Effects of Bioactive Glass Scaffold and BMP-2 in Segmental Defects

poster abstractReconstruction of segmental defects in the load-bearing area has long been a challenge in orthopaedics. We have demonstrated the feasibility of a biodegradable load-bearing scaffold fabricated from poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) loaded with bone morphogenetic protein-2 (BMP-2) to successfully induce healing in those defects. However, there is limited osteoconduction observed with the PPF/TCP scaffold itself. Furthermore, a recent review on BMP-2 revealed greater risks in radiculities, ectopic bone formation, osteolysis and poor global outcome in association with the use of BMP-2 for spinal fusion. The aims of this study were to evaluate the potential use of a more osteoconductive material 13-93 bioactive glass and the potential side effects of locally delivered BMP-2 on adjacent bones. 13-93 glass scaffolds were fabricated by indirect selective laser sintering and implanted into critical size defects created in rat right femurs with and without 10 micrograms of BMP-2. The X-ray and micro-CT results showed that bridging callus was found as soon as 3 weeks and progressed gradually in the BMP group while minimal bone formation was observed in the control group. As expected, stiffness, peak load and energy to break of the BMP group were all higher than the control group. Higher healing rates in the 13-93 group was found compared to the healing rate in PPF/TCP group evaluated in the past indicating a more osteoconductive nature of the 13-93 scaffolds. The scaffolds of both control and BMP groups were partially degraded after 15 weeks as seen in the histological images. For the effects of local BMP-2 delivery to adjacent bones, no statistical difference in the bone area, mineral content and mineral density was found between control and BMP groups. In conclusion, a 13-93 bioactive glass scaffold with local BMP-2 delivery has been demonstrated for its potential application in treating large bone defects

Using Sidereal Rotation Period Expressions to Calculate the Sun’s Rotation Period through Observation of Sunspots

We utilize sidereal rotation period expressions to calculate the sun’s rotation period via sunspot observation. From the well-known astronomical sites, we collected sunspot diagrams for 14 months, from January 2013 to February 2014, to analyze, compare, and implement statistical research. In addition to acquiring the average angular rate of the movement of sunspots, we found that even the same number of sunspots moved at different angular rates, and generally the life of larger sunspots is longer than 10 days. Therefore the larger sunspots moved around the back of the sun, and a handful of relatively smaller sunspots disappeared within a few days. The results show that the solar rotation period varied with the latitude. However, if we take the average of the sunspots at high and low latitudes, we find that the calculated value is very close to the accredited values

Genetic copy number variants in myocardial infarction patients with hyperlipidemia

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is the chief cause of death in Taiwan and many countries, of which myocardial infarction (MI) is the most serious condition. Hyperlipidemia appears to be a significant cause of myocardial infarction, because it causes atherosclerosis directly. In recent years, copy number variation (CNV) has been analyzed in genomewide association studies of complex diseases. In this study, CNV was analyzed in blood samples and SNP arrays from 31 myocardial infarction patients with hyperlipidemia.</p> <p>Results</p> <p>We identified seven CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001), at 1p21.3, 1q31.2 (<it>CDC73</it>), 1q42.2 (<it>DISC1</it>), 3p21.31 (<it>CDCP1</it>), 10q11.21 (<it>RET</it>) 12p12.3 (<it>PIK3C2G</it>) and 16q23.3 (<it>CDH13</it>), respectively. In particular, the CNV region at 10q11.21 was examined by quantitative real-time PCR, the results of which were consistent with microarray findings.</p> <p>Conclusions</p> <p>Our preliminary results constitute an alternative method of evaluating the relationship between CNV regions and cardiovascular disease. These susceptibility CNV regions may be used as biomarkers for early-stage diagnosis of hyperlipidemia and myocardial infarction, rendering them valuable for further research and discussion.</p

Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration

10.1194/jlr.M073684Journal of Lipid Research5891785-179

A Method of Upgrading a Hydrostatic Model to a Nonhydrostatic Model

As the sigma-p coordinate under hydrostatic approximation can be interpreted as the mass coordinate with out the hydro static approximation, we propose a method that up grades a hydro static model to a nonhydrostatic model with relatively less effort. The method adds to the primitive equations the extra terms omitted by the hydro static approximation and two prognostic equations for vertical speed w and nonhydrostatic part pres sure p'. With properly formulated governing equations, at each time step, the dynamic part of the model is first integrated as that for the original hydro static model and then nonhydrostatic contributions are added as corrections to the hydro static solutions. In applying physical parameterizations after the dynamic part integration, all physics pack ages of the original hydro static model can be directly used in the nonhydrostatic model, since the up graded nonhydrostatic model shares the same vertical coordinates with the original hydro static model. In this way, the majority codes of the nonhydrostatic model come from the original hydro static model. The extra codes are only needed for the calculation additional to the primitive equations. In order to handle sound waves, we use smaller time steps in the nonhydrostatic part dynamic time integration with a split-explicit scheme for horizontal momentum and temperature and a semi-implicit scheme for w and p'. Simulations of 2-dimensional mountain waves and density flows associated with a cold bubble have been used to test the method. The idealized case tests demonstrate that the pro posed method realistically simulates the nonhydrostatic effects on different atmospheric circulations that are revealed in the oretical solutions and simulations from other nonhydrostatic models. This method can be used in upgrading any global or mesoscale models from a hydrostatic to nonhydrostatic model

Clinical and Epidemiologic Research Ethnic Variation in Early Age-Related Macular Degeneration Lesions Between White Australians and Singaporean Asians

Citation: Joachim N, Mitchell P, Younan C, et al. Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians. Invest Ophthalmol Vis Sci. 2014;55:4421-4429. DOI:10.1167/iovs.14-14476 PURPOSE. We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians. METHODS. Participants of the Blue Mountains Eye Study (BMES; whites, n ¼ 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n ¼ 3280, Indian, n ¼ 3400, and Chinese, n ¼ 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD. RESULTS. After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ‡500 to &lt;3000 lm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (&lt;500 lm radius). CONCLUSIONS. Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p

A Novel Histone Deacetylase Inhibitor Exhibits Antitumor Activity via Apoptosis Induction, F-Actin Disruption and Gene Acetylation in Lung Cancer

BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. METHODOLOGY/PRINCIPAL FINDINGS: The cytotoxicity effect of OSU-HDAC-44 was examined in three human NSCLC cell lines including A549 (p53 wild-type), H1299 (p53 null), and CL1-1 (p53 mutant). The antiproliferative mechanisms of OSU-HDAC-44 were investigated by flow cytometric cell cycle analysis, apoptosis assays and genome-wide chromatin-immunoprecipitation-on-chip (ChIP-on-chip) analysis. Mice with established A549 tumor xenograft were treated with OSU-HDAC-44 or vehicle control and were used to evaluate effects on tumor growth, cytokinesis inhibition and apoptosis. OSU-HDAC-44 was a pan-HDAC inhibitor and exhibits 3-4 times more effectiveness than suberoylanilide hydroxamic acid (SAHA) in suppressing cell viability in various NSCLC cell lines. Upon OSU-HDAC-44 treatment, cytokinesis was inhibited and subsequently led to mitochondria-mediated apoptosis. The cytokinesis inhibition resulted from OSU-HDAC-44-mediated degradation of mitosis and cytokinesis regulators Auroroa B and survivin. The deregulation of F-actin dynamics induced by OSU-HDAC-44 was associated with reduction in RhoA activity resulting from srGAP1 induction. ChIP-on-chip analysis revealed that OSU-HDAC-44 induced chromatin loosening and facilitated transcription of genes involved in crucial signaling pathways such as apoptosis, axon guidance and protein ubiquitination. Finally, OSU-HDAC-44 efficiently inhibited A549 xenograft tumor growth and induced acetylation of histone and non-histone proteins and apoptosis in vivo. CONCLUSIONS/SIGNIFICANCE: OSU-HDAC-44 significantly suppresses tumor growth via induction of cytokinesis defect and intrinsic apoptosis in preclinical models of NSCLC. Our data provide compelling evidence that OSU-HDAC-44 is a potent HDAC targeted inhibitor and can be tested for NSCLC chemotherapy

Human pharyngeal microbiota in age-related macular degeneration.

BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A