Abstract Chronic inflammatory neuropathies represent a heterogeneous group of disorders which affect patients' functional status and quality of life. We conducted a systematic review of the ...scientific literature on the effects of both disease and treatment interventions on health-related quality of life (HRQoL) in this patient population. The available data are limited, as few studies have systematically considered HRQoL in patients with inflammatory neuropathies. Moreover, in treatment trials, HRQoL measures have exclusively been used as secondary outcome measures. There is some evidence suggesting that baseline pre-treatment HRQoL reports are lower in patients with chronic inflammatory neuropathy than in age and gender-matched controls. Following treatment interventions, improvements in self-reported measures were consistently documented in the physical domain of HRQoL, which in turn correlated with improvements in traditional strength and functional scales. The impact of available treatments on the quality of life of patients with inflammatory neuropathies remains largely under-investigated. Interestingly, recent, although limited evidence from generic HRQoL measures may partly or completely contradict the results found with the primary, traditional outcome measures used (rituximab for anti-MAG neuropathy; immunoglobulins versus corticosteroids for chronic inflammatory demyelinating polyneuropathy). Similarly, HRQoL measures may suggest superiority, rather than equivalence, of certain drug administration methods (subcutaneous over intravenous immunoglobulins). Further research is needed to assess HRQOL in patients with untreated chronic inflammatory neuropathies in comparison to normative values, as well as precisely quantify treatment benefit. The role of both generic and disease-specific HRQoL measures in the evaluation of patients with chronic inflammatory neuropathies is also worthy of further consideration.
2‐Monoacylglycerols (2‐MAG) with a high content of oleic acid at sn‐2 position was synthesized by enzymatic ethanolysis of refined olive pomace oil, which is a byproduct of olive oil processing. Six ...lipases from different microbial sources were used in the synthesis of 2‐MAG. Immobilized lipase from Candida antarctica gave the highest product yield among the selected lipases. Response surface methodology was applied to optimize reaction conditions; time (4 to 10 h), temperature (45 to 60 °C), enzyme load (10 to 18 wt%), and ethanol:oil molar ratio (30:1 to 60:1). The predicted highest 2‐MAG yield (84.83%) was obtained at 45 °C using 10 (wt%) enzyme load and 50:1 ethanol:oil molar ratio for 5 h reaction time. Experiments to confirm the predicted results at optimum conditions presented a 2‐MAG yield of 82.54%. The purification yield (g 2‐MAG extracted/100 g of total product) was 80.10 and 69.00 for solvent extraction and low‐temperature crystallization, respectively. The purity of the synthesized 2‐MAG was found to be higher than 96%.
Practical Application
Olive pomace oil is a highly abundant, natural, and inexpensive side product of olive oil processing. Synthesis of 2‐monoacylglycerol (2‐MAG) rich in oleic acid at sn‐2 position from olive pomace oil can be a good potential way for valorization of olive pomace. Oleic acid rich 2‐MAG may be used in the synthesis of new specifically targeted structured triacylglycerols with improved nutritional and functional quality. In addition, this synthesized 2‐MAG may have potential applications especially in pharmaceutical and cosmetic fields.
This work presents the experimental results of narrow gap butt welding of steel plates with large thickness by using the Metal Active Gas (MAG) welding method.The typical defects are accompanied with ...this process such as the infusion in the side wall and the porosity due to the narrow gap which affect on the melting process. Thus, some publications noted the results of welding for the thickness up to 20−30 mm and the chamfer angle about 30° using GMAW/MIG, GTAW/TIG, SMAW and new development such as laser – arc hybrid, laser multi- pass technique, super -TIG welding etc. But the production requires the solution to save the costs by the reduction of time, labour and investment keeping the standard quality. That is the aim of this study. In order to improve the quality of weld joint and increase the productivity of the process, is it suggested to develop the innovative welding process, in which the welding voltage – Uw, the translational velocity of the tip – Vt, and rotational velocity of the tip – Vr, are changing. This helped to increase the thickness of steel plates up to 50 mm and the chamfer angle decreased at 15°, providing the satisfied quality of the weld. The micrography study serve as the preliminary proof of this hypothesis.
The microstructures in 4 regions, such as the weld center zone, heat-affected zone (HAZ), parent metal region, and the boundary between the weld metal and the HAZ were examined. The microstructures of 13 positions from different experiments are investigated using the optical microscope (Axiovert 25).These experiments covered all specific points (node) locating accordingly to three layers from bottom to top of the weld joint . The findings proved the welding quality is similar in case of narrow gap but the chamfer angle is twice lower and the thickness is increased. The result of the study enhances the productivity due to saving the labour cost and the welding materials. It is recommended to consider the effect of other factors (such as cooling conditions, dwell time when the arc approaching the side walls) to optimize the weld quality. There is the huge volume of the heavy steel constructions with the thick steel construction and specific narrow gap in industry. The results of this study with the optimization and more deeper evaluation the influence of main parameters of welding process to eliminate the typical defects will be the valuable reco mmendation for the managers and engineers in the production of metallic constructions
Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate ...antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are
O
-linked to a CD4
+
T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer. To ensure broad coverage within the human population, the tetanus toxoid-derived peptide TT830-844 was selected as a T-helper epitope because it can bind to various HLA-DRB molecules. We showed that the MAG-Tn3 vaccine, which was formulated with the GSK proprietary immunostimulant AS15 and designed for human cancer therapy, is able to induce an anti-Tn antibody response in mice of various H-2 haplotypes, and this response correlates with the ability to induce a specific T cell response against the TT830-844 peptide. The universality of the TT830-844 peptide was extended to new H-2 and HLA-DRB molecules that were capable of binding this T cell epitope. Finally, the MAG-Tn3 vaccine was able to induce anti-Tn antibody responses in cynomolgus monkeys, which targeted Tn-expressing tumor cells and mediated tumor cell death both in vitro and in vivo. Thus, MAG-Tn3 is a highly promising anticancer vaccine that is currently under evaluation in a phase I clinical trial.
Mature retinal ganglion cells (RGCs), like other CNS neurons, cannot regrow injured axons into a myelin-rich environment. If stimulated by macrophage-derived factors, however, RGCs can regenerate ...their axons for considerable distances through the distal optic nerve. Using this "sensitized background," we investigated the effects of either increasing the expression or suppressing the activity of the Nogo receptor (NgR). NgR mediates the growth-inhibiting effects of three myelin proteins, Nogo, OMgp (oligodendrocyte-myelin glycoprotein), and MAG (myelin-associated glycoprotein). Transfecting growth-sensitized RGCs with adeno-associated viruses expressing a dominant-negative form of NgR (NgR(DN)) increased axon regeneration several-fold; however, when the growth program of RGCs was not activated, NgR(DN) expression had no beneficial effects. Overexpression of wild-type NgR blocked almost all regeneration from growth-sensitized RGCs and caused axons proximal to the lesion site to retract. We conclude that gene therapy is an effective approach to enhancing axon regeneration in the CNS and that inactivation of NgR functioning greatly enhances axon regeneration provided the intrinsic growth program of neurons is activated.
Les polyneuropathies associées à une gammapathie monoclonale IgM dirigée contre la glycoprotéine associée à la myéline (PNMAG) sont différentes des autres neuropathies dysimmunes.
Les données ...cliniques, biologiques, électrophysiologiques d’une cohorte de 13 patients atteints de PNMAG ont été recueillies dans une étude rétrospective.
Sept hommes et six femmes étaient suivis en moyenne depuis deux ans (0,5–6,5 ans). L’âge au diagnostic était de 61 ans (44,5 ans ; 85,5 ans). Les patients décrivaient des paresthésies symétriques et bilatérales (11/13) prédominantes aux membres inférieurs. Neuf patients présentaient une ataxie proprioceptive à l’orthostatisme et quatre patients un déficit moteur distal modéré des membres inférieurs. L’échelle
Overall Neuropathy Limitation Scale était en moyenne de 2,3 (0 ; 5). L’électroneuromyogramme montrait une démyélinisation distale : allongement des latences distales sur les nerfs médians (en moyenne, 206 % de la normale) et ulnaires (en moyenne, 150 % de la normale) ; index de latences terminales inférieurs à 0,25 sur au moins deux nerfs pour 7/13 patients. Dix patients présentaient une gammapathie monoclonale de signification indéterminée et trois patients un lymphome non hodgkinien. Un dépôt d’IgM et une décompaction des lamelles des gaines de myéline étaient mis en évidence sur 5/7 biopsies de nerf sural. Tous les patients avaient des anticorps anti-MAG en technique
Enzyme-Linked Immunosorbent Assay et 8/12 en
western blot.
Les PNMAG sont des neuropathies à nette prédominance sensitive et ataxiante. Le handicap fonctionnel est souvent modéré. Les données électrophysiologiques sont caractéristiques et fortement évocatrices dans plus de 50 % des cas. Les techniques de détection des anticorps anti-MAG doivent être combinées pour améliorer la sensibilité et la spécificité.
Polyneuropathies associated with IgM paraproteinemia and anti-myelin associated glycoprotein (MAG) antibodies (MAG-PN) have to be differentiated from chronic inflammatory demyelinating polyneuropathies.
In a retrospective study, we have analyzed clinical, electrophysiological, biological and pathological data from MAG-PN patients.
Seven male and six female patients were followed in the department for a mean 2 years (0.5–6.5 years). Mean age at diagnosis was 61 years (44.5–85.5 years). Patients had symmetrical bilateral paresthesia (11/13) and hypoesthesia (11/13) prominent in the lower limbs. Nine patients developed gait ataxia and four patients had moderate distal weakness in the lower limbs. Mean Overall Neuropathy Limitation Scale was 2.3 (0–5). Nerve conduction study showed demyelinating features though delayed distal motor latency on median (206 % of normal value) and ulnar nerves (150% of normal value). Seven out of thirteen patients had at least two nerves with terminal latency index below 0.25. IgM paraproteinemia was of undetermined significance in ten cases and three patients had non-Hodgkin lymphoma. IgM deposits and widening of the peripheral myelin were observed in 5/7 sural nerve biopsies. Anti-MAG antibodies were detected in the sera of all patients using enzyme-linked immunosorbent assay and in 8/12 patients using western blot analysis.
MAG-PN have distinctive clinical, electrophysiological and pathological features. It is a chronic, slowly progressive, predominantly sensory and ataxic neuropathy. Disability is usually moderate. Electrophysiological study shows distal demyelinating process and is highly suggestive of MAG-PN in more than one half of our patients. Several techniques may detect anti-MAG antibodies, they have to be associated to improve sensitivity and specificity of the test.
An efficient method for the synthesis of 1-chloro(dimethyl)silylmethyl-o-carborane, 1-dichloro(methyl)silylmethyl-
o
-carborane, 1-trichlorosilylmethyl-
o
-carborane, and 1-trichlorosilylmethyl- ...2-methyl-
o
-carborane using 1-bromomagnesiummethyl-
o
-carborane, 1-bromomagnesiummethyl-2-methyl-
o
-carborane, and organochlorosilanes was developed.
Arc “jump sidewall” phenomenon is observed during P-MAG welding in narrow gap conditions. The mechanism and formation conditions are analyzed, and the phenomenon is found to be the arc channel ...re-establishment process, which results from large changes in the welding current. The arc channel position is the result of the balance between the electric field force and the magnetic field force. The current characteristics of P-MAG welding in a narrow groove provide adequate conditions for a “jump sidewall” phenomenon. The influences of a narrow gap groove on droplet transfer and arc signal of P-MAG power supply with modified I-I external characteristics are discussed. The research results lay a foundation for arc sensor-based welding seam tracking technology in narrow gap P-MAG welding.
In this paper, an efficient and sensitive analytical method for the simultaneous determination of three trace sterols including ergosterol, stigmasterol and β-sitosterol in complicated biological ...samples was developed by gas chromatography–mass spectrometry (GC–MS) coupled with extraction using novel β-sitosterol magnetic molecularly imprinted polymer (mag-MIP) beads. Physical tests suggested that β-sitosterol mag-MIP beads prepared by a rapid microwave synthesis method possessed the porous morphology, narrow size distribution, stable chemical and thermal property. Due to the greatly enlarging surface area and the strong recognition to the target molecules, β-sitosterol mag-MIP beads have a higher enrichment factor for β-sitosterol (∼20-fold) and the higher selectivity for β-sitosterol and its analogs than that of β-sitosterol magnetic nonimprinted polymer (mag-NIP) beads. Under the optimum analytical conditions, all the target compounds achieved good chromatographic separation and sensitive detection without matrix interference. It was interesting that three target sterols were actually found in mushroom samples, and stigmasterol and β-sitosterol were actually found in serum and watermelon samples. The recoveries of spiked sample tests were in range of 71.6–88.2% with RSDs of 2.4–10.0% (
n
=
3). This method is reliable and applicable for the simultaneous determination of trace sterols in real biological samples based on the β-sitosterol mag-MIP bead extraction.
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