Bone marrow fibrosis is a critical component of primary myelofibrosis (PMF). But the origin of myofibroblasts that drive fibrosis is unknown. Using genetic fate mapping we found that bone marrow Leptin receptor (Lepr) – expressing mesenchymal stromal lineage cells expanded extensively and were the fibrogenic cells in PMF. These stromal cells down-regulated the expression of key haematopoietic stem cell (HSC)- supporting factors and up-regulated genes associated with fibrosis and osteogenesis, indicating fibrogenic conversion. Administration of imatinib or conditional deletion of platelet-derived growth factor receptor a (Pdgfra) from Lepr+ stromal cells suppressed their expansion and ameliorated bone marrow fibrosis. Conversely, activation of the PDGFRa pathway in bone marrow Lepr+ cells led to expansion of these cells and extramedullary haematopoiesis, features of PMF. Our data identify Lepr+ stromal lineage cells as the origin of myofibroblasts in PMF and suggest that targeting PDGFRa signaling could be an effective way to treat bone marrow fibrosis.

Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.

Health professions students with higher levels of religiosity and lower levels of self-reported familiarity with various religious perspectives on sex reported less positive attitudes toward LGBT individuals. Results suggest that personal factors may be important to address in interprofessional curriculum related to LGBT patient care. Self-report biases and other factors may limit the accuracy and generalizability of the findings.

Cervical kyphotic deformity can be a debilitating condition with symptoms ranging from mechanical neck pain, radiculopathy, and myelopathy to impaired swallowing and horizontal gaze. Surgical correction of cervical kyphosis has the potential to halt progression of neurological and clinical deterioration and even restore function. There are various operative approaches and deformity correction techniques. Choosing the optimal strategy is predicated on a fundamental understanding of spine biomechanics. Preoperative characterization of cervical malalignment, assessment of deformity rigidity, and defining postoperative clinical and radiographic objectives are paramount to formulating a surgical plan that balances clinical benefit with morbidity. This review of cervical deformity treatment provides an overview of the biomechanics of cervical kyphosis, radiographic classification, algorithm-based management, surgical techniques, and current surgical outcome studies.

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