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Find video protocols related to scientific articles indexed in Pubmed.
Design and synthesis of resveratrol-salicylate hybrid derivatives as CYP1A1 inhibitors.
J Enzyme Inhib Med Chem
PUBLISHED: 11-20-2014
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Abstract Resveratrol and aspirin are known to exert potential chemopreventive effects through modulation of numerous targets. Considering that the CYP450 system is responsible for the activation of environmental procarcinogens, the aim of this study was to design a new class of hybrid resveratrol-aspirin derivatives possessing the stilbene and the salicylate scaffolds. Using HepG2 cells, we evaluated (a) the inhibition of TCDD-mediated induction of CYP1A1 exerted by resveratrol-aspirin derivatives using the EROD assay, and (b) CYP1A1 mRNA in vitro. We observed significant inhibition (84%) of CYP1A1 activity and a substantial decrease in CYP1A1 mRNA with compound 3, compared to control. Resveratrol did not exert inhibition under the same experimental conditions. This inhibitory profile was supported by docking studies using the crystal structure of human CYP1A1. The potential effect exerted by compound 3 (the most active), provide preliminary evidence supporting the design of hybrid molecules combining the chemical features of resveratrol and aspirin.
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[Determination of von Willebrand factor multimers in Mexican population].
Cir Cir
PUBLISHED: 11-14-2014
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Von Willebrand disease is an inherited disease in which the structure, function, and concentration of von Willebrand factor are altered, as well as the platelet von Willebrand factor endothelium interaction. In Mexico there are no epidemiological records of the disease. Only a few isolated studies have been reported from the clinical and hematological standpoint.
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LONG-TERM FOLLOW-UP OF PHOTORECEPTOR LOSS AND RECOVERY AFTER HALF-FLUENCE PHOTODYNAMIC THERAPY FOR CHRONIC CENTRAL SEROUS CHORIORETINOPATHY.
Retin Cases Brief Rep
PUBLISHED: 11-11-2014
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To describe a case of chronic central serous chorioretinopathy with apparent transient, reversible loss of photoreceptor outer segments after half-fluence photodynamic therapy (PDT).
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Bilateral vocal cord paralysis requiring tracheostomy due to neuroborreliosis.
Chest
PUBLISHED: 11-05-2014
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Neuroborreliosis can cause multiple cranial and peripheral neuropathies; however, involvement of both recurrent laryngeal nerves is rare. We report the case of a 90-year-old man who presented with dysphonia and right upper and lower extremity weakness. His course was complicated by bilateral vocal cord paralysis and respiratory failure requiring tracheostomy. The diagnosis of borreliosis was made by detection of IgM and IgG antibodies against Borrelia burgdorferi on enzyme immunoassay and Western blot. The patient received IV ceftriaxone for 2 weeks, followed by complete recovery of motor and vocal function over 2 months. Our case is the third report of bilateral vocal cord paralysis in the literature, and the first one, to our knowledge, presenting with respiratory failure requiring an artificial airway. Physicians should be aware of this unusual complication of neuroborreliosis.
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[Idiopathic scrotal elephantiasis. A case report].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 10-11-2014
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Penoscrotal lymphedema (scrotal elephantiasis) is a condition that has been described in areas in which filariasis is endemic.
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Chronic Obstructive Pulmonary Disease, cognitive impairment and development of disability: The Health and Retirement Study.
Ann Am Thorac Soc
PUBLISHED: 10-07-2014
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Rationale: The relationship between chronic obstructive pulmonary disease (COPD) and cognitive impairment in leading to disability has not been characterized. Objectives: We aimed to investigate prevalence and cumulative incidence of disability among adults with and without COPD and the association of COPD and cognitive impairment with disability. Methods: We analyzed 2006-2008 waves of the Health and Retirement Study, a nationally-representative longitudinal health survey. COPD was self-reported. Prevalent disability was defined as baseline dependency in ?1 activities of daily living (ADLs) and incident disability as ?1 additional ADL dependencies. We used a performance-based measure of cognition to identify dementia and mild cognitive impairment (MCI). Covariates were 7 chronic diseases, 4 geriatric syndromes, and sociodemographics. We used logistic regression to test associations between COPD, cognitive status and prevalent/incident disability. Results: Of 17,535 participants ?53 years old in wave 2006 (representing 77.7 million Americans), 9.5% reported COPD and 13.5% MCI; 17.5% of those with COPD had MCI. Prevalent disability for COPD was 12.8% (5.2% for no-COPD, p<0.001); an additional 9.2% with COPD developed incident disability at 2 years (4.0% for no-COPD, p<0.001). In adjusted models, COPD was associated with baseline (OR 2.0) and incident disability (OR 2.1, additionally adjusted for baseline disability), and MCI had an additive effect to COPD. The COPD-disability association, prevalent/incident, was of similar or greater magnitude than that of other chronic diseases (e.g. stroke, diabetes). Conclusion: Both COPD and MCI increase the risk of disability. The risk conferred by COPD is significant and similar or higher than other chronic diseases.
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Principal findings of systematic reviews for chronic treatment in childhood asthma.
J Asthma
PUBLISHED: 10-03-2014
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Abstract Objective: To summarize the principal findings pertaining to most effective long-term pharmacologic treatment of childhood asthma. Methods: Systematic reviews of randomized clinical trials (SRCTs) on pharmacologic chronic treatment in children (1-18 years) with persistent asthma were retrieved through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR (up to January2014). Results: One hundred eighty-three SRCTs were searched from databases. Among those, 39 SRCTs were included: two were related to step 1, 24 to step 2, nine to steps 3 and 4, and four to step 5 (according with NAEPP and GINA guidelines). The methodological quality of these SRCTs was determined by using the AMSTAR tool. Results: For step 1: addition of ipatropium bromide to short-acting beta2-agonists does not show any benefit. For step 2: in preschoolers, inhaled corticosteroids (ICSs) reduce severe exacerbations and improve other clinical and lung function parameters. In children, ICSs are superior to leukotriene receptor antagonist (LTRA), cromones, or xantines in reducing severe exacerbations, improving lung function and other clinical outcomes. Fluticasone propionate (FP) is better than beclomethasone dipropionate (BDP) or budesonide only for lung function; but similar to hydrofluoroalkane-BDP or to ciclosenide. Compared to low ICSs doses, moderate doses result in only better lung function, but this is not true for FP. For steps 3 and 4: adding LTRA to ICS confers a small benefit; adding LABA improves lung function but does not reduce exacerbations more than double or higher ICS doses. For step 5: adding omalizumab decreases exacerbations. Conclusions: SRCTs are useful for guiding decisions in chronic childhood asthma treatment.
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Rat eradication and the resistance and resilience of passerine bird assemblages in the Falkland Islands.
J Anim Ecol
PUBLISHED: 09-03-2014
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Norway rats (Rattus norvegicus) were introduced to the Falkland Islands and are detrimental to native passerines. Rat eradication programs are being used to help protect the avifauna. The present study assesses the effectiveness of eradication programs while using this conservation practice as a natural experiment to explore the ecological resistance, resilience, and homeostasis of bird communities. We conducted bird surveys on 230 islands: 85 in the presence of rats, 108 that were historically free of rats, and 37 from which rats had been eradicated. Bird detection data were used to build occupancy models for each species and estimate species-area relationships. Count data were used to estimate relative abundance and community structure. Islands with invasive rats had reduced species richness of passerines and a different community structure than islands on which rats were historically absent. Although the species richness of native passerines was remarkably similar on eradicated and historically rat-free islands, community structure on eradicated islands was more similar to that of rat-infested islands than to historically rat-free islands. The results suggest that in the Falkland Islands, species richness of passerines is not resistant to invasive rats, but seems to be resilient following their removal. In contrast, community structure seems to be neither resistant nor resilient. From a conservation perspective, rat eradication programs in the Falkland Islands appear to be effective at restoring native species richness, but they are not necessarily beneficial for species of conservation concern. For species that do not recolonize, translocations following eradications may be necessary. This article is protected by copyright. All rights reserved.
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Contribution of ethnic group and socioeconomic status to degree of disability in rheumatoid arthritis in Chilean patients.
Rheumatol. Int.
PUBLISHED: 09-02-2014
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The aim of this study was to estimate the contributions of ethnic group and socioeconomic status as social determinants related to disability and disease activity in Chilean Mapuche and non-Mapuche patients with rheumatoid arthritis (RA). Descriptive cross-sectional study with a stratified hospital-based sample of 189 patients in treatment with disease-modifying anti-rheumatic drugs. We assessed disability as categorical variable with the Health Assessment Questionnaire, disease activity with the Disease Activity Score instrument, and socioeconomic status with a standard questionnaire used by the Chilean government. Measures of association, stratified analyses and a multiple logistic regression model were used to analyze the data using the Stata 12.1 software package. Low socioeconomic status (annual income below US$ 7,200) is associated with disability (OR 3.87 CI 1.68-9.20) and Mapuche ethnic identity also contributes to disability (OR 2.48, CI 1.09-5.89). Relevant but not statistically significant in multivariable models were variables such as age, gender and place of residence. RA patients with a low socioeconomic status have almost three times the odds of having a moderate to high disability, independent of their ethnic group, gender or place of residence. Therefore, healthcare efforts should be aimed at promoting early diagnosis and prompt treatment among populations with high levels of poverty, which in the region of the Araucanía means primarily indigenous rural areas.
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Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.
PLoS ONE
PUBLISHED: 08-22-2014
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Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.
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Toxicology of antimicrobial nanoparticles for prosthetic devices.
Int J Nanomedicine
PUBLISHED: 08-20-2014
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Advances in nanotechnology are producing an accelerated proliferation of new nanomaterial composites that are likely to become an important source of engineered health-related products. Nanoparticles with antifungal effects are of great interest in the formulation of microbicidal materials. Fungi are found as innocuous commensals and colonize various habitats in and on humans, especially the skin and mucosa. As growth on surfaces is a natural part of the Candida spp. lifestyle, one can expect that Candida organisms colonize prosthetic devices, such as dentures. Macromolecular systems, due to their properties, allow efficient use of these materials in various fields, including the creation of reinforced nanoparticle polymers with antimicrobial activity. This review briefly summarizes the results of studies conducted during the past decade and especially in the last few years focused on the toxicity of different antimicrobial polymers and factors influencing their activities, as well as the main applications of antimicrobial polymers in dentistry. The present study addresses aspects that are often overlooked in nanotoxicology studies, such as careful time-dependent characterization of agglomeration and ion release.
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Ageing and the epidemiology of multimorbidity.
Eur. Respir. J.
PUBLISHED: 08-19-2014
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The world's population is ageing and an important part of this demographic shift is the development of chronic illness. In short, a person who does not die of acute illnesses, such as infections, and survives with chronic illnesses is more likely to develop additional chronic illnesses. Chronic respiratory diseases are an important component of these diseases associated with ageing. This article reviews the relationship between ageing and chronic respiratory disease, and also how certain chronic diseases cluster with others, either on the basis of underlying risk factors, complication of the primary disease or other factors, such as an increased state of inflammation. While death is inevitable, disabling chronic illnesses are not. Better understanding of how individuals can age healthily without the development of multiple chronic illnesses should lead to an improved global quality of life.
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Effect of MLH1 -93G>A on gene expression in patients with colorectal cancer.
Med. Oncol.
PUBLISHED: 08-13-2014
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The DNA repair machinery plays a key role in maintaining genomic stability by preventing the emergence of mutations. Furthermore, the -93G>A polymorphism in the MLH1 gene has been associated with an increased risk of developing colorectal cancer. Therefore, the aim of this study was to examine the expression pattern and effect of this polymorphism in normal and tumour samples from patients with colorectal cancer. The MLH1 -93G>A (rs1800734) polymorphism was detected by PCR-RFLP in 49 cases of colorectal cancer. MLH1 expression was investigated using real-time quantitative PCR. The results indicate a significant decrease in MLH1 expression in tumour samples compared to their normal counterparts. The MLH1 gene was also significantly repressed in samples from patients who had some degree of tumour invasion into other organs. Similarly, those patients who were in a more advanced tumour stage (TNM III and IV) exhibited a significant reduction in MLH1 gene expression. Finally, the mutant genotype AA of MLH1 was associated with a significant decrease in the expression of this gene. This finding suggests that this polymorphism could increase the risk of developing colorectal cancer by a defective mismatch repair system, particularly through the loss of MLH1 expression in an allele-specific manner.
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[Primary Immune thrombocytopenia in adults in Mexico: national characteristics and the relation to international literature].
Gac Med Mex
PUBLISHED: 08-08-2014
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In order to identify the clinical approach of a sample of Mexican hematologists for primary immune thrombocytopenia (ITP) in adults in Mexico, we applied an electronic survey via the internet to identify common practices for the diagnosis and treatment of ITP and draw a comparison between the information from these hematologists with international guidelines or the international literature. The results were analyzed using measures of central tendency. The sample was 21 medical hematologists, predominantly from Mexico City (average age: 51.4 years). A total of 66.7% of the surveyed physicians use international guidelines to make therapeutic decisions, and 43% defined ITP including the numerical concept (< 100 x 10(9)/l). We found some differences between requested clinical exams and tests indicated by the guidelines. In first-line treatment (except emergency), 91% of the participants start with prednisone and 24% use dexamethasone. Danazol is used in persistent ITP by most (41%) of the specialists. In second-line treatment, 67% would indicate splenectomy. Some differences were found between clinical practice of the hematologists in Mexico versus guidelines recommendations.
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Effect of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in patients with colorectal cancer.
Int J Mol Sci
PUBLISHED: 08-07-2014
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It has been hypothesized that genetic variation in base excision repair (BER) might modify colorectal adenoma risk. Thus, we evaluated the influence of APE1 T2197G (Asp148Glu) polymorphism on APE1, XRCC1, PARP1 and OGG1 expression in normal and tumor samples from patients with colorectal cancer. The results indicate a downregulation of OGG1 and an upregulation of XRCC1 expression in tumor tissue. Regarding the anatomical location of APE1, OGG1 and PARP-1, a decrease in gene expression was observed among patients with cancer in the rectum. In patients with or without some degree of tumor invasion, a significant downregulation in OGG1 was observed in tumor tissue. Interestingly, when taking into account the tumor stage, patients with more advanced grades (III and IV) showed a significant repression for APE1, OGG1 and PARP-1. XRCC1 expression levels were significantly enhanced in tumor samples and were correlated with all clinical and histopathological data. Concerning the polymorphism T2197G, GG genotype carriers exhibited a significantly reduced expression of genes of the BER repair system (APE1, XRCC1 and PARP1). In summary, our data show that patients with colorectal cancer present expression changes in several BER genes, suggesting a role for APE1, XRCC1, PARP1 and OGG1 and APE1 polymorphism in colorectal carcinogenesis.
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A computational approach to enzyme design: predicting ?-aminotransferase catalytic activity using docking and MM-GBSA scoring.
J Chem Inf Model
PUBLISHED: 07-22-2014
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Enzyme design is an important area of ongoing research with a broad range of applications in protein therapeutics, biocatalysis, bioengineering, and other biomedical areas; however, significant challenges exist in the design of enzymes to catalyze specific reactions of interest. Here, we develop a computational protocol using an approach that combines molecular dynamics, docking, and MM-GBSA scoring to predict the catalytic activity of enzyme variants. Our primary focuses are to understand the molecular basis of substrate recognition and binding in an S-stereoselective ?-aminotransferase (?-AT), which naturally catalyzes the transamination of pyruvate into alanine, and to predict mutations that enhance the catalytic efficiency of the enzyme. The conversion of (R)-ethyl 5-methyl-3-oxooctanoate to (3S,5R)-ethyl 3-amino-5-methyloctanoate in the context of several ?-AT mutants was evaluated using the computational protocol developed in this work. We correctly identify the mutations that yield the greatest improvements in enzyme activity (20-60-fold improvement over wild type) and confirm that the computationally predicted structure of a highly active mutant reproduces key structural aspects of the variant, including side chain conformational changes, as determined by X-ray crystallography. Overall, the protocol developed here yields encouraging results and suggests that computational approaches can aid in the redesign of enzymes with improved catalytic efficiency.
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Allele-selective inhibition of mutant atrophin-1 expression by duplex and single-stranded RNAs.
Biochemistry
PUBLISHED: 07-11-2014
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Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disorder that currently has no curative treatments. DRPLA is caused by an expansion of a CAG trinucleotide repeat region within the protein-encoding sequence of the atrophin-1 (ATN-1) gene. Inhibition of mutant ATN-1 protein expression is one strategy for treating DRPLA, and allele-selective gene silencing agents that block mutant expression over wild-type expression would be lead compounds for therapeutic development. Here we develop an assay for distinguishing mutant from wild-type ATN-1 protein by gel electrophoresis. We use this assay to evaluate duplex RNAs and single-stranded silencing RNAs (ss-siRNAs) for allele-selective inhibition of ATN-1 protein expression. We observed potent and allele-selective inhibition by RNA duplexes that contain mismatched bases relative to the CAG target and have the potential to form miRNA-like complexes. ss-siRNAs that contained mismatches were as selective as mismatch-containing duplexes. We also report allele-selective inhibition by duplex RNAs containing unlocked nucleic acids or abasic substitutions, although selectivities are not as high. Five compounds that showed >8-fold allele selectivity for mutant ATN-1 were also selective for inhibiting the expression of two other trinucleotide repeat disease genes, ataxin-3 (ATXN-3) and huntingtin (HTT). These data demonstrate that the expanded trinucleotide repeat within ATN-1 mRNA is a potential target for compounds designed to achieve allele-selective inhibition of ATN-1 protein, and one agent may allow the targeting of multiple disease genes.
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Exposure to ozone induces a systemic inflammatory response: possible source of the neurological alterations induced by this gas.
Inhal Toxicol
PUBLISHED: 07-03-2014
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The World Health Organization identified urban outdoor air pollution as the eighth highest mortality risk factor in high-income countries. Exposure to ambient pollutants such as ozone (O3) increases the number of hospital admissions. O3 is a highly reactive gas that reacts with cells lining the airways, producing the formation of reactive oxygen species and inflammation. Beyond the respiratory system, O3 exposure also produces fatigue, lethargy, headaches, and significant decrease in rapid-eye-movement sleep related to an increase in slow-wave sleep. Interestingly, these sleep changes can be significantly mitigated by treatment with indomethacin, which suggests that an inflammatory mechanism may be responsible for these neurological symptoms. To characterize the inflammatory mechanisms by which O3 affects tissues outside the pulmonary system, we evaluated inflammatory factors in both lung and brain. Rats exposed to 1 part per million O3 for 1, 3 or 6 h, as well as rats exposed daily for 1 or 3 h over five consecutive days, showed increases in TNF-? and IL-6 levels within the lungs as well as increases in TNF-?, IL-6, NF-?B p50 and GFAP levels in the cerebral cortex. These results support the hypothesis that the neuroinflammatory response may be responsible for the central nervous system effects of O3 exposure.
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Validation of the Spanish version of the childhood asthma control test (cACT) in a population of Hispanic children.
J Asthma
PUBLISHED: 06-05-2014
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There is a critical need for additional validation studies of questionnaires designed to assess the level of control of asthma in pediatric patients.
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Farm, household, and farmer characteristics associated with changes in management practices and technology adoption among dairy smallholders.
Trop Anim Health Prod
PUBLISHED: 06-03-2014
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This study explored whether technology adoption and changes in management practices were associated with farm structure, household, and farmer characteristics and to identify processes that may foster productivity and sustainability of small-scale dairy farming in the central highlands of Mexico. Factor analysis of survey data from 44 smallholders identified three factors-related to farm size, farmer's engagement, and household structure-that explained 70 % of cumulative variance. The subsequent hierarchical cluster analysis yielded three clusters. Cluster 1 included the most senior farmers with fewest years of education but greatest years of experience. Cluster 2 included farmers who reported access to extension, cooperative services, and more management changes. Cluster 2 obtained 25 and 35 % more milk than farmers in clusters 1 and 3, respectively. Cluster 3 included the youngest farmers, with most years of education and greatest availability of family labor. Access to a network and membership in a community of peers appeared as important contributors to success. Smallholders gravitated towards easy to implement technologies that have immediate benefits. Nonusers of high investment technologies found them unaffordable because of cost, insufficient farm size, and lack of knowledge or reliable electricity. Multivariate analysis may be a useful tool in planning extension activities and organizing channels of communication to effectively target farmers with varying needs, constraints, and motivations for change and in identifying farmers who may exemplify models of change for others who manage farms that are structurally similar but performing at a lower level.
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Sub-Chronic Copper Pretreatment Reduces Oxidative Damage in an Experimental Huntington's Disease Model.
Biol Trace Elem Res
PUBLISHED: 06-02-2014
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Quinolinic acid (QUIN) striatal injection in rat reproduces the main neurochemical features of Huntington's disease (HD), including oxidative damage. In this study, we evaluated the effect of a copper (Cu) supplement in drinking water (90 ppm Cu, 28 days) on the QUIN-induced HD model in the rat. Copper exposure caused no signs of liver toxicity; however, it produced significant Cu accumulation in striatum. It is noteworthy that QUIN also caused increased striatal Cu content; when the supplement was administered to animals with QUIN-injury, an even higher metal striatal accumulation was observed. Cu pre-treatment preserved striatal gamma-aminobutyric acid (GABA) content, which was reduced by QUIN intrastriatal injection. Similarly, apomorphine-induced circling behavior was reduced in Cu-pretreated QUIN-damaged rats. Metal supplement in drinking water prevented both lipid peroxidation and reactive oxygen species (ROS) formation caused by QUIN in striatum. In Cu-treated groups, superoxide dismutase-1 (SOD1) activity showed a significant increase, while SOD2 activity was slightly enhanced. Although the pathophysiological role for higher Cu levels in patients with HD and in experimental models of the disease is not fully understood, results in the present study suggest that Cu oral intake stimulates anti-oxidant defenses, an effect that may be a potential factor for reducing the progression of HD.
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[Effect of metformin addition to an acute lymphoblastic leukemia chemotherapy treatment].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 06-01-2014
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Recently it has been reported a benefit effect with the use of metformin in patients with malignant disease. Our objective was to evaluate the effect of adding metformin to chemotherapy regimen over the percentage of early relapse in acute lymphoblastic leukemia.
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[Isolated bacteria from nasal cultures. Are they important in patients with acute leukemia?].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 06-01-2014
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The nasal colonization by Staphylococcal (epidermidis or aureus) is frequent and it has importance when it is associated to bacteremia in immunocompromised patients. The objective was to determine the frequency of strains that colonize the nasal mucosa in patients with leukemia and its relationship with peripheral blood cultures.
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Lack of validation of variants associated with cervical dystonia risk: A GWAS replication study.
Mov. Disord.
PUBLISHED: 05-14-2014
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A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region.
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[Rosai-Dorfman disease presented with involvement of the adrenal gland. A clinical case reported].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 04-25-2014
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Adrenal gland involvement is a very rare extranodal presentation of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Its pathogenesis still remains unknown with many theories about its probable cause. Symptoms and signs of adrenal involvement presentation are uncertain. Although, it is a disease with a good prognosis and a favorable clinical course in most cases, the low index of suspicion and difficulty in radiological differential diagnosis lead to radical treatment.
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The link between rhinitis and rapid-eye-movement sleep breathing disturbances in children with obstructive sleep apnea.
Am J Rhinol Allergy
PUBLISHED: 04-11-2014
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Rhinitis and obstructive sleep apnea (OSA) often coexist during childhood. To delineate this clinical association, we examined OSA severity and polysomnogram (PSG) features in children with rhinitis and OSA. Given that rapid-eye-movement (REM) sleep is characterized by nasal congestion, we hypothesized that children with rhinitis have more REM-related breathing abnormalities.
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On the ultrasonic degradation of Rhodamine B in water: kinetics and operational conditions effect.
Environ Technol
PUBLISHED: 04-08-2014
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The aim of this present study was to investigate the degradation of Rhodamine B (RhB) in aqueous solution under the influence of ultrasound irradiation. An ultrasonic reactor was used to investigate the effect of different operational parameters such as dye initial concentration, ultrasound power, pH and electrical conductivity. The results showed an increase in decolourization rate with decreasing pH, but colour removal efficiency decreased with increasing initial dye concentration. It was found that an optimum electrical conductivity of the solution exists on enhancing the degree of RhB degradation. Sonolytic degradation data from the present and other works in the literature were analysed by Langmuir-type kinetics. The apparent reaction rate constant was strongly influenced by both irradiation power density and frequency, and based on the experimental data a mathematical correlation between them was obtained.
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Relationship between target organ damage and blood pressure, retinal vessel calibre, oxidative stress and polymorphisms in VAV-2 and VAV-3 genes in patients with hypertension: a case-control study protocol (LOD-Hipertension).
BMJ Open
PUBLISHED: 04-05-2014
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Target organ damage (TOD) is associated with increased cardiovascular risk. The study objectives were to analyse the relationship of TOD to blood pressure, size of retinal arteries and veins, oxidative stress and different polymorphisms in the VAV-2 and VAV-3 genes in participants with hypertension.
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Acute left main coronary artery thrombosis as the first manifestation of systemic lupus erythematosus and catastrophic antiphospholipid syndrome.
Am J Emerg Med
PUBLISHED: 04-04-2014
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Most coronary events in young adults are related to atherosclerosis; however, approximately 20% of coronary heart disease in young adults is related to nonatherosclerotic factors such as coronary abnormalities, connective tissue disorders, and autoimmune diseases. Different initial manifestations of systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) have been reported. Myocardial infarction is observed in patients with SLE in all age groups; it appears during the course of the disease; and it is unusual in the APS. We present a unique case of a 28-year-old young man previously healthy who has an ST-elevation myocardial infarction by total acute thrombosis of the left main coronary artery. Laboratory studies demonstrated the presence of antibodies for SLE and APS. The patient was treated successfully with percutaneous coronary intervention. He developed catastrophic APS despite an adequate anticoagulation and was treated with intravenous steroids and plasmapheresis. Clinical evolution was satisfactory, and he discharged from the hospital. This case highlights the importance of considering in the emergency department, the prothrombotic states such as SLE and APS in young patients presenting with acute myocardial infarction caused by an unexplained intracoronary thrombosis. Early diagnosis of catastrophic APS and aggressive therapies are essential to help such patients from succumbing to this potentially fatal condition.
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Internet access and use by COPD patients in the National Emphysema/COPD Association Survey.
BMC Pulm Med
PUBLISHED: 03-26-2014
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Technology offers opportunities to improve healthcare, but little is known about Internet use by COPD patients. We tested two hypotheses: Internet access is associated with socio-demographic disparities and frequency of use is related to perceived needs.
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Feasibility and cost-effectiveness of stroke prevention through community screening for atrial fibrillation using iPhone ECG in pharmacies. The SEARCH-AF study.
Thromb. Haemost.
PUBLISHED: 03-13-2014
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Atrial fibrillation (AF) causes a third of all strokes, but often goes undetected before stroke. Identification of unknown AF in the community and subsequent anti-thrombotic treatment could reduce stroke burden. We investigated community screening for unknown AF using an iPhone electrocardiogram (iECG) in pharmacies, and determined the cost-effectiveness of this strategy.Pharmacists performedpulse palpation and iECG recordings, with cardiologist iECG over-reading. General practitioner review/12-lead ECG was facilitated for suspected new AF. An automated AF algorithm was retrospectively applied to collected iECGs. Cost-effectiveness analysis incorporated costs of iECG screening, and treatment/outcome data from a United Kingdom cohort of 5,555 patients with incidentally detected asymptomatic AF. A total of 1,000 pharmacy customers aged ?65 years (mean 76 ± 7 years; 44% male) were screened. Newly identified AF was found in 1.5% (95% CI, 0.8-2.5%); mean age 79 ± 6 years; all had CHA2DS2-VASc score ?2. AF prevalence was 6.7% (67/1,000). The automated iECG algorithm showed 98.5% (CI, 92-100%) sensitivity for AF detection and 91.4% (CI, 89-93%) specificity. The incremental cost-effectiveness ratio of extending iECG screening into the community, based on 55% warfarin prescription adherence, would be $AUD5,988 (€3,142; $USD4,066) per Quality Adjusted Life Year gained and $AUD30,481 (€15,993; $USD20,695) for preventing one stroke. Sensitivity analysis indicated cost-effectiveness improved with increased treatment adherence.Screening with iECG in pharmacies with an automated algorithm is both feasible and cost-effective. The high and largely preventable stroke/thromboembolism risk of those with newly identified AF highlights the likely benefits of community AF screening. Guideline recommendation of community iECG AF screening should be considered.
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ALK1 heterozygosity increases extracellular matrix protein expression, proliferation and migration in fibroblasts.
Biochim. Biophys. Acta
PUBLISHED: 02-19-2014
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Fibrosis is a pathological situation in which excessive amounts of extracellular matrix (ECM) are deposited in the tissue. Myofibroblasts play a crucial role in the development and progress of fibrosis as they actively synthesize ECM components such as collagen I, fibronectin and connective tissue growth factor (CTGF) and cause organ fibrosis. Transforming growth factor beta 1 (TGF-?1) plays a major role in tissue fibrosis. Activin receptor-like kinase 1 (ALK1) is a type I receptor of TGF-?1 with an important role in angiogenesis whose function in cellular biology and TGF-? signaling is well known in endothelial cells, but its role in fibroblast biology and its contribution to fibrosis is poorly studied. We have recently demonstrated that ALK1 regulates ECM protein expression in a mouse model of obstructive nephropathy. Our aim was to evaluate the role of ALK1 in several processes involved in fibrosis such as ECM protein expression, proliferation and migration in ALK1(+/+) and ALK1(+/-) mouse embryonic fibroblasts (MEFs) after TGF-?1 stimulations and inhibitors. ALK1 heterozygous MEFs show increased expression of ECM proteins (collagen I, fibronectin and CTGF/CCN2), cell proliferation and migration due to an alteration of TGF-?/Smad signaling. ALK1 heterozygous disruption shows an increase of Smad2 and Smad3 phosphorylation that explains the increases in CTGF/CCN2, fibronectin and collagen I, proliferation and cell motility observed in these cells. Therefore, we suggest that ALK1 plays an important role in the regulation of ECM protein expression, proliferation and migration.
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2'-OMe-phosphorodithioate-modified siRNAs show increased loading into the RISC complex and enhanced anti-tumour activity.
Nat Commun
PUBLISHED: 02-17-2014
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Improving small interfering RNA (siRNA) efficacy in target cell populations remains a challenge to its clinical implementation. Here, we report a chemical modification, consisting of phosphorodithioate (PS2) and 2'-O-Methyl (2'-OMe) MePS2 on one nucleotide that significantly enhances potency and resistance to degradation for various siRNAs. We find enhanced potency stems from an unforeseen increase in siRNA loading to the RNA-induced silencing complex, likely due to the unique interaction mediated by 2'-OMe and PS2. We demonstrate the therapeutic utility of MePS2 siRNAs in chemoresistant ovarian cancer mouse models via targeting GRAM domain containing 1B (GRAMD1B), a protein involved in chemoresistance. GRAMD1B silencing is achieved in tumours following MePS2-modified siRNA treatment, leading to a synergistic anti-tumour effect in combination with paclitaxel. Given the previously limited success in enhancing siRNA potency with chemically modified siRNAs, our findings represent an important advance in siRNA design with the potential for application in numerous cancer types.
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Cost-utility analysis of daily versus intermittent inhaled corticosteroids in mild-persistent asthma.
Pediatr. Pulmonol.
PUBLISHED: 02-14-2014
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Despite the many benefits that have been demonstrated by the continuous administration of inhaled corticosteroids (ICS) in persistent asthma, a new strategy for mild-asthma is emerging, consisting of using intermittent or as-needed ICS treatment in conjunction with short-acting beta2 agonists in response to symptoms. However, no previous studies have reported an economic evaluation comparing these two therapeutic strategies.
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Enhancer RNA facilitates NELF release from immediate early genes.
Mol. Cell
PUBLISHED: 01-31-2014
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Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons. eRNAs are synthesized prior to the culmination of target gene transcription and interact with the NELF complex. Knockdown of eRNAs expressed at neuronal enhancers impairs transient release of NELF from the specific target promoters during transcriptional activation, coinciding with a decrease in target mRNA induction. The enhancer-promoter interaction was unaffected by eRNA knockdown. Instead, chromatin looping might enable eRNAs to act locally at a specific promoter. Our findings highlight the spatiotemporally regulated action mechanism of eRNAs during early transcriptional elongation.
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Intramyocardial hemorrhage in spontaneously reperfused myocardial infarction.
Rev. Invest. Clin.
PUBLISHED: 01-28-2014
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OBJECTIVE. The presence of intramyocardial hemorrhage (IMH) is frequent in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PPCI). We aim for the presence IMH using cMRI in patients who presented AMI and did not undergo PPCI or thrombolysis. Cardiac magnetic resonance has proven to be a highly sensitive method for detect its presence in the ischemic damaged tissue. MATERIAL AND METHODS. Patients admitted with diagnosis of ST elevation myocardial infarction > 24 h after initial presentation and without reperfusion therapy were enrolled in the study. All patients underwent cardiac magnetic resonance for detecting edema, microvascular obstruction and intramyocardial hemorrhage, followed by coronary angiography. RESULTS. Seven male patients, with median age of 53 years, were enrolled. Cardiac magnetic resonance showed that all patients had microvascular obstruction and edema. Two of them had intramyocardial hemorrhage in association with spontaneous reperfusion demonstrated by angiography. CONCLUSION. The results of our study show that in patients with acute myocardial infarction, intramyocardial hemorrhage occurs not only after therapeutic, but also after spontaneous reperfusion. This is the first time that its presence is demonstrated by cardiac magnetic resonance.
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Validation of the Spanish version of the Test for Respiratory and Asthma Control in Kids (TRACK) in a population of Hispanic preschoolers.
J Allergy Clin Immunol Pract
PUBLISHED: 01-22-2014
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There is a critical need for validation studies of questionnaires designed to assess the level of control of asthma in children younger than 5 years old.
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Characterization of cytomegalovirus lung infection in non-HIV infected children.
Viruses
PUBLISHED: 01-21-2014
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Cytomegalovirus (CMV) is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2-4.9 years), using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%), hypoxemia (100%), diffuse adventitious breath sounds (100%) and increased respiratory effort (93%). All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate) or histology/immunohistochemistry in lung biopsy (100% detection rate). CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.
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Taking Healthy Steps: rationale, design and baseline characteristics of a randomized trial of a pedometer-based Internet-mediated walking program in veterans with chronic obstructive pulmonary disease.
BMC Pulm Med
PUBLISHED: 01-16-2014
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Low levels of physical activity are common in patients with chronic obstructive pulmonary disease (COPD), and a sedentary lifestyle is associated with poor outcomes including increased mortality, frequent hospitalizations, and poor health-related quality of life. Internet-mediated physical activity interventions may increase physical activity and improve health outcomes in persons with COPD.
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Clinical and computed tomographic predictors of chronic bronchitis in COPD: a cross sectional analysis of the COPDGene study.
Respir. Res.
PUBLISHED: 01-14-2014
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Chronic bronchitis (CB) has been related to poor outcomes in Chronic Obstructive Pulmonary Disease (COPD). From a clinical standpoint, we have shown that subjects with CB in a group with moderate to severe airflow obstruction were younger, more likely to be current smokers, male, Caucasian, had worse health related quality of life, more dyspnea, and increased exacerbation history compared to those without CB. We sought to further refine our clinical characterization of chronic bronchitics in a larger cohort and analyze the CT correlates of CB in COPD subjects. We hypothesized that COPD patients with CB would have thicker airways and a greater history of smoking, acute bronchitis, allergic rhinitis, and occupational exposures compared to those without CB.
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Impact of self-reported gastroesophageal reflux disease in subjects from COPDGene cohort.
Respir. Res.
PUBLISHED: 01-10-2014
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The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.
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Monitoring of chemotherapy leukemia treatment using Raman spectroscopy and principal component analysis.
Lasers Med Sci
PUBLISHED: 01-10-2014
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In this research, we used the Raman spectroscopy to distinguish between normal and leukemia blood serum and identify the different types of leukemia based on serum biochemistry. In addition, monitoring of patients under chemotherapy leukemia treatment (CHLT) was studied. Blood samples were obtained from seven patients who were clinically diagnosed with three leukemia types and 21 healthy volunteers. In addition, other five leukemia patients were monitored during the CHLT, two patients were declared healthy, one patient suspended it; the health of the other two patients worsened, and no improvement was observed along CHLT. The serum samples were put under an Olympus microscope integrated to the Raman system, and several points were chosen for the Raman measurement. The Horiba Jobin Yvon LabRAM HR800 Raman system is equipped with a liquid nitrogen-cooled detector and a laser of 830 nm with a power irradiation of 17 mW. It is shown that the serum samples from patient with leukemia and from the control group can be discriminated when multivariate statistical methods of principal component analysis (PCA) and linear discriminant analysis (LDA) are applied to their Raman spectra obtaining two large clusters corresponding to the control and leukemia serum samples and three clusters inside the leukemia group associated with the three leukemia types. The major differences between leukemia and control spectra were at 1,338 (Trp, ?-helix, phospholipids), 1,447 (lipids), 1,523 (?-carotene), 1,556 (Trp), 1,587 (protein, Tyr), 1,603 (Tyr, Phe), and 1,654 (proteins, amide I, ?-helix, phospholipids) cm(-1), where these peaks were less intense in the leukemia spectrum. Minor differences occurred at 661 (glutathione), 890 (glutathione), 973 (glucosamine), 1,126 (protein, phospholipid C-C str), 1,160 (?-carotene), 1,174 (Trp, Phe), 1,208 (Trp), 1,246 (amide III), 1,380 (glucosamine), and 1,404 (glutathione) cm(-1). Leukemia spectrum showed a peak at 917 cm(-1) associated with glutathione, but it was absent in the control spectrum. The results suggest that the Raman spectroscopy and PCA could be a technique with a strong potential of support for current techniques to detect and identify the different leukemia types by using a serum sample. Nevertheless, with the construction of a data library integrated with a large number of leukemia and control Raman spectra obtained from a wide range of healthy and leukemic population, the Raman-PCA technique could be converted into a new technique for minimally invasive real-time diagnosis of leukemia from serum samples. In addition, complementary results suggest that using these techniques is possible to monitor CHLT.
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Ancestral resurrection of the Drosophila S2E enhancer reveals accessible evolutionary paths through compensatory change.
Mol. Biol. Evol.
PUBLISHED: 01-09-2014
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Upstream regulatory sequences that control gene expression evolve rapidly, yet the expression patterns and functions of most genes are typically conserved. To address this paradox, we have reconstructed computationally and resurrected in vivo the cis-regulatory regions of the ancestral Drosophila eve stripe 2 element and evaluated its evolution using a mathematical model of promoter function. Our feed-forward transcriptional model predicts gene expression patterns directly from enhancer sequence. We used this functional model along with phylogenetics to generate a set of possible ancestral eve stripe 2 sequences for the common ancestors of 1) D. simulans and D. sechellia; 2) D. melanogaster, D. simulans, and D. sechellia; and 3) D. erecta and D. yakuba. These ancestral sequences were synthesized and resurrected in vivo. Using a combination of quantitative and computational analysis, we find clear support for functional compensation between the binding sites for Bicoid, Giant, and Krüppel over the course of 40-60 My of Drosophila evolution. We show that this compensation is driven by a coupling interaction between Bicoid activation and repression at the anterior and posterior border necessary for proper placement of the anterior stripe 2 border. A multiplicity of mechanisms for binding site turnover exemplified by Bicoid, Giant, and Krüppel sites, explains how rapid sequence change may occur while maintaining the function of the cis-regulatory element.
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Elevation of rat brain tyrosine levels by phenelzine is mediated by its active metabolite ?-phenylethylidenehydrazine.
Prog. Neuropsychopharmacol. Biol. Psychiatry
PUBLISHED: 01-08-2014
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Phenelzine, a non-selective irreversible inhibitor of monoamine oxidase (MAO), has been used in the treatment of depression and anxiety disorders for several decades. It is a unique inhibitor of MAO as it is also a substrate for MAO, with one of the metabolites being ?-phenylethylidenehydrazine (PEH), and it also inhibits several transaminases (e.g. GABA transaminase) in the brain when administered i.p. to rats. Administration of either phenelzine or PEH to rats has been reported to produce dramatic increases in rat brain levels of GABA and alanine while reducing levels of glutamine; these effects are abolished for phenelzine, but not for PEH, when the animals are pre-treated with another MAO inhibitor, suggesting that they are mediated by the MAO-catalyzed formation of PEH from phenelzine. In the present report, we have found that phenelzine and E- and Z-geometric isomers of PEH significantly increased rat whole brain concentrations of L-tyrosine. In a time-response study, acute administration of phenelzine, E-PEH and Z-PEH (30 mg/kg i.p.) elevated rat whole brain L-tyrosine levels at 3 and 6h following injection, reaching approximately 265-305% of vehicle-treated controls at 3h. To determine whether the effect on L-tyrosine is MAO-dependent, animals were pre-treated with the non-selective MAO inhibitor tranylcypromine (1mg/kg i.p.) prior to administration of phenelzine, racemic PEH or vehicle controls. This pre-treatment reversed the effects of phenelzine, but not of PEH, on brain L-tyrosine levels, suggesting that the tyrosine-elevating property of phenelzine is largely the result of its active metabolite PEH. These results are discussed in relation to possible therapeutic applications of these drugs.
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Prevalence of conventional risk factors and lipid profiles in patients with acute coronary syndrome and significant coronary disease.
Ther Clin Risk Manag
PUBLISHED: 01-01-2014
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Among patients with coronary artery disease (CAD), 80%-90% present at least one conventional risk factor. On the other hand, lipid profile modification after a cardiovascular event related to acute coronary syndrome (ACS) has been recognized. The prevalence of conventional risk factors and the lipid profile at the time of admission in patients with ACS and significant CAD (stenosis ?50%) determined through coronary angiography is not well described.
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L-endoglin overexpression increases renal fibrosis after unilateral ureteral obstruction.
PLoS ONE
PUBLISHED: 01-01-2014
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Transforming growth factor-? (TGF-?) plays a pivotal role in renal fibrosis. Endoglin, a 180 KDa membrane glycoprotein, is a TGF-? co-receptor overexpressed in several models of chronic kidney disease, but its function in renal fibrosis remains uncertain. Two membrane isoforms generated by alternative splicing have been described, L-Endoglin (long) and S-Endoglin (short) that differ from each other in their cytoplasmic tails, being L-Endoglin the most abundant isoform. The aim of this study was to assess the effect of L-Endoglin overexpression in renal tubulo-interstitial fibrosis. For this purpose, a transgenic mouse which ubiquitously overexpresses human L-Endoglin (L-ENG+) was generated and unilateral ureteral obstruction (UUO) was performed in L-ENG+ mice and their wild type (WT) littermates. Obstructed kidneys from L-ENG+ mice showed higher amounts of type I collagen and fibronectin but similar levels of ?-smooth muscle actin (?-SMA) than obstructed kidneys from WT mice. Smad1 and Smad3 phosphorylation were significantly higher in obstructed kidneys from L-ENG+ than in WT mice. Our results suggest that the higher increase of renal fibrosis observed in L-ENG+ mice is not due to a major abundance of myofibroblasts, as similar levels of ?-SMA were observed in both L-ENG+ and WT mice, but to the higher collagen and fibronectin synthesis by these fibroblasts. Furthermore, in vivo L-Endoglin overexpression potentiates Smad1 and Smad3 pathways and this effect is associated with higher renal fibrosis development.
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Blue rubber bleb nevus syndrome as a cause of lower digestive bleeding.
Case Rep Surg
PUBLISHED: 01-01-2014
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Introduction. Blue rubber bleb nevus syndrome is a rare disorder that is characterized by multiple recurrent vascular malformations that involve the skin and the gastrointestinal tract. The disease can present chronic anemia and severe episodes of gastrointestinal bleeding. Case Report. A 41-year-old man was admitted with recurrent episodes of lower gastrointestinal bleeding and anemia that had worsened over the last 3 months. The physical examination showed soft, diffuse, compressible, bluish nodules on all of the skin surfaces of the body. A biopsy from one of these skin lesions allowed a histological diagnosis of cavernous hemangioma. He submitted to a colonoscopy, which showed hemorrhoids and a plane vascular lesion mainly located on the right colon with recent signs of bleeding; this lesion was treated by local excision and sclerosis. The pathological study of the colon specimens also reflected the presence of cavernous hemangioma. The cutaneous hemangiomas and the presence of colonic venous malformations were compatible with blue rubber bleb nevus syndrome. The patient presented a favorable follow-up with clinical control of the anemia and without relapse of the gastrointestinal bleeding two years after the procedure. Conclusion. Although rarely diagnosed, blue rubber bleb nevus syndrome may be responsible for lower digestive bleeding.
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Current standing and frontiers of gene therapy for meningiomas.
Neurosurg Focus
PUBLISHED: 12-03-2013
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Meningiomas are among the most common intracranial tumors. The treatment of choice for these lesions is complete resection, but in 50% of cases it is not achieved due to tumor location and/or surgical morbidities. Moreover, benign meningiomas have high recurrence rates of up to 32% in long-term follow-up. Molecular analyses have begun to uncover the genetics behind meningiomas, giving rise to potential genetics-based treatments, including gene therapy. The authors performed a literature review on the most relevant genes associated with meningiomas and both current and potential gene therapy strategies to treat these tumors. Wild-type NF2 gene insertion, oncolytic viruses, and transfer of silencing RNA have all shown promising results both in vitro and in mice. These strategies have decreased meningioma cell growth, proliferation, and angiogenesis. However, no clinical trial has been done to date. Future research and trials in gene insertion, selective inhibition of oncogenes, and the use of oncolytic viruses, among other potential treatment approaches, may shape the future of meningioma management.
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Allele-selective inhibition of expression of huntingtin and ataxin-3 by RNA duplexes containing unlocked nucleic Acid substitutions.
Biochemistry
PUBLISHED: 11-27-2013
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Unlocked nucleic acid (UNA) is an acyclic analogue of RNA that can be introduced into RNA or DNA oligonucleotides. The increased flexibility conferred by the acyclic structure fundamentally affects the strength of base pairing, creating opportunities for improved applications and new insights into molecular recognition. Here we test how UNA substitutions affect allele-selective inhibition of expression of trinucleotide repeat genes Huntingtin (HTT) and Ataxin-3 (ATX-3). We find that the either the combination of mismatched bases and UNA substitutions or UNA substitutions alone can improve potency and selectivity. Inhibition is potent, and selectivities of >40-fold for inhibiting mutant versus wild-type expression can be achieved. Surprisingly, even though UNA preserves the potential for complete base pairing, the introduction of UNA substitutions at central positions within fully complementary duplexes leads to >19-fold selectivity. Like mismatched bases, the introduction of central UNA bases disrupts the potential for cleavage of substrate by argonaute 2 (AGO2) during gene silencing. UNA-substituted duplexes are as effective as other strategies for allele-selective silencing of trinucleotide repeat disease genes. Modulation of AGO2 activity by the introduction of UNA substitutions demonstrates that backbone flexibility is as important as base pairing for catalysis of fully complementary duplex substrates. UNA can be used to tailor RNA silencing for optimal properties and allele-selective action.
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Integrin-Free Tetraspanin CD151 Can Inhibit Tumor Cell Motility upon Clustering and Is a Clinical Indicator of Prostate Cancer Progression.
Cancer Res.
PUBLISHED: 11-12-2013
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Normal physiology relies on the organization of transmembrane proteins by molecular scaffolds, such as tetraspanins. Oncogenesis frequently involves changes in their organization or expression. The tetraspanin CD151 is thought to contribute to cancer progression through direct interaction with the laminin-binding integrins ?3?1 and ?6?1. However, this interaction cannot explain the ability of CD151 to control migration in the absence of these integrins or on non-laminin substrates. We demonstrate that CD151 can regulate tumor cell migration without direct integrin binding and that integrin-free CD151 (CD151(free)) correlates clinically with tumor progression and metastasis. Clustering CD151(free) through its integrin-binding domain promotes accumulation in areas of cell-cell contact, leading to enhanced adhesion and inhibition of tumor cell motility in vitro and in vivo. CD151(free) clustering is a strong regulator of motility even in the absence of ?3 expression but requires PKC?, suggesting that CD151 can control migration independent of its integrin associations. The histologic detection of CD151(free) in prostate cancer correlates with poor patient outcome. When CD151(free) is present, patients are more likely to recur after radical prostatectomy and progression to metastatic disease is accelerated. Multivariable analysis identifies CD151(free) as an independent predictor of survival. Moreover, the detection of CD151(free) can stratify survival among patients with elevated prostate-specific antigen levels. Cumulatively, these studies demonstrate that a subpopulation of CD151 exists on the surface of tumor cells that can regulate migration independent of its integrin partner. The clinical correlation of CD151(free) with prostate cancer progression suggests that it may contribute to the disease and predict cancer progression. Cancer Res; 74(1); 1-15. ©2013 AACR.
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[The lymph nodes imprint for the diagnosis of lymphoid neoplasms].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 10-23-2013
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lymphoma is the most frequent lymphoid neoplasm in our country. Its diagnosis is based on histopathological findings. The lymph node imprint has been used for more than 40 years. The aim was to establish the sensitivity, specificity, positive predictive value and negative predictive value of lymph node imprint and estimate the inter-observer rate.
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Robust spectral analysis of thoraco-abdominal motion and oxymetry in obstructive sleep apnea.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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The diagnosis of obstructive sleep apnea (OSA) relies on polysomnography (PSG), a multidimensional biosignal recording that is conducted in sleep laboratories. Standard PSG montage involves the use of nasal-oral airflow sensors to visualize cyclic episodes of upper airflow interruption, which are considered diagnostic of sleep apnea. Given the high-cost and discomfort associated with in-laboratory PSG, there is an emergent need for novel technology that simplifies OSA screening and diagnosis with less expensive methods. The main goal of this project was to identify novel OSA signatures based on the spectral analysis of thoraco-abdominal motion channels. Our main hypothesis was that proper spectral analysis can detect OSA cycles in adults using simultaneous recording of oxygen saturation (SaO2) and either, chest or abdominal motion. A sample study on 35 individuals was conducted with statistically significant results that suggest a strong relationship between airflow-independent signals and oxygen saturation. The impact of this new approach is that it may allow the design of more comfortable and reliable portable devices for screening, diagnosis and monitoring of OSA, functioning only with oximetry and airflow-independent (abdominal or chest) breathing sensors.
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Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide-releasing diazeniumdiolate-based aspirin derivatives.
J. Med. Chem.
PUBLISHED: 10-08-2013
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Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have successfully reduced the side effect of gastrointestinal ulceration without affecting anti-inflammatory activity, but they may increase the risk of myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces platelet aggregation, preconditions against myocardial infarction, and enhances contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms are described for these compounds. In addition to protection against stomach ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung carcinoma cells (A549), but they were not appreciably toxic toward endothelial cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant sarcomere shortening on murine ventricular myocytes compared to control. Together, these anti-inflammatory, antineoplasic, and contractile properties suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or heart failure.
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Validation of a scale to assess the severity of bronchiolitis in a population of hospitalized infants.
J Asthma
PUBLISHED: 09-19-2013
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Although assessment of the severity of bronchiolitis using severity scores is important both in daily practice and as an outcome measure in clinical trials, many of these scores have not been formally validated or have been only partially validated.
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[Clinical practice guideline. Traumatic urethral stenosis in males].
Rev Med Inst Mex Seguro Soc
PUBLISHED: 09-12-2013
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The incidence of urethral stenosis in Mexico had not been documented. At the Centro Médico Nacional La Raza, during the year 2010, 629 patients with urethral stenosis were attended as outpatient consultation: 85 % with previous urethral stenosis and 15 % with urethral treatment complication. Urethral stenosis is a chronic illness, with multiple etiological origins and the handling is controversial. It has a great negative impact for the patients and the recurrence reaches 85 %. The treatment consisted of an invasive approach (urethral dilations, endoscopy procedure) and open surgery (urethroplasty). The World Health Organization and World Alliance take the world challenge about the urinary tract infections associated with the attention of patients, focused on urethral stenosis. The objective of the following clinical guide is to offer to the health professional a clinical tool for making decisions in the handling of the hardship or masculine urethral stenosis, based on the best available evidence, carrying out in systematized form with bibliographical research using validated terms of the MeSH: urethral structures, in the databases Trip database, PubMed, Guideline Clearinghouse, Cochrane Library and Ovid.
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Influence of body mass index on the association of weight changes with mortality in hemodialysis patients.
Clin J Am Soc Nephrol
PUBLISHED: 09-05-2013
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A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts.
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HDL-cholesterol in coronary artery disease risk: Function or structure?
Clin. Chim. Acta
PUBLISHED: 08-20-2013
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High-density lipoproteins (HDL) are inversely related with coronary artery disease (CAD) and HDL-cholesterol is the only standardized and reproducible parameter available to estimate plasma concentration of these lipoproteins. However, pharmacological interventions intended to increase HDL-cholesterol have not been consistently associated to an effective CAD risk reduction. Among patients with a myocardial infarction, 43 and 44% of men and women, respectively, had normal plasma levels of HDL-cholesterol, whereas genetic studies have failed to show a causal association between HDL-cholesterol and CAD risk. Instead, HDL functionality seems to be the target to be evaluated, but the existing methods are still poorly reproducible and far to be adapted to the clinical laboratory. HDL subclasses rise as a potential alternative for the evaluation of CAD risk; HDL subclasses are a surrogate of intravascular metabolism of these lipoproteins and probably of their functionality. Low levels of large HDL and increased proportions of small particles are the most remarkable features associated to an increased risk of type 2 diabetes mellitus (T2DM) or CAD. However, inflammation and other environmental factors are related with abnormal HDL structure, and, as a consequence, more prospective studies are needed to better support the clinical usefulness of HDL subclasses. New insights from proteome and lipidome profiles of HDL will provide potential HDL-related biomarkers in the coming years.
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Stomatin-domain protein interactions with acid-sensing ion channels modulate nociceptor mechanosensitivity.
J. Physiol. (Lond.)
PUBLISHED: 08-19-2013
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Acid-sensing ion channels (ASICs) and their interaction partners of the stomatin family have all been implicated in sensory transduction. Single gene deletion of asic3, asic2, stomatin, or stoml3 all result in deficits in the mechanosensitivity of distinct cutaneous afferents in the mouse. Here, we generated asic3(-/-):stomatin(-/-), asic3(-/-):stoml3(-/-) and asic2(-/-):stomatin(-/-) double mutant mice to characterize the functional consequences of stomatin-ASIC protein interactions on sensory afferent mechanosensitivity. The absence of ASIC3 led to a clear increase in mechanosensitivity in rapidly adapting mechanoreceptors (RAMs) and a decrease in the mechanosensitivity in both A?- and C-fibre nociceptors. The increased mechanosensitivity of RAMs could be accounted for by a loss of adaptation which could be mimicked by local application of APETx2 a toxin that specifically blocks ASIC3. There is a substantial loss of mechanosensitivity in stoml3(-/-) mice in which ?35% of the myelinated fibres lack a mechanosensitive receptive field and this phenotype was found to be identical in asic3(-/-):stoml3(-/-) mutant mice. However, A?-nociceptors showed much reduced mechanosensitivity in asic3(-/-):stoml3(-/-) mutant mice compared to asic3(-/)(-) controls. Interestingly, in asic2(-/-):stomatin(-/-) mutant mice many A?-nociceptors completely lost their mechanosensitivity which was not observed in asic2(-/-) or stomatin(-/-) mice. Examination of stomatin(-/-):stoml3(-/-) mutant mice indicated that a stomatin/STOML3 interaction is unlikely to account for the greater A?-nociceptor deficits in double mutant mice. A key finding from these studies is that the loss of stomatin or STOML3 in asic3(-/-) or asic2(-/-) mutant mice markedly exacerbates deficits in the mechanosensitivity of nociceptors without affecting mechanoreceptor function.
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The small GTPase N-Ras regulates extracellular matrix synthesis, proliferation and migration in fibroblasts.
Biochim. Biophys. Acta
PUBLISHED: 07-09-2013
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In addition to their role as oncogenes, Ras GTPases are key regulators of cell function. There is a proven relationship between the signaling pathways of transforming growth factor-?1 (TGF- ?1) and Ras GTPases. Each of the Ras isoforms (H, N and K) exhibits specific modulatory activity on different cellular pathways. Our purpose has been to study some of the mechanisms involved in the development of renal fibrosis, assessing the individual role of N-Ras in basal and TGF-?1-mediated extracellular matrix (ECM) synthesis, proliferation, and migration in immortalized N-Ras deficient fibroblasts (N-ras(-/-)). Compared to normal counterparts, fibroblasts deficient for N-Ras exhibited higher basal activity levels of phosphatidylinositol-3-kinase (PI3K)/Akt and MEK/Erk, accompanied by upregulated collagen synthesis and diminished proliferation and migration rates. We found that the absence of N-Ras did not affect TGF-?1-induced proliferation and migration, which required PI3K/Akt but not Erk1/2 activation. Similar effector pathway dependence was found for fibronectin and collagen type I expression. Our results indicate that N-Ras might contribute to renal fibrosis through the down-regulation of ECM synthesis and up-regulation proliferation and migration modulating Akt activation. N-Ras also regulates TGF-?1-induced collagen I and fibronectin expression through Erk-independent pathways.
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Oximetry Signal Processing Identifies REM Sleep-Related Vulnerability Trait in Asthmatic Children.
Sleep Disord
PUBLISHED: 06-30-2013
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Rationale. The sleep-related factors that modulate the nocturnal worsening of asthma in children are poorly understood. This study addressed the hypothesis that asthmatic children have a REM sleep-related vulnerability trait that is independent of OSA. Methods. We conducted a retrospective cross-sectional analysis of pulse-oximetry signals obtained during REM and NREM sleep in control and asthmatic children (n = 134). Asthma classification was based on preestablished clinical criteria. Multivariate linear regression model was built to control for potential confounders (significance level P ? 0.05). Results. Our data demonstrated that (1) baseline nocturnal respiratory parameters were not significantly different in asthmatic versus control children, (2) the maximal % of SaO2 desaturation during REM, but not during NREM, was significantly higher in asthmatic children, and (3) multivariate analysis revealed that the association between asthma and REM-related maximal % SaO2 desaturation was independent of demographic variables. Conclusion. These results demonstrate that children with asthma have a REM-related vulnerability trait that impacts oxygenation independently of OSA. Further research is needed to delineate the REM sleep neurobiological mechanisms that modulate the phenotypical expression of nocturnal asthma in children.
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IgG4-associated vasculitis.
Curr Rheumatol Rep
PUBLISHED: 06-25-2013
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Elevated IgG4 is characteristic of cases of IgG4-RD, a newly recognized systemic disease. However, several chronic inflammatory conditions, including rheumatic diseases, can also be associated with increased levels of IgG4. There have also recently been several reports describing an increased IgG4 immune response to some vasculitis syndromes, in particular Churg-Strauss syndrome and granulomatosis with polyangiitis. To avoid misdiagnosis, clinicians must be aware that the clinical manifestations of IgG4-RD and ANCA-associated vasculitis may overlap. The meaning of these observations is not yet understood, and more studies are needed to determine the true significance of the increased IgG4 response to vasculitis syndromes, especially anti-neutrophil cytoplasmatic antibodies (ANCA)-associated vasculitis.
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Predictors of hospitalization for asthma in children: Results of a 1-year prospective study.
Pediatr. Pulmonol.
PUBLISHED: 06-16-2013
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Although hospital admissions for pediatric asthma constitute a significant problem in high-income countries, they are an even greater health problem in low- and middle-income countries (LMIC). However, previous studies that aimed to identify predictors of hospital admission for asthma in children have mainly been conducted in high-income countries, and these findings might not be applicable to LMIC.
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Predictive value of MicroRNAs in the progression of barrett esophagus to adenocarcinoma in a long-term follow-up study.
Ann. Surg.
PUBLISHED: 06-05-2013
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The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE.
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Heterozygous disruption of activin receptor-like kinase 1 is associated with increased renal fibrosis in a mouse model of obstructive nephropathy.
Kidney Int.
PUBLISHED: 06-03-2013
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Tubulointerstitial fibrosis is characterized by an accumulation of extracellular matrix in the renal interstitium, myofibroblast activation, cell infiltration, and tubular cell apoptosis, leading to chronic renal failure. Activin receptor-like kinase 1 (ALK1) is a transforming growth factor-?1 type I receptor with a pivotal role in endothelial proliferation and migration, but its role in the development of renal fibrosis is unknown. To assess this we used the unilateral ureteral obstruction model of tubulointerstitial fibrosis in ALK1 haploinsufficient (ALK1(+/-)) and wild-type mice. After 15 days, there was an increase in extracellular matrix protein expression in the obstructed kidneys from both ALK1(+/+) and ALK1(+/-) mice, but obstructed kidneys from ALK1(+/-) mice showed significantly higher expression of type I collagen than those from wild-type mice. Ureteral obstruction increased kidney myofibroblasts markers (?-smooth muscle actin and S100A4), without differences between mouse genotypes. ALK1 expression was increased after ureteral obstruction, and this increased expression was located in myofibroblasts. Moreover, cultured renal fibroblasts from ALK1(+/-) mice expressed more collagen type I and fibronectin than fibroblasts derived from wild-type mice. Thus, ALK1 modulates obstruction-induced renal fibrosis by increased extracellular matrix synthesis in myofibroblasts, but without differences in myofibroblast number.Kidney International advance online publication, 14 August 2013; doi:10.1038/ki.2013.292.
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Cervical cancer detection based on serum sample Raman spectroscopy.
Lasers Med Sci
PUBLISHED: 06-01-2013
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The use of Raman spectroscopy to analyze the biochemical composition of serum samples and hence distinguish between normal and cervical cancer serum samples was investigated. The serum samples were obtained from 19 patients who were clinically diagnosed with cervical cancer, 3 precancer, and 20 healthy volunteer controls. The imprint was put under an Olympus microscope, and around points were chosen for Raman measurement.All spectra were collected at a Horiba Jobin-Yvon LabRAM HR800 Raman Spectrometer with a laser of 830-nm wavelength and 17-mW power irradiation. Raw spectra were processed by carrying out baseline correction, smoothing, andnormalization to remove noise, florescence, and shot noise and then analyzed using principal component analysis (PCA). The control serum spectrum showed the presence of higher amounts of carotenoids indicated by peaks at 1,002, 1,160, and 1,523 cm(-1)and intense peaks associated with protein components at 754, 853, 938, 1,002, 1,300-1,345, 1,447, 1,523, 1,550, 1,620, and 1,654 cm(-1). The Raman bands assigned to glutathione (446, 828, and 1,404 cm(-1)) and tryptophan (509, 1,208, 1,556, 1,603, and 1,620 cm(-1)) in cervical cancer were higher than those of control samples, suggesting that their presence may also play a role in cervical cancer. Furthermore, weak bands in the control samples attributed to tryptophan (545, 760, and 1,174 cm(-1)) and amide III (1,234-1,290 cm(-1)) seem to disappear and decrease in the cervical cancer samples, respectively. It is shown that the serum samples from patients with cervical cancer and from the control group can be discriminated with high sensitivity and specificity when the multivariate statistical methods of PCA is applied to Raman spectra. PCA allowed us to define the wavelength differences between the spectral bands of the control and cervical cancer groups by confirming that the main molecular differences among the control and cervical cancer samples were glutathione, tryptophan, ? carotene, and amide III. The preliminary results suggest that Raman spectroscopy could be a highly effective technique with a strong potential of support for current techniques as Papanicolaou smear by reducing the number of these tests; nevertheless, with the construction of a data library integrated with a large number of cervical cancer and control Raman spectra obtained from a wide range of healthy and cervical cancer population, Raman-PCA technique could be converted into a new technique for noninvasive real-time diagnosis of cervical cancer from serum samples.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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