Letter to the editor: From Min Gong et al: "Risk for infections during treatment with denosumab for osteoporosis: a systematic review and meta-analysis"

To the editor: We read with great interest the systematic review by Diker-Cohen et al (1) about the risk of infection under the treatment of denosumab for osteoporosis. This is a well-conducted systematic review that provided us with valuable information about the safety of denosumab. We would like to point out some concerns about the analytic methods used in the systematic review. We noticed that the main outcome of this systematic review was the serious adverse events of infections (SAEIs), and the authors reported the results measured by risk ratio (RR) and risk difference (RD). The authors claimed that they used RD with the Mantel-Haenszel method to deal with studies with no events in both arms. We totally agree with this. However, for RR, they failed to use a valid method to deal with studies with no events; instead, they discarded such studies in the meta-analysis. This is problematic as such studies generally indicate no difference for treatment effects for balanced trials, and discarding them is expected to result in an overestimate of the effects (2). In their systematic review of SAEI outcome, 9 out of 34 studies had no events in both arms, and 5 of them had balanced sample size in treatment and control arms.Scopu

Fatigue crack propagation behavior of Ni-based superalloys after overloading at elevated temperatures

AbstractThe fatigue crack propagation behavior of three superalloys subjected to a single overloading at elevated temperatures was investigated. The fatigue crack propagation rate FCPR versus stress intensity factor range data da/dN—ΔK were calculated using the two-point secant method. It was found that the crack growth rates of the investigated materials were retarded after overloading with an overload ratio ROL=1.6. The size of the plastic zone in the front of the crack tip and its relation to loading level were discussed. The overload retardation effects are attributed to crack closure. The fatigue damage in the plastic zone can also be a factor to explain the overload retardation

Increased Neutralizing Antibody Production and Interferon-γ Secretion in Response to Porcine Reproductive and Respiratory Syndrome Virus Immunization in Genetically Modified Pigs

T cell-mediated immunity plays a prominent role in combating pathogens infection. Both the engagement of the T cell receptor with the peptide-bound major histocompatibility complex and a costimulatory signal are needed for the complete activation of the T cell. To determine whether host immune responses to vaccination could be improved by enhancing CD28-mediated costimulation and verify whether the boosted immune responses could protect the host against viral challenge, we produced a transgenic pig line expressing an extra copy of the CD28 gene controlled by its own promoter at the Rosa26 locus. As expected, in response to porcine reproductive and respiratory syndrome virus (PRRSV) strain vaccination, CD4+ T cells was remarkably increased in CD28 transgenic pigs and a similar response in CD8+ T cells was elicited after challenge. Importantly, because of increased T cell frequencies, the virus-neutralizing antibody against JXA-1 (a highly pathogenic Chinese PRRSV strain), as well as interferon-γ secretion, were enhanced in transgenic pigs. These findings in our translational study provide a novel concept for farm animal breeding in disease resistance, in which we may use the transgenic technology to force overexpression of confirmed immunity-promoting molecules like CD28 and produce an animal with enhanced immune responses to vaccination and broad-spectrum resistance to infectious diseases

Development and application of an antigen capture ELISA assay for diagnosis of Japanese encephalitis virus in swine, human and mosquito

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis (JE) is a serious zoonosis caused by the Japanese encephalitis virus (JEV) which is a mosquito-borne pathogen of the family <it>Flavivirus</it>. However, the application of several developed laboratory methods for the detection of JEV antigens or antibodies are limited by their requirements of laboratory operations, skilled technicians and special facilities.</p> <p>Results</p> <p>To develop a method for detecting JEV antigen in swine, human, mosquito and other clinical specimens specifically, conveniently and effectively, an antigen capture enzyme-linked immunosorbent assay (ELISA) was established in this study. Sensitivity, specificity, repeatability and stability of the developed method were evaluated, and 60 clinical samples were tested in this study. The results demonstrated that the antigen capture ELISA was capable in detecting JEV antigen with high sensitivity and specificity compared with conventional methods. 14 samples showed the positive result with coincidence rate of 70%, and 46 displayed negative result with coincidence rate of 100% as compared to that of reverse transcription-polymerase chain reaction (RT-PCR).</p> <p>Conclusions</p> <p>The developed ELISA assay provides a convenient and specific method for the large-scale determination of JEV antigen in infected swine, human and mosquito samples with high sensitivity and specificity.</p

Classification of human coronary atherosclerotic plaques with T1, T2 and Ultrashort TE MRI

Multicontrast MRI with T1, T2 and Ultrashort TE (UTE) sequences is used to image atherosclerotic plaque in human coronary arteries. MRI classification of the plaques is compared with their histological classification and found to correlate extremely well. The addition of UTE MRI adds significant value to the imaging of human coronary artery plaque by MRI

Left ventricular remodeling following myocardial infarction revealed with a quantitative diffusion MRI tractography framework

A cardiac-tailored framework for 3D Diffusion Tensor MRI tractography is developed and used to characterize myofiber architecture in normal and remodeled myocardium. We show that myofibers in the subepicardium of the remote infarct zone become less oblique (more circumferential) as the heart dilates and remodels. This fiber realignment may play an important role in the loss of contractile function in the remote zone over time