Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-Carboximidamides

The over production of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) owing to the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamides (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why 2 commercially developed T2C inhibitors exhibit selectivity for human nNOS over human eNOS. As with many of the aminopyridine inhibitors, a critical active site Asp residue in nNOS vs Asn in eNOS is largely responsible for controlling selectivity. We also present thermodynamic integration results to better understand the change in pKa and thus charge of inhibitors once bound to the active site. In addition, relative free energy calculations underscore the importance of enhanced electrostatic stabilization of inhibitors bound to the nNOS active site compared to eNOS

Park characteristics, use, and physical activity: A review of studies using SOPARC (System for Observing Play and Recreation in Communities)

The System for Observing Play and Recreation in Communities (SOPARC) can obtain information on park users and their physical activity using momentary time sampling. We conducted a literature review of studies using the SOPARC tool to describe the observational methods of each study, and to extract public park use overall and by demographics and physical activity levels. We searched PubMed, Embase, and SPORTDiscus for full-length observational studies published in English in peer-reviewed journals through 2014. Twenty-four studies from 34 articles were included. The number of parks observed per study ranged from 3 to 50. Most studies observed parks during one season. The number of days parks were observed ranged from 1 to 16, with 16 studies observing 5 or more days. All studies included at least one weekday and all but two included at least one weekend day. Parks were observed from 1 to 14 times/day, with most studies observing at least 4 times/day. All studies included both morning and afternoon observations, with one exception. There was a wide range of park users (mean 1.0 to 152.6 people/park/observation period), with typically more males than females visiting parks and older adults less than other age groups. Park user physical activity levels varied greatly across studies, with youths generally more active than adults and younger children more active than adolescents. SOPARC was adapted to numerous settings and these review results can be used to improve future studies using the tool, demonstrate ways to compare park data, and inform park promotions and programming

Using Systematic Observations to Understand Conditions that Promote Interracial Experiences in Neighbourhood Parks

We analysed observations from 31 neighbourhood parks, with each park mapped into smaller target areas for study, across five US cities generated using the System for Observing Play and Recreation in the Community (SOPARC). In areas where at least two people were observed, less than one-third (31.6%) were populated with at least one white and one non-white person. Park areas that were supervised, had one or more people engaged in vigorous activity, had at least one male and one female present, and had one or more teens present were significantly more likely to involve interracial groups (p \u3c 0.01 for each association). Observations in parks located in interracial neighbourhoods were also more likely to involve interracial groups (p \u3c 0.05). Neighbourhood poverty rate had a significant and negative relationship with the presence of interracial groups, particularly in neighbourhoods that are predominantly non-white. Additional research is needed to confirm the impact of these interactions. Urban planning and public health practitioners should consider the health benefits of interracial contact in the design and programming of neighbourhood parks

Physical and Social Contexts of Physical Activities Among Adolescent Girls

Background: With limited opportunities for physical activity during school hours, it is important to understand the contexts of physical activities done outside of school time. Given the importance of physical and social aspects of environments, the purpose of this study was to describe where and with whom girls participate in physical activities outside of school. Methods: Participants were 1925 sixth-grade girls in the Trial of Activity for Adolescent Girls (TAAG). At baseline, they completed a 3-day physical activity recall (3DPAR), reporting the main activity performed during 30-minute intervals and the physical and social contexts of physical activities. Results: The most frequently reported physical activities done outside of school time were house chores, walking (for transportation or exercise), dance, basketball, playing with younger children, and running or jogging. The most common location for these activities was at home or in the neighborhood. With the exception of household chores, these activities were typically done with at least one other person. Conclusions: Interventions that promote physical activities that can be done at or around home or developing supportive social networks for physical activity would be consistent with the current physical activity contexts of adolescent girls

Longitudinal Analysis of Adolescent Girls' Activity Patterns: Understanding the Influence of the Transition to Licensure

The proportion of teens and young adults with driver's licenses has declined sharply in many industrialized countries including the United States. Explanations for this decline have ranged from the introduction of graduated driver licensing programs to the increase in online social interaction. We used a longitudinal cohort study of teenage girls in San Diego and Minneapolis to evaluate factors associated with licensure and whether teens' travel patterns become more independent as they aged. We found that licensure depended not only on age, but on race and ethnicity as well as variables that correlate with household income. Results also showed evidence that teen travel became more independent as teen's age, and that acquiring a license is an important part of this increased independence. However, we found limited evidence that teen's travel-activity patterns changed as a result of acquiring a driver's license. Rather, teen independence resulted in less parental chauffeuring, but little shift in travel patterns. For the larger debate on declining Millennial mobility, our results suggest the need for more nuanced attention to variation across demographic groups and consideration of the equity implications if declines in travel and licensure are concentrated in low-income and minority populations

Structural Basis for Isoform Selective Nitric Oxide Synthase Inhibition by Thiophene-2-Carboximidamides

The over production of nitric oxide in the brain by neuronal nitric oxide synthase (nNOS) is associated with a number of neurodegenerative diseases. Although inhibiting nNOS is an important therapeutic goal, it is important not to inhibit endothelial NOS (eNOS) owing to the critical role played by eNOS in maintaining vascular tone. While it has been possible to develop nNOS selective aminopyridine inhibitors, many of the most potent and selective inhibitors exhibit poor bioavailability properties. Our group and others have turned to more biocompatible thiophene-2-carboximidamides (T2C) inhibitors as potential nNOS selective inhibitors. We have used crystallography and computational methods to better understand how and why 2 commercially developed T2C inhibitors exhibit selectivity for human nNOS over human eNOS. As with many of the aminopyridine inhibitors, a critical active site Asp residue in nNOS vs Asn in eNOS is largely responsible for controlling selectivity. We also present thermodynamic integration results to better understand the change in pKa and thus charge of inhibitors once bound to the active site. In addition, relative free energy calculations underscore the importance of enhanced electrostatic stabilization of inhibitors bound to the nNOS active site compared to eNOS

The First National Study of Neighborhood Parks

An extensive infrastructure of neighborhood parks supports leisure time physical activity in most U.S. cities; yet, most Americans do not meet national guidelines for physical activity. Neighborhood parks have never been assessed nationally to identify their role in physical activity

How Much Observation Is Enough? Refining the Administration of SOPARC

The Systematic Observation of Play and Recreation in Communities (SOPARC) was designed to estimate the number and characteristics of people using neighborhood parks by assessing them 4 times/day, 7 days/week. We tested whether this schedule was adequate and determined the minimum number of observations necessary to provide a robust estimate of park user characteristics and their physical activity levels

Physical Activity Surveillance in Parks Using Direct Observation

IntroductionPrimary features of observational public health surveillance instruments are that they are valid, can reliably estimate physical activity behaviors, and are useful across diverse geographic settings and seasons by different users. Previous studies have reported the validity and reliability of Systematic Observation of Play and Recreation in Communities (SOPARC) to estimate park and user characteristics. The purpose of this investigation was to establish the use of SOPARC as a surveillance instrument and to situate the findings from the study in the context of the previous literature.MethodsWe collected data by using SOPARC for more than 3 years in 4 locations: Philadelphia, Pennsylvania; Columbus, Ohio; Chapel Hill/Durham, North Carolina; and Albuquerque, New Mexico during spring, summer, and autumn.ResultsWe observed a total of 35,990 park users with an overall observer reliability of 94% (range, 85%–99%) conducted on 15% of the observations. We monitored the proportion of park users engaging in moderate-to-vigorous physical activity (MVPA) and found marginal differences in MVPA by both city and season. Park users visited parks significantly more on weekend days than weekdays and visitation rates tended to be lower during summer than spring.ConclusionSOPARC is a highly reliable observation instrument that can be used to collect data across diverse geographic settings and seasons by different users and has potential as a surveillance system

The Prevalence and Use of Walking Loops in Neighborhood Parks: A National Study

BACKGROUND: Previous studies indicate that the design of streets and sidewalks can influence physical activity among residents. Park features also influence park use and park-based physical activity. Although individuals can walk on streets and sidewalks, walking loops in parks offer a setting to walk in nature and to avoid interruptions from traffic. OBJECTIVES: Here we describe the use of walking loops in parks and compare the number of park users and their physical activity in urban neighborhood parks with and without walking loops. METHODS: We analyzed data from the National Study of Neighborhood Parks in which a representative sample of neighborhood parks (n = 174) from 25 U.S. cities with > 100,000 population were observed systematically to document facilities and park users by age group and sex. We compared the number of people and their physical activity in parks with and without walking loops, controlling for multiple factors, including park size, facilities, and population density. RESULTS: Overall, compared with parks without walking loops, on average during an hourly observation, parks with walking loops had 80% more users (95% CI: 42, 139%), and levels of moderate-to-vigorous physical activity were 90% higher (95% CI: 49, 145%). The additional park use and park-based physical activity occurred not only on the walking loops but throughout the park. CONCLUSIONS: Walking loops may be a promising means of increasing population level physical activity. Further studies are needed to confirm a causal relationship. Citation: Cohen DA, Han B, Evenson KR, Nagel C, McKenzie TL, Marsh T, Williamson S, Harnik P. 2017. The prevalence and use of walking loops in neighborhood parks: a national study. Environ Health Perspect 125:170-174; http://dx.doi.org/10.1289/EHP293