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Find video protocols related to scientific articles indexed in Pubmed.
Effect of interaction heterogeneity on colloidal arrangements at a curved oil-water interface.
Soft Matter
PUBLISHED: 11-20-2014
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We report the unique arrangement behaviour of colloidal particles at a curved oil-water interface. Particles trapped at a centrosymmetrically curved oil-water interface, formed by placing an oil lens at a neat air-water interface, organize into diverse arrangement structures due to electrostatic repulsion under the gravitational field. To reveal a possible mechanism behind the observed diversity, we investigate the interactions between pairs of particles at the curved oil-water interface. The magnitude of electrostatic repulsive interactions between pairs of particles is determined by minimizing the total potential of the particle pairs. We show that the pair interactions are quite heterogeneous, following a Gamma distribution. Using the experimentally determined pair potential and the heterogeneity in the potential as input parameters for Monte Carlo simulations, we show that such interaction heterogeneity affects the particle arrangements at the curved interface and results in an observed diversity in the particle arrangement structures. We believe that this work prompts further experimental and simulation studies to extensively understand hierarchical relations from small scale measurements (e.g., pair interactions and heterogeneity) to bulk scale properties (e.g., microstructure and interfacial rheology).
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Importance of regular testing of private drinking water systems in North Carolina.
N C Med J
PUBLISHED: 11-18-2014
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North Carolina state laws require that water from newly constructed private wells be tested for chemical and microbiologic contamination, but existing wells are not routinely tested. This commentary highlights the importance of regular testing of all private sources of drinking water.
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Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy.
Endocr. J.
PUBLISHED: 11-14-2014
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To assess the total daily inulin dose (TDD) and contribution of basal insulin to TDD and to identify the predictive factors for insulin requirement profiles in subjects with type 2 diabetes, we retrospectively examined insulin requirement profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy (BBT) (mean age, 60.1 ± 12.9 years; HbA1c, 10.2 ± 4.5%). Target plasma glucose level was set between 80 and 129 mg/dL before breakfast and between 80 and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also analyzed the relationship between the insulin requirement profiles (TDD and basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical parameters. The mean TDD was 0.463 ± 0.190 unit/kg/day (range, 0.16-1.13 unit/kg/day). The mean B/TD ratio was 0.300 ± 0.099 (range, 0.091-0.667). A positive correlation of TDD with B/TD ratio was revealed by linear regression analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post-breakfast glucose levels before titrating insulin as an independent determinant of the insulin requirement profile [Std ? (standard regression coefficient) = 5.71E-4, p<0.01 for TDD, Std ? = -2.39E-4, p <0.01 for B/TD ratio]. The TDD was <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects in the present study. These findings may have relevance in improving glycemic control and decreasing the risk of hypoglycemia and weight gain in subjects with type 2 diabetes treated with BBT.
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Depression in Caregivers of Status-Naïve Pediatric HIV Patients Participating in a Status Disclosure Study in Haiti and the Dominican Republic: Preliminary Report.
J. Trop. Pediatr.
PUBLISHED: 11-13-2014
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A pilot study is underway to assess safety and acceptability of an intervention to disclose their HIV infection status to status-naïve pediatric antiretroviral therapy patients in Hispaniola [the island shared by Haiti and the Dominican Republic (DR)]. Of 22 Haiti and 47 DR caregivers recruited to date, 68.2% Haiti and 34.0% DR caregivers had clinically significant depressive symptomatology at the time of enrollment (p = 0.008). Depressive symptom prevalence was higher in Haiti caregivers who were female (81.3% vs. 0 in males; p = 0.02) and in DR caregivers who were patients' mothers (50.0%) or grandmothers (66.7%; 56.0% combined) than others (9.1%), (p < 0.001). Internalized stigma was more commonly reported by Haiti (85.7%) than DR (53.2%; p = 0.01) caregivers; 56.4% of Haiti and DR caregivers reporting internalized stigma vs. 26.1% of caregivers denying it had depressive symptoms (p = 0.02). Depression is common in Hispaniola caregivers possibly affecting disclosure timing. Study participation presents opportunities for addressing caregiver depression.
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Synthesis, Structure, and Properties of Supramolecular Photoswitches Based on Ammonioalkyl Derivatives of Crown-Ether Styryl Dyes.
J. Org. Chem.
PUBLISHED: 11-12-2014
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The synthesis of new styryl dyes derived from 4-pyridine and 4-quinoline and having an ammonioalkyl N-substituent and a benzocrown-ether moiety of different size and with different sets of heteroatoms was developed. Spontaneous "head-to-tail" dimerization of these dyes via the formation of numerous hydrogen bonds between the terminal NH3+ groups and crown-ether moieties was detected in MeCN solutions. The stability constants of the dimeric complexes having pseudocyclic structure were studied by 1H NMR titration. The most stable complexes (logKd up to 8.2) were found in the case of dyes with the (aza)-18-crown-6-ether moiety, which is most complementary for binding a primary ammonium group. Stacking interaction of the conjugated systems in the dimeric complexes contributes to their stability to a much lesser extent. In dimeric complexes, the ethylene bonds of the dyes are pre-organized for stereospecific [2+2] photocycloaddition (PCA) induced by visible light. The PCA yields only rctt isomers of bis-crown-containing cyclobutane derivatives. The dyes were studied by X-ray diffraction; it was found that the dimeric arrangement is also retained in the crystalline state. The possibility of topochemical PCA of the dyes in single crystals without their destruction was demonstrated. The possibility of retro-PCA of the obtained cyclobutane derivatives to give the starting dyes was shown. The elucidated regularities of PCA can be used to fabricate optical data recording systems based on ammonioalkyl derivatives of crown-ether styryl dyes.
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Surgical lung biopsy to diagnose Behcet's vasculitis with adult respiratory distress syndrome.
Lung India
PUBLISHED: 11-08-2014
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A 34-year-old female presented with fever and abdominal pain. Past medical history includes Crohn's and Behcet's disease. Examination revealed multiple skin ulcerations, oral aphthae, and bilateral coarse rales. She developed respiratory distress with diffuse bilateral alveolar infiltrates on chest radiograph requiring intubation. PaO2/FiO2 ratio was 132. The chest computed tomography revealed extensive nodular and patchy ground-glass opacities. Bronchoalveolar lavage demonstrated a predominance of neutrophils. Methylprednisolone 60 mg every 6 h and broad-spectrum antimicrobials were initiated. No infectious etiologies were identified. Surgical lung biopsy demonstrated diffuse alveolar damage (DAD) mixed with lymphocytic and necrotizing vasculitis with multiple small infarcts and thrombi consistent with Behcet's vasculitis. As she improved, steroids were tapered and discharged home on oral cyclophosphamide. Pulmonary involvement in Behcet's is unusual and commonly manifests as pulmonary artery aneurysms, thrombosis, infarction, and hemorrhage. Lung biopsy findings demonstrating DAD are consistent with the clinical diagnosis of adult respiratory distress syndrome. The additional findings of necrotizing vasculitis and infarcts may have led to DAD.
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Prevalence of and factors influencing impaired glucose tolerance among hepatitis B carriers: a nationwide cross-sectional study in the republic of Korea.
Medicine (Baltimore)
PUBLISHED: 11-04-2014
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Diabetes is associated with a poor prognosis for liver disease, particularly in chronic hepatitis carriers. We investigated the prevalence of factors associated with impaired glucose tolerance (IGT) including diabetes and impaired fasting glucose (IFG) among individuals with hepatitis B virus (HBV) infection.We used data from the Korean National Health and Nutrition Examination Survey, a nationwide cross-sectional survey conducted between 2007 and 2011. Sociodemographic information was collected using a structured questionnaire. The HBV surface antigen, liver enzymes, and lipid profile were measured from blood samples.IFG was found in 18.1% of HBV carriers and 19.3% of noncarriers (P?=?0.25). Diabetes was observed in 10.0% of HBV carriers and 12.2% of noncarriers (P?=?0.08). Lower level of educational attainment was associated with a higher prevalence of IGT: high school education (odds ratio [OR]?=?1.94 [95% confidence interval (CI) 1.14-3.29] and less than a high school education (OR?=?3.20 [95% CI, 1.66-6.15] vs more than or equal to a college education. Elevated alanine transaminase and triglyceride by 10 were associated with increased risk of IGT (OR?=?1.10 [95% CI, 1.01-1.20] and OR?=?1.04 [95% CI, 1.01-1.07], respectively). Being a man and older in age were associated with a higher prevalence of IGT, and individuals with a low body mass index were at lower risk for IGT.Given the synergistic effect of diabetes and HBV infection on liver disease prognosis, we recommend targeted IGT screening and follow-up for HBV carriers. These efforts should include health policies and intervention programs aimed at reducing educational disparities and encouraging early control of elevated liver enzymes or lipid profiles.
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Synchrotron-Based Imaging of Chromium and ?-H2AX Immunostaining in the Duodenum Following Repeated Exposure to Cr(VI) in Drinking Water.
Toxicol. Sci.
PUBLISHED: 10-28-2014
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Current drinking water standards for chromium are for the combined total of both hexavalent and trivalent chromium (Cr(VI) and Cr(III)). However, recent studies have shown that Cr(III) is not carcinogenic to rodents, whereas mice chronically exposed to high levels of Cr(VI) developed duodenal tumors. These findings may suggest the need for environmental standards specific for Cr(VI). Whether the intestinal tumors arose through a mutagenic or non-mutagenic mode of action (MOA) greatly impacts how drinking water standards for Cr(VI) are derived. Herein, X-ray fluorescence (spectro)microscopy (µ-XRF) was used to image the Cr content in the villus and crypt regions of duodena from B6C3F1 mice exposed to 180?mg/l Cr(VI) in drinking water for 13 weeks. DNA damage was also assessed by ?-H2AX immunostaining. Exposure to Cr(VI) induced villus blunting and crypt hyperplasia in the duodenum-the latter evidenced by lengthening of the crypt compartment by ?2-fold with a concomitant 1.5-fold increase in the number of crypt enterocytes. ?-H2AX immunostaining was elevated in villi, but not in the crypt compartment. µ-XRF maps revealed mean Cr levels >30 times higher in duodenal villi than crypt regions; mean Cr levels in crypt regions were only slightly above background signal. Despite the presence of Cr and elevated ?-H2AX immunoreactivity in villi, no aberrant foci indicative of transformation were evident. These findings do not support a MOA for intestinal carcinogenesis involving direct Cr-DNA interaction in intestinal stem cells, but rather support a non-mutagenic MOA involving chronic wounding of intestinal villi and crypt cell hyperplasia.
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Targeting c-MET/HGF Signaling Pathway in Upper Gastrointestinal Cancers: Rationale and Progress.
Curr Drug Targets
PUBLISHED: 10-20-2014
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Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALK-rearrangement. However several important questions remain to be unanswered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including upper-gastrointestinal-cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, as well as the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in treatment of upper gastrointestinal-cancers.
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Histological features of chronic hepatitis C in haemodialysis patients.
Liver Int.
PUBLISHED: 09-20-2014
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HCV infection in haemodialysis (HD) patients is still a matter of investigation. The aim of this study was to determine the histology of chronic hepatitis C (CHC) in HCV-infected HD patients within the context of a comparative analysis including non-uraemic patients with CHC. The relative importance of virological, demographic and clinical parameters on disease manifestation was examined.
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Leptin induced GRP78 expression through the PI3K-mTOR pathway in neuronal cells.
Sci Rep
PUBLISHED: 09-09-2014
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Leptin is a circulating hormone that plays a critical role in regulating energy expenditure and food intake. Evidence to suggest the involvement of endoplasmic reticulum (ER) stress in the development of obesity is increasing. To adapt against ER stress, cells trigger the unfolded protein response (UPR). The 78?kDa glucose-regulated protein (GRP78) is an ER chaperone that protects cells against ER stress by inducing protein folding. In the present study, we hypothesized that leptin may activate UPR and protect against ER stress associated with obesity. SH-SY5Y, a human neuroblastoma cell line stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb), was treated with leptin. We demonstrated that leptin induced GRP78 expression. We then validated the mechanism responsible for the leptin-induced expression of GRP78. Interestingly, leptin-induced GRP78 expression was not dependent on IRE1-XBP1 pathway. On the other hand, the PI3K inhibitor, LY294002, and mTOR inhibitor, rapamycin, inhibited the leptin-induced expression of GRP78. These results suggested that the leptin-induced expression of GRP78 may be dependent on the PI3K-mTOR pathway. Leptin specifically induced GRP78 because the induction of the ER-apoptotic marker, CHOP, was not detected in leptin-treated cells. Therefore, leptin may upregulate the expression of GRP78, thereby protecting against ER stress associated with obesity.
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Disclosure of Their Status to Youth with Human Immunodeficiency Virus Infection in the Dominican Republic: A Mixed-Methods Study.
AIDS Behav
PUBLISHED: 09-04-2014
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A mixed-methods study was conducted to determine the proportion of HIV-infected children who knew their status, identify characteristics associated with children's knowledge of their status, and describe caregivers' and adolescents' experiences relevant to disclosure in the Dominican Republic (DR). Of 327 patients aged 6-18 years treated in the principal DR pediatric HIV facilities, 74 (22.6 %) knew their status. Patients aged 13 years or older and/or who had participated in non-clinical activities for HIV-infected children were more likely to know their status. Caregivers who had disclosed cited healthcare providers' advice, children's desire to know and concerns that children might initiate sexual activity before knowing or discover their status by accidental or malicious disclosure. Non-disclosing caregivers worried that children would be traumatized by disclosure and/or stigmatized if they revealed it to others. Adolescents supported disclosure by 10-12 years of age, considered withholding of children's HIV diagnosis ill-advised, and recommended a disclosure process focused initially on promoting non-stigmatizing attitudes about HIV.
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Assessment of the mode of action for hexavalent chromium-induced lung cancer following inhalation exposures.
Toxicology
PUBLISHED: 08-28-2014
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Inhalation of hexavalent chromium [Cr(VI)] is associated with increased lung cancer risk among workers in several industries, most notably chromate production workers exposed to high concentrations of Cr(VI) (?100?g/m(3)), for which clear exposure-response relationships and respiratory irritation and tissue damage have been reported. Data from this industry are used to assess lung cancer risk associated with environmental and current occupational exposures, occurring at concentrations that are significantly lower. There is considerable uncertainty in the low dose extrapolation of historical occupational epidemiology data to assess risk at current exposures because no published or well recognized mode of action (MOA) for Cr(VI)-induced lung tumors exists. We conducted a MOA analysis for Cr(VI)-induced lung cancer evaluating toxicokinetic and toxicological data in humans and rodents and mechanistic data to assess plausibility, dose-response, and temporal concordance for potential MOAs. Toxicokinetic data support that extracellular reduction of Cr(VI), which limits intracellular absorption of Cr(VI) and Cr(VI)-induced toxicity, can be overwhelmed at high exposure levels. In vivo genotoxicity and mutagenicity data are mostly negative and do not support a mutagenic MOA. Further, both chronic bioassays and the epidemiologic literature support that lung cancer occurs at exposures that cause tissue damage. Based on this MOA analysis, the overall weight of evidence supports a MOA involving deposition and accumulation of particulate chromium in the bifurcations of the lung resulting in exceedance of clearance mechanisms and cellular absorption of Cr(VI). Once inside the cell, reduction of Cr(VI) results in oxidative stress and the formation of Cr ligands. Subsequent protein and DNA damage lead to tissue irritation, inflammation, and cytotoxicity. These effects, concomitant with increased cell proliferation, result in changes to DNA sequences and/or methylation status that can lead to tumorigenesis. This MOA supports the use of non-linear approaches when extrapolating lung cancer risk occurring at high concentration occupational exposures to environmentally-relevant exposures.
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Amino Acid derivatives of ligustrazine-oleanolic Acid as new cytotoxic agents.
Molecules
PUBLISHED: 08-25-2014
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A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3?-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3?-L-lysine ester-6g not only displayed good cytotoxicity (IC50 < 3.5 ?M) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50 = 4.884 ?M) had lower nephrotoxicity than both 6g (IC50 = 2.310 ?M) and cisplatin (CDDP, IC50 = 3.691 ?M) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.
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Noise in hospital rooms and sleep disturbance in hospitalized medical patients.
Environ Health Toxicol
PUBLISHED: 08-18-2014
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Hospitalized patients are vulnerable to sleep disturbances because of environmental stresses including noise. While most previous studies on hospital noise and sleep have been performed for medical machines in intensive care units, there is a limited data for patients hospitalized in medical wardrooms. The purpose of present study was to measure noise level of medical wardrooms, identify patient-perceived sources of noise, and to examine the association between noise levels and sleep disturbances in hospitalized patients.
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Prehabilitation for men undergoing radical prostatectomy: a multi-centre, pilot randomized controlled trial.
BMC Surg
PUBLISHED: 08-02-2014
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An emerging field of research describes the role of preoperative health behaviours, known as prehabilitation. The preoperative period may be a more physically and emotionally salient time to introduce and foster chronic adherence to health behaviours, such as exercise, in patients compared to post-treatment during recovery. Moreover, physical and psychosocial improvements during the preoperative period may translate into an enhanced recovery trajectory with reduced operative complications and postoperative adverse effects. No studies have assessed prehabilitation for men with prostate cancer undergoing radical prostatectomy.
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Rethinking obesity counseling: having the French fry discussion.
J Obes
PUBLISHED: 07-17-2014
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Childhood obesity is a complex problem that warrants early intervention. General recommendations for obesity prevention and nutrition counseling exist. However, these are notably imprecise with regard to early and targeted interventions to prevent and treat obesity in pediatric populations. This study examines family medicine primary care providers' (PCPs) perceived barriers for preventing and treating pediatric obesity and their related practice behavior during well-child visits. Methods. A written survey addressing perceived barriers and current practices addressing obesity at well-child visits were administered to PCPs at eleven family medicine clinics in the Duke University Health System. Results. The most common perceived barriers identified by PCPs to prevention or treatment of obesity in children were families not getting enough exercise (93%) and families too often having fast food meals (86%). Most PCPs do not discuss fast foods at or prior to the twelve-month well-child visit. The two-year visit is the first well-child visit at which a majority of PCPs (68%) discuss fast food. Conclusion. No clear consensus exists as to when PCPs should discuss fast food in early well-child checks. Previous research has shown a profound shift in children's dietary habits toward fast foods, such as French fries, that occurs between the one- and two-year well-child checks. Consideration should be given to having a "French Fry Discussion" at every twelve-month well-child care visit.
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Cost-effectiveness of liver cancer screening in adults at high risk for liver cancer in the republic of Korea.
Cancer Res Treat
PUBLISHED: 07-15-2014
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This study was conducted in order to determine the most cost-effective strategy, in terms of interval and age range, forliver cancer screening in the high-risk population of Korea.
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Evidence that cognitive deficit in children is associated not only with iron deficiency, but also with blood lead concentration: A preliminary study.
J Trace Elem Med Biol
PUBLISHED: 07-02-2014
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To investigate whether blood lead concentrations are elevated in iron-deficient children, and to examine the association between iron deficiency and/or elevated blood lead concentration and cognitive deficits in children.
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Galectin-4 expression is associated with reduced lymph node metastasis and modulation of Wnt/?-catenin signalling in pancreatic adenocarcinoma.
Oncotarget
PUBLISHED: 07-01-2014
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Galectin-4 (Gal-4) has been recently identified as a pivotal factor in the migratory capabilities of a set of defined pancreatic ductal adenocarcinoma (PDAC) cell lines using zebrafish as a model system. Here we evaluated the expression of Gal-4 in PDAC tissues selected according to their lymph node metastatic status (N0 vs. N1), and investigated the therapeutic potential of targeting the cross-link with the Wnt signaling pathway in primary PDAC cells. Analysis of Gal-4 expression in PDACs showed high expression of Gal-4 in 80% of patients without lymph node metastasis, whereas 70% of patients with lymph node metastases had low Gal-4 expression. Accordingly, in primary PDAC cells high Gal-4 expression was negatively associated with migratory and invasive ability in vitro and in vivo. Knockdown of Gal-4 in primary PDAC cells with high Gal-4 expression resulted in significant increase of invasion (40%) and migration (50%, P<0.05), whereas enforced expression of Gal-4 in primary cells with low Gal-4 expression reduced the migratory and invasive behavior compared to the control cells. Gal-4 markedly reduces ?-catenin levels in the cell, counteracting the function of Wnt signaling, as was assessed by down-regulation of survivin and cyclin D1. Furthermore, Gal-4 sensitizes PDAC cells to the Wnt inhibitor ICG-001, which interferes with the interaction between CREB binding protein (CBP) and ?-catenin. Collectively, our data suggest that Gal-4 lowers the levels of cytoplasmic ?-catenin, which may lead to lowered availability of nuclear ?-catenin, and consequently diminished levels of nuclear CBP-?-catenin complex and reduced activation of the Wnt target genes. Our findings provide novel insights into the role of Gal-4 in PDAC migration and invasion, and support the analysis of Gal-4 for rational targeting of Wnt/?-catenin signaling in the treatment of PDAC.
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miR-211 modulates gemcitabine activity through downregulation of ribonucleotide reductase and inhibits the invasive behavior of pancreatic cancer cells.
Nucleosides Nucleotides Nucleic Acids
PUBLISHED: 06-19-2014
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Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from gemcitabine-based chemotherapy, thus the identification of novel prognostic factors is essential. In a high-throughput, microRNA (miRNA) array, miR-211 emerged as the best discriminating miRNA, with high expression associated with long survival. Here, we further explored the biological role of miRNA-211 in gemcitabine activity in the human PDAC cells (SUIT-2) subclones SUIT2-007 and SUIT2-028. Our results showed that miR-211 was expressed differentially in PDAC cells characterized by differential metastatic capability. In particular, S2-028 with lower metastatic ability had a higher expression of miR-211, compared to the S2-007 with higher metastatic capacity. Enforced expression of miR-211 via pre-miR-211 significantly reduced cell migration and invasion (e.g., 40% reduction of invasion of SUIT2 cells, compared to control; p<.05). Moreover, we demonstrated that induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2). In conclusion, miR-211 functional analyses suggested the role of RRM2 as a target of miR-211 in the modulation of gemcitabine sensitivity. Moreover, inhibition of cell migration and invasion might explain the less aggressive behavior of pancreatic cancer cells with higher expression levels of miR-211.
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The radiologic technologists' health study in South Korea: study design and baseline results.
Int Arch Occup Environ Health
PUBLISHED: 06-13-2014
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To describe the study design, methods, and baseline results of a prospective cohort of radiologic technologists which we have initiated in South Korea.
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An alternative surgical technique for repair of anomalous origin of the left coronary artery from the pulmonary artery.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 06-05-2014
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For the surgical management of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), there have been various techniques that reduce the tension and kinking of the coronary artery during reimplantation to the aorta. The aim of this study is to describe the results of our modified technique of coronary reimplantation for the treatment of ALCAPA.
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Magnetic tweezers for the measurement of twist and torque.
J Vis Exp
PUBLISHED: 06-05-2014
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Single-molecule techniques make it possible to investigate the behavior of individual biological molecules in solution in real time. These techniques include so-called force spectroscopy approaches such as atomic force microscopy, optical tweezers, flow stretching, and magnetic tweezers. Amongst these approaches, magnetic tweezers have distinguished themselves by their ability to apply torque while maintaining a constant stretching force. Here, it is illustrated how such a "conventional" magnetic tweezers experimental configuration can, through a straightforward modification of its field configuration to minimize the magnitude of the transverse field, be adapted to measure the degree of twist in a biological molecule. The resulting configuration is termed the freely-orbiting magnetic tweezers. Additionally, it is shown how further modification of the field configuration can yield a transverse field with a magnitude intermediate between that of the "conventional" magnetic tweezers and the freely-orbiting magnetic tweezers, which makes it possible to directly measure the torque stored in a biological molecule. This configuration is termed the magnetic torque tweezers. The accompanying video explains in detail how the conversion of conventional magnetic tweezers into freely-orbiting magnetic tweezers and magnetic torque tweezers can be accomplished, and demonstrates the use of these techniques. These adaptations maintain all the strengths of conventional magnetic tweezers while greatly expanding the versatility of this powerful instrument.
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Assessment of vitrification outcome by xenotransplantation of ovarian cortex pieces in ?-irradiated mice: morphological and molecular analyses of apoptosis.
J. Assist. Reprod. Genet.
PUBLISHED: 05-19-2014
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The aim of this study was the investigation of caspase-3/7 activity and apoptosis related gene expression after vitrification and xenotransplantation of human ovarian fragments.
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Correlation of breast cancer incidence with the number of motor vehicles and consumption of gasoline in Korea.
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-13-2014
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While several reproductive and lifestyle-related factors are already well-known as established risk factors for breast cancer, environmental factors have attracted attention only recently. The objective of the current study was to assess the association between the breast cancer incidences in females, the mortality rate and the number of motor vehicles on the one side and the consumption of gasoline which could work as a major source of air pollution at the other side. The breast cancer incidences and the mortality trends were compared with various indices of westernization like dietary patterns or industrialization with 10 years lag of time. Geographical variations with 10, 15 and 20 years lag of time were assessed between the breast cancer incidence in 2010 and the number of motor vehicles as well as the consumption of gasoline. The upward trend of motor vehicle numbers proved to be comparable to those of breast cancer incidence and mortality. However, the consumption of gasoline started to decrease since the mid-1990s. The geographic distribution of motor vehicle numbers and gasoline consumption in 1990 is in a positive correlation with the breast cancer incidence rates in 2010 and the 20-year lag time (R2 0.379 with the number of motor vehicles and 0.345 with consumption of gasoline). In a linear relationship between the breast cancer incidences in 2010 and the log transformed number of motor vehicles, the log transformed consumption of gasoline in 2000 also showed a positive relationship (R2 0.367 with the number of motor vehicles and 0.329 with consumption of gasoline). The results of the current study indicate that there may be a positive relation between the number of vehicles, gasoline consumption and the incidence of breast cancer from the aspects of long-term trends and geographical variation.
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A polymorphism in the promoter is associated with EZH2 expression but not with outcome in advanced pancreatic cancer patients.
Pharmacogenomics
PUBLISHED: 05-07-2014
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EZH2 expression is a prognostic marker in radically resected pancreatic ductal adenocarcinoma (PDAC) patients. Here we investigated its role in locally advanced/metastatic patients, as well as candidate polymorphisms.
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Considering the prominent complaint as a guide in medical therapy for overactive bladder syndrome in women over 45 years.
J. Obstet. Gynaecol. Res.
PUBLISHED: 04-23-2014
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The aim of this study was to evaluate the response of women over 45 years with overactive bladder and detrusor overactivity to a 12-week course of oxybutynin or tolterodine treatment.
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Maternal blood manganese level and birth weight: a MOCEH birth cohort study.
Environ Health
PUBLISHED: 04-16-2014
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Manganese (Mn) is an essential trace element for humans and animals, but excess intake of Mn can lead to adverse developmental outcome. Few studies have investigated the effects of deficiency or excess of Mn on the human foetus. In this study, we assessed the quantitative relationship between maternal blood Mn and birth weight of a newborn.
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Surgery for partial anomalous pulmonary venous connections: modification of the warden procedure with a right atrial appendage flap.
Korean J Thorac Cardiovasc Surg
PUBLISHED: 04-10-2014
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Surgical repair of a partial anomalous pulmonary venous connection (PAPVC) to the superior vena cava (SVC) may be complicated by sinus node dysfunction or SVC obstruction. We modified the Warden procedure by using a right atrial auricular flap to decrease the occurrence of these complications.
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The associations between ADHD and asthma in Korean children.
BMC Psychiatry
PUBLISHED: 03-06-2014
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The aim of this study was to investigate the associations between attention deficit hyperactivity disorder (ADHD), the most common neuropsychiatric disorder in school children, and childhood allergic disease by evaluating their respective prevalence.
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Barriers to cancer screening among medical aid program recipients in the Republic of Korea: a qualitative study.
Asian Pac. J. Cancer Prev.
PUBLISHED: 02-27-2014
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Few studies have examined reasons why those with low socioeconomic status do not adequately receive cancer screening. We therefore conducted a qualitative study to assess the barriers to cancer screening in people with low socioeconomic status, and to examine the reasons why Medical Aid Program (MAP) recipients do not participate in the National Cancer Screening Program (NCSP). A focus group methodology was used. Participants included MAP recipients (men aged 45-79 years, women aged 35-79 years) who had been invited to cancer screening at least twice based on the NCSP protocol, but had not been screened for any cancer from 2009-2012. We recruited participants living in the cities of Goyang and Paju. A total of 23 MAP recipients participated in four focus group discussions, including 12 men and 11 women. In this qualitative study, we identified six barriers to screening: lack of trust in the NCSP and cancer screening units; fear of being diagnosed with cancer; discomfort or pain from the screening procedure; lack of time, lack of knowledge about cancer screening or lack of awareness of the existence of the NCSP; physical disability or underlying disease; and logistic barriers. Interventions such as individualized counseling, letters and reminders, or other individually-targeted strategies, especially for those with lower socioeconomic status are required to increase participation and reduce disparities in cancer screening.
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Homelessness and Other Risk Factors for HIV Infection in the Current Outbreak Among Injection Drug Users in Athens, Greece.
Am J Public Health
PUBLISHED: 02-15-2014
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Objectives. We examined HIV prevalence and risk factors among injection drug users (IDUs) in Athens, Greece, during an HIV outbreak. Methods. We used respondent-driven sampling (RDS) to recruit 1404 IDUs to the Aristotle intervention in August to October 2012. We interviewed participants and tested for HIV. We performed bivariate and multivariate analyses. Results. Estimated HIV prevalence was 19.8% (RDS-weighted prevalence?=?14.8%). Odds of infection were 2.3 times as high in homeless as in housed IDUs and 2.1 times as high among IDUs who injected at least once per day as among less frequent injectors (both, P?
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Notes from the field: elemental mercury spill in school bus and residence - North Carolina, 2013.
MMWR Morb. Mortal. Wkly. Rep.
PUBLISHED: 02-14-2014
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On September 16, 2013, the North Carolina Division of Public Health was notified of an elemental (metallic and liquid) mercury spill on a school bus. An elementary student boarded the bus with approximately 1 pound (454 g) of elemental mercury contained in a film canister, which the student had taken from an adult relative who had found it in a neighbor's shed. The canister was handled by several students before the contents spilled on the bus floor. Ten passengers aboard the bus were exposed, including eight students and two staff members. Although elemental mercury is not readily absorbed from skin contact or ingestion, it does vaporize at room temperatures and inhalation of the vapor can be harmful. The bus driver promptly notified school officials. Firefighters and a local hazardous materials team directed decontamination procedures (i.e., changing clothes and washing hands and shoes) for the 10 exposed passengers. The bus was immediately taken out of service and sent for disposal because of its age and the cost of decontamination.
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Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems.
Antimicrob. Agents Chemother.
PUBLISHED: 02-10-2014
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Carbapenemase-producing Klebsiella pneumoniae strains (CP-Kps) are currently among the most important nosocomial pathogens. An observational study was conducted during 2009 to 2010 in two hospitals located in a high-prevalence area (Athens, Greece). The aims were (i) to evaluate the clinical outcome of patients with CP-Kp bloodstream infections (BSIs), (ii) to identify predictors of mortality, and (iii) to evaluate the various antibiotic schemes employed. A total of 205 patients with CP-Kp BSIs were identified: 163 (79.5%) were infected with KPC or KPC and VIM, and 42 were infected with VIM producers. For definitive treatment, 103 patients received combination therapy (two or more active drugs), 72 received monotherapy (one active drug), and 12 received therapy with no active drug. The remaining 18 patients died within 48 h after the onset of bacteremia. The all-cause 28-day mortality was 40%. A significantly higher mortality rate was observed in patients treated with monotherapy than in those treated with combination therapy (44.4% versus 27.2%; P=0.018). The lowest mortality rate (19.3%) was observed in patients treated with carbapenem-containing combinations. In the Cox proportion hazards model, ultimately fatal disease (hazards ratio [HR], 3.25; 95% confidence interval [CI], 1.51 to 7.03; P=0.003), the presence of rapidly fatal underlying diseases (HR, 4.20; 95% CI, 2.19 to 8.08; P<0.001), and septic shock (HR, 2.15; 95% CI, 1.16 to 3.96; P=0.015) were independent predictors of death. Combination therapy was strongly associated with survival (HR of death for monotherapy versus combination, 2.08; 95% CI, 1.23 to 3.51; P=0.006), mostly due to the effectiveness of the carbapenem-containing regimens.
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Population health initiatives for primary care at Duke University School of Medicine.
N C Med J
PUBLISHED: 02-04-2014
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To help shape the future of health care in North Carolina, Duke University School of Medicine has implemented several new initiatives aimed at providing primary care providers with the knowledge, skills, and attitudes required to improve population health and health care.
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Characterization of Topographically Specific Sleep Spindles in Mice.
Sleep
PUBLISHED: 01-31-2014
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Sleep spindles in humans have been classified as slow anterior and fast posterior spindles; recent findings indicate that their profiles differ according to pharmacology, pathology, and function. However, little is known about the generation mechanisms within the thalamocortical system for different types of spindles. In this study, we aim to investigate the electrophysiological behaviors of the topographically distinctive spindles within the thalamocortical system by applying high-density EEG and simultaneous thalamic LFP recordings in mice.
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Evaluation of an HIV Adherence Counseling Program in La Romana, Dominican Republic.
J Int Assoc Provid AIDS Care
PUBLISHED: 01-30-2014
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Research has demonstrated that adherence to antiretroviral therapy (ART) results in lower rates of morbidity and mortality associated with HIV infection, yet adherence remains a challenge in resource-limited settings like the Dominican Republic. Clínica de Familia La Romana addressed this problem with an education-based adherence program for adult patients new to ART, and this retrospective cohort study aimed to evaluate the impact of this intervention. Appointment adherence and biological markers were assessed in cases and controls through 12 months. A total of 101 participants were included, with 61 controls and 40 cases. The baseline CD4 count was 162 and 157 cells/mm(3) in controls and cases, respectively. Cases showed a 15-fold increase in CD4 count compared with a 2.5-fold increase in controls. Cases were more likely to adhere to appointments with adherence rates of 86% versus 76% in controls. There was no difference between the rates of treatment abandonment, transfer of care, or death.
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An alcohol message beneath the surface of ER: how implicit memory influences viewers' health attitudes and intentions using entertainment-education.
J Health Commun
PUBLISHED: 01-30-2014
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While previous research on entertainment-education has assessed its effectiveness, primarily at the conscious level (e.g., free recall and self-reported change in knowledge), few studies have explored its effect on viewers' implicit knowledge. To fill this gap, this study examined the mechanism through which viewers form implicit memory of short health messages inserted in a primetime TV show and its preconscious effects on viewers' health attitudes and intentions. An experiment was conducted using a 3-group (health message: present vs. absent vs. control), posttest-only design with additional planned analyses of differences by subject variables (past experience and involvement). Overall, findings supported the hypothesized effects of implicit memory of a brief antialcohol message embedded in an ER episode on college students' attitudes and intentions against binge drinking. Results showed that participants who were exposed to the health message reported less positive attitudes toward binge drinking and lower intentions to binge drink, compared with those who were not exposed; the causal relations among viewers' implicit memory, attitudes, and intentions were also validated. Results also showed that individuals' past experience and involvement moderated the effects of the health message on attitudes and intentions. Theoretical explanations and practical implications are discussed.
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Prenatal exposure to PM?? and NO? and children's neurodevelopment from birth to 24 months of age: mothers and Children's Environmental Health (MOCEH) study.
Sci. Total Environ.
PUBLISHED: 01-28-2014
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Previous studies have suggested adverse effects of maternal exposure to air pollution on neurodevelopment in early childhood.
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Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.
J Appl Toxicol
PUBLISHED: 01-07-2014
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Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant. Copyright © 2014 John Wiley & Sons, Ltd.
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ent-kaurane and ent-pimarane diterpenes from Siegesbeckia pubescens inhibit lipopolysaccharide-induced nitric oxide production in BV2 microglia.
Biol. Pharm. Bull.
PUBLISHED: 01-07-2014
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The extract of Siegesbeckia pubescens herb and its chemical constituents were tested for the ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglia. The methanol extract and the 90% MeOH fraction of S. pubescens effectively attenuated lipopolysaccharide-induced nitric oxide production. Several steps of chromatography yielded eight ent-kaurane diterpenes (1-8) and one ent-pimarane diterpene (9) from the 90% MeOH fraction. Among these compounds, compounds 2-9 showed significant inhibitory effect on lipopolysaccharide-induced nitric oxide production in BV2 microglia. Compounds 3 and 9 concentration-dependently decreased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), supported by quantitative real time polymerase chain reaction (PCR) and Western blot analysis. These results suggest that ent-kaurane and ent-pimarane diterpenes isolated from S. pubescens are expected to be potential candidates against neuroinflammation-related disease.
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High concentrations of hexavalent chromium in drinking water alter iron homeostasis in F344 rats and B6C3F1 mice.
Food Chem. Toxicol.
PUBLISHED: 01-03-2014
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Hexavalent chromium [Cr(VI)] induces hematological signs of microcytic anemia in rodents. Considering that Cr(VI) can oxidize ferrous (Fe(2+)) to ferric (Fe(3+)) iron, and that only the former is transported across the duodenum, we hypothesize that, at high concentrations, Cr(VI) oxidizes Fe(2+) in the lumen of the small intestine and perturbs iron absorption. Herein we report that 90-day exposure to Cr(VI) in drinking water resulted in dose-dependent decreases in Fe levels in the duodenum, liver, serum, and bone marrow. Toxicogenomic analyses from the duodenum indicate responses consistent with Fe deficiency, including significant induction of divalent metal transporter 1 (DMT1, Slc11a2) and transferrin receptor 1 (TFR1, Tfr1). In addition, at ?20mg Cr(VI)/L in drinking water, Cr RBC:plasma ratios in rats were increased and exceeded unity, indicating saturation of reductive capacity and intracellular absorption of Cr(VI) into red blood cells (RBCs). These effects occurred in both species but were generally more severe in rats. These data suggest that high concentrations of Cr(VI) in drinking limit Fe absorption and alter iron homeostasis. Furthermore, some effects observed at high doses in recent Cr(VI) chronic and subchronic bioassays may be explained, at least in part, by iron deficiency and disruption of homeostasis.
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Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks.
J Int AIDS Soc
PUBLISHED: 01-01-2014
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The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains.
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Factors associated with alcohol consumption in hepatitis B carriers: a nationwide study in the republic of Korea.
PLoS ONE
PUBLISHED: 01-01-2014
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This study was conducted to investigate the prevalence of alcohol consumption and identify the sociodemographic factors associated with alcohol consumption among individuals with hepatitis B virus(HBV) infection. We used data from the Korean National Health and Nutrition Examination Surveys, a nationwide survey conducted between 2007 and 2011. "Monthly alcohol consumption" was defined as having consumed alcohol at least once per month during the past year, and "high-risk alcohol consumption" was defined as having consumed alcohol twice or more per week and, for males, having consumed at least 60 g of alcohol on one occasion or, for females, having consumed at least 40 g of alcohol on more than one occasion. The prevalence of monthly alcohol consumption was 53.2%, and that of high-risk alcohol consumption was 11.8% among HBV carriers. Less education was associated with both monthly and high-risk alcohol consumption(OR?=?1.75 [95% CI?=?1.02-3.02] for monthly alcohol consumption among those with less than a high school education; OR?=?2.48 [95% CI?=?1.19-5.17] for high-risk alcohol consumption among those with less than a high school education and OR?=?2.02 [95% CI?=?1.12-3.64] among those with a high school education). Additionally, smoking and being male increased the risk of alcohol consumption, and older age and having a normal body mass index decreased the risk. HBV carriers who were less educated, overweight, and smokers were more likely to consume alcohol or meet criteria for high-risk drinking. Health policies and intervention programs aimed at promoting a generally healthy lifestyle in HBV carriers should consider educational inequalities and alcohol consumption.
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The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.
Front Public Health
PUBLISHED: 01-01-2014
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The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24?years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.
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AKT1 and SELP polymorphisms predict the risk of developing cachexia in pancreatic cancer patients.
PLoS ONE
PUBLISHED: 01-01-2014
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Pancreatic ductal adenocarcinoma (PDAC) patients have the highest risk of developing cachexia, which is a direct cause of reduced quality of life and shorter survival. Novel biomarkers to identify patients at risk of cachexia are needed and might have a substantial impact on clinical management. Here we investigated the prognostic value and association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia in PDAC. Genotyping was performed in DNA from blood samples of a test and validation cohorts of 151 and 152 chemo-naive locally-advanced/metastatic PDAC patients, respectively. The association of SELP-rs6136, IL6-rs1800796 and AKT1-rs1130233 polymorphisms with cachexia as well as the correlation between cachexia and the candidate polymorphisms and overall survival were analyzed. Akt expression and phosphorylation in muscle biopsies were evaluated by specific ELISA assays. SELP-rs6136-AA and AKT1-rs1130233-AA/GA genotypes were associated with increased risk of developing cachexia in both cohorts (SELP: p = 0.011 and p = 0.045; AKT1: p = 0.004 and p = 0.019 for the first and second cohorts, respectively), while patients carrying AKT1-rs1130233-GG survived significantly longer (p = 0.002 and p = 0.004 for the first and second cohorts, respectively). In the multivariate analysis AKT1-rs1130233-AA/GA genotypes were significant predictors for shorter survival, with an increased risk of death of 1.7 (p = 0.002) and 1.6 (p = 0.004), in the first and second cohorts, respectively. This might be explained by the reduced phosphorylation of Akt1 in muscle biopsies from patients harboring AKT1-rs1130233-AA/GA (p = 0.003), favoring apoptosis induction. In conclusion, SELP and AKT1 polymorphisms may play a role in the risk of cachexia and death in PDAC patients, and should be further evaluated in larger prospective studies.
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Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma.
J Affect Disord
PUBLISHED: 01-01-2014
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There is currently insufficient evidence to confirm the effect of ambient air pollution on mental disorders, especially among susceptible populations. This study investigated the short-term effect of ambient air pollution on the risk of depressive episode and the effect modification across disease subpopulations.
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Relationship between Social Network and Stage of Adoption of Gastric Cancer Screening among the Korean Population.
Asian Pac. J. Cancer Prev.
PUBLISHED: 12-03-2013
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Few studies have examined the relationship between social support and stages of adoption of cancer screening. Here we investigated associations between both structural and functional aspects of social support and stages of adoption of gastric cancer screening in the general population of Korea. The study population was derived from the 2011 Korean National Cancer Screening Survey (KNCSS), an annual cross-sectional survey that uses nationally representative random sampling to investigate cancer screening rates. Data were analyzed from 3,477 randomly selected respondents aged 40-74 years. Respondents were classified according to their stage of adoption of gastric cancer screening: precontemplation (13.2%), contemplation (18.0%), action/maintenance (56.1%), relapse risk (8.5%), and relapse stage (4.1%). Respondents with larger social networks were more likely to be in the contemplation/action/maintenance, or the relapse risk/relapse stages versus the precontemplation stage (OR=1.91, 95%CI: 1.52-2.91; p for tend=0.025). Emotional and instrumental supports were not associated with any stage of adoption of gastric cancer screening. However, respondents who reported receiving sufficient informational support were more likely to be in the relapse risk/relapse stages versus the precontemplation, or the contemplation/action/maintenance stage (p for trend=0.016). Interventions involving interactions between social network members could play an important role in increasing participation in gastric cancer screening.
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Neuroprotective Benzyl Benzoate Glycosides from Disporum viridescens Roots in HT22 Hippocampal Neuronal Cells.
J. Nat. Prod.
PUBLISHED: 11-18-2013
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Bioassay-guided fractionation of the EtOAc extract from Disporum viridescens roots led to the isolation of five new benzyl benzoate glycosides, BBGs (1-5). The neuroprotective activities of the BBGs were screened using neuronal HT22 hippocampal cells. BBG-D (4) significantly protected murine hippocampal HT22 cells against glutamate-induced neurotoxicity by maintaining the antioxidative defense systems such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and the glutathione content. BBG-D, in a dose-and time-dependent manner, increased HO-1 expression through the selective activation of pERK signaling among the MAPK pathways. These results suggest that BBG-D could be a promising candidate for the treatment of neurodegenerative diseases related to glutamate-induced oxidative neuronal cytotoxicity.
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Focused renal sonography performed and interpreted by internal medicine residents.
J Ultrasound Med
PUBLISHED: 10-25-2013
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Intensivist-performed focused sonography, including renal sonography, is becoming accepted practice. Whether internal medicine residents can be trained to accurately rule out renal obstruction and identify sonographic findings of chronic kidney disease is unknown. The purpose of this study was to test the ability of residents to evaluate for this specific constellation of findings.
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Neuroprotective biflavonoids of Chamaecyparis obtusa leaves against glutamate-induced oxidative stress in HT22 hippocampal cells.
Food Chem. Toxicol.
PUBLISHED: 10-07-2013
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Four biflavonoids (1-4), five flavonoids glycosides (5-9), two catechins (10, 11), two lignans (12-13), neolignan glycoside (14) and phenylpropanoid glycoside (15) were isolated from the leaves of Chamaecyparis obtusa (Cupressaceae). Neuroprotective effects of the isolated compounds were evaluated employing HT22 mouse hippocampal cells, a model system to study glutamate-induced oxidative stress. The glutamate injured HT22 cells were protected significantly by amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-?-D-xylopyranoside (9). The reduced activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione reductase (GR) in response to high concentration of glutamate were preserved by pre-treatment of 3, 4 or 9, while the activities of glutathione peroxidase (Gpx) and catalase (CAT) were little affected. The reduced content of GSH induced by glutamate was also recovered by 3, 4 or 9 in accommodation with the decrease in ROS production. In addition, the phosphorylation of ERK1/2 induced by glutamate insult was clearly prevented by 3, while little changed by 4. Taken together, amentoflavone (3), ginkgetin (4) and (-)-epitaxifolin 3-O-?-D-xylopyranoside (9) derived from C. obtusa could protect HT22 neuronal cells against glutamate-induced oxidative damage through preserving antioxidant enzymes activities and/or inhibiting ERK1/2 activation.
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Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven pancreatic carcinoma.
Cancer Res.
PUBLISHED: 10-01-2013
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Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem. Most drugs that pass preclinical tests fail in these patients, emphasizing the need of improved preclinical models to test novel anticancer strategies. Here, we developed four orthotopic mouse models using primary human PDAC cells genetically engineered to express firefly- and Gaussia luciferase, simplifying the ability to monitor tumor growth and metastasis longitudinally in individual animals with MRI and high-frequency ultrasound. In these models, we conducted detailed histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic characteristics were compared with the originator tumor and primary tumor cells using array-based comparative genomic hybridization, using frozen specimens obtained by laser microdissection. Notably, the orthotopic human xenografts in these models recapitulated the phenotype of human PDACs, including hypovascular and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an increased copy number and overexpression of c-Met in one of the models; we examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In particular, we found that crizotinib decreased tumor dimension, prolonged survival, and increased blood and tissue concentrations of gemcitabine, synergizing with a cytidine deaminase-mediated mechanism of action. Together, these more readily imaged orthotopic PDAC models displayed genetic, histopathologic, and metastatic features similar to their human tumors of origin. Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination of drugs warranting clinical evaluation for PDAC treatment.
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Confronting carbapenemase-producing Klebsiella pneumoniae.
Future Microbiol
PUBLISHED: 09-12-2013
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The ongoing spread of carbapenemase-producing (CP) multidrug-resistant enterobacteria, primarily Klebsiella pneumoniae, has undoubtedly caused a public health crisis of unprecedented dimensions. The scientific community has been struggling with these highly problematic nosocomial pathogens for more than a decade. Faced with the current situation, one cannot help but wish we could have done better, earlier. However, significant steps have been and are currently being made towards a better understanding of transmission routes of CP microorganisms and in designing strategies that could effectively curb this devastating epidemic. Most importantly, the systematic evaluation of accumulating experimental and clinical data has paved the way to a more rational management of CP-infected patients. In addition, systematic efforts of the industry have led to the development of novel antibacterial agents that are active against CP strains and expected to be introduced to clinical practice in the immediate future.
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Synthesis, structure, and characterization of chromo(fluoro)ionophores with cation-triggered emission based on N-methylaza-crown-ether styryl dyes.
J. Org. Chem.
PUBLISHED: 09-12-2013
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Novel 2-benzothiazole-, 4-pyridine-, and 2- and 4-quinoline-based styryl dyes containing an N-methylbenzoaza-15(18)-crown-5(6)-ether moiety were synthesized. A detailed electronic spectroscopy study revealed high performance of these compounds as optical molecular sensors for alkali and alkaline-earth metal cations. They were shown to considerably surpass analogous chromoionophores based on N-phenylaza-crown ethers regarding both the ionochromism and the cation-binding ability. In addition, they act as fluorescent sensors for the metal cations by demonstrating cation-triggered emission. Upon complexation with Ba(2+), the fluorescence enhancement factor reaches 61. The structural features of dyes and their metal complexes were studied by NMR spectroscopy and X-ray diffraction. The high degree of macrocycle preorganization was found to be one of the factors determining the high cation-binding ability of the sensor molecules based on N-methylbenzoaza-crown ethers.
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Cost-effectiveness of Koreas National Cervical Cancer Screening Program.
Asian Pac. J. Cancer Prev.
PUBLISHED: 09-03-2013
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Cervical cancer, which is common in developing countries, is also a major health issue in Korea. Our aim was to evaluate the cost-effectiveness of Koreas National Cancer Screening Program (NCSP), implemented in 1999.
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Bridging the information gap between health and the environment in North Carolina.
J Public Health Manag Pract
PUBLISHED: 07-31-2013
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To better understand relationships between health and environmental hazards in North Carolina, a transdisciplinary group of participants from government and nongovernmental organizations (NFPs and universities) were appointed by the Research Triangle Environmental Health Collaborative to identify databases that when linked could lead toward improved environmental public health surveillance.
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Enhancement of the antiproliferative activity of gemcitabine by modulation of c-Met pathway in pancreatic cancer.
Curr. Pharm. Des.
PUBLISHED: 07-23-2013
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Pancreatic-ductal-adenocarcinoma (PDAC) is amongst the most lethal malignancies, mainly because of its metastatic spread and multifactorial chemoresistance. Since c-Met is a marker of pancreatic-cancer-stem-cells (CSC), playing a key role in metastasis and chemoresistance, this study evaluated the therapeutic potential of the novel c-Met/ALK inhibitor crizotinib against PDAC cells, including the Capan-1-gemcitabine-resistant cells (Capan-1-R). Crizotinib inhibited PDAC cell-growth with IC50 of 1.5 ?M in Capan-1-R, and synergistically enhanced the antiproliferative and proapoptotic activity of gemcitabine, as detected by sulforhodamine-B-assay, flow cytometry and combination-index method. Capan-1-R had higher expression of the CSC markers CD44+/CD133+/CD326+, but their combined expression was significantly reduced by crizotinib, as detected by quantitative-RT-PCR and FACS-analysis. Similarly, Capan-1-R cells had significantly higher protein-expression of c-Met (?2-fold), and increased migratory activity, which was reduced by crizotinib (e.g., > 50% reduction of cell-migration in Capan-1-R after 8-hour exposure, compared to untreated-cells), in association with reduced vimentin expression. Capan-1-R had also significantly higher mRNA expression of the gemcitabine catabolism-enzyme CDA, potentially explaining the higher CDA activity and statistically significant lower levels of gemcitabine-nucleotides in Capan-1-R compared to Capan-1, as detected by Liquid-chromatography-massspectrometry. Conversely, crizotinib significantly reduced CDA expression in both Capan-1 and Capan-1-R cells. In aggregate, these data show the ability of crizotinib to specifically target CSC-like-subpopulations, interfere with cell-proliferation, induce apoptosis, reduce migration and synergistically interact with gemcitabine, supporting further studies on this novel therapeutic approach for PDAC.
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Salicortin-derivatives from Salix pseudo-lasiogyne twigs inhibit adipogenesis in 3T3-L1 cells via modulation of C/EBP? and SREBP1c dependent pathway.
Molecules
PUBLISHED: 07-22-2013
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Obesity is reported to be associated with excessive growth of adipocyte mass tissue as a result of increases in the number and size of adipocytes differentiated from preadipocytes. To search for anti-adipogenic phytochemicals, we screened for inhibitory activities of various plant sources on adipocyte differentiation in 3T3-L1 preadipocytes. Among the sources, a methanolic extract of Salix pseudo-lasiogyne twigs (Salicaceae) reduced lipid accumulation in a concentration-dependent manner. During our search for anti-adipogenic constituents from S. pseudo-lasiogyne, five salicortin derivatives isolated from an EtOAc fraction of this plant and bearing 1-hydroxy-6-oxo-2-cyclohexene-carboxylate moieties, namely 2,6-O-acetylsalicortin (1), 2-O-acetylsalicortin (2), 3-O-acetylsalicortin (3), 6-O-acetylsalicortin (4), and salicortin (5), were found to significantly inhibit adipocyte differentiation in 3T3-L1 cells. In particular, 2,6-O-acetylsalicortin (1) had the most potent inhibitory activity on adipocyte differentiation, with an IC?? value of 11.6 ?M, and it significantly down-regulated the expressions of CCAAT/enhancer binding protein ? (C/EBP?) and sterol regulatory element binding protein 1 (SREBP1c). Furthermore, 2,6-O-acetylsalicortin (1) suppressed mRNA expression levels of C/EBP? during the early stage of adipocyte differentiation and stearoyl coenzyme A desaturase 1 (SCD-1), acetyl-CoA carboxylase (ACC), and fatty acid synthase (FAS) expression, target genes of SREBP1c. In the present study, we demonstrate that the anti-adipogenesis mechanism of 2,6-O-acetylsalicortin (1) may be mediated via down-regulation of C/EBP? and SREBP1c dependent pathways. Through their anti-adipogenic activity, salicortin derivatives may be potential novel therapeutic agents against obesity.
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Prenatal bisphenol A and birth outcomes: MOCEH (Mothers and Childrens Environmental Health) study.
Int J Hyg Environ Health
PUBLISHED: 07-01-2013
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Bisphenol A (BPA) is used primarily in the production of polycarbonate plastics and epoxy resins. Widespread exposure to BPA has created a great deal of concern regarding its potential adverse effects on human health. This study examined the relationship between prenatal BPA exposure and birth outcomes, including birth weight, birth length, and ponderal index considering gender difference. A multi-center birth cohort study, Mothers and Childrens Environmental Health (MOCEH) has been established in Korea since 2006. Study subjects are 757 pregnant women from the original cohort, who had their urinary BPA level measured during the third trimester, as well as information on birth outcome, prior medical history, psychosocial status, health behavior, environmental exposure as well as socio-demographic characteristics. Regression analysis was performed to assess the effect of BPA on birth outcome. The geometric mean concentration of BPA in pregnant women was 1.29?g/L (1.87?g/g creatinine) during late pregnancy. Urinary BPA concentrations were shown to be higher in women with a higher income level. Univariate regression analysis revealed a significant association between BPA levels and birth weight. In adjusted analysis, the second tertile of maternal BPA exposure exhibited an increase in birth weight, relative to the first tertile (p=0.04). These relationships were more pronounced in male neonates. Also, prenatal exposure to BPA was associated with an increase of ponderal index in total, and especially female neonates. This study shows that the association of prenatal exposure to BPA with anthropometric measures, such as birth weight and birth length, differed by gender. Further study is required to more fully elaborate this relationship between prenatal BPA exposure and birth outcome.
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Reference levels of blood mercury and association with metabolic syndrome in Korean adults.
Int Arch Occup Environ Health
PUBLISHED: 06-20-2013
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Mercury (Hg) is a nonessential and toxic metal that is widely distributed in the environment. This study was performed to estimate the representative blood Hg level, to determine the contributing factors to Hg exposure, and to analyze the association of blood Hg with metabolic syndrome in Korean adults.
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The effects of perchlorate, nitrate, and thiocyanate on free thyroxine for potentially sensitive subpopulations of the 2001-2002 and 2007-2008 National Health and Nutrition Examination Surveys.
J Expo Sci Environ Epidemiol
PUBLISHED: 06-19-2013
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Among women with urinary iodine concentration <100??g/l in the 2001-2002 National Health and Nutrition Examination Survey (NHANES), urinary perchlorate was associated with significant changes in thyroid stimulating hormone and total thyroxine (T4). Although perchlorate, nitrate, and thiocyanate all potentially act to inhibit iodide uptake, free T4 was not found to be associated with exposure to these chemicals in the same data. Fetuses of pregnant mothers with iodine deficiency are thought to be a sensitive subpopulation for perchlorate exposure, but the potential associations between free T4 and exposure to these chemicals among pregnant mothers in NHANES 2001-2002 and 2007-2008 have not been specifically evaluated to date. This study investigates the potential associations between urinary perchlorate, nitrate, and thiocyanate and serum free T4 in individuals with low urinary iodine levels and pregnant women. Multivariate regression models of free T4 were conducted and included urinary perchlorate, nitrate, thiocyanate, and covariates known to have an impact on the thyroid (anti-thyroid peroxidase (TPO) antibodies, age, race/ethnicity, body mass index, and hours of fasting). Meta-analyses were also conducted on non-pregnant and on pregnant women from the two survey cycles. Urinary nitrate was associated with serum free T4 in non-pregnant women of NHANES 2001-2002 who had urinary iodine ?100??g/l. In the meta-analysis, urinary perchlorate, nitrate, and thiocyanate were significant predictors of serum free T4 in non-pregnant women. No association was found in men and pregnant women. TPO antibodies were significant predictors of free T4 among non-pregnant women only when the models included urinary perchlorate, nitrate, or thiocyanate. Risk assessment for perchlorate exposure should consider co-exposure to nitrate and thiocyanate.Journal of Exposure Science and Environmental Epidemiology advance online publication, 23 October 2013; doi:10.1038/jes.2013.67.
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The effect of meeting physical activity guidelines for cancer survivors on quality of life following radical prostatectomy for prostate cancer.
J Cancer Surviv
PUBLISHED: 06-05-2013
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Recent literature has shown that preoperative physical activity (PA) can positively influence surgical outcomes. It is unknown whether the effect of meeting PA guidelines for cancer survivors can impact quality of life following radical prostatectomy for prostate cancer.
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Cost-effectiveness outcomes of the national gastric cancer screening program in South Korea.
Asian Pac. J. Cancer Prev.
PUBLISHED: 06-04-2013
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Although screening is necessary where gastric cancer is particularly common in Asia, the performance outcomes of mass screening programs have remained unclear. This study was conducted to evaluate cost-effectiveness outcomes of the national cancer screening program (NCSP) for gastric cancer in South Korea.
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Korean Environmental Health Survey in Children and Adolescents (KorEHS-C): Survey design and pilot study results on selected exposure biomarkers.
Int J Hyg Environ Health
PUBLISHED: 05-27-2013
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For the first nationwide representative survey on the environmental health of children and adolescents in Korea, we designed the Korean Environmental Health Survey in Children and Adolescents (KorEHS-C) as a two-phase survey and planned a sampling strategy that would represent the whole population of Korean children and adolescents, based on the school unit for the 6-19 years age group and the household unit for the 5 years or less age group. A pilot study for 351 children and adolescents aged 6 to 19 years in elementary, middle, and high school of two cities was performed to validate several measurement methods and tools, as well as to test their feasibility, and to elaborate the protocols used throughout the survey process. Selected exposure biomarkers, i.e., lead, mercury, cadmium in blood, and bisphenol A, metabolites of diethylhexyl phthalate and di-n-butyl phthalate and cotinine in urine were analyzed. We found that the levels of blood mercury (Median: 1.7 ug/L) and cadmium (Median: 0.30 ug/L) were much higher than those of subjects in Germany and the US, while metabolites of phthalates and bisphenol A showed similar levels and tendencies by age; the highest levels of phthalate metabolites and bisphenol A occurred in the youngest group of children. Specific investigations to elucidate the exposure pathways of major environmental exposure need to be conducted, and the KorEHS-C should cover as many potential environmental hazards as possible.
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Structural and torsional properties of the RAD51-dsDNA nucleoprotein filament.
Nucleic Acids Res.
PUBLISHED: 05-22-2013
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Human RAD51 is a key protein in the repair of DNA by homologous recombination. Its assembly onto DNA, which induces changes in DNA structure, results in the formation of a nucleoprotein filament that forms the basis of strand exchange. Here, we determine the structural and mechanical properties of RAD51-dsDNA filaments. Our measurements use two recently developed magnetic tweezers assays, freely orbiting magnetic tweezers and magnetic torque tweezers, designed to measure the twist and torque of individual molecules. By directly monitoring changes in DNA twist on RAD51 binding, we determine the unwinding angle per RAD51 monomer to be 45°, in quantitative agreement with that of its bacterial homolog, RecA. Measurements of the torque that is built up when RAD51-dsDNA filaments are twisted show that under conditions that suppress ATP hydrolysis the torsional persistence length of the RAD51-dsDNA filament exceeds that of its RecA counterpart by a factor of three. Examination of the filaments torsional stiffness for different combinations of divalent ions and nucleotide cofactors reveals that the Ca(2+) ion, apart from suppressing ATPase activity, plays a key role in increasing the torsional stiffness of the filament. These quantitative measurements of RAD51-imposed DNA distortions and accumulated mechanical stress suggest a finely tuned interplay between chemical and mechanical interactions within the RAD51 nucleoprotein filament.
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The National Cancer Screening Program for breast cancer in the Republic of Korea: is it cost-effective?
Asian Pac. J. Cancer Prev.
PUBLISHED: 05-18-2013
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This goal of this research was to evaluate the cost-effectiveness of the National Cancer Screening Program (NCSP) for breast cancer in the Republic of Korea from a government expenditure perspective. In 2002-2003 (baseline), a total of 8,724,860 women aged 40 years or over were invited to attend breast cancer screening by the NCSP. Those who attended were identified using the NCSP database, and women were divided into two groups, women who attended screening at baseline (screened group) and those who did not (non-screened group). Breast cancer diagnosis in both groups at baseline, and during 5-year follow-up was identified using the Korean Central Cancer Registry. The effectiveness of the NCSP for breast cancer was estimated by comparing 5-year survival and life years saved (LYS) between the screened and the unscreened groups, measured using mortality data from the Korean National Health Insurance Corporation and the National Health Statistical Office. Direct screening costs, indirect screening costs, and productivity costs were considered in different combinations in the model. When all three of these costs were considered together, the incremental cost to save one life year of a breast cancer patient was 42,305,000 Korean Won (KW) (1 USD=1,088 KW) for the screened group compared to the non-screened group. In sensitivity analyses, reducing the false-positive rate of the screening program by half was the most cost-effective (incremental cost-effectiveness ratio, ICER=30,110,852 KW/LYS) strategy. When the upper age limit for screening was set at 70 years, it became more cost-effective (ICER=39,641,823 KW/LYS) than when no upper age limit was set. The NCSP for breast cancer in Korea seems to be accepted as cost-effective as ICER estimates were around the Gross Domestic Product. However, cost-effectiveness could be further improved by increasing the sensitivity of breast cancer screening and by setting appropriate age limits.
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A chronic oral reference dose for hexavalent chromium-induced intestinal cancer.
J Appl Toxicol
PUBLISHED: 05-15-2013
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High concentrations of hexavalent chromium [Cr(VI)] in drinking water induce villous cytotoxicity and compensatory crypt hyperplasia in the small intestines of mice (but not rats). Lifetime exposure to such cytotoxic concentrations increases intestinal neoplasms in mice, suggesting that the mode of action for Cr(VI)-induced intestinal tumors involves chronic wounding and compensatory cell proliferation of the intestine. Therefore, we developed a chronic oral reference dose (RfD) designed to be protective of intestinal damage and thus intestinal cancer. A physiologically based pharmacokinetic model for chromium in mice was used to estimate the amount of Cr(VI) entering each intestinal tissue section (duodenum, jejunum and ileum) from the lumen per day (normalized to intestinal tissue weight). These internal dose metrics, together with corresponding incidences for diffuse hyperplasia, were used to derive points of departure using benchmark dose modeling and constrained nonlinear regression. Both modeling techniques resulted in similar points of departure, which were subsequently converted to human equivalent doses using a human physiologically based pharmacokinetic model. Applying appropriate uncertainty factors, an RfD of 0.006?mg?kg(-1) ?day(-1) was derived for diffuse hyperplasia-an effect that precedes tumor formation. This RfD is protective of both noncancer and cancer effects in the small intestine and corresponds to a safe drinking water equivalent level of 210 µg l(-1) . This concentration is higher than the current federal maximum contaminant level for total Cr (100 µg l(-1) ) and well above levels of Cr(VI) in US drinking water supplies (typically???5 µg l(-1) ). © 2013 The Authors. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
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