Edible insects are often considered a nutritious, protein-rich, environmentally sustainable alternative to traditional livestock with growing popularity among North American consumers. While the nutrient composition of several insects is characterized, all potential health impacts have not been evaluated. In addition to high protein levels, crickets contain chitin and other fibers that may influence gut health. In this study, we evaluated the effects of consuming 25 grams/day whole cricket powder on gut microbiota composition, while assessing safety and tolerability. Twenty healthy adults participated in this six-week, double-blind, crossover dietary intervention. Participants were randomized into two study arms and consumed either cricket-containing or control breakfast foods for 14 days, followed by a washout period and assignment to the opposite treatment. Blood and stool samples were collected at baseline and after each treatment period to assess liver function and microbiota changes. Results demonstrate cricket consumption is tolerable and non-toxic at the studied dose. Cricket powder supported growth of the probiotic bacterium, Bifidobacterium animalis, which increased 5.7-fold. Cricket consumption was also associated with reduced plasma TNF-α. These data suggest that eating crickets may improve gut health and reduce systemic inflammation; however, more research is needed to understand these effects and underlying mechanisms.

Nociceptive sensitization is a common feature in chronic pain, but its basic cellular mechanisms are only partially understood. The present study used the model system and a candidate gene approach to identify novel components required for modulation of an injury-induced nociceptive sensitization pathway presumably downstream of Hedgehog. This study demonstrates that RNAi silencing of a member of the Bone Morphogenetic Protein (BMP) signaling pathway, Decapentaplegic (Dpp), specifically in the Class IV multidendritic nociceptive neuron, significantly attenuated ultraviolet injury-induced sensitization. Furthermore, overexpression of Dpp in Class IV neurons was sufficient to induce thermal hypersensitivity in the absence of injury. The requirement of various BMP receptors and members of the SMAD signal transduction pathway in nociceptive sensitization was also demonstrated. The effects of BMP signaling were shown to be largely specific to the sensitization pathway and not associated with changes in nociception in the absence of injury or with changes in dendritic morphology. Thus, the results demonstrate that Dpp and its pathway play a crucial and novel role in nociceptive sensitization. Because the BMP family is so strongly conserved between vertebrates and invertebrates, it seems likely that the components analyzed in this study represent potential therapeutic targets for the treatment of chronic pain in humans. This report provides a genetic analysis of primary nociceptive neuron mechanisms that promote sensitization in response to injury. larvae whose primary nociceptive neurons were reduced in levels of specific components of the BMP signaling pathway, were injured and then tested for nocifensive responses to a normally subnoxious stimulus. Results suggest that nociceptive neurons use the BMP2/4 ligand, along with identified receptors and intracellular transducers to transition to a sensitized state. These findings are consistent with the observation that BMP receptor hyperactivation correlates with bone abnormalities and pain sensitization in fibrodysplasia ossificans progressiva (Kitterman et al., 2012). Because nociceptive sensitization is associated with chronic pain, these findings indicate that human BMP pathway components may represent targets for novel pain-relieving drugs.

Purpose: Radiation and cetuximab are therapeutics used in management of head and neck squamous cell carcinoma (HNSCC). Despite clinical success with these modalities, development of both intrinsic and acquired resistance is an emerging problem in the management of this disease. The purpose of this study was to investigate signaling of the receptor tyrosine kinase AXL in resistance to radiation and cetuximab treatment.Experimental Design: To study AXL signaling in the context of treatment-resistant HNSCC, we used patient-derived xenografts (PDXs) implanted into mice and evaluated the tumor response to AXL inhibition in combination with cetuximab or radiation treatment. To identify molecular mechanisms of how AXL signaling leads to resistance, three tyrosine residues of AXL (Y779, Y821, Y866) were mutated and examined for their sensitivity to cetuximab and/or radiation. Furthermore, reverse phase protein array (RPPA) was employed to analyze the proteomic architecture of signaling pathways in these genetically altered cell lines.Results: Treatment of cetuximab-and radiation-resistant PDXs with AXL inhibitor R428 was sufficient to overcome resistance. RPPA analysis revealed that such resistance emanates from signaling of tyrosine 821 of AXL via the tyrosine kinase c-ABL. In addition, inhibition of c-ABL signaling resensitized cells and tumors to cetuximab or radiotherapy even leading to complete tumor regression without recurrence in head and neck cancer models.Conclusions: Collectively, the studies presented herein suggest that tyrosine 821 of AXL mediates resistance to cetuximab by activation of c-ABL kinase in HNSCC and that targeting of both EGFR and c-ABL leads to a robust antitumor response.

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Background 2D digital subtraction angiography (DSA) is utilized qualitatively to assess blood velocity changes that occur during arterial interventions. Quantitative angiographic metrics, such as blood velocity, could be used to standardize endpoints during angiographic interventions. Purpose To assess the accuracy and precision of a quantitative 2D DSA (qDSA) technique and to determine its feasibility for in vivo measurements of blood velocity. Materials and methods A quantitative DSA technique was developed to calculate intra-procedural blood velocity. In vitro validation was performed by comparing velocities from the qDSA method and an ultrasonic flow probe in a bifurcation phantom. Parameters of interest included baseline flow rate, contrast injection rate, projection angle, and magnification. In vivo qDSA analysis was completed in five different branches of the abdominal aorta in two 50 kg swine and compared to 4D Flow MRI. Linear regression, Bland-Altman, Pearson’s correlation coefficient and chi squared tests were used to assess the accuracy and precision of the technique. Results In vitro validation showed strong correlation between qDSA and flow probe velocities over a range of contrast injection and baseline flow rates (slope = 1.012, 95% CI [0.989,1.035], Pearson’s r = 0.996, p < .0001). The application of projection angle and magnification corrections decreased variance to less than 5% the average baseline velocity (p = 0.999 and p = 0.956, respectively). In vivo validation showed strong correlation with a small bias between qDSA and 4D Flow MRI velocities for all five abdominopelvic arterial vessels of interest (slope = 1.01, Pearson’s r = 0.880, p = <.01, Bias = 0.117 cm/s). Conclusion The proposed method allows for accurate and precise calculation of blood velocities, in near real-time, from time resolved 2D DSAs.