Supervising for Home Safety Program: A Randomized Controlled Trial (RCT) Testing Community-Based Group Delivery.

Objective: The individually delivered Supervising for Home Safety (SHS) program improves caregivers' injury-related beliefs and supervision practices. The current randomized controlled trial used a group delivery in a community setting and assessed program impact, feasibility, and acceptance. Methods: Caregivers of 2-5-year-olds were randomized to receive either the SHS or an attention-matched control program. Results: In the SHS group only, there were increases from baseline to postintervention in the following: beliefs about children's vulnerability to injury, caregiver preventability of injuries, and self-efficacy to do so; readiness for change in supervision; and watchful supervision. Face-to-face recruitment by staff at community organizations proved most successful. Caregivers' satisfaction ratings were high, as was caregiver engagement (95% completed at least seven of the nine sessions). Conclusion: The SHS program can be delivered to groups of caregivers in community settings, is positively received by caregivers, and produces desirable changes that can be expected to improve caregivers' home safety practices.

Examining the influence of a text message-based sleep and physical activity intervention among young adult smokers in the United States.

BACKGROUND: Sleep and physical activity are two health behaviors associated with improved smoking cessation outcomes. Text message-based interventions have previously been used to promote physical activity and smoking cessation; however, this type of intervention has not targeted sleep habits. This study examined the effectiveness of a text message-based active control intervention in improving sleep and physical activity habits among a U.S. national sample of young adult smokers participating in a smoking cessation intervention. METHODS: This study was a secondary analysis of data from the Stop My Smoking USA randomized controlled trial. Baseline and 3-month follow-up data were collected from 116 young adult smokers (mean age 21.8 years, SD = 2.1) who were randomized at a 2:1 ratio to receive a 6-week text messaging program focused on either smoking cessation (n = 72), or improving sleep and physical activity (n = 44). Three main outcomes were assessed: 1) sleep quantity (on work/school nights, and non-work/non-school nights), 2) sleep quality, and 3) physical activity at follow-up. Multivariable linear regression analysis was used to quantify the differences in these outcomes between the groups. To identify possible effect modification by baseline sleep and physical activity, the sample was stratified by indicators defined for both of these variables. RESULTS: At follow-up, sleep quantity and quality were similar for participants in the smoking cessation and sleep/activity groups when assessed among the total sample and those sleeping ≥6 hours/night at baseline. Among short sleepers (<6 hours/night at baseline), sleep quantity on work/school nights improved for those receiving sleep/activity messages compared to those receiving smoking cessation messages, after adjusting for covariates (^ß = 1.373, 95% CI [0.262, 2.484]; p = 0.02). Physical activity at follow-up was similar for the two groups, when examined among the total sample and when stratified by baseline activity level. CONCLUSIONS: This study provides preliminary evidence that a text message-based intervention may be a promising approach for improving sleep quantity among young adult smokers who are short sleepers and interested in quitting smoking. Similar programs should be further explored as a novel approach for improving sleep habits among individuals with insufficient sleep. TRIAL REGISTRATION: ClinicalTrials.gov NCT01516632.

Investigating the candidacy of LPS-based glycoconjugates to prevent invasive meningococcal disease: conjugates based on core oligosaccharides.

In this study we have prepared glycoconjugates with core oligosaccharides (OS) from the lipopolysaccharide (LPS) of Neisseria meningitidis, thus avoiding the neo-epitopes of the deacylated lipid A region of the derived LPS molecule identified in our previous studies. A comprehensive investigation was performed with glycoconjugates prepared from the most extended to the most truncated core OS still maintaining the conserved inner core epitope. As previously, we have established reproducible bactericidal killing of the homologous antigen elaborating strain, but a failure to kill wild-type strains. In these studies it was evident that the linker molecules used in the conjugation methodologies were dominating the immune response. However, when galE core OS based conjugates were prepared without utilizing linkers, via direct reductive amination, we failed to generate an immune response to even the homologous antigen. We also identified that immunisation with the galE antigen via linker methodologies provoked an immune response that was dependent upon key residues of the conserved inner core OS structure, whereas the immune responses to lgtB and lgtA antigens did not involve the inner core OS. This comprehensive study has, despite our best efforts, cast significant doubt as to the utility of the conserved inner core region of the meningococcal LPS as a potential vaccine antigen.

Parents and Tots Together: Pilot randomized controlled trial of a family-based obesity prevention intervention in Canada.

OBJECTIVE: To test the feasibility, acceptability and preliminary impact of Parents and Tots Together (PTT), a family-based obesity prevention intervention, in Canada. PARTICIPANTS: Canadian parents of preschoolers (aged 2-5 years). SETTING: Ontario Early Years centres in southwestern Ontario. INTERVENTION: A pilot randomized controlled trial involving 48 parents who received either the PTT intervention (n = 27) or an attention-matched control home safety intervention (n = 21). To evaluate the feasibility of PTT, we assessed participant retention and outcome evaluation completion rates. To evaluate acceptability, we assessed program attendance and parents' responses to program satisfaction surveys. To evaluate preliminary impact, we assessed children's body mass index (BMI) at baseline, after intervention (end of 9-week intervention) and at 9-month follow-up. As well, at each time point, parents completed surveys assessing stress and self-efficacy related to parenting, children's sleep, activity, TV viewing and diet. OUTCOMES: Retention rates were high in the intervention (93%) and control (84%) study arms, and 87% of parents reported that they would highly recommend PTT to a friend. At 9-month follow-up, intervention parents reported lower parenting stress (ßï¼¾ = 15.83, 95% confidence interval [CI] -29.57, -2.07, p = 0.02) and greater self-efficacy in managing their child's behaviour (ßï¼¾ = 0.16, 95% CI 0.002, 0.33, p = 0.05) than control parents. PTT had minimal influence on children's weight-related behaviours and BMI. CONCLUSIONS: The results suggest that PTT can feasibly be implemented and tested in the Canadian context. Preliminary impact results suggest that the program may be effective in changing general parenting; however, program content should be modified to adequately address children's weight-related behaviours.

Granulocyte colony-stimulating factor for poor graft function after allogeneic stem cell transplantation: 3 days of G-CSF identifies long-term responders.

Poor graft function (PGF) is a frequent cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). To study the value of granulocyte colony-stimulating factor (G-CSF) in PGF, we retrospectively analyzed 81 episodes of PGF in 66 patients transplanted from 01/94 to 01/99 from an HLA-identical sibling (n = 45) or an unrelated (n = 21) donor. Median age was 29 years, 55 patients had malignancies. A total of 11 patients received a CD34+ selected graft. Viral infections (25%), myelotoxic drug (33%), fungal/bacterial infections (14%), and GVHD (31%) were present before PGF diagnosis. Median time from allo-HSCT to PGF was 75 (25-474) days. All patients were treated with G-CSF. In 77/81 episodes, there was a response that was sustained in 57. A total of 27 patients presented an increase of white cell count (WBC) >0.1 x 10(9)/l after 3 days of G-CSF. The 5-year survival was 37% and was significantly better in patients with increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (65 vs 18%, P < 0.0001). In multivariate analysis, increased WBC > 0.1 x 10(9)/l after 3 days of G-CSF (P = 0.002) was associated with better survival, while BuCy-based conditioning (P = 0.02) and GVHD (P = 0.005) were associated with higher risk of death. In conclusion, hematological response after 3 days with G-CSF predicted a better survival for patients with PGF after allo-SCT.

Translation fidelity in the aging mammal: studies with an accurate in vitro system on aged rats.

The accuracy of poly(U) translation was measured in the post-mitochondrial supernatant from whole brain of 7- and 33-month-old Fischer 344 rats. Measurements were made: under in vitro conditions in which translation fidelity was similar to what is known about the accuracy of translation in vivo; and under stresses of varying Mg2+ concentrations (3-12 mM), pH (6.6-8.4), temperature (26-42 degrees C) and in the presence or absence of 2.4% ethanol. No significant difference could be detected between the responses of old and young extracts, the activities of their Phe- and Leu-tRNA synthetases, and their endogenous amounts of Phe-tRNA and Leu-tRNA, despite the fact that the rats studied corresponded in age (by actuarial criteria) to 90-year-old human beings. The accuracy of poly(U) translation was also studied: in liver and hippocampus extracts from 7- and 33-month-old rats; and in brain extracts from 3- and 29-month-old rats. The results were similar to those obtained in brain extracts from 7-month-old rats. Explanations are provided for the inconsistencies which exist in the literature regarding the effect of aging on the accuracy of protein synthesis. It is shown that the inconsistencies are likely to reflect inadequate methodology in three previous studies rather than biological diversity in the control of translation fidelity in aged animals.

Poster - Thur Eve - 38: Review of couch parameters using an FMEA.

To improve patient safety during positioning, we undertook a systematic review of the processes used by our center to obtain couch positions. We used a Failure Mode and Effects Analysis (FMEA) framework and fifteen different possible failures were identified and rated. The three major failures were 1) Loss of planned couch position and bias from the previous day's couch position, 2) DICOM origin or isocenter is different between two plans (imaging or treatment), and 3) Patient shift in opposite direction than intended. The main effect of these failures was to cause an override of couch parameters. Based on these results, we modified our processes, introduced new QA and software checks and developed new tolerance tables so as to improve system robustness and increase our success rate at catching failures before they can affect the patient. It has been a year since we made these modifications. Based on our results, we have reduced the number of overrides at our center from a maximum of 20.5% to a maximum of 6.3%, with an average at 4% of daily treatments. Our results suggest that FMEA is an effective tool in improving treatment quality that could be used in other centers.

Association of drug metabolism gene polymorphisms with toxicities, graft-versus-host disease and survival after HLA-identical sibling hematopoietic stem cell transplantation for patients with leukemia.

Individual differences in drug efficacy or toxicity can be influenced by genetic factors. We investigated whether polymorphisms of pharmacogenes that interfere with metabolism of drugs used in conditioning regimen and graft-versus-host disease (GvHD) prophylaxis could be associated with outcomes after HLA-identical hematopoietic stem cell transplantation (HSCT). Pharmacogenes and their polymorphisms were studied in 107 donors and patients with leukemia receiving HSCT. Candidate genes were: P450 cytochrome family (CYP2B6), glutathione-S-transferase family (GST), multidrug-resistance gene, methylenetetrahydrofolate reductase (MTHFR) and vitamin D receptor (VDR). The end points studied were oral mucositis (OM), hemorrhagic cystitis (HC), toxicity and venoocclusive disease of the liver (VOD), GvHD, transplantation-related mortality (TRM) and survival. Multivariate analyses, using death as a competing event, were performed adjusting for clinical factors. Among other clinical and genetic factors, polymorphisms of CYP2B6 genes that interfere with cyclophosphamide metabolism were associated with OM (recipient CYP2B6(*)4; P=0.0067), HC (recipient CYP2B6(*)2; P=0.03) and VOD (donor CYP2B6(*)6; P=0.03). Recipient MTHFR polymorphisms (C677T) were associated with acute GvHD (P=0.03), and recipient VDR TaqI with TRM and overall survival (P=0.006 and P=0.04, respectively).Genetic factors that interfere with drug metabolisms are associated with treatment-related toxicities, GvHD and survival after HLA-identical HSCT in patients with leukemia and should be investigated prospectively.

Comparative analysis of translation accuracy in an Escherichia coli and a mammalian cell-free system.

The effect of environmental stress on the accuracy of protein synthesis in an Escherichia coli and a rat brain cell-free system was investigated. Poly-U was translated in a rat brain and an E. coli cell-free extract under identical ionic conditions. The fidelity of translation, both in the E. coli and the rat brain extracts, was commensurate with what is known about the accuracy of translation in vivo. The incorporation of phenylalanine (code: UUU) and leucine (code: CUU, UUG or A) was measured at various Mg2+ concentrations (3 to 22 mM), various pH's (6.6 to 8.6), various temperatures (23 to 42 degrees C), and in the presence or absence of 2.4% (v/v) ethanol. It was observed that (i) the accuracy of translation was generally higher in extracts from E. coli than from rat brain, and (ii) relative to that in E. coli, the translation fidelity in rat brain extracts was about 2 times more sensitive to ethanol, at least 5 times more sensitive to temperature, and at least 50 times more sensitive to pH. It was found that this differential sensitivity was not due to a differential behavior of the bacterial and the mammalian aminoacyl-tRNA synthetases under stress, but rather to the process of chain elongation itself. It is concluded that the accuracy of protein synthesis is more resistant to environmental stress in E. coli extracts than in extracts from at least one mammalian tissue.

Mistranslation in twelve Escherichia coli ribosomal proteins. Cysteine misincorporation at neutral amino acid residues other than tryptophan.

The misincorporation of cysteine (codon: UGU/C) into twelve ribosomal proteins devoid of cysteine has been studied. Although it is generally assumed that cysteine is misincorporated at arginine and tryptophan residues (codons: CGU/U and UGG respectively), our results are consistent with the idea that cysteine is also misincorporated at phenylalanine residues (codon: UUU/C) through a second-position C:U mismatch. Cysteine was found in ribosomal proteins L29, L32/L33 and S10, under conditions where only its misincorporation at neutral residues was measured. Since these proteins contain no tryptophan, the date imply that cysteine has replaced a neutral amino acid other than tryptophan. Because there was a statistically significant correlation between the total level of cysteine in the twelve proteins under study and their content of phenylalanine and arginine residues, we conclude that there is a likelihood of cysteine misincorporation at phenylalanine residues, in addition to its misincorporation at arginine and tryptophan residues. Our measurements are consistent with the existence of a cluster of ribosomal proteins having an average mistranslation frequency of 2.5 X 10(-4)/residue and another having an average mistranslation frequency of 10(-3)/residue. There was three times less cysteine misincorporated into ribosomal protein L1 than into L7/L12, although the L1 mRNA contains eleven CGU/C codons and four UUU/C codons while the L7/L12 mRNA contains only one arginine and two phenylalanine codons (both proteins are free of tryptophan). Furthermore, the mRNAs for both L1 and L7/L12 contain a CGU codon located in the context GUA-codon-GG and there was as much cysteine incorporated at this codon in L7/L12 [Bouadloun, F., Donner, D. and Kurland, C.G. (1983) EMBO J. 2, 1351-1356] than in the whole of L1. This suggests that, relatively speaking, little cysteine is to be found at the phenylalanine and the other ten arginine positions of L1 and that the phenylalanine residues of L7/L12 are particularly error-prone.

Effect of ethanol, phenol, formamide, dimethyl sulfoxide, paromomycin, and deuterium oxide on the fidelity of translation in a brain cell-free system.

The effects of six different agents (ethanol, phenol, formamide, dimethyl sulfoxide, heavy water, and a misreading-inducing antibiotic, paromomycin) on the activity and the accuracy of poly(U) translation have been compared under a range (2.5-12 mM) of Mg2+ concentrations in a rat brain cell-free system. The effect of most of these agents was remarkably sensitive to the Mg2+ concentration under which the assay was made. Ethanol decreased the fidelity of translation, and the efficiency of ethanol was increased 3-10-fold by higher Mg2+ concentrations. The effect of paromomycin was identical with that of ethanol, despite its very different structure. Formamide, a "RNA denaturant", increased the accuracy of translation under all Mg2+ concentrations tested. Dimethyl sulfoxide, another type of RNA denaturant, decreased the accuracy of translation under all Mg2+ concentrations tested. Phenol increased the accuracy of translation at high Mg2+ concentrations but decreased it at low Mg2+ concentrations. D2O did not change to any appreciable extent the accuracy of translation, at all the Mg2+ concentrations used. There exists a cooperativity between the effects of Mg2+ and ethanol, Mg2+ and paromomycin, and Mg2+ and dimethyl sulfoxide on the fidelity of translation; no such cooperativity was detected between Mg2+ and formamide and between Mg2+ and D2O. The differential effects of dimethyl sulfoxide and formamide are interpreted in terms of their different dielectric constants. The dielectric constant of dimethyl sulfoxide is higher than that of water, while that of formamide is low er.

The activity of cholesterol ester hydrolase in the enzymatic determination of cholesterol: comparison of five enzymes obtained commercially.

The use of five cholesterol ester hydrolases (CEH), numbered 1 to 5, for the enzymatic determination of total cholesterol of human and rat serum are compared. All CEH gave approximately the same value (no statistical difference) for human serum. However, when rat serum cholesterol was determined, CEH-2 yielded a value significantly lower when compared to the four other CEH. The ability of each CEH to hydrolyze individual cholesterol esters was tested. During a 15-min incubation, all CEH were capable of hydrolyzing nearly 100% of cholesteryl oleate and linoleate. In contrast, the hydrolysis of cholesteryl arachidonate was only partial and varied from 20 to 80% depending on the CEH used. The highest hydrolysis was obtained by CEH-1 while the value given by CEH-2 was only 22% of that obtained by CEH-1. The rate of hydrolysis of cholesteryl arachidonate differed markedly among the CEH. The CEH-2-hydrolyzed the cholesteryl arachidonate at a rate seven times lower than the rate obtained with CEH-1. The data suggest that, Under our incubation conditions, CEH-2 did not properly hydrolyze the cholesteryl arachidonate. This phenomenon may be crucial whenever total cholesterol has to be determined enzymatically in the serum of species that contain large amount of cholesteryl arachidonate such as rat, mouse, or dog serum.