126 research outputs found

    Vermont Restaurant Owner & Manager Perspectives on Creating Heart-Healthy Kids Meals

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    Introduction: The prevalence of sugar sweetened beverages and fried foods combined with a lack of healthy children’s menu options has contributed to the obesity epidemic among young Americans. Recent legislation in New York City and San Francisco instituted strict nutritional requirements on children’s menu items. We performed a cross-sectional study that focused on independently owned restaurants with printed children’s menus in Vermont. We investigated the nutritional content of children’s menu items, restaurant owner and manager perspectives on customer ordering habits, and barriers that restaurants would face if they made children’s menu items healthier.https://scholarworks.uvm.edu/comphp_gallery/1220/thumbnail.jp

    Self-Esteem and Feelings of Community Connectedness of At-Risk Adolescents Attending Community-Based Afterschool Programs

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    This research investigated the relationship between adolescent afterschool program attendance, self-esteem and feelings of community connectedness. Thirty-nine of the 61 at-risk adolescents enrolled in two federally funded, community based afterschool programs participated in the study. Participants completed a 10-item self-esteem questionnaire and a 5-item section of the Youth Involved in Community Issues Survey (YICI) to measure perceptions of community connectedness. Attendance records were also collected from the sites. Data were analyzed using Pearson Correlations. Results indicated that there was not a significant relationship between the total variables. The individual item analysis, however, did find a significant relationship between adolescent community connectedness and self esteem items. Findings suggest that there is a relationship to be explored and strengthened through means of community outreach for adolescents. Conclusions from this study have important implications for youth practice. Specifically, program leaders need to help adolescents get involved in the community as contributing members

    The role of the Cucumber mosaic virus 2b protein in viral movement and symptom induction

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    The Cucumber mosaic virus (CMV) 2b protein is a counter-defense factor and symptom determinant. Conserved domains in the 2b protein sequence were mutated in the 2b gene of strain Fny-CMV. The effects of these mutations were assessed by infection of Nicotiana tabacum, N. benthamiana, and Arabidopsis thaliana (ecotype Col-0) with mutant viruses and by expression of mutant 2b transgenes in A. thaliana. We confirmed that two nuclear localization signals were required for symptom induction and found that the N-terminal domain was essential for symptom induction. The C-terminal domain and two serine residues within a putative phosphorylation domain modulated symptom severity. Further infection studies were conducted using Fny-CMVΔ2b, a mutant that cannot express the 2b protein and that induces no symptoms in N. tabacum, N. benthamiana, or A. thaliana ecotype Col-0. Surprisingly, in plants of A. thaliana ecotype C24, Fny-CMVΔ2b induced severe symptoms similar to those induced by the wild-type virus. However, C24 plants infected with the mutant virus recovered from disease while those infected with the wild-type virus did not. Expression of 2b transgenes from either Fny-CMV or from LS-CMV (a mild strain) in Col-0 plants enhanced systemic movement of Fny-CMVΔ2b and permitted symptom induction by Fny-CMVΔ2b. Taken together, the results indicate that the 2b protein itself is an important symptom determinant in certain hosts. However, they also suggest that the protein may somehow synergize symptom induction by other CMV-encoded factors

    Self-Esteem and Feelings of Community Connectedness of At-Risk Adolescents Attending Community-Based Afterschool Programs

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    This research investigated the relationship between adolescent afterschool program attendance, self-esteem and feelings of community connectedness. Thirty-nine of the 61 at-risk adolescents enrolled in two federally funded, community based afterschool programs participated in the study. Participants completed a 10-item self-esteem questionnaire and a 5-item section of the Youth Involved in Community Issues Survey (YICI) to measure perceptions of community connectedness. Attendance records were also collected from the sites. Data were analyzed using Pearson Correlations. Results indicated that there was not a significant relationship between the total variables. The individual item analysis, however, did find a significant relationship between adolescent community connectedness and self esteem items. Findings suggest that there is a relationship to be explored and strengthened through means of community outreach for adolescents. Conclusions from this study have important implications for youth practice. Specifically, program leaders need to help adolescents get involved in the community as contributing members

    Results of a phase I/II multi-center investigation of udenafil in adolescents after fontan palliation

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    BACKGROUND: The Fontan operation results in a circulation that is dependent on low pulmonary vascular resistance to maintain an adequate cardiac output. Medical therapies that lower pulmonary vascular resistance may augment cardiac output and improve long-term outcomes. OBJECTIVES: This phase I/II clinical trial conducted by the Pediatric Heart Network was designed to evaluate short-term safety, pharmacokinetics (PK), and preliminary efficacy of udenafil in adolescents following Fontan. METHODS: A 5-day dose-escalation trial was conducted in five study cohorts of six subjects each (37.5, 87.5, and 125 mg daily, 37.5 and 87.5 mg by mouth twice daily). A control cohort with 6 subjects underwent exercise testing only. Adverse events (AEs) were recorded, PK samples were collected on study days six through eight, and clinical testing was performed at baseline and day five. RESULTS: The trial enrolled 36 subjects; mean age 15.8 years (58% male). There were no significant differences in subject characteristics between cohorts. No drug-related serious AEs were reported during the study period; 24 subjects had AEs possibly or probably related to study drug. Headache was the most common AE, occurring in 20 of 30 subjects. The 87.5 mg bid cohort was well tolerated, achieved the highest maximal concentration (506 ng/mL) and the highest average concentration over the dosing interval (279 ng/mL), and was associated with a suggestion of improvement in myocardial performance. Exercise performance did not improve in any of the dosing cohorts. CONCLUSIONS: Udenafil was well-tolerated at all dosing levels. The 87.5 mg bid cohort achieved the highest plasma drug level and was associated with a suggestion of improvement in myocardial performance. These data suggest that the 87.5 mg bid regimen may be the most appropriate for a Phase III clinical trial

    An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

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    Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

    Protein complexes are under evolutionary selection to assemble via ordered pathways

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    Is the order in which proteins assemble into complexes important for biological function? Here, we seek to address this by searching for evidence of evolutionary selection for ordered protein complex assembly. First, we experimentally characterize the assembly pathways of several heteromeric complexes and show that they can be simply predicted from their three-dimensional structures. Then, by mapping gene fusion events identified from fully sequenced genomes onto protein complex assembly pathways, we demonstrate evolutionary selection for conservation of assembly order. Furthermore, using structural and high-throughput interaction data, we show that fusion tends to optimize assembly by simplifying protein complex topologies. Finally, we observe protein structural constraints on the gene order of fusion that impact the potential for fusion to affect assembly. Together, these results reveal the intimate relationships among protein assembly, quaternary structure, and evolution and demonstrate on a genome-wide scale the biological importance of ordered assembly pathways

    Prevalence and architecture of de novo mutations in developmental disorders.

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    The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year
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