More Kindergarteners are Exempted from Required School Vaccinations than in the Past

The percentage of kindergarteners being granted exemption from vaccination is growing across the U.S. as parents increasingly request exemptions for philosophical reasons. During the 2017-18 school year, 2.2% of kindergartners were exempted from vaccination. This is up from 1.6% during the 2011-12 school year

Unhealthier States have Lower COVID-19 Testing Rates

This data slice dissects the various rates of state testing for COVID-19 across the country, and explains implications of the low test rates in the unhealthier states

COVID-19 Testing Rates are Lower in States with More Black and Poor Residents

This data slice shows that testing rates to date have been lower in states with higher percent black populations and higher poverty rates. Without proper testing and physical distancing protocols, these states risk a surge in severe COVID-19 cases, overwhelming their already resource strapped healthcare systems

Geographic Disparities in COVID-19 Testing: An Urgent Call to Action

This research brief shows that testing rates are lower in states with the unhealthiest populations and worst health care access. Disparities in testing rates are troubling because delays in testing increase the risk of a surge in silent spread and severe COVID-19 cases in these states

Rural-Urban and Within-Rural Differences in COVID-19 Mortality Rates

Since late-2020, COVID-19 mortality rates have been higher in rural than in urban America, but there has also been substantial within-rural heterogeneity. Using CDC data, we compare COVID-19 mortality rates across the rural-urban continuum as well as within rural counties across different types of labor markets and by metropolitan adjacency. As of October 1, 2021, the cumulative COVID-19 mortality rate was 247.0 per 100,000 population in rural counties compared to 200.7 in urban counties. Higher COVID-19 mortality rates in rural counties are explained by lower average educational attainment and lower median household income. Within rural counties, mortality rates have been highest in farming-dependent counties and lowest in recreation-dependent counties. Those differences are similarly explained by differences in educational attainment and median household income. Our findings have implications for ongoing COVID-19 prevention and vaccination efforts as well as for informing preparation efforts for future infectious disease outbreaks

Rural COVID-19 Mortality Rates are Highest in Counties with the Largest Percentages of Blacks and Hispanics

COVID-19 mortality risk is not distributed equally across the U.S. Among rural counties, the average daily increase in COVID-19 mortality rates has been significantly higher in counties with the largest percentages of Black and Hispanic residents

Democratic Erosion Predicts Rising Deaths from Drug Poisoning and Infectious Disease

Strong democratic functioning is good for population health. However, democratic functioning eroded in many U.S. states in recent decades. The erosion was especially pronounced for one aspect of democratic functioning—electoral democracy, which refers to free and fair elections. This brief summarizes findings from a study examining how changes in electoral democracy in the 50 states predicted changes in the risk of death among adults ages 25-64 during 2000-2019. Findings demonstrate that democratic erosion strongly predicts rising deaths from drug poisoning, infectious disease, suicide, and homicide

Functional Analysis of Cdc42 Residues Required for Guanine Nucleotide Exchange

Guanine nucleotide exchange factors (GEFs) directly engage small GTPases to facilitate the exchange of bound GDP for GTP, leading to GTPase activation. Several recent crystal structures of GEFs in complex with Rho family GTPases highlight the conserved interactions and conformational alterations necessary for catalyzing exchange. In the present study, functional roles were defined for specific residues within Cdc42 implicated by the crystal structures as important for physiological exchange of guanine nucleotides within Rho GTPases. In particular, this study highlights the paramount importance of the phosphate-binding loop and interactions with the magnesium co-factor as critical for proper regulation of RhoGEF-catalyzed exchange. Other conformational alterations of the GTPases affecting interactions with the sugar and base of guanine nucleotides are also important but are secondary. Of particular note, substitution of alanine for cysteine at position 18 of Cdc42 leads to a fast cycling phenotype for Cdc42 with heightened affinity for RhoGEFs and produces a dominant negative form of Cdc42 capable of inhibiting RhoGEFs both in vitro and in vivo

Multifunctional Roles for the PH Domain of Dbs in Regulating Rho GTPase Activation

Dbl family members are guanine nucleotide exchange factors specific for Rho guanosine triphosphatases (GTPases) and invariably possess tandem Dbl (DH) and pleckstrin homology (PH) domains. Dbs, a Dbl family member specific for Cdc42 and RhoA, exhibits transforming activity when overexpressed in NIH 3T3 mouse fibroblasts. In this study, the PH domain of Dbs was mutated to impair selectively either guanine nucleotide exchange or phosphoinositide binding in vitro and resulting physiological alterations were assessed. As anticipated, substitution of residues within the PH domain of Dbs integral to the interface with GTPases reduced nucleotide exchange and eliminated the ability of Dbs to transform NIH 3T3 cells. More interestingly, substitutions within the PH domain that prevent interaction with phosphoinositides yet do not alter in vitro activation of GTPases also do not transform NIH 3T3 cell and fail to activate RhoA in vivo despite proper subcellular localization. Therefore, the PH domain of Dbs serves multiple roles in the activation of GTPases and cannot be viewed as a simple membrane-anchoring device. In particular, the data suggest that binding of phosphoinositides to the PH domain within the context of membrane surfaces may direct orientations or conformations of the linked DH and PH domains to regulate GTPases activation

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes severe coronavirus disease 2019 (COVID‐19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS‐CoV‐2, but our understanding of the cellular immune parameters that contribute to severe COVID‐19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID‐19 in unvaccinated patients with acute disease. We found that circulating CD27negCD45RA+CX3CR1+ Vδ1effector cells expressing Granzymes (Gzms) were enriched in COVID‐19 patients with acute disease. Moreover, higher frequencies of GzmB+ Vδ2+ T cells were observed in acute COVID‐19 patients. SARS‐CoV‐2 infection did not alter the γδ T cell receptor repertoire of either Vδ1+ or Vδ2+ subsets. Our work demonstrates an association between effector populations of γδ T cells and acute COVID‐19 in unvaccinated individuals