Gliomas are the most common type of primary brain tumors, presenting high mortality and recurrence rates that highlight the need for the development of more efficient therapies. In that context, we ...investigated iron(
iii
) (FeL) and copper(
ii
) (CuL) complexes containing the tetradentate ligand 2-{(3-chloro-2-hydroxy-propyl)-pyridin-2-ylmethyl-amino-methyl}-phenol (L) as potential antimetastatic compounds in glioma cells. These complexes were designed to act as mimetics of antioxidant metalloenzymes (catalases and superoxide dismutase) and thus interfere with the production of reactive oxygen species (ROS), important signaling molecules that have been linked to the induction of Epithelial-Mesenchymal Transition (EMT) in cancer cells, a process associated with cancer invasion and aggressiveness. The results obtained have revealed that,
in vitro
, both compounds act as superoxide dismutase or catalase mimetics, and this translated in glioma cells into a decrease in ROS levels in FeL-treated cells. In addition, both complexes were found to inhibit the migration of monolayer-grown H4 cells and lead to decreased expression of EMT markers. More importantly, this behavior was recapitulated in 3D spheroids models, where CuL in particular was found to completely inhibit the invasion ability of glioma cells, with or without cellular irradiation with X-rays, which is suggestive of these compounds' potential to be used in combination with radiotherapy. Overall, the results herein obtained describe the novel use of these complexes as agents that are able to interfere with regulation of EMT and the invasive behavior of glioma cells, an application that deserves to be further explored.
Iron and copper complexes with antioxidant activity able to inhibit tumor metastasis by inhibiting epithelial-mesenchymal transition in glioma cells.
The effects of multisystemic therapy (MST) in treating violent and chronic juvenile offenders and their families in the absence of ongoing treatment fidelity checks were examined. Across 2 public ...sector mental health sites, 155 youths and their families were randomly assigned to MST versus usual juvenile justice services. Although MST improved adolescent symptomology at posttreatment and decreased incarceration by 47% at a 1.7-year follow-up, findings for decreased criminal activity were not as favorable as observed on other recent trials of MST. Analyses of parent, adolescent, and therapist reports of MST treatment adherence, however, indicated that outcomes were substantially better in cases where treatment adherence ratings were high. These results highlight the importance of maintaining treatment fidelity when disseminating complex family-based services to community settings.
The New Horizons spacecraft carried three instruments that measured the space environment near Pluto as it flew by on 14 July 2015. The Solar Wind Around Pluto (SWAP) instrument revealed an ...interaction region confined sunward of Pluto to within about 6 Pluto radii. The region's surprisingly small size is consistent with a reduced atmospheric escape rate, as well as a particularly high solar wind flux. Observations from the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument suggest that ions are accelerated and/or deflected around Pluto. In the wake of the interaction region, PEPSSI observed suprathermal particle fluxes equal to about 1/10 of the flux in the interplanetary medium and increasing with distance downstream. The Venetia Burney Student Dust Counter, which measures grains with radii larger than 1.4 micrometers, detected one candidate impact in ±5 days around New Horizons' closest approach, indicating an upper limit of <4.6 kilometers(-3) for the dust density in the Pluto system.
The IBEX-Lo Sensor Fuselier, S. A.; Bochsler, P.; Chornay, D. ...
Space science reviews,
08/2009, Volume:
146, Issue:
1-4
Journal Article
Peer reviewed
Open access
The IBEX-Lo sensor covers the low-energy heliospheric neutral atom spectrum from 0.01 to 2 keV. It shares significant energy overlap and an overall design philosophy with the IBEX-Hi sensor. Both ...sensors are large geometric factor, single pixel cameras that maximize the relatively weak heliospheric neutral signal while effectively eliminating ion, electron, and UV background sources. The IBEX-Lo sensor is divided into four major subsystems. The entrance subsystem includes an annular collimator that collimates neutrals to approximately 7°×7° in three 90° sectors and approximately 3.5°×3.5° in the fourth 90° sector (called the high angular resolution sector). A fraction of the interstellar neutrals and heliospheric neutrals that pass through the collimator are converted to negative ions in the ENA to ion conversion subsystem. The neutrals are converted on a high yield, inert, diamond-like carbon conversion surface. Negative ions from the conversion surface are accelerated into an electrostatic analyzer (ESA), which sets the energy passband for the sensor. Finally, negative ions exit the ESA, are post-accelerated to 16 kV, and then are analyzed in a time-of-flight (TOF) mass spectrometer. This triple-coincidence, TOF subsystem effectively rejects random background while maintaining high detection efficiency for negative ions. Mass analysis distinguishes heliospheric hydrogen from interstellar helium and oxygen. In normal sensor operations, eight energy steps are sampled on a 2-spin per energy step cadence so that the full energy range is covered in 16 spacecraft spins. Each year in the spring and fall, the sensor is operated in a special interstellar oxygen and helium mode during part of the spacecraft spin. In the spring, this mode includes electrostatic shutoff of the low resolution (7°×7°) quadrants of the collimator so that the interstellar neutrals are detected with 3.5°×3.5° angular resolution. These high angular resolution data are combined with star positions determined from a dedicated star sensor to measure the relative flow difference between filtered and unfiltered interstellar oxygen. At the end of 6 months of operation, full sky maps of heliospheric neutral hydrogen from 0.01 to 2 keV in 8 energy steps are accumulated. These data, similar sky maps from IBEX-Hi, and the first observations of interstellar neutral oxygen will answer the four key science questions of the IBEX mission.
Summary Background The evolving epidemic of type 2 diabetes has challenged health-care providers to assess the safety and efficacy of various diabetes prevention strategies. The CANOE (CAnadian ...Normoglycemia Outcomes Evaluation) trial investigated whether low-dose combination therapy would affect development of type 2 diabetes. Methods In this double-blind, randomised controlled trial undertaken in clinics in Canadian centres, 207 patients with impaired glucose tolerance were randomly assigned to receive combination rosiglitazone (2 mg) and metformin (500 mg) twice daily or matching placebo for a median of 3·9 years (IQR 3·0–4·6). Randomisation was computer-generated in blocks of four, with both participants and investigators masked to treatment allocation. The primary outcome was time to development of diabetes, measured by an oral glucose tolerance test or two fasting plasma glucose values of 7·0 mmol/L or greater. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00116932. Findings 103 participants were assigned to rosiglitazone and metformin, and 104 to placebo; all were analysed. Vital status was obtained in 198 (96%) participants, and medication compliance (taking at least 80% of assigned medication) was 78% (n=77) in the metformin and rosiglitazone group and 81% (n=80) in the placebo group. Incident diabetes occurred in significantly fewer individuals in the active treatment group (n=14 14%) than in the placebo group (n=41 39%; p<0·0001). The relative risk reduction was 66% (95% CI 41–80) and the absolute risk reduction was 26% (14–37), yielding a number needed to treat of 4 (2·70–7·14). 70 (80%) patients in the treatment group regressed to normal glucose tolerance compared with 52 (53%) in the placebo group (p=0·0002). Insulin sensitivity decreased by study end in the placebo group (median −1·24, IQR −2·38 to −0·08) and remained unchanged with rosiglitazone and metformin treatment (−0·39, −1·30 to 0·84; p=0·0006 between groups). The change in β-cell function, as measured by the insulin secretion-sensitivity index-2, did not differ between groups (placebo −252·3, −382·2 to −58·0 vs rosiglitazone and metformin −221·8, −330·4 to −87·8; p=0·28). We recorded an increase in diarrhoea in participants in the active treatment group compared with the placebo group (16 16% vs 6 6%; p=0·0253). Interpretation Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs. Funding GlaxoSmithKline.
Abstract Osteoporosis Canada's 2010 Clinical Practice Guidelines for the Diagnosis and Management of Osteoporosis in Canada focus on the clinical impact of fragility fractures, and on the assessment ...and management of women and men at high risk for fragility fracture. These guidelines now integrate a 10-year absolute fracture risk prediction into an overall management approach by using validated risk assessment tools. There currently is a large gap between optimal practices and those that are now being provided to Canadians with osteoporosis. These guidelines are part of a concerted effort to close this gap. Key changes from the 2002 guidelines of interest and relevance to radiologists are highlighted in this report.
There have been 28 previously reported cases of neuroblastoma associated with congenital heart disease. Because many of these have been defects of the conotruncal region, it has been proposed that ...abnormal neural crest cell migration or maturation may be a factor that links these normally disparate pathologic conditions. Most neuroblastomas in these cases have been detected at autopsy or by radiologic studies conducted in the evaluation of the cardiac anomalies. Recently, we discovered an occult posterior mediastinal neuroblastoma in a patient undergoing a unifocalization procedure for tetralogy of Fallot with pulmonary atresia and major aortopulmonary collaterals. The tumor was resected, and the patient has demonstrated no evidence of residual or metastatic neuroblastoma.
Nonalcoholic fatty liver disease (NAFLD) is emerging as a component of the metabolic syndrome, although it is not known whether markers of NAFLD, including elevated concentrations of aspartate ...aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALK), predict the development of metabolic syndrome. Our objective was to investigate the associations of elevated AST, ALT, and other liver markers, including C-reactive protein (CRP), with incident National Cholesterol Education Program-defined metabolic syndrome among 633 subjects in the Insulin Resistance Atherosclerosis Study who were free of metabolic syndrome at baseline. Insulin sensitivity (Si) and acute insulin response (AIR) were directly measured from the frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years. After 5.2 years, 127 individuals had developed metabolic syndrome. In separate logistic regression models adjusting for age, sex, ethnicity, clinic, and alcohol consumption, subjects in the upper quartiles of ALT, ALK, and CRP were at significantly increased risk of incident metabolic syndrome compared with those in the lowest quartile: ALT, odds ratio 2.50 (95% CI 1.38-4.51); ALK, 2.28 (1.24-4.20); and CRP, 1.33 (1.09-1.63). Subjects in the upper quartile of the AST-to-ALT ratio were at significantly reduced metabolic syndrome risk (0.40 0.22-0.74). After further adjustment for waist circumference, Si, AIR, and impaired glucose tolerance, the associations of ALT and the AST-to-ALT ratio with incident metabolic syndrome remained significant (ALT, 2.12 1.10-4.09; the AST-to-ALT ratio, 0.48 0.25-0.95). These associations were not modified by ethnicity or sex, and they remained significant after exclusion of former and heavy drinkers. In conclusion, NAFLD markers ALT and the AST-to-ALT ratio predict metabolic syndrome independently of potential confounding variables, including directly measured Si and AIR.
The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and ...obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories.
We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes.
WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34).
This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.
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