352 research outputs found

    Molecular characterization of polar organosulfates in secondary organic aerosol from the green leaf volatile 3-Z-hexenal

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    Evidence is provided That the green leaf volatiles 3-Z- hexenal serves as a precursor for biogenic secondary organic aersol through the formation of polar organosulfates (Os) with molecular weight (MW) 226. The MW 226 C-6-OSs were Chemically elucidated, along with structurally similar MW 212 C-5-OSs, whose biogenic precursor is likely related to 3-Z-hexenal but still remains unknown. The MW: 226 and 212 OSs have a substantial abundance in ambient fine aerosol from K-puszta, Hungary, which is comparable to that of the isoprene-related MW 216 OSs, known to be formed: through sulfation of C-5-epoxydiols, second-generation gas-phase photooxidation products of isoprene. Using detailed interpretation of negative-ion electrospray ionization mass spectral data, the MW 226, compounds are assigned to isomeric sulfate esters of 3,4-dihydroxyhex-5-enoic acid with the sulfate group located or C-4 position. Two MW 212 compounds present in: ambient fine aerosol are attributed to isomeric sulfate :esters of 2,3-dihydroxypent-4-enoic acid, of which two are sulfated at C-3 and one is sulfated at C-2. The formation of the MW 226 :OSs is tentatively explained through photooxidation of 3-Z-hexenal in, the gas phase, resulting in alkoxy radical, followed by a rearrangement and subsequent sulfation of the epoxy group in the particle phase

    Primary intrathoracic malignant mesenchymal tumours: computed tomography features of a rare group of chest neoplasms

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    OBJECTIVES: To describe the computed tomography (CT) features in a case series of primary intrathoracic extracardiac malignant mesenchymal tumours (sarcomas). METHODS: A 5-year retrospective research was conducted, and 18 patients were selected. CT exams were reviewed by two chest radiologists, blinded to tumour pathological type, origin and grade. Lesions were described in relation to location, size, shape, margins, enhancement, presence of cavitation, calcifications, ground glass component, intratumoural enhanced vessels, pleural effusion, pleural tags, lymphangitis, chest wall/rib involvement and pathological lymph nodes. RESULTS: The readers described five pulmonary, six mediastinal and seven pleural/wall based lesions. Mean largest diameter was 103 mm. The most frequent shape was irregular (n = 12), most predominant margin was smooth (n = 12) and enhancement was mostly heterogeneous (n = 8). Intratumoural vessels and pleural effusion were seen in 11 patients. Pathological lymph nodes were present in four cases and calcifications in two cases. CONCLUSIONS: Some frequent radiological features were described independently of tumour location and subtype. A sarcoma should be included as a major differential diagnosis when the radiologist faces an intrathoracic mass of large size (>70 mm) but with well defined smooth or lobulated margins, especially if presenting intratumoural vessels, associated pleural effusion but no significant lymphadenopathy. MAIN MESSAGES: • Malignant mesenchymal tumours (sarcomas) are rare and can arise from any structure in the chest. • Intrathoracic sarcomas show some frequent radiological features, independent of location and type. • Some CT features may help the radiologist suspect for a sarcoma instead of other more common tumours

    Association of Lowering Low‐Density Lipoprotein Cholesterol With Contemporary Lipid‐Lowering Therapies and Risk of Diabetes Mellitus: A Systematic Review and Meta‐Analysis

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    Background The relationship between lowering LDL (low‐density lipoprotein) cholesterol with contemporary lipid‐lowering therapies and incident diabetes mellitus (DM) remains uncertain. Methods and Results Thirty‐three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline, Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid‐lowering therapy. More intensive lipid‐lowering therapy was defined as the more potent pharmacological strategy (PCSK9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta‐analyses were conducted using a random‐effects model. No significant association was noted between 1‐mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid‐lowering therapy (risk ratio: 0.95; 95% CI, 0.87–1.04; P=0.30; R2=14%) or for statins or PCSK9 inhibitors. More intensive lipid‐lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI, 1.03–1.11; P\u3c0.001; I2=0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI, 1.05–1.15; P\u3c0.001; I2=0%), whereas PCSK9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI, 0.93–1.07; P=0.96; I2=0%; P=0.02 for interaction). Conclusions Among intensive lipid‐lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM. The risk of incident DM was higher with statins, whereas PCSK9 inhibitors had no association with risk of incident DM

    Helium-Electrospray: an improved sample delivery system for single-particle imaging with X-ray lasers

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    Imaging the structure and observing the dynamics of isolated proteins using single-particle X-ray diffractive imaging (SPI) is one of the potential applications of X-ray free-electron lasers (XFELs). Currently, SPI experiments on isolated proteins are limited by three factors: low signal strength, limited data and high background from gas scattering. The last two factors are largely due to the shortcomings of the aerosol sample delivery methods in use. Here we present our modified electrospray ionization (ESI) source, which we dubbed Helium-ESI (He-ESI). With it, we increased particle delivery into the interaction region by a factor of 10, for 26 nm-sized biological particles, and decreased the gas load in the interaction chamber corresponding to an 80% reduction in gas scattering when compared to the original ESI. These improvements will lead to a significant increase in the quality and quantity of SPI diffraction patterns in future experiments using He-ESI, resulting in higher-resolution structures

    Association of Lowering Low�Density Lipoprotein Cholesterol With Contemporary Lipid�Lowering Therapies and Risk of Diabetes Mellitus: A Systematic Review and Meta�Analysis

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    Background The relationship between lowering LDL (low�density lipoprotein) cholesterol with contemporary lipid�lowering therapies and incident diabetes mellitus (DM) remains uncertain. Methods and Results Thirty�three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline, Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid�lowering therapy. More intensive lipid�lowering therapy was defined as the more potent pharmacological strategy (PCSK9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta�analyses were conducted using a random�effects model. No significant association was noted between 1�mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid�lowering therapy (risk ratio: 0.95; 95% CI, 0.87–1.04; P=0.30; R2=14%) or for statins or PCSK9 inhibitors. More intensive lipid�lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI, 1.03–1.11; P<0.001; I2=0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI, 1.05–1.15; P<0.001; I2=0%), whereas PCSK9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI, 0.93–1.07; P=0.96; I2=0%; P=0.02 for interaction). Conclusions Among intensive lipid�lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM. The risk of incident DM was higher with statins, whereas PCSK9 inhibitors had no association with risk of incident DM

    From bench to bedside - current clinical and translational challenges in fibula free flap reconstruction.

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    Fibula free flaps (FFF) represent a working horse for different reconstructive scenarios in facial surgery. While FFF were initially established for mandible reconstruction, advancements in planning for microsurgical techniques have paved the way toward a broader spectrum of indications, including maxillary defects. Essential factors to improve patient outcomes following FFF include minimal donor site morbidity, adequate bone length, and dual blood supply. Yet, persisting clinical and translational challenges hamper the effectiveness of FFF. In the preoperative phase, virtual surgical planning and artificial intelligence tools carry untapped potential, while the intraoperative role of individualized surgical templates and bioprinted prostheses remains to be summarized. Further, the integration of novel flap monitoring technologies into postoperative patient management has been subject to translational and clinical research efforts. Overall, there is a paucity of studies condensing the body of knowledge on emerging technologies and techniques in FFF surgery. Herein, we aim to review current challenges and solution possibilities in FFF. This line of research may serve as a pocket guide on cutting-edge developments and facilitate future targeted research in FFF

    Linear and conformational determinants of visceral leishmaniasis diagnostic antigens rK28 and rK39.

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    BACKGROUND: Recombinant antigens rK39 (based on kinesin sequence) and rK28 (comprising kinesin and HASPB sequences) are a mainstay of serological diagnosis for visceral leishmaniasis (VL). However, their key epitopes and the significance of their structural conformation are not clearly defined, particularly in relation to reported cross-reactivity with sera from patients with malaria, schistosomiasis, and tuberculosis. METHODS: To assess the effect of conformation on antigenicity with Sudanese VL sera, antigens rK39 and rK28 were heat-denatured at 95 °C for 10 min and then assayed by enzyme-linked immunosorbent assay (ELISA). Amino acid sequences of rK39 and rK28 were submitted to NCBI BLASTp to assess homology with Plasmodium, Schistosoma, and Mycobacterium. RESULTS: Heat denaturation significantly diminished the antigenicity of rK39 compared to non-denatured antigen (P = 0.001), but not for rK28 (P = 0.275). In BLASTp searches, HASPB sequences from rK28 had similarities with sequences from Plasmodium, encompassing software-predicted B-cell epitopes. CONCLUSIONS: The antigenicity of rK39 appears to be dependent on structural conformation, whereas that of rK28 depends on linear sequence. HASPB sequence homology with Plasmodium may be responsible for the reported cross-reactivity of rK28 with malaria sera. Further work is warranted to refine the specificity of these antigens
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