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A general and practical route to carbohydrate-aryl ethers by nucleophilic aromatic substitution (SNAr) is reported. Upon treatment with KHMDS, C-O bond formation occurs between carbohydrate alcohols and a diverse range of fluorinated (hetero)aromatics to provide the targets in good to excellent yields. Commercially available arylating agents, high atom economy, and high regioselectivity are notable features of the protocol. The aryl ether products have potential for wide-ranging applications as exemplified by the synthesis of a novel chiral P,N-ligand.

Individuals with a history of recurrent depression have a high risk of repeated depressive relapse/recurrence. Maintenance antidepressant medication (m-ADM) for at least 2 years is the current recommended treatment, but many individuals are interested in alternatives to m-ADM. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce the risk of relapse/recurrence compared with usual care but has not yet been compared with m-ADM in a definitive trial.

To establish whether MBCT with support to taper and/or discontinue antidepressant medication (MBCT-TS) is superior to and more cost-effective than an approach of m-ADM in a primary care setting for patients with a history of recurrent depression followed up over a 2-year period in terms of preventing depressive relapse/recurrence. Secondary aims examined MBCT's acceptability and mechanism of action.

Single-blind, parallel, individual randomised controlled trial.

UK general practices.

Adult patients with a diagnosis of recurrent depression and 73. See the NIHR Journals Library website for further project information.

In chronic obstructive pulmonary disease (COPD), the problem of poor patient participation in studies of self-management (SM) and pulmonary rehabilitation (PR) programmes (together referred to as COPD support programmes) is established. Understanding this problem beyond the previously reported socio-demographics and clinical factors is critical.

The aim of this study was to explore factors that explain patient participation in studies of COPD support programmes.

Thematic 'framework' synthesis was conducted on literature published from 1984 to 1 February 2015. Emergent themes and subthemes were mapped onto the adapted 'attitude-social influence-external barriers' and the 'self-regulation' models to produce analytical themes.

Ten out of 12 studies were included PR (n=9) and SM (n=1). Three descriptive themes with 38 subthemes were mapped onto the models' constructs, and it generated four analytical themes 'attitude', 'social influences' and 'illness' and 'intervention representations'. The following facosocial factors including perceived practical/physical concerns related to attendance influenced patients' participation in COPD support programmes. Addressing the negative beliefs/perceptions via behaviour change interventions may help improve participation in COPD support programmes and, ultimately, patient outcomes.Abrin, obtained from the seeds of Abrus precatorius plant, is a potent toxin belonging to the family of type II ribosome-inactivating proteins. Recently, a recombinant vaccine consisting of the A subunits of abrin and its homolog Abrus precatorius agglutinin (APA) was demonstrated to protect mice from abrin lethality. Toward identifying neutralizing epitopes recognized during this response, we generated monoclonal antibodies against the proposed vaccine candidate. One antibody, namely A7C4, the corresponding epitope of which was found to be distal to the active site of the enzymatic A chain, prevented abrin-mediated toxicity on cells and abrin-induced lethality in mice but did not inhibit the catalytic activity of the A chain. The in vivo protection conferred by monoclonal antibody A7C4 highlights the potential use of this antibody as a promising immunotherapeutic.We developed a simple, sensitive inner filter effect (IFE)-based fluorescent assay for sensing H2O2 and cholesterol. In the process, poly(vinylpyrrolidone)-protected gold nanoparticles (PVP-AuNPs) and fluorescent BSA-protected gold nanoclusters (BSA-AuNCs) were used as an IFE absorber/fluorophore pair. PVP-AuNPs can be a powerful absorber to influence the emission of the fluorophore, BSA-AuNCs, in the IFE-based fluorescent assays. That is due to the high extinction coefficient of AuNPs and the complementary overlap between the surface plasmon resonance (SPR) absorption of PVP-AuNPs and the excitation of BSA-AuNCs. The PVP-Au seeds, produced by directly mixing PVP with HAuCl4, were able to catalyze H2O2 to enlarge AuNPs. read more The SPR absorption of PVP-AuNPs was enhanced with an increased concentration of H2O2 and, subsequently, induced significant fluorescence quenching of BSA-AuNCs. The IFE-based fluorescent assay enabled the detection of H2O2 and generation of H2O2 in the presence of O2/cholesterol and cholesterol oxidase (ChOx) by the fluorescence response of BSA-AuNCs. The present IFE-based approach can detect H2O2 ranging from 1 to 100 μM with a detection limit of 0.8 μM and cholesterol ranging from 1 to 100 μM with a detection limit of 1.4 μM.Small-cell lung cancer (SCLC) accounts for nearly 15% of lung cancer cases and exhibits aggressive clinical behavior characterized by rapid growth and metastatic spread to multiple organs. About 70% of patients with SCLC present with extensive disease and distant metastases at diagnosis. HSP90 is a 90-kDa molecular chaperone whose association is required for the stability and function of its numerous "client proteins." Here, we assessed the therapeutic potential of the HSP90 inhibitor 17-DMAG in SCLC. Notably, 17-DMAG hindered the viability of human SCLC cell lines-regardless of their chemosensitivity-via the decreased expression of client proteins, including the proto-oncogene c-Raf (also known as RAF1). In an in vivo imaging model of SCLC multiple-organ metastasis with the human SCLC cell line SBC-5, treatment with 17-DMAG remarkably inhibited the formation of metastatic sites in the liver, but was ineffective in hindering the progression of bone lesions. The latter was likely the result of activation of osteoclasts. IGF-1, which is supposed to be rich in bone environment, preserved c-Raf expression and maintained viability of SBC-5 cells treated with 17-DMAG. Furthermore, the combined use of a bisphosphonate with 17-DMAG significantly attenuated the progression of metastases in both the liver and the bone. These findings suggest that therapeutic effects of HSP90 inhibitors may be organ-specific and should be carefully monitored in SCLC clinical trials.

Imparting surgical change to the nasal tip remains one of the most challenging aspects of rhinoplasty. The surgeon must assess the tip preoperatively and execute the necessary maneuvers to impart the desired change.

To assess nasal tip resistance to compression in a cadaveric model before and after specific rhinoplasty maneuvers using a novel method.

Open rhinoplasty maneuvers were performed at an academic tertiary care center on 6 fresh-thawed cadaver heads. Assessment of tip support was performed with a motorized, computer-controlled test stand equipped with a digital load cell. Tip support was assessed by compression to a depth of 2.5 mm from contact both preoperatively and after each surgical maneuver. All force data were recorded in pound-force and converted to newtons (N) following analysis.

Nasal tip support, measured as resistance to compression, before and after various rhinoplasty maneuvers.

Following the elevation of the skin-soft-tissue envelope with septoplasty, resistance to compression (1.82 N) was not significantly different from the preoperative assessment (1.60 N for all specimens). Tip support following placement of a caudal extension graft was significantly different from all other conditions (3.16 N; P < .01), showing support increased by more than 66% from preoperative assessment. Placement of columellar strut (1.28 N) did not show significant increase in tip support. Tip support was decreased slightly after placement of intradomal sutures, which was significant (1.22 N; P < .01).

This study demonstrates the use of materials testing equipment to assess and quantify change in tip support after several rhinoplasty maneuvers. Minor supporting maneuvers that rely on healing and scar do not significantly alter tip support in a cadaveric model. Caudal extension graft is an important maneuver imparting significant effect on nasal tip support.

NA.

NA.New data on the nature of the protein targets of uranium (U) within zebrafish gills were collected after waterborne exposure, with the aim of a better understanding of U toxicity mechanisms. Some common characteristics of the U protein target binding properties were found, such as their role in the regulation of other essential metals and their phosphorus content. In total, 21 potential protein targets, including hemoglobin, are identified and discussed in terms of the literature.

Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size.

A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes.

Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (-) were 93.0% and 72.5% (P < .001), 90.8% and 63.3% (P < .001), and 86.4% and 59.9% (P < .001), respectively.

This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system.

This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system.

To evaluate the distance between the cementoenamel junction and the alveolar bone crest before and after orthodontic treatment using cone beam computed tomography (CBCT).

The sample comprised 30 patients with Angle Class I malocclusion and mild to moderate crowding. The study database comprised dental CBCT scans obtained before and after orthodontic treatment. The distance between the cementoenamel junction to the bone crest of the buccal (n  =  720) and lingual (n  =  720) surfaces was measured in 24 teeth for each patient using a specific software tool (Xoran version 3.1.62). The Wilcoxon test was used for statistical analysis, and the level of significance was set at P < .05.

The distance between the cementoenamel junction and the bone crest increased in 822 (57%) of the 1440 surfaces after orthodontic treatment. The buccal surface of the lower central incisors had the greatest frequency of increased distance (75%), and the lingual surface of lateral incisors had the lowest (40%). The distance between the cementoenamel junction and the alveolar bone crest was greater than 2 mm (alveolar bone dehiscence) in 162 (11%) of the 1440 surfaces before orthodontic treatment and in 279 (19%) after treatment.