613 research outputs found

    Spectral and Structural Characterization of 5,6-Chrysenequinone Diimine Complexes of Rhodium(III): Evidence for a pH-Dependent Ligand Conformational Switch

    Get PDF
    Rhodium(III) complexes containing 9,10-phenanthrenequinone diimine (phi) ligands have been broadly applied for the construction of DNA binding and recognition molecules, and more recently, derivatives containing the 5,6-chrysenequinone diimine (chrysi) ligand have been shown specifically to recognize base mismatches in DNA. Here the structural properties of [Rh(bpy)_2(chrysi)]Cl_3 and spectroscopic properties of derivatives are examined and compared to those of phi complexes of rhodium. Although similar in many respects, phi and chrysi complexes display distinctly different protonation behavior. The pK_a values of chrysi complexes are as much as 1 unit lower than analogous phi compounds, and visible spectra of the chrysi complexes differ markedly from the phi counterparts in acidic but not basic solution. This protonation behavior is traced to the presence of a steric clash between a proton on the aromatic ring of the chrysi ligand and the acidic immino proton of the metal complex. In avoidance of this steric clash, a significant disruption in the planarity of the chrysi ligand is evident crystallographically in the structure of [Rh(bpy)_2(chrysi)]Cl_3·3CH_3CN·2H_2O (triclinic crystal system, space group P1̄ (No. 2), Z = 2, a = 9.079(3) Å, b = 10.970(3) Å, c = 21.192(8) Å, α = 86.71(3)°, β = 89.21(3)°, γ = 78.58(3)°, V = 2065.4(12) Å^3). Phi complexes, lacking the additional aromatic ring, require no similar distortion from ligand planarity. NMR spectra support this pH-dependent structural distortion for the chrysi complex. Rhodium complexes of chrysenequinone diimine, therefore, not only represent new DNA binding molecules targeted to mismatches but also provide an illustration of a pH “gated” ligand conformational switch

    Undernutrition and stage of gestation influence fetal adipose tissue gene expression

    Get PDF
    Funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division (RESAS), including the Strategic Partnership for Animal Science Excellence (SPASE) and the U.S. National Institutes of Health (HD045784). None of the authors had any financial or personal conflicts of interest.Peer reviewedPostprin

    Rivastigmine for gait stability in patients with Parkinson's disease (ReSPonD): a randomised, double-blind, placebo-controlled, phase 2 trial

    Get PDF
    Background Falls are a frequent and serious complication of Parkinson's disease and are related partly to an underlying cholinergic deficit that contributes to gait and cognitive dysfunction in these patients. Gait dysfunction can lead to an increased variability of gait from one step to another, raising the likelihood of falls. In the ReSPonD trial we aimed to assess whether ameliorating this cholinergic deficit with the acetylcholinesterase inhibitor rivastigmine would reduce gait variability. Methods We did this randomised, double-blind, placebo-controlled, phase 2 trial at the North Bristol NHS Trust Hospital, Bristol, UK, in patients with Parkinson's disease recruited from community and hospital settings in the UK. We included patients who had fallen at least once in the year before enrolment, were able to walk 18 m without an aid, had no previous exposure to an acetylcholinesterase inhibitor, and did not have dementia. Our clinical trials unit randomly assigned (1:1) patients to oral rivastigmine or placebo capsules (both taken twice a day) using a computer-generated randomisation sequence and web-based allocation. Rivastigmine was uptitrated from 3 mg per day to the target dose of 12 mg per day over 12 weeks. Both the trial team and patients were masked to treatment allocation. Masking was achieved with matched placebo capsules and a dummy uptitration schedule. The primary endpoint was difference in step time variability between the two groups at 32 weeks, adjusted for baseline age, cognition, step time variability, and number of falls in the previous year. We measured step time variability with a triaxial accelerometer during an 18 m walking task in three conditions: normal walking, simple dual task with phonemic verbal fluency (walking while naming words beginning with a single letter), and complex dual task switching with phonemic verbal fluency (walking while naming words, alternating between two letters of the alphabet). Analysis was by modified intention to treat; we excluded from the primary analysis patients who withdrew, died, or did not attend the 32 week assessment. This trial is registered with ISRCTN, number 19880883. Findings Between Oct 4, 2012 and March 28, 2013, we enrolled 130 patients and randomly assigned 65 to the rivastigmine group and 65 to the placebo group. At week 32, compared with patients assigned to placebo (59 assessed), those assigned to rivastigmine (55 assessed) had improved step time variability for normal walking (ratio of geometric means 0·72, 95% CI 0·58–0·88; p=0·002) and the simple dual task (0·79; 0·62–0·99; p=0·045). Improvements in step time variability for the complex dual task did not differ between groups (0·81, 0·60–1·09; p=0·17). Gastrointestinal side-effects were more common in the rivastigmine group than in the placebo group (p<0·0001); 20 (31%) patients in the rivastigmine group versus three (5%) in the placebo group had nausea and 15 (17%) versus three (5%) had vomiting

    Long-Term Consequences of Methamphetamine Exposure in Young Adults Are Exacerbated in Glial Cell Line-Derived Neurotrophic Factor Heterozygous Mice

    Get PDF
    Methamphetamine abuse in young adults has long-term deleterious effects on brain function that are associated with damage to monoaminergic neurons. Administration of glial cell line-derived neurotrophic factor (GDNF) protects dopamine neurons from the toxic effects of methamphetamine in animal models. Therefore, we hypothesized that a partial GDNF gene deletion would increase the susceptibility of mice to methamphetamine neurotoxicity during young adulthood and possibly increase age-related deterioration of behavior and dopamine function. Two weeks after a methamphetamine binge (4 x 10 mg/kg, i.p., at 2 h intervals), GDNF +/- mice had a significantly greater reduction of tyrosine hydroxylase immunoreactivity in the medial striatum, a proportionally greater depletion of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the striatum, and a greater increase in activated microglia in the substantia nigra than wild-type mice. At 12 months of age, methamphetamine-treated GDNF +/- mice exhibited less motor activity and lower levels oftyrosine hydroxylase-immunoreactivity, dopamine, DOPAC, and serotoninthanwild-typemice. Greater striatal dopaminetransporter activity in GDNF +/- mice may underlie their differential response to methamphetamine. These data suggest the possibility that methamphetamine use in young adults, when combined with lower levels of GDNF throughout life, may precipitate the appearance of parkinsonian-like behaviors during aging

    Rapid reduction of central line infections in hospitalized pediatric oncology patients through simple quality improvement methods

    Full text link
    Background Pediatric hematology–oncology (PHO) patients are at significant risk for developing central line‐associated bloodstream infections (CLA‐BSIs) due to their prolonged dependence on such catheters. Effective strategies to eliminate these preventable infections are urgently needed. In this study, we investigated the implementation of bundled central line maintenance practices and their effect on hospital‐acquired CLA‐BSIs. Materials and Methods CLA‐BSI rates were analyzed within a single‐institution's PHO unit between January 2005 and June 2011. In May 2008, a multidisciplinary quality improvement team developed techniques to improve the PHO unit's safety culture and implemented the use of catheter maintenance practices tailored to PHO patients. Data analysis was performed using time‐series methods to evaluate the pre‐ and post‐intervention effect of the practice changes. Results The pre‐intervention CLA‐BSI incidence was 2.92 per 1,000‐patient days (PD) and coagulase‐negative Staphylococcus was the most prevalent pathogen (29%). In the post‐intervention period, the CLA‐BSI rate decreased substantially (45%) to 1.61 per 1,000‐PD ( P  < 0.004). Early on, blood and marrow transplant (BMT) patients had a threefold higher CLA‐BSI rate compared to non‐BMT patients ( P  < 0.033). With additional infection control countermeasures added to the bundled practices, BMT patients experienced a larger CLA‐BSI rate reduction such that BMT and non‐BMT CLA‐BSI rates were not significantly different post‐intervention. Conclusions By adopting and effectively implementing uniform maintenance catheter care practices, learning multidisciplinary teamwork, and promoting a culture of patient safety, the CLA‐BSI incidence in our study population was significantly reduced and maintained. Pediatr Blood Cancer 2013;60:262–269. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95163/1/24187_ftp.pd

    Physical activity in relation to urban environments in 14 cities worldwide: a cross-sectional study

    Get PDF
    Background Physical inactivity is a global pandemic responsible for over 5 million deaths annually through its effects on multiple non-communicable diseases. We aimed to document how objectively measured attributes of the urban environment are related to objectively measured physical activity, in an international sample of adults. Methods We based our analyses on the International Physical activity and Environment Network (IPEN) adult study, which was a coordinated, international, cross-sectional study. Participants were sampled from neighbourhoods with varied levels of walkability and socioeconomic status. The present analyses of data from the IPEN adult study included 6822 adults aged 18–66 years from 14 cities in ten countries on five continents. Indicators of walkability, public transport access, and park access were assessed in 1·0 km and 0·5 km street network buffers around each participant's residential address with geographic information systems. Mean daily minutes of moderate-to-vigorous-intensity physical activity were measured with 4–7 days of accelerometer monitoring. Associations between environmental attributes and physical activity were estimated using generalised additive mixed models with gamma variance and logarithmic link functions. Results Four of six environmental attributes were significantly, positively, and linearly related to physical activity in the single variable models: net residential density (exp[b] 1·006 [95% CI 1·003–1·009]; p=0·001), intersection density (1·069 [1·011–1·130]; p=0·019), public transport density (1·037 [1·018–1·056]; p=0·0007), and number of parks (1·146 [1·033–1·272]; p=0·010). Mixed land use and distance to nearest public transport point were not related to physical activity. The difference in physical activity between participants living in the most and least activity-friendly neighbourhoods ranged from 68 min/week to 89 min/week, which represents 45–59% of the 150 min/week recommended by guidelines. Interpretation Design of urban environments has the potential to contribute substantially to physical activity. Similarity of findings across cities suggests the promise of engaging urban planning, transportation, and parks sectors in efforts to reduce the health burden of the global physical inactivity pandemic. Funding Funding for coordination of the IPEN adult study, including the present analysis, was provided by the National Cancer Institute of National Institutes of Health (CA127296) with studies in each country funded by different sources

    Differences in adolescent activity and dietary behaviors across home, school, and other locations warrant location-specific intervention approaches

    Get PDF
    Background Investigation of physical activity and dietary behaviors across locations can inform “setting-specific” health behavior interventions and improve understanding of contextual vulnerabilities to poor health. This study examined how physical activity, sedentary time, and dietary behaviors differed across home, school, and other locations in young adolescents. Methods Participants were adolescents aged 12–16 years from the Baltimore-Washington, DC and the Seattle areas from a larger cross-sectional study. Participants (n = 472) wore an accelerometer and Global Positioning Systems (GPS) tracker (Mean days = 5.12, SD = 1.62) to collect location-based physical activity and sedentary data. Participants (n = 789) completed 24-h dietary recalls to assess dietary behaviors and eating locations. Spatial analyses were performed to classify daily physical activity, sedentary time patterns, and dietary behaviors by location, categorized as home, school, and “other” locations. Results Adolescents were least physically active at home (2.5 min/hour of wear time) and school (2.9 min/hour of wear time) compared to “other” locations (5.9 min/hour of wear time). Participants spent a slightly greater proportion of wear time in sedentary time when at school (41 min/hour of wear time) than at home (39 min/hour of wear time), and time in bouts lasting ≥30 min (10 min/hour of wear time) and mean sedentary bout duration (5 min) were highest at school. About 61% of daily energy intake occurred at home, 25% at school, and 14% at “other” locations. Proportionately to energy intake, daily added sugar intake (5 g/100 kcal), fruits and vegetables (0.16 servings/100 kcal), high calorie beverages (0.09 beverages/100 kcal), whole grains (0.04 servings/100 kcal), grams of fiber (0.65 g/100 kcal), and calories of fat (33 kcal/100 kcal) and saturated fat (12 kcal/100 kcal) consumed were nutritionally least favorable at “other” locations. Daily sweet and savory snacks consumed was highest at school (0.14 snacks/100 kcal). Conclusions Adolescents’ health behaviors differed based on the location/environment they were in. Although dietary behaviors were generally more favorable in the home and school locations, physical activity was generally low and sedentary time was higher in these locations. Health behavior interventions that address the multiple locations in which adolescents spend time and use location-specific behavior change strategies should be explored to optimize health behaviors in each location

    Associations of built environment and proximity of food outlets with weight status:Analysis from 14 cities in 10 countries

    Get PDF
    The study aimed to examine associations of neighborhood built environments and proximity of food outlets (BE measures) with body weight status using pooled data from an international study (IPEN Adult). Objective BE measures were calculated using geographic information systems for 10,008 participants (4463 male, 45%) aged 16-66 years in 14 cities. Participants self-reported proximity to three types of food outlets. Outcomes were body mass index (BMI) and overweight/obesity status. Male and female weight status associations with BE measures were estimated by generalized additive mixed models. Proportion (95% CI) of overweight (BMI 25 to = 30) from 2.9% (1.3, 4.4) to 31.3% (27.7, 34.7), with Hong Kong being the lowest and Cuernavaca, Mexico highest for both proportions. Results differed by sex. Greater street intersection density, public transport density and perceived proximity to restaurants (males) were associated with lower odds of overweight/obesity (BMI >= 25). Proximity to public transport stops (females) was associated with higher odds of overweight/obesity. Composite BE measures were more strongly related to BMI and overweight/obesity status than single variables among men but not women. One standard deviation improvement in the composite measures of BE was associated with small reductions of 0.1-0.5% in BMI but meaningful reductions of 2.5-5.3% in the odds of overweight/obesity. Effects were linear and generalizable across cities. Neighborhoods designed to support public transport, with food outlets within walking distance, may contribute to global obesity control
    corecore