The physiological functions of platelet-derived growth factor receptors (PDGFRs) α and β in osteoblast biology and bone metabolism remain to be established. Here, we show that PDGFRA and PDGFRB genes are expressed by osteoblast-lineage canopy and reversal cells in close proximity to PDGFB-expressing osteoclasts within human trabecular bone remodeling units. We also report that, although removal of only one of the two PDGFRs in Osterix-positive cells does not affect bone phenotype, suppression of both PDGFRs in those osteoblast lineage cells increases trabecular bone volume in male mice as well as in female gonad-intact and ovariectomized mice. Furthermore, osteoblast lineage-specific suppression of PDGFRs reduces Csf1 expression, bone marrow level of macrophage colony-stimulating factor (M-CSF), number of osteoclasts, and, therefore, bone resorption, but does not change bone formation. Finally, abrogation of PDGFR signaling in osteoblasts blocks PDGF-induced ERK1/2-mediated Csf1 expression and M-CSF secretion in osteoblast cultures and calcitriol-mediated osteoclastogenesis in co-cultures. In conclusion, our results indicate that PDGFR signaling in osteoblast lineage cells controls bone resorption through ERK1/2-mediated Csf1 expression. © 2020 American Society for Bone and Mineral Research (ASBMR).Presentation with severe acute kidney injury due to cast nephropathy (CN) is a medical emergency in multiple myeloma (MM), with high risk of dialysis-dependent renal failure and death. Accrual of patients with CN into interventional studies is difficult, while phase III trials exclude patients with severe renal insufficiency. Real-world data are warranted. We assessed 2252 patients from the population-based Danish Multiple Myeloma Registry (DMMR) who were diagnosed between 2013 and 2017. We identified 204 patients with clinically-suspected CN, defined as serum creatinine concentration >177 μmol/L and serum free light chain (sFLC) concentration >1000 mg/L at the time of diagnosis. The median age was 72 years.  https://www.selleckchem.com/products/Temsirolimus.html  Thirty-one percent of patients presented with dialysis-dependent renal failure. Kidney biopsies were performed in 19% of patients and showed CN in 74% of cases. Despite prompt initiation of bortezomib-based therapy in 94% of patients, 33% of patients died in the first year after diagnosis. Compared with the rest of the patients in the DMMR with symptomatic MM, patients with clinically-suspected CN had worse overall survival (OS) irrespective of transplant eligibility. Achievement of renal recovery was associated with deep reductions of involved sFLC. Achievement of very good partial response or better in the first line of therapy and/or deep reduction of involved sFLC at 3 months after initiation of therapy were associated with superior OS. In conclusion, MM patients presenting with clinically-suspected CN have an alarmingly high one-year mortality when treated with current standards of care. Early and deep hematologic response is crucial for survival.Cardiac computed tomography (CT) is increasingly used to plan transcatheter structural heart interventions. However, intraoperative guidance relies on transesophageal echocardiography (TEE) and fluoroscopy. This study sought to develop a stepwise CT multi-planar reconstruction manipulation method to mimic TEE, bridging the gap between preoperative planning and intraoperative guidance tools. This CT manipulation reproduced similar configurations as TEE views in the mid-esophageal left ventricle (LV) views, transgastric LV 2-chamber views for mitral apparatus, and other miscellaneous views. Stepwise cardiac CT manipulation to mimic TEE is the final piece of the puzzle in the mental co-registration of these three crucial imaging modalities. Now, we can predict the TEE images and fluoroscopy projections in a preoperative rehearsal, thus improving the intraoperative accuracy of interventions.Chromosomal abnormalities are frequently observed in patients with chronic lymphocytic leukemia (CLL) and have prognostic value. Deletions of the short arm of chromosome 17 (and/or mutations TP53) predict resistance to chemoimmunotherapy and shorter progression-free survival after targeted therapies. Although the complex karyotype (CK) is strongly predictive of a poor prognosis in hematologic malignancies such acute myeloid leukemia or myelodysplastic syndrome, its value in CLL is subject to debate. Here, we review the literature on the CK in CLL and examine its prognostic value with different treatments. We also propose a standardized method for defining a CK in all types of hematopoietic neoplasm.Compartmentalization and spatial organization of biochemical reactions are essential for the establishment of complex metabolic pathways inside synthetic cells. Phospholipid and fatty acid membranes are the most natural candidates for this purpose, but also polymers have shown great potential as enclosures of artificial cell mimics. Herein, we report on the formation of giant vesicles in a size range of 1 μm-100 μm using amphiphilic elastin-like polypeptides. The peptide vesicles can accommodate cell-free gene expression reactions, which is demonstrated by the transcription of a fluorescent RNA aptamer and the production of a fluorescent protein. Importantly, gene expression inside the vesicles leads to a strong growth of their size-up to an order of magnitude in volume in several cases-which is driven by changes in osmotic pressure, resulting in fusion events and uptake of membrane peptides from the environment.Three years of high-dose vitamin D supplementation (400 IU, 4000 IU, 10,000 IU) in healthy vitamin D-sufficient individuals aged 55 to 70 years (serum 25(OH)D 30-125 nmol/L at baseline), resulted in a negative dose-response relationship for bone density and strength. This study examined whether response differed between males and females. A total of 311 participants (53% male) were randomized to 400 IU (male = 61, female = 48), 4000 IU (male = 51, female = 49), or 10,000 IU (male = 53, female = 49) daily vitamin D3 . Participants were scanned with high-resolution peripheral quantitative computed tomography (HR-pQCT) to measure total volumetric BMD (TtBMD) at baseline, 6, 12, 24, and 36 months. Finite element analysis estimated bone strength. Balance, physical function, and clinical biochemistry parameters were also assessed. Constrained linear mixed effects models determined time-by-treatment group-by-sex interactions. Baseline, 3-month, and 3-year levels of 25(OH)D were 76.3, 76.7, and 77.4 nmol/L (400 IU); 81.