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1.
Health Promot Pract ; : 15248399231218938, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153140

RESUMO

PURPOSE: To examine differences in dietary, physical activity, and food selection behaviors of Utah SNAP-Ed participants who had varied breadth of engagement with various components of multilevel programming. METHOD: SNAP-Ed participants received a survey approximately 1 year after participating in nutrition classes. The survey measured diet, physical activity, and food selection behaviors and breadth of engagement with components of SNAP-Ed programming. Components of programming included nutrition education for adults and youth, nudge programs in food pantries and corner stores, farmers' market booths, social marketing campaign materials, and social media platforms. Kruskal-Wallis tests assessed differences in behaviors between varying breadths of program engagement. RESULTS: Among the 124 respondents, certain dietary behaviors improved with increased breadth of program engagement including intake of vegetables, low-fat dairy, and lean protein. Food selection behaviors including using MyPlate and preparing healthy foods on a budget, also improved with increased engagement. Physical activity was not impacted by additional breadth of exposure. CONCLUSIONS AND IMPLICATIONS: Findings suggest that multilevel comprehensive programming may enhance the impact of SNAP-Ed education for certain behaviors. Additional research is warranted on the impact of SNAP-Ed multilevel programming on targeted behaviors and health outcomes.

2.
Health Promot Pract ; 22(5): 685-691, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32075430

RESUMO

Purpose. To evaluate the impact of a nudge program on food pantry clients' self-reported selection and use of healthy foods. Method. A convenience sample of clients of six urban food pantries in Utah were surveyed about their experience with the Thumbs Up for Healthy Choices nudge program. Chi-square tests were used to identify associations between demographic characteristics and self-reported program impact. Results. Ninety-four percent (n = 158) of respondents agreed that the program made it easier to make healthy choices. Sixty-five percent reported healthier diets since its implementation. Additionally, Hispanic respondents were more likely to report positive impacts than non-Hispanic respondents. Conclusions and Implications. Nudge programs are effective in increasing the selection of healthy foods among pantry clients in Utah. Impacts seemed to be particularly positive for Hispanic pantry users in Utah. Nutrition programs should consider implementing these low-cost strategies to improve dietary quality of pantry users.


Assuntos
Assistência Alimentar , Dieta Saudável , Alimentos , Abastecimento de Alimentos , Humanos , Utah
3.
Health Promot Pract ; 18(6): 869-878, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28669242

RESUMO

OBJECTIVE: The objective of this study was to identify benefits and barriers to using a farmers' market (FM) incentive program among program participants. DESIGN: In qualitative semistructured interviews, participants were asked about their experiences with shopping at FM, using FM incentives, barriers to fruit and vegetable (F&V) intake, and changes in dietary intake. Interviews were recorded and transcribed. Inductive content analysis was used to code, categorize, and develop themes based on the transcriptions. SETTING: A FM in Northern Utah. SUBJECTS: A convenience sample of participants ( n = 14) completed a 45- to 60-minute interview after receiving FM incentives for an 8-week intervention period. RESULTS: FM incentives reduced barriers associated with shopping at FM such as cost and accessibility among program participants. Incentives provided participants with greater spending flexibility, allowing parents to provide children with F&V that previously did not fit into their food budget. Participants reported greater family and community involvement when shopping at FM. However, the limited hours and days of operation were factors that reduced the use of FM among participants, even when incentives were provided. CONCLUSIONS: The perceived benefits and barriers to shopping at FM and receiving FM incentives should be considered by future programmers and funding agencies.


Assuntos
Assistência Alimentar/organização & administração , Abastecimento de Alimentos/economia , Abastecimento de Alimentos/métodos , Frutas , Verduras , Adolescente , Adulto , Conscientização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Pobreza , Pesquisa Qualitativa , Estados Unidos , Utah , Adulto Jovem
4.
J Immunother Cancer ; 12(8)2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142718

RESUMO

Engagement of programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) can interfere with the CD28 signaling requisite for T-cell activation. While immune checkpoint inhibitors (ICIs) can relieve this suppression, they are unable to drive CD28 costimulation that may mechanistically contribute to ICI resistance. Thus, CD28 costimulation in the context of checkpoint inhibition may activate immunosuppressed T-cells in the tumor microenvironment. Davoceticept (ALPN-202) is an Fc fusion of a CD80 variant immunoglobulin domain (vIgD) designed to mediate PD-L1-dependent CD28 costimulation while inhibiting the PD-L1 and CTLA-4 checkpoints. PD-L1-restriction of davoceticept's CD28 costimulatory activity may minimize systemic T-cell activation and avoid untoward systemic toxicities. At the same time, preclinical studies have suggested that treatment with davoceticept during PD-1 inhibition may enhance antitumor activity by upregulating PD-L1, potentially synergizing with davoceticept's PD-L1-dependent costimulatory mechanism. This report details two cases of fatal cardiac events following treatment with davoceticept in combination with pembrolizumab (anti-PD-1) in the phase 1 study, NEON-2. Both events occurred in females in their 60s; one with choroidal melanoma and prior immunotherapy, the other with ICI-naïve microsatellite stable colorectal cancer. The clinical courses were fulminant with symptom onset at 2 weeks, followed by rapid decline. Cardiac autopsy from one patient confirmed immune-related myocarditis, and immunosequencing revealed expansion of a single T-cell clone that was not present in the pretreatment tumor. These cases highlight the importance of understanding risk factors that may contribute to immune-related myocarditis and other severe immune-related adverse events when CD28 agonism is targeted in the context of checkpoint inhibition.NEON-2 (NCT04920383).


Assuntos
Anticorpos Monoclonais Humanizados , Inibidores de Checkpoint Imunológico , Miocardite , Feminino , Humanos , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inibidores , Antígenos CD28/metabolismo , Antígeno CTLA-4/antagonistas & inibidores , Evolução Fatal , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Miocardite/induzido quimicamente , Ensaios Clínicos Fase I como Assunto
5.
J Immunother Cancer ; 12(8)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097413

RESUMO

BACKGROUND: Davoceticept (ALPN-202) is an Fc fusion of a CD80 variant immunoglobulin domain designed to mediate programmed death-ligand 1 (PD-L1)-dependent CD28 co-stimulation while inhibiting the PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) checkpoints. The safety and efficacy of davoceticept monotherapy and davoceticept and pembrolizumab combination therapy in adult patients with advanced solid tumors were explored in NEON-1 and NEON-2, respectively. METHODS: In NEON-1 (n=58), davoceticept 0.001-10 mg/kg was administered intravenous either once weekly (Q1W) or once every 3 weeks (Q3W). In NEON-2 (n=29), davoceticept was administered intravenously at 2 dose levels (0.1 or 0.3 mg/kg) Q1W or Q3W with pembrolizumab (400 mg once every 6 weeks). In both studies, primary endpoints included incidence of dose-limiting toxicities (DLT); type, incidence, and severity of adverse events (AEs) and laboratory abnormalities; and seriousness of AEs. Secondary endpoints included antitumor efficacy assessed using RECIST v1.1, pharmacokinetics, anti-drug antibodies, and pharmacodynamic biomarkers. RESULTS: The incidence of treatment-related AEs (TRAEs) and immune-related adverse events (irAEs) was 67% (39/58) and 36% (21/58) with davoceticept monotherapy, and 62% (18/29) and 31% (9/29) with davoceticept and pembrolizumab combination, respectively. The incidence of ≥grade (Gr)3 TRAEs and ≥Gr3 irAEs was 12% (7/58) and 5% (3/58) with davoceticept monotherapy, and 24% (7/29) and 10% (3/29) with davoceticept and pembrolizumab combination, respectively. One DLT of Gr3 immune-related gastritis occurred during davoceticept monotherapy 3 mg/kg Q3W. During davoceticept combination with pembrolizumab, two Gr5 cardiac DLTs occurred; one instance each of cardiogenic shock (0.3 mg/kg Q3W, choroidal melanoma metastatic to the liver) and immune-mediated myocarditis (0.1 mg/kg Q3W, microsatellite stable metastatic colorectal adenocarcinoma), prompting early termination of both studies. Across both studies, five patients with renal cell carcinoma (RCC) exhibited evidence of clinical benefit (two partial response, three stable disease). CONCLUSIONS: Davoceticept was generally well tolerated as monotherapy at intravenous doses up to 10 mg/kg. Evidence of clinical activity was observed with davoceticept monotherapy and davoceticept in combination with pembrolizumab, notably in RCC. However, two fatal cardiac events occurred with the combination of low-dose davoceticept and pembrolizumab. Future clinical investigation with davoceticept should not consider combination with programmed death-1-inhibitor anticancer mechanisms, until its safety profile is more fully elucidated. TRIAL REGISTRATION NUMBER: NEON-1 (NCT04186637) and NEON-2 (NCT04920383).


Assuntos
Anticorpos Monoclonais Humanizados , Antígeno CTLA-4 , Neoplasias , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Masculino , Feminino , Neoplasias/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Adulto , Antígeno CTLA-4/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Idoso de 80 Anos ou mais , Antígenos CD28
6.
Arthritis Rheum ; 64(6): 1730-9, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22147649

RESUMO

OBJECTIVE: CXCL10 (also known as interferon-γ-inducible 10-kd protein [IP-10]) is a chemokine that potentially plays a role in the immunopathogenesis of rheumatoid arthritis (RA). We undertook this phase II study to evaluate the efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti-IP-10) monoclonal antibody, in RA patients whose disease responded inadequately to methotrexate (MTX). METHODS: Patients with active RA receiving stable doses of MTX (10-25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) on day 85, and patients were followed up for safety to day 141. RESULTS: The ACR20 response rate was significantly higher among MDX-1100-treated patients than among placebo-treated patients (54% versus 17%; P = 0.0024). Statistically significant differences in the ACR20 response rate between treatments were observed starting on day 43 (P < 0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the groups. Overall, 51.4% of MDX-1100-treated patients and 30.3% of placebo-treated patients experienced at least 1 adverse event (AE). No study drug-related serious AEs were reported. CONCLUSION: MDX-1100 was well tolerated and demonstrated clinical efficacy in RA patients whose disease responded inadequately to MTX. This is the first study to demonstrate clinical efficacy of a chemokine inhibitor in RA and supports the notion of a potential role of IP-10 in the immunopathogenesis of RA.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Quimiocina CXCL10/antagonistas & inibidores , Metotrexato/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Resultado do Tratamento
7.
Arch Environ Contam Toxicol ; 63(3): 378-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22772597

RESUMO

Pesticides are currently regulated individually but are present in aquatic systems as mixtures of toxicants. In this study, the lethal effects of three agricultural insecticides--chlorpyrifos, imidacloprid and dimethoate--on Chironomus dilutus larvae were examined. Ninety-six-hour static bioassays were performed using single, binary, and ternary toxicant mixtures. The effects of the binary mixtures were investigated using the MIXTOX model to determine if the mixtures behaved additively, synergistically, or antagonistically. Dimethoate was much less toxic than chlorpyrifos or imidacloprid. Chlorpyrifos and dimethoate were not additive in mixture despite their common mode of action (MOA) and resulted in opposing effects (synergism and antagonism, respectively) when combined with imidacloprid. Synergism was observed in the ternary mixture. These results suggest that current mixture models based on MOA alone may not always be adequate in describing mixture effects, as in the current situation of mixtures with relatively few components. Other factors, such as water solubility, secondary MOA, and mechanisms of toxicity, should also be considered in future investigations of multichemical-mixture effects.


Assuntos
Clorpirifos/toxicidade , Dimetoato/toxicidade , Imidazóis/toxicidade , Inseticidas/toxicidade , Nitrocompostos/toxicidade , Poluentes Químicos da Água/toxicidade , Agricultura , Animais , Chironomidae , Água Doce , Neonicotinoides , Medição de Risco
8.
Nat Med ; 8(3): 274-81, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11875499

RESUMO

The importance of Bax for induction of tumor apoptosis through death receptors remains unclear. Here we show that Bax can be essential for death receptor--mediated apoptosis in cancer cells. Bax-deficient human colon carcinoma cells were resistant to death-receptor ligands, whereas Bax-expressing sister clones were sensitive. Bax was dispensable for apical death-receptor signaling events including caspase-8 activation, but crucial for mitochondrial changes and downstream caspase activation. Treatment of colon tumor cells deficient in DNA mismatch repair with the death-receptor ligand apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selected in vitro or in vivo for refractory subclones with Bax frameshift mutations including deletions at a novel site. Chemotherapeutic agents upregulated expression of the Apo2L/TRAIL receptor DR5 and the Bax homolog Bak in Baxminus sign/minus sign cells, and restored Apo2L/TRAIL sensitivity in vitro and in vivo. Thus, Bax mutation in mismatch repair--deficient tumors can cause resistance to death receptor--targeted therapy, but pre-exposure to chemotherapy rescues tumor sensitivity.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Apoptose/fisiologia , Glicoproteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2 , Proteínas Proto-Oncogênicas/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Antineoplásicos Fitogênicos/farmacologia , Proteínas Reguladoras de Apoptose , Proteína Agonista de Morte Celular de Domínio Interatuante com BH3 , Camptotecina/farmacologia , Proteínas de Transporte/metabolismo , Caspase 8 , Caspase 9 , Caspases/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Ativação Enzimática , Etoposídeo/farmacologia , Proteína de Domínio de Morte Associada a Fas , Feminino , Citometria de Fluxo , Humanos , Glicoproteínas de Membrana/uso terapêutico , Camundongos , Camundongos Nus , Mitocôndrias/metabolismo , Mutação , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases , Proteínas/metabolismo , Proteínas Proto-Oncogênicas/genética , Distribuição Aleatória , Ligante Indutor de Apoptose Relacionado a TNF , Transplante Heterólogo , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/uso terapêutico , Proteína X Associada a bcl-2
9.
Nat Cancer ; 2(1): 18-33, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-35121890

RESUMO

Innate pattern recognition receptor agonists, including Toll-like receptors (TLRs), alter the tumor microenvironment and prime adaptive antitumor immunity. However, TLR agonists present toxicities associated with widespread immune activation after systemic administration. To design a TLR-based therapeutic suitable for systemic delivery and capable of safely eliciting tumor-targeted responses, we developed immune-stimulating antibody conjugates (ISACs) comprising a TLR7/8 dual agonist conjugated to tumor-targeting antibodies. Systemically administered human epidermal growth factor receptor 2 (HER2)-targeted ISACs were well tolerated and triggered a localized immune response in the tumor microenvironment that resulted in tumor clearance and immunological memory. Mechanistically, ISACs required tumor antigen recognition, Fcγ-receptor-dependent phagocytosis and TLR-mediated activation to drive tumor killing by myeloid cells and subsequent T-cell-mediated antitumor immunity. ISAC-mediated immunological memory was not limited to the HER2 ISAC target antigen since ISAC-treated mice were protected from rechallenge with the HER2- parental tumor. These results provide a strong rationale for the clinical development of ISACs.


Assuntos
Imunoterapia , Neoplasias , Imunidade Adaptativa , Animais , Antígenos de Neoplasias , Imunoterapia/métodos , Camundongos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
10.
Curr Dev Nutr ; 5(12): nzab135, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34934898

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic profoundly affected food systems including food security. Understanding how the COVID-19 pandemic impacted food security is important to provide support and identify long-term impacts and needs. OBJECTIVE: The National Food Access and COVID research Team (NFACT) was formed to assess food security over different US study sites throughout the pandemic, using common instruments and measurements. This study presents results from 18 study sites across 15 states and nationally over the first year of the COVID-19 pandemic. METHODS: A validated survey instrument was developed and implemented in whole or part through an online survey of adults across the sites throughout the first year of the pandemic, representing 22 separate surveys. Sampling methods for each study site were convenience, representative, or high-risk targeted. Food security was measured using the USDA 6-item module. Food security prevalence was analyzed using ANOVA by sampling method to assess statistically significant differences. RESULTS: Respondents (n = 27,168) indicate higher prevalence of food insecurity (low or very low food security) since the COVID-19 pandemic, compared with before the pandemic. In nearly all study sites, there is a higher prevalence of food insecurity among Black, Indigenous, and People of Color (BIPOC), households with children, and those with job disruptions. The findings demonstrate lingering food insecurity, with high prevalence over time in sites with repeat cross-sectional surveys. There are no statistically significant differences between convenience and representative surveys, but a statistically higher prevalence of food insecurity among high-risk compared with convenience surveys. CONCLUSIONS: This comprehensive study demonstrates a higher prevalence of food insecurity in the first year of the COVID-19 pandemic. These impacts were prevalent for certain demographic groups, and most pronounced for surveys targeting high-risk populations. Results especially document the continued high levels of food insecurity, as well as the variability in estimates due to the survey implementation method.

11.
J Nutr Educ Behav ; 51(3): 342-347, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30341007

RESUMO

OBJECTIVE: To evaluate the effect of the Utah Double Up Food Bucks (DUFB) program on fruit and vegetable (F&V) intake and food security status among Supplemental Nutrition Assistance Program (SNAP) recipients. METHODS: Data were collected in 2015, using a before-and-after study design. At the farmers' market, a convenience sample of SNAP recipients was recruited for a survey and a 4-week telephone follow-up survey. Differences between the 2 surveys in food security and F&V intake were tested using the Wilcoxon signed-rank test. RESULTS: Follow-up surveys were completed with 138 (40%) of the 339 baseline participants. Median F&V consumption increased from 2.82 times per day to 3.29 times per day (median, interquartile range 1.48-3.99 and 3.28-5.02, respectively, P = .002). The percentage of DUFB participants who were food secure increased by 15% (P = .001). CONCLUSIONS AND IMPLICATIONS: The present results add to the growing literature indicating farmers' market incentives are associated with increased F&V consumption and decreased food insecurity. Although more research is needed, farmers' market incentives may be an effective area of policy intervention.


Assuntos
Dieta/estatística & dados numéricos , Assistência Alimentar , Abastecimento de Alimentos , Promoção da Saúde/métodos , Adulto , Fazendeiros , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Pobreza , Avaliação de Programas e Projetos de Saúde , Utah , Verduras
12.
J Sch Health ; 88(2): 139-149, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29333641

RESUMO

BACKGROUND: Having breakfast is correlated with health and academic benefits; yet, many children do not consume breakfast, and participation in the federal School Breakfast Program remains low. The purpose of this study was to examine parent perceptions of school breakfast and identify relationships between those who consume breakfast at school and those who do not. METHODS: A random sample of 100 schools, representing 29 school districts, across the state of Utah was selected to participate in the survey. Administrators were asked to distribute an online survey link to the parents of their school. Parents answered questions about their oldest kindergarten through 12th grade child. Qualitative and quantitative analyses were performed. RESULTS: A total of 488 parents completed the survey. In a multilevel model, child grade level, participation in free and reduced-price lunch, and perceive benefits to school breakfast were significantly related to eating breakfast at school. Some major themes from the qualitative analysis included no need for school breakfast, perception of regional values, and logistical issues. CONCLUSIONS: Parent perception of school meals is related to participation. This study identifies several areas of perception that could be address through parent education to increase school breakfast participation.


Assuntos
Desjejum , Serviços de Alimentação/estatística & dados numéricos , Pais/psicologia , Instituições Acadêmicas/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Masculino , Características de Residência , Utah
13.
Clin Cancer Res ; 24(20): 5178-5189, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30021910

RESUMO

Purpose: The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in a large percentage of human small cell lung cancer (SCLC) tumors, but absent in most normal adult tissues, making it a promising target in immuno-oncology. This study was undertaken to evaluate the preclinical efficacy of BMS-986012, a novel, nonfucosylated, fully human IgG1 antibody that binds specifically to FucGM1.Experimental Design: The antitumor activity of BMS-986012 was evaluated in in vitro assays using SCLC cells and in mouse xenograft and syngeneic tumor models, with and without chemotherapeutic agents and checkpoint inhibitors.Results: BMS-986012 showed a high binding affinity for FcγRIIIa (CD16), which resulted in enhanced antibody-dependent cellular cytotoxicity (ADCC) against FucGM1-expressing tumor cell lines. BMS-986012-mediated tumor cell killing was also observed in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) assays. In several mouse SCLC models, BMS-986012 demonstrated efficacy and was well tolerated. In the DMS79 xenograft model, tumor regression was achieved with BMS-986012 doses of 0.3 mg/kg and greater; antitumor activity was enhanced when BMS-986012 was combined with standard-of-care cisplatin or etoposide. In a syngeneic model, tumors derived from a genetically engineered model of SCLC were treated with BMS-986012 or anti-FucGM1 with a mouse IgG2a Fc and their responses evaluated; when BMS-986012 was combined with anti-PD-1 or anti-CD137 antibody, therapeutic responses significantly improved.Conclusions: Single-agent BMS-986012 demonstrated robust antitumor activity, with the addition of chemotherapeutic or immunomodulatory agents further inhibiting SCLC growth in the same models. These preclinical data supported evaluation of BMS-986012 in a phase I clinical trial of patients with relapsed, refractory SCLC. Clin Cancer Res; 24(20); 5178-89. ©2018 AACR.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Gangliosídeo G(M1)/análogos & derivados , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Gangliosídeo G(M1)/antagonistas & inibidores , Gangliosídeo G(M1)/imunologia , Gangliosídeo G(M1)/metabolismo , Humanos , Imuno-Histoquímica , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Ligação Proteica , Receptores de IgG/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
14.
J Nutr Educ Behav ; 48(1): 70-76.e1, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26598911

RESUMO

OBJECTIVE: To determine whether participation in a farmers' market incentive pilot program had an impact on food security and fruit and vegetable (F&V) intake of participants. METHODS: Participants in the Supplemental Nutrition Assistance Program were eligible to receive a dollar-per-dollar match up to $10/wk in farmers' market incentives. The researchers used a pretest-posttest design to measure F&V intake and food security status of 54 adult participants before and after receiving farmers' market incentives. The 6-item Behavior Risk Factor Surveillance System questionnaire and US Household Food Security Survey Module were used to measure F&V intake and food security, respectively. Wilcoxon signed-rank test was used to compare scores of F&V intake. RESULTS: After receiving incentives, fewer individuals reported experiencing food insecurity-related behaviors. A significantly increased intake (P < .05) was found among selected vegetables. CONCLUSION AND IMPLICATIONS: Participation in a farmers' market incentive program was positively related to greater food security and intake of select vegetables among participants in the Supplemental Nutrition Assistance Program.


Assuntos
Comportamento Alimentar , Assistência Alimentar , Abastecimento de Alimentos/métodos , Frutas , Verduras , Adulto , Idoso , Idoso de 80 Anos ou mais , Fazendeiros , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto Jovem
15.
J Nutr Educ Behav ; 47(1): 81-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25270972

RESUMO

OBJECTIVE: To determine whether participation in selected Supplemental Nutrition Assistance Program-Education (SNAP-Ed) lessons had an impact on the intent to improve nutrition-related behaviors of participants. METHODS: A quantitative study using a retrospective post-then-pre design to measure SNAP-Ed outcomes of 203 adult participants after selected nutrition lessons in 14 counties across the state of Utah. After the intervention participants completed a retrospective post-then-pre survey evaluating intent to improve nutrition behaviors related to the SNAP-Ed lessons. Wilcoxon signed rank test with Bonferroni correction and paired t test were used. RESULTS: Participants reported sometimes engaging in nutrition related behaviors before attending SNAP-Ed lessons and intent to usually engage in these behaviors after attending SNAP-Ed lessons. CONCLUSION AND IMPLICATIONS: This study demonstrated that participation in selected SNAP-Ed lessons was positively related to the intent of participants to improve nutrition-related behaviors.


Assuntos
Política Nutricional , Ciências da Nutrição/educação , Cooperação do Paciente , Adolescente , Adulto , Inquéritos sobre Dietas , Feminino , Assistência Alimentar , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Utah , Adulto Jovem
16.
J Immigr Minor Health ; 17(2): 482-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24946935

RESUMO

Resettled refugees experience high levels of food insecurity because of low English proficiency, limited job skills, and lack of understanding of the United States food system. This study evaluated integrating Supplemental Nutrition Assistance Program Education (SNAP-Ed) into English as Second Language (ESL) classes taught at a worksite- training program for recently resettled refugees and the feasibility of using food purchase receipts. A convenience sample of resettled refugees participated in SNAP-Ed one hour for 12 weeks during ESL classes. Food purchase receipts were collected for purchases one week prior to, first three weeks, last three weeks, and one week after classes. Participants were from 17 countries and 50% completed 12 lessons. Fifty-nine participants turned in receipts and 93% used SNAP funds. By integrating SNAP-Ed into ESL classes at a worksite-training center a hard-to-reach eligible population was reached. Further validation is needed to use food purchase receipts.


Assuntos
Assistência Alimentar/organização & administração , Educação em Saúde/organização & administração , Refugiados/educação , Cultura , Feminino , Humanos , Idioma , Masculino , Fatores Socioeconômicos , Estados Unidos
18.
Cancer Immunol Res ; 2(9): 846-56, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24872026

RESUMO

The programmed death-1 (PD-1) receptor serves as an immunologic checkpoint, limiting bystander tissue damage and preventing the development of autoimmunity during inflammatory responses. PD-1 is expressed by activated T cells and downmodulates T-cell effector functions upon binding to its ligands, PD-L1 and PD-L2, on antigen-presenting cells. In patients with cancer, the expression of PD-1 on tumor-infiltrating lymphocytes and its interaction with the ligands on tumor and immune cells in the tumor microenvironment undermine antitumor immunity and support its rationale for PD-1 blockade in cancer immunotherapy. This report details the development and characterization of nivolumab, a fully human IgG4 (S228P) anti-PD-1 receptor-blocking monoclonal antibody. Nivolumab binds to PD-1 with high affinity and specificity, and effectively inhibits the interaction between PD-1 and its ligands. In vitro assays demonstrated the ability of nivolumab to potently enhance T-cell responses and cytokine production in the mixed lymphocyte reaction and superantigen or cytomegalovirus stimulation assays. No in vitro antibody-dependent cell-mediated or complement-dependent cytotoxicity was observed with the use of nivolumab and activated T cells as targets. Nivolumab treatment did not induce adverse immune-related events when given to cynomolgus macaques at high concentrations, independent of circulating anti-nivolumab antibodies where observed. These data provide a comprehensive preclinical characterization of nivolumab, for which antitumor activity and safety have been demonstrated in human clinical trials in various solid tumors.


Assuntos
Anticorpos Monoclonais/imunologia , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/imunologia , Animais , Anticorpos Monoclonais/biossíntese , Células Apresentadoras de Antígenos/imunologia , Linhagem Celular Tumoral , Feminino , Humanos , Imunoterapia , Macaca fascicularis , Masculino , Camundongos , Camundongos Transgênicos , Neoplasias/terapia , Nivolumabe , Testes de Toxicidade , Microambiente Tumoral
19.
J Nutr Educ Behav ; 44(5): 407-14, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22796309

RESUMO

OBJECTIVE: To develop an online certification program for nutrition education paraprofessionals to increase knowledge and confidence and to overcome training barriers of programming time and travel expenses. DESIGN: An online interactive certification course based on Supplemental Nutrition Assistance Program-Education and Expanded Food and Nutrition Education Program core competencies was delivered to employees of both programs. Traditional vs online training was compared. Course content validity was determined through expert review by registered dietitians. Parameters studied included increase of nutrition knowledge and teaching technique/ability, educator satisfaction, and programming costs related to training. SETTING: Utah State University Extension. PARTICIPANTS: Twenty-two Supplemental Nutrition Assistance Program-Education and Expanded Food and Nutrition Education Program educators in Utah. MAIN OUTCOME MEASURES: Knowledge and skills were measured using pre/posttest statistics. Participant satisfaction was measured with a survey. ANALYSIS: Paired t test; satisfaction survey. RESULTS: The change in paraprofessional knowledge score was statistically significant (P < .001). Forty percent of paraprofessionals strongly agreed and 60% agreed they were better prepared as nutrition educators because of the training. An estimated $16,000 was saved by providing the training online as compared to a face-to-face training. CONCLUSIONS AND IMPLICATIONS: This interactive online program is a cost-effective way to increase paraprofessional knowledge and job satisfaction.


Assuntos
Certificação , Educação a Distância/métodos , Educação em Saúde/métodos , Educadores em Saúde/psicologia , Ciências da Nutrição/educação , Adulto , Análise Custo-Benefício , Educação a Distância/economia , Feminino , Educação em Saúde/economia , Humanos , Internet , Satisfação no Emprego , Masculino , Desenvolvimento de Programas/métodos , Utah
20.
Photosynth Res ; 95(2-3): 279-84, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-17922301

RESUMO

Rhodobacter capsulatus contains lhaA and pucC genes that have been implicated in light-harvesting complex 1 and 2 (LH1 and LH2) assembly. The proteins encoded by these genes, and homologues in other photosynthetic organisms, have been classified as the bacteriochlorophyll delivery (BCD) family of the major facilitator superfamily. A new BCD family phylogenetic tree reveals that several PucC, LhaA and Orf428-related sequences each form separate clusters, while plant and cyanobacterial homologues cluster more distantly. The PucC protein is encoded in the pucBACDE superoperon which also codes for LH2 alpha (PucA) and beta (PucB) proteins. PucC was previously shown to be necessary for formation of LH2. This article gives evidence indicating that PucC has a shepherding activity that keeps the homologous alpha and beta proteins of LH1 and LH2 apart, allowing LH1 to assemble properly. This shepherding function was indicated by a 62% reduction in LH1 levels in DeltaLHII strains carrying plasmids encoding pucBA along with a C-terminally truncated pucC gene. More severe reductions in LH1 were seen when the truncated pucC gene was co-expressed in the presence of C-terminal PucC::PhoA fusion proteins. It appears that interaction between truncated PucC::PhoA fusion proteins and the truncated PucC protein disrupts LH1 assembly, pointing towards a PucC dimeric or multimeric functional unit.


Assuntos
Proteínas de Bactérias/fisiologia , Complexos de Proteínas Captadores de Luz/fisiologia , Complexo de Proteína do Fotossistema II/fisiologia , Rhodobacter capsulatus/fisiologia , Proteínas de Bactérias/classificação , Complexo de Proteína do Fotossistema II/classificação , Filogenia
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