Absorption, single-dose and steady-state metabolism, excretion, and pharmacokinetics of adagrasib, a KRAS inhibitor.

Objective: This study investigated absorption, metabolism, and excretion of adagrasib after a single oral 600 mg dose (1 µCi [C]-adagrasib) in 7 healthy subjects and compared the metabolite profile to the profile at steady-state in 4 patients dosed at 600 mg twice daily.

Methods: Plasma, urine, and feces were collected post [C]-adagrasib administration and total radioactivity and pooled sample metabolite profiles were determined. Adagrasib pharmacokinetics were determined in plasma and urine.

Identification of the Clinical Candidate (), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer.

Mutant BRAF is one of the most common oncogenic drivers in metastatic melanoma. While first generation BRAF inhibitors are capable of controlling tumors systemically, they are unable to adequately treat tumors that have metastasized to the brain due to insufficient penetration across the blood-brain barrier (BBB). Through a combination of structure-based drug design (SBDD) and the optimization of physiochemical properties to enhance BBB penetration, we herein report the discovery of the brain-penetrant BRAF inhibitor () In mice studies, proved to be highly brain-penetrant and was able to drive regressions of A375 BRAF tumors implanted both subcutaneously and intracranially.

Discovery of 5-Azaquinoxaline Derivatives as Potent and Orally Bioavailable Allosteric SHP2 Inhibitors.

SHP2 has emerged as an important target for oncology small-molecule drug discovery. As a nonreceptor tyrosine phosphatase within the MAPK pathway, it has been shown to control cell growth, differentiation, and oncogenic transformation. We used structure-based design to find a novel class of potent and orally bioavailable SHP2 inhibitors.

Racial, ethnic, and gender differences in the association between higher state minimum wages and health and mental well-being in US adults with low educational attainment.

Background: To date, research evaluating the association between minimum wage and health has been heterogenous and varies based on the specific subpopulation or health outcomes under evaluation while associations across racial, ethnic, and gender identities have been understudied.

Methods: A triple difference-in-differences strategy using modified Poisson regression was used to evaluate the associations between minimum wage and obesity, hypertension, fair or poor general health, and moderate psychological distress in 25-64-year-old adults with a high school education/GED or less. Data from the 1999-2017 Panel Study of Income Dynamics was linked to state policies and characteristics to estimate the risk ratio (RR) associated with a $1 increase in current and 2-year lagged state minimum wages overall and by race, ethnicity, and gender (non-Hispanic or non-Latino (NH) White men, NH White women, Black, indigenous, or people of color (BIPOC) men, and BIPOC women) adjusting for individual and state-level confounding.

Work-Related Factors Associated With Health and Well-Being of Early Care and Education Workers.

Objective: We assessed and examined relationships between the health and working conditions of early care and education workers.

Methods: We surveyed early care and education workers ( n = 2242) about their socioeconomic characteristics; work organization; psychosocial, physical, and ergonomic exposures; coping behaviors; and health.

Results: Nearly half of respondents reported chronic health conditions.

Food security and food access during the COVID-19 pandemic: Impacts, adaptations, and looking ahead.

The coronavirus disease 2019 (COVID-19) pandemic continues to alter US household food consumption and food spending. Although terminology used to describe food insecurity has varied during the COVID-19 pandemic, many reliable estimates illustrate a dramatic increase in food insecurity from approximately 10% of US households before the pandemic to 25%-30% of households during the pandemic, with an even higher prevalence reported by more vulnerable and socially disadvantaged populations. To address the increase in food and economic insecurity, food and nutrition assistance policies and programs made innovative and temporary changes, and enrollment in these programs generally increased.

Insights from Washington State's COVID-19 Response: A Mixed-Methods Evaluation of WIC Remote Services and Expanded Food Options Using the RE-AIM Framework.

Background: In response to the COVID-19 pandemic, Washington State's Supplemental Nutrition Program for Women, Infants, and Children (WA WIC) adopted federal waivers to transition to remote service delivery for certification and education appointments. WA WIC also expanded the approved food list without using federal waivers, adding more than 600 new items to offset challenges participants experienced accessing foods in stores.

Objective: This study aimed to assess the reach and effectiveness of the programmatic changes instituted by WA WIC during the COVID-19 pandemic; the processes, facilitators, and challenges involved in their implementation; and considerations for their continuation in the future.

Early Care and Education Workers' Experience and Stress during the COVID-19 Pandemic.

Early care and education (ECE) workers experience many job-related stressors. During the COVID-19 pandemic, ECE programs either closed or remained open while workers faced additional demands. We deployed a survey of the center-based ECE workforce in Washington State (United States) one year into the COVID-19 pandemic to assess impacts and workers' perceived stress levels.

Diet quality and exposure to endocrine-disrupting chemicals among US adults.

Human exposure to endocrine-disrupting chemicals (EDCs) may increase risk for chronic disease. Diet is a significant source of EDC exposure, yet healthy diets recommended for chronic disease prevention have not been thoroughly examined for associations with EDC exposure. Using data from the National Health and Nutrition Examination Survey 2013-2016, we examined associations of dietary patterns with exposure to non-persistent EDCs potentially consumed through diet.

A Multi-Site Analysis of the Prevalence of Food Insecurity in the United States, before and during the COVID-19 Pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs.

Objective: The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements.

Making seafood accessible to low-income and nutritionally vulnerable populations on the U.S. West Coast.

Along the U.S. West Coast, sustainable management has rebuilt fish stocks, providing an opportunity to supply nutrient-rich food to adjacent coastal communities where food insecurity and diet-based diseases are common.

Inedible Food Waste Linked to Diet Quality and Food Spending in the Seattle Obesity Study SOS III.

Americans waste about a pound of food per day. Some of this is represented by inedible food waste at the household level. Our objective was to estimate inedible food waste in relation to diet quality and participant socio-economic status (SES).

Food Insecurity Is Associated with Depression among a Vulnerable Workforce: Early Care and Education Workers.

We aimed to explore the association between food insecurity and depression among early care and education (ECE) workers, a vulnerable population often working in precarious conditions. We utilized cross-sectional data from a study exploring the effects of wage on ECE centers. Participants were enrolled between August 2017 and December 2018.

Identification of the Clinical Development Candidate , a Covalent KRAS Inhibitor for the Treatment of Cancer.

Capping off an era marred by drug development failures and punctuated by waning interest and presumed intractability toward direct targeting of KRAS, new technologies and strategies are aiding in the target's resurgence. As previously reported, the tetrahydropyridopyrimidines were identified as irreversible covalent inhibitors of KRAS that bind in the switch-II pocket of KRAS and make a covalent bond to cysteine 12. Using structure-based drug design in conjunction with a focused in vitro absorption, distribution, metabolism and excretion screening approach, analogues were synthesized to increase the potency and reduce metabolic liabilities of this series.

Association of State Minimum Wage Rates and Health in Working-Age Adults Using the National Health Interview Survey.

States adopt minimum wages to improve workers' economic circumstances and well-being. Many studies, but not all, find evidence of health benefits from higher minimum wages. This study used a rigorous "triple difference" strategy to identify the associations between state minimum wages and adult obesity, body mass index (weight (kg)/height (m)2), hypertension, diabetes, fair or poor health, and serious psychological distress.

Low-income workers' perceptions of wages, food acquisition, and well-being.

Although studies have demonstrated an association between increased economic resources and improvements in food security and health, there is a paucity of qualitative research regarding the relationships between household resources, food security, and health. Policy changes related to increasing low wages are potential opportunities to understand changes to material resources. The aims of this analysis were to describe how low-wage workers perceive household resources in relation to food acquisition and to explore how workers in low-wage jobs connect food and diet to perceptions of health and well-being.

The Culture Of Health In Early Care And Education: Workers' Wages, Health, And Job Characteristics.

Little is known about the health of the 2.2 million early care and education (ECE) workers responsible for the care, well-being, and success of the approximately ten million children younger than age six enrolled in ECE, or the extent to which ECE environments and employers play a role in workers' health. The purpose of this analysis was to describe the health of an ECE worker sample by wage and by job and center characteristics and to begin to explore the relationships between these factors and workers' health.

The Impact of a City-Level Minimum Wage Policy on Supermarket Food Prices by Food Quality Metrics: A Two-Year Follow Up Study.

: To examine the effects of increasing minimum wage on supermarket food prices in Seattle over 2 years of policy implementation, overall and differentially across food quality metrics. Prices for the UW Center for Public Health Nutrition (CPHN) market basket of 106 foods were obtained for 6 large supermarket chain stores in Seattle ("intervention") and for the same chain stores in King County ("control") at four time points: 1-month pre- (March 2015), 1-month post- (May 2015), 1-year post- (May 2016), and 2-years post-policy implementation (May 2017). Prices for all food items were standardized and converted to price per 100 kcal.

The development and adoption of the first statewide comprehensive policy on food service guidelines (Washington State Executive Order 13-06) for improving the health and productivity of state employees and institutionalized populations.

National health authorities uniformly express an urgent need for large-scale policies that incorporate population-based strategies to improve diet-related population health outcomes. On October 30, 2013, Washington State passed the first statewide comprehensive policy on food service guidelines (i.e.

Low-Calorie Sweetened Beverages and Cardiometabolic Health: A Science Advisory From the American Heart Association.

In the United States, 32% of beverages consumed by adults and 19% of beverages consumed by children in 2007 to 2010 contained low-calorie sweeteners (LCSs). Among all foods and beverages containing LCSs, beverages represent the largest proportion of LCS consumption worldwide. The term LCS includes the 6 high-intensity sweeteners currently approved by the US Food and Drug Administration and 2 additional high-intensity sweeteners for which the US Food and Drug Administration has issued no objection letters.

Examining Relationships between Food Procurement Characteristics and Nutritional Quality in Washington State Child Care Settings.

Background: Sixty percent of US children 5 years old and under receive up to two-thirds of their daily nutrition in early care and education (ECE) settings. Although participation in the federal Child and Adult Care Food Program (CACFP) is shown to improve nutrition, little is known about the relationship between procurement practices (where and how child care programs purchase food) and nutrition in ECE settings or whether these practices differ depending on participation in CACFP.

Methods: We assessed self-reported nutrition practices and procurement practices by CACFP participation using a 2013 cross-sectional survey of 690 Washington ECE centers ("Centers") and 1260 family homes (family home child care [FHCCs]) serving children aged 2-5 years old using validated survey tools.