1,386 research outputs found

    Toxic Effects of Silver Ions on Early Developing Zebrafish Embryos Distinguished From Silver Nanoparticles

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    Currently, effects of nanomaterials and their ions, such as silver nanoparticles (Ag NPs) and silver ions (Ag+), on living organisms are not yet fully understood. One of the vital questions is whether nanomaterials have distinctive effects on living organisms from any other conventional chemicals (e.g., their ions), owing to their unique physicochemical properties. Due to various experimental protocols, studies of this crucial question have been inconclusive, which hinders rational design of effective regulatory guidelines for safely handling NPs. In this study, we chronically exposed early developing zebrafish embryos (cleavage-stage, 2 hours post-fertilization, hpf) to a dilution series of Ag+ (0–1.2 μM) in egg water (1 mM NaCl, solubility of Ag+ = 0.18 μM) until 120 hpf. We systematically investigated effects of Ag+ on developing embryos and compared them with our previous studies of effects of purified Ag NPs on developing embryos. We found the concentration- and time-dependent effects of Ag+ on embryonic development, and only half of the embryos developed normally after being exposed to 0.25 μM (27 μg/L) Ag+ until 120 hpf. As the Ag+ concentration increases, the number of embryos that developed normally decreases, while the number of embryos that became dead increases. The number of abnormally developing embryos increases as the Ag+ concentration increases from 0 to 0.3 μM and then decreases as the concentration increases from 0.3 to 1.2 μM because the number of embryos that became dead increases. The concentration-dependent phenotypes were observed, showing fin fold abnormality, tail and spinal cord flexure, and yolk sac edema at low Ag+ concentrations (≤0.2 μM) and head and eye abnormalities along with fin fold abnormality, tail and spinal cord flexure, and yolk sac edema at high concentrations (≥0.3 μM). Severities of phenotypes and the number of abnormally developing embryos were far less than those observed in Ag NPs. The results also show concentration-dependent effects on heart rates and hatching rates of developing embryos, attributing to the dose-dependent abnormally developing embryos. In summary, the results show that Ag+ and Ag NPs have distinctive toxic effects on early developing embryos, and toxic effects of Ag+ are far less severe than those of Ag NPs, which further demonstrates that the toxicity of Ag NPs toward embryonic development is attributed to the NPs themselves and their unique physicochemical properties but not the release of Ag+ from the Ag NPs

    Binding of the Bacillus subtilis LexA protein to the SOS operator

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    The Bacillus subtilis LexA protein represses the SOS response to DNA damage by binding as a dimer to the consensus operator sequence 5′-CGAACN(4)GTTCG-3′. To characterize the requirements for LexA binding to SOS operators, we determined the operator bases needed for site-specific binding as well as the LexA amino acids required for operator recognition. Using mobility shift assays to determine equilibrium constants for B.subtilis LexA binding to recA operator mutants, we found that several single base substitutions within the 14 bp recA operator sequence destabilized binding enough to abolish site-specific binding. Our results show that the AT base pairs at the third and fourth positions from the 5′ end of a 7 bp half-site are essential and that the preferred binding site for a LexA dimer is 5′-CGAACATATGTTCG-3′. Binding studies with LexA mutants, in which the solvent accessible amino acid residues in the putative DNA binding domain were mutated, indicate that Arg-49 and His-46 are essential for binding and that Lys-53 and Ala-48 are also involved in operator recognition. Guided by our mutational analyses as well as hydroxyl radical footprinting studies of the dinC and recA operators we docked a computer model of B.subtilis LexA on the preferred operator sequence in silico. Our model suggests that binding by a LexA dimer involves bending of the DNA helix within the internal 4 bp of the operator

    Perceived Effectiveness, Cost, and Availability of Patient Education Methods and Materials

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    To determine the efficacy of and need for patient education methods and media, a needs assessment was sent to 816 members of the American Association of Diabetes Educators. Respondents (n=325, 40%) included 62% RNs, 36% RDs, 1% other; 62% CDEs. Their mean number of years experience in diabetes education was 8.5, and 99% routinely provided patient education. Respondents indicated that videotapes and slide tapes were the most educationally effective media and books and audiotapes were the least effective. Booklets and videotapes were the most cost-effective and computer-assisted instruction the least effective. While respondents perceived one-to-one counseling, skills training, and diabetes content sessions to be the three most educationally effective methods, support groups and large and small discussion groups were seen as the three most cost-effective educational methods. Among nine potential barriers to quality patient education listed, educators rated lack of third-party reimbursement as a major barrier most frequently and national availability of quality education materials as a barrier least frequently.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68739/2/10.1177_014572179201800207.pd

    Mercury Exposure and Antinuclear Antibodies among Females of Reproductive Age in the United States: NHANES

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    Background: Immune dysregulation associated with mercury has been suggested, though data in the general population are lacking. Chronic exposure to low levels of methylmercury (organic) and inorganic mercury is common, such as through fish consumption and dental amalgams. Objective: To examine associations between mercury biomarkers and antinuclear antibody (ANA) positivity and titer strength. Methods: Among females 16-49 years (n=1352) from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, we examined cross-sectional associations between mercury and ANAs (indirect immunofluorescence; cutoff ≥1:80). Three biomarkers of mercury exposure were utilized: hair (available 1999-2000) and total blood (1999-2004) predominantly represented methylmercury, and urinary (1999-2002) inorganic. Survey statistics were used. Multivariable modeling adjusted for several covariates, including age and omega-3 fatty acids. Results: 16% of females were ANA-positive; 96% of ANA-positives had a nuclear staining pattern of speckled. Mercury geometric means (standard deviations) were: 0.22 (0.03) ppm hair, 0.92 (0.05) µg/L blood, and 0.62 (0.04) µg/L urinary. Hair and blood, but not urinary, mercury were associated with ANA positivity (sample sizes 452, 1352, and 804, respectively), adjusting for confounders: hair odds ratio (OR)=4.10 (95% CI: 1.66, 10.13); blood OR=2.32 (95% CI: 1.07, 5.03) comparing highest versus lowest quantiles. Magnitudes of association were strongest for high-titer (≥1:1280) ANA: hair OR=11.41 (95% CI: 1.60, 81.23); blood OR=5.93 (95% CI: 1.57, 22.47). Conclusions: Methylmercury, at low levels generally considered safe, was associated with subclinical autoimmunity among reproductive-age females. Autoantibodies may predate clinical disease by years, thus methylmercury exposure may be relevant to future autoimmune disease risk.This work was supported by NIH/NIEHS K01ES019909, NIH/NIEHS P30ES017885, and NIH/NCRR UL1RR024986. ECS was supported in part by an Arthritis Foundation Health Professional New Investigator Award.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/1/SOMERS_EHP.AdvancePubl 02102015.acco.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110512/2/Somers_EHP Suppl-1408751.s001.508.pdf114Description of SOMERS_EHP.AdvancePubl 02102015.acco.pdf : Main ArticleDescription of Somers_EHP Suppl-1408751.s001.508.pdf : Supplementary Materia

    Empowerment: An Idea Whose Time Has Come in Diabetes Education

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    We have learned much in the past 10 years about how to help patients to acquire diabetes-related knowledge and skills and how to use strategies to help patients change behaviors. However, the application ofknowledge and techniques should be guided by a relevant, coherent, educational philosophy. Empowerment offers a practical conceptual framework for diabetes patient education. Empowering patients provides them with the knowledge, skills, and responsibility to effect change and has the potential to promote overall health and maximize the use of available resources. It is an idea whose time has come for diabetes education.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68779/2/10.1177_014572179101700108.pd

    Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

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    The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

    Effect of Calcium Supplementation on Blood Lead Levels in Pregnancy: A Randomized Placebo-Controlled Trial

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    Background: Prenatal lead exposure is associated with deficits in fetal growth and neurodevelopment. Calcium supplementation may attenuate fetal exposure by inhibiting mobilization of maternal bone lead and/or intestinal absorption of ingested lead. Objective: Our goal was to evaluate the effect of 1,200 mg dietary calcium supplementation on maternal blood lead levels during pregnancy. Methods: In a double-blind, randomized, placebo-controlled trial conducted from 2001 through 2003 in Mexico City, we randomly assigned 670 women in their first trimester of pregnancy to ingest calcium (n = 334) or placebo (n = 336). We followed subjects through pregnancy and evaluated the effect of supplementation on maternal blood lead, using an intent-to-treat analysis by a mixed-effects regression model with random intercept, in 557 participants (83%) who completed follow-up. We then conducted as-treated analyses using similar models stratified by treatment compliance. Results: Adjusting for baseline lead level, age, trimester of pregnancy, and dietary energy and calcium intake, calcium was associated with an average 11% reduction (0.4 μg/dL) in blood lead level relative to placebo (p = 0.004). This reduction was more evident in the second trimester (−14%, p lesss than 0.001) than in the third (−8%, p = 0.107) and was strongest in women who were most compliant (those who consumed ≥ 75% calcium pills; −24%, p less than 0.001), had baseline blood lead greater than 5 μg/dL (−17%, p less than 0.01), or reported use of lead-glazed ceramics and high bone lead (−31%, p less than 0.01). Conclusion: Calcium supplementation was associated with modest reductions in blood lead when administered during pregnancy and may constitute an important secondary prevention effort to reduce circulating maternal lead and, consequently, fetal exposure

    Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe

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    Aims/hypothesis: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. Methods: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. Results: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24–28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35–37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. Conclusions/interpretation: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies
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