The Role of Osteocytes in Targeted Bone Remodeling: A Mathematical Model

Until recently many studies of bone remodeling at the cellular level have focused on the behavior of mature osteoblasts and osteoclasts, and their respective precursor cells, with the role of osteocytes and bone lining cells left largely unexplored. This is particularly true with respect to the mathematical modeling of bone remodeling. However, there is increasing evidence that osteocytes play important roles in the cycle of targeted bone remodeling, in serving as a significant source of RANKL to support osteoclastogenesis, and in secreting the bone formation inhibitor sclerostin. Moreover, there is also increasing interest in sclerostin, an osteocyte-secreted bone formation inhibitor, and its role in regulating local response to changes in the bone microenvironment. Here we develop a cell population model of bone remodeling that includes the role of osteocytes, sclerostin, and allows for the possibility of RANKL expression by osteocyte cell populations. This model extends and complements many of the existing mathematical models for bone remodeling but can be used to explore aspects of the process of bone remodeling that were previously beyond the scope of prior modeling work. Through numerical simulations we demonstrate that our model can be used to theoretically explore many of the most recent experimental results for bone remodeling, and can be utilized to assess the effects of novel bone-targeting agents on the bone remodeling process

Towards a New Spatial Representation of Bone Remodeling

Irregular bone remodeling is associated with a number of bone diseases such as osteoporosis and multiple myeloma. Computational and mathematical modeling can aid in therapy and treatment as well as understanding fundamental biology. Different approaches to modeling give insight into different aspects of a phenomena so it is useful to have an arsenal of various computational and mathematical models. Here we develop a mathematical representation of bone remodeling that can effectively describe many aspects of the complicated geometries and spatial behavior observed. There is a sharp interface between bone and marrow regions. Also the surface of bone moves in and out, i.e. in the normal direction, due to remodeling. Based on these observations we employ the use of a level-set function to represent the spatial behavior of remodeling. We elaborate on a temporal model for osteoclast and osteoblast population dynamics to determine the change in bone mass which influences how the interface between bone and marrow changes. We exhibit simulations based on our computational model that show the motion of the interface between bone and marrow as a consequence of bone remodeling. The simulations show that it is possible to capture spatial behavior of bone remodeling in complicated geometries as they occur \emph{in vitro} and \emph{in vivo}. By employing the level set approach it is possible to develop computational and mathematical representations of the spatial behavior of bone remodeling. By including in this formalism further details, such as more complex cytokine interactions and accurate parameter values, it is possible to obtain simulations of phenomena related to bone remodeling with spatial behavior much as \emph{in vitro} and \emph{in vivo}. This makes it possible to perform \emph{in silica} experiments more closely resembling experimental observations.Comment: Math. Biosci. Eng., 9(2), 201

Modeling and Simulation of the Effects of Cyclic Loading on Articular Cartilage Lesion Formation

We present a model of articular cartilage lesion formation to simulate the effects of cyclic loading. This model extends and modifies the reaction-diffusion-delay model by Graham et al. 2012 for the spread of a lesion formed though a single traumatic event. Our model represents "implicitly" the effects of loading, meaning through a cyclic sink term in the equations for live cells. Our model forms the basis for in silico studies of cartilage damage relevant to questions in osteoarthritis, for example, that may not be easily answered through in vivo or in vitro studies. Computational results are presented that indicate the impact of differing levels of EPO on articular cartilage lesion abatement

Forecast of Future Aviation Fuels. Part 1: Scenarios

A preliminary set of scenarios is described for depicting the air transport industry as it grows and changes, up to the year 2025. This provides the background for predicting the needs for future aviation fuels to meet the requirements of the industry as new basic sources, such as oil shale and coal, which are utilized to supplement petroleum. Five scenarios are written to encompass a range of futures from a serious resource-constrained economy to a continuous and optimistic economic growth. A unique feature is the choice of one immediate range scenario which is based on a serious interruption of economic growth occasioned by an energy shortfall. This is presumed to occur due to lags in starting a synfuels program

The Impact Use of a Multimedia Program of Investigating Model in Learning Health and Biological Science Material

Abstract: This study was done with the aim of making and testing multimedia program in Biology and Hygiene course by using scientific exploration model in Birjand. The method which is used is Quasi-experimental and the research population consists of the students of a guidance school in Birjand. This study consists of 40 individuals that have been chosen by available method and the students were considered homogeneously with average, parents, educational levels and  social status. Educational attainment in high and low levels of cognitive domain was measured in pre-test and post- test. The results of analyzing research by using combined ANOVA and repeated measurement indicates that the educational progress in both levels (upper and lower) of the cognitive area in the experimental group with compare to the control group was  significantly higher. On the other hand t-test analysis results showed that the teaching by multimedia method has been increased the period of memories in the students

Association of RS4784227-casc16 (Loc643714 locus) and RS4782447-ACSF3 polymorphisms and their association with breast cancer risk among iranian population

Peer reviewedPublisher PD

Potential miRNA biomarkers and therapeutic targets for early atherosclerotic lesions

Identification of potential therapeutic targets and biomarkers indicative of burden of early atherosclerosis that occur prior to advancement to life-threatening unstable plaques is the key to eradication of CAD prevalence and incidences. We challenged 16 baboons with a high cholesterol, high fat diet for 2 years and evaluated early-stage atherosclerotic lesions (fatty streaks, FS, and fibrous plaques, FP) in formalin-fixed common iliac arteries (CIA). We used small RNA sequencing to identify expressed miRNAs in CIA and in baseline blood samples of the same animals. We found 412 expressed miRNAs in CIA and 356 in blood samples. Eight miRNAs (miR-7975, -486-5p, -451a, -191-5p, -148a-3p, -17-5p, -378c, and -144-3p) were differentially expressed between paired fatty streak lesion and no-lesion sites of the tissue, and 27 miRNAs (e.g., miR-92a-3p, -5001, -342-3p, miR-28-3p, -21-5p, -221-3p, 146a-5p, and -16-5p) in fibrous plaques. The expression of 14 blood miRNAs significantly correlated with extent of lesions and the number of plaques. We identified coordinately regulated miRNA-gene networks in which miR-17-5p and miR-146a-5p are central hubs and miR-5001 and miR-7975 are potentially novel miRNAs associated with early atherosclerosis. In summary, we have identified miRNAs expressed in lesions and in blood that correlate with lesion burden and are potential therapeutic targets and biomarkers. These findings are a first step in elucidating miRNA regulated molecular mechanisms that underlie early atherosclerosis in a baboon model, enabling translation of our findings to humans

Postchemotherapy retroperitoneal lymph node dissection in patients with nonseminomatous testicular cancer: A single center experiences

Background: Testicular cancer accounts for about 1 - 1.5 of all malignancies in men. Radical orchiectomy is curative in 75 of patients with stage I disease, but advance stage with retroperitoneal lymph node involvement needs chemotherapy. All patients who have residual masses � 1 cm after chemotherapy should undergo postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Objectives: Treatment of advanced nonseminomatous testicular cancer is usually a combination of chemotherapy and surgery. We described our experience about postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in our center. Patients and Methods: In a retrospective cross-sectional study between 2006 and 2011, patients with a history of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) in Imam Khomeini hospital were evaluated. All patients had normal postchemotherapy serum tumor markers and primary nonseminomatous cancer. We reviewed retrospectively clinical, pathological, and surgical parameters associated with PC-RPLND in our center. Results: Twenty-one patients underwent bilateral PC-RPLND. Mean age was 26.3 years (ranged 16 - 47). Mean size of retroperitoneal mass after chemotherapy was 7.6 cm. Mean operative time was 198 minutes (120 - 246 minutes). Mean follow-up time was 38.6 months. Pathologic review showed presence of fibrosis/necrosis, viable germ cell tumor and teratoma in 8 (38.1), 10 (47.6) and 3 (14.28) patients, respectively. One patient in postoperative period of surgery and three patients in two first years after surgery were expired. Of 17 alive patients, only two (11.8) had not retrograde ejaculation. Conclusions: PC-RPLND is one the major operations in the field of urology, which is associated with significant adjunctive surgeries. In appropriate cases, PC-RPLND was associated with good cancer specific survival in tertiary oncology center. © 2015, Nephrology and Urology Research Center