Endogenous PTH Deficiency Impairs Fracture Healing and Impedes the Fracture-Healing Efficacy of Exogenous PTH(1-34)

Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice.Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing

Cd2+ Toxicity to a Green Alga Chlamydomonas reinhardtii as Influenced by Its Adsorption on TiO2 Engineered Nanoparticles

In the present study, Cd2+ adsorption on polyacrylate-coated TiO2 engineered nanoparticles (TiO2-ENs) and its effect on the bioavailability as well as toxicity of Cd2+ to a green alga Chlamydomonas reinhardtii were investigated. TiO2-ENs could be well dispersed in the experimental medium and their pHpzc is approximately 2. There was a quick adsorption of Cd2+ on TiO2-ENs and a steady state was reached within 30 min. A pseudo-first order kinetics was found for the time-related changes in the amount of Cd2+ complexed with TiO2-ENs. At equilibrium, Cd2+ adsorption followed the Langmuir isotherm with the maximum binding capacity 31.9, 177.1, and 242.2 mg/g when the TiO2-EN concentration was 1, 10, and 100 mg/l, respectively. On the other hand, Cd2+ toxicity was alleviated in the presence of TiO2-ENs. Algal growth was less suppressed in treatments with comparable total Cd2+ concentration but more TiO2-ENs. However, such toxicity difference disappeared and all the data points could be fitted to a single Logistic dose-response curve when cell growth inhibition was plotted against the free Cd2+ concentration. No detectable amount of TiO2-ENs was found to be associated with the algal cells. Therefore, TiO2-ENs could reduce the free Cd2+ concentration in the toxicity media, which further lowered its bioavailability and toxicity to C. reinhardtii

Detection and Phylogenetic Analysis of Wolbachia in the Asiatic Rice Leafroller, Cnaphalocrocis medinalis, in Chinese Populations

Wolbachia are a group of intracellular inherited endosymbiontic bacteria infecting a wide range of insects. In this study the infection status of Wolbachia (Rickettsiales: Rickettsiaceae) was measured in the Asiatic rice leafroller, Cnaphalocrocis medinalis (Guenée) (Lepidoptera: Pyralidae), from twenty locations in China by sequencing wsp, ftsZ and 16S rDNA genes. The results showed high infection rates of Wolbachia in C. medinalis populations. Wolbachia was detected in all geographically separate populations; the average infection rate was ∼ 62.5%, and the highest rates were 90% in Wenzhou and Yangzhou populations. The Wolbachia detected in different C. medinalis populations were 100% identical to each other when wsp, ftsZ, and 16S rDNA sequences were compared, with all sequences belonging to the Wolbachia B supergroup. Based on wsp, ftsZ and 16S rDNA sequences of Wolbachia, three phylogenetic trees of similar pattern emerged. This analysis indicated the possibility of inter-species and intra-species horizontal transmission of Wolbachia in different arthropods in related geographical regions. The migration route of C. medinalis in mainland China was also discussed since large differentiation had been found between the wsp sequences of Chinese and Thai populations

Small bowel MR enterography: problem solving in Crohn’s disease

Magnetic resonance enterography (MRE) is fast becoming the first-line radiological investigation to evaluate the small bowel in patients with Crohn’s disease. It can demonstrate both mural and extramural complications. The lack of ionizing radiation, together with high-contrast resolution, multiplanar capability and cine-imaging make it an attractive imaging modality in such patients who need prolonged follow-up. A key question in the management of such patients is the assessment of disease activity. Clinical indices, endoscopic and histological findings have traditionally been used as surrogate markers but all have limitations. MRE can help address this question. The purpose of this pictorial review is to (1) detail the MRE protocol used at our institution; (2) describe the rationale for the MR sequences used and their limitations; (3) compare MRE with other small bowel imaging techniques; (4) discuss how MRE can help distinguish between inflammatory, stricturing and penetrating disease, and thus facilitate management of this difficult condition

Subgroup Economic Analysis for Glioblastoma in a Health Resource-Limited Setting

BACKGROUND: The aim of this research was to evaluate the economic outcomes of radiotherapy (RT), temozolomide (TMZ) and nitrosourea (NT) strategies for glioblastoma patients with different prognostic factors. METHODOLOGY/PRINCIPAL FINDINGS: A Markov model was developed to track monthly patient transitions. Transition probabilities and utilities were derived primarily from published reports. Costs were estimated from the perspective of the Chinese healthcare system. The survival data with different prognostic factors were simulated using Weibull survival models. Costs over a 5-year period and quality-adjusted life years (QALYs) were estimated. Probabilistic sensitivity and one-way analyses were performed. The baseline analysis in the overall cohort showed that the TMZ strategy increased the cost and QALY relative to the RT strategy by $25,328.4 and 0.29, respectively; and the TMZ strategy increased the cost and QALY relative to the NT strategy by$23,906.5 and 0.25, respectively. Therefore, the incremental cost effectiveness ratio (ICER) per additional QALY of the TMZ strategy, relative to the RT strategy and the NT strategy, amounts to $87,940.6 and$94,968.3, respectively. Subgroups with more favorable prognostic factors achieved more health benefits with improved ICERs. Probabilistic sensitivity analyses confirmed that the TMZ strategy was not cost-effective. In general, the results were most sensitive to the cost of TMZ, which indicates that better outcomes could be achieved by decreasing the cost of TMZ. CONCLUSIONS/SIGNIFICANCE: In health resource-limited settings, TMZ is not a cost-effective option for glioblastoma patients. Selecting patients with more favorable prognostic factors increases the likelihood of cost-effectiveness

Sesquiterpenes and lignans from the flower buds of Daphne genkwa and their nitric oxide inhibitory activities.

Chemical investigation of the Daphne genkwa has led to the isolation of four sesquiterpenes (1a/1b, 2 and 3), including one pair of sesquiterpene enantiomers (1a/1b), 1a is a new compound (+)-4-hydroxy-10-epirotundone, and twelve lignans (4-15). Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1a/1b were determined by CD analysis. All compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in BV-2 microglial cells, and compounds 7-10 exhibited pronounced inhibition on NO production with IC50 values in the range of 5.8-10.2 μM, being more active than the positive control, quercetin (IC50 = 17.0 μM)

The Dijet Mass Spectrum and a Search for Quark Compositeness in bar{p}p Collisions at sqrt{s} = 1.8 TeV

Using the DZero detector at the 1.8 TeV pbarp Fermilab Tevatron collider, we have measured the inclusive dijet mass spectrum in the central pseudorapidity region |eta_jet| < 1.0 for dijet masses greater than 200 Gev/c^2. We have also measured the ratio of spectra sigma(|eta_jet| < 0.5)/sigma(0.5 < |eta_jet| < 1.0). The order alpha_s^3 QCD predictions are in good agreement with the data and we rule out models of quark compositeness with a contact interaction scale < 2.4 TeV at the 95% confidence level.Comment: 11 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let