Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies

A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow— stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers. SIGNIFICANCE: We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics.</p

How mental health occupational therapists address issues of diet with their clients: A qualitative study

Background: Poor diet is a contributing factor to the high rates of obesity and related comorbidities in people with severe mental illness, and dietary change is a key treatment strategy. Providing healthy lifestyle interventions is a recognised role for occupational therapists. However, the existing literature fails to elucidate boundaries of this role. To begin to address this gap in the literature, this study explored the attitudes, actions and beliefs of mental health occupational therapists about providing diet-related interventions. Methods: Semi-structured interviews were conducted with mental health occupational therapists working in one Area Health Service in New South Wales. Purposive sampling was used. Data were analysed using Constructivist Grounded Theory methods, where meaning is co-constructed by, and the theory ultimately grounded in the experiences of, the participant and researcher. Results: The participants felt confident providing clients with interventions to promote diet-related skill development and providing general healthy eating education to support this development. However, they were not comfortable providing clients with specific dietary advice. Participants identified a need for further training and support to enhance their effectiveness in providing healthy eating education and highlighted the need for more dietitians in mental health services. Conclusions: The occupational therapists in this study identified clear boundaries of their role in providing diet-related interventions for people with severe mental illness. Suggestions for improvement in this area included further training for occupational therapists as well as increased access to dietitians for those services that lie outside the occupational therapy role

Pediatric traumatic brain injury:Language outcomes and their relationship to the arcuate fasciculus

Pediatric traumatic brain injury (TBI) may result in long-lasting language impairments alongside dysarthria, a motor-speech disorder. Whether this co-morbidity is due to the functional links between speech and language networks, or to widespread damage affecting both motor and language tracts, remains unknown.Here we investigated language function and diffusion metrics (using diffusion-weighted tractography) within the arcuate fasciculus, the uncinate fasciculus, and the corpus callosum in 32 young people after TBI (approximately half with dysarthria) and age-matched healthy controls (. n=. 17). Only participants with dysarthria showed impairments in language, affecting sentence formulation and semantic association. In the whole TBI group, sentence formulation was best predicted by combined corpus callosum and left arcuate volumes, suggesting this "dual blow" seriously reduces the potential for functional reorganisation. Word comprehension was predicted by fractional anisotropy in the right arcuate. The co-morbidity between dysarthria and language deficits therefore seems to be the consequence of multiple tract damage. © 2013 Elsevier Inc

Antimicrobial susceptibility of Histophilus somni isolated from clinically affected cattle in Australia

This study investigated antimicrobial resistance traits, clonal relationships and epidemiology of Histophilus somni isolated from clinically affected cattle in Queensland and New South Wales, Australia. Isolates (n = 53) were subjected to antimicrobial susceptibility testing against six antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tetracycline, tilmicosin and tulathromycin) using disc diffusion and minimum inhibitory concentration (MIC) assays. Clonal relationships were assessed using repetitive sequence PCR and descriptive epidemiological analysis was performed. The H. somni isolates appeared to be geographically clonal, with 27/53 (47%) isolates grouping in one cluster from one Australian state. On the basis of disc diffusion, 34/53 (64%) isolates were susceptible to all antimicrobial agents tested; there was intermediate susceptibility to tulathromycin in 12 isolates, tilmicosin in seven isolates and resistance to tilmicosin in one isolate. Using MIC, all but one isolate was susceptible to all antimicrobial agents tested; the non-susceptible isolate was resistant to tetracycline, but this MIC result could not be compared to disc diffusion, since there are no interpretative guidelines for disc diffusion for H. somni against tetracycline. In this study, there was little evidence of antimicrobial resistance in H. somni isolates from Australian cattle. Disc diffusion susceptibility testing results were comparable to MIC results for most antimicrobial agents tested; however, results for isolates with intermediate susceptibility or resistance to tilmicosin and tulathromycin on disc diffusion should be interpreted with caution in the absence of MIC results

A qualitative study of older adults’ and healthcare professionals’ perspectives on the potential of functional food products to support healthy ageing

Providing Mediterranean Diet (MD) nutrients in a minimally-processed functional food product may support healthy ageing, mediating favourable gut microbiota profiles when MD adherence is challenging. We thematically analysed stakeholders’ perspectives of functional food products targeting healthy ageing, through semi-structured individual and group interviews in Ireland, with 47 older-adults (recruited through social, retirement and disease-support groups); and 26 HCPs across a range of disciplines. Functional food products could provide a “boost” of hard-to-reach nutrients, supplementary fibre and/or protein, but there is caution with “silver bullet” products. Changing dentition (texture), appetite (portion size), dexterity (packaging; preparation ease) must be reflected, without stigmatising branding/presentation, while cost and availability were considered important. It was perceived that “sugar is the enemy”, while plant-based proteins were welcomed. In summary, novel food products could supplement, but not replace, a balanced diet for older adults, providing additional protein and fibre in a convenient, sustainable, carefully branded product