Implementation of the Navajo fruit and vegetable prescription programme to improve access to healthy foods in a rural food desert.

OBJECTIVE: To utilise a community-based participatory approach in the design and implementation of an intervention targeting diet-related health problems on Navajo Nation. DESIGN: A dual strategy approach of community needs/assets assessment and engagement of cross-sectorial partners in programme design with systematic cyclical feedback for programme modifications. SETTING: Navajo Nation, USA. PARTICIPANTS: Navajo families with individuals meeting criteria for programme enrolment. Participant enrolment increased with iterative cycles. RESULTS: The Navajo Fruit and Vegetable Prescription (FVRx) Programme. CONCLUSIONS: A broad, community-driven and culturally relevant programme design has resulted in a programme able to maintain core programmatic principles, while also allowing for flexible adaptation to changing needs.

Clinical impact of molecular features in diffuse large B-cell lymphoma and follicular lymphoma.

Our understanding of the pathogenesis and heterogeneity of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) has been dramatically enhanced by recent attempts to profile molecular features of these lymphomas. In this article, we discuss ways in which testing for molecular features may impact DLBCL and FL management if clinical trials are designed to incorporate such tests. Specifically, we discuss how distinguishing lymphomas on the basis of cell-of-origin subtypes or the presence of other molecular features is prognostically and therapeutically significant. Conversely, we discuss how the molecular similarities of DLBCL and FL have provided insight into the potential of both DLBCL and FL cases to respond to agents targeting alterations they have in common. Through these examples, we demonstrate how the translation of our understanding of cancer biology into improvements in patient outcomes depends on analyzing the molecular correlates of treatment outcomes in clinical trials and in routinely treated patients.

Mutational and structural analysis of diffuse large B-cell lymphoma using whole-genome sequencing.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous cancer composed of at least 2 molecular subtypes that differ in gene expression and distribution of mutations. Recently, application of genome/exome sequencing and RNA-seq to DLBCL has revealed numerous genes that are recurrent targets of somatic point mutation in this disease. Here we provide a whole-genome-sequencing-based perspective of DLBCL mutational complexity by characterizing 40 de novo DLBCL cases and 13 DLBCL cell lines and combining these data with DNA copy number analysis and RNA-seq from an extended cohort of 96 cases. Our analysis identified widespread genomic rearrangements including evidence for chromothripsis as well as the presence of known and novel fusion transcripts. We uncovered new gene targets of recurrent somatic point mutations and genes that are targeted by focal somatic deletions in this disease. We highlight the recurrence of germinal center B-cell-restricted mutations affecting genes that encode the S1P receptor and 2 small GTPases (GNA13 and GNAI2) that together converge on regulation of B-cell homing. We further analyzed our data to approximate the relative temporal order in which some recurrent mutations were acquired and demonstrate that ongoing acquisition of mutations and intratumoral clonal heterogeneity are common features of DLBCL. This study further improves our understanding of the processes and pathways involved in lymphomagenesis, and some of the pathways mutated here may indicate new avenues for therapeutic intervention.

Understanding Impacts of SNAP Fruit and Vegetable Incentive Program at Farmers' Markets: Findings from a 13 State RCT.

Disparities in healthy food access and consumption are a major public health concern. This study reports the findings from a two-year randomized control trial conducted at 77 farmers' markets (FMs) in 13 states and the District of Columbia that sought to understand the impact of fruit and vegetable (FV) incentive vouchers, randomly issued at varied incentive levels to Supplemental Nutrition Assistance Program (SNAP) recipients, for use at FMs. Measures included FV and overall household food purchasing; FV consumption; food insecurity; health status; market expenditure; and demographics. A repeated-measures mixed-effects analysis and the Complier Average Causal Effect (CACE) were used to examine outcomes. Despite 82% reporting food insecurity in the prior year, the findings showed that financial incentives at FMs had statistically significant, positive effects on FV consumption; market expenditures increased with added incentives. SNAP recipients receiving an incentive of USD 0.40 for every USD 1.00 in SNAP spent an average of USD 19.03 per transaction, while those receiving USD 2 for every USD 1 (2:1) spent an average of USD 36.28 per transaction. The data showed that the incentive program at the highest level (2:1) maximally increased SNAP FM expenditure and FV consumption, increasing the latter by 0.31 daily cups among those who used their incentive (CACE model).

Identification and evolutionary implications of neurotransmitter-ciliary interactions underlying the behavioral response to hypoxia in Lymnaea stagnalis embryos.

Acceleration of embryonic rotation is a common response to hypoxia among pond snails. It was first characterized in Helisoma trivolvis embryos, which have a pair of sensorimotor neurons that detect hypoxia and release serotonin onto postsynaptic ciliary cells. The objective of the present study was to determine how the hypoxia response is mediated in Lymnaea stagnalis, which differ from H. trivolvis by having both serotonergic and dopaminergic neurons, and morphologically distinct ciliated structures at comparative stages of embryonic development. Time-lapse video recordings of the rotational behavior in L. stagnalis revealed similar rotational features to those previously observed in H. trivolvis, including rotational surges and rotational responses to hypoxia. Serotonin and dopamine increased the rate of rotation with similar potency. In contrast, serotonin was more potent than dopamine in stimulating the ciliary beat frequency of isolated pedal cilia. Isolated apical plate cilia displayed an irregular pattern of ciliary beating that precluded the measurement of ciliary beat frequency. A qualitative assessment of ciliary beating revealed that both serotonin and dopamine were able to stimulate apical plate cilia. The ciliary responses to dopamine were reversible in both pedal and apical plate cilia, whereas the responses to serotonin were only reversible at concentrations below 100 µmol l(-1). Mianserin, a serotonin receptor antagonist, and SKF83566, a dopamine receptor antagonist, effectively blocked the rotational responses to serotonin and dopamine, respectively. The rotational response to hypoxia was only partially blocked by mianserin, but was fully blocked by SKF83566. These data suggest that, despite the ability of serotonin to stimulate ciliary beating in L. stagnalis embryos, the rotational response to hypoxia is primarily mediated by the transient apical catecholaminergic neurons that innervate the ciliated apical plate.

Predictors of Supplemental Nutrition Assistance Program Use at Farmers' Markets With Monetary Incentive Programming.

PURPOSE: Healthy food incentive program implementation targeting people receiving Supplemental Nutrition Assistance Program (SNAP) benefits is supported by the federal Food Insecurity Nutrition Incentive (FINI) grant program. This study examined factors contributing to increased SNAP use at farmers' markets with an FINI-funded incentive program. DESIGN: Implementation evaluation. SETTING: Sixteen states and District of Columbia. PARTICIPANTS: Two hundred eighty-two FINI-funded farmers' markets open in 2016. MEASURES: Weekly SNAP sales and transactions per 1000 SNAP households in the Zip Code Tabulation Areas around markets. ANALYSIS: Two-level hierarchical regression modeling. RESULTS: Most farmers' markets (53%) had less than 100 SNAP transactions in 2016. Weekly SNAP sales and transactions per 1000 SNAP households were 69.9% and 47.7% higher, respectively, if more than 1 incentive was available versus 1. Not having paid market staff resulted in declines in these sales (-34.3%) and transactions (-38.1%) compared to markets with paid staff. There was a 6.2% and 5.1% increase in SNAP sales and transactions for each additional produce vendor. Weekly SNAP sales and transactions were about 2 to 3 times higher in rural areas compared to metropolitan. Clustering of markets within states explained 10% of the variation in weekly SNAP sales and transactions. CONCLUSION: Four implementation factors were identified that may facilitate the reach of SNAP-based monetary incentive programs at farmers' markets to maximize reach and impact among SNAP shoppers.

HOXB4 Immunoreactivity in Endometrial Tissues From Women With or Without Endometriosis.

Endometriosis is a common disease characterized by the presence of ectopic endometrial tissue. Although the pathogenesis of endometriosis remains unclear, several factors have been implicated, including the dysregulation of homeobox ( HOX) genes. Our objective was to investigate the localization and immunoreactivity of HOXB4 in endometrial tissues from women with or without endometriosis. We studied samples of eutopic endometrium (EE), endometriomas (Eoma), superficial endometriosis (SE), and deep infiltrating endometriosis (DIE) from 34 women with endometriosis, as well as eutopic endometrium from 38 women without endometriosis (EC). HOXB4 localization and immunoreactivity was assessed using immunohistochemistry and histoscore analysis. Data were analyzed with and without stratification by menstrual cycle phase. HOXB4 protein was present in the nuclei of endometrial glandular epithelial cells but not in stromal cells. HOXB4 immunoreactivity was reduced in DIE samples compared to all other groups. A smaller reduction in HOXB4 immunoreactivity was observed in SE samples compared to EC samples. HOXB4 immunoreactivity was significantly greater in proliferative compared to secretory phase samples in the EC group but not in EE, Eoma, or DIE groups. Among only proliferative phase samples, HOXB4 immunoreactivity was reduced in EE, Eoma, and DIE groups compared to EC. Based on these data, we suggest that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness.

MEF2 transcription factors: developmental regulators and emerging cancer genes.

The MEF2 transcription factors have roles in muscle, cardiac, skeletal, vascular, neural, blood and immune system cell development through their effects on cell differentiation, proliferation, apoptosis, migration, shape and metabolism. Altered MEF2 activity plays a role in human diseases and has recently been implicated in the development of several cancer types. In particular, MEF2B, the most divergent and least studied protein of the MEF2 family, has a role unique from its paralogs in non-Hodgkin lymphomas. The use of genome-scale technologies has enabled comprehensive MEF2 target gene sets to be identified, contributing to our understanding of MEF2 proteins as nodes in complex regulatory networks. This review surveys the molecular interactions of MEF2 proteins and their effects on cellular and organismal phenotypes. We include a discussion of the emerging roles of MEF2 proteins as oncogenes and tumor suppressors of cancer. Throughout this article we highlight similarities and differences between the MEF2 family proteins, including a focus on functions of MEF2B.

Driver and passenger mutations in cancer.

Next-generation sequencing has allowed identification of millions of somatic mutations and epigenetic changes in cancer cells. A key challenge in interpreting cancer genomes and epigenomes is distinguishing which genetic and epigenetic changes are drivers of cancer development. Frequency-based and function-based approaches have been developed to identify candidate drivers; we discuss the advantages and drawbacks of these methods as well as their latest refinements. We focus particularly on identification of the types of drivers most likely to be missed, such as genes affected by copy number alterations, mutations in noncoding regions, dysregulation of microRNA, epigenetic changes, and mutations in chromatin modifiers.

MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.

Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial-mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis.

Integrative biology of an embryonic respiratory behaviour in pond snails: the 'embryo stir-bar hypothesis'.

Embryos of freshwater snails undergo direct development from single cell to juvenile inside egg masses that are deposited on vegetation and other substratum in pond, lake and stream habitats. Helisoma trivolvis, a member of the Planorbidae family of basommatophoran snails, has served as a model for studying the developmental and physiological roles for neurotransmitters during embryogenesis. Early studies revealed that H. trivolvis embryos from stage E15 to E30, the period between gastrulation and the trochophore-juvenile transition, display a cilia-driven behaviour consisting of slow basal rotation and transient periods of rapid rotation. The discovery of a bilateral pair of early serotonergic neurons, named ENC1, which project an apical process to the embryo surface and basal neurites to ciliated cells, prompted the hypothesis that each ENC1 is a dual-function sensory and motor neuron mediating a physiological embryonic response. This article reviews our past and present studies and addresses questions concerning this hypothesis, including the following. (1) What environmental signal regulates ENC1 activity and rotational behaviour? (2) Does ENC1 function as both a primary sensory and motor neuron underlying the rotational behaviour? (3) What are the sensory transduction mechanisms? (4) How does ENC1 regulate ciliary beating? (5) Do other basommatophoran species have similar neural-ciliary pathways and behavioural responses? (6) How is the behaviour manifest in the dynamic natural environment? In this review, we introduce the ;embryo stir-bar hypothesis', which proposes that embryonic rotation is a hypoxia-sensitive respiratory behaviour responsible for mixing the egg capsule fluid, thereby enhancing delivery of environmental oxygen to the embryo.