Healthy Options: A Community-Based Program to Address Food Insecurity

The objectives of this study are to better understand the lived experience of food insecurity in our community and to examine the impact of a community-based program developed to increase access to local, healthy foods. Participants were given monthly vouchers to spend at local farmers’ markets and invited to engage in a variety of community activities. Using a community-based participatory research framework, mixed methods were employed. Survey results suggest that most respondents were satisfied with the program and many increased their fruit and vegetable consumption. However, over 40% of respondents reported a higher level of stress over having enough money to buy nutritious meals at the end of the program. Photovoice results suggest that the program fostered cross-cultural exchanges, and offered opportunities for social networking. Building upon the many positive outcomes of the program, community partners are committed to using this research to further develop policy-level solutions to food insecurity

Effects of a Mobile Fueling Station on Performance in Division III Soccer Players

Topics in Exercise Science and Kinesiology Volume 4: Issue 1, Article 11, 2023. This study aimed to determine if there was an ergogenic effect of utilizing a mobile fueling station in Division III soccer teams. Mobile fueling stations have been shown to be a feasible and sustainable option to support nutrition periodization in college-aged athletes. To date, no studies have analyzed the effect of these stations on athletic performance. We analyzed the effects of this fueling strategy on sprint speed, sprint count, and athlete acceptance during soccer practices and competitions. Athletes from the DeSales University Men’s and Women’s soccer teams (n=35) completed two weeks of data collection in a randomized, crossover design, with one week of fueling using the mobile fueling station (WS), and one week without fueling (NS). In the WS condition, participants ate a carbohydrate-containing snack before soccer practice or competition and ate a snack containing carbohydrates and protein after. Sprint data were collected using GPS sensors, and a post-study questionnaire evaluated athlete acceptance and perceived effectiveness. An a priori alpha level for significance was set at 0.05, and sprint data were analyzed using univariate analysis of variance. While there were no statistically significant differences (p\u3e0.05) in peak (WS=7.65 m/s, NS=7.9 m/s) and mean (WS=6.93 m/s, NS=7.01 m/s) sprint speed or maximum (WS=13, NS=12.16) and mean (WS=8.16, NS=7.46) sprint count, survey responses indicated that 100% of athletes found that mobile fueling stations improved their athletic performance and would like it to be a permanent fixture of their athletic program. These results indicate that mobile fueling stations are perceived as beneficial by Division III soccer players

Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure

Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. > 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells

An adaptive signaling network in melanoma inflammatory niches confers tolerance to MAPK signaling inhibition

Mitogen-activated protein kinase (MAPK) pathway antagonists induce profound clinical responses in advanced cutaneous melanoma, but complete remissions are frustrated by the development of acquired resistance. Before resistance emerges, adaptive responses establish a mutation-independent drug tolerance. Antagonizing these adaptive responses could improve drug effects, thereby thwarting the emergence of acquired resistance. In this study, we reveal that inflammatory niches consisting of tumor-associated macrophages and fibroblasts contribute to treatment tolerance through a cytokine-signaling network that involves macrophage-derived IL-1β and fibroblast-derived CXCR2 ligands. Fibroblasts require IL-1β to produce CXCR2 ligands, and loss of host IL-1R signaling in vivo reduces melanoma growth. In tumors from patients on treatment, signaling from inflammatory niches is amplified in the presence of MAPK inhibitors. Signaling from inflammatory niches counteracts combined BRAF/MEK (MAPK/extracellular signal–regulated kinase kinase) inhibitor treatment, and consequently, inhibiting IL-1R or CXCR2 signaling in vivo enhanced the efficacy of MAPK inhibitors. We conclude that melanoma inflammatory niches adapt to and confer drug tolerance toward BRAF and MEK inhibitors early during treatmen

Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma

Abstract Background Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. Methods There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy. Discussion This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma. Trial registration ClinicalTrials.gov NCT03307616, registered October 12, 2017

Targeting endothelin receptor signalling overcomes heterogeneity driven therapy failure

Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. > 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells

Inhibiting drivers of non-mutational drug tolerance is a salvage strategy for targeted melanoma therapy

Once melanomas have progressed with acquired resistance to mitogen-activated protein kinase (MAPK)-targeted therapy, mutational heterogeneity presents a major challenge. We therefore examined the therapy phase before acquired resistance had developed and discovered the melanoma survival oncogene MITF as a driver of an early non-mutational and reversible drug-tolerance state, which is induced by PAX3-mediated upregulation of MITF. A drug-repositioning screen identified the HIV1-protease inhibitor nelfinavir as potent suppressor of PAX3 and MITF expression. Nelfinavir profoundly sensitizes BRAF and NRAS mutant melanoma cells to MAPK-pathway inhibitors. Moreover, nelfinavir is effective in BRAF and NRAS mutant melanoma cells isolated from patients progressed on MAPK inhibitor (MAPKi) therapy and in BRAF/NRAS/PTEN mutant tumors. We demonstrate that inhibiting a driver of MAPKi-induced drug tolerance could improve current approaches of targeted melanoma therapy

Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort123

Background: Exposure to polyunsaturated fatty acids (PUFAs) in early life may influence adiposity development