JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
HIV-2 and HTLV-1 infections in Spain, a non-endemic region.
AIDS Rev
PUBLISHED: 09-03-2014
Show Abstract
Hide Abstract
The annual workshop of the Spanish HIV?2/HTLV Study Group was held at the Instituto de Salud Carlos III in Madrid on December 11, 2013. Nearly 100 experts and researchers in retroviruses other than HIV?1, the classical AIDS agent, convened for a one?day meeting devoted to updating knowledge on the epidemiology of HIV?2 and HTLV-1 infections and discussing new diagnostic and therapeutic strategies, with special attention to non?endemic regions such as Spain. The Group was funded 25 years ago and since then has been responsible for the national registry of cases, recording all relevant information for each subject and inviting them to enroll in a prospective cohort and biobank. Up to the end of 2013, a total of 297 individuals with HIV?2 infection were reported in Spain. All but 10 carry HIV?2 subtype A, with the rest being infected with subtype B. Overall, 71% came from sub?Saharan Africa. During the last decade, the incidence of new HIV?2 infections in Spain has remained fairly stable with around 20 cases per year. At the time of diagnosis, plasma HIV?2 RNA was undetectable in 61% of individuals and values in viremic subjects tended to be low (2.8 logs on average). To date, only 26% of HIV?2 individuals have been treated with antiretrovirals. The CD4 counts, however, only increased above 200 cells/mm³ in 42% of them. On the other hand, 74% of non?treated HIV?2 individuals have > 500 CD4+ T?cells/mm³. As in HIV?1 infection, X4 tropism in HIV?2 is associated with lower CD4 counts. A total of 253 individuals with HTLV-1 infection were reported in Spain by the end of 2013. Overall, 58% came from Latin America. HTLV-1?associated myelopathy was diagnosed in 29 patients and adult T?cell leukemia/lymphoma in 18. The highest incidence occurred in 2013, with 34 new HTLV-1 diagnoses, largely as result of expanding HTLV screening in blood banks. Attempts to reduce HTLV-1 proviral load in symptomatic or asymptomatic patients with elevated HTLV-1 DNA using antiretrovirals have produced poor results, although integrase inhibitors could be more successful. Although no cases of HTLV?3 or ?4 have been identified so far in Spain, 769 individuals have been diagnosed with HTLV?2 infection. Up to 85% of the latest cases are coinfected with HIV?1 and are former intravenous drug users.
Related JoVE Video
Bisphosphonate-related osteonecrosis of the jaw: an Italian post-marketing surveillance analysis.
Expert Opin Drug Saf
PUBLISHED: 08-30-2014
Show Abstract
Hide Abstract
Although bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) is well recognized, little is known about it in terms of pathophysiology, epidemiology or management. We analyzed all suspected BRONJ reports sent to the Italian Pharmacovigilance Adverse Event Spontaneous Reporting System (Rete Nazionale Farmacovigilanza [RNF]) to determine their pattern and add new information about this relevant issue.
Related JoVE Video
The epigenetic basis of adaptation and responses to environmental change: perspective on human reproduction.
Adv. Exp. Med. Biol.
PUBLISHED: 08-06-2014
Show Abstract
Hide Abstract
Not only genetic but also epigenetic mechanisms regulate gene expression, cellular differentiation and development processes. Additionally, "environmental epigenetics" studies the interaction between the environment and the epigenome, and its potential role in the regulation of gene activity. Several studies have shown that the impact of environmental exposures on the epigenome takes on more importance during early fertilization and embryonic development, given that during these periods epigenetic reprogramming occurs and the new epigenetic profile of the offspring is established. Epigenetic alterations in the germline are especially relevant since they can be transmitted trans-generationally and could be associated with a wide range of diseases including several reproductive disorders. In this chapter we review some epigenetic mechanisms, focusing mainly on DNA methylation and histone modifications, which are related to reproductive aspects, and we discuss the controversies in the literature surrounding how environmental conditions, such as exposure to toxic substances or treatment with assisted reproductive techniques (ART), may be involved in epigenetic alterations that affect reproductive success.
Related JoVE Video
Tracking (Poly)phenol components from raspberries in ileal fluid.
J. Agric. Food Chem.
PUBLISHED: 07-21-2014
Show Abstract
Hide Abstract
The (poly)phenols in ileal fluid after ingestion of raspberries were analyzed by targeted and nontargeted LC-MS(n) approaches. Targeted approaches identified major anthocyanin and ellagitannin components at varying recoveries and with considerable interindividual variation. Nontargeted LC-MS(n) analysis using an orbitrap mass spectrometer gave exact mass MS data which were sifted using a software program to select peaks that changed significantly after supplementation. This method confirmed the recovery of the targeted components but also identified novel raspberry-specific metabolites. Some components (including ellagitannin and previously unidentified proanthocyanidin derivatives) may have arisen from raspberry seeds that survived intact in ileal samples. Other components include potential breakdown products of anthocyanins, unidentified components, and phenolic metabolites formed either in the gut epithelia or after absorption into the circulatory system and efflux back into the gut lumen. The possible physiological roles of the ileal metabolites in the large bowel are discussed.
Related JoVE Video
Effect of VKORC1, CYP2C9 and CYP4F2 genetic variants in early outcomes during acenocoumarol treatment.
Pharmacogenomics
PUBLISHED: 06-24-2014
Show Abstract
Hide Abstract
To analyze VKORC1, CYP2C9 and CYP4F2 polymorphisms in relation to the main outcomes in the first stages of acenocoumarol therapy.
Related JoVE Video
The effect of tomato juice supplementation on biomarkers and gene expression related to lipid metabolism in rats with induced hepatic steatosis.
Eur J Nutr
PUBLISHED: 05-27-2014
Show Abstract
Hide Abstract
Tomato products are a dietary source of natural antioxidants, especially lycopene, which accumulates in the liver, where it exerts biological effects. Taking into consideration this fact, the aim of the present study was to ascertain the effect of tomato consumption on biomarkers and gene expression related to lipid metabolism in rats with induced steatosis.
Related JoVE Video
[Acoustic voice analysis using the Praat program: comparative study with the Dr. Speech program].
Acta Otorrinolaringol Esp
PUBLISHED: 03-26-2014
Show Abstract
Hide Abstract
The European Laryngological Society (ELS) basic protocol for functional assessment of voice pathology includes 5 different approaches: perception, videostroboscopy, acoustics, aerodynamics and subjective rating by the patient. In this study we focused on acoustic voice analysis. The purpose of the present study was to correlate the results obtained by the commercial software Dr. Speech and the free software Praat in 2 fields: 1. Narrow-band spectrogram (the presence of noise according to Yanagihara, and the presence of subharmonics) (semi-quantitative). 2. Voice acoustic parameters (jitter, shimmer, harmonics-to-noise ratio, fundamental frequency) (quantitative).
Related JoVE Video
SOX2 expression in hypopharyngeal, laryngeal, and sinonasal squamous cell carcinoma.
Hum. Pathol.
PUBLISHED: 03-25-2014
Show Abstract
Hide Abstract
Squamous cell carcinoma (SCC) of the head and neck display high frequencies of DNA copy number gains at chromosomal region 3q26-27. Recently SOX2 has been postulated as a driver oncogene for these amplifications; however, its role as a prognostic marker is still a matter of debate. The aim of this study was to evaluate the involvement of SOX2 protein expression in three different sublocalizations of head and neck SCC and its possible role as prognostic marker. SOX2 expression was analyzed by immunohistochemistry in 102 pharyngeal, 67 laryngeal, and 51 sinonasal SCCs, and the relation to clinicopathological and follow-up data was studied by ?(2) and Kaplan-Meier analysis. SOX2 expression was significantly (P = .002) more frequent in hypopharyngeal and laryngeal SCC (38%, 39/101) and (42%, 28/67), respectively, compared to sinonasal cancer SCC (14%, 7/51). SOX2 expression did not correlate to disease stage, T or N classification, lymph node metastasis, recurrence or clinical outcome in any of the three sublocalizations. These results indicate that SOX2 expression is a common event in hypopharynx and larynx, but not in sinonasal SCC. The absence of correlation to clinical outcome, may suggest a role for SOX2 in tumor initiation, but not in tumor progression.
Related JoVE Video
Second species of Augochlorodes (Hymenoptera: Halictidae: Augochlorini) with known males and first record for the genus in Argentina.
Zootaxa
PUBLISHED: 03-10-2014
Show Abstract
Hide Abstract
The bee genus Augochlorodes Moure, up to now only known from Brazil, is recorded for the first time for Argentina. Augochlorodes politus Gonçalves & Melo was found in the south of the province of Buenos Aires, mideastern Argentina, being the southernmost record for the genus. The female of A. politus is redescribed and the male described for the first time, being the second male known for this genus. The phylogenetic position of Augochlorodes among Augochlorini is briefly discussed.
Related JoVE Video
Brucella ceti infection in dolphins from the Western Mediterranean sea.
BMC Vet. Res.
PUBLISHED: 03-02-2014
Show Abstract
Hide Abstract
Background Brucella ceti infections have been increasingly reported in cetaceans. Brucellosis in these animals is associated with meningoencephalitis, abortion, discospondylitis¿, subcutaneous abscesses, endometritis and other pathological conditions B. ceti infections have been frequently described in dolphins from both, the Atlantic and Pacific Oceans. In the Mediterranean Sea, only two reports have been made: one from the Italian Tyrrhenian Sea and the other from the Adriatic Sea.ResultsWe describe the clinical and pathological features of three cases of B. ceti infections in three dolphins stranded in the Mediterranean Catalonian coast. One striped dolphin had neurobrucellosis, showing lethargy, incoordination and lateral swimming due to meningoencephalitis, A B. ceti infected bottlenose dolphin had discospondylitis, and another striped dolphin did not show clinical signs or lesions related to Brucella infection. A detailed characterization of the three B. ceti isolates was performed by bacteriological, molecular, protein and fatty acid analyses.ConclusionsAll the B. ceti strains originating from Mediterranean dolphins cluster together in a distinct phylogenetic clade, close to that formed by B. ceti isolates from dolphins inhabiting the Atlantic Ocean. Our study confirms the severity of pathological signs in stranded dolphins and the relevance of B. ceti as a pathogen in the Mediterranean Sea.
Related JoVE Video
Minimally invasive video-assisted parathyroidectomy without intraoperative parathyroid hormone monitoring.
Acta Otorrinolaringol Esp
PUBLISHED: 03-01-2014
Show Abstract
Hide Abstract
surgical treatment of primary hyperparathyroidism has evolved from the classical bilateral neck exploration to minimally invasive techniques due to recent advances in preoperative localisation methods. The additional value of intraoperative parathyroid hormone (PTH) monitoring is questioned. The aim of this study was to analyse the results of minimally invasive video-assisted parathyroidectomy (MIVAP) without intraoperative PTH monitoring.
Related JoVE Video
Role of Genetic Polymorphisms in NFKB-Mediated Inflammatory Pathways in Response to Primary Chemoradiation Therapy for Rectal Cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
To investigate whether polymorphisms of genes related to inflammation are associated with pathologic response (primary endpoint) in patients with rectal cancer treated with primary chemoradiation therapy (PCRT).
Related JoVE Video
Stimulation of large-conductance calcium-activated potassium channels inhibits neurogenic contraction of human bladder from patients with urinary symptoms and reverses acetic acid-induced bladder hyperactivity in rats.
Eur. J. Pharmacol.
PUBLISHED: 02-05-2014
Show Abstract
Hide Abstract
We have analysed the effects of large-conductance calcium-activated potassium channel (BK) stimulation on neurogenic and myogenic contraction of human bladder from healthy subjects and patients with urinary symptoms and evaluated the efficacy of activating BK to relief bladder hyperactivity in rats. Bladder specimens were obtained from organ donors and from men with benign prostatic hyperplasia (BPH). Contractions elicited by electrical field stimulation (EFS) and carbachol (CCh) were evaluated in isolated bladder strips. in vivo cystometric recordings were obtained in anesthetized rats under control and acetic acid-induced hyperactive conditions. Neurogenic contractions of human bladder were potentiated by blockade of BK and small-conductance calcium-activated potassium channels (SK) but were unaffected by the blockade of intermediate calcium-activated potassium channels (IK). EFS-induced contractions were inhibited by BK stimulation with NS-8 or NS1619 or by SK/IK stimulation with NS309 (3µM). CCh-induced contractions were not modified by blockade or stimulation of BK, IK or SK. The anti-cholinergic agent, oxybutynin (0.3µM) inhibited either neurogenic or CCh-induced contractions. Neurogenic contractions of bladders from BPH patients were less sensitive to BK inhibition and more sensitive to BK activation than healthy bladders. The BK activator, NS-8 (5mg/kg; i.v.), reversed bladder hyperactivity induced by acetic acid in rats, while oxybutynin was ineffective. NS-8 did not significantly impact blood pressure or heart rate. BK stimulation specifically inhibits neurogenic contractions in patients with urinary symptoms and relieves bladder hyperactivity in vivo without compromising bladder contractile capacity or cardiovascular safety, supporting its potential therapeutic use for relieving bladder overactivity.
Related JoVE Video
Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation.
Thromb. Haemost.
PUBLISHED: 01-29-2014
Show Abstract
Hide Abstract
There are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation.We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2-VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09-2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2-VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2-VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65?% increase in miR-146a-5p levels, while TT individuals only showed a 28?% increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52?% vs 26?%). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p.
Related JoVE Video
Regulation of Coagulation Factor XI Expression by MicroRNAs in the Human Liver.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
High levels of factor XI (FXI) increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs) in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK) demonstrated a direct interaction between miR-181a-5p and 3'untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.
Related JoVE Video
Epistatic interaction of ERAP1 and HLA-B in Behçet disease: a replication study in the Spanish population.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Behçet's disease (BD) is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078) and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987) associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.
Related JoVE Video
A rosemary extract rich in carnosic acid selectively modulates caecum microbiota and inhibits ?-glucosidase activity, altering fiber and short chain fatty acids fecal excretion in lean and obese female rats.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Carnosic acid (CA) and rosemary extracts (RE) show body-weight, energy metabolism and inflammation regulatory properties in animal models but the mechanisms are not yet understood. Gut microbiota plays an important role in the host metabolism and inflammatory status and is modulated by the diet. The aim of this research was to investigate whether a RE enriched in CA affected caecum microbiota composition and activity in a rat model of genetic obesity.
Related JoVE Video
Corporal punishment in rural Colombian families: Prevalence, family structure and socio-demographic variables.
Child Abuse Negl
PUBLISHED: 10-05-2013
Show Abstract
Hide Abstract
Objective: To reveal the prevalence of corporal punishment in a rural area of Colombia and its correlates to family structure and other socio-demographic variables. Method: A survey about childrearing and childcare was developed for this study, including a specific question about corporal punishment that was developed based on the Conflict Tactics Scale (CTS). Family structure was categorized as follows, based on previous literature: nuclear family, single parent family, extended family, simultaneous family and composed family. Results: Forty-one percent of the parents surveyed admitted they had used corporal punishment of their children as a disciplinary strategy. The type of family structure, the number of children living at home, the age of the children, the gender of the parent who answered the survey, and the age and gender of the partner were significant predictors of corporal punishment. Conclusion: Family structure is an important variable in the understanding of corporal punishment, especially in regard to nuclear families that have a large number of children and parents who started their parental role early in life.
Related JoVE Video
Piezoelectric vs. conventional drilling in implant site preparation: pilot controlled randomized clinical trial with crossover design.
Clin Oral Implants Res
PUBLISHED: 09-09-2013
Show Abstract
Hide Abstract
To compare implant stability throughout osseointegration, peri-implant marginal bone loss, and success rates of implants placed with conventional and mixed drilling/piezoelectric osteotomy.
Related JoVE Video
Ocular dermoids: 116 consecutive cases.
Eye Contact Lens
PUBLISHED: 07-17-2013
Show Abstract
Hide Abstract
The aim was to describe the demographic and clinical data of 116 consecutive cases of ocular dermoids.
Related JoVE Video
Heparin modulates the mitogenic activity of fibroblast growth factor by inducing dimerization of its receptor. a 3D view by using NMR.
Chembiochem
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
In vitro mitogenesis assays have shown that sulfated glycosaminoglycans (GAGs; heparin and heparan sulfate) cause an enhancement of the mitogenic activity of fibroblast growth factors (FGFs). Herein, we report that the simultaneous presence of FGF and the GAG is not an essential requisite for this event to take place. Indeed, preincubation with heparin (just before FGF addition) of cells lacking heparan sulfate produced an enhancing effect equivalent to that observed when the GAG and the protein are simultaneously added. A first structural characterization of this effect by analytical ultracentrifugation of a soluble preparation of the heparin-binding domain of fibroblast growth factor receptor 2 (FGFR2) and a low molecular weight (3 kDa) heparin showed that the GAG induces dimerization of FGFR2. To derive a high resolution structural picture of this molecular recognition process, the interactions of a soluble heparin-binding domain of FGFR2 with two different homogeneous, synthetic, and mitogenically active sulfated GAGs were analyzed by NMR spectroscopy. These studies, assisted by docking protocols and molecular dynamics simulations, have demonstrated that the interactions of these GAGs with the soluble heparin-binding domain of FGFR induces formation of an FGFR dimer; its architecture is equivalent to that in one of the two distinct crystallographic structures of FGFR in complex with both heparin and FGF1. This preformation of the FGFR dimer (with similar topology to that of the signaling complex) should favor incorporation of the FGF component to form the final assemblage of the signaling complex, without major entropy penalty. This cascade of events is probably at the heart of the observed activating effect of heparin in FGF-driven mitogenesis.
Related JoVE Video
miR-133a regulates vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1), a key protein in the vitamin K cycle.
Mol. Med.
PUBLISHED: 05-10-2013
Show Abstract
Hide Abstract
Regulation of key proteins by microRNAs (miRNAs) is an emergent field in biomedicine. Vitamin K 2,3-epoxide reductase complex subunit 1 (VKORC1) is a relevant molecule for cardiovascular diseases, since it is the target of oral anticoagulant drugs and plays a role in soft tissue calcification. The objective of this study was to determine the influence of miRNAs on the expression of VKORC1. Potential miRNAs targeting VKORC1 mRNA were searched by using online algorithms. Validation studies were carried out in HepG2 cells by using miRNA precursors; direct miRNA interaction was investigated with reporter assays. In silico studies identified two putative conserved binding sites for miR-133a and miR-137 on VKORC1 mRNA. Ex vivo studies showed that only miR-133a was expressed in liver; transfection of miRNA precursors of miR-133a in HepG2 cells reduced VKORC1 mRNA expression in a dose-dependent manner, as assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) as well as protein expression. Reporter assays in HEK293T cells showed that miR-133a interacts with the 3UTR of VKORC1. Additionally, miR-133a levels correlated inversely with VKORC1 mRNA levels in 23 liver samples from healthy subjects. In conclusion, miR-133a appears to have a direct regulatory effect on expression of VKORC1 in humans; this regulation may have potential importance for anticoagulant therapy or aortic calcification.
Related JoVE Video
Polymorphisms in xenobiotic metabolizing genes (EPHX1, NQO1 and PON1) in lymphoma susceptibility: a case control study.
BMC Cancer
PUBLISHED: 05-01-2013
Show Abstract
Hide Abstract
The interplay between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. EPHX1, NQO1 and PON1 are three genes encoding proteins directly involved in the detoxification of potential carcinogens.
Related JoVE Video
IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.
Mol. Biol. Rep.
PUBLISHED: 04-29-2013
Show Abstract
Hide Abstract
To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.
Related JoVE Video
Communication benefits of bilateral cochlear implantation. Retrospective study in 12-year-old children.
Acta Otorrinolaringol Esp
PUBLISHED: 04-28-2013
Show Abstract
Hide Abstract
Some studies suggest that simultaneous or sequential cochlear implantation in a short period of time offers additional benefits. There is controversy regarding the existence of an age limit after which a second implantation offers less benefit for the acquisition of communication skills. The objectives of this study were to confirm that sequential cochlear implantation offers benefits compared to unilateral implantation and to study whether, at 12 years of age, there are significant differences regarding the age at the time of the second implantation.
Related JoVE Video
Bone turnover markers in patients with prostate carcinoma: influence of sex steroids levels.
J. Bone Miner. Metab.
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
There are limited data about bone turnover markers (BTM) in androgen deprivation therapy (ADT)-treated prostate cancer (PCa) patients, and the relationship between sex steroids, bone mass, and BTM has not been explored. Our objective was to analyze the influence of sex steroids levels on BTM in patients with PCa treated with or without ADT. We performed a cross-sectional study including 83 subjects with PCa (54 % with ADT). BTM, bone mineral density (BMD), and sex steroids were determined. BTM were inversely related to serum level of estrogens. Tartrate-specific acid phosphatase (TRAP-5b) showed a negative correlation with free estradiol (Free E) (r = -0.274, p = 0.014) and Bio E (r = -0.256, p = 0.022) that remained after adjustment for age: Free E (? = -0.241, p = 0.03) and Bio E (? = -0.213, p = 0.063). Bone-specific alkaline phosphatase (BSAP) concentrations were inversely related to Free E (r = -0.281, p = 0.011, age-adjusted ? = -0.256, p = 0.024). There was a negative correlation between osteocalcin (OC) levels and Free E (r = -0.195, p = 0.082; age-adjusted ? = -0.203, p = 0.076) and Bio E (r = -0.215, p = 0.054; age-adjusted ? = -0.240, p = 0.039). BTM and androgens were inversely related to TRAP-5b: total testosterone (total T) (r = -0.238, p = 0.033), Free T (r = -0.309, p = 0.05), and Bio T (r = -0.310, p = 0.05), but these correlations disappeared after age-adjustment. We did not find any relationship between BMD at different locations and sex steroids. In conclusion, in patients with PCa, estrogen levels influence bone resorption and bone formation whereas androgens may exert actions only in bone resorption. These results suggest that estradiol is the main sex steroid that regulates bone metabolism in males with prostate carcinoma.
Related JoVE Video
Neural restrictive silencer factor and choline acetyltransferase expression in cerebral tissue of Alzheimers Disease patients: A pilot study.
Genet. Mol. Biol.
PUBLISHED: 03-04-2013
Show Abstract
Hide Abstract
Decreased Choline Acetyltransferase (ChAT) brain level is one of the main biochemical disorders in Alzheimers Disease (AD). In rodents, recent data show that the CHAT gene can be regulated by a neural restrictive silencer factor (NRSF). The aim of the present work was to evaluate the gene and protein expression of CHAT and NRSF in frontal, temporal, entorhinal and parietal cortices of AD patient brains. Four brains from patients with AD and four brains from subjects without dementia were studied. Cerebral tissues were obtained and processed by the guanidine isothiocyanate method for RNA extraction. CHAT and NRSF gene and protein expression were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. CHAT gene expression levels were 39% lower in AD patients as compared to the control group (p < 0.05, U test). ChAT protein levels were reduced by 17% (p = 0.02, U test). NRSF gene expression levels were 86% higher in the AD group (p = 0.001, U test) as compared to the control group. In the AD subjects, the NRSF protein levels were 57% higher (p > 0.05, U test) than in the control subjects. These findings suggest for the first time that in the brain of AD patients high NRSF protein levels are related to low CHAT gene expression levels.
Related JoVE Video
Control of post-translational modifications in antithrombin during murine post-natal development by miR-200a.
J. Biomed. Sci.
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Developmental haemostatic studies may help identifying new elements involved in the control of key haemostatic proteins like antithrombin, the most relevant endogenous anticoagulant.
Related JoVE Video
VEGF-releasing biodegradable nanospheres administered by craniotomy: a novel therapeutic approach in the APP/Ps1 mouse model of Alzheimers disease.
J Control Release
PUBLISHED: 02-13-2013
Show Abstract
Hide Abstract
This study attempts to develop a novel nanotechnology-based strategy to deliver vascular endothelial growth factor (VEGF) to the brain, as a possible therapeutic approach for AD. For this purpose, VEGF was encapsulated in biodegradable poly(lactic-co-glycolic acid) (PLGA) nanospheres (VEGF-NS). The nanosphere particle size was about 200 nm, with a narrow size distribution, and the zeta potential around -30 mV. The encapsulation efficiency of VEGF was 44.06±5.61%, showing a biphasic release profile in vitro. The biological activity and neuroprotective effect of encapsulated VEGF were investigated in neuronal cell cultures, confirming the neuronal proliferative effect and the protection against A??? induced neurotoxicity. In vivo studies were carried out in amyloid precursor protein/presenilin-1 (APP/Ps1) mice administering VEGF-NS through minimally invasive craniotomy. The results obtained showed that VEGF-NS were able to improve behavioral deficits, decrease A? deposits and promote angiogenesis, as well as reduce neuronal loss and cerebrovascular abnormalities. Furthermore, their ability to protect neuronal cultures against neuroinflammation induced by LPS provides new insight for future therapeutic approaches in other neurodegenerative disorders.
Related JoVE Video
Expansion of the clinical ocular spectrum of Wolfram Syndrome in a family carrying a novel WFS1 gene deletion.
Ophthalmic Genet.
PUBLISHED: 02-01-2013
Show Abstract
Hide Abstract
To present the results of the clinical and molecular analyses of a familial case of Wolfram Syndrome (WFS) associated with a novel ocular anomaly.
Related JoVE Video
Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 01-10-2013
Show Abstract
Hide Abstract
Elevated levels of amyloid beta (A?) peptide, hyperphosphorylation of tau protein, and inflammation are pathological hallmarks in Alzheimers disease (AD). Phosphodiesterase 7 (PDE7) regulates the inflammatory response through the cyclic adenosine monophosphate signaling cascade, and thus plays a central role in AD. The aim of this study was to evaluate the efficacy of an inhibitor of PDE7, named S14, in a mouse model of AD. We report that APP/Ps1 mice treated daily for 4 weeks with S14 show: (1) significant attenuation in behavioral impairment; (2) decreased brain A? deposition; (3) enhanced astrocyte-mediated A? degradation; and (4) decreased tau phosphorylation. These effects are mediated via the cyclic adenosine monophosphate/cyclic adenosine monophosphate response element-binding protein signaling pathway, and inactivation of glycogen synthase kinase (GSK)3. Our data support the use of PDE7 inhibitors, and specifically S14, as effective therapeutic agents for the prevention and treatment of AD.
Related JoVE Video
Intranasal delivery of plasma and platelet growth factors using PRGF-Endoret system enhances neurogenesis in a mouse model of Alzheimers disease.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Neurodegeneration together with a reduction in neurogenesis are cardinal features of Alzheimers disease (AD) induced by a combination of toxic amyloid-? peptide (A?) and a loss of trophic factor support. Amelioration of these was assessed with diverse neurotrophins in experimental therapeutic approaches. The aim of this study was to investigate whether intranasal delivery of plasma rich in growth factors (PRGF-Endoret), an autologous pool of morphogens and proteins, could enhance hippocampal neurogenesis and reduce neurodegeneration in an amyloid precursor protein/presenilin-1 (APP/PS1) mouse model. Neurotrophic and neuroprotective actions were firstly evident in primary neuronal cultures, where cell proliferation and survival were augmented by Endoret treatment. Translation of these effects in vivo was assessed in wild type and APP/PS1 mice, where neurogenesis was evaluated using 5-bromodeoxyuridine (BdrU), doublecortin (DCX), and NeuN immunostaining 5 weeks after Endoret administration. The number of BrdU, DCX, and NeuN positive cell was increased after chronic treatment. The number of degenerating neurons, detected with fluoro Jade-B staining was reduced in Endoret-treated APP/PS1 mice at 5 week after intranasal administration. In conclusion, Endoret was able to activate neuronal progenitor cells, enhancing hippocampal neurogenesis, and to reduce A?-induced neurodegeneration in a mouse model of AD.
Related JoVE Video
Novel associations of VKORC1 variants with higher acenocoumarol requirements.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Algorithms combining both clinical and genetic data have been developed to improve oral anticoagulant therapy. Three polymorphisms in two genes, VKORC1 and CYP2C9, are the main coumarin dose determinants and no additional polymorphisms of any relevant pharmacogenetic importance have been identified.
Related JoVE Video
Neurogenesis in Alzheimer´s disease: a realistic alternative to neuronal degeneration?
Curr Signal Transduct Ther
PUBLISHED: 11-30-2011
Show Abstract
Hide Abstract
Neural stem cells (NSC) are cells that have the capacity to generate multiple types of differentiated brain cells. In conditions in which there is a loss of key functional cell groups, such as neurons, inducing or introducing neural stem cells to replace the function of those cells that were lost during the disease has the greatest potential therapeutic applications. Indeed, the achievement of one of the main objectives of various investigations is already on the horizon for some conditions, such as Alzheimers disease. It is not known whether impaired neurogenesis contributes to neuronal depletion and cognitive dysfunction in Alzheimers disease (AD). The results of the different investigations are controversial; some studies have found that neurogenesis is increased in AD brains, but others have not.
Related JoVE Video
Regulation of neural stem cell in the human SVZ by trophic and morphogenic factors.
Curr Signal Transduct Ther
PUBLISHED: 11-05-2011
Show Abstract
Hide Abstract
The subventricular zone (SVZ), lining the lateral ventricular system, is the largest germinal region in mammals. In there, neural stem cells express markers related to astoglial lineage that give rise to new neurons and oligodendrocytes in vivo. In the adult human brain, in vitro evidence has also shown that astrocytic cells isolated from the SVZ can generate new neurons and oligodendrocytes. These proliferative cells are strongly controlled by a number of signals and molecules that modulate, activate or repress the cell division, renewal, proliferation and fate of neural stem cells. In this review, we summarize the cellular composition of the adult human SVZ (hSVZ) and discuss the increasing evidence showing that some trophic modulators strongly control the function of neural stem cells in the SVZ.
Related JoVE Video
Mother and youth access (MAYA) maternal chlorhexidine, counselling and paediatric fluoride varnish randomized clinical trial to prevent early childhood caries.
Int J Paediatr Dent
PUBLISHED: 10-17-2011
Show Abstract
Hide Abstract
Mexican-American children have a higher caries prevalence than the U.S. average. The Mothers and Youth Access (MAYA) study was a randomized clinical trial initiated to address this problem.
Related JoVE Video
Synthesis and decarbonylation reactions of the triiron phosphinidene complex [Fe3Cp3(?-H)(?3-PPh)(CO)4]: easy cleavage and formation of P-H and Fe-Fe bonds.
Inorg Chem
PUBLISHED: 10-07-2011
Show Abstract
Hide Abstract
The binuclear phosphine complex [Fe(2)Cp(2)(?-CO)(2)(CO)(PH(2)Ph)] (Cp = ?(5)-C(5)H(5)) reacted with the acetonitrile adduct [Fe(2)Cp(2)(?-CO)(2)(CO)(NCMe)] in dichloromethane at 293 K to give the trinuclear hydride-phosphinidene derivative [Fe(3)Cp(3)(?-H)(?(3)-PPh)(CO)(4)] as a mixture of cis,anti and trans isomers (Fe-Fe = 2.7217(6) Å for the cis,anti isomer). In contrast, photochemical treatment of the phosphine complex with [Fe(2)Cp(2)(CO)(4)] gave the phosphide-bridged complex trans-[Fe(3)Cp(3)(?-PHPh)(?-CO)(2)(CO)(3)] as the major product, along with small amounts of the binuclear hydride-phosphide complexes [Fe(2)Cp(2)(?-H)(?-PHPh)(CO)(2)] (cis and trans isomers), which are more selectively prepared from [Fe(2)Cp(2)(CO)(4)] and PH(2)Ph at 388 K. The photochemical decarbonylation of either of the mentioned triiron compounds led reversibly to three different products depending on the reaction conditions: (a) the 48-electron phosphinidene cluster [Fe(3)Cp(3)(?-H)(?(3)-PPh)(?-CO)(2)] (Fe-Fe = 2.592(2)-2.718(2) Å); (b) the 50-electron complex [Fe(3)Cp(3)(?-H)(?(3)-PPh)(?-CO)(CO)(2)], also having carbonyl- and hydride-bridged metal-metal bonds (Fe-Fe = 2.6177(3) and 2.7611(4) Å, respectively); and (c) the 48-electron phosphide cluster [Fe(3)Cp(3)(?-PHPh)(?(3)-CO)(?-CO)(2)], an isomer of the latter phosphinidene complex now having three intermetallic bonds (Fe-Fe = 2.5332(8)-2.6158(8) Å).
Related JoVE Video
Antimicrobial activity and cytotoxic effects of Magnolia dealbata and its active compounds.
Nat Prod Commun
PUBLISHED: 09-20-2011
Show Abstract
Hide Abstract
Multi-drug resistance is of great concern for public health worldwide and necessitates the search for new antimicrobials from sources such as plants. Several Magnolia (Magnoliaceae) species have been reported to exert antimicrobial effects on sensitive and multidrug-resistant microorganisms. However, the antimicrobial properties of Magnolia dealbata have not been experimentally evaluated. The antimicrobial effects of an ethanol extract of Magnolia dealbata seeds (MDE) and its active compounds honokiol (HK) and magnolol (MG) were tested against the phytopathogen Clavibacter michiganensis subsp. michiganensis and several human multi-drug resistant pathogens using the disk-diffusion assay. The effects of MDE and its active compounds on the viability of human peripheral blood mononuclear cells (PBMC) were evaluated using MTT assay. MDE and its active compounds had antimicrobial activity (inhibition zone > 10 mm) against C. michiganensis, Pseudomonas aeruginosa, Acinetobacter baumannii, Acinetobacter lwoffii, Candida albicans, Candida tropicalis and Trichosporon belgeii. The results suggest that M. dealbata and its active compounds have selective antimicrobial effects against drug-resistant fungal and Gram (-) bacteria and exert minimal toxic effects on human PMBC.
Related JoVE Video
Serum osteoprotegerin and sex steroid levels in patients with prostate cancer.
J. Androl.
PUBLISHED: 09-08-2011
Show Abstract
Hide Abstract
The relationship between sex steroids and osteoprotegerin (OPG) in patients with prostate cancer is not well established. Our aim was to evaluate serum OPG levels in patients with prostate cancer and its relationship with sex steroids, bone mineral density, bone turnover markers, and fractures. We performed a cross-sectional study including 91 patients with prostate cancer. We determined: bone mineral density by dual-energy x-ray absorptiometry, bone turnover markers, serum levels of sex steroids and osteoprotegerin, and prevalent radiographic vertebral fractures. Serum OPG levels were higher in patients with vertebral fractures (8.02 ± 2.0 vs 4.91 ± 0.28 pmol/L; P < .05). OPG level and the duration of hormonal therapy were related (r = 0.299, P = .004), but this association did not persist after adjustment for age. In patients without androgen deprivation therapy, serum OPG levels were correlated with the levels of total testosterone (r = 0.508, P = .001) and bioavailable testosterone (r = 0.311, P = .037). In patients receiving androgen deprivation therapy, serum OPG levels were correlated with levels of total estradiol (r = 0.199, P = .18), bioavailable estradiol (r = 0.37, P = .009), and free estradiol (r = 0.349, P = .016). In conclusion, in patients with prostate cancer treated with androgen deprivation therapy, serum OPG levels were correlated with the levels of total estradiol, bioavailable estradiol, and free estradiol. Our hypothesis is that in patients with androgen deprivation therapy, the higher relative estrogen levels could stimulate OPG production in response to the higher resorption state. Future prospective studies are needed to clarify the role of OPG in androgen deprivation therapy-mediated bone loss.
Related JoVE Video
Postcesarean thromboprophylaxis with two different regimens of bemiparin.
Obstet Gynecol Int
PUBLISHED: 07-30-2011
Show Abstract
Hide Abstract
Objectives. To compare the effectiveness of postcesarean thromboprophylaxis with two different regimens of bemiparin. Material and Methods. The study included 646 women with cesarean delivery in our hospital within a 1-year period, randomly assigned to one of two groups for prophylaxis with 3500?IU bemiparin once daily for 5 days or 3500?IU bemiparin once daily for 10 days. Results. There was one case of pulmonary embolism (first day following cesarean). An additional risk factor was present in 98.52% of the women, most frequently emergency cesarean, anemia, or obesity. The only risk factors for thromboembolic disease significantly related to pulmonary thromboembolism were placental abruption and prematurity. There were no differences in thromboembolic events among the two thromboprophylaxis regimens. Conclusions. Cesarean-related thromboembolic events were reduced in our study population due to the thromboprophylactic measures taken. Thromboprophylaxis with 3500?IU bemiparin once daily for 5 days following cesarean was sufficient to avoid thromboembolic events.
Related JoVE Video
Heterometallic derivatives of [Fe2Cp2(?-PCy)(?-CO)(CO)2]: rational synthesis of polynuclear complexes from neutral precursors having pyramidal-phosphinidene bridges.
Inorg Chem
PUBLISHED: 07-20-2011
Show Abstract
Hide Abstract
The title complex (Cp = ?(5)-C(5)H(5)) reacted with the labile carbonyl complexes [M(CO)(5)(THF)] (M = Cr, Mo, W) and [MnCp(CO)(2)(THF)] (Cp = ?(5)-C(5)H(4)Me) to give phosphinidene-bridged trimetallic compounds of formula [Fe(2)MCp(2)(?(3)-PCy)(?-CO)(CO)(7)] (Cr-P = 2.479(1) Å) and [Fe(2)MnCp(2)Cp(?(3)-PCy)(?-CO)(CO)(4)], respectively, after formation of a new M-P bond in each case, and related heterometallic complexes [Fe(2)MClCp(2)(?(3)-PCy)(?-CO)(CO)(2)] (M = Cu, Au; Au-P = 2.262(1) Å) were cleanly formed upon reaction with CuCl or the labile tetrahydrothiophene (THT) complex [AuCl(THT)]. The reaction with [Fe(2)(CO)(9)] proceeded analogously to give the triiron derivative [Fe(3)Cp(2)(?(3)-PCy)(?-CO)(CO)(6)] in high yield (new Fe-P bond =2.318(1) Å), along with a small amount of the pentanuclear compound [{Fe(CO)(3)}{(?(3)-PCy)Fe(2)Cp(2)(?-CO)(CO)(2)}(2)], the latter displaying a central Fe(CO)(3)P(2) core with a distorted bipyramidal geometry (P-Fe-P = 164.2(1)°). In contrast, the reaction with [Co(2)(CO)(8)] resulted in a full disproportionation process to give the salt [{Co(CO)(3)}{(?(3)-PCy)Fe(2)Cp(2)(?-CO)(CO)(2)}(2)][Co(CO)(4)], having a pentanuclear Fe(4)Co cation comparable to the above Fe(5) complex (P-Co-P = 165.3(2)°). The attempted photochemical decarbonylation of the above trinuclear complexes gave results strongly dependent on the added metal fragment. Thus, the irradiation with visible or visible-UV light of the new Fe(3) and Fe(2)Cr species caused no decarbonylation but a tautomerization of the metal framework to give the corresponding isomers [Fe(2)MCp(2)(?(3)-PCy)(?-CO)(CO)(n)] now exhibiting a dangling FeCp(CO)(2) moiety (M = Cr, n = 7, Cr-Fe = 2.7370(3) Å; M = Fe, n = 6, new Fe-Fe bond = 2.6092(9) Å) as a result of the cleavage of the Fe-Fe bond in the precursor and subsequent formation of a new M-Fe bond. These processes are reversible, since the new isomers gave back the starting complexes under low (Cr) or moderate (Fe) thermal activation. In contrast, the manganese-diiron complex [Fe(2)MnCp(2)Cp(?(3)-PCy)(?-CO)(CO)(4)] could be decarbonylated stepwise, to give first the tetracarbonyl complex [Fe(2)MnCp(2)Cp(?(3)-PCy)(?-CO)(2)(CO)(2)] and then the tricarbonyl cluster [Fe(2)MnCp(2)Cp(?(3)-PCy)(?-CO)(3)], the latter having a closed triangular metal core (Fe-Fe = 2.568(7) Å; Mn-Fe = 2.684(8) and 2.66(1) Å).
Related JoVE Video
Raspberry juice consumption, oxidative stress and reduction of atherosclerosis risk factors in hypercholesterolemic golden Syrian hamsters.
Food Funct
PUBLISHED: 06-13-2011
Show Abstract
Hide Abstract
The effects of raspberries on early atherosclerosis in Syrian hamsters were investigated using three juices prepared from var. Cardinal, Glen Ample and Tulameen berries. The hamsters received an atherogenic diet for 12 weeks and at the same time a juice at a daily dose corresponding to the consumption of 275 ml by a 70 kg human. A control group received the same diet with water instead juice. The principal polyphenolic compounds in the juices were anthocyanins and ellagitannins, which were present at concentrations of 218-305 ?g mL(-1) and 45-72 ?g mL(-1), respectively. The three juices had similar but not identical effects. They all inhibited cardiac and aortic production of superoxide anion and increased hepatic glutathione peroxidase activity although only Tulameen juice brought about a significant increase in superoxide dismutase activity. Glen Ample was the only juice to significantly increase plasma paraoxonase activity. All the juices lowered plasma triglyceride level while consumption of Tulameen and Cardinal, but not Glen Ample, significantly lowered plasma total cholesterol and LDL-cholesterol. Cardinal was the sole juice to significantly increase HDL-cholesterol and likewise it also significantly reduced body weight. These findings suggest that moderate consumption of raspberry juices can help to prevent the development of early atherosclerosis, with the underlying mechanisms related to improved antioxidant status and serum lipid profiles.
Related JoVE Video
Colonic catabolism of ellagitannins, ellagic acid, and raspberry anthocyanins: in vivo and in vitro studies.
Drug Metab. Dispos.
PUBLISHED: 05-27-2011
Show Abstract
Hide Abstract
Red raspberries contain principally anthocyanins and ellagitannins. After ingestion of raspberries by humans, trace levels of anthocyanins, absorbed in the upper gastrointestinal tract, are excreted in urine in amounts corresponding to <0.1% of intake. Urine also contains urolithin-O-glucuronides derived from colonic metabolism of the ellagitannins. Raspberry feedings with ileostomists show that substantial amounts of the anthocyanin and ellagitannin intake are excreted in ileal fluid. In subjects with an intact functioning colon, these compounds would pass to the large intestine. The aim of this study was to identify raspberry-derived phenolic acid catabolites that form in the colon and those that are subsequently excreted in urine. In vitro anaerobic incubation of ellagitannins with fecal suspensions demonstrated conversion to ellagic acid and several urolithins. Fecal suspensions converted 80% of added ellagic acid to urolithins. In vivo, urolithins are excreted in urine as O-glucuronides, not aglycones, indicating that the colonic microflora convert ellagitannins to urolithins, whereas glucuronidation occurs in the wall of the large intestine and/or postabsorption in the liver. Unlike ellagitannins, raspberry anthocyanins were converted in vitro to phenolic acids by anaerobic fecal suspensions. Urinary excretion of phenolic acids after ingestion of raspberries indicates that after formation in the colon some phenolic acids undergo phase II metabolism, resulting in the formation of products that do not accumulate when anthocyanins are degraded in fecal suspensions. There is a growing realization that colonic catabolites such as phenolic acids and urolithins may have important roles in the protective effects of a fruit- and vegetable-rich diet.
Related JoVE Video
Prognostic significance of postoperative wound infections after total laryngectomy.
Head Neck
PUBLISHED: 05-20-2011
Show Abstract
Hide Abstract
In oncologic surgery, the relationship between postoperative wound infections and prognosis remains unclear. The purpose of this study was to establish the prognostic significance of surgical wound infections in laryngectomized patients.
Related JoVE Video
Neck injuries.
Acta Otorrinolaringol Esp
PUBLISHED: 05-18-2011
Show Abstract
Hide Abstract
Neck injuries are of great clinical interest because they can induce very significant consequences if not handled properly and can even lead to death. The aim of our study was to analyse external deep cervical trauma in our hospital.
Related JoVE Video
Role of GSTT1 and M1 null genotypes as risk factors for B-cell lymphoma: influence of geographical factors and occupational exposure.
Mol. Carcinog.
PUBLISHED: 05-06-2011
Show Abstract
Hide Abstract
The interrelationship between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. Both factors need to be considered to enable assessment of disease risk associated with a given individual under certain environmental conditions. GSTT1 and GSTM1 are two genes whose proteins are involved in the detoxification of potential carcinogens. We have studied the prevalence of GSTT1 and GSTM1 null polymorphisms using a novel PCR multiplex protocol in a group of 158 patients with B-cell lymphoma (BCL, 138 with non-Hodgkin lymphoma and 20 with Hodgkin lymphoma) and 214 healthy controls. A questionnaire regarding occupational exposure and lifestyle factors was also completed by both groups. GSTM1 null genotype showed no significant differences between patients and controls (46.9% and 55.6%, respectively). In contrast, GSTT1 null genotype was observed in 25.3% of patients and 15.4% of controls (P=0.013; OR=1.85; CI (95%):1.11-3.09), suggesting a role for the GSTT1 null genotype in the development of BCL. This effect was even more evident in females (27.5% vs. 14%: P=0.014). No significant association was observed between GST genotypes and disease risk in relation to smoking or occupational exposure.
Related JoVE Video
Inhibition of vascular endothelial growth factor (VEGF)-induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate.
Eur. J. Pharmacol.
PUBLISHED: 04-18-2011
Show Abstract
Hide Abstract
Vascular endothelial growth factor (VEGF) is a key factor in angiogenesis and vascular permeability which is associated with many pathological processes. 2,5-hydroxybenzene sulfonate (DHBS; dobesilate) is a small molecule with anti-angiogenic activity that has been described as an inhibitor of fibroblast growth factors (FGF). The aim of the present study was to evaluate the effects of DHBS on VEGF-induced actions. The effects of DHBS were evaluated on VEGF-induced proliferation in human umbilical vein endothelial cells (HUVEC) and rat aorta relaxation, as well as on in vivo VEGF-induced skin vascular permeability and neovascularization in rats. DHBS at 50 and 100 ?M concentration significantly inhibited the proliferation of HUVEC induced by VEGF (10 ng/ml), without significantly affecting HUVEC proliferation in the absence of VEGF. Rapid VEGF-induced activation of Akt in HUVEC was also prevented by DHBS (100 ?M). Additionally, DHBS (2 ?M) specifically inhibited the relaxation of rat aorta induced by VEGF (0.1 to 30 ng/ml), but not endothelium-dependent relaxation to acetylcholine (1 nM to 10 ?M). The in vivo enhancement of vascular permeability caused by VEGF injection (50 ?l at 10 ng/ml) in rat skin was also inhibited by DHBS co-administration (200 ?M) (74.8±3.8% inhibition of dye extravasation). Administration of DHBS (200 mg/kg/day; i.p.) also reduced VEGF-induced angiogenesis in vivo. DHBS inhibits main responses elicited in vitro and in vivo by VEGF. As a dual antagonist of VEGF and FGF activities, DHBS could be of therapeutic interest in the treatment of diseases related to VEGF/FGF overproduction and excessive angiogenesis.
Related JoVE Video
International Nosocomial Infection Control Consortium (INICC) report, data summary of 36 countries, for 2004-2009.
Am J Infect Control
PUBLISHED: 04-13-2011
Show Abstract
Hide Abstract
The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortiums ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries ICUs was remarkably similar to that reported in US ICUs in the CDCs NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortiums ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia).
Related JoVE Video
Antimicrobial and cytotoxic effects of Mexican medicinal plants.
Nat Prod Commun
PUBLISHED: 03-21-2011
Show Abstract
Hide Abstract
The antimicrobial effects of the Mexican medicinal plants Guazuma ulmifolia, Justicia spicigera, Opuntia joconostle, O. leucotricha, Parkinsonia aculeata, Phoradendron longifolium, P. serotinum, Psittacanthus calyculatus, Tecoma stans and Teucrium cubense were tested against several human multi-drug resistant pathogens, including three Gram (+) and five Gram (-) bacterial species and three fungal species using the disk-diffusion assay. The cytotoxicity of plant extracts on human cancer cell lines and human normal non-cancerous cells was also evaluated using the MTT assay. Phoradendron longifolium, Teucrium cubense, Opuntia joconostle, Tecoma stans and Guazuma ulmifolia showed potent antimicrobial effects against at least one multidrug-resistant microorganism (inhibition zone > 15 mm). Only Justicia spicigera and Phoradendron serotinum extracts exerted active cytotoxic effects on human breast cancer cells (IC50 < or = 30 microg/mL). The results showed that Guazuma ulmifolia produced potent antimicrobial effects against Candida albicans and Acinetobacter lwoffii, whereas Justicia spicigera and Phoradendron serotinum exerted the highest toxic effects on MCF-7 and HeLa, respectively, which are human cancer cell lines. These three plant species may be important sources of antimicrobial and cytotoxic agents.
Related JoVE Video
Iron deficiency enhances bioactive phenolics in lemon juice.
J. Sci. Food Agric.
PUBLISHED: 03-08-2011
Show Abstract
Hide Abstract
This study was designed to describe the phenolic status of lemon juice obtained from fruits of lemon trees differing in iron (Fe) nutritional status. Three types of Fe(III) compound were used in the experiment, namely a synthetic chelate and two complexes derived from natural polymers of humic and lignine nature.
Related JoVE Video
A new bilayer chitosan scaffolding as a dural substitute: experimental evaluation.
World Neurosurg
PUBLISHED: 03-03-2011
Show Abstract
Hide Abstract
To evaluate whether bilayer chitosan scaffolding (BChS) can provide a watertight dural closure and permit regeneration by fibroblasts in an experimental in vivo model.
Related JoVE Video
UV and MS identification of Urolithins and Nasutins, the bioavailable metabolites of ellagitannins and ellagic acid in different mammals.
J. Agric. Food Chem.
PUBLISHED: 01-25-2011
Show Abstract
Hide Abstract
Urolithins are microbial metabolites produced from ellagic acid after the intake of dietary ellagitannins by different animals. Urolithin metabolites have distinct UV spectra that enable their detection and differentiation by HPLC coupled with UV photodiode array detectors. Correlations between structural characteristics, including conjugation, with the UV spectra and retention times are established. The production of urolithin derivatives in different animals feeding on ellagitannins, including rodents (rats and mice), humans, pigs, squirrels, beavers, sheep, bull calves, birds, and insects, was investigated. All mammals produced urolithins, and their glucuronyl and sulfate conjugates were the main metabolites detected in plasma and urine. Unconjugated urolithins were detected in feces, ruminal content, and beaver castoreum. Different urolithin hydroxylation patterns were observed for different animal species, suggesting that the microbiota responsible for the metabolism of ellagitannins in each animal species produces dehydroxylases for the removal of specific hydroxyls from the ellagic acid residue. Metabolites were characterized using HR HPLC-TOF-MS and ion trap MS/MS. Insects and birds feeding on ellagitannin-containing foods did not produce urolithins, although they released ellagic acid. Beavers and pigs were able to produce dehydroxyellagic acid derivatives (nasutin A), showing that in some cases the removal of hydroxyl groups from the ellagic acid nucleus can be carried out before the lactone ring is opened to produce urolithins.
Related JoVE Video
Stress by noise produces differential effects on the proliferation rate of radial astrocytes and survival of neuroblasts in the adult subgranular zone.
Neurosci. Res.
PUBLISHED: 01-12-2011
Show Abstract
Hide Abstract
The subgranular zone (SGZ) in the dentate gyrus contains radial astrocytes, known as Type-1 or Type-B cells, which generate neuroblasts (Type-2 cells or Type-D cells) that give rise to granular neurons. Stress increases glucocorticoid levels that target SGZ and modify the proliferation and apoptosis of hippocampal cells. Yet, it is not well-known whether stress differentially affects SGZ progenitors. We investigated the effects of noise-induced stress on the rate of proliferation and apoptosis of the Type-1 cells, Type-2 cells and newly generated granular neurons in the SGZ. We exposed Balb/C mice to noise using a standardized rodents audiogram-fitted adaptation of a human noisy environment. We measured corticosterone serum levels at different time points. Animals received BrdU injections for 3 days and sequential sacrifices were done to carry out double-immunohistochemical analyses. We found that a 24-h noise exposure did not produce adaptative response in the curve of corticosterone as compared to a 12-h noise exposure. The percentage of BrdU+/GFAP+ cells was significantly reduced in the stress group as compared to controls. A high proportion of CASP-3+/GFAP+ radial astrocytes were found in the stress group. The percentage of BrdU+/doublecortin+ cells was higher in controls than in the stress group. Interestingly, the apoptosis rate of doublecortin-expressing cells in the stress group was slightly lesser than in controls. Remarkably, we did not find significant differences in the number of BrdU+/NeuN+ and CASP-3+/NeuN+ neurons. These data indicate that stress differentially affects the rate of proliferation and apoptosis in SGZ progenitors and suggest a possible compensatory mechanism to keep the net number of granular neurons.
Related JoVE Video
[Biological markers. Utility in the management of patients with pulmonary hypertension].
Arch. Bronconeumol.
PUBLISHED: 01-01-2011
Show Abstract
Hide Abstract
A biological marker can be defined as any substance that can be objectively measured and evaluated as an indicator of a normal biological process, a pathogenic process or pharmacological responses to a therapeutic intervention. In pulmonary hypertension (PH), in addition to routine markers (hemodynamic and functional), there are a growing number of biomarkers that allow an increasingly comprehensive approach to knowledge of susceptibility to this disease and to diagnosis, prognosis and treatment response. These markers can be both constitutive (genetic) and disease-related (related to right ventricular failure, such as BMP/NT-proBNP, endothelial dysfunction, such as endothelin-1, or inflammation, such as certain cytokines and chemokines). Novel insights in genomics and proteomics may allow major advances in this field.
Related JoVE Video
[Tuberculosis in a cohort of patients with systemic lupus erythematosus].
Reumatol Clin
PUBLISHED: 09-16-2010
Show Abstract
Hide Abstract
1) To study tuberculosis (TB) infection in a cohort of patients with systemic lupus erythematosus (SLE) and to compare its frequency and characteristics with that of others series. 2) To look for differential characteristic among SLE patients with and without TB. 3) To investigate if there was any relationship between TBs most severe forms and higher doses of glucocorticoids (GC) or other immunosuppressants.
Related JoVE Video
Influence of the F12 -4 C>T polymorphism on hemostatic tests.
Blood Coagul. Fibrinolysis
PUBLISHED: 09-04-2010
Show Abstract
Hide Abstract
The common F12 -4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 -4T allele, associated with reduced levels of FXII (P < 0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P < 0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 -4T allele. Moreover, individuals with the F12 -4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 -4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P < 0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 -4 C>T polymorphism on hemostatic tests widely used in routine clinical practice.
Related JoVE Video
Genetic polymorphisms and atrial fibrillation: Insights into the prothrombotic state and thromboembolic risk.
Ann. Med.
PUBLISHED: 08-04-2010
Show Abstract
Hide Abstract
The pathophysiology of thromboembolism in atrial fibrillation (AF) is a multifactorial and complex process. Abnormalities of haemostasis, fibrinolysis, endothelium, and platelets have all been described in AF. This prothrombotic state observed in AF appears to be additive to the presence of clinical and echocardiography risk factors for thromboembolism. Nonetheless, the precise mechanistic pathway(s) leading to the prothrombotic state in AF remain to be elucidated. Of note, there are limited data on the influence of genetic polymorphisms in thromboembolic risk associated with AF. On the other hand, the response to coumarin derivatives depends on several factors, such as sex, age, diet, or interacting drugs. Optimal anticoagulation control is usually hampered by significant interindividual variability in dose requirements for a given target level of anticoagulation. There is increasing evidence that interindividual sensitivity and side-effects to coumarinics may be largely determined genetically. Thus, genetic polymorphisms could explain the individual risk of developing an adverse drug reaction (bleeding) or drug inefficacy (thrombosis) with oral anticoagulation. In this article, we provide an overview of the limited data about the possible influence of genetic polymorphisms on thromboembolic risk in AF, as well as the genetic influences on anticoagulant drug responsiveness.
Related JoVE Video
CALU A29809G polymorphism in coronary atherothrombosis: Implications for coronary calcification and prognosis.
Ann. Med.
PUBLISHED: 08-03-2010
Show Abstract
Hide Abstract
Arterial calcification is a risk factor for atherosclerosis. Calumenin (CALU), a protein regulating proteins involved in coagulation and arterial calcification also has extracellular functions related to atherosclerosis. We recently described that CALU polymorphism A29809G was related to acenocoumarol requirements, and we wanted to evaluate its role in arterial calcification and prognosis.
Related JoVE Video
[Prevalence of the A1555G MTDNA mutation in sporadic hearing-impaired patients without known history of aminoglycoside treatment].
Acta Otorrinolaringol Esp
PUBLISHED: 07-13-2010
Show Abstract
Hide Abstract
The A1555G mitochondrial DNA (mtDNA) mutation is responsible for maternally inherited non-syndromic hearing loss that is increased by aminoglycoside exposure. The objective of this study was to ascertain the frequency of the A1555G mutation among patients without family history of hearing loss or known exposition to aminoglycosides.
Related JoVE Video
[Tuberculosis and coccidiodomycosis in two patients without immune acquired deficiency].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 07-02-2010
Show Abstract
Hide Abstract
Coccidioidomycosis results from inhaling the spores (arthroconidia) of Coccidioides species (Coccidioides immitis or Coccidioides posadasii). Tuberculosis is caused by the Mycobacterium tuberculosis complex, classified as acid-fast bacilli. It is most commonly transmitted from a patient with infectious pulmonary tuberculosis to other persons by droplet nuclei, which are aerosolized by coughing, sneezing, or speaking. Northern Mexico is an endemic zone for coccidioidomycosis and tuberculosis, both diseases usually appear in an isolated way. However, in cases of immunosuppressant in endemic zones, both pathologies tend to coexist. In all of the cases, determining the correct diagnosis is very difficult because they share epidemiological, clinical, radiographic, and even histopathological characteristics. In this paper we present two cases of tuberculosis and coccidioidomycosis coexistence. One case presented pulmonary disease from both entities, while the other was a relapsing of disseminated coccidioidomycosis associated with systemic tuberculosis. The presence of similar cases should alert the clinician to consider an early diagnosis of both entities in every patient with compatible clinical features. The most important concept is to remember that the diagnosis of one of them doesnt exclude the possible existence of the other.
Related JoVE Video
Related JoVE Video
Antiglioma effects of a new, low molecular mass, inhibitor of fibroblast growth factor.
Neurosci. Lett.
PUBLISHED: 05-12-2010
Show Abstract
Hide Abstract
Despite the deployment of multimodal therapies involving neurosurgical resection, radio- and polychemotherapy, the prognosis for glioblastoma patients remains poor. These tumors are pathologically characterized by their associated angiogenesis and diffuse brain invasion, processes that are probably closely linked to the unfavorable prognosis of this disease. Accordingly, pharmacological inhibition of glioblastoma invasion and approaches that impede angiogenesis are considered to be promising therapeutic strategies to combat these tumors. Nevertheless, the anti-angiogenic therapies for glioblastoma currently available are transient and palliative at best. Blocking the effects of fibroblast growth factor (FGF) may represent a novel mean of inhibiting the angiogenesis associated with glioblastoma, as it mediates the angiogenesis induced by other factors and it is an angiogenic factor by itself. In addition, the survival of glioma cells and their resistance to chemotherapeutic agents are highly FGF-dependent. We show here that a recently described inhibitor of FGF, 2,5-dihydroxyphenyl-sulfonate (2,5DHPS, dobesilate), stimulates the apoptosis of tumor cells, inhibits glioblastoma invasion and suppresses its associated angiogenesis. Moreover, this agent augments the efficiency of chemotherapeutic agents in a rat model of orthotopic brain tumor. These results suggest that 2,5DHPS treatment may represent a promising therapy for malignant glioma.
Related JoVE Video
[Pre-surgical nursing visit: evaluating the effectiveness of nursing intervention and patient perception].
Enferm Clin
PUBLISHED: 04-15-2010
Show Abstract
Hide Abstract
To determine patient satisfaction with the pre-surgical visit, explore the specific contents of interventions performed, and analyse their effectiveness in post-surgical outcomes.
Related JoVE Video
Megalin interacts with APP and the intracellular adapter protein FE65 in neurons.
Mol. Cell. Neurosci.
PUBLISHED: 03-25-2010
Show Abstract
Hide Abstract
Increasing evidence has implicated megalin, a low-density lipoprotein receptor-related protein, in the pathogenesis of Alzheimers disease (AD). In the brain, megalin is expressed in brain capillaries, ependymal cells and choroid plexus, where it participates in the clearance of brain amyloid ?-peptide (A?) complex. Recently, megalin has also been detected in oligodendrocytes and astrocytes. In this study we demonstrate that megalin is widely distributed in neurons throughout the brain. Additionally, given that FE65 mediates the interaction between the low density lipoprotein receptor-related protein-1 and the amyloid precursor protein (APP) to modulate the rate of APP internalization from the cell surface, we hypothesize that megalin could also interact with APP in neurons. Our results confirm that megalin interacts with APP and FE65, suggesting that these three proteins form a tripartite complex. Moreover, our findings imply that megalin may participate in neurite branching. Taken together, these results indicate that megalin has an important role in A?-mediated neurotoxicity, and therefore may be involved in the neurodegenerative processes that occur in AD.
Related JoVE Video
Bioavailability of anthocyanins and ellagitannins following consumption of raspberries by healthy humans and subjects with an ileostomy.
J. Agric. Food Chem.
PUBLISHED: 03-12-2010
Show Abstract
Hide Abstract
The fate of anthocyanins, ellagic acid, and ellagitannins was studied following the consumption of 300 g of raspberries by healthy human volunteers and subjects with an ileostomy. Postingestion plasma and urine from the former and ileal fluid and urine from the latter group were collected and analyzed by HPLC-PDA-MS(2). Plasma from the healthy volunteers did not contain detectable quantities of either the native raspberry polyphenolics or their metabolites. The three main raspberry anthocyanins were excreted in urine in both healthy and ileostomy volunteers 0-7 h after ingestion, in quantities corresponding to <0.1% of intake. This indicates a low level of absorption in the small intestine. With ileostomy volunteers 40% of anthocyanins and 23% of the ellagitannin sanguiin H-6 were recovered in ileal fluid with the main excretion period being the first 4 h after raspberry consumption. The recovery of ellagic acid in ileal fluid was 241%, indicating hydrolysis of ellagitannins in the stomach and/or the small intestine. Urinary excretion of ellagic acid and an ellagic acid-O-glucuronide was <1% of intake. No intact or conjugated forms of ellagitannins were detected in urine from either healthy subjects or ileostomy volunteers. However, in healthy subjects, but not the ileostomists, ellagitannins were catabolized with the appearance of urolithin A-O-glucuronide, two of its isomers, and urolithin B-O-glucuronide in urine collected 7-48 h after raspberry consumption. There was marked variation in the urolithin profile of individual volunteers, indicating differences in the colonic microflora responsible for ellagitannin degradation.
Related JoVE Video
[Severe infections in a cohort of patients with systemic lupus erythematosus].
Med Clin (Barc)
PUBLISHED: 03-11-2010
Show Abstract
Hide Abstract
To study severe infectious complications in a cohort of patients with systemic lupus erythematosus (SLE).
Related JoVE Video
Dynamic effects of cofactors and DNA on the oligomeric state of human mitochondrial DNA helicase.
J. Biol. Chem.
PUBLISHED: 03-08-2010
Show Abstract
Hide Abstract
We examined the effects of cofactors and DNA on the stability, oligomeric state and conformation of the human mitochondrial DNA helicase. We demonstrate that low salt conditions result in protein aggregation that may cause dissociation of oligomeric structure. The low salt sensitivity of the mitochondrial DNA helicase is mitigated by the presence of magnesium, nucleotide, and increased temperature. Electron microscopic and glutaraldehyde cross-linking analyses provide the first evidence of a heptameric oligomer and its interconversion from a hexameric form. Limited proteolysis by trypsin shows that binding of nucleoside triphosphate produces a conformational change that is distinct from the conformation observed in the presence of nucleoside diphosphate. We find that single-stranded DNA binding occurs in the absence of cofactors and renders the mitochondrial DNA helicase more susceptible to proteolytic digestion. Our studies indicate that the human mitochondrial DNA helicase shares basic properties with the SF4 replicative helicases, but also identify common features with helicases outside the superfamily, including dynamic conformations similar to other AAA(+) ATPases.
Related JoVE Video

What is Visualize?

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

How does it work?

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

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

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.