Pilot evaluation of a walking school bus program in a low-income, urban community

<p>Abstract</p> <p>Background</p> <p>To evaluate the impact of a walking school bus (WSB) program on student transport in a low-income, urban neighborhood.</p> <p>Methods</p> <p>The design was a controlled, quasi-experimental trial with consecutive cross-sectional assessments. The setting was three urban, socioeconomically disadvantaged, public elementary schools (1 intervention vs. 2 controls) in Seattle, Washington, USA. Participants were ethnically diverse students in kindergarten-5^thgrade (aged 5–11 years). The intervention was a WSB program consisting of a part-time WSB coordinator and parent volunteers. Students' method of transportation to school was assessed by a classroom survey at baseline and one-year follow-up. The Pearson Chi-squared test compared students transported to school at the intervention versus control schools at each time point. Due to multiple testing, we calculated adjusted p-values using the Ryan-Holm stepdown Bonferroni procedure. McNemar's test was used to examine the change from baseline to 12-month follow-up for walking versus all other forms of school transport at the intervention or control schools.</p> <p>Results</p> <p>At baseline, the proportions of students (n = 653) walking to the intervention (20% +/- 2%) or control schools (15% +/- 2%) did not differ (<it>p </it>= 0.39). At 12-month follow up, higher proportions of students (n = 643, <it>p </it>= 0.001)) walked to the intervention (25% +/- 2%) versus the control schools (7% +/- 1%). No significant changes were noted in the proportion of students riding in a car or taking the school bus at baseline or 12-month follow up (all <it>p </it>> 0.05). Comparing baseline to 12-month follow up, the numbers of students who walked to the intervention school increased while the numbers of students who used the other forms of transport did not change (<it>p </it>< 0.0001). In contrast, the numbers of students who walked to the control schools decreased while the numbers of students who used the other forms of transport did not change (<it>p </it>< 0.0001).</p> <p>Conclusion</p> <p>A WSB program is a promising intervention among urban, low-income elementary school students that may promote favorable changes toward active transport to school.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00402701</p

Historical trends in survival of hospitalized heart failure patients: 2000 versus 1995

BACKGROUND: Population-based secular trends in survival of patients with congestive heart failure (CHF) are central to public health research on the burden of the syndrome. METHODS: Patients 35–79 years old with a CHF discharge code in 1995 or 2000 were identified in 22 Minneapolis-St. Paul hospitals. A sample of the records was abstracted (50% of 1995 records; 38% of 2000 records). A total of 2,257 patients in 1995 and 1,825 patients in 2000 were determined to have had a CHF-related hospitalization. Each patient was followed for one year to ascertain vital status. RESULTS: The risk profile of the 2000 patient cohort was somewhat worse than that of the 1995 cohort in both sex groups, but the distributions of age and left ventricular ejection fraction were similar. Within one year of admission in 2000, 28% of male patients and 27% of female patients have died, compared to 36% and 27% of their counterparts in 1995, respectively. In various Cox regression models the average year effect (2000 vs. 1995) was around 0.75 for men and 0.95 to 1.00 for women. The use of angiotensin converting-enzyme inhibitors and beta-blockers was associated with substantially lower hazard of death during the subsequent year. CONCLUSION: Survival of men who were hospitalized for CHF has improved during the second half of the 1990s. The trend in women was very weak, compatible with little to no change. Documented benefits of angiotensin converting-enzyme inhibitors and beta-blockers were evident in these observational data in both men and women

Validity of instruments to assess students' travel and pedestrian safety

<p>Abstract</p> <p>Background</p> <p>Safe Routes to School (SRTS) programs are designed to make walking and bicycling to school safe and accessible for children. Despite their growing popularity, few validated measures exist for assessing important outcomes such as type of student transport or pedestrian safety behaviors. This research validated the SRTS school travel survey and a pedestrian safety behavior checklist.</p> <p>Methods</p> <p>Fourth grade students completed a brief written survey on how they got to school that day with set responses. Test-retest reliability was obtained 3-4 hours apart. Convergent validity of the SRTS travel survey was assessed by comparison to parents' report. For the measure of pedestrian safety behavior, 10 research assistants observed 29 students at a school intersection for completion of 8 selected pedestrian safety behaviors. Reliability was determined in two ways: correlations between the research assistants' ratings to that of the Principal Investigator (PI) and intraclass correlations (ICC) across research assistant ratings.</p> <p>Results</p> <p>The SRTS travel survey had high test-retest reliability (κ = 0.97, n = 96, p < 0.001) and convergent validity (κ = 0.87, n = 81, p < 0.001). The pedestrian safety behavior checklist had moderate reliability across research assistants' ratings (ICC = 0.48) and moderate correlation with the PI (r = 0.55, p =< 0.01). When two raters simultaneously used the instrument, the ICC increased to 0.65. Overall percent agreement (91%), sensitivity (85%) and specificity (83%) were acceptable.</p> <p>Conclusions</p> <p>These validated instruments can be used to assess SRTS programs. The pedestrian safety behavior checklist may benefit from further formative work.</p

NeuN/Rbfox3 Nuclear and Cytoplasmic Isoforms Differentially Regulate Alternative Splicing and Nonsense-Mediated Decay of Rbfox2

Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45–50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45–50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism

NeuN/Rbfox3 Nuclear and Cytoplasmic Isoforms Differentially Regulate Alternative Splicing and Nonsense-Mediated Decay of Rbfox2

Anti-NeuN (Neuronal Nuclei) is a monoclonal antibody used extensively to specifically detect post-mitotic neurons. Anti-NeuN reactivity is predominantly nuclear; by western it detects multiple bands ranging in molecular weight from 45 kDa to >75 kDa. Expression screening putatively identified R3hdm2 as NeuN; however immunoprecipitation and mass spectrometry of the two major NeuN species at 45–50 kDa identified both as the RNA binding protein Rbfox3 (a member of the Fox family of alternative splicing factors), confirming and extending the identification of the 45 kDa band as Rbfox3 by Kim et al. Mapping of the anti-NeuN reactive epitopes in both R3hdm2 and Rbfox3 reveals a common proline- and glutamine-rich domain that lies at the N-terminus of the Rbfox3 protein. Our data suggests that alternative splicing of the Rbfox3 pre-mRNA itself leads to the production of four protein isoforms that migrate in the 45–50 kDa range, and that one of these splicing choices regulates Rbfox3/NeuN sub-cellular steady-state distribution, through the addition or removal of a short C-terminal extension containing the second half of a bipartite hydrophobic proline-tyrosine nuclear localization signal. Rbfox3 regulates alternative splicing of the Rbfox2 pre-mRNA, producing a message encoding a dominant negative form of the Rbfox2 protein. We show here that nuclear Rbfox3 isoforms can also enhance the inclusion of cryptic exons in the Rbfox2 mRNA, resulting in nonsense-mediated decay of the message, thereby contributing to the negative regulation of Rbfox2 by Rbfox3 through a novel mechanism

Is There Any Association between Use of Smokeless Tobacco Products and Coronary Heart Disease in Bangladesh?

BACKGROUND: Most epidemiological studies exploring the association between smokeless tobacco (SLT) use and coronary heart disease (CHD) have been in Western populations, and have focused on SLT products used in those countries. Few studies come from South Asian countries. Our objective was to determine the association between SLT use and CHD among non-smoking adults in Bangladesh. METHODS: A matched case-control study of non-smoking Bangladeshi adults aged 40–75 years was conducted in 2010. Incident cases of CHD were selected from two cardiac hospitals. Community controls, matched to CHD cases, were selected from neighbourhoods, and hospital controls were selected from outpatient departments of the same hospitals. The Rose Angina Questionnaire (RAQ) was also used to re-classify cases and controls. RESULTS: The study enrolled 302 cases, 1,208 community controls and 302 hospital controls. Current use was higher among community controls (38%) compared to cases (33%) and hospital controls (32%). Current use of SLT was not significantly associated with an increased risk of CHD when community controls were used (adjusted OR 0.87, 95% CI 0.63–1.19), or when hospital controls were used (adjusted OR 1.00, 95% CI 0.63–1.60), or when both control groups were combined (adjusted OR 1.00, 95% CI 0.74–1.34). Risk of CHD did not increase with use of individual types except gul, frequency, duration, past use of SLT products, or using the RAQ to re-classify cases and controls. There was a significant association between gul use and CHD when both controls were combined (adjusted OR 2.93, 95% CI 1.28–6.70). CONCLUSIONS: There was no statistically significant association between SLT use in general and CHD among non-smoking adults in Bangladesh. Further research on the association between gul use and CHD in Bangladesh along with SLT use and CHD in other parts of the subcontinent will guide public health policy and interventions that focus on SLT-related diseases.Muhammad Azia Rahman, Nicola Spurrier, Mohammad Afzal Mahmood, Mahmudur Rahman, Soehl Reza Choudhury and Stephen Leede

Mural Cell Associated VEGF Is Required for Organotypic Vessel Formation

Background: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells) and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. Methods and Findings: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. Conclusions: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation

The Heterotrimeric Laminin Coiled-Coil Domain Exerts Anti-Adhesive Effects and Induces a Pro-Invasive Phenotype

Laminins are large heterotrimeric cross-shaped extracellular matrix glycoproteins with terminal globular domains and a coiled-coil region through which the three chains are assembled and covalently linked. Laminins are key components of basement membranes, and they serve as attachment sites for cell adhesion, migration and proliferation. In this work, we produced a recombinant fragment comprising the entire laminin coiled-coil of the α1-, β1-, and γ1-chains that assemble into a stable heterotrimeric coiled-coil structure independently of the rest of the molecule. This domain was biologically active and not only failed to serve as a substrate for cell attachment, spreading and focal adhesion formation but also inhibited cell adhesion to laminin when added to cells in a soluble form at the time of seeding. Furthermore, gene array expression profiling in cells cultured in the presence of the laminin coiled-coil domain revealed up-regulation of genes involved in cell motility and invasion. These findings were confirmed by real-time quantitative PCR and zymography assays. In conclusion, this study shows for the first time that the laminin coiled-coil domain displays anti-adhesive functions and has potential implications for cell migration during matrix remodeling