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ObjectiveTo use cognitive interviewing and pilot testing to develop a survey instrument feasible for administering in the food pantry setting to assess daily intake frequency from several major food groups and dietary correlates (e.g. fruit and vegetable barriers) - the FRESH Foods Survey.DesignNew and existing survey items were adapted and refined following cognitive interviews. After piloting the survey with food pantry users in the USA, preliminary psychometric and construct validity analyses were performed.SettingThree US food banks and accompanying food pantries in Atlanta, GA, San Diego, CA, and Buffalo, NY.ParticipantsFood pantry clients (n 246), mostly female (68 %), mean age 54·5 (sd 14·7) years.ResultsMeasures of dietary correlates performed well psychometrically: Cronbach's α range 0·71-0·90, slope (α) parameter range 1·26-6·36, and threshold parameters (β) indicated variability in the 'difficulty' of the items. Additionally, all scales had only one eigenvalue above 1·0 (range 2·07-4·71), indicating unidimensionality. Average (median, Q1-Q3) daily intakes (times/d) across six dietary groups were: fruits and vegetables (2·87, 1·87-4·58); junk foods (1·16, 0·58-2·16); fast foods and similar entrées (1·45, 0·58-2·03); whole-grain foods (0·87, 0·58-1·71); sugar-sweetened beverages (0·58, 0·29-1·29); milk and milk alternatives (0·71, 0·29-1·29). Significant correlations between dietary groups and dietary correlates were largely in the directions expected based on the literature, giving initial indication of convergent and discriminant validity.ConclusionsThe FRESH Foods Survey is efficient, tailored to food pantry populations, can be used to monitor dietary behaviours and may be useful to measure intervention impact.

Author(s): Lisa M. Boyd [sup.1] , Renee Mehra [sup.2] , Jordan Thomas [sup.3] , Jessica B. Lewis [sup.2] , Shayna D. Cunningham [sup.4] Author Affiliations: (1) grid.47100.32, 0000000419368710, Yale School [...], Objectives Community health worker (CHW) programs are a promising strategy to improve maternal and child health outcomes, particularly among low-resource women. Yet, little is known about which aspects of CHW-client relationships are most salient for promoting positive change. This paper examines features of the CHW-client relationship that perinatal women with chronic conditions reported as being beneficial for their experience of prenatal care and pregnancy. Methods Focus groups and interviews were conducted with 18 CHWs and 39 clients from three Merck for Mothers-funded programs in the Eastern United States. Data were analyzed using a grounded theory-informed thematic approach. Results CHWs built trust-based relationships through emotional attendance, authenticity, and prioritization of clients' needs. They provided instrumental, informational, and emotional support that clients reported facilitated greater engagement with the healthcare system, improved health behaviors, and reduced stress. CHWs and clients alike viewed their relationships as having long-lasting impacts, made possible by the trust-based bond between them. Discussion Strong, trusting relationships with CHWs may be one avenue through which to improve maternal and infant health for vulnerable perinatal women. Community health care programs should promote trust-building as an explicit program goal. Trust-based CHW-client relationships may serve as an exemplar for transforming traditional care relationships between providers and clients, leading to greater client engagement in care and improved health.

The molecular mechanism through which the interaction of a clonotypic αβ T-cell receptor (TCR) with a peptide-loaded major histocompatibility complex (p/MHC) leads to T-cell activation is not yet fully understood. Here we exploit a high-affinity TCR (B4.2.3) to examine the structural changes that accompany binding to its p/MHC ligand (P18-I10/H2-Dd). In addition to conformational changes in complementarity-determining regions (CDRs) of the TCR seen in comparison of unliganded and bound X-ray structures, NMR characterization of the TCR β-chain dynamics reveals significant chemical shift effects in sites removed from the MHC-binding site. Remodelling of electrostatic interactions near the Cβ H3 helix at the membrane-proximal face of the TCR, a region implicated in interactions with the CD3 co-receptor, suggests a possible role for an allosteric mechanism in TCR signalling. The contribution of these TCR residues to signal transduction is supported by mutagenesis and T-cell functional assays.

As part of its strategy to evade detection by the host immune system, murine cytomegalovirus (MCMV) encodes three proteins that modulate cell surface expression of major histocompatibility complex class I (MHC-I) molecules: the MHC-I homolog m152/gp40 as well as the m02-m16 family members m04/gp34 and m06/gp48. Previous studies of the m04 protein revealed a divergent Ig-like fold that is unique to immunoevasins of the m02-m16 family. Here, we engineer and characterize recombinant m06 and investigate its interactions with full-length and truncated forms of the MHC-I molecule H2-L(d) by several techniques. Furthermore, we employ solution NMR to map the interaction footprint of the m06 protein on MHC-I, taking advantage of a truncated H2-L(d), "mini-H2-L(d)," consisting of only the α1α2 platform domain. Mini-H2-L(d) refolded in vitro with a high affinity peptide yields a molecule that shows outstanding NMR spectral features, permitting complete backbone assignments. These NMR-based studies reveal that m06 binds tightly to a discrete site located under the peptide-binding platform that partially overlaps with the β2-microglobulin interface on the MHC-I heavy chain, consistent with in vitro binding experiments showing significantly reduced complex formation between m06 and β2-microglobulin-associated MHC-I. Moreover, we carry out NMR relaxation experiments to characterize the picosecond-nanosecond dynamics of the free mini-H2-L(d) MHC-I molecule, revealing that the site of interaction is highly ordered. This study provides insight into the mechanism of the interaction of m06 with MHC-I, suggesting a structural manipulation of the target MHC-I molecule at an early stage of the peptide-loading pathway.

Immunoevasins are key proteins used by viruses to subvert host immune responses. Determining their high-resolution structures is key to understanding virus-host interactions toward the design of vaccines and other antiviral therapies. Mouse cytomegalovirus encodes a unique set of immunoevasins, the m02-m06 family, that modulates major histocompatibility complex class I (MHC-I) antigen presentation to CD8+ T cells and natural killer cells. Notwithstanding the large number of genetic and functional studies, the structural biology of immunoevasins remains incompletely understood, largely because of crystallization bottlenecks. Here we implement a technology using sparse nuclear magnetic resonance data and integrative Rosetta modeling to determine the structure of the m04/gp34 immunoevasin extracellular domain. The structure reveals a β fold that is representative of the m02-m06 family of viral proteins, several of which are known to bind MHC-I molecules and interfere with antigen presentation, suggesting its role as a diversified immune regulation module.

Introduction Adverse drug reactions (ADRs) have been defined by the World Health Organization (WHO) as noxious and unintended responses to a drug given at a dose established for the prophylaxis, [...], Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all [HLA-B*57:01.sup.+] patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse [CD8.sup.+] T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo. In immunocompetent Tg animals, ABC induced [CD8.sup.+] T cells with an anergy-like phenotype that did not lead to ADRs. In contrast, in vivo depletion of [CD4.sup.+] T cells prior to ABC administration enhanced DC maturation to induce systemic ABC-reactive [CD8.sup.+] T cells with an effector-like and skin-homing phenotype along with [CD8.sup.+] infiltration and inflammation in drug-sensitized skin. B7 costimulatory molecule blockade prevented [CD8.sup.+] T cell activation. These Tg mice provide a model for ABC tolerance and for the generation of HLA-B*57:01-restricted, ABC-reactive [CD8.sup.+] T cells dependent on both HLA genetic risk and immunoregulatory host factors.

Within a response to intervention framework, Tier 2 is commonly conceptualized as a supplemental, 30-minute intervention that is provided in addition to the core instructional program. Given the resource constraints that many schools face, this type of model might not be feasible. However, in the light of data that suggest a need for a well-designed, targeted intervention system, schools need to do something. This article describes one school's approach to data evaluation and Tier 2 implementation for struggling first grade readers. Working within resource constraints, the school was able to realize positive outcomes for its struggling readers by adhering to effective instructional principles, responding to data, and challenging the conventional wisdom of core plus supplement. (Contains 1 note and 1 figure.)