A systematic review of the differences in the efficacy of dipeptidyl peptidase‐4 (DPP‐4) inhibitors between Japanese and non‐Japanese subjects was conducted. We searched for randomized controlled ...trials in patients with type 2 diabetes mellitus (T2DM) that studied the intervention of a DPP‐4 inhibitor once‐daily vs. placebo, as monotherapy or as add‐on therapy. Data regarding placebo‐corrected HbA1c reduction and trough DPP‐4 inhibition rate after ≥12 weeks' treatment were extracted. In the 12 eligible studies, linear regression analysis revealed that the hemoglobin A1c (HbA1c) reduction at each DPP‐4 inhibition level was larger in studies involving Japanese patients than in studies involving non‐Japanese patients, with statistical significance between the two groups (P < 0.0001). Sensitivity analysis excluding studies of add‐on therapies supported the robustness of the result. Our study indicated that DPP‐4 inhibitors show greater efficacy in Japanese patients than in non‐Japanese patients, which may be an important consideration in the global development strategy of new diabetic medications.
This in vitro study assessed the efficacy of functionalized graphene oxide (f-GO) nanocomposites on the decalcification of dentin, because dental caries of the root surface is becoming one of the new ...problems in aged society. Hydroxyapatite plates (HAP) and dentin slices were coated with f-GO nanocomposites by comparing them to silver diamine fluoride as a positive control, then treated with decalcification solutions such as ethylenediaminetetraacetic acid and citrate at 37°C for 24 h. Scanning electron microscopy (SEM) revealed significant protection of the surface morphology of HAP and dentin. On the other hand, a cariogenic Streptococcus mutans growth was inhibited by f-GO nanocomposites. In addition, cytotoxicity of them to epithelial cells was much less than that of povidone-iodine, which is commonly used for oral disinfectant. We synthesized 5 different f-GO nanocomposites such as GO–silver (Ag), GO-Ag–calcium fluoride (CaF2), GO-CaF2, GO-zinc, and GO–tricalcium phosphate (Ca3(PO4)2). They were standardized by evaluating under SEM, transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetry analysis (TGA), and Raman spectra after being synthesized in an aseptic technique. The abilities of GO-Ag, GO-Ag-CaF2, and GO-CaF2 nanocomposites were most preventive for decalcification. In addition, GO-Ag and GO-Ag-CaF2 almost completely inhibited S. mutans growth. However, they did not exhibit cytotoxicity to epithelial cells except at the highest concentration (0.1 w/v%) of GO-Ag and GO-Ag-CaF2. Furthermore, these f-GO nanocomposites exhibited less or no discoloration of dentin, although commonly used silver diamine fluoride causes discoloration of dentin to black. Thus, these f-GO nanocomposites are useful to protect dental caries on the tooth root that becomes a social problem in aged society.
Conventional superconductivity follows Bardeen-Cooper-Schrieffer(BCS) theory of electrons-pairing in momentum-space, while superfluidity is the Bose-Einstein condensation(BEC) of atoms paired in ...real-space. These properties of solid metals and ultra-cold gases, respectively, are connected by the BCS-BEC crossover. Here we investigate the band dispersions in FeTe(0.6)Se(0.4)(Tc = 14.5 K ~ 1.2 meV) in an accessible range below and above the Fermi level(EF) using ultra-high resolution laser angle-resolved photoemission spectroscopy. We uncover an electron band lying just 0.7 meV (~8 K) above EF at the Γ-point, which shows a sharp superconducting coherence peak with gap formation below Tc. The estimated superconducting gap Δ and Fermi energy Symbol: see textF indicate composite superconductivity in an iron-based superconductor, consisting of strong-coupling BEC in the electron band and weak-coupling BCS-like superconductivity in the hole band. The study identifies the possible route to BCS-BEC superconductivity.
•Tabs do not only enhance but also suppress jet entrainment and diffusion.•Tabs generally decreases entrainment velocity represented by velocity gradient.•Entrainment area significantly affects the ...entrainment rate.•Directional characteristics of jet diffusion can be controlled by optimizing tabs.
Effects of half delta-wing tabs on mixing and diffusion in an axisymmetric jet are experimentally investigated. The tabs are installed at the jet exit circumferentially with an equal interval. The number of the tab is varied from 1 to 6. The jet Reynolds number is set to 20,000. Instantaneous streamwise and radial (vertical or horizontal) velocities and temperature are mainly measured by a composite probe which consists of an X-type hot-wire and an I-type cold-wire. The results show that mixing with the ambient fluid is more enhanced with increasing the number of the tab near the jet exit. However, in the downstream region, it is suppressed in the cases with 4, 5, and 6 tabs and most suppressed in the case with 6 tabs, while it is most enhanced in the case with 3 tabs. The analysis based on the mean velocity distribution indicates that, although the spatially-averaged entrainment velocity is basically decreased by the tabs, the mixing and entrainment can be enhanced when the entrainment area is significantly increased. Thermal diffusion is more enhanced with increasing the number of the tab near the jet exit but, in the downstream region, it is equivalent or suppressed in the cases with the tabs. These results are caused by the mixed effects of the tabs: enhancement of not only mixing and diffusion but also the energy dissipation. The present study suggests that it is feasible to both promote and suppress mixing of the jet by the half delta-wing tabs, and directional characteristics of the jet diffusion can be controlled by optimizing configuration of the tabs.
The Guerrero seismic gap is presumed to be a major source of seismic and tsunami hazard along the Mexican subduction zone. Until recently, there were limited observations at the shallow portion of ...the plate interface offshore Guerrero, so we deployed instruments there to better characterize the extent of the seismogenic zone. Here we report the discovery of episodic shallow tremors and potential slow slip events in Guerrero offshore. Their distribution, together with that of repeating earthquakes, seismicity, residual gravity and bathymetry, suggest that a portion of the shallow plate interface in the gap undergoes stable slip. This mechanical condition may not only explain the long return period of large earthquakes inside the gap, but also reveals why the rupture from past M < 8 earthquakes on adjacent megathrust segments did not propagate into the gap to result in much larger events. However, dynamic rupture effects could drive one of these nearby earthquakes to break through the entire Guerrero seismic gap.
Smoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, ...regardless of the first cancer sites.
In total, 29 795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression.
Ever smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites.
These findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.
West syndrome is a developmental and epileptic encephalopathy characterized by epileptic spasms, neurodevelopmental regression, and a specific EEG pattern called hypsarrhythmia. Our aim was to ...investigate the brain activities related to hypsarrhythmia at onset and focal epileptiform discharges in the remote period in children with West syndrome using simultaneous electroencephalography and fMRI recordings.
Fourteen children with West syndrome underwent simultaneous electroencephalography and fMRI at the onset of West syndrome. Statistically significant blood oxygen level-dependent responses related to hypsarrhythmia were analyzed using an event-related design of 4 hemodynamic response functions with peaks at 3, 5, 7, and 9 seconds after the onset of each event. Six of 14 children had focal epileptiform discharges after treatment and underwent simultaneous electroencephalography and fMRI from 12 to 25 months of age.
At onset, positive blood oxygen level-dependent responses were seen in the brainstem (14/14 patients), thalami (13/14), basal ganglia (13/14), and hippocampi (13/14), in addition to multiple cerebral cortices. Group analysis using hemodynamic response functions with peaks at 3, 5, and 7 seconds showed positive blood oxygen level-dependent responses in the brainstem, thalamus, and hippocampus, while positive blood oxygen level-dependent responses in multiple cerebral cortices were seen using hemodynamic response functions with peaks at 5 and 7 seconds. In the remote period, 3 of 6 children had focal epileptiform discharge-related positive blood oxygen level-dependent responses in the thalamus, hippocampus, and brainstem.
Positive blood oxygen level-dependent responses with hypsarrhythmia appeared in the brainstem, thalamus, and hippocampus on earlier hemodynamic response functions than the cerebral cortices, suggesting the propagation of epileptogenic activities from the deep brain structures to the neocortices. Activation of the hippocampus, thalamus, and brainstem was still seen in half of the patients with focal epileptiform discharges after adrenocorticotropic hormone therapy.
EZH2 overexpression occurs in various malignancies and is associated with a poor outcome. We have so far demonstrated that EZH2 downregulates the important genes such as E-cadherin and RUNX3 by ...increasing histone H3K27 trimethylation. However, the mechanism of EZH2 overexpression in various cancer cells remains unclear. In this study we carried out a promoter analysis of the EZH2 gene and investigated whether a survival signal that is upregulated in cancer cells is related to overexpression at the transcription level. We also explored the clinical relevance of the signaling pathway that leads to EZH2 overexpression in breast cancer and demonstrated that MEK-ERK1/2-Elk-1 pathway leads to EZH2 overexpression. The triple-negative and ERBB2-overexpressing subtypes of breast cancer are known to contain more rapidly proliferating breast cancer cells. The signaling pathway connected to EZH2 overexpression was associated with both aggressive subtypes of breast cancer. We show the significance that overexpression of histone modifier protein EZH2 in cancer cells and our study could pave the way for EZH2 inhibition to become an efficient treatment for more aggressive breast cancers.
The rapid increase in the number and volume of chemical substances being used in modern society has been accompanied by a large number of potentially hazardous chemicals being found in environmental ...samples. In Vietnam, the monitoring of chemical substances is mainly limited to a small number of known pollutants in spite of rapid economic growth and urbanization, and there is an urgent need to examine a large number of chemicals to prevent impacts from expanding environmental pollution. However, it is difficult to analyze a large number of chemicals using existing methods, because they are time consuming and expensive. In the present study, we determined 1153 substances to grasp a pollution picture of microcontaminants in the aquatic environment. To achieve this objective, we have used two comprehensive analytical methods: (1) solid-phase extraction (SPE) and LC-TOF-MS analysis, and (2) SPE and GC-MS analysis. We collected 42 samples from northern (the Red River and Hanoi), central (Hue and Danang), and southern (Ho Chi Minh City and Saigon-Dongnai River) Vietnam. One hundred and sixty-five compounds were detected at least once. The compounds detected most frequently (>40 % samples) at μg/L concentrations were sterols (cholesterol, beta-sitosterol, stigmasterol, coprostanol), phthalates (bis(2-ethylhexyl) phthalate and di-
n
-butyl phthalate), and pharmaceutical and personal care products (caffeine, metformin). These contaminants were detected at almost the same detection frequency as in developed countries. The results reveal that surface waters in Vietnam, particularly in the center of large cities, are polluted by a large number of organic micropollutants, with households and business activities as the major sources. In addition, risk quotients (MEC/PNEC values) for nonylphenol, sulfamethoxazole, ampicillin, acetaminophen, erythromycin and clarithromycin were higher than 1, which indicates a possibility of adverse effects on aquatic ecosystems.
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