Contextual Factors Influencing the Adoption of Physical Activity Direct Education and Policy, Systems, and Environmental Change Initiatives by Virginia EFNEP and SNAP-Ed Staff.

OBJECTIVE: To explore factors influencing the adoption of direct education programs and policy, systems, and environmental (PSE) change initiatives focused on physical activity for Supplemental Nutrition Assistance Program-eligible audiences by Virginia Expanded Food and Nutrition Education Program and Supplemental Nutrition Assistance Program-Education (SNAP-Ed) staff. METHODS: Online survey with Expanded Food and Nutrition Education Program and SNAP-Ed peer (paraprofessional) educators (n = 28) and SNAP-Ed agents (master of science level) (n = 9) in Virginia. Descriptive statistics were computed for sociodemographic characteristics and responses to questions on the basis of Likert-type scales. Exploratory factor analyses were run to identify the underlying structures of the different variables. RESULTS: The main factors for peer educators were related to substituting nutrition programs or content for physical activity programs. Other factors included staff qualifications and expectations about leading vs teaching physical activities. For PSEs, the top factors were the capacity to reach many community members, attract new partners and stakeholders, and personal interest in the PSE. CONCLUSIONS AND IMPLICATIONS: The results provide insight into potential barriers and motivators for adopting physical activity education and PSEs within community-based initiatives and can be used to inform program planning and staff training. Additional research is warranted to examine other factors influencing the adoption and implementation of physical activity programs and PSEs.

Distinct Patterns of Clonal Evolution Drive Myelodysplastic Syndrome Progression to Secondary Acute Myeloid Leukemia.

Clonal evolution in myelodysplastic syndrome (MDS) can result in clinical progression and secondary acute myeloid leukemia (sAML). To dissect changes in clonal architecture associated with this progression, we performed single-cell genotyping of paired MDS and sAML samples from 18 patients. Analysis of single-cell genotypes revealed patient-specific clonal evolution and enabled the assessment of single-cell mutational cooccurrence. We discovered that changes in clonal architecture proceed via distinct patterns, classified as static or dynamic, with dynamic clonal architectures having a more proliferative phenotype by blast count fold change. Proteogenomic analysis of a subset of patients confirmed that pathogenic mutations were primarily confined to primitive and mature myeloid cells, though we also identify rare but present mutations in lymphocyte subsets. Single-cell transcriptomic analysis of paired sample sets further identified gene sets and signaling pathways involved in two cases of progression. Together, these data define serial changes in the MDS clonal landscape with clinical and therapeutic implications. SIGNIFICANCE: Precise clonal trajectories in MDS progression are made possible by single-cell genomic sequencing. Here we use this technology to uncover the patterns of clonal architecture and clonal evolution that drive the transformation to secondary AML. We further define the phenotypic and transcriptional changes of disease progression at the single-cell level. See related article by Menssen et al., p. 330 (31). See related commentary by Romine and van Galen, p. 270. This article is highlighted in the In This Issue feature, p. 265.

The Reovirus σ3 Protein Inhibits NF-κB-Dependent Antiviral Signaling.

Viral antagonism of innate immune pathways is a common mechanism by which viruses evade immune surveillance. Infection of host cells with reovirus leads to the blockade of NF-κB, a key transcriptional regulator of the hosts' innate immune response. One mechanism by which reovirus infection results in inhibition of NF-κB is through a diminishment in levels of upstream activators, IKKß and NEMO. Here, we demonstrate a second, distinct mechanism by which reovirus blocks NF-κB. We report that expression of a single viral protein, σ3, is sufficient to inhibit expression of NF-κB target genes. Further, σ3-mediated blockade of NF-κB occurs without changes to IκB kinase (IKK) levels or activity. Among NF-κB targets, the expression of type I interferon is significantly diminished by σ3 expression. Expression of NF-κB target genes varies following infection with closely related reovirus strains. Our genetic analysis identifies that these differences are controlled by polymorphisms in the amino acid sequence of σ3. This work identifies a new role for reovirus σ3 as a viral antagonist of NF-κB-dependent antiviral pathways. IMPORTANCE Host cells mount a response to curb virus replication in infected cells and prevent spread of virus to neighboring, as yet uninfected, cells. The NF-κB family of proteins is important for the cell to mediate this response. In this study, we show that a single protein, σ3, produced by mammalian reovirus, impairs the function of NF-κB. We demonstrate that by blocking NF-κB, σ3 diminishes the hosts' response to infection to promote viral replication. This work identifies a second, previously unknown, mechanism by which reovirus blocks this aspect of the host cell response.