Estimating the avoidable burden of certain modifiable risk factors in osteoporotic hip fracture using Generalized Impact Fraction (GIF) model in Iran

Backgrounds: The number of hip fractures, the most common complication of osteoporosis, has increased rapidly over the past decades. The goal of this study is to estimate the avoidable burden of certain modifiable risk factor of the condition using the Generalized Impact Fraction (GIF) model, which has been suggested and used by epidemiologists to overcome the drawbacks associated with the use of Attributable Fraction index. In addition to preventing a risk factor or the avoidable fraction of burden, this index can also calculate the change in the burden, when a risk factor is altered.Methods: International databases were searched through PubMed, CINAHLD, Embase using OVID and Google scholar. National resources were searched through IranDoc, IranMedex, SID and Journal sites. Other resources include abstract books and articles sent to the IOF congress. The following search strategy was used: (" Osteoporotic fracture" OR " Fragility Hip fracture" OR " Calcium" OR " vitamin D" OR " BMI" OR " lean body weight" OR " Physical activity" OR " exercise" OR " Smoke" ) AND (" prevalence" OR " incidence" OR " relative risk" ) and limited to " humans." Results: With regards to different scenarios already explained in modifying the studied risk factors, the greatest impact in reducing the prevalence of risk factors on osteoporotic hip fractures, was seen in low serum vitamin D levels, low physical activity and low intake of calcium and vitamin D, respectively. According to the fact that interventions for low serum vitamin D and low intake of calcium and vitamin D, are related to each other, it can be concluded that implementing interventions to change these two risk factors, in the easy, moderate and difficult scenarios, would result in approximately a 5%, 11% and 17% decrease in the burden of osteoporotic hip fractures, respectively. The addition of interventions addressing low physical activity in the easy, moderate and difficult scenarios, an 8%, 21% and 35% reduction in the burden of osteoporotic hip fractures would be reported, respectively.Conclusion: Improving serum vitamin D levels, recommending the consumption of calcium and vitamin D supplementations and advocating physical activity are the most effective interventions to reduce the risk of osteoporotic hip fractures. © 2013 Shahnazari et al; licensee BioMed Central Ltd

Influence of B cells in liver fibrosis associated with hepatitis B virus harboring basal core promoter mutations

The development of the liver disease in chronic hepatitis B with common viral variants can be determined through the interaction between the virus and the host immune response. B cells constitute half of the intrahepatic lymphocyte population with an impact on fibrosis. A proliferation-inducing ligand (APRIL) has been shown to have a co-stimulatory activity on B cells. For this study HBV DNA was amplified and then sequenced to show the presence of the basal core promoter (BCP) mutations in the serum from 57 patients with chronic hepatitis B. The range of IgD-positive B cells was detected by immunohistochemistry in liver biopsies; and patients serum was assayed for APRIL levels by enzyme immunoassay. Twenty-seven patients (47.4) harbored the A1762T-G1764A BCP mutations. Coefficients of logistic regression showed that the effect of increasing IgD-positive B cells in rising odds of the liver disease is the same in the patients with BCP mutation A1762T-G1764A and in the patients without mutation, nevertheless the effect of APRIL is not similar in these two groups of patients. Logistic regression in patients with BCP A1762T-G1764A mutations demonstrated that increasing one score of APRIL decreased the odds of fibrosis stage about 8. These results suggest that in infection with viral variants of hepatitis B virus, the population of IgD-positive B cells may play a decisive role in later stages of the liver disease which is reduced by APRIL in chronic hepatitis patients with BCP mutations. J. Med. Virol. 84:18891896, 2012. (c) 2012 Wiley Periodicals, Inc

The Increased Level of Serum p53 in Hepatitis B-Associated Liver Cirrhosis

BACKGROUND: The ability of tumour suppressor protein p53 (P53) to regulate cell cycle processes can be modulated by hepatitis B virus (HBV). While preliminary evidences indicates the involvement of protein-x of HBV (HBx) in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients. METHODS: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay (ELISA) was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis. RESULTS: There was a significant association between the serum p53 and cirrhosis (OR=1.81 95 CI: 1.017-3.2, P=0.044). Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV (1.98+/-1.22 vs. 1.29+/-0.72 U/ml, P=0.05). No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase (ALP) and alanine aminotransferase (ALT) with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33. CONCLUSION: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach

Microarchitecture and Nanomechanical Properties of Trabecular Bone After Strontium Administration in Osteoporotic Goats

Strontium (Sr) ralenate is a new agent used for the prevention and treatment of osteoporosis. As a bone-seeking element, 98% of Sr is deposited in the bone and teeth after oral ingestion. However, the effect of Sr treatment on bone microarchitecture and bone nanomechanical properties remains unclear. In this study, 18 osteoporotic goats were divided into four groups according to the treatment regimen: control, calcium alone (Ca), calcium and Sr at 24 mg/kg (Ca + 24Sr), and calcium and Sr at 40 mg/kg (Ca + 40Sr). The effects of Sr administration on bone microarchitecture and nanomechanical properties of trabecular bones were analyzed with micro-CT and nanoindentation test, respectively. Serum Sr levels increased six- and tenfold in the Ca + 24Sr and Ca + 40Sr groups, respectively. Similarly, Sr in the bone increased four- and sixfold in these two groups. Sr administration significantly increased trabecular bone volume fraction, trabecular thickness, and double-labeled new bone area. Sr administration, however, did not significantly change the nanomechanical properties of trabecular bone (elastic modulus and hardness). The data suggested that Sr administration increased trabecular bone volume and improved the microarchitecture while maintaining the intrinsic tissue properties in the osteoporotic goat model

Deleterious Effects of Simulated Spaceflight on Bone and Microvasculature in Adult Mice

Long-term spaceflight leads to extensive changes in the musculoskeletal system attributable, in part, to unloading during microgravity exposure. Additionally, irradiation at doses similar to that of a solar flare or a round-trip sojourn to Mars may cause significant depletion of stem/progenitor cell pools throughout the body as well as inflammation associated with prompt skeletal-tissue degradation. Previously, we demonstrated that irradiation leads to rapid bone loss, which can be mitigated in the short term by injection of a potent antioxidant (-lipoic acid). Furthermore, simulated weightlessness in adult mice adversely affects skeletal responses to low linear energy transfer (LET) radiation (137Cs). Here, we hypothesized that simulated weightlessness exacerbates the adverse effects of simulated space radiation (including both protons and 56Fe ions) by adversely affecting skeletal structure and functions as well as associated vasculature. Furthermore, we hypothesized that an antioxidant cocktail, which has been shown to be protective in other tissues, mitigates space radiation induced bone loss

Inhibition of the Progesterone Nuclear Receptor during the Bone Linear Growth Phase Increases Peak Bone Mass in Female Mice

Augmentation of the peak bone mass (PBM) may be one of the most effective interventions to reduce the risk of developing osteoporosis later in life; however treatments to augment PBM are currently limited. Our study evaluated whether a greater PBM could be achieved either in the progesterone nuclear receptor knockout mice (PRKO) or by using a nuclear progesterone receptor (nPR) antagonist, RU486 in mice. Compared to their wild type (WT) littermates the female PRKO mice developed significantly higher cancellous and cortical mass in the distal femurs, and this was associated with increased bone formation. The high bone mass phenotype was partially reproduced by administering RU486 in female WT mice from 1–3 months of age. Our results suggest that the inhibition of the nPR during the rapid bone growth period (1–3 months) increases osteogenesis, which results in acquisition of higher bone mass. Our findings suggest a crucial role for progesterone signaling in bone acquisition and inhibition of the nPR as a novel approach to augment bone mass, which may have the potential to reduce the burden of osteoporosis

Management Science Letters Solving a mixed-integer linear programming model for a multi-skilled project scheduling problem by simulated annealing

A multi-skilled project scheduling problem (MSPSP) has been generally presented to schedule a project with staff members as resources. Each activity in project network requires different skills and also staff members have different skills, too. This causes the MSPSP becomes a special type of a multi-mode resource-constrained project scheduling problem (MM-RCPSP) with a huge number of modes. Given the importance of this issue, in this paper, a mixed integer linear programming for the MSPSP is presented. Due to the complexity of the problem, a metaheuristic algorithm is proposed in order to find near optimal solutions. To validate performance of the algorithm, results are compared against exact solutions solved by the LINGO solver. The results are promising and show that optimal or near-optimal solutions are derived for small instances and good solutions for larger instances in reasonable time

Solving a mixed-integer linear programming model for a multi-skilled project scheduling problem by simulated annealing

A multi-skilled project scheduling problem (MSPSP) has been generally presented to schedule a project with staff members as resources. Each activity in project network requires different skills and also staff members have different skills, too. This causes the MSPSP becomes a special type of a multi-mode resource-constrained project scheduling problem (MM-RCPSP) with a huge number of modes. Given the importance of this issue, in this paper, a mixed integer linear programming for the MSPSP is presented. Due to the complexity of the problem, a meta-heuristic algorithm is proposed in order to find near optimal solutions. To validate performance of the algorithm, results are compared against exact solutions solved by the LINGO solver. The results are promising and show that optimal or near-optimal solutions are derived for small instances and good solutions for larger instances in reasonable time

Solving a novel multi-skilled project scheduling model by scatter search

A multi-skilled project scheduling problem (MSPSP) has generally been presented to schedule information technology projects in deterministic conditions. The contribution of this model is to consider the resources, called staff members. These members are regarded as valuable, renewable, and discrete resources with different multiple skills. The different skills of staff members, as well as the project networks activity requirement of different skills, cause this problem to become a special type of multi-mode resource-constrained project scheduling problem (MM-RCPSP), with a huge number of modes. Taking into account the importance of this issue and the few studies performed on this problem, a novel mathematical model for the MSPSP is presented. Since the complexity of this problem is NP-hard, an efficient scatter search (SS) algorithm is developed to solve such a difficult problem. This proposed SS is capable of generating optimised solutions in small sizes, and the excellent solutions in large sizes are compared with the solutions reported by a proposed Tabu search (TS) algorithm