics of 99 consecutive previously diagnosed CLL patients and 50 healthy controls. The distribution of lymphocyte subsets at diagnosis was retrospectively analyzed. Compared with controls, leukemia patients showed an expansion of NK and CD8 T cells at diagnosis. The relative number of CD8 T cells at diagnosis was associated with time to treatment, suggesting that CD8 T cells may modify disease progression. The distribution of lymphocyte subsets was analyzed again when patients were enrolled in this study. The median time since these patients were diagnosed was 277 weeks. Compared with diagnosis, the absolute number of CD8 T cells significantly decreased in these patients, reaching similar values to healthy controls; however NK cells kept significantly elevated overtime. Nevertheless, NK cells showed an impaired expression of NKG2D receptor and a defective cytotoxic activity. This down-regulation of NKG2D expression was further enhanced in patients with advanced and progressive disease. Additionally, membrane NKG2D levels significantly decreased on CD8 T cells, but a significant increase of NKG2D+CD4+ T cells was observed in CLL patients. The cytotoxic activity of NK cells was diminished in CLL patients; however the treatments with IL-2, IL-15, IL-21 and lenalidomide were able to restore their activity. The effect of IL-2 and IL-15 was associated with the increase of NKG2D expression on immune cells, but the effect of IL-21 and lenalidomide was not due to NKG2D up-regulation. The expansion of NK cells and the reversibility of NK cell defects provide new opportunities for the immunotherapeutic intervention in CLL.
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Effective removal of staphylococcal biofilms by the endolysin LysH5.
PLoS ONE
PUBLISHED: 01-01-2014
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Staphylococcal biofilms are a major concern in both clinical and food settings because they are an important source of contamination. The efficacy of established cleaning procedures is often hindered due to the ability of some antimicrobial compounds to induce biofilm formation, and to the presence of persister cells, a small bacterial subpopulation that exhibits multidrug tolerance. Phage lytic enzymes have demonstrated antimicrobial activity against planktonic and sessile bacteria. However, their ability to lyse and/or select persister cells remains largely unexplored so far. In this work, the lytic activity of the endolysin LysH5 against Staphylococcus aureus and Staphylococcus epidermidis biofilms was confirmed. LysH5 reduced staphylococcal sessile cell counts by 1-3 log units, compared with the untreated control, and sub-inhibitory concentrations of this protein did not induce biofilm formation. LysH5-surviving cells were not resistant to the lytic activity of this protein, suggesting that no persister cells were selected. Moreover, to prove the lytic ability of LysH5 against this subpopulation, both S. aureus exponential cultures and persister cells obtained after treatment with rifampicin and ciprofloxacin were subsequently treated with LysH5. The results demonstrated that besides the notable activity of endolysin LysH5 against staphylococcal biofilms, persister cells were also inhibited, which raises new opportunities as an adjuvant for some antibiotics.
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Brain renin-angiotensin system and dopaminergic cell vulnerability.
Front Neuroanat
PUBLISHED: 01-01-2014
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Although the renin-angiotensin system (RAS) was classically considered as a circulating system that regulates blood pressure, many tissues are now known to have a local RAS. Angiotensin, via type 1 receptors, is a major activator of the NADPH-oxidase complex, which mediates several key events in oxidative stress (OS) and inflammatory processes involved in the pathogenesis of major aging-related diseases. Several studies have demonstrated the presence of RAS components in the basal ganglia, and particularly in the nigrostriatal system. In the nigrostriatal system, RAS hyperactivation, via NADPH-oxidase complex activation, exacerbates OS and the microglial inflammatory response and contributes to progression of dopaminergic degeneration, which is inhibited by angiotensin receptor blockers and angiotensin converting enzyme (ACE) inhibitors. Several factors may induce an increase in RAS activity in the dopaminergic system. A decrease in dopaminergic activity induces compensatory upregulation of local RAS function in both dopaminergic neurons and glia. In addition to its role as an essential neurotransmitter, dopamine may also modulate microglial inflammatory responses and neuronal OS via RAS. Important counterregulatory interactions between angiotensin and dopamine have also been observed in several peripheral tissues. Neurotoxins and proinflammatory factors may also act on astrocytes to induce an increase in RAS activity, either independently of or before the loss of dopamine. Consistent with a major role of RAS in dopaminergic vulnerability, increased RAS activity has been observed in the nigra of animal models of aging, menopause and chronic cerebral hypoperfusion, which also showed higher dopaminergic vulnerability. Manipulation of the brain RAS may constitute an effective neuroprotective strategy against dopaminergic vulnerability and progression of Parkinson's disease.
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Molecular Bases for the Regulation of NKG2D Ligands in Cancer.
Front Immunol
PUBLISHED: 01-01-2014
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NKG2D is an activating receptor expressed by NK and T cells primarily involved in the elimination of transformed and infected cells. NKG2D ligands are self-proteins restrictedly expressed in healthy tissues, but induced in response to signaling pathways commonly associated with transformation. Proliferative, tumor suppressor, and stress signaling pathways linked to the tumorigenic process induce the expression of NKG2D ligands, initiating an immune response against the incipient tumor. Nevertheless, the activity of NKG2D ligands is counter-regulated in vivo by the immunoediting of cancer cells, resulting in the expression of multiple mechanisms of immune evasion in advanced tumors. The redundancy of NKG2D ligands, besides increasing the complexity of their regulation, may impair the generation of these immune evasion mechanisms. In this review, we attempt to integrate the mechanisms and pathways involved in the regulation of NKG2D ligand expression in cancer.
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Phenanthroline ligands are biologically more active than their corresponding ruthenium(ii) arene complexes.
Dalton Trans
PUBLISHED: 12-11-2013
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New cationic, half-sandwich Ru(ii) arene compounds of general formula [(?(6)-arene)RuCl(?(2)-N,N-L)]X (where L are functionalized phenanthrolines such as 1,10-phenanthroline-5-amine (aphen); 5,6-epoxy-5,6-dihydro-[1,10]phenanthroline (ephen); or 4,7-dihydroxy-1,10-phenanthroline (dhphen)) have been prepared to study their anticancer potential. All the isolated complexes have been fully characterized by spectroscopic and analytical techniques. The structure of endo-[(?(6)-p-cymene)RuCl(?(2)-N,N-ephen)]BF4, , has been determined by X-ray crystallography. The in vitro cytotoxicity of the aphen and ephen phenanthrolines and their Ru derivatives [(?(6)-p-cymene)RuCl(?(2)-N,N-L)]Cl ( and , respectively) assessed in tumour cell lines has shown that the free ligands are more active than the organometallic products, with aphen being the most potent specimen. Furthermore, the binding interaction of both and aphen with calf thymus DNA (CT-DNA) has been investigated using a variety of thermodynamic and kinetic techniques. The aphen free ligand intercalates into DNA at low ligand content, whereas forms with DNA a bifunctional partially intercalated-covalent complex, in which the intercalation constant is nearly three orders of magnitude lower than that of aphen. This finding demonstrates that the covalent binding noticeably weakens the intercalation, a feature presumably related to the higher cytotoxic activity of aphen relative to that of .
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Terpene downregulation triggers defense responses in transgenic oranges leading to resistance against fungal pathogens.
Plant Physiol.
PUBLISHED: 11-05-2013
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Terpenoid volatiles are isoprene compounds that are emitted by plants to communicate with the environment. In addition to their function in repelling herbivores and attracting carnivorous predators in green tissues, the presumed primary function of terpenoid volatiles released from mature fruits is the attraction of seed-dispersing animals. Mature oranges primarily accumulate terpenes in peel oil glands, with D-limonene accounting for approximately 97% of the total volatile terpenes. In a previous report, we showed that downregulation of a D-limonene synthase gene alters monoterpene levels in orange antisense (AS) fruits leading to resistance against Penicillium digitatum infection. A global gene expression analysis of AS vs. empty vector (EV) transgenic fruits revealed that the downregulation of D-limonene upregulated genes involved in the innate immune response. Basal levels of jasmonic acid (JA) were substantially higher in the EV compared to AS oranges. Upon fungal challenge, salicylic acid (SA) levels were triggered in EV samples while JA metabolism and signaling were drastically increased in AS orange peels. In nature, D-limonene levels increase in orange fruit once the seeds are fully viable. The inverse correlation between the increase in D-limonene content and the decrease in the defense response suggests that D-limonene promotes the infection by microorganisms that are likely involved in facilitating access to the pulp for seed-dispersing frugivores.
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Novel 3-nitro-1H-1,2,4-triazole-based compounds as potential anti-Chagasic drugs: in vivo studies.
Future Med Chem
PUBLISHED: 10-23-2013
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Chagas disease is caused by the parasite Trypanosoma cruzi, is endemic in Latin America and leads to an estimated 14,000 deaths per year and around 100 million people at risk of infection. Drugs currently used in the treatment of Chagas are old, partially effective and have numerous side effects.
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Heteroscorpionate magnesium alkyls bearing unprecedented apical ?-C(sp3)-mg bonds: heteroselective ring-opening polymerization of rac-lactide.
Inorg Chem
PUBLISHED: 10-16-2013
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The previously described reaction of the low sterically hindered heteroscorpionate lithium acetamidinates [Li(?(3)-pbpamd)(THF)] and [Li(?(3)-tbpamd)(THF)] with a series of commercially available Grignard reagents RMgCl in an equimolecular ratio yielded the magnesium monoalkyls [Mg(R)(?(3)-NNN)] (NNN = pbpamd, R = CH2SiMe3, Et (1), Bn (2); NNN = tbpamd, R = CH2SiMe3, Et (3), Bn (4)). However, subsequent reaction of these monoalkyls [Mg(R)(?(3)-NNN)] with two additional equivalents of the same RMgCl in tetrahydrofuran gave rise to dinuclear dialkyls of the type [RMg(?(3)-N,N,N;?(2)-C,N)MgR(thf)] (?(3)-N,N,N;?(2)-C,N = pbpamd(-), R = CH2SiMe3 (5), Et (6); ?(3)-N,N,N;?(2)-C,N = tbpamd(-), R = CH2SiMe3 (7), Et (8)). Furthermore, when the reaction was carried out in a mixture of tetrahydrofuran/dioxane with the same stoichiometry, a new family of tetranuclear tetraalkyl magnesium complexes [{RMg(?(3)-N,N,N;?(2)-C,N)MgR}2{?-O,O-(C4H8)}] (?(3)-N,N,N;?(2)-C,N = pbpamd(-), R = CH2SiMe3 (9), Et (10), Bn (11); ?(3)-N,N,N;?(2)-C,N = tbpamd(-), R = CH2SiMe3 (12), Et (13), Bn (14)) was obtained. In both families, an apical methine C-H activation process on the heteroscorpionate takes place. The single-crystal X-ray structures of 4, 8, 9, and 12 confirm the nuclearity of each family, with 4-coordinative arrangements for all magnesium atoms. More importantly, the presence in the di- and tetranuclear complexes of unprecedented apical carbanions with a direct ?-C(sp(3))-Mg covalent bond, and as a result, the existence of stereogenic magnesium centers, have been unambiguously confirmed. Interestingly, the dinuclear dialkyls 5 and 7, as well as the tetranuclear tetraalkyls 9, 10, and 12, can act as highly efficient single-component living initiators for the ring-opening polymerization of ?-caprolactone and lactides. Lactide (LA) polymerizations afforded polylactide (PLA) materials with medium molecular weights in only a few minutes even at 20 °C for L-LA and in a few hours at 50 °C for rac-LA propagations. More importantly, microstructural analysis of the poly(rac-lactide) materials revealed that the tetranuclear tetra-alkyl 12 exerts enhanced levels of heteroselectivity on the PLAs under mild conditions, with Ps values up to 0.78.
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Impact of Cooking, Proving, and Baking on the (Poly)phenol Content of Wild Blueberry.
J. Agric. Food Chem.
PUBLISHED: 10-03-2013
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Accumulating evidence suggests that diets rich in (poly)phenols may have positive effects on human health. Currently there is limited information regarding the effects of processing on the (poly)phenolic content of berries, in particular in processes related to the baking industry. This study investigated the impact of cooking, proving, and baking on the anthocyanin, procyanidin, flavonol, and phenolic acid contents of wild blueberry using HPLC with UV and fluorescence detection. Anthocyanin levels decreased during cooking, proving, and baking, whereas no significant changes were observed for total procyanidins. However, lower molecular weight procyanidins increased and high molecular weight oligomers decreased during the process. Quercetin and ferulic and caffeic acid levels remained constant, whereas increases were found for chlorogenic acid. Due to their possible health benefits, a better understanding of the impact of processing is important to maximize the retention of these phytochemicals in berry-containing products.
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Berry (Poly)phenols and Cardiovascular Health.
J. Agric. Food Chem.
PUBLISHED: 09-25-2013
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Berries are a rich source of (poly)phenols, including anthocyanins, flavan-3-ols, procyanidins, flavonols, ellagitannins, and hydroxycinnamates. Epidemiological evidence indicates that the cardiovascular health benefits of diets rich in berries are related to their (poly)phenol content. These findings are supported by small-scale randomized controlled studies (RCTs) that have shown improvements in several surrogate markers of cardiovascular risk such as blood pressure, endothelial function, arterial stiffness, and blood lipids after acute and short-term consumption of blueberries, strawberries, cranberries, or purified anthocyanin extracts in healthy or diseased individuals. However, firm conclusions regarding the preventive value of berry (poly)phenols cannot be drawn due to the small number of existing studies and limitations that apply to the available data, such as lack of controls or failure to assess the absorption and metabolism of (poly)phenols. Although the current evidence is promising, more long-term RCTs are needed to establish the role of berry (poly)phenols to support cardiovascular health.
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Pesticide removal from aqueous solutions by adding salting out agents.
Int J Mol Sci
PUBLISHED: 09-16-2013
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Phase segregation in aqueous biphasic systems (ABS) composed of four hydrophilic ionic liquids (ILs): 1-butyl-3-methylimidazolium methylsulfate and 1-ethyl-3-methylimidazolium methylsulfate (C(n)C?im C?SO?, n = 2 and 4), tributylmethyl phosphonium methylsulfate (P???? C?SO?) and methylpyridinium methylsulfate (C?Py C?SO?) and two high charge density potassium inorganic salts (K?CO? and K?HPO?) were determined by the cloud point method at 298.15 K. The influence of the addition of the selected inorganic salts to aqueous mixtures of ILs was discussed in the light of the Hofmeister series and in terms of molar Gibbs free energy of hydration. The effect of the alkyl chain length of the cation on the methylsulfate-based ILs has been investigated. All the solubility data were satisfactorily correlated to several empirical equations. A pesticide (pentachlorophenol, PCP) extraction process based on the inorganic salt providing a greater salting out effect was tackled. The viability of the proposed process was analyzed in terms of partition coefficients and extraction efficiencies.
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Fuchs superficial marginal keratitis managed with circumferential marginal corneoscleral lamellar patch graft.
Eur J Ophthalmol
PUBLISHED: 09-05-2013
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Purpose: To report a case of Fuchs superficial marginal keratitis managed with circumferential marginal corneoscleral lamellar patch graft.

Methods: Interventional case report.

Results: A 34-year-old man presented with several years history of ill-defined symptoms of binocular ocular irritation associated with vision loss, mostly in the left eye. A superior marginal corneal thinning was found at biomicroscopy of the left eye, with 2 finely vascularized descemetoceles, and a gray epithelial demarcation line without lipid infiltrates. The right eye was clinically normal. Anterior segment optical coherence tomography demonstrated an important corneal thinning from the 7 oclock to 3 oclock positions, without scleral involvement. A circumferential marginal corneoscleral lamellar patch graft was done involving 3 mm of sclera and 3 mm of cornea.

Conclusions: Fuchs superficial marginal keratitis is a rare entity, mostly affecting young adults. It should be considered part of a spectrum of corneal thinning disorders, together with Terriens marginal degeneration. Definitive treatment with a marginal corneoscleral lamellar patch graft with or without conjunctival autograft is suggested.

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Outcomes of robotic sacrocolpopexy using barbed delayed absorbable sutures.
J Minim Invasive Gynecol
PUBLISHED: 09-03-2013
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To evaluate one year outcomes of robotic sacrocolpopexy (RSC) for pelvic organ prolapse (POP) using barbed delayed absorbable sutures.
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Heteroscorpionate aluminium complexes as chiral building blocks to engineer helical architectures.
Dalton Trans
PUBLISHED: 08-16-2013
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Treatment of heteroscorpionate ligand precursors pbptamH, pbpamH, sbpamH and (S)-mbpamH with 2 equivalents of AlR3 (R = Et, Me) yielded the corresponding binuclear organoaluminium complexes [Al2R4(?-pbptam)] (R = Me 1, Et 2), [Al2R4(?-pbpam)] (R = Me 3, Et 4), [Al2R4(?-sbpam)] (R = Me 5, Et 6) and [Al2R4{?-(S)-mbpam}] (R = Me 7, Et 8). These complexes have helical chirality due to the demands of the fixed pyrazole rings. The stereoisomerism and the self-assembly processes of these helicates have been studied in some detail in solution by NMR and in the solid state by X-ray diffraction. Mixtures of M- and P-handed enantiomers and mixtures of M- and P-handed diastereoisomers were obtained when achiral (1–4) and chiral (5–8) heteroscorpionate ligands were used as scaffolds, respectively. Re-crystallization from hexane allowed us to obtain M-homochiral architectures in the solid state for the helical complexes [Al2Et4(?-sbpam)] (6) and [Al2Et4{?-(S)-mbpam}] (8). The reaction of heteroscorpionate ligands with 3 equivalents of AlR3 (R = Me, Et) led to the corresponding trinuclear organoaluminium complexes [Al3R7(?3-pbptam)] (R = Me 9, Et 10), [Al3R7(?3-pbpam)] (R = Me 11, Et 12), [Al3R7(?3-sbpam)] (R = Me 13, Et 14) and [Al3R7{?3-(S)-mbpam}] (R = Me 15, Et 16). The extra AlR3 molecule contributes to the formation of a diastereomeric excess of the PS helicate for complexes 15 and 16. X-ray determination of some of the helical complexes allowed us to witness a versatile and efficient self-assembly process of the building blocks (heteroscorpionate aluminium complexes) directed by noncovalent intermolecular CH–? interactions. The structures of these complexes have been determined by spectroscopic methods and the X-ray crystal structures of 2, 6, 8, and 16 have also been established. Concentration-dependent 1H pulsed field-gradient spin echo (PFGSE) NMR experiments provided evidence for the self-assembly of the single molecular species of complex 2 in solution. The degree of aggregation was calculated for complex 2, with the average number of units constituting the aggregate (N) estimated to be a maximum of 4 molecules in solution before reaching the solid state.
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The impact of pelvic retroperitoneal invasion and distant nodal metastases in epithelial ovarian cancer.
Surg Oncol
PUBLISHED: 08-07-2013
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The absence of disease after debulking surgery is the most important prognostic factor in the treatment of advanced epithelial ovarian cancer (EOC). Occasionally, the presence of extra-abdominal disease complicates the ability to obtain a complete surgery, considering some locations of the metastatic disease as unresectable. The objective of the study was to estimate the survival impact of pelvic retroperitoneal invasion and extrapelvic and aortic distant nodal metastases in EOC patients. The anatomical landmarks of primary cytoreductive surgery will be discussed.
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A role for hippocampal PSA-NCAM and NMDA-NR2B receptor function in flavonoid-induced spatial memory improvements in young rats.
Neuropharmacology
PUBLISHED: 07-17-2013
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The increase in incidence and prevalence of neurodegenerative diseases highlights the need for a more comprehensive understanding of how food components may affect neural systems. In particular, flavonoids have been recognized as promising agents capable of influencing different aspects of synaptic plasticity resulting in improvements in memory and learning in both animals and humans. Our previous studies highlight the efficacy of flavonoids in reversing memory impairments in aged rats, yet little is known about the effects of these compounds in healthy animals, particularly with respect to the molecular mechanisms by which flavonoids might alter the underlying synaptic modifications responsible for behavioral changes. We demonstrate that a 3-week intervention with two dietary doses of flavonoids (Dose I: 8.7 mg/day and Dose II: 17.4 mg/day) facilitates spatial memory acquisition and consolidation (24 recall) (p < 0.05) in young healthy rats. We show for the first time that these behavioral improvements are linked to increased levels in the polysialylated form of the neural adhesion molecule (PSA-NCAM) in the dentate gyrus (DG) of the hippocampus, which is known to be required for the establishment of durable memories. We observed parallel increases in hippocampal NMDA receptors containing the NR2B subunit for both 8.7 mg/day (p < 0.05) and 17.4 mg/day (p < 0.001) doses, suggesting an enhancement of glutamate signaling following flavonoid intervention. This is further strengthened by the simultaneous modulation of hippocampal ERK/CREB/BDNF signaling and the activation of the Akt/mTOR/Arc pathway, which are crucial in inducing changes in the strength of hippocampal synaptic connections that underlie learning. Collectively, the present data supports a new role for PSA-NCAM and NMDA-NR2B receptor on flavonoid-induced improvements in learning and memory, contributing further to the growing body of evidence suggesting beneficial effects of flavonoids in cognition and brain health.
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Impact of human papillomavirus vaccination on cervical cytology screening, colposcopy, and treatment.
Am. J. Epidemiol.
PUBLISHED: 07-10-2013
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The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial randomized 7,466 women aged 18-25 years, 1:1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.
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CORRELATION BETWEEN GLYCEMIC CONTROL AND THE INCIDENCE OF PERITONEAL AND CATHETER TUNNEL AND EXIT-SITE INFECTIONS IN DIABETIC PATIENTS UNDERGOING PERITONEAL DIALYSIS.
Perit Dial Int
PUBLISHED: 07-01-2013
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Diabetes mellitus, especially if complicated by poor glycemic control, portends an increased risk of infection. The significance of this association in the case of diabetic patients undergoing peritoneal dialysis (PD) has not been assessed.
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A prospective study of absolute risk and determinants of human papillomavirus incidence among young women in Costa Rica.
BMC Infect. Dis.
PUBLISHED: 06-25-2013
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High risk human papillomaviruses (HR-HPV) are known to be extremely common, sexually transmitted infections, but more information is needed regarding the absolute risks of type-specific HR-HPV infections in the years following sexual debut.
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Initial experience with robotic retropubic urethropexy compared to open retropubic urethropexy.
Obstet Gynecol Int
PUBLISHED: 06-13-2013
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Study Objective. To compare the clinical outcomes of robotic retropubic urethropexy versus open retropubic urethropexy. Design. Retrospective case-control study (II-2). Setting. University Hospital. Patients. All patients who underwent robotic retropubic urethropexy from 1/1/12 to 6/1/12 by a single gynecologic surgeon were included in the case series. The control cases consisted of the last five consecutive open retropubic urethropexies performed by the same surgeon. Main Results. A total of 10 patients (5 robotic cases and 5 open cases) were included in this study. Both groups were similar with respect to age, BMI, and obstetrical history. Mean hospital stay length and mean EBL were overall less for robotic cases than for open cases (1.2 days versus 2.6 days; 169?mL versus 300?mL). One of the 5 patients who underwent the open approach and 2 of the 5 patients who underwent the robotic approach sustained a minor intraoperative complication. All but one patient from each group experienced resolution of incontinence after the procedure. Two of the patients who underwent the open approach had postoperative complications. Conclusions. Robotic retropubic urethropexy may be a feasible alternative to open retropubic urethropexy. A larger study is necessary to support our observations.
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