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Glucocorticoid-induced osteoporosis (GIOP) is associated with elevated fracture risk. Practice guidelines have been published to reduce this risk but are insufficiently followed in everyday practice. The objectives of this study were to estimate fracture incidence in patients exposed to oral glucocorticoids and to analyse the impact of glucocorticoid use on fracture incidence.This retrospective cohort study was performed using the Medical Data Vision (MDV) claims database from Japan. All patients aged ≥ 18 years initiating oral glucocorticoids and fulfilling Japanese guideline criteria for starting prophylactic osteoporosis treatment between 2009 and 2019 were identified. These were matched to a cohort of unexposed controls using propensity score matching. Fracture incidence in the two cohorts were compared using a Fine-Gray proportional sub-distribution hazard model.13,090 glucocorticoid-exposed cases were compared to 13,090 unexposed controls. The 1-year fracture rate (all sites) was 9.3 [95% CI 8.8-9.8] in cases and 5.8 [5.4-6.2] in controls. One-year vertebral fracture rates were 4.3 [4.0-4.7] and 2.3 [2.1-2.6] respectively. In the multivariate analysis, the use of glucocorticoids was associated with an increase in the incidence of osteoporotic fractures (hazard ratio: 1.63 [1.51-1.76]). The glucocorticoid-associated risk tended to be higher in subgroups of patients with rheumatoid arthritis, asthma, COPD and in those aged 65 years.Oral glucocorticoid use is associated with an increase in fracture incidence. It is necessary to raise awareness of GIOP and to take public health measures to change the perceptions and behaviour of doctors prescribing glucocorticoids.

Purpose Oncolytic viral therapy for neuroblastoma (NB) cells with Sindbis virus (SINV) is a promising strategy for treating high-risk NB. Here, we evaluated the possibility of using SINV structural proteins as therapeutic agents for NB since UV-inactivated SINV could induce cytopathogenic effects. Methods The cytotoxicity of UV-inactivated SINV toward human NB cell lines NB69, NGP, GOTO, NLF, SK-N-SH, SH-SY5Y, CHP134, NB-1, IMR32, and RT-BM-1 were analyzed. Apoptosis was confirmed by TUNEL assays. To determine the components of SINV responsible for the cytotoxicity of UV-inactivated SINV, expression vectors encoding the structural proteins, namely capsid, E2, and E1, were transfected in NB cells. Cytotoxicity was evaluated by MTT assays. Results UV-inactivated SINV elicited more significant cytotoxicity in NB69, NGP, and RT-BM-1 than in normal human fibroblasts. Results of the transfection experiments showed that all NB cell lines susceptible to UV-inactivated SINV were highly susceptible to the E1 protein, whereas fibroblasts transfected with vectors harboring capsid, E1, or E2 were not. Conclusions We demonstrated that the cytotoxicity of the UV-inactivated SINV is due to apoptosis induced by the E1 structural protein of SINV, which can be used selectively as a therapeutic agent for NB.

Background: MicroRNAs (miRNAs) are involved in essential biological activities, and have been reported to exhibit differential expression profiles in various cancers. Our previous study demonstrated that intercellular adhesion molecule-2 (ICAM2) inhibition induces radiosensitisation in oral squamous cell carcinoma (OSCC) cells. Thus, we hypothesised that certain miRNAs play crucial roles in radioresistance in OSCC by regulating ICAM2 expression. Methods: Because predicted target gene analyses revealed that microRNA-125b (miR-125b) potentially regulates ICAM2 mRNA expression, we examined the association between miR-125b and radioresistance. The expression of miR-125b was investigated by real-time quantitative reverse transcriptase–PCR. For a functional analysis, miR-125b was transfected to OSCC-derived cells. Results: A downregulated expression of miR-125b was found in OSCC-derived cell lines and OSCC samples. The miR-125b-transfected cells showed a decreased proliferation rate, enhanced radiosensitivity to X-ray irradiation and diminished ICAM2 mRNA expression. Moreover, miR-125b expression correlated with OSCC tumour staging and survival. Conclusion: These findings suggested that the downregulated miR-125b expression was associated with proliferation and radioresistance mechanisms, probably through ICAM2 signalling. Thus, controlling the expression or activity of miR-125b might contribute to suppressing proliferation and overcoming radioresistance in OSCC.

Stathmin is an intracellular phosphoprotein that is overexpressed in a number of human malignancies. Our previous study using proteomic profiling showed that significant upregulation of stathmin occurs in oral squamous-cell carcinoma (OSCC)-derived cell lines. In the current study, to determine the potential involvement of stathmin in OSCC, we evaluated the state of stathmin protein and mRNA expression in OSCC-derived cell lines and human primary OSCCs. A significant increase in stathmin expression was observed in all OSCC-derived cell lines examined compared to human normal oral keratinocytes. In immunohistochemistry, 65% of the OSCCs were positive for stathmin, and no immunoreaction was observed in corresponding normal tissues. Real-time quantitative reverse transcriptase–polymerase chain reaction data were consistent with the protein expression status. Moreover, stathmin expression status was correlated with the TNM stage grading. Furthermore, we found a statistical correlation between the protein expression status and disease-free survival (P=0.029). These results suggest that expression of stathmin could contribute to cancer progression/prognosis, and that stathmin may have potential as a biomarker and a therapeutic target for OSCC.

Diblock copolymers consisting of electron-donating poly[2,7-(9,9-dihexylfluorene)] (PF) rods and electron-withdrawing poly(pendent isoindigo) (Piso) coils were designed and synthesized through a click reaction. The electronic properties and interchain organization of the copolymers could be tuned by varying the PF/Piso ratio (PF14-b-Pison (n=10, 20, 60 and 100)). The highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels of the studied polymers were progressively reduced as the length of Piso increased, affecting the charge trapping and intramolecular charge transfer environment between PF and Piso domains. Thermally treated PF14-b-Pison thin films exhibited a clear nanofibrillar structure, and the d-spacing was enhanced systematically as the Piso chain length increased. Resistive memory characteristics were explored with a sandwich indium tin oxide/PF14-b-Pisons/Al device configuration. The enhanced conjugated PF conducting channels led to stable resistance switching behavior, exhibiting volatile SRAM (static random access memory) (PF14-b-Piso10) and nonvolatile WORM (write-once-read-many-times) (PF14-b-Piso20, PF14-b-Piso60, PF14-b-Piso100) characteristics with a large ON/OFF ratio (106) and a stable retention time (104 s). A more appealing feature is that such memory cells were integrated on a soft poly(dimethylsiloxane) substrate, allowing for the development of a stretchable data storage device. Reliable and reproducible electrical characteristics, including SRAM- and WORM-type memories, could be explored as the device was stretched under an applied tensile strain ranging from 0 to 50%. The studied donor–acceptor copolymers indeed showed great potential for stretchable electronic applications with controllable digital information storage characteristics. A copolymer whose electrical properties can be tuned by varying the ratio of its two blocks is promising for wearable data storage devices. Polymer–based memory devices have excited much interest because of their flexibility, low cost and printability, but so far no stretchable memory devices based on copolymers made up of electron–donating and –accepting blocks have been made. Now, Wen–Chang Chen of National Taiwan University and co–workers have fabricated a series of copolymers made of electron-donating rods and electron–accepting coils. The rods impart the copolymer with superior electrical properties, while the coils give it flexibility. Varying the ratio of the rods to coils allows the copolymer's properties to be varied. The researchers demonstrated that reproducible electrical characteristics can be obtained even when tensile strains of up to 50% are applied. Stretchable resistive memories were created using donor–acceptor rod-coil diblock copolymers, poly(polyfluorene)-b-poly(pendent isoindigo), with different block ratios. Reliable and reproducible electrical characteristics of volatile SRAM- and nonvolatile WORM-type memories were exhibited under applied tensile strains ranging from 0 to 50 %, demonstrating the potential to serve as promising candidates for high-performance wearable devices.

The effect of the addition of Cr(NO3)3 on graphite-furnace atomic absorption spectrometry for lead in the presence of MgCl2 was investigated from the viewpoint of its mechanism. X-Ray photoelectron spectrometry for the charring product of a mixture of MgCl2, Cr(NO3)3 and lead indicated the presence of Pb(II), Cr(III) and Cr(VI). An analysis of the charring product of a mixture of MgCl2 and Cr(NO3)3 by ion chromatography indicated a remarkable loss of chloride ions at a lower charring temperature (620K), before the fusion of lead chloride occurred. It was suggested that the loss of chloride ions resulted from the for mation of gaseous species, produced by redox reaction. Atomic absorption measurements of lead and its kinetic analysis were carried out in Mg(NO3)2, MgCl2, MgCl2 with Cr(NO3)3, Cr(NO3)3, CrCl3, (NH4)2CrO4 and K2Cr2O7. A comparison of the appearance temperatures of the lead signal and the Arrhenius activation energies of lead atomization among each matrix showed that Cr(III), e.g. Cr2O3, dominantly affected the atomization of lead.

Although graphite furnace atomic absorption spectrometry is favorable for the analysis of trace amounts of lead, severe matrix interferences of various sulfates on the sensitivity of lead have been reported. "2 Frech et a1.3 reported the distribution of lead in various species in the presence of sulfur by the theoretical equilibrium calculations and pointed out that the interference effect from sulfur should be strong. Although the interference effect of sodium sulfate on the atomic absorbance of lead was strong, the interference mechanism was not explained.1 In this work, as lead atomic absorption was measured in nitrates and sulfates of zinc, copper, magnesium, aluminum, nickel and cobalt, different matrix effects were observed between the nitrate and the sulfate matrices. This investigation provides a mechanism of the interference effect from sulfur.