Summary
Background
Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results.
Objectives
To ...analyse the association between T1DM and atopic dermatitis (AD) in a population‐based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD.
Methods
From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12 725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD.
Results
The overall incidence rate of AD was 1·40‐fold (significantly) higher in the T1DM cohort than in the non‐T1DM cohort (3·31 vs. 2·35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort adjusted hazard ratio (HR) 1·76, 95% confidence interval (CI) 1·29–2·39 than in those without T1DM. Compared with the non‐T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30·1, 95% CI 18·7–48·5) or hospitalizations (adjusted HR 70·3, 95% CI 45·6–114·5) had a higher risk of subsequent AD.
Conclusions
This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.
What's already known about this topic?
Some studies have reported that atopic dermatitis (AD) is associated with a lower risk of type 1 diabetes mellitus (T1DM).
An inverse association was theorized between T1DM and AD because the T‐helper 1/2 immune responses of these two diseases are mutually inhibitory.
What does this study add?
This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.
The overall AD incidence rate was 1·40‐fold (significantly) higher in the T1DM cohort than in the non‐T1DM cohort (3·31 vs. 2·35 per 1000 person years).
Linked Comment: Ezzedine and Barbarot, Br J Dermatol 2016; 174: 16.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments.
Methods
...We applied k‐means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes.
Results
Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil‐predominant or neutrophil‐predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil‐predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil‐predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil‐predominant asthma may be associated with corticosteroid nonresponsiveness.
Conclusion
Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.
Neutrophil‐predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Five distinct phenotypes of childhood asthma identified in this study with differences in lung function, symptom frequency, healthcare utilization, percentages of eosinophils and neutrophils in peripheral blood, and serum IgE. Gene expression signature in PBMC constitutes an easier way to objectively identify corticosteroid‐resistant asthma in clinical settings.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
From an analysis of the long cadence light curves of M and K dwarfs obtained by the K2 observations, 3589 flares on 548 M dwarfs and 1647 flares on 343 K dwarfs have been identified. We compared the ...M and K dwarfs' flares with the G dwarfs' flares reported by Shibayama et al. The later type stars' flare occurrence frequencies are higher than those of the earlier type stars, but the earlier type stars produce more powerful flares than those of the later type stars. For the stars of all spectral types, the flare activities, including the flare energy, peak amplitude, and percentage of magnetic activity, increase with faster rotation of stars. The longer the flare duration is, the more energy the flare releases, but an upper limit exists. The saturation energy of M, K, and G dwarfs are derived to be about 1 × 1035 erg, 4 × 1035 erg and 1 × 1036 erg, respectively, in the present study. We estimated the power-law indices of the flare frequency distributions of three spectral type stars. They are 1.82 0.02 (M dwarfs) and 1.86 0.02 (K dwarfs) in comparison to the 2.01 0.03 for the G dwarfs found by Shibayama et al. For stars with Prot ≤ 10 days, they are 1.78 0.02 (M dwarfs), 1.82 0.03 (K dwarfs), and 2.09 0.04 (G dwarfs). The power-law indices of flare frequency distributions of the fast-rotating M- and K-type stars are nearly the same. This indicates that the flare or magnetic mechanisms of different types of low-mass stars may be similar in some sense.
From a study of the light curves of the M dwarfs observed by the Kepler space telescope in its primary mission, a number of flare events with the peak flux increases reaching more than the nominal ...stellar luminosity have been found. One of them, KIC 9201463, produced an extreme flare with the peak flux increase jumping to five times the quiet-time value. In relative terms, this class of hyperflares is much stronger than the superflares of the solar-type stars and could have a very important influence on the atmospheric evolution and the potential development of biospheres of habitable super-Earths orbiting around M dwarf stars. A cross-correlation of the flare activities of some of these M dwarf stars and their H equivalent width (EW) values derived from the LAMOST project indicates that the H EW values can be used to monitor the occurrence of hyperflares as well as the level of flare activity of different classes of M dwarfs with fast to slow rotations, and hence the long-term environmental effects of star-planet interaction of exoplanets.
Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Prostate cancer cells escape growth inhibition from transforming growth factor β (TGFβ) by downregulating TGFβ receptors. However, the mechanism by which cancer cells downregulate TGFβ receptors in ...prostate is not clear. Here, we showed that coordinated action of miR-21 and androgen receptor (AR) signaling had a critical role in inhibiting TGFβ receptor II (TGFBR2) expression in prostate cancer cells. Our results revealed that miR-21 suppresses TGFBR2 levels by binding to its 3'-UTR and AR signaling further potentiates this effect in both untransformed and transformed human prostate epithelial cells as well as in human prostate cancers. Analysis of primary prostate cancers showed that increased miR-21/AR expression parallel a significantly reduced expression of TGFBR2. Manipulation of androgen signaling or the expression levels of AR or miR-21 negatively altered TGFBR2 expression in untransformed and transformed human prostate epithelial cells, human prostate cancer xenografts and mouse prostate glands. Importantly, we demonstrated that miR-21 and AR regulated each other's expression resulting in a positive feedback loop. Our results indicated that miR-21/AR mediate its tumor-promoting function by attenuating TGFβ-mediated Smad2/3 activation, cell growth inhibition, cell migration and apoptosis. Together, these results suggest that the AR and miR-21 axis exerts its oncogenic effects in prostate tumors by downregulating TGFBR2, hence inhibiting the tumor-suppressive activity of TGFβ pathway. Targeting miR-21 alone or in combination with AR may restore the tumor inhibitory activity of TGFβ in prostate cancer.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nanodiamond (ND) has been proposed for various biomedical applications, including bioimaging, biosensing and drug delivery, owing to its physical‐chemical properties and biocompatibility. ...Particularly, ND has been demonstrated as fluorescence‐ and Raman‐detectable labels in many cellular models. Different surface functionalization methods have been developed, varying the ND's surface properties and rendering the possibility to attach biomolecules to provide interaction with biological targets. For this, toxicity is of major concern in animal models. Aside from cellular models, a cost‐effective animal test will greatly facilitate the development of applications. In this study, we use the rapid, sensitive and reproducible zebrafish embryo model for in vivo nanotoxicity test. We optimize the conditions for using this animal model and analyze the zebrafish embryonic development in the presence of ND. ND is observed in the embryo in vivo using laser confocal fluorescence microscopy and fluorescence lifetime imaging. Using the zebrafish model for a safety evaluation of ND‐based nanolabel is discussed.
The defects originated color centers of nanodiamond emit visible fluorescence upon laser illumination. With nanodiamond's low toxicity, it can be used as a biocompatible biolabel in the zebrafish model. When injected with nanodiamond, the green fluorescence from nanodiamond at the head of the larval zebrafish is brightly visible; and the nanodiamond can be traced in the zebrafish in vivo.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end‐stage liver disease in children with biliary atresia (BA). A ...retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow‐up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty‐seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety‐six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty‐five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in‐hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6‐month, 1‐year and 5‐year actual recipient survival rates were 99%, 98% and 98%, respectively.
In 100 biliary atresia patients undergoing living donor liver transplantation at a single center, the overall mortality rate was 3% and the 5 year actual recipient survival rate was 98%.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To provide a summary of evidence for the diagnostic accuracies of three multiplex PCR systems (mPCRs)—BioFire FilmArray RP (FilmArray), Nanosphere Verigene RV+ test (Verigene RV+) and Hologic ...Gen-Probe Prodesse assays—on the detection of viral respiratory infections.
A comprehensive search up to 1 July 2017 was conducted on Medline and Embase for studies that utilized FilmArray, Verigene RV+ and Prodesse for diagnosis of viral respiratory infections. A summary of diagnostic accuracies for the following five viruses were calculated: influenza A virus (FluA), influenza B virus, respiratory syncytial virus, human metapneumovirus and adenovirus. Hierarchical summary receiver operating curves were used for estimating the viral detection performance per assay.
Twenty studies of 5510 patient samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with area under the receiver operating characteristic curve (AUROC) equal to or more than 0.98 for all the above viruses except for adenovirus (AUROC 0.89). FilmArray, Verigene RV+ and ProFlu+ (the only Prodesse assay with enough data) demonstrated a summary sensitivity for FluA of 0.911 (95% confidence interval, 0.848–0.949), 0.949 (95% confidence interval, 0.882–0.979) and 0.954 (95% confidence interval, 0.871–0.985), respectively. The three mPCRs were comparable in terms of detection of FluA.
Point estimates calculated from eligible studies showed that the three mPCRs (FilmArray, Verigene RV+ and ProFlu+) are highly accurate and may provide important diagnostic information for early identification of respiratory virus infections. In patients with low pretest probability for FluA, these three mPCRs can predict a low possibility of infection and may justify withholding empirical antiviral treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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