Summary
Background
Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify ...the pathogenesis of asthma by systemic review.
Objective
We applied a 1H‐NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers.
Method
A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H‐NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target‐profiling procedure.
Results
Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O‐phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects).
Conclusion & Clinical Relevance
These data showed that 1H‐NMR‐based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.
Background
Sevoflurane is widely used in paediatric anaesthesia but frequently causes emergence agitation (EA). This study evaluated whether limiting the sevoflurane concentration by combining ...remifentanil with sevoflurane reduced the incidence of EA.
Methods
Eighty‐four preschool children scheduled for adenotonsillectomy were randomly assigned to either the remifentanil or sevoflurane group. In the remifentanil group, anaesthesia was induced with thiopental, rocuronium, and 1% sevoflurane. It was maintained with 1% sevoflurane, 60% nitrous oxide in oxygen, and a continuous infusion of remifentanil. For the sevoflurane group, anaesthesia was induced with thiopental, rocuronium, and 8% sevoflurane, and was maintained with 2–3% sevoflurane. Both groups received ketorolac 1 mg/kg and dexamethasone 0.15 mg/kg. EA was measured using the paediatric anaesthesia emergence delirium (PAED) scale and a four‐point EA scale in the post‐anaesthesia care unit.
Results
The scores on the PAED scales were significantly lower in the remifentanil group than in the sevoflurane group median (interquartile range); 6 (4.25–10.25) vs. 11 (7.75–14.0), P = 0.007, and the proportion of patients with PAED scores ≥ 10 was significantly lower in the remifentanil group than in the sevoflurane group 15 (35.7%) vs. 27 (64.2%), P = 0.009. The incidence of EA evaluated using the four‐point scale was also lower in the remifentanil group 11 (26.1%) vs. 21 (50%), respectively, P = 0.025.
Conclusion
The incidence of EA was lower in children undergoing adenotonsillectomy who received a lower concentration of sevoflurane combined with remifentanil than in those given a higher concentration of sevoflurane without remifentanil.
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Through-silicon via (TSV) has been used for 3-dimentional integrated circuits. Mechanical stresses in Cu and Si around the TSV were measured using synchrotron X-ray microdiffraction. ...The hydrostatic stress in Cu TSV went from high tensile of 234MPa in the as-fabricated state, to −196MPa (compressive) during thermal annealing (in situ measurement), to 167MPa in the post-annealed state. Due to this stress, the keep-away distance in Si was determined to be about 17μm. Our results suggest that Cu stress may lead to reliability as well as integration issues, while Si stress may lead to device performance concerns.
Abstract
The role of the cosmic web in shaping galaxy properties is investigated in the Galaxy And Mass Assembly (GAMA) spectroscopic survey in the redshift range 0.03 ≤ z ≤ 0.25. The stellar mass, ...u − r dust corrected colour and specific star formation rate (sSFR) of galaxies are analysed as a function of their distances to the 3D cosmic web features, such as nodes, filaments and walls, as reconstructed by DisPerSE. Significant mass and type/colour gradients are found for the whole population, with more massive and/or passive galaxies being located closer to the filament and wall than their less massive and/or star-forming counterparts. Mass segregation persists among the star-forming population alone. The red fraction of galaxies increases when closing in on nodes, and on filaments regardless of the distance to nodes. Similarly, the star-forming population reddens (or lowers its sSFR) at fixed mass when closing in on filament, implying that some quenching takes place. These trends are also found in the state-of-the-art hydrodynamical simulation Horizon-AGN. These results suggest that on top of stellar mass and large-scale density, the traceless component of the tides from the anisotropic large-scale environment also shapes galactic properties. An extension of excursion theory accounting for filamentary tides provides a qualitative explanation in terms of anisotropic assembly bias: at a given mass, the accretion rate varies with the orientation and distance to filaments. It also explains the absence of type/colour gradients in the data on smaller, non-linear scales.
Aim
To explore the involvement of TLR5 in pulp inflammation and to examine the effects of TLR5 activation with its ligand, FlaB protein, on pro‐inflammatory gene expression.
Methodology
TLR5 ...expression in dental pulp tissues and human dental pulp cells (hDPCs) were determined by immunohistochemistry, immunocytochemistry, Western blots and RT‐PCR analyses. To examine the role of TLR5, hDPCs were treated with recombinant FlaB protein (500 ng mL−1) to activate the receptor or with a small interfering RNA against TLR5 (si‐TLR5) to downregulate the receptor. After exposure to FlaB, the expression of inflammation‐related proteins was screened using a protein array kit. Western blots or qRT‐PCR analyses were performed to identify changes in the expression of uPA (urokinase plasminogen activator), TIMPs (tissue inhibitor of metalloproteinases), and IL‐6 and to determine their signalling pathways. Statistical analysis was performed using one‐way analysis of variance (anova) with Tukey post hoc test; P < 0.05 was considered statistically significant.
Result
TLR5 expression was identified in pulp tissues and hDPCs. In the protein array analysis, treatment with FlaB significantly increased uPA expression (P < 0.01) and significantly decreased TIMP1/4 (P < 0.05). FlaB treatment also significantly increased expression of the inflammatory marker IL‐6 (P < 0.01). FlaB treatment increased phosphorylation of the NF‐κB p65 subunit, JNK, p38 and ERK. Chemical inhibitors of NF‐κB (Bay11‐7082), p38 (SB202190) or ERK (U0126) decreased the FlaB induction of uPA expression. Downregulation of TLR5 expression by siRNA decreased the FlaB induction of uPA protein and p65 phosphorylation.
Conclusion
TLR5 activation with FlaB treatment induced the expression of uPA via the NF‐κB and MAPK signalling pathways. Flagellin‐bearing oral bacteria may cause pulp inflammation through TLR5. The findings provide new clues to control pulpal diseases by targeting TLR5 signalling pathways.
Summary
Background
Atrophic gastritis and intestinal metaplasia are premalignant conditions for gastric cancer. Their reversibility by Helicobacter pylori eradication remains controversial.
Aim
To ...evaluate the reversibility of atrophic gastritis and intestinal metaplasia by H. pylori eradication with long‐term follow‐up.
Methods
598 subjects were prospectively enrolled and followed for up to 10 years. They were categorised as H. pylori‐negative (n = 65), H. pylori non‐eradicated (n = 91), and H. pylori‐eradicated (n = 442). Histological assessment was performed for antrum and corpus by Sydney classification.
Results
Histological follow‐up was performed regularly at 1, 2, 3‐4 and ≥5 years, with mean follow‐up of 1.07 ± 0.21, 2.29 ± 0.83, 3.93 ± 1.02, and 6.45 ± 1.28 years, respectively. Atrophic gastritis in antrum and corpus gradually and significantly (both P < .05 for all timepoints) improved only in the H. pylori‐eradicated group compared to that at baseline. Significant difference in atrophic gastritis between H. pylori‐eradicated and H. pylori‐negative groups disappeared from 1‐year follow‐up. Similarly, intestinal metaplasia in antrum and corpus improved significantly (both P < .05 for all timepoints) only in the H. pylori‐eradicated group in comparison with that at baseline. Significant difference in intestinal metaplasia between H. pylori‐eradicated and H. pylori‐negative groups disappeared from ≥5 years of follow‐up in the antrum and from 3 years of follow‐up in the corpus.
Conclusion
H. pylori eradication may be a preventative strategy for intestinal‐type gastric cancer by regression of atrophic gastritis and intestinal metaplasia.
Linked ContentThis article is linked to Genta and Kim and Hwang papers. To view these articles visit https://doi.org/10.1111/apt.14491 and https://doi.org/10.1111/apt.14524.
Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in ...chiral magnet Co
Zn
Mn
raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate ...is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
To determine the frequency and predictive impact of ROS1 rearrangements on treatment outcomes in never-smoking patients with lung adenocarcinoma.
We concurrently analyzed ROS1 and ALK rearrangements ...and mutations in the epidermal growth factor receptor (EGFR), and KRAS in 208 never smokers with lung adenocarcinoma. ROS1 and ALK rearrangements were identified by fluorescent in situ hybridization.
Of 208 tumors screened, 7 (3.4%) were ROS1 rearranged, and 15 (7.2%) were ALK-rearranged. CD74-ROS1 fusions were identified in two patients using reverse transcriptase–polymerase chain reaction. The frequency of ROS1 rearrangement was 5.7% (6 of 105) among EGFR/KRAS/ALK-negative patients. Patients with ROS1 rearrangement had a higher objective response rate (ORR; 60.0% versus 8.5%; P = 0.01) and a longer median progression-free survival (PFS; not reached versus 3.3 months; P = 0.008) to pemetrexed than those without ROS1/ALK rearrangement. The PFS to EGFR-tyrosine kinase inhibitors in patients harboring ROS1 rearrangement was shorter than those without ROS1/ALK rearrangement (2.5 versus 7.8 months; P = 0.01).
The frequency of ROS1 rearrangements in clinically selected patients is higher than that reported for unselected patients, suggesting that ROS1 rearrangement is a druggable target in East-Asian never smokers with lung adenocarcinoma. Given the different treatment outcomes to conventional therapies and availability of ROS1 inhibitors, identification of ROS1 rearrangement can lead to successful treatment in ROS1-rearranged lung adenocarcinomas.
In this double-blind, randomized, placebo-controlled study, we evaluated the effects of magnesium sulphate on neuromuscular blocking agent requirements and analgesia in children with cerebral palsy ...(CP).
We randomly divided 61 children with CP undergoing orthopaedic surgery into two groups. The magnesium group (Group M) received magnesium sulphate 50 mg kg−1 i.v. as a bolus and 15 mg kg−1 h−1 by continuous infusion during the operation. The control group (Group S) received the same amount of isotonic saline. Rocuronium was administered 0.6 mg kg−1 before intubation and 0.1 mg kg−1 additionally when train-of-four counts were 2 or more. I.V. fentanyl and ketorolac were used to control postoperative pain. Total infused analgesic volumes and pain scores were evaluated at postoperative 30 min, and at 6, 24, and 48 h.
The rocuronium requirement of Group M was significantly less than that of Group S 0.29 (0.12) vs 0.42 (0.16) mg kg−1 h−1, P<0.05. Cumulative analgesic consumption in Group M was significantly less after operation at 24 and 48 h (P<0.05), and pain scores in Group M were lower than in Group S during the entire postoperative period (P<0.05). Serum magnesium concentrations in Group M were higher until 24 h after operation (P<0.05). The incidence of postoperative nausea and vomiting and rescue drug injections was similar in the two groups. No shivering or adverse effects related to hypermagnesaemia were encountered.
I.V. magnesium sulphate reduces rocuronium requirements and postoperative analgesic consumption in children with CP.
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