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Regions of hypoxia occur in most tumors and are a predictor of poor patient prognosis. Hypoxia-activated prodrugs (HAPs) provide an ideal strategy to target the aggressive, hypoxic, fraction of a tumor, while protecting the normal tissue from toxicity. A key challenge associated with the development of novel HAPs, however, is the ability to visualize the delivery of the prodrug to hypoxic regions and determine where it has been activated. Here, we report a modified version of the commonly used nitroimidazole bioreductive group that incorporates the fluoroethyl epitope of the antibody-based hypoxia imaging agent, EF5. Attachment of this group to the red fluorescent dye, dicyanomethylene (DCM), enabled us to correlate the release of the DCM dye with imaging of the reduced bioreductive group using the EF5 antibody. This study confirmed that the antibody was imaging reduction and fragmentation of the pro-fluorophore. We next employed the modified bioreductive group to synthesize a new prodrug of the KDAC inhibitor Panobinostat, EF5-Pano. Release of EF5-Pano in hypoxic multiple myeloma cells was imaged using the EF5 antibody, and the presence of an imaging signal correlated with apoptosis and a reduction in cell viability. Therefore, EF5-Pano is an imageable HAP with a proven cytotoxic effect in multiple myeloma, which could be utilized in future in vivo experiments.

The focus on interprofessional education (IPE) for professional training programs in allied health professions, such as speech-language pathology, has recently increased. There is currently limited pedagogical literature regarding both the instruction and application of IPE in any given discipline. This paper will outline challenges CSD graduate programs may face when implementing IPE content within the existing curricula and explore possible solutions. Delineation of preparation and integration process of an IPE course taught at a small liberal arts university where it was cross-listed in two undergraduate pre-professional programs in speech-language pathology and social work will be provided. Elements of the course, including delivery, descriptions of assignments, and projects, will also be discussed and how this undergraduate course may facilitate implementing IPE content into the graduate curriculum.

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation.

The professions of social work (SWK) and speech language pathology (SLP) often involve the provision of services to a diverse group of client populations in a variety of settings; this is particularly true when meeting the complex needs of children and their families. It is widely accepted that collaborative treatment approaches utilizing multidisciplinary teams is an effective method of practice when serving children who are developmentally delayed or challenged, yet there is little information in the literature regarding the quantity, quality, and efficacy of collaboration among professional disciplines serving child populations. This article addresses the identified gap in the pedagogical literature regarding collaborative case management approaches between social workers (SWKs) and speech language pathologists (SLPs) using a case example describing a child in need of early intervention services. Following the case study, sample assessment questions are provided (utilizing the professional standards from both SWK and SLP) as a measure of professional competency and practice behavior. Finally, a discussion of the practical ways SWKs and SLPs can be trained in order to be mutually supportive in meeting the needs of children requiring multidisciplinary services through a collaborative or trans-team approach is provided.

Simple Summary: Whilst multiple myeloma (MM) remains incurable, two clinical priorities are to prolong remission and reduce complications, of which fragility fractures are a major source of morbidity. To this end, there is the need to develop biomarkers that can accurately track tumour burden and bone loss to guide treatment decisions. Here, we conducted a pilot feasibility study exploring the value of novel serum bone turnover and plasma cell burden markers and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) when added to standard clinical assessment in patients with MM, monoclonal gammopathy of undetermined significance (MGUS) and smouldering MM (SMM). We show serum DKK1 and BCMA as possible correlates of tumour burden, and that serum sclerostin may correlate with bone mineral density. Furthermore, we validate DW-MRI in longitudinal assessment of tumour volume. Our study highlights emerging serum and radiological biomarkers for assessment of tumour burden and bone loss, which require further study in larger cohorts to validate these findings and understand their clinical utility. Novel biomarkers for tumour burden and bone disease are required to guide clinical management of plasma cell dyscrasias. Recently, bone turnover markers (BTMs) and Diffusion-Weighted Magnetic Resonance Imaging (DW-MRI) have been explored, although their role in the prospective assessment of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) is unclear. Here, we conducted a pilot observational cohort feasibility study combining serum BTMs and DW-MRI in addition to standard clinical assessment. Fifty-five patients were recruited (14 MGUS, 15 smouldering MM, 14 new MM and 12 relapsed MM) and had DW-MRI and serum biomarkers (P1NP, CTX-1, ALP, DKK1, sclerostin, RANKL:OPG and BCMA) measured at baseline and 6-month follow-up. Serum sclerostin positively correlated with bone mineral density (r = 0.40−0.54). At baseline, serum BCMA correlated with serum paraprotein (r = 0.42) and serum DKK1 correlated with serum free light chains (r = 0.67); the longitudinal change in both biomarkers differed between International Myeloma Working Group (IMWG)-defined responders and non-responders. Myeloma Response Assessment and Diagnosis System (MY-RADS) scoring of serial DW-MRI correlated with conventional IMWG response criteria for measuring longitudinal changes in tumour burden. Overall, our pilot study suggests candidate radiological and serum biomarkers of tumour burden and bone loss in MM/MGUS, which warrant further exploration in larger cohorts to validate the findings and to better understand their clinical utility. [ABSTRACT FROM AUTHOR]