Universal School Meals During the Pandemic: A Mixed Methods Analysis of Parent Perceptions from California and Maine.

BACKGROUND: In response to the COVID-19 pandemic, the United States Congress authorized the United States Department of Agriculture to waive a variety of school meal regulations and funded school meals daily for all students at no charge regardless of family income. Since federal Universal Free School Meals (UFSM) ended with the 2021-2022 school year, several states, including California and Maine, adopted state-level UFSM policies. OBJECTIVE: This study aimed to understand parent perceptions of school meals and the federal and new state UFSM policies in California and Maine, including potential challenges and benefits to students and households. DESIGN: A mixed methods study design was used. A quantitative cross-sectional survey was administered, and semi-structured interviews were conducted in English and Spanish during the 2021-2022 school year. PARTICIPANTS/SETTING: The quantitative survey was administered to parents of students in elementary, middle, and high schools in rural, suburban, and urban communities in California (n=1,110) and Maine (n=80). Qualitative interviews were then conducted with a subset of these parents in California (n=46) and Maine (n=20) using ZoomTM. Most survey participants (708 out of 1,190; 59.5%) and interviewees (40 out of 66; 60.6%) were parents of students who were eligible for free or reduced-price meals (FRPM). MAIN OUTCOME MEASURES: Parents' perceptions of UFSM, school meal quality, and experiences applying for FRPM were examined. ANALYSES PERFORMED: Tests of proportions were used to analyze survey data. Using grounded theory, interview transcripts were analyzed qualitatively by 2 trained research assistants, applying principles of content analysis to identify themes and domains. Inter-rater reliability was conducted. RESULTS: Parents perceived that school meals and UFSM saved families money and time, as parents had fewer meals to purchase and prepare for their children. Additionally, UFSM reduced parents' stress and reduced stigma for children and for parents, who described feelings of embarrassment when they previously filled out paperwork for FRPM. While parent perceptions of school meal quality and healthfulness were mixed, most parents reported feeling grateful for school meals. CONCLUSIONS: Parents had mixed opinions on the quality and healthfulness of school meals, but believed UFSM saved them money and time and reduced their stress. Parents also felt UFSM reduced stigma for families.

Parent Perceptions of School Meals Influence Student Participation in School Meal Programs.

OBJECTIVE: To evaluate if parent perceptions of school meals influence student participation. DESIGN: In May 2022, an online survey was used to evaluate parents' perceptions of school meals and their children's participation. PARTICIPANTS: A total of 1,110 California parents of kindergarten through 12th-grade students. MAIN OUTCOME MEASURES: Student participation in school lunch and breakfast. ANALYSIS: Principal component analysis and Poisson regression models. RESULTS: Three groups of parental perceptions were identified: (1) positive perceptions (eg, liking school meals and thinking that they are tasty and healthy), (2) perceived benefits to families (eg, school meals save families money, time, and stress), and (3) negative (eg, concerns about the amount of sugar in school meals and stigma). More positive parental perceptions about school meals and their benefits to families were associated with greater student meal participation. In contrast, more negative parental perceptions were associated with reduced student participation in school meals (P < 0.05). CONCLUSION AND IMPLICATIONS: Parent perceptions of school meals may affect student participation in school meal programs. Working to ensure parents are familiar with the healthfulness and quality of school meals and the efforts schools are making to provide high-quality, appealing meals may be critical for increasing school meal participation rates.

United States Department of Agriculture nutrition assistance programs during the COVID-19 pandemic: A scoping review protocol.

OBJECTIVE: The goal of this scoping review is to examine the published research on federal nutrition assistance programs administered by the United States (U.S.) Department of Agriculture during the COVID-19 pandemic, in the U.S., U.S. territories, and tribal nations. The review will identify the scope of the available research and provide research and policy recommendations. INTRODUCTION: The COVID-19 pandemic made individuals more vulnerable to experiencing food insecurity. Federal nutrition assistance programs help to address food insecurity and have been rapidly adapting to meet food and nutrition needs among affected communities during the COVID-19 pandemic. It is important to understand the scope of the current research on this topic to help inform future research, practice, and policy recommendations. INCLUSION CRITERIA: This review will include studies focused on federal nutrition assistance programs administered by the U.S. Department of Agriculture during the COVID-19 pandemic. The scoping review will consider all primary research designs. METHODS: Pubmed, CINHAL, Scopus, and Proquest's Health Management databases will be used for the literature search. Only articles published in English since March 1, 2020 will be considered. Titles/abstracts followed by full-text articles will be reviewed to determine which articles meet the inclusion criteria and should be included in the review. Data will be extracted from each included article using a data extraction template in Covidence that will be developed by the study team. Data extracted will include information on key findings related to the review questions. At each step, two independent reviewers will be assigned to each article. Data will be summarized and presented in tables, charts, and narrative summary.

Implementation of Universal School Meals during COVID-19 and beyond: Challenges and Benefits for School Meals Programs in Maine.

School meals play a major role in supporting children's diets and food security, and policies for universal school meals (USM) have the potential to contribute to positive child health outcomes. During the COVID-19 pandemic, schools provided free school meals to all students in the United States, but this national USM policy ended in school year (SY) 2022-2023; however, a few states have adopted policies to continue USM statewide for SY 2022-2023. Research examining the challenges and strategies for successful continuation of USM is essential, along with studying pandemic-related challenges that are likely to persist in schools. Therefore, we conducted a study in Maine (with a USM policy) to evaluate the impact of COVID-19 and the concurrent implementation of USM, as well as examine differences in implementation by school characteristics, throughout the state. A total of n = 43 school food authorities (SFAs) throughout Maine completed surveys. SFAs reported multiple benefits of USM including increased school meal participation; reductions in the perceived stigma for students from lower-income households and their families; and no longer experiencing unpaid meal charges and debt. SFAs also experienced challenges due to the COVID-19 pandemic, particularly regarding costs. When considering future challenges, most respondents were concerned with obtaining income information from families, product and ingredient availability, and the costs/financial sustainability of the school meal programs. Overall, USM may have multiple important benefits for students and schools, and other states should consider implementation of a USM policy.

Estimates of the Nutritional Impact of Non-Participation in the National School Lunch Program during COVID-19 School Closures.

The COVID-19 pandemic resulted in widespread school closures, reducing access to school meals for millions of students previously participating in the US Department of Agriculture (USDA) National School Lunch Program (NSLP). School-prepared meals are, on average, more nutritious than home-prepared meals. In the absence of recent data measuring changes in children's diets during the pandemic, this article aims to provide conservative, back-of-the-envelope estimates of the nutritional impacts of the pandemic for school-aged children in the United States. We used administrative data from the USDA on the number of NSLP lunches served in 2019 and 2020 and nationally representative data from the USDA School Nutrition and Meal Cost Study on the quality of school-prepared and home-prepared lunches. We estimate changes in lunchtime calories and nutrients consumed by NSLP participants from March to November 2020, compared to the same months in 2019. We estimate that an NSLP participant receiving no school meals would increase their caloric consumption by 640 calories per week and reduce their consumption of nutrients such as calcium and vitamin D. Because 27 to 78 million fewer lunches were served per week in March-November 2020 compared to the previous year, nationally, students may have consumed 3 to 10 billion additional calories per week. As students return to school, it is vital to increase school meal participation and update nutrition policies to address potentially widening nutrition disparities.

"On a Positive Path": School Superintendents' Perceptions of and Experiences With Local School Wellness Policy Implementation and Evaluation.

Renewed federal requirements for local school wellness policies highlighted the continued importance of supporting school districts as they implement and evaluate wellness initiatives. Superintendents-as school district leaders-play a critical role in wellness policy implementation and evaluation; however, to our knowledge, no studies examine their perspectives or experiences with the most recent federal rule or wellness initiatives more broadly. This study qualitatively examined superintendents' perspectives, experiences, and recommendations with wellness policy implementation and evaluation. Focus groups (n = 39) and follow-up interviews (n = 14 of the focus group participants) were conducted with superintendents from March to July 2017. Coders organized and coded transcript data using Atlas.ti, Version 8 to facilitate thematic analysis. Superintendents had overall positive perceptions of wellness policies and reported that implementation improved over time. Most described wellness approaches beyond typical wellness policy domains, including social-emotional learning and staff wellness. Evaluation of wellness policies was noted to be a challenge, and superintendents requested more tools and resources, as well as opportunities to learn from "best practices." Increased local and state accountability were recommended to facilitate motivation for other superintendents to engage with wellness. This study adds to the literature on a critical stakeholder in the school wellness field. Advocates and technical assistance providers can apply superintendents' recommendations to engage more district leaders in these initiatives.

Feeding Students During COVID-19-Related School Closures: A Nationwide Assessment of Initial Responses.

OBJECTIVE: To conduct a nationwide assessment of child nutrition administrative agencies' responses to meal service provision during coronavirus disease 2019-related school closures. DESIGN: Systematic coding of government websites (February-May 2020) regarding school meal provision in all 50 US states and the District of Columbia, 5 US territories, and the US Department of Interior Bureau of Indian Education. PARTICIPANTS: All US jurisdictions (N = 57). VARIABLES MEASURED: Seven coding criteria were established to assess the strengths and weaknesses of jurisdictions' responses derived from emergency declarations, school closure announcements, and government websites on emergency school meals. ANALYSIS: Descriptive analyses. RESULTS: Most jurisdictions mentioned school meal provisions in school closure announcements (76.4%), provided easily interpretable information and/or maps about meal sites (57.9%), and included detailed information about school meal provisions in their coronavirus disease 2019 landing webpages (n = 26, 51%). Fewer provided updated and comprehensive implementation guidance (39.3%), referenced school closures in emergency declarations (37.5%), had clear communication/outreach to families (21.4%), or partnered with antihunger organizations (11.6%). CONCLUSIONS AND IMPLICATIONS: Understanding initial jurisdictions' approaches are critical to current and future emergency planning during school closures and reopening to help address food insecurity better, limit disease transmission, and prevent health disparities, particularly among at-risk populations.

School Closures During COVID-19: Opportunities for Innovation in Meal Service.

In 2019, the National School Lunch Program and School Breakfast Program served approximately 15 million breakfasts and 30 million lunches daily at low or no cost to students.Access to these meals has been disrupted as a result of long-term school closures related to the COVID-19 pandemic, potentially decreasing both student nutrient intake and household food security. By the week of March 23, 2020, all states had mandated statewide school closures as a result of the pandemic, and the number of weekly missed breakfasts and lunches served at school reached a peak of approximately 169.6 million; this weekly estimate remained steady through the final week of April.We highlight strategies that states and school districts are using to replace these missed meals, including a case study from Maryland and the US Department of Agriculture waivers that, in many cases, have introduced flexibility to allow for innovation. Also, we explore lessons learned from the pandemic with the goal of informing and strengthening future school nutrition policies for out-of-school time, such as over the summer.

Wellness School Assessment Tool Version 3.0: An Updated Quantitative Measure of Written School Wellness Policies.

Schools play an important role in promoting student wellness. As directed by the Healthy Hunger-Free Kids Act, the US Department of Agriculture updated the requirements for written school wellness policies in 2016. The WellSAT (Wellness School Assessment Tool) is an online tool that provides a quantitative score for wellness policy comprehensiveness and strength. The WellSAT has been updated 3 times over the past decade to remain current with federal law and best practices. In this article, we describe the process of updating to WellSAT 3.0. The steps included: reviewing the language of each item linked to a federal provision; adding and deleting items based on frequencies from the National Wellness Policy Study and the empirical support for specific policies; gathering feedback from a survey of experts (N = 77) about best practices and measure usability; and establishing intercoder reliability in a national sample (N = 50) of policies. We conclude with recommendations and guidance for the use of WellSAT 3.0.

Removing competitive foods v. nudging and marketing school meals: a pilot study in high-school cafeterias.

OBJECTIVE: To compare federally reimbursable school meals served when competitive foods are removed and when marketing and nudging strategies are used in school cafeterias operating the National School Lunch Program (NSLP). The second objective was to determine how marketing and nudging strategies influence competitive food sales. DESIGN: In the Healthy Choices School, all competitive foods were removed; the Healthy Nudging School retained competitive foods and promoted the school meal programme using marketing and nudging strategies; a third school made no changes. Cafeteria register data were collected from the beginning of the 2013-2014 school year through the four-week intervention. Outcome measures included daily entrées served; share of entrées served with vegetables, fruit and milk; and total competitive food sales. Difference-in-difference models were used to examine outcome measure changes. SETTING: Three high schools in a diverse, Northeast US urban district with universally free meals. PARTICIPANTS: High-school students participating in the NSLP. RESULTS: During the intervention weeks, the average number of entrées served daily was significantly higher in the Healthy Choices School (82·1 (se 33·9)) and the Healthy Nudging School (107·4 (se 28·2)) compared with the control school. The only significant change in meal component selection was a 6 % (se 0·02) higher rate of vegetable servings in the Healthy Choices School compared with the control school. Healthy Nudging School competitive food sales did not change. CONCLUSIONS: Both strategies - removing competitive foods and marketing and nudging - may increase school meal participation. There was no evidence that promoting school meals decreased competitive food sales.

Juice Displaces Milk and Fruit in High School Lunches.

OBJECTIVE: To compare beverages and foods selected by high school students on days when juice was offered (juice days) and not offered (non-juice days) with the reimbursable school meal. METHODS: Lunch register data from 386 days across 3 low-income Northeast high schools were used to compare juice and non-juice days for average daily selections of meal components and à la carte water and 100% juice sales. RESULTS: On juice days, 9.9% fewer milks (P < .01) and 7.4% fewer fruits (P < .01) were selected with lunches. In addition, on juice days, 8.2% fewer bottles of water and 24.4% fewer bottles of 100% juice were sold à la carte (P < .05). CONCLUSIONS AND IMPLICATIONS: Reducing juice availability in the reimbursable school lunch may increase selection of milk and fruit. Future research is warranted to assess how juice availability influences selection of milk, fruit, and water across a range of student populations.

Implementing School-Based Policies to Prevent Obesity: Cluster Randomized Trial.

INTRODUCTION: Healthier school environments can benefit students, and school wellness policies may result in meaningful enhancements. Schools participating in federal child nutrition programs must implement wellness policies as mandated by law. The primary study objective is to assess effectiveness of implementing school-based nutrition and physical activity policies on student BMI trajectories. STUDY DESIGN: Cluster randomized trial using 2 × 2 factorial design. SETTING/PARTICIPANTS: Twelve randomly selected schools in an urban district. Students were followed for 3 years through middle school, fifth to eighth grades (2011-2015, n=595 students, 92.3% participation, 85.2% retention). INTERVENTION: Specific to randomized condition, support was provided for implementation of nutrition policies (e.g., alternatives to food-based rewards/celebrations) and physical activity policies (e.g., opportunities for physical activity during/after school). MAIN OUTCOME MEASURES: Sex-/age-adjusted BMI percentile and BMI z-score; behavioral indicators. Data collected via standardized protocols. RESULTS: Analyses followed intention-to-treat principles, with planned secondary analyses (conducted 2016-2018). Students at schools randomized to receive support for nutrition policy implementation had healthier BMI trajectories over time (F=3.20, p=0.02), with a greater magnitude over time and cumulatively significant effects 3 years post-intervention (ß=-2.40, p=0.04). Overall, students at schools randomized to receive the nutrition intervention had an increase in BMI percentile of <1%, compared with students in other conditions, whereas BMI percentile increased 3%-4%. There was no difference in student BMI between those in schools with and without physical activity policy implementation. Examining behavioral correlates in eighth grade, students at schools randomized to the nutrition condition consumed fewer unhealthy foods and sugar-sweetened beverages, and ate less frequently at fast-food restaurants (all p<0.03). CONCLUSIONS: This cluster randomized trial demonstrated effectiveness of providing support for implementation of school-based nutrition policies, but not physical activity policies, to limit BMI increases among middle school students. Results can guide future school interventions. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02043626.

Student Acceptance of Plain Milk Increases Significantly 2 Years after Flavored Milk Is Removed from School Cafeterias: An Observational Study.

BACKGROUND: Previous studies document decreases in lunchtime milk consumption immediately after flavored milk is removed. Less is known about longer-term effects. OBJECTIVE: Plain milk selection and consumption were measured the first year flavored milk was removed in a school district (2010 to 2011 [Time 1]) and 2 years later (2012 to 2013 [Time 2]). Four behavioral economic interventions to promote milk were tested in one school at Time 2. DESIGN: This was a longitudinal, observational study. PARTICIPANTS/SETTING: Participants were kindergarten through grade 8 students in two schools in an urban district. Primary data were collected 10 times per school year at Time 1 and Time 2, yielding 40 days of data and 13,883 student observations. The milk promotion interventions were tested on 6 additional days. MAIN OUTCOME MEASURES: Outcomes were the percentage of students selecting milk at lunch, the ounces of milk consumed per carton, and the ounces of milk consumed school-wide per student. STATISTICAL ANALYSES: Logistic regressions were used to assess how sex, grade, time, availability of 100% juice, and behavioral interventions affected milk selection and consumption. RESULTS: At Time One, 51.5% of students selected milk and drank 4 oz (standard deviation=3.2 oz) per carton, indicating school-wide per-student consumption of 2.1 oz (standard deviation=3.0 oz). At Time Two, 72% of students selected milk and consumed 3.4 oz per carton (standard deviation=3.2 oz), significantly increasing the school-wide per-student consumption to 2.5 oz (standard deviation=3.1 oz). Older students and boys consumed significantly more milk. Availability of 100% fruit juice was associated with a 16-percentage point decrease in milk selection. None of the behavioral economic interventions significantly influenced selection. CONCLUSIONS: These data suggest that after flavored milk is removed from school cafeterias, school-wide per-student consumption of plain milk increases over time. In addition, the presence of 100% juice is associated with lower milk selection.

High School Students' Recommendations to Improve School Food Environments: Insights From a Critical Stakeholder Group.

BACKGROUND: The Healthy, Hunger-Free Kids Act of 2010 (HHFKA) directed the US Department of Agriculture (USDA) to revise school meal standards. Students are most affected by efforts to improve the school food environment; yet, few studies directly include students. This study examined high school students' experiences of school meal reform to gain insight into implementation recommendations. METHODS: We conducted 5 focus groups with high school students (N = 15) from high schools across 9 states. We also conducted follow-up interviews to further explore personal experiences. Focus groups and interview transcripts were coded and organized in Atlas.ti v7 by analysts, following principles of constant comparative analysis. RESULTS: Students reported overall positive perceptions of the revised school meal standards and supported continued efforts to improve the food environment. Recommendations to improve the food environment included engaging students, focusing on the quality and palatability of meal items, moving toward scratch-cooking, and addressing cafeteria infrastructure. CONCLUSIONS: Students' recommendations point to opportunities where school districts, as well as local, state, and federal organizations can work to improve the school food environment. Their insights are directly relevant to USDA's recently released Local School Wellness Policy final rule, of which school meal standards are one provision.

New school meal regulations increase fruit consumption and do not increase total plate waste.

BACKGROUND: The 2010 Healthy, Hunger-Free Kids Act required the USDA to update the nutrition standards of the National School Lunch Program. New policies were implemented in the 2012-2013 school year. These changes were followed by anecdotal reports of increased food waste. Empirical research is needed to reliably measure student intake and plate waste before and after this policy change. METHODS: Food consumption and waste was collected annually from a cohort of middle school students in 12 schools in an urban, low-income school district before (spring 2012) and after (spring 2013 and 2014) policy changes. Generalized linear regression was used to compare pre- versus postpolicy selection and consumption of entrées, fruits, vegetables, and milk. RESULTS: Comparing 2012 to 2014, the percentage of students choosing fruit significantly increased from 54% to 66% and fruit consumption remained high at 74%. Student selection of fruit increased by 9% for each additional type of fruit offered with the meal. The proportion of students who chose a vegetable dropped from 68% to 52%, but students selecting vegetables ate nearly 20% more of them, effectively lowering vegetable waste. Entrée consumption increased significantly from 71% to 84%, thereby also decreasing waste. CONCLUSIONS: Students responded positively to the new lunches. They consumed more fruit, threw away less of the entrees and vegetables, and consumed the same amount of milk. Overall, the revised meal standards and policies appear to have significantly lowered plate waste in school cafeterias.

Impact of the Smoothened inhibitor, IPI-926, on smoothened ciliary localization and Hedgehog pathway activity.

A requisite step for canonical Hedgehog (Hh) pathway activation by Sonic Hedgehog (Shh) ligand is accumulation of Smoothened (Smo) to the primary cilium (PC). Activation of the Hh pathway has been implicated in a broad range of cancers, and several Smo antagonists are being assessed clinically, one of which is approved for the treatment of advanced basal cell carcinoma. Recent reports demonstrate that various Smo antagonists differentially impact Smo localization to the PC while still exerting inhibitory activity. In contrast to other synthetic small molecule Smo antagonists, the natural product cyclopamine binds to and promotes ciliary accumulation of Smo and "primes" cells for Hh pathway hyper-responsiveness after compound withdrawal. We compared the properties of IPI-926, a semi-synthetic cyclopamine analog, to cyclopamine with regard to potency, ciliary Smo accumulation, and Hh pathway activity after compound withdrawal. Like cyclopamine, IPI-926 promoted accumulation of Smo to the PC. However, in contrast to cyclopamine, IPI-926 treatment did not prime cells for hyper-responsiveness to Shh stimulation after compound withdrawal, but instead demonstrated continuous inhibition of signaling. By comparing the levels of drug-induced ciliary Smo accumulation with the degree of Hh pathway activity after compound withdrawal, we propose that a critical threshold of ciliary Smo is necessary for "priming" activity to occur. This "priming" appears achievable with cyclopamine, but not IPI-926, and is cell-line dependent. Additionally, IPI-926 activity was evaluated in a murine tumor xenograft model and a pharmacokinetic/pharmacodynamic relationship was examined to assess for in vivo evidence of Hh pathway hyper-responsiveness. Plasma concentrations of IPI-926 correlated with the degree and duration of Hh pathway suppression, and pathway activity did not exceed baseline levels out to 96 hours post dose. The overall findings suggest that IPI-926 possesses unique biophysical and pharmacological properties that result in Hh pathway inhibition in a manner that differentiates it from cyclopamine.

The pre-clinical absorption, distribution, metabolism and excretion properties of IPI-926, an orally bioavailable antagonist of the hedgehog signal transduction pathway.

1. IPI-926 is a novel semisynthetic cyclopamine derivative that is a potent and selective Smoothened inhibitor that blocks the hedgehog signal transduction pathway. 2. The in vivo clearance of IPI-926 is low in mouse and dog and moderate in monkey. The volume of distribution is high across species. Oral bioavailability ranges from moderate in monkey to high in mouse and dog. Predicted human clearance using simple allometry is low (24 L h(-1)), predicted volume of distribution is high (469 L) and predicted half-life is long (20 h). 3. IPI-926 is highly bound to plasma proteins and has minimal interaction with human α-1-acid glycoprotein. 4. In vitro metabolic stability ranges from stable to moderately stable. Twelve oxidative metabolites were detected in mouse, rat, dog, monkey and human liver microsome incubations and none were unique to human. 5. IPI-926 is not a potent reversible inhibitor of CYP1A2, 2C8, 2C9 or 3A4 (testosterone). IPI-926 is a moderate inhibitor of CYP2C19, 2D6 and 3A4 (midazolam) with KI values of 19, 16 and 4.5 µM, respectively. IPI-926 is both a substrate and inhibitor (IC50 = 1.9 µM) of P-glycoprotein. 6. In summary, IPI-926 has desirable pre-clinical absorption, distribution, metabolism and excretion properties.

Small changes approach promotes initial and continued weight loss with a phone-based follow-up: nine-month outcomes from ASPIRES II.

PURPOSE: To examine the impact of a small-changes weight loss program across a 3-month intervention followed by a 6-month follow-up program. DESIGN: A one-group pre-post intervention study. SETTING: Medium-sized Southwestern university. PARTICIPANTS: Twenty-five obese adult women (mean body mass index [BMI]  =  31.8 kg/m(2), standard deviation [SD]  =  4.9). INTERVENTION: Participants were asked to choose and adopt small changes in their diet and physical activity relative to baseline during weekly group-based meetings over 3 months. Participants then received bi-weekly phone calls across a 6-month follow-up period. MEASURES: Weight change was the primary outcome. Secondary outcomes included waist circumference, daily step count, and caloric intake. ANALYSES: Intention-to-treat analysis of change from baseline and completers-only analysis (n  =  22) for secondary outcomes. RESULTS: Participants achieved clinically significant weight loss (mean [M]  =  -3.2 kg, standard error [SE]  =  .47 kg, p < .001) across the initial small changes treatment program. Moreover, participants continued to lose weight across the 6-month phone-based follow-up program (M  =  -2.1 kg, SE  =  .83 kg, p < .017), totaling >5% weight loss across the 9-month program (M  =  5.3 kg, SE  =  1.1 kg, p < .001). CONCLUSION: Using a small changes approach, participants achieved weight loss in an initial group-based program, which continued with minimal phone-based follow-up. Larger randomized studies comparing a small changes approach to traditional obesity treatment are warranted.

New developments in the discovery of small molecule Hedgehog pathway antagonists.

The Hedgehog (Hh) signaling pathway is crucial for normal embryonic development. Aberrant Hh signaling is implicated in numerous pathologic conditions including proliferative diseases such as cancer. During the past decade, academic and industrial research efforts have resulted in the discovery of a variety of Hh pathway antagonists. This review focuses on the most recent advances in this field with particular emphasis on the medicinal chemistry approaches used to discover these Hh antagonists. While most of the small molecule modulators of the Hh pathway were discovered through screening and subsequent medicinal chemistry, a number of them originated from rational design or natural products.

Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926).

Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.