Survival of children with chronic medical illnesses is leading to an increase in secondary osteoporosis due to impaired peak bone mass (PBM). Insulin-like growth factor type 1 (IGF-1) levels correlate with the pattern of bone mass accrual and many chronic illnesses are associated with low IGF-1 levels. Reduced serum levels of IGF-1 minimally affect the integrity of the skeleton, whereas recent studies suggest that skeletal IGF-I regulates PBM. To determine the role of IGF-1 in postnatal bone mass accrual regardless of source, we established an inducible type 1 Igf receptor Cre/lox knockout mouse model, in which the type 1 Igf receptor was deleted inducibely in the mesenchymal stem cells (MSCs) from 3-7 weeks of age. The size of the mouse was not affected as knockout and wild type mice had similar body weights and nasoanal and femoral lengths. However, bone volume and trabecular bone thickness were decreased in the secondary spongiosa of female knockout mice relative to wild type controls, indicating that IGF-1 is critical for bone mass. IGF-1 signaling in MSCs in vitro has been implicated to be involved in both migration to the bone surface and differentiation into bone forming osteoblasts. To clarify the exact role of IGF-1 in bone, we found by immunohistochemical analysis that a similar number of Osterix-positive osteoprogenitors were on the bone perimeter, indicating migration of MSCs was not affected. Most importantly, 56% fewer osteocalcin-positive mature osteoblasts were present on the bone perimeter in the secondary spongiosa in knockout mice versus wild type littermates. These in vivo data demonstrate that the primary role of skeletal IGF-1 is for the terminal differentiation of osteoprogenitors, but refute the role of IGF-1 in MSC migration in vivo. Additionally, these findings confirm that impaired IGF-1 signaling in bone MSCs is sufficient to impair bone mass acquisition. Keywords: osteoblasts; knockout mice; cell migration; IGF receptor; nestin Bone Research (2013) 2: 186-194. doi: 10.4248 /BR201302007 IntroductionBone mass normally peaks in mid to late adolescence, plateaus for several years and then declines over time (1-5). Acquisition of a higher peak bone mass (PBM) in adolescence is associated with reduced subsequent fracture risk, whereas impaired acquisition of PBM or loss of bone in childhood is associated with greater fracture risk. Chronic illness in childhood impairs PBM acquisition. Survival of many chronic illnesses in childhood are leading to a growing incidence of secondary osteoporosis (6). The prevention of secondary osteoporosis in children with chronic illnesses depends on protecting the bones of this at-risk population. However, before treatment can be developed, the regulation of cellular signaling mechanisms involved in the acquisition of bone mass needs to be further elucidated.Janet L. Crane et al. www.boneresearch.org | Bone Research 187The only cells that form new bone are osteoblasts, which are non-replicative mononuclear cells derived from mesenchymal stem cells (MSC) (7-...
Primary cardiac tumours are a rare clinical entity that can present with myriad of non-specific cardiopulmonary symptoms. We describe a case of a 61-year-old previously healthy woman who presented with progressive dyspnoea and lower extremity swelling, suggestive of acute left-sided heart failure. Transthoracic echocardiogram revealed a large, 3.7×3.2 cm intracardiac mass resulting in severe mitral valvular dysfunction. The patient underwent surgical resection of the mass, however, negative margins were not obtained, and the tumour quickly returned. Histological and molecular analysis was consistent with the diagnosis of undifferentiated pleomorphic sarcoma with murine double minute 2 (MDM2) amplification. Given the overall grim prognosis, the patient chose to pursue comfort-based care. She died at home 9 months after the initial diagnosis. Here, we provide an updated review of the literature for the classification of undifferentiated pleomorphic cardiac sarcoma and potential treatment modalities.
Background:There is an increasing interest in using digitized whole-slide imaging (WSI) for routine surgical pathology diagnoses. Screencasts are digital recordings of computer screen output with advanced interactive features that allow for the preparation of videos. Screencasts that include hyperlinks to WSIs could help teach pathology residents how to become familiar with technologies that they are likely to use in their future career.Materials and Methods:Twenty screencasts were prepared with Camtasia 2.0 software (TechSmith, Okemos, MI, USA). They included clinical history, videos of chest X-rays and/or chest computed tomography images, links to WSI digitized with an Aperio Turbo AT scanner (Leica Biosystems, Buffalo Grove, IL, USA), pre- and posttests, and faculty-narrated videos of the WSI in a manner closely resembling a slide seminar and other educational materials. Screencasts were saved in a hospital network, Screencast.com, YouTube.com, and Vimeo.com. The screencasts were viewed by 12 pathology residents and fellows who made diagnoses, answered the quizzes, and took a survey with questions designed to evaluate their perception of the quality of this technology. Quiz results were automatically e-mailed to faculty. Pre- and posttest results were compared using a paired t-test.Results:Screencasts can be viewed with Windows PC and Mac operating systems and mobile devices; only videos saved in our network and screencast.com could be used to generate quizzes. Participants’ feedback was very favorable with average scores ranging from 4.5 to 4.8 (on a scale of 5). Mean posttest scores (87.0% [±21.6%]) were significantly improved over those in the pretest quizzes (48.5% [±31.2%]) (P < 0.0001).Conclusion:Screencasts with WSI that allow residents and fellows to diagnose cases using digital microscopy may prove to be a useful technology to enhance the pathology education. Future studies with larger numbers of screencasts and participants are needed to optimize various teaching strategies.
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