Home-based oral health program for adults with intellectual disabilities: An intervention study.

BACKGROUND: Poor oral health is common in adults with intellectual disabilities leading to risk of mouth and lung infections. Yet, little is known about the benefits of preventative oral health programs. OBJECTIVE/HYPOTHESIS: This prospective longitudinal experimental mixed methods study evaluated the efficacy of an oral health program aimed at improving knowledge and behaviours in adults with intellectual disabilities living in supported housing. METHODS: A 90-min training session was provided to residents and their staff at 12 houses (56 residents; 67 staff). Follow-up training sessions (at 1 week, 1,2,3 months) were tailored to the learning abilities, behavioural/physical challenges, and independence of residents. Outcome measures were collected pre, 1, 2 and 3 months (n = 36): dental exam, plaque index, gingival signs, tongue coating index and behavioural rating scale. At 3 months, support workers (n = 10) and residents (n = 19) were interviewed. Residents' interviews were supported by Talking Mats®. RESULTS: Most residents (94%) required support for oral cares; with 63% fully dependant on their support workers. 24 (63%) residents had significantly improved plaque scores at 3 months (p < .001). Resident interviews were restricted by communication competency but supported interviews indicated positive responses to 3-sided toothbrush 91%, interdental brush/flosser 60%, and mouthwash 100%. Support worker interviews revealed perceived health and social benefits including fresher breath and benefits of routines. CONCLUSIONS: Oral health programs for adults with intellectual disabilities living in supported housing are well received by staff and residents, leading to changes in oral care routines and measurable changes in oral health.

Genome-wide analysis of DNA-PK-bound MRN cleavage products supports a sequential model of DSB repair pathway choice.

The Mre11-Rad50-Nbs1 (MRN) complex recognizes and processes DNA double-strand breaks for homologous recombination by performing short-range removal of 5' strands. Endonucleolytic processing by MRN requires a stably bound protein at the break site-a role we postulate is played by DNA-dependent protein kinase (DNA-PK) in mammals. Here we interrogate sites of MRN-dependent processing by identifying sites of CtIP association and by sequencing DNA-PK-bound DNA fragments that are products of MRN cleavage. These intermediates are generated most efficiently when DNA-PK is catalytically blocked, yielding products within 200 bp of the break site, whereas DNA-PK products in the absence of kinase inhibition show greater dispersal. Use of light-activated Cas9 to induce breaks facilitates temporal resolution of DNA-PK and Mre11 binding, showing that both complexes bind to DNA ends before release of DNA-PK-bound products. These results support a sequential model of double-strand break repair involving collaborative interactions between homologous and non-homologous repair complexes.

THE OLYMPIC MOUNTAINS EXPERIMENT (OLYMPEX).

OLYMPEX is a comprehensive field campaign to study how precipitation in Pacific storms is modified by passage over coastal mountains.

Accelerated cardiac magnetic resonance imaging in the mouse using an eight-channel array at 9.4 Tesla.

MRI has become an important tool to noninvasively assess global and regional cardiac function, infarct size, or myocardial blood flow in surgically or genetically modified mouse models of human heart disease. Constraints on scan time due to sensitivity to general anesthesia in hemodynamically compromised mice frequently limit the number of parameters available in one imaging session. Parallel imaging techniques to reduce acquisition times require coil arrays, which are technically challenging to design at ultrahigh magnetic field strengths. This work validates the use of an eight-channel volume phased-array coil for cardiac MRI in mice at 9.4 T. Two- and three-dimensional sequences were combined with parallel imaging techniques and used to quantify global cardiac function, T(1)-relaxation times and infarct sizes. Furthermore, the rapid acquisition of functional cine-data allowed for the first time in mice measurement of left-ventricular peak filling and ejection rates under intravenous infusion of dobutamine. The results demonstrate that a threefold accelerated data acquisition is generally feasible without compromising the accuracy of the results. This strategy may eventually pave the way for routine, multiparametric phenotyping of mouse hearts in vivo within one imaging session of tolerable duration.

High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes.

AIMS: To measure the activity of the key phosphotransfer enzymes creatine kinase (CK), adenylate kinase (AK), and glycolytic enzymes in two common mouse models of chronic heart failure. METHODS AND RESULTS: C57BL/6 mice were subjected to transverse aortic constriction (TAC), myocardial infarction induced by coronary artery ligation (CAL), or sham operation. Activities of phosphotransfer enzymes CK, AK, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 3-phosphoglycerate kinase (PGK), and pyruvate kinase were assessed spectrophotometrically. Mice were characterized by echocardiography or magnetic resonance imaging 5- to 8-week post-surgery and selected for the presence of congestive heart failure. All mice had severe left ventricular hypertrophy, impaired systolic function and pulmonary congestion compared with sham controls. A significant decrease in myocardial CK and maximal CK reaction velocity was observed in both experimental models of heart failure. However, the activity of AK and its isoforms remained unchanged, despite a reduction in its protein expression. In contrast, the activities of glycolytic phosphotransfer mediators GAPDH and PGK were 19 and 12% higher in TAC, and 31 and 23% higher in CAL models, respectively. CONCLUSION: Chronic heart failure in the mouse is characterized by impaired CK function, unaltered AK, and increased activity of glycolytic phosphotransfer enzymes. This pattern of altered phosphotransfer activity was observed independent of the heart failure aetiology.

A high-throughput eight-channel probe head for murine MRI at 9.4 T.

Murine MRI studies are conducted on dedicated MR systems, typically equipped with ultra-high-field magnets (>or=4.7 T; bore size: approximately 12-25 cm), using a single transmit-receive coil (volume or surface coil in linear or quadrature mode) or a transmit-receive coil combination. Here, we report on the design and characterization of an eight-channel volume receive-coil array for murine MRI at 400 MHz. The array was combined with a volume-transmit coil and integrated into one probe head. Therefore, the animal handling is fully decoupled from the radiofrequency setup. Furthermore, fixed tune and match of the coils and a reduced number of connectors minimized the setup time. Optimized preamplifier design was essential for minimizing the noise coupling between the elements. A comprehensive characterization of transmit volume resonator and receive coil array is provided. The performance of the coil array is compared to a quadrature-driven birdcage coil with identical sensitive volume. It is shown that the miniature size of the elements resulted in coil noise domination and therefore reduced signal-to-noise-ratio performance in the center compared to the quadrature birdcage. However, it allowed for 3-fold accelerated imaging of mice in vivo, reducing scan time requirements and thus increasing the number of mice that can be scanned per unit of time.

Fast left ventricular mass and volume assessment in mice with three-dimensional guide-point modeling.

PURPOSE: To investigate the accuracy (vs. standard manual analysis) and precision (scan-rescan reproducibility) of three-dimensional guide-point modeling (GPM) for the assessment of left ventricular (LV) function in mice. METHODS: Six male wildtype C57/Bl6 mice (weight 26.2 +/- 1.1 g) were scanned twice, 3 days apart. Each scan was performed twice, at 0.2 mm/pixel with one average and at 0.1 mm/pixel with two averages. The 24 studies were anonymized and analyzed in blinded fashion using GPM and standard manual slice summation. RESULTS: The average error between GPM and standard analysis was 2.3 +/- 5.8 mg in mass, 1.7 +/- 3.2 microL in end-diastolic volume, 2.3 +/- 3.1 microL in end-systolic volume, -2.7 +/- 4.3% in ejection fraction, -0.6 +/- 3.3 microL in stroke volume, and -0.31 +/- 1.56 ml . min(-1) in cardiac output (mean difference +/- SD of differences, n = 24). The average time taken was 8.0 +/- 2.5 minutes for 3D GPM and 48.5 +/- 8.9 minutes for standard analysis (n = 24). Scan-rescan reproducibility results were similar to the standard analysis. No significant differences were found using linear mixed effects modeling in either accuracy or precision between scan resolutions or analysis method. CONCLUSION: 3D GPM enables fast analysis of mouse LV function, with similar accuracy and reproducibility to standard analysis. An image resolution of 0.2 mm/pixel with one average is adequate for LV function studies.

Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI.

Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement MRI (3D-LGE). Myocardial T1 relaxation was quantified at 9.4 Tesla in five mice, and reproducibility was tested by repeat imaging after 5 days. In a separate set of healthy and infarcted mice (n = 8 of each), continuous T1 measurements were made following intravenous or intraperitoneal injection of a contrast agent (0.5 micromol/g gadolinium-diethylenetriamine pentaacetic acid). The time course of T1 contrast development between viable and nonviable myocardium was thereby determined, with optimal postinjection imaging windows and inversion times identified. Infarct sizes were quantified using 3D-LGE and compared with triphenyltetrazolium chloride histology on day 1 after infarction (n = 8). Baseline myocardial T1 was highly reproducible: the mean value was 952 +/- 41 ms. T1 contrast peaked earlier after intravenous injection than with intraperitoneal injection; however, contrast between viable and nonviable myocardium was comparable for both routes (P = 0.31), with adequate contrast remaining for at least 60 min postinjection. Excellent correlation was obtained between infarct sizes derived from 3D-LGE and histology (r = 0.91, P = 0.002), and Bland-Altman analysis indicated good agreement free from systematic bias. We have validated an improved 3D MRI method to noninvasively quantify infarct size in mice with unsurpassed spatial resolution and tissue contrast. This method is particularly suited to studies requiring early quantification of initial infarct size, for example, to measure damage before intervention with stem cells.

Ultra-fast and accurate assessment of cardiac function in rats using accelerated MRI at 9.4 Tesla.

MRI can accurately and reproducibly assess cardiac function in rodents but requires relatively long imaging times. Therefore, parallel imaging techniques using a 4-element RF-coil array and MR sequences for cardiac MRI in rats were implemented at ultra-high magnetic fields (9.4 Tesla [T]). The hypothesis that these developments would result in a major reduction in imaging time without loss of accuracy was tested on female Wistar rats under isoflurane anesthesia. High-resolution, contiguous short-axis slices (thickness 1.5 mm) were acquired covering the entire heart. Two interleaved data sets (i) with the volume coil (eight averages) and (ii) with the four-element coil array (one average) were obtained. In addition, two-, three-, and fourfold accelerated data sets were generated through postprocessing of the coil array data, followed by a TGRAPPA reconstruction, resulting in five data sets per rat (in-plane voxel size 100 x 100 microm). Using a single blinded operator, excellent agreement was obtained between volume coil (acquisition time: 88 min) and the fourfold accelerated (<3 min) data sets (e.g., LV mass 436 +/- 21 mg vs 433 +/- 19 mg; ejection fraction 74 +/- 5% vs 75 +/- 4%). This finding demonstrates that it is possible to complete a rat cine-MRI study under 3 min with low variability and without losing temporal or spatial resolution, making high throughput screening programs feasible.

Copper-catalyzed oxidation of a structured lipid-based emulsion containing alpha-tocopherol and citric acid: influence of pH and NaCl.

The effects of salt and pH on copper-catalyzed lipid oxidation in structured lipid-based emulsions were evaluated. Ten percent oil-in-water emulsions were formulated with a canola oil/caprylic acid structured lipid and stabilized with 0.5% whey protein isolate. alpha-Tocopherol and citric acid were added to the emulsions to determine how changes in pH or the addition of NaCl affected their antioxidant activity. The peroxide values and anisidine values of emulsions stored at 50 degrees C were measured over an 8-day period. Increased lipid oxidation occurred in the pH 7.0 emulsions and when 0.5 M NaCl was added to the pH 3.0 samples. Adding alpha-tocopherol, citric acid, or a combination of the two compounds slowed the formation of hydroperoxides and their subsequent decomposition products in pH 3.0 emulsions.

Effects of alpha-tocopherol, beta-carotene, and soy isoflavones on lipid oxidation of structured lipid-based emulsions.

Structured lipids (SLs) are triacylglycerols that have been modified to change the fatty acid composition and/or positional distribution in the glycerol backbone by chemically and/or enzymatically catalyzed reactions and/or genetic engineering. Ten percent oil-in-water emulsions were formulated with a canola oil/caprylic acid SL and stabilized with 0.5% whey protein isolate (WPI) or sucrose fatty acid ester (SFE). The effects of alpha-tocopherol, beta-carotene, genistein, and daidzein (added at 0.02 wt % of oil) on lipid oxidation were evaluated over a 15-day period in emulsion samples. Significantly (p < 0.05) less total oxidation (calculated from peroxide value and anisidine value measurements) occurred in the WPI emulsions compared to their SFE counterparts. In this study, alpha-tocopherol, beta-carotene, and both soy isoflavones exhibited prooxidant activities in SFE emulsions. Because of their ability to exhibit prooxidant activity under certain conditions, manufacturers must experiment with these compounds before adding them to SL-based products as functional ingredients.