Balloon dilation of the eustachian tube is a new therapeutic option for eustachian tube dysfunction. One of the limiting factors of wider adoption of this technique in many parts of the world is the ...high cost of the devices, in spite of regulatory approval of safety.
Evaluate the performance and usability of standard less-expensive endovascular balloons for eustachian tube dilation in comparison to an approved device in a preclinical study.
Comparative cadaver feasibility study.
University tertiary care facility.
Ten eustachian tube dilations were performed with an approved eustachian tube dilation device. Ten other procedures were carried out with an endovascular balloon of similar dimensions. Cone beam computerized tomography was performed to evaluate the extent of dilation and possible damages. The lumen and mucosal lining were inspected endoscopically post-dilation. Volume measurements were compared before and after the procedure in both groups using contrast enhancement.
All 20 eustachian tube dilations were carried out successfully. No tissue damages could be identified on cone-beam computerized tomography or via endoscopic examination. There was a statistically significant difference of eustachian tube volumes between pre- and post-dilations, with no statistically significant difference between the devices.
Eustachian tube dilation with a less costly endovascular balloon achieved similar results to an approved eustachian tube dilation device. No damages or any other safety concerns were identified in a cadaver study.
The International Continental Scientific Drilling Program (ICDP) has long espoused studies of deep subsurface life, and has targeted fundamental questions regarding subsurface life, including the ...following: "(1) What is the extent and diversity of deep microbial life and what are the factors limiting it? (2) What are the types of metabolism/carbon/energy sources and the rates of subsurface activity? (3) How is deep microbial life adapted to subsurface conditions? (4) How do subsurface microbial communities affect energy resources? And (5) how does the deep biosphere interact with the geosphere and atmosphere?" (Horsfield et al., 2014) Many ICDP-sponsored drilling projects have included a deep-life component; however, to date, not one project has been driven by deep-life goals, in part because geomicrobiologists have been slow to initiate deep biosphere-driven ICDP projects. Therefore, the Deep Carbon Observatory (DCO) recently partnered with the ICDP to sponsor a workshop with the specific aim of gathering potential proponents for deep-life-driven ICDP projects and ideas for candidate drilling sites. Twenty-two participants from nine countries proposed projects and sites that included compressional and extensional tectonic environments, evaporites, hydrocarbon-rich shales, flood basalts, Precambrian shield rocks, subglacial and subpermafrost environments, active volcano-tectonic systems, megafan deltas, and serpentinizing ultramafic environments. The criteria and requirements for successful ICDP applications were presented. Deep-life-specific technical requirements were discussed and it was concluded that, while these procedures require adequate planning, they are entirely compatible with the sampling needs of other disciplines. As a result of this workshop, one drilling workshop proposal on the Basin and Range Physiographic Province (BRPP) has been submitted to the ICDP, and several other drilling project proponents plan to submit proposals for ICDP-sponsored drilling workshops in 2016.
Pluripotency makes human pluripotent stem cells (hPSCs) promising for regenerative medicine, but the teratoma formation has been considered to be a major obstacle for their clinical applications. ...Here, we determined that the downregulation of miR-302 suppresses the teratoma formation, hampers the self-renewal and pluripotency, and promotes hPSC differentiation. The underlying mechanism is that the high endogenous expression of miR-302 suppresses the AKT1 expression by directly targeting its 3'UTR and subsequently maintains the pluripotent factor OCT4 at high level. Our findings reveal that miR-302 regulates OCT4 by suppressing AKT1, which provides hPSCs two characteristics related to their potential for clinical applications: the benefit of pluripotency and the hindrance of teratoma formation. More importantly, we demonstrate that miR-302 upregulation cannot lead OCT4 negative human adult mesenchymal stem cells (hMSCs) to acquire the teratoma formation in vivo. Whether miR-302 upregulation can drive hMSCs to acquire a higher differentiation potential is worthy of deep investigation.
We have successfully grown centimeter-sized layered RSrNiO4 single crystals under high oxygen pressures of 120–150 bar by the floating zone technique. This enabled us to perform neutron scattering ...experiments where we observe close to quarter-integer magnetic peaks below ∼77K that are accompanied by steep upwards dispersing spin excitations. Within the high-frequency Ni–O bond stretching phonon dispersion, a softening at the propagation vector for a checkerboard modulation can be observed. We were able to simulate the magnetic excitation spectra using a model that includes two essential ingredients, namely checkerboard charge disproportionation and nano phase separation. The results thus suggest that charge disproportionation is preferred instead of a Jahn–Teller distortion even for this layered Ni3+ system.
To investigate whether mono-exponential and bi-exponential diffusion-weighted imaging (DWI)-related parameters of the primary tumour can evaluate the status of lymphovascular space invasion (LVSI) ...and lymph node metastasis (LNM) in patients with cervical carcinoma preoperatively.
Eighty patients with cervical carcinoma were enrolled, who underwent preoperative multi b-value DWI and radical hysterectomy. They were classified into LVSI(+) versus LVSI(–) and LNM(+) versus LNM(–) according to postoperative pathology. The apparent diffusion coefficient (ADC), pure molecular diffusion (D), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) were calculated from the whole tumour (_whole) and tumour margin (_margin). All parameters were compared between LVSI(+) and LVSI(–) and between LNM(+) and LNM(–). Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to evaluate the diagnostic performance of these parameters.
f_margin and D∗_whole showed significant differences in differentiating LVSI(+) from LVSI(–) tumours (p=0.002, 0.008, respectively), while LNM(+) tumours presented with significantly higher ADC_margin than that of LNM(–) tumours (p=0.009). The other parameters were not independent related factors with the status of LVSI or LNM according to logistic regression analysis (p>0.05). The area under the ROC curve of f_margin combined with D∗_whole in discriminating LVSI(+) from LVSI(–) was 0.826 (95% confidence interval CI: 0.691–0.961), while ADC_margin in differentiating LNM(+) from LNM(–) was 0.788 (95% CI: 0.648–0.928).
The parameters generated from mono-exponential and bi-exponential DWI of the primary cervical carcinoma could help discriminate its status regarding LVSI (f_margin and D∗_whole) and LNM (ADC_margin).
•ADC and IVIM offer valuable information for status of LVSI/LNM in cervical cancer.•ADC, f, D showed better diagnostic performance on tumour margin than tumour entirety.•f_margin and D∗_whole could help discriminate invasion status of lymphovascular space.•ADC_margin could help differentiate invasion status of lymph nodes.
Li2CuO2 is a typical charge transfer insulator with CuO2 chains that are composed of edge-shared CuO4 plaquettes. The existence of oxygen vacancies for single crystals prepared under various oxygen ...partial pressures has been confirmed by the chemical and thermogravimetric analyses. The puzzling discovery of extra magnetic moment near the oxygen site by earlier neutron scattering studies has been verified by a thorough Curie-Weiss law analysis of spin susceptibilities, and resolved quantitatively with a molecular orbital model of edge-sharing CuO2 chains containing oxygen vacancies.
Helicobacter pylori
(
H. pylori
) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying ...mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic
H. pylori
infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and β-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of
H. pylori
in mice was evaluated by rapid urease test, H&E staining and Warthin‒Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in
H. pylori
infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of
Wnt2
. Studies in chronic
H. pylori
infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that
H. pylori
infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/β-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively,
H. pylori
chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/β-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.
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Thrombomodulin (TM) is a type-I transmembrane glycoprotein expressed on the surfaces of endothelial cells and epidermal keratinocytes. It is known to regulate blood coagulation, ...inflammation, and cell-cell adhesion. A recombinant TM, which contains an epidermal growth factor-like domain and serine/threonine-riches domain, has been demonstrated to stimulate cell proliferation and migration of keratinocytes and wound healing. In this study, we developed the biodegradable hydrogels and evaluated the efficacy of sustained release of rhTM from the hydrogel for the treatment of diabetic wounds. The hydrogels were composed of gelatin with or without hyaluronic acid, and fabricated by chemical cross-linking followed by lyophilization. Gelatin-based hydrogels had porous structure, good swelling property, and were biodegradable with characteristics of slow rhTM release in a short term. The once every-3-day rhTM-loaded hydrogel (with hyaluronic acid) markedly promoted wound healing and were superior to rhTM solution, once daily rhTM hydrogel (without hyaluronic acid), hydrogel controls, and once every-3-day rhEGF hydrogel treatment groups. The rhTM hydrogels enhanced granulation tissue formation, re-epithelialization, collagen deposition, and angiogenesis in wound repair. The once every-3-day rhTM hydrogel was stable and drug release was maintained up to 11-month of storage at 4 °C. The developed rhTM hydrogels could meet the needs for clinical practice, and may have future medical applications for wound care in diabetic patients.
Thrombin modulates the formation of atherosclerotic lesions by stimulating a variety of cellular effects through protease-activated receptor-1 (PAR-1) activation. Thrombomodulin (TM) inhibits ...thrombin effects by binding thrombin through its domains 2 and 3 (TMD23). We investigated whether recombinant TMD23 (rTMD23) could inhibit atherosclerosis via its thrombin-binding ability.
Wild-type mouse rTMD23 and three mutants with altered thrombin-binding sites, rTMD23 (I425A), rTMD23 (D424A/D426A), and rTMD23 (D424A/I425A/D426A), were expressed and purified in the Pichia pastoris expression system. Wild-type rTMD23 and rTMD23 (D424A/D426A) could effectively bind thrombin, activate protein C, and prolong thrombin clotting time, whereas rTMD23 (I425A) and rTMD23 (D424A/I425A/D426A) lost these functions. Wild-type rTMD23, but not rTMD23 (I425A), decreased both the thrombin-induced surface PAR-1 internalization and the increase in cytoplasmic Ca(2+) concentrations in endothelial cells (ECs). Wild-type rTMD23 and rTMD23 (D424A/D426A) also inhibited thrombin-induced adhesion molecules and monocyte chemoattractant protein-1 expression and increased permeability in ECs, whereas rTMD23 (I425A) and rTMD23 (D424A/I425A/D426A) had no such effects. Furthermore, wild-type rTMD23 and rTMD23 (D424A/D426A) were effective in reducing carotid ligation-induced neointima formation in C57BL/6 mice and atherosclerotic lesion formation in apolipoprotein E-deficient (ApoE-/-) mice, whereas rTMD23 with the I425A mutation showed impairment of this function. Wild-type rTMD23, but not rTMD23 (I425A), also markedly suppressed the PAR-1, the adhesion molecules expression, and the macrophage content in the carotid ligation model and ApoE-/- mice.
rTMD23 protein significantly reduces atherosclerosis and neointima formation through its thrombin-binding ability.
Growth of periocular basal cell carcinomas Tan, E.; Lin, F.P.Y.; Sheck, L.H.N. ...
British journal of dermatology (1951),
04/2015, Letnik:
172, Številka:
4
Journal Article
Recenzirano
Summary
Background
Basal cell carcinomas (BCCs) are generally regarded as slow‐growing tumours. There is a paucity of data on the rate of BCC growth and the impact of delayed excision.
Objectives
To ...measure the growth rate and assess the impact of delayed excision on the growth of periocular BCC (pBCC).
Methods
Patients referred to an oculoplastic service for excision of pBCC were recruited. The tumour dimensions and patient demographic data were recorded at the first specialist appointment (FSA). Measurement of the pBCC was repeated when the patient attended for tumour excision by Mohs micrographic surgery (MMS). Correlation analyses were performed to determine whether the histological subtype and patient factors affected the pBCC growth rates.
Results
The study included 112 patients and 115 pBCCs. The primary ethnicity was European with Fitzpatrick type I and II skin. The mean size of the pBCC at FSA was 8 × 6 mm (range 6–12 × 4–8 mm) with a mean area of 68·5 mm2. The average waiting time for MMS was 157 ± 87 days. The pBCCs grew at a mean rate of 11·2 mm2 every 30 days. From the FSA to the MMS, a mean increase of 41·9 mm2 was observed. Recurrent tumours, larger tumours at presentation and male sex were associated with a faster growth rate.
Conclusions
Periocular basal cell carcinomas can grow rapidly, and many have aggressive histological subtypes. Rapid growth is more likely in recurrent tumours, larger tumours and in men.
What's already known about this topic?
Basal cell carcinomas (BCCs) have traditionally been regarded as slow‐growing tumours.
Few studies have prospectively and methodologically assessed the growth of BCCs.
What does this study add?
BCCs in the periorbital region grow rapidly, at a rate of 11·2 mm2 monthly or 0·76 mm in diameter per month.
Most tumours grew in spite of an incisional or shave biopsy performed at the first appointment.
Factors that were related to a faster growth were large initial tumour size, male sex and a recurrent tumour. This growth could result in increased morbidity.
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