Human ZBP1 induces cell death-independent inflammatory signaling via RIPK3 and RIPK1.

ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death is widely described, whether and how it promotes inflammatory signaling is unclear. Here, we report a ZBP1-induced inflammatory signaling pathway mediated by K63- and M1-linked ubiquitin chains, which depends on RIPK1 and RIPK3 as scaffolds independently of cell death. In human HT29 cells, ZBP1 associated with RIPK1 and RIPK3 as well as ubiquitin ligases cIAP1 and LUBAC. ZBP1-induced K63- and M1-linked ubiquitination of RIPK1 and ZBP1 to promote TAK1- and IKK-mediated inflammatory signaling and cytokine production. Inhibition of caspase activity suppressed ZBP1-induced cell death but enhanced cytokine production in a RIPK1- and RIPK3 kinase activity-dependent manner. Lastly, we provide evidence that ZBP1 signaling contributes to SARS-CoV-2-induced cytokine production. Taken together, we describe a ZBP1-RIPK3-RIPK1-mediated inflammatory signaling pathway relayed by the scaffolding role of RIPKs and regulated by caspases, which may induce inflammation when ZBP1 is activated below the threshold needed to trigger a cell death response.

Evaluating a psychological support service focused on the needs of critical care and theatres staff in the first wave of COVID-19.

BACKGROUND: In response to COVID-19, the authors used clinical psychology resources from their hospital's Pain Medicine Department to provide direct support to critical areas. AIMS: The degree to which the service met the needs of staff and managers between March and August 2020 was evaluated. METHODS: A total of 51 staff were referred. Most were nurses (43%), followed by theatre practitioners (36%), healthcare assistants (9%), consultants (8%), administrative (2%) and support staff (2%). Working status, reason for referral and presenting difficulties at first appointment and outcome were recorded. Staff were sent an anonymous survey following intervention. FINDINGS: Staff reported high rates of burnout, anxiety and low mood, with 22% experiencing exacerbation of pre-existing mental health problems. All staff reported benefit from the intervention and managers provided positive feedback. CONCLUSION: Establishing a supportive service that included psychology benefited both staff and managers at the peak of the pandemic. Recommendations are provided.

Addressing Food Insecurity through a Health Equity Lens: a Case Study of Large Urban School Districts during the COVID-19 Pandemic.

Reduced access to school meals during public health emergencies can accelerate food insecurity and nutritional status, particularly for low-income children in urban areas. To prevent the exacerbation of health disparities, there is a need to understand the implementation of meal distribution among large urban school districts during emergencies and to what degree these strategies provide equitable meal access. Our case study of four large urban school districts during the COVID-19 pandemic aims to address these knowledge gaps. Guided by the Getting to Equity (GTE) framework, we conducted a mixed-methods study evaluating emergency meal distribution and strategy implementation in four large urban school districts (Chicago Public Schools, Houston Independent School District, Los Angeles Unified School District, and New York City Department of Education). We gathered data from school district websites on (1) meal service and delivery sites and (2) district documents, policies, communication, and resources. Using qualitative coding approaches, we identified unique and shared district strategies to address meal distribution and communications during the pandemic according to the four components of the GTE framework: increase healthy options, reduce deterrents, build on community capacity, and increase social and economic resources. We matched district census tract boundaries to demographic data from the 2018 American Community Survey and United States Department of Agriculture food desert data, and used geographic information systems (GIS) software to identify meal site locations relative to student population, areas of high poverty and high minority populations, and food deserts. We found that all districts developed strategies to optimize meal provision, which varied across case site. Strategies to increase healthy options included serving adults and other members of the general public, providing timely information on meal site locations, and promoting consumption of a balanced diet. The quantity and frequency of meals served varied, and the degree to which districts promoted high-quality nutrition was limited. Reducing deterrents related to using inclusive language and images and providing safety information on social distancing practices in multiple languages. Districts built community capacity through partnering with first responder, relief, and other community organizations. Increased social and economic resources were illustrated by providing technology assistance to families, childcare referrals for essential workers, and other wellness resources. Geospatial analysis suggests that service locations across cities varied to some degree by demographics and food environment, with potential gaps in reach. This study identifies strategies that have the potential to increase equitable access to nutrition assistance programs. Our findings can support (1) ongoing efforts to address child food insecurity during the pandemic and (2) future meal provision through programs like the Summer Food Service Program and Seamless Summer Option. Future research should further examine the rationale behind meal site placement and how site availability changed over time.

Local Measures to Curb Dollar Store Growth: A Policy Scan.

In recent years, advocates have expressed concern about the exponential growth of dollar stores in low-income communities, given their limited stock of healthy foods, and several municipalities in the U.S. have passed novel policies to curb the proliferation of these stores. The purpose of this scan is to create a legal database to inform future healthy retail policies and programs. Legal mapping methods were used to identify local policies aimed at moderating dollar store proliferation. A search yielded 25 policies that met the inclusion criteria, all enacted between 2018 and 2020. Recent policies aiming to slow local dollar store growth were mostly passed in low-income communities of color. All identified policies were passed in either the Midwest or South. The majority of municipalities that passed the policies had populations where more than half of residents identified as non-Hispanic Black or Hispanic and where the poverty rate was greater than the national average. Twelve (48%) municipalities imposed temporary moratoria halting new dollar stores from opening, and ten (40%) banned new construction within a specified distance of an existing dollar store. Key themes identified from analysis of policies' purpose statements included increasing healthy food availability, diversifying local businesses, and improving community safety. These findings may be useful to leaders in other communities seeking to potentially moderate the impact of dollar stores on community health, as well as researchers and policy makers seeking to evaluate the efficacy of existing policies.

Comparison of Missing School Meals among Public Schools: How Did New York State Do during COVID-19?

BACKGROUND: The COVID-19 pandemic created barriers to participation in school meals. As a result, many students may have missed out on school meals. The objectives of this study are (1) to compare the number of school meals served by New York State public schools during the first spring and summer of the COVID-19 pandemic to the number served before the COVID-19 pandemic, and (2) to determine relationships between the number of meals served and the levels of school district need and urbanicity. METHODS: This study is a secondary analysis of administrative data. The percentage change in the number of school breakfasts and lunches served was calculated for each month and by school district need level and urbanicity level. RESULTS: The number of school meals served decreased during the first spring of the pandemic compared to the spring of the previous school year (-43% in April, -51% in May), while the number of school meals served increased during the first summer of the pandemic compared to the summer of the previous school year (+92% in July, +288% in August). CONCLUSIONS: Waivers may provide flexibility to increase participation in school meals, especially during the summer.

Cutaneous expression of growth-associated protein 43 is not a compelling marker for human nerve regeneration in carpal tunnel syndrome.

Growth-associated protein 43 (GAP-43) has long been used as a marker for nerve regeneration following nerve injury, with numerous in vitro and animal studies showing its upregulation in regenerating neurons. In humans, expression of GAP-43 has predominantly been examined in skin biopsies from patients with peripheral neuropathies; with several studies showing a reduction in GAP-43 immunoreactive cutaneous nerve fibres. However, it remains elusive whether cutaneous GAP-43 is a valid marker for human nerve regeneration. Here, we present a cohort of 22 patients with electrodiagnostically confirmed carpal tunnel syndrome (CTS), used as a model system for focal nerve injury and neural regeneration after decompression surgery. We evaluate GAP-43 immunoreactivity and RNA expression levels in finger skin biopsies taken before and 6 months after surgery, relative to healthy controls. We further classify patients as 'regenerators' or 'non-regenerators' based on post-surgical epidermal re-innervation. We demonstrate that patients with CTS have lower GAP-43 positive intra-epidermal nerve fibre density (IENFD) before surgery than healthy controls. However, this difference disappears when normalising for total IENFD. Of note, we found surgery did not change GAP-43 expression in IENF, with no differences both in patients who were classified as regenerators and non-regenerators. We also did not identify pre-post surgical differences in cutaneous GAP-43 gene expression or associations with regeneration. These findings suggest cutaneous GAP-43 may not be a compelling marker for nerve regeneration in humans.

State and Local Healthy Kids' Meal Laws in the United States: A Review and Content Analysis.

BACKGROUND: To address unhealthy restaurant food intake among children, localities and states are passing healthy restaurant kids' meal laws. However, there is limited knowledge of what these policies require and how they compare with expert and industry nutrition standards. OBJECTIVES: The aim of this study was to develop a research instrument to evaluate healthy kids' meal laws and assess their alignment with expert and industry nutrition standards. DESIGN: The study team conducted a content analysis of healthy kids' meal laws passed between January 2010 and August 2020 in the United States. Using a structured codebook, two researchers abstracted policy elements and implementation language from laws, regulations, fiscal notes, and policy notes. Nutritional criteria for kids' beverages and meals were compared with existing expert and industry nutrition standards for meals and beverages. MAIN OUTCOME MEASURES: Measures included law characteristics, implementation characteristics, enforcement characteristics, definitions of key terms, and nutritional requirements for meals and default beverage options and alignment with expert and industry nutrition standards. STATISTICAL ANALYSES PERFORMED: Interrater reliability of the coding tool was estimated using the Cohen kappa statistic, and researchers calculated descriptive statistics of policy elements. RESULTS: Twenty laws were identified. Eighteen were healthy default beverage policies, two were toy restriction policies, and one was a nutrition standards policy. The nutrition standards, default beverage offerings, and implementation characteristics varied by location. No law met the expert nutrition standards for kids' meals or beverages. CONCLUSIONS: The variations in policy specifications may influence how restaurants implement the policies, and, consequently, the policies' influences on children's consumption. Future policies could use expert nutrition standards to inform the standards set for kids' meals and specify supports for implementation.

Qualitative Study of Participation Facilitators and Barriers for Emergency School Meals and Pandemic Electronic Benefits (P-EBT) in an Urban Setting during COVID-19.

During the COVID-19 pandemic, significantly fewer of New York City's (NYC's) 1.1 million public school children participated in emergency grab-and-go meals-heightening the risk of inadequate nutrition security for many of NYC's most vulnerable residents. This study sought to examine student families' facilitators and barriers to participation in the grab-and-go meal service and their experiences with pandemic-electronic benefit transfer (P-EBT) funds, a cash benefit distributed when schools were closed. We recruited 126 parents of children in NYC public schools who had participated in the grab-and-go service. Using opened-ended questions, we interviewed 101 parents in 25 1-h online focus groups. We identified four main themes which broadly impacted school meal participation: communication, logistics, meal appeal, and personal circumstances. Key facilitating subthemes included clear communication, ease of accessing sites, and high variety. Key sub-themes negatively impacting participation included limited communication and low meal variety. Accurate, timely communication; easily accessible distribution locations; and convenient distribution times could have increased participation and satisfaction. For P-EBT, parents welcomed the funds and used them readily, but some experienced difficulties obtaining payments. The simultaneous inclusion of community-based research in the evaluation of emergency feeding programs could improve future outcomes for school meal participation and electronic benefits.

Expanding and Enhancing Food and Nutrition Education in New York City Public Schools: An Examination of Program Characteristics and Distribution.

To expand their capacity, many schools partner with food and nutrition education programs (FNPs). Public policies and funding can support FNPs, but comprehensive data on the organizations that run FNPs, their program characteristics, or distribution across schools did not exist in NYC. This study aims to help local education and health agencies assess the characteristics of food and nutrition education in schools, as well as to measure progress implementing school policies and practices. A cross-sectional study on NYC FNPs was conducted during the 2016-2017 school year. Survey data on organizations and the FNPs they operate were collected. Data on schools in which FNPs operate were gathered. To determine distribution of FNPs across schools and by school demographics, the database of FNPs in schools was combined with a publicly available database of NYC schools. In 2016-2017, 40 organizations operated 101 FNPs in 56% of NYC public schools. These FNPs varied by goals, content, activities, location, and populations served. Information on these variations can help policymakers, advocates, funders, and schools expand school-based food and nutrition education. To ensure equitable access, more coordination, investment, and collaboration are needed.

Checkpoint signaling and error correction require regulation of the MPS1 T-loop by PP2A-B56.

During mitosis, the formation of microtubule-kinetochore attachments is monitored by the serine/threonine kinase monopolar spindle 1 (MPS1). MPS1 is recruited to unattached kinetochores where it phosphorylates KNL1, BUB1, and MAD1 to initiate the spindle assembly checkpoint. This arrests the cell cycle until all kinetochores have been stably captured by microtubules. MPS1 also contributes to the error correction process rectifying incorrect kinetochore attachments. MPS1 activity at kinetochores requires autophosphorylation at multiple sites including threonine 676 in the activation segment or "T-loop." We now demonstrate that the BUBR1-bound pool of PP2A-B56 regulates MPS1 T-loop autophosphorylation and hence activation status in mammalian cells. Overriding this regulation using phosphomimetic mutations in the MPS1 T-loop to generate a constitutively active kinase results in a prolonged mitotic arrest with continuous turnover of microtubule-kinetochore attachments. Dynamic regulation of MPS1 catalytic activity by kinetochore-localized PP2A-B56 is thus critical for controlled MPS1 activity and timely cell cycle progression.

Cross-modal attention-switching is impaired in autism spectrum disorders.

This investigation aimed to determine if children with ASD are impaired in their ability to switch attention between different tasks, and whether performance is further impaired when required to switch across two separate modalities (visual and auditory). Eighteen children with ASD (9-13 years old) were compared with 18 typically-developing children matched with the ASD group for mental age, and also with 18 subjects with learning difficulties matched with the ASD group for mental and chronological age. Individuals alternated between two different visual tasks, and between a different visual task and an auditory task. Children with ASD performed worse than both comparison groups at both switching tasks. Moreover, children with ASD had greater difficulty when different modalities were required than where only one modality was required in the switching task in comparison with participants matched in terms of mental and chronological age.

Hibernation reduces pancreatic amylase levels in ground squirrels.

Pancreatic enzyme levels in mammals are influenced by food intake and dietary composition. In this study, we examined the activity and expression of pancreatic amylase in a hibernating mammal, a natural model for long-term fasting. Pancreatic tissues were obtained from summer-active 13-lined ground squirrels and hibernating squirrels that had not eaten for at least 6 weeks. Amylase specific activity was reduced by approximately 50% in the torpid hibernators compared with summer squirrels, and immunoblot analysis revealed that amylase protein expression was reduced by approximately 40% in the hibernators. Similar reductions in amylase specific activity were observed in interbout euthermic hibernators. These results support a strong influence of food intake on pancreatic enzyme expression in hibernating mammals. The maintenance of basal levels of this key digestive enzyme at approximately 50% of summer values despite the extended winter fast likely facilitates the rapid resumption of digestive function after terminal arousal in the spring.