How Does the Gus Schumacher Nutrition Incentive Program Work? A Theory of Change

Increased fruit and vegetable (FV) intake is associated with decreased risk of nutrition-related chronic diseases. Sociodemographic disparities in FV intake indicate the need for strategies that promote equitable access to FVs. The United States Department of Agriculture’s Gus Schumacher Nutrition Incentive Program (GusNIP) supports state and local programs that offer nutrition incentives (NIs) that subsidize purchase of FVs for people participating in the Supplemental Nutrition Assistance Program (SNAP). While a growing body of research indicates NIs are effective, the pathways through which GusNIP achieves its results have not been adequately described. We used an equity-focused, participatory process to develop a retrospective Theory of Change (TOC) to address this gap. We reviewed key program documents; conducted a targeted NI literature review; and engaged GusNIP partners, practitioners, and participants through interviews, workshops, and focus groups in TOC development. The resulting TOC describes how GusNIP achieves its long-term outcomes of increased participant FV purchases and intake and food security and community economic benefits. GusNIP provides NIs and promotes their use, helps local food retailers develop the capacity to sell FVs and accept NIs in accessible and welcoming venues, and supports local farmers to supply FVs to food retailers. The TOC is a framework for understanding how GusNIP works and a tool for improving and expanding the program.     

Circulating tumor DNA predicts efficacy of a dual AKT/p70S6K inhibitor (LY2780301) plus paclitaxel in metastatic breast cancer: plasma analysis of the TAKTIC phase IB/II study

The phosphatidylinositol‐3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway is frequently activated in HER2‐negative breast cancer and may play a role in taxane resistance. The phase IB/II TAKTIC trial ({"type":"clinical-trial","attrs":{"text":"NCT01980277","term_id":"NCT01980277"}}NCT01980277) has shown that combining a dual AKT and p70 ribosomal protein S6 kinase (p70S6K) inhibitor (LY2780301) taken orally with weekly paclitaxel in HER2‐negative advanced breast cancer is feasible, with preliminary evidence of efficacy. We wanted to explore whether circulating tumor DNA (ctDNA) may be a surrogate marker of treatment efficacy in this setting. Serial plasma samples were collected and cell‐free DNA was sequenced using low‐coverage whole‐genome sequencing, and analysis was completed with droplet digital polymerase chain reaction (PCR) for some patients with driver mutations. Baseline tumor fraction (TF) and TF after 7 weeks on treatment were compared to progression‐free survival (PFS) and the overall response rate. We also explored circulating copy number alterations associated with treatment failure. Of the 51 patients enrolled in the TAKTIC trial, at least one plasma sample was available for 44 cases (96 timepoints). All patients with tumor TP53, PI3KCA, or AKT1 mutations harbored at least one of these alterations in plasma. TF at inclusion was correlated with PFS (6m‐PFS was 92% for ctDNAneg patients vs 68% for ctDNApos cases; hazard ratio [HR] = 3.45, 95% confidence interval [CI] [1.34–8.90], P = 0.007). ctDNA status at week 7 was not correlated with prognosis. Even though most circulating copy number alterations were conserved at disease progression, some genomic regions of interest were altered in post‐progression samples. In conclusion, ctDNA detection at baseline was associated with shorter PFS in patients included in the TAKTIC trial. Plasma‐based copy number analysis may help to identify alterations involved in resistance to treatment.     

Pathway analysis tools and toxicogenomics reference databases for risk assessment

The pharmaceutical industry has begun to leverage a range of new technologies (proteomics, pharmacogenomics, metabolomics and molecular toxicology [e.g., toxicogenomics]) and analysis tools that are becoming increasingly integrated in the area of drug discovery and development. The approach of analyzing the vast amount of toxicogenomics data generated using molecular pathway and networks analysis tools in combination with analysis of reference data will be the main focus of this review. We will demonstrate how this combined approach can increase the understanding of the molecular mechanisms that lead to chemical-induced toxicity and application of this knowledge to compound risk assessment. We will provide an example of the insights achieved through a molecular toxicology analysis based on the well-known hepatotoxicant lipopolysaccharide to illustrate the utility of these new tools in the analysis of complex data sets, both in vivo and in vitro. The ultimate objective is a better lead selection process that improves the chances for success across the different stages of drug discovery and development.     

To the point: medical education reviews--providing feedback

Formative feedback is an essential component of effective teaching and learning. Without it, the learner flounders. Furthermore, the Liaison Committee on Medical Education requires formative feedback within the clerkship and specifies that students must have the time and ability to remediate deficiencies before completing the clerkship. Few articles in the medical literature address how to give effective feedback. However, the themes within these articles are consistent. Formative feedback should be an interactive activity between the teacher and learner. Feedback must be approached with mutual respect and should be provided in a safe environment. Quality feedback is timely, specific to the situation, constructive, based on direct observation and nonjudgmental. With effective feedback, learners (and teachers) can discover what to improve, as well as which behaviors and skills to reinforce and augment. Learners appreciate and request specific feedback. In addition, learners tend to rate teachers who provide feedback more highly than they rate teachers who do not provide feedback. This article in the "To the Point" series will focus on the components of effective feedback and provide a practical and effective approach to giving feedback.     

Walnut Oil Reduces Aβ Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease

(1) Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ_1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ_1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.     

Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.