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Find video protocols related to scientific articles indexed in Pubmed.
Hyperoxia-Induced Changes in Estradiol Metabolism in Postnatal Airway Smooth Muscle.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 11-17-2014
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Supplemental oxygen, used to treat hypoxia in preterm and term neonates, increases the risk of neonatal lung diseases such as bronchopulmonary dysplasia (BPD) and asthma. There is a known sex predilection for BPD, but the underlying mechanisms are not clear. We tested the hypothesis that altered, local estradiol following hyperoxia contributes to pathophysiologic changes observed in immature lung. In human fetal airway smooth muscle (fASM) cells exposed to normoxia or hyperoxia, we measured the expression of proteins involved in estrogen metabolism and cell proliferation responses to estradiol. In fASM cells, CYP1a1 expression was increased by hyperoxia while hyperoxia-induced enhancement of cell proliferation was blunted by estradiol. Pharmacological studies indicated these effects were attributable to upregulation of CYP1a1 and subsequent increased metabolism of estradiol to a downstream intermediate 2-methoxyestradiol. Microarray analysis of mouse lung exposed to 14 days hyperoxia showed the most significant alteration in CYP1a1 expression, with minimal changes in expression of five other genes related to estrogen receptors, synthesis and metabolism. Our novel results on estradiol metabolism in fetal and early postnatal lung in the context of hyperoxia indicate CYP1a1 as a potential mechanism for the protective effect of estradiol in hyperoxia-exposed immature lung, which may help explain the sex difference in neonatal lung diseases.
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Using solution- and solid-state S K-edge X-ray absorption spectroscopy with density functional theory to evaluate M-S bonding for MS4(2-) (M = Cr, Mo, W) dianions.
Dalton Trans
PUBLISHED: 10-15-2014
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Herein, we have evaluated relative changes in M-S electronic structure and orbital mixing in Group 6 MS4(2-) dianions using solid- and solution-phase S K-edge X-ray absorption spectroscopy (XAS; M = Mo, W), as well as density functional theory (DFT; M = Cr, Mo, W) and time-dependent density functional theory (TDDFT) calculations. To facilitate comparison with solution measurements (conducted in acetonitrile), theoretical models included gas-phase calculations as well as those that incorporated an acetonitrile dielectric, the latter of which provided better agreement with experiment. Two pre-edge features arising from S 1s ? e* and t electron excitations were observed in the S K-edge XAS spectra and were reasonably assigned as (1)A1 ? (1)T2 transitions. For MoS4(2-), both solution-phase pre-edge peak intensities were consistent with results from the solid-state spectra. For WS4(2-), solution- and solid-state pre-edge peak intensities for transitions involving e* were equivalent, while transitions involving the t orbitals were less intense in solution. Experimental and computational results have been presented in comparison to recent analyses of MO4(2-) dianions, which allowed M-S and M-O orbital mixing to be evaluated as the principle quantum number (n) for the metal valence d orbitals increased (3d, 4d, 5d). Overall, the M-E (E = O, S) analyses revealed distinct trends in orbital mixing. For example, as the Group 6 triad was descended, e* (?*) orbital mixing remained constant in the M-S bonds, but increased appreciably for M-O interactions. For the t orbitals (?* + ?*), mixing decreased slightly for M-S bonding and increased only slightly for the M-O interactions. These results suggested that the metal and ligand valence orbital energies and radial extensions delicately influenced the orbital compositions for isoelectronic ME4(2-) (E = O, S) dianions.
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Misclassification of outcome in case-control studies: Methods for sensitivity analysis.
Stat Methods Med Res
PUBLISHED: 09-14-2014
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Case-control studies are potentially open to misclassification of disease outcome which may be unrelated to risk factor exposure (non-differential), thus underestimating associations, or related to risk factor exposure (differential), thus causing more serious bias. We conducted a systematic literature review for methods of adjusting for outcome misclassification in case-control studies. We also applied methods to simulated data with known outcome misclassification to assess performance of these methods. Finally, real data from the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial gauged the usefulness of these methods. Adjustment methods range from recalculating cell frequencies to probabilistic sensitivity modelling and Bayesian models, which incorporate uncertainty in sensitivity and specificity estimates. Simulated data indicated that substantial bias in either direction resulted from differential misclassification. More sophisticated methods, incorporating uncertainty into estimates of misclassification, provided appropriately wide confidence intervals for corrected estimates of risk factor-disease association. Method choice depends on whether the objective is to assess if an observed association can be explained by bias, or to provide a 'corrected' estimate for the primary analysis. Accurate estimation of the degree of misclassification is important for the latter; otherwise further bias may be introduced.
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The association of time between diagnosis and major resection with poorer colorectal cancer survival: a retrospective cohort study.
BMC Cancer
PUBLISHED: 08-31-2014
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Colorectal cancer survival in the UK is lower than in other developed countries, but the association of time interval between diagnosis and treatment on excess mortality remains unclear.
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Socioeconomic differences in childhood length/height trajectories in a middle-income country: a cohort study.
BMC Public Health
PUBLISHED: 08-29-2014
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Socioeconomic disadvantage is associated with shorter adult stature. Few studies have examined socioeconomic differences in stature from birth to childhood and the mechanisms involved, particularly in middle-income former Soviet settings.
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Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the ProtecT randomised phase 3 trial.
Lancet Oncol.
PUBLISHED: 08-19-2014
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Prostate cancer is a major public health problem with considerable uncertainties about the effectiveness of population screening and treatment options. We report the study design, participant sociodemographic and clinical characteristics, and the initial results of the testing and diagnostic phase of the Prostate testing for cancer and Treatment (ProtecT) trial, which aims to investigate the effectiveness of treatments for localised prostate cancer.
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Adherence to dietary and lifestyle recommendations and prostate cancer risk in the prostate testing for cancer and treatment (ProtecT) trial.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 07-13-2014
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The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) published eight recommendations for cancer prevention, but they are not targeted at prostate cancer prevention. We investigated whether adherence to the WCRF/AICR recommendations and a prostate cancer dietary index is associated with prostate cancer risk.
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Severity of neonatal hyperoxia determines structural and functional changes in developing mouse airway.
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 06-20-2014
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Wheezing is a major long-term respiratory morbidity in preterm infants with and without bronchopulmonary dysplasia. We hypothesized that mild vs. severe hyperoxic exposure in neonatal mice differentially affects airway smooth muscle hypertrophy and resultant airway reactivity. Newborn mice were exposed to 7 days of mild (40% oxygen) or severe (70% oxygen) hyperoxia vs. room air controls. Respiratory system resistance (Rrs), compliance (Crs), and airway reactivity were measured 14 days after oxygen exposure ended under ketamine/xylazine anesthesia. Baseline Rrs increased and Crs decreased in both treatment groups. Methacholine challenge dose dependently increased Rrs and decreased Crs in 40% oxygen-exposed mice, whereas Rrs and Crs responses were similar between 70% oxygen-exposed and normoxic controls. Airway smooth muscle thickness was increased in 40%- but not 70%-exposed mice, whereas collagen increased and both alveolar number and radial alveolar counts decreased after 40% and 70% oxygen. These data indicate that severity of hyperoxia may differentially affect structural and functional changes in the developing mouse airway that contribute to longer-term hyperreactivity. These findings may be important to our understanding of the complex role of neonatal supplemental oxygen therapy in postnatal development of airway responsiveness.
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Associations between APOE and low-density lipoprotein cholesterol genotypes and cognitive and physical capability: the HALCyon programme.
Age (Dordr)
PUBLISHED: 06-18-2014
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The APOE ?2/3/4 genotype has been associated with low-density lipoprotein cholesterol (LDL-C) and Alzheimer disease. However, evidence for associations with measures of cognitive performance in adults without dementia has been mixed, as it is for physical performance. Associations may also be evident in other genotypes implicated in LDL-C levels. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, genotypic information was obtained for APOE ?2/3/4, rs515135 (APOB), rs2228671 (LDLR) and rs629301 (SORT1) from eight cohorts of adults aged between 44 and 90 + years. We investigated associations with four measures of cognitive (word recall, phonemic fluency, semantic fluency and search speed) and physical capability (grip strength, get up and go/walk speed, timed chair rises and ability to balance) using meta-analyses. Overall, little evidence for associations between any of the genotypes and measures of cognitive capability was observed (e.g. pooled beta for APOE ?4 effect on semantic fluency z score = -0.02; 95 % CI = -0.05 to 0.02; p value = 0.3; n = 18,796). However, there was borderline evidence within studies that negative effects of APOE ?4 on nonverbal ability measures become more apparent with age. Few genotypic associations were observed with physical capability measures. The findings from our large investigation of middle-aged to older adults in the general population suggest that effects of APOE on cognitive capability are at most modest and are domain- and age-specific, while APOE has little influence on physical capability. In addition, other LDL-C-related genotypes have little impact on these traits.
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Investigation of thorium salts as candidate materials for direct observation of the (229m)Th nuclear transition.
Inorg Chem
PUBLISHED: 06-17-2014
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Recent efforts to measure the (229m)Th ? (229g)Th nuclear transition sparked interest in understanding the electronic structure of wide-gap thorium salts. Such materials could be used to measure this nuclear transition using optical spectroscopy in solid-state devices. Here, we present screened hybrid density functional theory and many-body G0W0 calculations of two candidate materials, namely, Na2ThF6 and ThF4, for such a measurement. Our results show an electronic gap larger than 10 eV for both materials, suggesting that the internal conversion nuclear de-excitation channel would be suppressed in these materials. We also present results for ThX4 (X = Cl, Br, I), materials with smaller gaps significantly easier to access experimentally.
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Vitamin D Attenuates Cytokine-Induced Remodeling in Human Fetal Airway Smooth Muscle Cells.
J. Cell. Physiol.
PUBLISHED: 06-02-2014
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Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D3 metabolite, calcitriol (1,25-dihydroxyvitamin D3 ; 1,25(OH)2 D3 ), modulates responses to inflammation; however this concept has not been explored in developing airways in the context of pediatric asthma. We used human fetal airway smooth muscle (ASM) cells as a model of the early postnatal airway to explore how calcitriol modulates remodeling induced by pro-inflammatory cytokines. Cells were pre-treated with calcitriol and then exposed to TNF? or TGF? for up to 72?h. Matrix metalloproteinase (MMP) activity, production of extracellular matrix (ECM), and cell proliferation were assessed. Calcitriol attenuated TNF? enhancement of MMP-9 expression and activity. Additionally, calcitriol attenuated TNF? and TGF?-induced collagen III expression and deposition, and separately, inhibited proliferation of fetal ASM cells induced by either inflammatory mediator. Analysis of signaling pathways suggested that calcitriol effects in fetal ASM involve ERK signaling, but not other major inflammatory pathways. Overall, our data demonstrate that calcitriol can blunt multiple effects of TNF? and TGF? in developing airway, and point to a potentially novel approach to alleviating structural changes in inflammatory airway diseases of childhood. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.
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Proteomic analysis of adult Ascaris suum fluid compartments and secretory products.
PLoS Negl Trop Dis
PUBLISHED: 06-01-2014
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Strategies employed by parasites to establish infections are poorly understood. The host-parasite interface is maintained through a molecular dialog that, among other roles, protects parasites from host immune responses. Parasite excretory/secretory products (ESP) play major roles in this process. Understanding the biology of protein secretion by parasites and their associated functional processes will enhance our understanding of the roles of ESP in host-parasite interactions.
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Is restricted fetal growth associated with later adiposity? Observational analysis of a randomized trial.
Am. J. Clin. Nutr.
PUBLISHED: 04-30-2014
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Several recent "developmental origins" studies have reported increased long-term risks of adiposity, especially truncal adiposity, among children born small for gestational age (SGA).OBJECTIVE: We assessed the effects of SGA birth and weight gain in early infancy on adiposity at age 11.5 y.DESIGN: From a cluster-randomized breastfeeding promotion trial in 17,046 Belarusian children, we measured height, weight, waist and hip circumferences, triceps and subscapular skinfold thicknesses, and bioimpedance measures of percentage body fat at age 11.5 y. Children born SGA (birth weight <10th percentile) and those born large for gestational age (LGA; >90th percentile for gestational age) were compared with those born appropriate for gestational age (AGA). Weight gain from birth to 6 mo was categorized as high (>0.67-SD increase in weight-for-age), low (>0.67-SD decrease in weight-for-age), or normal. Multilevel statistical models accounted for clustered measurement and controlled for maternal and paternal height and body mass index (BMI), maternal education, geographic region, urban compared with rural residence, and the child's exact age at follow-up.RESULTS: Children born SGA had a significantly lower BMI, percentage body fat, and fat mass index than did those born AGA, with a dose-response effect across 2 subcategories of SGA (P < 0.001 for all comparisons). No difference was observed in waist-to-hip ratio, although the subscapular-to-triceps skinfold ratio was slightly but significantly (P < 0.001) higher in children born SGA. Differences among the study groups continued to increase since the previous follow-up at 6.5 y. SGA infants with catch-up growth in the first 3-6 mo had growth and adiposity measures intermediate between those born SGA without catch-up and those born AGA. Opposite effects of similar magnitude were observed in children born LGA.CONCLUSION: The 11.5-y-old Belarusian children born SGA were shorter, were thinner, and had less body fat than their non-SGA peers, irrespective of postnatal weight gain. The Promotion of Breastfeeding Intervention Trial was registered at www.isrctn.org as ISRCTN-37687716.
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Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma.
J. Allergy Clin. Immunol.
PUBLISHED: 04-28-2014
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TH2 cells can further differentiate into dual-positive TH2/TH17 cells. The presence of dual-positive TH2/TH17 cells in the airways and their effect on asthma severity are unknown.
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Genetic variation in prostate-specific antigen-detected prostate cancer and the effect of control selection on genetic association studies.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 04-21-2014
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Only a minority of the genetic components of prostate cancer risk have been explained. Some observed associations of SNPs with prostate cancer might arise from associations of these SNPs with circulating prostate-specific antigen (PSA) because PSA values are used to select controls.
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The role of atypical infections and macrolide therapy in patients with asthma.
J Allergy Clin Immunol Pract
PUBLISHED: 04-07-2014
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For many years, the clinical benefit of macrolide use has been recognized in specific groups of patients with pulmonary disease. Dramatic improvement in survival of patients with diffuse panbronchiolitis is the most striking example of successful macrolide use as well as treatment of community acquired pneumonia caused by the atypical bacteria Mycoplasma, Chlamydophila, and Legionella. There also has been documentation of reduction in the exacerbation rate and of improvement in quality of life in patients with cystic fibrosis, bronchiectasis, chronic obstructive pulmonary disease, and reduction in post-lung transplantation bronchiolitis frequency. There has long been an interest in treating patients with severe asthma by using macrolides, but research results have not shown consistent clinical benefit in their use in the "general" population of patients with severe asthma. Rather, the successful use of macrolides seems to be in those patients with either documented Mycoplasma or Chlamydophila infection, or noneosinophilic asthma. Patients with neutrophil predominant phenotype severe asthma tend to show a decline in exacerbation rate, improved peak expiratory flows, and improved quality of life when treated with macrolides. This article will review the use of macrolides in the treatment of asthma.
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Effects of promoting longer-term and exclusive breastfeeding on childhood eating attitudes: a cluster-randomized trial.
Int J Epidemiol
PUBLISHED: 04-04-2014
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Observational studies suggest that breastfeeding benefits later maternal child-feeding practices, which in turn may contribute to positive eating attitudes. We investigated the effect of a randomized intervention to increase duration and exclusivity of breastfeeding on pre-adolescent eating attitudes.
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In silico design of porous polymer networks: high-throughput screening for methane storage materials.
J. Am. Chem. Soc.
PUBLISHED: 03-24-2014
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Porous polymer networks (PPNs) are a class of advanced porous materials that combine the advantages of cheap and stable polymers with the high surface areas and tunable chemistry of metal-organic frameworks. They are of particular interest for gas separation or storage applications, for instance, as methane adsorbents for a vehicular natural gas tank or other portable applications. PPNs are self-assembled from distinct building units; here, we utilize commercially available chemical fragments and two experimentally known synthetic routes to design in silico a large database of synthetically realistic PPN materials. All structures from our database of 18,000 materials have been relaxed with semiempirical electronic structure methods and characterized with Grand-canonical Monte Carlo simulations for methane uptake and deliverable (working) capacity. A number of novel structure-property relationships that govern methane storage performance were identified. The relationships are translated into experimental guidelines to realize the ideal PPN structure. We found that cooperative methane-methane attractions were present in all of the best-performing materials, highlighting the importance of guest interaction in the design of optimal materials for methane storage.
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Reporting of drug induced depression and fatal and non-fatal suicidal behaviour in the UK from 1998 to 2011.
BMC Pharmacol Toxicol
PUBLISHED: 03-23-2014
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Psychiatric adverse drug reactions (ADRs) are distressing for patients and have important public health implications. We identified the drugs with the most frequent spontaneous reports of depression, and fatal and non-fatal suicidal behaviour to the UK's Yellow Card Scheme from 1998 to 2011.
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Unravelling the mechanism of the asymmetric hydrogenation of acetophenone by [RuX2(diphosphine)(1,2-diamine)] catalysts.
J. Am. Chem. Soc.
PUBLISHED: 02-21-2014
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The mechanism of catalytic hydrogenation of acetophenone by the chiral complex trans-[RuCl2{(S)-binap}{(S,S)-dpen}] and KO-t-C4H9 in propan-2-ol is revised on the basis of DFT computations carried out in dielectric continuum and the most recent experimental observations. The results of these collective studies suggest that neither a six-membered pericyclic transition state nor any multibond concerted transition states are involved. Instead, a hydride moiety is transferred in an outer-sphere manner to afford an ion-pair, and the corresponding transition state is both enantio- and rate-determining. Heterolytic dihydrogen cleavage proceeds neither by a (two-bond) concerted, four-membered transition state, nor by a (three-bond) concerted, six-membered transition state mediated by a solvent molecule. Instead, cleavage of the H-H bond is achieved via deprotonation of the ?(2)-H2 ligand within a cationic Ru complex by the chiral conjugate base of (R)-1-phenylethanol. Thus, protonation of the generated (R)-1-phenylethoxide anion originates from the ?(2)-H2 ligand of the cationic Ru complex and not from NH protons of a neutral Ru trans-dihydride complex, as initially suggested within the framework of a metal-ligand bifunctional mechanism. Detailed computational analysis reveals that the 16e(-) Ru amido complex [RuH{(S)-binap}{(S,S)-HN(CHPh)2NH2}] and the 18e(-) Ru alkoxo complex trans-[RuH{OCH(CH3)(R)}{(S)-binap}{(S,S)-dpen}] (R = CH3 or C6H5) are not intermediates within the catalytic cycle, but rather are off-loop species. The accelerative effect of KO-t-C4H9 is explained by the reversible formation of the potassium amidato complexes trans-[RuH2{(S)-binap}{(S,S)-N(K)H(CHPh)2NH2}] or trans-[RuH2{(S)-binap}{(S,S)-N(K)H(CHPh)2NH(K)}]. The three-dimensional (3D) cavity observed within these molecules results in a chiral pocket stabilized via several different noncovalent interactions, including neutral and ionic hydrogen bonding, cation-? interactions, and ?-? stacking interactions. Cooperatively, these interactions modify the catalyst structure, in turn lowering the relative activation barrier of hydride transfer by ~1-2 kcal mol(-1) and the following H-H bond cleavage by ~10 kcal mol(-1), respectively. A combined computational study and analysis of recent experimental data of the reaction pool results in new mechanistic insight into the catalytic cycle for hydrogenation of acetophenone by Noyori's catalyst, in the presence or absence of KO-t-C4H9.
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Brain-derived neurotrophic factor in the airways.
Pharmacol. Ther.
PUBLISHED: 02-10-2014
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In addition to their well-known roles in the nervous system, there is increasing recognition that neurotrophins such as brain derived neurotrophic factor (BDNF) as well as their receptors are expressed in peripheral tissues including the lung, and can thus potentially contribute to both normal physiology and pathophysiology of several diseases. The relevance of this family of growth factors lies in emerging clinical data indicating altered neurotrophin levels and function in a range of diseases including neonatal and adult asthma, sinusitis, influenza, and lung cancer. The current review focuses on 1) the importance of BDNF expression and signaling mechanisms in early airway and lung development, critical to both normal neonatal lung function and also its disruption in prematurity and insults such as inflammation and infection; 2) how BDNF, potentially derived from airway nerves modulate neurogenic control of airway tone, a key aspect of airway reflexes as well as dysfunctional responses to allergic inflammation; 3) the emerging idea that local BDNF production by resident airway cells such as epithelium and airway smooth muscle can contribute to normal airway structure and function, and to airway hyperreactivity and remodeling in diseases such as asthma. Furthermore, given its pleiotropic effects in the airway, BDNF may be a novel and appealing therapeutic target.
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Repeated ?2-adrenergic receptor agonist therapy attenuates the response to rescue bronchodilation in a hyperoxic newborn mouse model.
Neonatology
PUBLISHED: 02-05-2014
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Preterm infants with neonatal lung injury are prone to wheezing and are often treated with ?2-adrenergic receptor (?-AR) agonists although the benefits of ?-AR agonists may be lost with chronic use.
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On the flexibility of metal-organic frameworks.
J. Am. Chem. Soc.
PUBLISHED: 01-30-2014
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Occasional, large amplitude flexibility in metal-organic frameworks (MOFs) is one of the most intriguing recent discoveries in chemistry and material science. Yet, there is at present no theoretical framework that permits the identification of flexible structures in the rapidly expanding universe of MOFs. Here, we propose a simple method to predict whether a MOF is flexible, based on treating it as a system of rigid elements, connected by hinges. This proposition is correct in application to MOFs based on rigid carboxylate linkers. We validate the method by correctly classifying known experimental MOFs into rigid and flexible groups. Applied to hypothetical MOFs, the method reveals an abundance of flexibility phenomena, and this seems to be at odds with the proportion of flexible structures among experimentally known MOFs. We speculate that the flexibility of a MOF may constitute an intrinsic impediment on its experimental realization. This highlights the importance of systematic prediction of large amplitude flexibility regimes in MOFs.
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Transcriptomic evaluation of the nicotinic acetylcholine receptor pathway in levamisole-resistant and -sensitive Oesophagostomum dentatum.
Mol. Biochem. Parasitol.
PUBLISHED: 01-27-2014
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Nematode anthelminthic resistance is widespread for the 3 major drug classes commonly used in agriculture: benzamidazoles, macrocyclic lactones, and nicotinic agonists e.g. levamisole. In parasitic nematodes the genetics of resistance is unknown other than to the benzimidazoles which primarily involve a single gene. In previous work with a levamisole resistant Oesophagostomum dentatum isolate, the nicotinic acetylcholine receptor (nAChR) exhibited decreased levamisole sensitivity. Here, using a transcriptomic approach on the same isolate, we investigate whether that decreased nAChR sensitivity is achieved via a 1-gene mechanism involving 1 of 27 nAChR pathway genes. 3 nAChR receptor subunit genes exhibited ?2-fold change in transcript abundance: acr-21 and acr-25 increased, and unc-63 decreased. 4 SNPs having a ?2-fold change in frequency were also identified. These data suggest that resistance is likely polygenic, involving modulated abundance of multiple subunits comprising the heteropentameric nAChR, and is not due to a simple 1-gene mechanism.
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Anti-inflammatory effect of caffeine is associated with improved lung function after lipopolysaccharide-induced amnionitis.
Neonatology
PUBLISHED: 01-09-2014
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Although caffeine enhances respiratory control and decreases the need for mechanical ventilation and resultant bronchopulmonary dysplasia, it may also have anti-inflammatory properties in protecting lung function.
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Leukotriene B4 receptor 1 is differentially expressed on peripheral T cells of steroid-sensitive and -resistant asthmatics.
Ann. Allergy Asthma Immunol.
PUBLISHED: 01-07-2014
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Numbers of CD8(+) T cells expressing the leukotriene B4 (LTB4) receptor, BLT1, have been correlated with asthma severity.
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Optimizing nanoporous materials for gas storage.
Phys Chem Chem Phys
PUBLISHED: 01-07-2014
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In this work, we address the question of which thermodynamic factors determine the deliverable capacity of methane in nanoporous materials. The deliverable capacity is one of the key factors that determines the performance of a material for methane storage in automotive fuel tanks. To obtain insights into how the molecular characteristics of a material are related to the deliverable capacity, we developed several statistical thermodynamic models. The predictions of these models are compared with the classical thermodynamics approach of Bhatia and Myers [Bhatia and Myers, Langmuir, 2005, 22, 1688] and with the results of molecular simulations in which we screen the International Zeolite Association (IZA) structure database and a hypothetical zeolite database of over 100,000 structures. Both the simulations and our models do not support the rule of thumb that, for methane storage, one should aim for an optimal heat of adsorption of 18.8 kJ mol(-1). Instead, our models show that one can identify an optimal heat of adsorption, but that this optimal heat of adsorption depends on the structure of the material and can range from 8 to 23 kJ mol(-1). The different models we have developed are aimed to determine how this optimal heat of adsorption is related to the molecular structure of the material.
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Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD.
Int J Chron Obstruct Pulmon Dis
PUBLISHED: 01-01-2014
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Small airway changes and dysfunction contribute importantly to airway obstruction in chronic obstructive pulmonary disease (COPD), which is currently treated with inhaled corticosteroids (ICS) and long-acting bronchodilators at Global initiative for Obstructive Lung Disease (GOLD) grades 2-4. This retrospective matched cohort analysis compared effectiveness of a representative small-particle ICS (extrafine beclomethasone) and larger-particle ICS (fluticasone) in primary care patients with COPD.
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The association of early childhood cognitive development and behavioural difficulties with pre-adolescent problematic eating attitudes.
PLoS ONE
PUBLISHED: 01-01-2014
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Few studies have prospectively investigated associations of child cognitive ability and behavioural difficulties with later eating attitudes. We investigated associations of intelligence quotient (IQ), academic performance and behavioural difficulties at 6.5 years with eating attitudes five years later.
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Investigation of acetylcholine receptor diversity in a nematode parasite leads to characterization of tribendimidine- and derquantel-sensitive nAChRs.
PLoS Pathog.
PUBLISHED: 01-01-2014
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Nicotinic acetylcholine receptors (nAChRs) of parasitic nematodes are required for body movement and are targets of important "classical" anthelmintics like levamisole and pyrantel, as well as "novel" anthelmintics like tribendimidine and derquantel. Four biophysical subtypes of nAChR have been observed electrophysiologically in body muscle of the nematode parasite Oesophagostomum dentatum, but their molecular basis was not understood. Additionally, loss of one of these subtypes (G 35 pS) was found to be associated with levamisole resistance. In the present study, we identified and expressed in Xenopus oocytes, four O. dentatum nAChR subunit genes, Ode-unc-38, Ode-unc-63, Ode-unc-29 and Ode-acr-8, to explore the origin of the receptor diversity. When different combinations of subunits were injected in Xenopus oocytes, we reconstituted and characterized four pharmacologically different types of nAChRs with different sensitivities to the cholinergic anthelmintics. Moreover, we demonstrate that the receptor diversity may be affected by the stoichiometric arrangement of the subunits. We show, for the first time, different combinations of subunits from a parasitic nematode that make up receptors sensitive to tribendimidine and derquantel. In addition, we report that the recombinant levamisole-sensitive receptor made up of Ode-UNC-29, Ode-UNC-63, Ode-UNC-38 and Ode-ACR-8 subunits has the same single-channel conductance, 35 pS and 2.4 ms mean open-time properties, as the levamisole-AChR (G35) subtype previously identified in vivo. These data highlight the flexible arrangements of the receptor subunits and their effects on sensitivity and resistance to the cholinergic anthelmintics; pyrantel, tribendimidine and/or derquantel may still be effective on levamisole-resistant worms.
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Effects of Promoting Longer Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years: A Cluster-Randomized, Controlled Trial.
Circulation
PUBLISHED: 12-03-2013
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The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood.
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Methane storage capabilities of diamond analogues.
Phys Chem Chem Phys
PUBLISHED: 11-08-2013
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Methane can be an alternative fuel for vehicular usage provided that new porous materials are developed for its efficient adsorption-based storage. Herein, we search for materials for this application within the family of diamond analogues. We used density functional theory to investigate structures in which tetrahedral C atoms of diamond are separated by -CC- or -BN- groups, as well as ones involving substitution of tetrahedral C atoms with Si and Ge atoms. The adsorptive and diffusive properties of methane are studied using classical molecular simulations. Our results suggest that the all-carbon structure has the highest volumetric methane uptake of 280 VSTP/V at p = 35 bar and T = 298 K. However, it suffers from limited methane diffusion. Alternatively, the considered Si and Ge-containing analogies have fast diffusive properties but their adsorption is lower, ca. 172-179 VSTP/V, at the same conditions.
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Micro-electro-fluidic grids for nematodes: a lens-less, image-sensor-less approach for on-chip tracking of nematode locomotion.
Lab Chip
PUBLISHED: 10-31-2013
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This paper reports on the development of a lens-less and image-sensor-less micro-electro-fluidic (MEF) approach for real-time monitoring of the locomotion of microscopic nematodes. The technology showed promise for overcoming the constraint of the limited field of view of conventional optical microscopy, with relatively low cost, good spatial resolution, and high portability. The core of the device was microelectrode grids formed by orthogonally arranging two identical arrays of microelectrode lines. The two microelectrode arrays were spaced by a microfluidic chamber containing a liquid medium of interest. As a nematode (e.g., Caenorhabditis elegans) moved inside the chamber, the invasion of part of its body into some intersection regions between the microelectrodes caused changes in the electrical resistance of these intersection regions. The worms presence at, or absence from, a detection unit was determined by a comparison between the measured resistance variation of this unit and a pre-defined threshold resistance variation. An electronic readout circuit was designed to address all the detection units and read out their individual electrical resistances. By this means, it was possible to obtain the electrical resistance profile of the whole MEF grid, and thus, the physical pattern of the swimming nematode. We studied the influence of a worms body on the resistance of an addressed unit. We also investigated how the full-frame scanning and readout rates of the electronic circuit and the dimensions of a detection unit posed an impact on the spatial resolution of the reconstructed images of the nematode. Other important issues, such as the manufacturing-induced initial non-uniformity of the grids and the electrotaxic behaviour of nematodes, were also studied. A drug resistance screening experiment was conducted by using the grids with a good resolution of 30 × 30 ?m(2). The phenotypic differences in the locomotion behaviours (e.g., moving speed and oscillation frequency extracted from the reconstructed images with the help of software) between the wild-type (N2) and mutant (lev-8) C. elegans worms in response to different doses of the anthelmintic drug, levamisole, were investigated. The locomotive parameters obtained by the MEF grids agreed well with those obtained by optical microscopy. Therefore, this technology will benefit whole-animal assays by providing a structurally simple, potentially cost-effective device capable of tracking the movement and phenotypes of important nematodes in various microenvironments.
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Smoking cessation treatment and risk of depression, suicide, and self harm in the Clinical Practice Research Datalink: prospective cohort study.
BMJ
PUBLISHED: 10-15-2013
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To compare the risk of suicide, self harm, and depression in patients prescribed varenicline or bupropion with those prescribed nicotine replacement therapy.
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Longitudinal prostate-specific antigen reference ranges: Choosing the underlying model of age-related changes.
Stat Methods Med Res
PUBLISHED: 10-11-2013
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Serial measurements of prostate-specific antigen (PSA) are used as a biomarker for men diagnosed with prostate cancer following an active monitoring programme. Distinguishing pathological changes from natural age-related changes is not straightforward. Here, we compare four approaches to modelling age-related change in PSA with the aim of developing reference ranges for repeated measures of PSA. A suitable model for PSA reference ranges must satisfy two criteria. First, it must offer an accurate description of the trend of PSA on average and in individuals. Second, it must be able to make accurate predictions about new PSA observations for an individual and about the entire PSA trajectory for a new individual.
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Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts.
Stat Methods Med Res
PUBLISHED: 10-09-2013
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Childhood growth is of interest in medical research concerned with determinants and consequences of variation from healthy growth and development. Linear spline multilevel modelling is a useful approach for deriving individual summary measures of growth, which overcomes several data issues (co-linearity of repeat measures, the requirement for all individuals to be measured at the same ages and bias due to missing data). Here, we outline the application of this methodology to model individual trajectories of length/height and weight, drawing on examples from five cohorts from different generations and different geographical regions with varying levels of economic development. We describe the unique features of the data within each cohort that have implications for the application of linear spline multilevel models, for example, differences in the density and inter-individual variation in measurement occasions, and multiple sources of measurement with varying measurement error. After providing example Stata syntax and a suggested workflow for the implementation of linear spline multilevel models, we conclude with a discussion of the advantages and disadvantages of the linear spline approach compared with other growth modelling methods such as fractional polynomials, more complex spline functions and other non-linear models.
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Perinatal factors in neonatal and pediatric lung diseases.
Expert Rev Respir Med
PUBLISHED: 10-03-2013
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Wheezing and asthma are significant clinical problems for infants and young children, particularly following premature birth. Recurrent wheezing in infants can progress to persistent asthma. As in adults, altered airway structure (remodeling) and function (increased bronchoconstriction) are also important in neonatal and pediatric airway diseases. Accumulating evidence suggests that airway disease in children is influenced by perinatal factors including perturbations in normal fetal lung development, postnatal interventions in the intensive care unit (ICU) and environmental and other insults in the neonatal period. Here, in addition to genetics, maternal health, environmental processes, innate immunity and impaired lung development/function can all influence pathogenesis of airway disease in children. We summarize current understanding of how prenatal and postnatal factors can contribute to development of airway diseases in neonates and children. Understanding these mechanisms will help identify and develop novel therapies for childhood airway diseases.
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Carbon K-edge X-ray absorption spectroscopy and time-dependent density functional theory examination of metal-carbon bonding in metallocene dichlorides.
J. Am. Chem. Soc.
PUBLISHED: 09-18-2013
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Metal-carbon covalence in (C5H5)2MCl2 (M = Ti, Zr, Hf) has been evaluated using carbon K-edge X-ray absorption spectroscopy (XAS) as well as ground-state and time-dependent hybrid density functional theory (DFT and TDDFT). Differences in orbital mixing were determined experimentally using transmission XAS of thin crystalline material with a scanning transmission X-ray microscope (STXM). Moving down the periodic table (Ti to Hf) has a marked effect on the experimental transition intensities associated with the low-lying antibonding 1a1* and 1b2* orbitals. The peak intensities, which are directly related to the M-(C5H5) orbital mixing coefficients, increase from 0.08(1) and 0.26(3) for (C5H5)2TiCl2 to 0.31(3) and 0.75(8) for (C5H5)2ZrCl2, and finally to 0.54(5) and 0.83(8) for (C5H5)2HfCl2. The experimental trend toward increased peak intensity for transitions associated with 1a1* and 1b2* orbitals agrees with the calculated TDDFT oscillator strengths [0.10 and 0.21, (C5H5)2TiCl2; 0.21 and 0.73, (C5H5)2ZrCl2; 0.35 and 0.69, (C5H5)2HfCl2] and with the amount of C 2p character obtained from the Mulliken populations for the antibonding 1a1* and 1b2* orbitals [8.2 and 23.4%, (C5H5)2TiCl2; 15.3 and 39.7%, (C5H5)2ZrCl2; 20.1 and 50.9%, (C5H5)2HfCl2]. The excellent agreement between experiment, theory, and recent Cl K-edge XAS and DFT measurements shows that C 2p orbital mixing is enhanced for the diffuse Hf (5d) and Zr (4d) atomic orbitals in relation to the more localized Ti (3d) orbitals. These results provide insight into how changes in M-Cl orbital mixing within the metallocene wedge are correlated with periodic trends in covalent bonding between the metal and the cyclopentadienide ancillary ligands.
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The effects of airway microbiome on corticosteroid responsiveness in asthma.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 09-13-2013
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The role of airway microbiome in corticosteroid response in asthma is unknown.
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Time from diagnosis to surgery and prostate cancer survival: a retrospective cohort study.
BMC Cancer
PUBLISHED: 07-05-2013
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A diagnosis of prostate cancer leads to emotional distress and anxiety, prompting calls for rapid diagnostic pathways. Nevertheless, it remains unclear what impact time between diagnosis and surgery has upon prostate cancer survival.
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Importance of fiberoptic bronchoscopy in identifying asthma phenotypes to direct personalized therapy.
Curr Opin Pulm Med
PUBLISHED: 07-03-2013
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This review summarizes the phenotyping of refractory asthma with an emphasis on how direct bronchoscopic observation and analysis of bronchoalveolar lavage (BAL), biopsy, and brushings of the airways helps direct specific personalized therapy. Additional testing used in phenotyping asthmatic patients is reviewed.
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Neonatal apnea and gastroesophageal reflux (GER): is there a problem?
Early Hum. Dev.
PUBLISHED: 07-02-2013
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Apnea of prematurity and gastroesophageal reflux (GER) are both common occurrences in preterm infants and widely perceived to be causally related. We seek in this review to provide a potential guideline for neonatal GER non-pharmacologic and pharmacologic therapy. Available physiologic data suggest that when there is a temporal relationship apnea may be more likely to predispose to GER via esophageal sphincter relaxation than vice versa. Measurement of multiple intraluminal impedance via esophageal catheter in addition to esophageal pH has enhanced our understanding of GER, although it also did not demonstrate a causal relationship between apnea and GER. The incidence of GER may be modified by thickening feeds and position change without adverse effects. In contrast, pharmacotherapy including acid suppression therapy may have adverse effects and should only be used in infants with clear evidence of clinical benefit.
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Computational cloning of drug target genes of a parasitic nematode, Oesophagostomum dentatum.
BMC Genet.
PUBLISHED: 06-14-2013
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Gene identification and sequence determination are critical requirements for many biological, genomic, and bioinformatic studies. With the advent of next generation sequencing (NGS) technologies, such determinations are predominantly accomplished in silico for organisms for which the genome is known or for which there exists substantial gene sequence information. Without detailed genomic/gene information, in silico sequence determination is not straightforward, and full coding sequence determination typically involves time- and labor-intensive PCR-based amplification and cloning methods.
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The association of vitamin D supplementation with the risk of cancer in postmenopausal women.
Cancer Causes Control
PUBLISHED: 06-06-2013
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There is inconclusive evidence on whether vitamin D therapy reduces cancer risk. We investigated the effect of vitamin D (±calcium) supplementation on the risk of breast, ovarian, uterine, colorectal, and lung cancer in women.
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"Lets get the best quality research we can": public awareness and acceptance of consent to use existing data in health research: a systematic review and qualitative study.
BMC Med Res Methodol
PUBLISHED: 05-29-2013
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Opt-in consent is usually required for research, but is known to introduce selection bias. This is a particular problem for large scale epidemiological studies using only pre-collected health data. Most previous studies have shown that members of the public value opt-in consent and can perceive research without consent as an invasion of privacy. Past research has suggested that people are generally unaware of research processes and existing safeguards, and that education may increase the acceptability of research without prior informed consent, but this recommendation has not been formally evaluated. Our objectives were to determine the range of public opinion about the use of existing medical data for research and to explore views about consent to a secondary review of medical records for research. We also investigated the effect of the provision of detailed information about the potential effect of selection bias on public acceptability of the use of data for research.
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Physicians prescribing preferences were a potential instrument for patients actual prescriptions of antidepressants.
J Clin Epidemiol
PUBLISHED: 05-17-2013
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To investigate whether physicians prescribing preferences were valid instrumental variables for the antidepressant prescriptions they issued to their patients.
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Lung inflammation induces IL-1? expression in hypoglossal neurons in rat brainstem.
Respir Physiol Neurobiol
PUBLISHED: 04-25-2013
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Perinatal inflammation is associated with respiratory morbidity. Immune modulation of brainstem respiratory control centers may provide a link for this pathobiology. We exposed 11-day old rats to intratracheal lipopolysaccharide (LPS, 0.5 ?g/g) to test the hypothesis that intrapulmonary inflammation increases expression of the proinflammatory cytokine IL-1? within respiratory-related brainstem regions. Intratracheal LPS resulted in a 32% increase in IL-1? protein expression in the medulla oblongata. In situ hybridization showed increased intensity of IL-1? mRNA but no change in neuronal numbers. Co-localization experiments showed that hypoglossal neurons express IL-1? mRNA and immunostaining showed a 43% increase in IL-1? protein-expressing cells after LPS exposure. LPS treatment also significantly increased microglial cell numbers though they did not express IL-1? mRNA. LPS-induced brainstem expression of neuronal IL-1? mRNA and protein may have implications for our understanding of the vulnerability of neonatal respiratory control in response to a peripheral proinflammatory stimulus.
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Characterization and comparison of pore landscapes in crystalline porous materials.
J. Mol. Graph. Model.
PUBLISHED: 03-06-2013
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Crystalline porous materials have many applications, including catalysis and separations. Identifying suitable materials for a given application can be achieved by screening material databases. Such a screening requires automated high-throughput analysis tools that characterize and represent pore landscapes with descriptors, which can be compared using similarity measures in order to select, group and classify materials. Here, we discuss algorithms for the calculation of two types of pore landscape descriptors: pore size distributions and stochastic rays. These descriptors provide histogram representations that encode the geometrical properties of pore landscapes. Their calculation involves the Voronoi decomposition as a technique to map and characterize accessible void space inside porous materials. Moreover, we demonstrate pore landscape comparisons for materials from the International Zeolite Association (IZA) database of zeolite frameworks, and illustrate how the choice of pore descriptor and similarity measure affects the perspective of material similarity exhibiting a particular emphasis and sensitivity to certain aspects of structures.
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Delivering perinatal psychiatric services in the neonatal intensive care unit.
Acta Paediatr.
PUBLISHED: 02-18-2013
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To describe characteristics of mothers who would likely benefit from on-site short-term psychiatric services while their infant is in the neonatal intensive care unit (NICU).
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Apnea of prematurity--perfect storm.
Respir Physiol Neurobiol
PUBLISHED: 02-10-2013
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With increased survival of preterm infants as young as 23 weeks gestation, maintaining adequate respiration and corresponding oxygenation represents a clinical challenge in this unique patient cohort. Respiratory instability characterized by apnea and periodic breathing occurs in premature infants because of immature development of the respiratory network. While short respiratory pauses and apnea may be of minimal consequence if oxygenation is maintained, they can be problematic if accompanied by chronic intermittent hypoxemia. Underdevelopment of the lung and the resultant lung injury that occurs in this population concurrent with respiratory instability creates the perfect storm leading to frequent episodes of profound and recurrent hypoxemia. Chronic intermittent hypoxemia contributes to the immediate and long term co-morbidities that occur in this population. In this review we discuss the pathophysiology leading to the perfect storm, diagnostic assessment of breathing instability in this unique population and therapeutic interventions that aim to stabilize breathing without contributing to tissue injury.
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Asthma outcomes and costs of therapy with extrafine beclomethasone and fluticasone.
J. Allergy Clin. Immunol.
PUBLISHED: 02-06-2013
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Characteristics of inhaled corticosteroids (ICSs) differ, but data comparing the real-life effectiveness of various ICSs for asthma are lacking.
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Derquantel and abamectin: effects and interactions on isolated tissues of Ascaris suum.
Mol. Biochem. Parasitol.
PUBLISHED: 02-05-2013
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Startect(®) is a novel anthelmintic combination of derquantel and abamectin. It is hypothesized that derquantel and abamectin interact pharmacologically. We investigated the effects of derquantel, abamectin and their combination on somatic muscle nicotinic acetylcholine receptors and pharyngeal muscle glutamate gated chloride receptor channels of Ascaris suum. We used muscle-strips to test the effects of abamectin, derquantel, and abamectin+derquantel together on the contraction responses to different concentrations of acetylcholine. We found that abamectin reduced the response to acetylcholine, as did derquantel. In combination (abamectin+derquantel), inhibition of the higher acetylcholine concentration response was greater than the predicted additive effect. A two-micropipette current-clamp technique was used to study electrophysiological effects of the anthelmintics on: (1) acetylcholine responses in somatic muscle and; (2) on l-glutamate responses in pharyngeal preparations. On somatic muscle, derquantel (0.1-30?M) produced a potent (IC50 0.22, CI 0.18-0.28?M) reversible antagonism of acetylcholine depolarizations. Abamectin (0.3?M) produced a slow onset inhibition of acetylcholine depolarizations. We compared effects of abamectin and derquantel on muscle preparations pretreated for 30min with these drugs. The effect of the combination was significantly greater than the predicted additive effect of both drugs at higher acetylcholine concentrations. On the pharynx, application of derquantel produced no significant effect by itself or on responses to abamectin and l-glutamate. Abamectin increased the input conductance of the pharynx (EC50 0.42, CI 0.13-1.36?M). Our study demonstrates that abamectin and derquantel interact at nicotinic acetylcholine receptors on the somatic muscle and suggested synergism can occur.
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Covalency in metal-oxygen multiple bonds evaluated using oxygen K-edge spectroscopy and electronic structure theory.
J. Am. Chem. Soc.
PUBLISHED: 01-28-2013
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Advancing theories of how metal-oxygen bonding influences metal oxo properties can expose new avenues for innovation in materials science, catalysis, and biochemistry. Historically, spectroscopic analyses of the transition metal MO(4)(x-) anions have formed the basis for new M-O bonding theories. Herein, relative changes in M-O orbital mixing in MO(4)(2-) (M = Cr, Mo, W) and MO(4)(-) (M = Mn, Tc, Re) are evaluated for the first time by nonresonant inelastic X-ray scattering, X-ray absorption spectroscopy using fluorescence and transmission (via a scanning transmission X-ray microscope), and time-dependent density functional theory. The results suggest that moving from Group 6 to Group 7 or down the triads increases M-O e* (?*) mixing; for example, it more than doubles in ReO(4)(-) relative to CrO(4)(2-). Mixing in the t(2)* orbitals (?*?+??*) remains relatively constant within the same Group, but increases on moving from Group 6 to Group 7. These unexpected changes in orbital energy and composition for formally isoelectronic tetraoxometalates are evaluated in terms of periodic trends in d orbital energy and radial extension.
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The preterm lung and airway: past, present, and future.
Pediatr Neonatol
PUBLISHED: 01-18-2013
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The tremendous advancement that has occurred in neonatal intensive care over the last 40-50 years can be largely attributed to greater understanding of developmental pathobiology in the newborn lung. Nonetheless, this improved survival from respiratory distress syndrome has been associated with continuing longer-term morbidity in the form of bronchopulmonary dysplasia (BPD). As a result, neonatal lung injury is a renewed focus of scientific interest. The onset of such an injury may begin in the delivery room, and this has generated interest in minimizing oxygen therapy and aggressive ventilatory support during the transition from fetal to neonatal lung. Fortunately, antenatal steroid therapy and selective use of surfactant therapy are now widely practiced, although fine tuning of this therapy for selected populations is ongoing. Newer therapeutic approaches address many aspects of BPD, including the pro-inflammatory component that characterizes this disorder. Finally, there is a greater need to understand the epidemiology and pathogenesis of the longer-term respiratory morbidity, most notably asthma, that persists in the preterm survivors of neonatal intensive care.
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Tetrahalide complexes of the [U(NR)2]2+ ion: synthesis, theory, and chlorine K-edge X-ray absorption spectroscopy.
J. Am. Chem. Soc.
PUBLISHED: 01-15-2013
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Synthetic routes to salts containing uranium bis-imido tetrahalide anions [U(NR)(2)X(4)](2-) (X = Cl(-), Br(-)) and non-coordinating NEt(4)(+) and PPh(4)(+) countercations are reported. In general, these compounds can be prepared from U(NR)(2)I(2)(THF)(x) (x = 2 and R = (t)Bu, Ph; x = 3 and R = Me) upon addition of excess halide. In addition to providing stable coordination complexes with Cl(-), the [U(NMe)(2)](2+) cation also reacts with Br(-) to form stable [NEt(4)](2)[U(NMe)(2)Br(4)] complexes. These materials were used as a platform to compare electronic structure and bonding in [U(NR)(2)](2+) with [UO(2)](2+). Specifically, Cl K-edge X-ray absorption spectroscopy (XAS) and both ground-state and time-dependent hybrid density functional theory (DFT and TDDFT) were used to probe U-Cl bonding interactions in [PPh(4)](2)[U(N(t)Bu)(2)Cl(4)] and [PPh(4)](2)[UO(2)Cl(4)]. The DFT and XAS results show the total amount of Cl 3p character mixed with the U 5f orbitals was roughly 7-10% per U-Cl bond for both compounds, which shows that moving from oxo to imido has little effect on orbital mixing between the U 5f and equatorial Cl 3p orbitals. The results are presented in the context of recent Cl K-edge XAS and DFT studies on other hexavalent uranium chloride systems with fewer oxo or imido ligands.
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Filter paper blood spot enzyme linked immunoassay for adiponectin and application in the evaluation of determinants of child insulin sensitivity.
PLoS ONE
PUBLISHED: 01-01-2013
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Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT).
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A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice.
Exp. Lung Res.
PUBLISHED: 12-20-2011
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Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4+ T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.
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Circulating insulin-like growth factors and IGF-binding proteins in PSA-detected prostate cancer: the large case-control study ProtecT.
Cancer Res.
PUBLISHED: 11-21-2011
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Circulating insulin-like growth factor-I (IGF-I) has been studied extensively in prostate cancer, but there is still little information about IGFs and IGF-binding proteins (IGFBP) in cancers detected by the prostate-specific antigen (PSA) test. Here, we report the findings of a U.K.-based case-control study to investigate circulating IGFs and IGFBPs in PSA-detected prostate cancer with regard to their potential associations with different cancer stages or grades. PSA testing was offered to 110,000 men aged 50 to 69 years from 2002 to 2009. Participants with an elevated level of PSA (?3.0 ng/mL) underwent prostate biopsy and measurements of blood serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 obtained at recruitment. We found that serum levels of IGF-II (OR per SD increase: 1.16; 95% CI: 1.08-1.24; P(trend) < 0.001), IGFBP-2 (1.18; 1.06-1.31; P(trend) < 0.01) and IGFBP-3 (1.27; 1.19-1.36; P(trend) < 0.001), but not IGF-I (0.99; 0.93-1.04; P(trend) = 0.62), were associated with PSA-detected prostate cancer. After controlling for IGFBP-3, IGF-II was no longer associated (0.99; 0.91-1.08; P(trend) = 0.62) and IGF-I was inversely associated (0.85; 0.79-0.91; P(trend) < 0.001) with prostate cancer. In addition, no strong associations existed with cancer stage or grade. Overall, these findings suggest potentially important roles for circulating IGF-II, IGFBP-2, and IGFBP-3 in PSA-detected prostate cancer, in support of recent in vitro evidence. Although our findings for IGF-I agree with previous results from PSA screening trials, they contrast with positive associations in routinely detected disease, suggesting that reducing levels of circulating IGF-I might not prevent the initiation of prostate cancer but might, nonetheless, prevent its progression.
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Intermittent hypoxic episodes in preterm infants: do they matter?
Neonatology
PUBLISHED: 10-03-2011
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Intermittent hypoxic episodes are typically a consequence of immature respiratory control and remain a troublesome challenge for the neonatologist. Furthermore, their frequency and magnitude are underestimated by clinically employed pulse oximeter settings. In extremely low birth weight infants the incidence of intermittent hypoxia progressively increases over the first 4 weeks of postnatal life, with a subsequent plateau followed by a slow decline beginning at weeks 6-8. Such episodic hypoxia/reoxygenation has the potential to sustain a proinflammatory cascade with resultant multisystem morbidity. This morbidity includes retinopathy of prematurity and impaired growth, as well as possible longer-term cardiorespiratory instability and poor neurodevelopmental outcome. Therapeutic approaches for intermittent hypoxic episodes comprise determination of optimal baseline saturation and careful titration of supplemental inspired oxygen, as well as xanthine therapy to prevent apnea of prematurity. In conclusion, characterization of the pathophysiologic basis for such intermittent hypoxic episodes and their consequences during early life is necessary to provide an evidence-based approach to their management.
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MicroRNA-21 inhibits toll-like receptor 2 agonist-induced lung inflammation in mice.
Exp. Lung Res.
PUBLISHED: 09-06-2011
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Impaired airway innate immunity (e.g., suppressed Toll-like receptor 2 [TLR2] signaling) has been reported in allergic lungs with bacterial infection. Recently, an allergic mouse lung milieu including the T-helper type 2 (Th2) cytokine interleukin-13 (IL-13) has been shown to up-regulate lung microRNA-21 (miR-21) expression. Whether miR-21 modulates in vivo TLR2 signaling is unknown. The goal of this study was to determine if in vivo, miR-21 regulates a TLR2 agonist-induced lung inflammatory response. Balb/c mice were intranasally pretreated with a locked nucleic acid (LNA) in vivo inhibitor probe for mouse miR-21 or a control probe, followed by intranasal instillation of a TLR2 agonist Pam3CSK4, or saline (control). Four and/or 24 hours later, mice treated with the miR-21 inhibitor probe, as compared to the control probe, significantly increased lung leukocytes, including neutrophils and the keratinocyte-derived chemokine (KC). IL-13 treatment for 72 hours increased (P < .05) miR-21 in cultured primary normal human airway epithelial cells. These results, for the first time, suggest an in vivo role of miR-21 in suppressing TLR2 signaling, and further support that IL-13 can up-regulate miR-21 in human airway epithelial cells. Functional studies on miR-21 likely provide novel approaches to modulate TLR2 signaling in Th2 cytokine-exposed airways.
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Is infant weight associated with childhood blood pressure? Analysis of the Promotion of Breastfeeding Intervention Trial (PROBIT) cohort.
Int J Epidemiol
PUBLISHED: 09-03-2011
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Weight gain during infancy may programme later health outcomes, but examination of this hypothesis requires appropriate lifecourse methods and detailed weight gain measures during childhood. We examined associations between weight gain in infancy and early childhood and blood pressure at the age of 6.5 years in healthy children born at term.
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Refractory asthma: importance of bronchoscopy to identify phenotypes and direct therapy.
Chest
PUBLISHED: 08-11-2011
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The pathophysiology of refractory asthma is not well understood; thus, treatment modalities are not targeted to specific phenotypes but rather to a broad-based treatment approach. The objective of this study was to develop refractory asthma phenotypes based on bronchoscopic evaluation and to develop from this information specific, directed, personalized therapy.
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Effects of peripheral and axial substitutions on electronic transitions of tin naphthalocyanines.
J Phys Chem A
PUBLISHED: 08-01-2011
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Tin naphthalocyanine molecules display strong absorption in the infrared region (IR), making them ideal as components of organic photodiodes and solar cells. We use density functional theory and time-dependent density functional theory (TD-DFT) at the B3LYP level to study the influence of axial and peripheral ligands on the absorption wavelength of tin naphthalocyanines. We find that TD-DFT is successful at reproducing the experimental absorption spectra of free base naphthalocyanine and tin naphthalocyanine molecules and can be used as a reliable tool to predict absorption spectra of substituted naphthalocyanines. Functional groups attached axially to tin (-F, -Cl, -Br, -I) and peripherally to the inner ring (-F, -Cl, -Br, -Ph, -OH, -COCH(3), -O(CH(2))(3)CH(3)) of the tin naphthalocyanine molecule tune the excitation wavelength in the near-infrared region between 770 and 940 nm. While substituents to the outer naphthalocyanine ring (-Cl, -Br) affect the intensity of the absorption peaks in the NIR region, they do not influence their absorption wavelength. Asymmetric substitution of naphthalocyanine pendant arms can be employed to decrease intensity of the absorption peaks in the visible region with respect to the intensity of the peaks in the NIR.
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The causal roles of vitamin B(12) and transcobalamin in prostate cancer: can Mendelian randomization analysis provide definitive answers?
Int J Mol Epidemiol Genet
PUBLISHED: 07-23-2011
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Circulating vitamin B(12) (cobalamin/B(12)) and total transcobalamin (tTC) have been associated with increased and reduced risk, respectively, of prostate cancer. Mendelian randomization has the potential to determine whether these are causal associations. We estimated associations of single nucleotide polymorphisms in B(12)-related genes (MTR, MTRR, FUT2, TCN2, TCN1, CUBN, and MUT) with plasma concentrations of B(12), tTC, holo-transcobalamin, holo-haptocorrin, folate, and homocysteine and with prostate cancer risk in a case-control study (913 cases, 895 controls) nested within the UK-wide population-based ProtecT study of prostate cancer in men age 45-69 years. Instrumental variable (IV) analysis was used to estimate odds ratios for effects of B(12) and tTC on prostate cancer. We observed that B(12) was lower in men with FUT2 204G>A (rs492602), CUBN 758C>T (rs1801222) and MUT 1595G>A (rs1141321) alleles (P(trend)<0.001); tTC was lower in men with the TCN2 776C>G (rs1801198) allele (P(trend)<0.001). FUT2 204G>A and CUBN 758C>T were selected as instruments for B(12); TCN2 776C>G for tTC. Conventional and IV estimates for the association of log(e)(B(12)) with prostate cancer were: OR=1.17 (95% CI 0.90-1.51), P=0.2 and OR=0.60 (0.16-2.15), P=0.4, respectively. Conventional and IV estimates for the association of loge(tTC) with prostate cancer were: OR=0.81 (0.54-1.20), P=0.3 and OR=0.41 (0.13-1.32), P=0.1, respectively. Confidence intervals around the IV estimates in our study were too wide to allow robust inference. Sample size estimates based on our data indicated that Mendelian randomization in this context requires much larger studies or multiple genetic variants that explain all of the variance in the intermediate phenotype.
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Serum insulin-like growth factors and mortality in localised and advanced clinically detected prostate cancer.
Cancer Causes Control
PUBLISHED: 07-07-2011
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Many studies have reported associations of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with prostate cancer development, but none have investigated their association with fatal progression of prostate cancer.
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What is Visualize?

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

How does it work?

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

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

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