Background
Chronic rhinosinusitis (CRS) can be classified into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays more intense eosinophilic infiltration and the ...presence of Th2 cytokines. Mucosal eosinophilia is associated with more severe symptoms and often requires multiple surgeries because of recurrence; however, even in eosinophilic CRS (ECRS), clinical course is variable. In this study, we wanted to set objective clinical criteria for the diagnosis of refractory CRS.
Methods
This was a retrospective study conducted by 15 institutions participating in the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC). We evaluated patients with CRS treated with endoscopic sinus surgery (ESS), and risk of recurrence was estimated using Cox proportional hazard models. Multiple logistic regression models and receiver operating characteristics curves were constructed to create the diagnostic criterion for ECRS.
Results
We analyzed 1716 patients treated with ESS. To diagnose ECRS, the JESREC scoring system assessed unilateral or bilateral disease, the presence of nasal polyps, blood eosinophilia, and dominant shadow of ethmoid sinuses in computed tomography (CT) scans. The cutoff value of the score was 11 points (sensitivity: 83%, specificity: 66%). Blood eosinophilia (>5%), ethmoid sinus disease detected by CT scan, bronchial asthma, aspirin, and nonsteroidal anti‐inflammatory drugs intolerance were associated significantly with recurrence.
Conclusion
We subdivided CRSwNP in non‐ECRS, mild, moderate, and severe ECRS according to our algorithm. This classification was significantly correlated with prognosis. It is notable that this algorithm may give useful information to clinicians in the refractoriness of CRS before ESS or biopsy.
A large variety of nanometre-scale devices have been investigated in recent years that could overcome the physical and economic limitations of current semiconductor devices. To be of technological ...interest, the energy consumption and fabrication cost of these 'nanodevices' need to be low. Here we report a new type of nanodevice, a quantized conductance atomic switch (QCAS), which satisfies these requirements. The QCAS works by controlling the formation and annihilation of an atomic bridge at the crossing point between two electrodes. The wires are spaced approximately 1 nm apart, and one of the two is a solid electrolyte wire from which the atomic bridges are formed. We demonstrate that such a QCAS can switch between 'on' and 'off' states at room temperature and in air at a frequency of 1 MHz and at a small operating voltage (600 mV). Basic logic circuits are also easily fabricated by crossing solid electrolyte wires with metal electrodes.
Synovial sarcoma (SS) is defined by the hallmark SS18-SSX fusion oncoprotein, which renders BAF complexes aberrant in two manners: gain of SSX to the SS18 subunit and concomitant loss of BAF47 ...subunit assembly. Here we demonstrate that SS18-SSX globally hijacks BAF complexes on chromatin to activate an SS transcriptional signature that we define using primary tumors and cell lines. Specifically, SS18-SSX retargets BAF complexes from enhancers to broad polycomb domains to oppose PRC2-mediated repression and activate bivalent genes. Upon suppression of SS18-SSX, reassembly of BAF47 restores enhancer activation, but is not required for proliferative arrest. These results establish a global hijacking mechanism for SS18-SSX on chromatin, and define the distinct contributions of two concurrent BAF complex perturbations.
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•SS18-SSX assembly results in concurrent gains and losses in genome-wide BAF complex targeting•Synovial sarcoma is transcriptionally distinct from other BAF complex-driven malignancies•SS18-SSX targets BAF complexes to broad polycomb domains to activate bivalent genes•BAF47 reassembly activates enhancers but is dispensable for proliferative arrest
Incorporation of the synovial sarcoma SS18-SSX fusion into BAF complexes results in concomitant eviction of BAF47. McBride et al. show that SS18-SSX retargets BAF complexes from enhancers to polycomb domains to oppose PRC2-mediated repression. Reincorporation of BAF47 upon suppression of SS18-SSX restores enhancer activation but is not required for proliferative arrest.
► Wear-resistant coatings are formed on β-titanium alloy by plasma electrolytic oxidation. ► Better coatings are formed at lower electrolyte temperatures. ► High speed video imaging was used to ...monitor the discharge behavior during the process.
Plasma electrolytic oxidation of single β-phase Ti–15 mass% V–3 mass% Al–3 mass% Cr–3 mass% Sn (hereafter denoted as Ti–15–3) alloy has been conducted in alkaline aluminate electrolyte at different electrolyte temperatures between 278 and 313K. The results obtained disclose the highly improved wear resistance of the coatings formed at the lowest temperature of 278K. The coating formed at this temperature has lower porosity and contains higher concentration of α-Al2O3 phase in addition to the Al2TiO5 major phase. In contrast, non-uniform coatings are formed at higher temperatures and their porosity is relatively high. Thus, the highest wear resistance of the Ti–15–3 is obtained when the coating is formed at 278K. Such influence of the electrolyte temperature on the coating morphology and composition is discussed by direct imaging based on direct video imaging data during the coating process.
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.
Background
Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis (AR), the factors that induce and sustain the pathogenesis of AR remain unclear. ...The recent development of sublingual immunotherapy (SLIT) is expected to allow changes to the underlying pathogenesis of AR. However, which Th2 cell subsets are important in house dust mite‐induced AR (HDM‐AR), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified.
Methods
The cytokine production and frequency of HDM‐reactive T‐cell subsets in peripheral blood mononuclear cells (PBMCs) were evaluated using flow cytometry in 89 HDM‐AR patients (placebo n = 43 and HDM 300 IR n = 46) who participated in a placebo‐controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52‐week study. The PBMCs were stained with CellTrace™ Violet (CTV) before culture with HDM extract, and HDM‐reactive T cells were detected as the proliferated cells with diminished CTV.
Results
HDM‐reactive IL‐5+IL‐13+CD27−CD161+CD4+ cells and ST2+CD45RO+CD4+ cells were observed in the peripheral blood from each patient with HDM‐AR; these cells significantly decreased after SLIT in the group treated with active tablets. HDM‐reactive ST2+CD45RO+CD4+ cells were significantly lower in active‐responders.
Conclusion
Allergen‐reactive ST2+CD45RO+CD4+ cells or those combined with IL‐5+IL‐13+CD27−CD161+CD4+ cells may be useful as markers indicating the successful treatment of SLIT. These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.
House dust mite (HDM)‐reactive IL‐5+IL‐13+CD27−CD161+CD4+ cells and ST2+CD45RO+CD4+ cells were observed in the peripheral blood from patient with HDM‐induced allergic rhinitis; these cells significantly decreased after sublingual immunotherapy. HDM‐reactive ST2+CD45RO+CD4+ cells were significantly lower after 1 year of sublingual immunotherapy in the responders in active group than those for the nonresponders. Allergen‐reactive ST2+CD45RO+CD4+ cells or those combined with IL‐5+IL‐13+CD27−CD161+CD4+ cells may be useful as markers indicating the successful treatment of sublingual immunotherapy.
Abstract This study estimated the cumulative incidence and risk ratio for osteonecrosis of the jaw (ONJ) after tooth extraction in patients with and without administration of bisphosphonates (BP) and ...identified potential risk factors for bisphosphonate-induced osteonecrosis of the jaw (BIONJ). A cohort study was conducted in all patients undergoing tooth extraction at a university hospital in Japan from April 2006 to June 2009. Of 3216 patients, 126 had BP administration, of whom 5 (3.9%, 95% confidence interval (CI): 1.2–9.2) developed ONJ, versus 1 (0.032%, 95% CI: 0.00081–0.18) among 3090 patients without BP administration. BP administration was associated with the development of ONJ after tooth extraction, with an unadjusted risk ratio of 122.6 (95% CI: 14.4–1041.8). When stratified by age and route of BP administration, the risk ratio for ONJ patients aged 65 years or older with intravenous BP administration compared to those without was 200.2 (95% CI: 23.8–1679.4, P < 0.001). Patients receiving BP showed a significant association between the incidence of BIONJ and alveolar bone loss score. The risk of ONJ is higher in patients with than without BP administration, particularly intravenous administration. Severe periodontitis might be a risk factor for BIONJ.
Pulmonary arterial hypertension (PAH) is a progressive disorder characterised by raised pulmonary artery pressures with pathological changes in small pulmonary arteries. Previous studies have shown ...that approximately 70% of familial PAH and also 11-40% of idiopathic PAH (IPAH) cases have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene. In addition, mutations in the activin receptor-like kinase 1 (ALK1) gene have been reported in PAH patients. Since both the BMPR2 and ALK1 belonging to the transforming growth factor (TGF)-beta superfamily are known to predispose to PAH, mutations in other genes of the TGF-beta/BMP signalling pathways may also predispose to PAH.
We screened for mutations in ENDOGLIN(ENG), SMAD1, SMAD2, SMAD3, SMAD4, SMAD5, SMAD6 and SMAD8 genes, which are involved in the TGF-beta/BMP signallings, in 23 patients with IPAH who had no mutations in BMPR2 or ALK1.
A nonsense mutation in SMAD8 designated c.606 C>A, p.C202X was identified in one patient. The father of this patient was also identified as having the same mutation. Functional analysis showed the truncated form of the SMAD8 C202X protein was not phosphorylated by constitutively active ALK3 and ALK1. The SMAD8 mutant was also unable to interact with SMAD4. The response to BMP was analysed using promoter-reporter activities with SMAD4 and/or ca-ALK3. The transcriptional activation of the SMAD8 mutant was inefficient compared with the SMAD8 wild type.
We describe the first mutation in SMAD8 in a patient with IPAH. Our findings suggest the involvement of SMAD8 in the pathogenesis of PAH.
The urban heat island effect has become a serious environmental problem with the expansion of cities and industrial areas. Prohibition of the use of groundwater has caused a further serious problem ...such as floating of subways, stations and buildings through an imbalance of the hydrologic cycle in a Japanese megalopolis. Most of the previous research has evaluated separately hydrologic and thermal cycles in atmospheric, land and water areas because of the complexity in this feedback mechanism. In this study, the author used the process-based National Integrated Catchment-based Eco-hydrology (NICE) model, which includes surface-unsaturated-saturated water processes coupled with the urban canopy and regional atmospheric models, to simulate the effect of urban geometry and anthropogenic exhaustion on the hydrothermal changes in the atmospheric/land areas of the Japanese megalopolis. The simulation was conducted with multi-scale in horizontal regional-urban-point levels and in vertical atmosphere-surface-unsaturated-saturated layers, and projected the effect of water resources use to ameliorate the heat island and its impact on the hydrologic change in the catchment. Finally, the author presented the procedure to visualize the missing role of hydrothermal interactions in atmospheric, land and water areas, which would be effective to recover a sound hydrologic cycle and to create thermally pleasing environments in an eco-conscious megalopolis.
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