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The dopamine D2 receptor (D2R) is known to elicit effects through activating two major signaling pathways mediated by either G proteins (Gi/o) or β-arrestins. However, the specific role of each pathway in physiological or therapeutic activities is not known with certainty. One approach to the dissection of these pathways is through the use of drugs that can selectively modulate one pathway vs. the other through a mechanism known as functional selectivity or biased signaling. Our laboratory has previously described a G protein signaling-biased agonist, MLS1547, for the D2R using a variety of in vitro functional assays. To further evaluate the biased signaling activity of this compound, we investigated its ability to promote D2R internalization, a process known to be mediated by β-arrestin. Using multiple cellular systems and techniques, we found that MLS1547 promotes little D2R internalization, which is consistent with its inability to recruit β-arrestin. Importantly, we validated these results in primary striatal neurons where the D2R is most highly expressed suggesting that MLS1547 will exhibit biased signaling activity in vivo. In an effort to optimize and further explore structure-activity relationships (SAR) for this scaffold, we conducted an iterative chemistry campaign to synthesize and characterize novel analogs of MLS1547. The resulting analysis confirmed previously described SAR requirements for G protein-biased agonist activity and, importantly, elucidated new structural features that are critical for agonist efficacy and signaling bias of the MLS1547 scaffold. One of the most important determinants for G protein-biased signaling is the interaction of a hydrophobic moiety of the compound with a defined pocket formed by residues within transmembrane five and extracellular loop two of the D2R. These results shed new light on the mechanism of biased signaling of the D2R and may lead to improved functionally-selective molecules.

Background: To determine whether schools with a formal indoor air quality management program were more likely than schools without a formal program to have policies and practices that promote superior indoor air quality. Methods: This study analyzed school-level data from the 2006 School Health Policies and Programs Study, a national study of school health programs and policies at the state, district, and school levels. Using chi-square analyses, the rates of policies and practices that promote indoor air quality were compared between schools with and schools without a formal indoor air quality program. Results: The findings of this study show that 51.4% of schools had a formal indoor air quality management program, and that those schools were significantly more likely than were schools without a program to have policies and use strategies to promote superior indoor air quality. Conclusions: These findings suggest that schools with a formal indoor air quality program are more likely support policies and engage in practices that promote superior indoor air quality. (Contains 3 tables and 1 figure.)

School health policies and programs provide the framework for a safe and supportive environment for students with asthma. School Health Policies and Programs Study 2006 data were examined to assess whether schools nationwide have policies and programs consistent with the "How Asthma-Friendly Is Your School?" checklist from the National Asthma Education and Prevention Program. Adherence to some of the recommendations on the checklist was high. For example, 80% or more of schools allowed students to carry and self-administer asthma medications, and obtained and kept asthma action plans. For other recommendations, however, far fewer schools had the recommended polices or programs; most notably, less than one third of schools had a full-time Registered Nurse. Improvements in many school policies and programs are needed so that students have a safe and supportive school environment to help them control their asthma while away from home. (Contains 1 table.)

Although asthma deaths in children are rare, most asthma deaths should be preventable. No information has been identified in the professional literature addressing the occurrence of asthma deaths in schools. This investigation identified asthma deaths that occurred in US schools between 1990 and 2003 and the circumstances surrounding those deaths. Data were obtained through newspaper articles in the LexisNexis database and death certificates. Between 1990 and 2003, 38 asthma school deaths were reported. Eighteen (47%) identified deaths occurred among black children and 12 (31%) among white. Twenty-seven (72%) of the deaths occurred among teens. Of the fatal asthma attacks, 16 (42%) occurred while the children were participating in a physically active event. Twelve (31%) children died while waiting for medical assistance. Due to the nature of these data, inferences may be subject to source bias. For the identified asthma deaths, key findings include the following: (1) most deaths occurred in teens and high school students; (2) frequently, the precipitating event was related in time to exercise: and (3) a delayed response or hesitancy of school staff to provide medical assistance may have contributed to some of the deaths. Although few school-related asthma deaths are reported each year, the true number is unknown. Key factors in managing the disease and preventing asthma deaths and exacerbations in schools include identification of students with diagnosed asthma, communication with parents and health care providers, removal of triggers in the immediate school environment, and maximizing access to needed medications.

INTRODUCTION Five key lessons for school-based asthma programs emerge from the research and case study findings reported in this special issue and from previous literature and the editors' experiences. Following [...]

CASE STUDY OBJECTIVES * To improve our case identification system for use in an annual asthma prevalence count for Anne Arundel County public schools * To simplify the system for [...]

Results of a research on Chinese preschool children revealed that weekly oral administration of iron to anemic subjects substantially improved their iron status with only negligible side effects. Follow-up studies on the benefits of weekly iron supplements in controlling iron deficiency are being conducted on pregnant women, adolescent girls and preschool children in eight nations through the WHO-United Nations University-UNICEF study.

Growth, activity, appetite and intestinal helminth infections were compared for 55 Kenyan primary school children with hookworm (93% prevalence), T. trichiura (84% prevalence) and A. lumbricoides (29% prevalence) before and 9 wk after treatment with three 400-mg doses of albendazole (Zentel) or placebo. Fecal samples were examined for helminth eggs using a modified Kato technique. Activity was measured during free-play with motion recorders on the dominant thigh. Children rated their appetites on a 5-point scale. After baseline measurements, children were randomly allocated to the albendazole-treated (n = 28) and placebo (n = 27) groups, treated, and re-examined 9 wk later. At follow-up, egg counts were significantly lower than at baseline in the albendazole-treated group (P [less than or equal to] 0.002), and gains in activity, reported appetite and most indices of growth were significantly greater for the albendazole-treated group than for the placebo group. We conclude that treatment of undernourished school children for intestinal helminth infections with albendazole may improve growth and appetite and increase spontaneous physical activity. J. Nutr. 124: 1199--1206, 1994.

A randomized, double-blind, placebo-controlled iron supplementation trial was conducted in Kenya to examine the effect of iron supplements on appetite and growth in 87 primary school children. Sustained-release ferrous sulfate (150 mg) or placebo tablets were provided daily at school for 14 wk. Prior to tablet administration, baseline anthropometry, iron nutritional status (hemoglobin and serum ferritin), parasitic infections and clinical indicators of morbidity were measured. A baseline appetite test was conducted twice on each child by quantitatively measuring the ad libitum consumption of a midmorning snack. In addition, each child was asked for a subjective assessment of his or her appetite. Follow-up exams and appetite tests were identical to those at baseline. Findings indicated that provision of iron supplements resulted in improved growth and improved appetite (in terms of both energy intake of the snack and child report of appetite) as compared with children receiving the placebo. The increased energy intake from the snack was 10% of the daily estimated energy intake for children of this same age group living elsewhere in Kenya. Further research into the underlying physiological mechanisms may shed light on the relationship between iron nutritional status and appetite.

We studied physical fitness with the Harvard Step Test, growth, and appetite in primary school boys infected with hookworm (96% baseline prevalence), Trichuris trichiura (98% prevalence) and Ascaris lumbricoides (41% prevalence) who received a single 600-mg dose of albendazole or an identical placebo. Boys were examined, allocated at random within pairs by descending hookworm egg count to placebo (n = 26) or albendazole (n = 27) groups, treated, and re-examined 4 mo later. Four months after treatment, the albendazole group showed highly significant improvements in fitness score, resting heart rate, and heart rates at 1, 2, 3 and 4 min after the Harvard Step Test, whereas the placebo group had not changed significantly. The albendazole group also exhibited significantly more rapid growth judged by weight gain (1.0 kg greater than the placebo group, P < 0.0002), height increment (0.6 cm more, P < 0.003), arm circumference (0.3 cm more, P < 0.0002), and triceps and subscapular skinfolds (1.0 mm more, P < 0.0002), and showed improved appetite with objective and subjective measures. We conclude that single-dose treatment with albendazole can allow improved physical fitness, growth, and appetite in school-age children in areas where these helminths and poor growth are highly prevalent.

We studied growth in infected children given one dose (600 mg) or two doses of albendazole per school year. Children were examined and allocated at random within sex by descending hookworm egg count to one of three groups: placebo (n = 93), one dose (1x, n = 96) or two doses (2x, n = 95). Each child was treated and then re-examined and treated 3.6 and 8.2 mo later (Exams 2 and 3). The 1x and 2x groups gained significantly more by Exam 3 than the placebo group in weight (1.1 and 0.9 kg more, respectively), percent weight-for-age (3.3 and 2.7 percentage points more), percent weight-for-height (3.1 and 2.9 percentage points more), percent arm circumference-for-age (2.3 and 2.0 percentage points more) and triceps and subscapular skinfolds but did not differ significantly from each other. The placebo group showed significant decreases between exams (P < 0.0002) in percent weight-for-age and percent arm circumference-for-age and no change in percent weight-for-height, whereas the 1x and 2x groups exhibited significant increases (P < 0.005). At Exam 3, arithmetic mean egg reduction rates for the 1x and 2x groups were 84 and 95% for hookworm, 42 and 32% for Trichuris and 55 and 87% for Ascaris, respectively. We conclude that one or two doses of albendazole per year resulted in similar growth improvements, despite reinfection, in school-age children in an area where these helminths and poor growth are prevalent. J. Nutr. 123: 656-665, 1993.

This article investigates how the dual demands of finance and social impact affect the relationships of founders to disruption, as a rhetorical function, material goal and relational context. Building on recent studies of innovation and entrepreneurship such as Bardinelli (2019), Irani (2019) and Lindtner (2020), the article offers a nuanced view of disruption that complicates unidimensional narratives of financialization as a singular force and accounts for the complexity of reconciling financial and social interests. Based on data gathered at a startup participating in a government-funded accelerator program in Melbourne, Australia, we analyse how the logics of finance impact entrepreneurial experience in an early-stage social enterprise startup. Our data suggests that, in their attempts to attract the attention and funding of financial investors, founders of early-stage startups focus more on proving the value of their disruption in a rhetorical sense than on refining the materially disruptive potential of their products to ensure real world social impact. By analysing disruption through a relational lens, we identify four layers of disruption (product innovation; social value; financial return; and labour relations) to which early-stage startups are aligned, and through which their products and personal lives are transformed.

ASTHMA'S EFFECT ON CHILDREN AND YOUTH IN THE UNITED STATES Asthma is a major public health problem of increasing concern in the United States; (1,2) between 1980 and 1996, the [...]

Asthma, a common chronic illness among children and youth, affects one school-aged child in 11, or two to three students in a class of 30. (1) Asthma accounts for 14 [...]