BackgroundPrepared food sources, including fast food restaurants and carry-outs, are common in low-income urban areas. These establishments provide foods high in calories, sugar, fat, and sodium. The aims of the study were to (1) describe the development and implementation of a carry-out intervention to provide and promote healthy food choices in prepared food sources, and (2) to assess its feasibility through a process evaluation.MethodsTo promote healthy eating in this setting, a culturally appropriate intervention was developed based on formative research from direct observation, interviews and focus groups. We implemented a 7-month feasibility trial in 8 carry-outs (4 intervention and 4 comparison) in low-income neighborhoods in Baltimore, MD. The trial included three phases: 1) Improving menu boards and labeling to promote healthier items; 2) Promoting healthy sides and beverages and introducing new items; and 3) Introducing affordable healthier combo meals and improving food preparation methods. A process evaluation was conducted to assess intervention reach, dose received, and fidelity using sales receipts, carry-out visit observations, and an intervention exposure assessment.ResultsOn average, Baltimore Healthy Carry-outs (BHC) increased customer reach at intervention carry-outs; purchases increased by 36.8% at the end of the study compared to baseline. Additionally, menu boards and labels were seen by 100.0% and 84.2% of individuals (n = 101), respectively, at study completion compared to baseline. Customers reported purchasing specific foods due to the presence of a photo on the menu board (65.3%) or menu labeling (42.6%), suggesting moderate to high dose received. Promoted entrée availability and revised menu and poster presence all demonstrated high fidelity and feasibility.ConclusionsThe results suggest that BHC is a culturally acceptable intervention. The program was also immediately adopted by the Baltimore City Food Policy Initiative as a city-wide intervention in its public markets.

These authors contributed equally to this work.Keywords: autophagy, CMML, CSF1, differentiation, primary monocyte, PRKAA1/AMPKa1, P2RY6Abbreviations: ACTB actin, b; CAMKK2, calcium/calmodulin-dependent protein kinase kinase 2, b; CASP8, caspase 8; apoptosisrelated cysteine peptidase; CFLAR CASP8 and FADD-like apoptosis regulator; CMML chronic myelomonocytic leukemia; CSF1 colony stimulating factor 1 (macrophage); CSF1R colony stimulating factor 1 receptor; DEFA1 defensin a 1; DEFA3 defensin a 3 neutrophil-specific; DRS; dorsomorphin; EMR1 EGF-like module-containing mucin-like hormone receptor-like 1; FADD Fas (TNFRSF6)-associated via death domain; ITGAM integrin a M; MAP1LC3B/LC3B microtubule-associated protein 1 light chain 3 b; P2RY6 pyrimidinergic receptor P2Y; G-protein coupled 6; PLCB3 phospholipase C; b 3 (phosphatidylinositol-specific); PLC phospholipase; PLCG2 phospholipase C gamma 2 (phosphatidylinositol-specific); PRKAA protein kinase AMP-activated; PRKAA1 protein kinase AMP-activated a 1 catalytic subunit; PRKAA2 protein kinase AMP-activated a 2 catalytic subunit; PRKAG1 protein kinase AMP-activated gamma 1 noncatalytic subunit; RIPK1 receptor (TNFRSF)-interacting serine-threonine kinase 1; STK11 serine/ threonine kinase 11; TFRC transferrin receptor; UDP uridine diphosphate; ULK1 unc-51 like autophagy activating kinase 1; WT wild-type.Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.

Velcade is one of the inescapable drug to treat patient suffering from multiple myeloma (MM) and resistance to this drug represents a major drawback for patients. However, the mechanisms underlying velcade resistance remain incompletely understood. We derived several U266 MM cell clones that resist to velcade. U266-resistant cells were resistant to velcade-induced cell death but exhibited a similar sensitivity to various proapoptotic stimuli. Careful analysis of proteosomal subunits and proteasome enzymatic activities showed that neither the composition nor the activity of the proteasome was affected in velcade-resistant cells. Elimination of velcade-induced poly-ubiquitinated proteins and protein aggregates was drastically stimulated in the resistant cells and correlated with increased cell survival. Inhibition of the lysosomal activity in velcade-resistant cells resulted in an increase of cell aggregates and decrease survival, indicating that aggregates are eliminated through lysosomal degradation. In addition, pangenomic profiling of velcade-sensitive and resistant cells showed that the small heat shock protein HSPB8 was overexpressed in resistant cells. Finally, gain and loss of function experiment demonstrated that HSPB8 is a key factor for velcade resistance. In conclusion, HSPB8 plays an important role for the elimination of aggregates in velcade-resistant cells that contributes to their enhanced survival.