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Polymyxin B (PB) and Polymyxin E (PE, also called colistin) are used as the last treatment resort for multidrug-resistant Gram-negative bacterial infections. The nephrotoxicity and neurotoxicity of polymyxins limit their clinical use, and guidelines recommend therapeutic drug monitoring (TDM) to optimize efficacy and reduce toxicity. However, there are limited analytical methods available for the determination of PB and PE. This study aimed to develop a simple and robust liquid chromatography with tandem mass spectrometry (LC-MS/MS) analytical method for determining the main compounds of PB and PE, namely PB1, PB2, ile-PB1, PE1, and PE2, in human plasma and to investigate of their pharmacokinetics in critically ill patients with the use of PB and PE, respectively. Plasma PB1, PB2, ile-PB1, PE1, and PE2 were chromatographically separated on a Welch LP-C18 column and detected using electrospray ionization mode coupled with multiple reaction monitoring. The calibration curve showed acceptable linearity over 20-10,000â¯ng/mL for PB1, PE1, and PE2 and 10-5000â¯ng/mL for PB2 and ile-PB1 in the plasma, respectively. After validation following approved guidelines, this method was successfully applied for PB and PE pharmacokinetic analysis and TDM in critically ill patients. Additionally, the composition of PB1, PB2, ile-PB1, PE1, and PE2 remains unchanged from 0 to 12â¯h after entering the patient's body.
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With the onset of the 5G era, wearable flexible electronic devices have developed rapidly and gradually entered the daily life of people. However, the vast majority of research focuses on the integration of functions and performance improvement, while ignoring electromagnetic hazards caused by devices. Herein, the 3D double conductive networks are constructed through a repetitive vacuum-assisted dip-coating technique to decorate the 2D MXene and 1D silver nanowires on the melamine foam. Benefiting from the unique porous structure and multi-scale interconnected frame, the resultant composite foam exhibited high electrical conductivity, low density, superb electromagnetic interference shielding (48.32 dB), and Joule heating performance (up to 90.8 °C under 0.8 V). Furthermore, a single-electrode triboelectric nanogenerator (TENG) with powerful energy harvesting capability is assembled by combining the composite foam with an ultra-thin Ecoflex film and a polyvinylidene fluoride film. Simultaneously, the foam-based TENG can also be considered a reliable wearable sensor for monitoring activity patterns in different parts of the human body. The versatility and scalable manufacturing of high-performance composite foams will provide new design ideas for the development of next-generation flexible wearable devices.
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Conductive hydrogels have received widespread attention in the field of flexible sensors. However, a single network structure inside the hydrogel sensor usually makes it difficult to bear larger mechanical loadings, greatly limiting practical applications. Developing a recoverable conductive hydrogel sensor with high toughness and adaptability is still challenging. Herein, a high-performance polyvinyl alcohol (PVA)-based conductive composite hydrogel was constructed, assisted by green cellulose nanofibrils (CNFs), magnesium chloride (MgCl2), ethylene glycol (EG), and liquid metal (LM). The synergistic effects between CNFs and LM enhanced the network structure inside the recoverable hydrogel. This resulted in an excellent tensile strength of 3.86 MPa with an elongation at break of as high as 918.4 % and compressive strength of 4.04 MPa at 80 % strain. In addition, the conductive network composed of MgCl2 and LM endowed the hydrogel good electrical conductivity. Moreover, it could be used as a flexible strain sensor for various application scenarios, e.g., micro-stress monitoring (water droplet falling) and information encryption transmission of Morse code. Such uniqueness will provide a design strategy for developing a new generation of hydrogel sensors.
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Celulosa , Alcohol Polivinílico , Conductividad Eléctrica , Hidrogeles , MetalesRESUMEN
Infliximab and its anti-drug antibody (ADA) serum concentrations exhibit a strong correlation with clinical response and loss of response. The use of therapeutic drug monitoring to measure the concentration of infliximab and ADA can facilitate clinical decision-making, helping patients attain optimal therapeutic effects. However, there are still limitations to the existing infliximab and its ADA detection methods. Therefore, this study aimed to develop and validate enzyme-linked immunosorbent assay (ELISA)-based methods for measuring infliximab and its ADA levels in human plasma according to the general recommendations for immunoassays. Free infliximab is bound by recombinant TNF-α and detected using HRP-labeled anti-human antibody. The ADA is captured by on-plate-coated infliximab and recognized by biotin-labeled infliximab. Two bridging ELISA assays were developed and after assay optimization and validation, these assays have been applied in ten patients with inflammatory bowel disease (IBD). In infliximab detection assay, a standard curve ranging from 0.10 µg/mL to 8.0 µg/mL with great precision and accuracy has been established. Drug tolerance of the ADA assay was that 100 ng/mL ADA could tolerate at least 5.0 µg/mL infliximab in the plasma using a commercially available monoclonal anti-infliximab antibody as the positive control. The ADA screening and confirmatory assays achieved a sensitivity of 36.74 ng/mL and 37.15 ng/mL, respectively. All other assay characteristics met the requirements. The mean concentration of infliximab in eight patients with IBD was 7.88 (1.87-21.1) µg/mL, and the ADA levels were all negative. Moreover, the concentrations of infliximab in the remaining two patients were below the LLOQ and the ADAs were positive. Thus, accurate and sensitive ELISA methods have been developed and validated for the detection of infliximab and its ADA concentrations and have been successfully applied to clinical therapeutic drug monitoring.
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Vinyl-functionalized graphene oxide (VGO) was used as a reactive compatibilizer to prepare poly(lactic acid)/polybutylene adipate-co-terephthalate (PLA/PBAT) blends. The linear rheological and scanning electron microscopy results confirmed that the VGO nanosheets were quite efficient in compatibilizing PLA/PBAT blends. The size of the PBAT dispersed phase was remarkably decreased in the presence of VGO nanosheets. Moreover, the VGO nanosheets exhibited strong nucleating effects on the crystallization process of PLA. The crystallinity of PLA component in the compatibilized blend with various VGO nanosheets was higher than 40%, upon the cooling rate of 20 °C/min. The prepared PLA/PBAT pellets were applied to 3D printing, using a self-developed screw-based 3D printer. The results showed that all the prepared PLA/PBAT blend pellets can be 3D printed successfully. The notched Izod impact test results showed that, in the presence of VGO, an increase of at least 142% in impact strength was achieved for PLA/PBAT blend. This could be attributed to the compatibilizing effect of the VGO nanosheets. Thus, this work provides a novel way to prepare tough PLA-based materials for 3D printing.
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Two-dimensional (2D) MXene has attracted vast attention in electromagnetic wave absorption (EWA), but there remains a contradiction between maintaining impedance matching and enhancing dielectric loss. Herein, the multi-scale architectures of ecoflex/2D MXene (Ti3C2Tx)@zero-dimensional CoNi sphere@one-dimensional carbon nanotube composite elastomers were successfully constructed by simple liquid-phase reduction and thermo-curing method. The binding between the hybrids as fillers and ecoflex as a matrix greatly enhanced the EWA capability of the obtained composite elastomer and improved its mechanical properties. Owing to its good impedance matching, abundant heterostructures, and synergistic electrical and magnetic losses, this elastomer exhibited an excellent minimum reflection loss of -67 dB at 9.46 GHz under a thickness of 2.98 mm. In addition, its ultrabroad effective absorption bandwidth reached 6.07 GHz. This achievement will pave the way for the exploitation of multi-dimensional heterostructures as high-performance electromagnetic absorbers with superior EWA ability.
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Nowadays, developing high-performance electromagnetic functional materials to eliminate the ever-increasing electromagnetic pollution problem is necessary for the complex electromagnetic environment. However, the materials with high electrical conductivity are prone to secondary electromagnetic pollution due to interface impedance mismatching. Herein, the wheat-like electrically conductive and magnetic silver nanowire@nickle (AgNW@Ni) composites were fabricated via a one-pot in-situ growth method. The electromagnetic properties of the composites could be regulated by adjusting different ratios of precursors, resulting in various morphological features of the nanowire as the core with different Ni shell thicknesses. When the Ag and Ni molar ratio was 1:1.1, the AgNW@Ni composite exhibited the optimal minimum reflection loss (RLmin) of -61.1 dB with an adequate effective absorption bandwidth (EAB) of 4.06 GHz owing to good impedance matching, abundant heterostructures, and synergistic electrical and magnetic losses. Even after three months, it still maintained an acceptable RLmin value of -39.7 dB and similar EAB, demonstrating its long-term operational stability. This unique composite is expected to be applied in more actual electromagnetic protection occasions.
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Basalt fibers (BFs) are environmentally friendly materials characterized by high strength and good wear resistance, and thus are popular candidates for reinforcing polymers. Herein, polyamide 6 (PA 6), BFs, and the styrene-ethylene-butylene-styrene (SEBS) copolymer were melt compounded sequentially to prepare fiber-reinforced PA 6-based composites. The results showed improved mechanical and tribological performances via the incorporation of BFs and SEBS into PA 6. Compared to neat PA 6, an average 83% increase in notched impact strength was achieved for the PA 6/SEBS/BF composites, which is mainly due to the good miscibility between SEBS and PA 6. The tensile strength of the composites, however, was only increased moderately, since the weak interfacial adhesion was not sufficiently efficient to transfer the load from the PA 6 matrix to the BFs. Interestingly, the wear rates of both the PA 6/SEBS blend and the PA 6/SEBS/BF composites were obviously lower than those of the neat PA 6. The PA 6/SEBS/BF composite with 10 wt.% of the BFs exhibited the lowest wear rate of 2.7 × 10-5 mm3/N·m, which was decreased by 95% compared to that of the neat PA 6. The facilitation of forming tribo-film with SEBS and the naturally good wear resistance of the BFs were responsible for the largely decreased wear rate. Moreover, the incorporation of SEBS and BFs into the PA 6 matrix transformed the wear mechanism from adhesive wear to abrasive wear.
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A sensitive and robust LC-MS/MS method has been developed and validated for olverembatinib quantification in human plasma and cerebrospinal fluid (CSF). The method involved liquid-liquid extraction with methyl tertiary butyl ether for plasma pretreatment and precipitation enrichment with methanol for CSF pretreatment. Separation was achieved on the C18 column with gradient elutions of 10 mM ammonium formate in water and methanol-acetonitrile (50:50,v/v). Analyte detection was conducted by electrospray ionization (ESI) in a positive ion mode using multiple reaction monitoring (MRM). The m/z transitions were 533.4â433.2 for olverembatinib and m/z 502.4â394.2 for the internal standard (IS, Imatinib-d8). Calibration curves ranged from 0.500 to 50.0 ng/mL for plasma and from 0.0100 to 1.00 ng/mL for CSF. The intra- and inter-day precision and accuracy were < 15% for both plasma and CSF with four different quality control concentrations. The relative matrix effect was < 10% in plasma and artificial CSF. This method was successfully utilized for the measurement of olverembatinib concentrations in plasma and CSF from chronic myeloid leukemia patients.
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Metanol , Espectrometría de Masas en Tándem , Humanos , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Piperidinas , Reproducibilidad de los ResultadosRESUMEN
A rapid, specific and accurate high-performance liquid chromatography with tunable ultraviolet detection method was developed to simultaneously determine azathioprine metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl mercaptopurine riboside (6-MMPr) in human red blood cells. Erythrocyte lysate sample was precipitated by perchloric acid under the protection of dithiothreitol, with 6-TGN and 6-MMPr being acid hydrolyzed to produce 6-thioguanine (6-TG) and 6-methymercaptopurine (6-MMP). A Waters Cortecs C18 column (2.1 × 150 mm, 2.7 µm) was used for chromatographic separation with a water (containing 0.01 mol/L ammonium acetate and 0.2% acetic acid)/methanol linear gradient at a flow rate of 0.45 mL/min in a 5.5 min. UV detection wavelengths were 340 nm for 6-TG, 303 nm for 6-MMP and the IS (5-bromouracil). The calibration curves fitted a least squares model (weighed 1/x 2) from 0.15 to 15 µmol/L for 6-TG (r 2 = 0.9999) and from 1 to 100 µmol/L for 6-MMP (r 2 = 0.9998). This method was validated according to the FDA bioanalytical method validation guidance and ICH M10 bioanalytical method validation and study sample analysis guidance for industry, and successfully utilized in ten IBD patients receiving azathioprine therapy.
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Wearable flexible sensors based on conductive hydrogels have received extensive attention in the fields of electronic skin and smart monitoring. However, conductive hydrogels contain a large amount of water, which greatly affects their performances in harsh environments. It is therefore necessary to prepare hydrogel sensors that are stable at low temperatures. Herein, metal ions (MgCl2) and ethylene glycol (EG) were combined with polyvinyl alcohol (PVA) to obtain a conductive PVA/EG hydrogel with tensile strength and elongation at break of 1.1 MPa and 442.3 %, respectively, which could withstand >6000-fold its own weight. The binary solvent system composed of water and EG contributed to the excellent anti-freezing properties and long-term storage (>1 week), flexibility, and stability of the hydrogel even at -20 °C. The wearable PVA/EG hydrogel as a flexible sensor possessed desirable sensing performances with a competitive GF value of 0.725 and fatigue resistance (50 cycles) when used to monitor various human motions and physiological signals. Overall, this hydrogel sensor shows strong potential for application in the fields of human motion monitoring, written information sensing, and information encryption and transmission.
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Frío , Hidrogeles , Humanos , Conductividad Eléctrica , Agua , Glicoles de EtilenoRESUMEN
OBJECTIVE: Nearly half of parapharyngeal space (PPS) tumors present as an intraoral mass, which is diagnostically challenging. In this study, we studied whether preoperative growth patterns were associated with histopathological diagnosis for planning surgery. METHODS: We performed a cross-sectional study in patients with PPS tumors. A simplified classification scheme based on intraoral tumor growth patterns (patterns 1 and 2) was then proposed. In pattern 1, tumors bulge submucosally to the oropharynx from the soft palate, with the center convexity above the uvula. In pattern 2, tumors bulge submucosally to the oropharynx from the lateral oropharynx wall, with the center convexity below the uvula. The association of this classification with postoperative histopathological diagnosis and surgical-related events was studied. RESULTS: Twenty-two patients were enrolled in this study (12 with pattern 1, 10 with pattern 2). Of these, 91.7% (11/12) of pattern 1 tumors were salivary gland tumors (P < .001), and 90% (9/10) of pattern 2 tumors were neurogenic (P < .001). Pattern 2 tumors had fewer bleeding complications or needed external approaches when a transoral approach was chosen. CONCLUSIONS: This new classification of PPS tumors facilitates the prediction of salivary gland and neurogenic tumors and can improve the accuracy of preoperative radiologic diagnosis. This system will be helpful for planning surgical interventions, such as implementing transoral approaches.
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Neoplasias Faríngeas , Neoplasias de las Glándulas Salivales , Humanos , Neoplasias Faríngeas/patología , Estudios Transversales , Neoplasias de las Glándulas Salivales/patología , Espacio Parafaríngeo/patología , Úvula/patología , Estudios RetrospectivosRESUMEN
Recently, the sustainable utilization of waste resources has become a low-cost and effective strategy to design high-performance functional materials to solve the increasingly serious environmental pollution problem. Herein, the flexible and highly stretchable polyurethane (PU) composite foams assisted by one-dimensional carbon nanotubes (CNTs) and zero-dimensional Fe3O4 were fabricated using waste tire rubbers (WTRs) as reinforcements during a simple self-foaming process. The collaborative introduction of conductive CNTs, magnetic Fe3O4, and WTRs with three-dimensional cross-linked structures enabled the construction of an efficient electronic transmission path and heterointerfaces inside the composite foam. The resulting composite foam possessed a desired minimum reflection loss (RLmin) of −47.43 dB, and also exhibited superior mechanical properties with a tensile strength of >3 MPa and multiple tensile deformation recovery abilities. In addition, increasing the temperature could significantly improve the electromagnetic wave absorption performance of the composite foam. This comprehensive composite foam derived from WTRs has shown a promising development potential for using waste materials to relieve electromagnetic pollution.
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High-performance polyether-ether-ketone (PEEK) is highly desirable for a plethora of engineering applications. The incorporation of conductive carbon nanotubes (CNTs) into PEEK can impart electrical conductivity to the otherwise non-conductive matrix, which can further expand the application realm for PEEK composites. However, a number of physical properties, which are central to the functionalities of the composite, are affected by the complex interplay of the crystallinity and presence of the nanofillers, such as CNTs. It is therefore of paramount importance to conduct an in-depth investigation to identify the process that optimizes the mechanical and electrical performance. In this work, PEEK/CNTs composites with different carbon nanotubes (CNTs) content ranging from 0.5 to 10.0 wt% are prepared by a parallel twin-screw extruder. The effects of CNTs content and annealing treatment on the crystallization behavior, mechanical properties and electrical conductivity of the PEEK/CNTs composites are investigated in detail. A non-isothermal crystallization kinetics test reveals a substantial loss in the composites' crystallinity with the increased CNTs content. On the other hand, mechanical tests show that with 5.0 wt% CNTs content, the tensile strength reaches a maximum at 118.2 MPa, which amounts to a rise of 30.3% compared with the neat PEEK sample after annealing treatment. However, additional annealing treatment decreases the electrical conductivity as well as EMI shielding performance. Such a decrease is mainly attributed to the relatively small crystal size of PEEK, which excludes the conductive fillers to the boundaries and disrupts the otherwise conductive networks.
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Recently, high-performance functional composites for electromagnetic wave absorption (EWA) with tunable nano/micro-structures have attracted extensive attention. Herein, the flower-like electrically conductive and magnetic cobalt-nickel@carbon (CoNi@C) composites derived from bimetallic metal-organic frameworks (MOFs) were fabricated via solvothermal method and pyrolysis. By adjusting the ratios of different precursors, different morphological features of composites were formed. When the molar ratio of Co and Ni was 1:2, the CoNi@C composites exhibited the optimal minimum reflection loss (RLmin) of -56.89 dB at 6.7 GHz with an effective absorption bandwidth of 4.7 GHz, due to the coordinated dielectric and magnetic loss caused by the electromagnetic properties of each component as well as the interactions between the unique three-dimensional (3D) interfaces of flower-like structures that promoted the absorption and dissipation of composites for microwaves. The composites are expected to become promising candidates as high-efficiency absorbers in the electromagnetic protection field.
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In this paper, a lead-bronze/steel bimetal composite was produced by vacuum diffusion welding technology. The microstructure, hardness and tribological properties under the dry sliding condition of the bimetal structured material were investigated and compared with two reference samples, i.e., lead-bronze and Mn/Si-brass. The wear mechanism of the three materials was also analyzed in detail. It was found that the bimetallic structure possessed the best wear resistance among the three samples. When paired with the ball bearing steel, the wear rates of the lead-bronze and Mn/Si-brass were 13 and 54 times higher than that of the bimetal composite. When paired with bearing steel, the wear rates of the two materials were 13 and 54 times higher than the bimetallic composite, respectively. This is because the steel layer served as a bearing layer to decrease the plastic deformation of the bronze layer. Furthermore, the lead can accelerate the formation of a dense hardened layer at the sliding interfaces to avoid subsequent wear of the bronze surface. Nevertheless, this hardened layer caused severe scuffing on the steel balls. Therefore, lead-bronze/steel structured material is recommended to match with hard counterface material, such as cemented carbide.
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Lightweight and efficient electromagnetic interference (EMI) shielding materials play a vital role in protecting high-precision electronic devices and human health. Porous PVDF/CNTs/urchin-like Ni composites with different cell sizes from nanoscale to microscale were fabricated through one-step supercritical carbon dioxide (CO2) foaming. The electrical conductivity and electromagnetic interference (EMI) shielding performance of the composites with different cell sizes were examined in detail. The results indicated that the nanoscale cell structure diminishes the EMI shielding performance of the composite, whereas the microscale cell structure with an appropriate size is beneficial for improving the EMI shielding performance. A maximum EMI shielding effectiveness (SE) of 43.4 dB was achieved by the composite foams which is about twice that of the solid composite. Furthermore, as the supercritical CO2 foaming process reduces the density of the composite by 25-50%, the EMI SSE (specific shielding effectiveness)/t(thickness) of the composite reaches 402 dB/(g/cm2), which is the highest value of polymer foam obtained to the best of the authors' knowledge. Finally, compression tests were performed to show that the composites still maintained excellent mechanical properties after the supercritical CO2 foaming process.
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Background: Apoptosis plays an essential role in the development and treatment of tumors, and caspase-8 (CASP8) plays an important role in the enzyme cascade reaction that leads to apoptosis. Human epidermal growth factor receptor 2 (HER-2) overexpressing breast cancer is highly aggressive and has a high recurrence rate and poor prognosis. This study investigated whether lentivirus-mediated Gag-CASP8 can effectively deliver activated CASP8 into primary human breast cancer cells overexpressing HER-2 to induce apoptosis and explore the underlying mechanism. Materials and Methods: HER-2 overexpressing primary human breast cancer cells were infected with lentivirus-like particles carrying Gag-CASP8. Results: After a 48h infection of primary human breast cancer cells with HER-2 by lentivirus-mediated Gag-CASP8, significant differences were observed in the survival rate, migration ability, S-phase number of cells, apoptosis rate, and intracellular activated CASP8 and caspase-3 levels in tumor cells compared with those in the control group (p < 0.05). Conclusions: Lentivirus-mediated Gag-CASP8 can deliver activated CASP8 into HER-2 overexpressing primary human breast cancer cells and induce apoptosis by activating caspase-3, a downstream apoptotic executive molecule. By blocking the S-phase to inhibit cell proliferation and migration, lentivirus-mediated Gag-CASP8 provides a reference for tumor gene therapy.
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Neoplasias de la Mama , Lentivirus , Humanos , Femenino , Caspasa 8/genética , Caspasa 3/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Neoplasias de la Mama/metabolismo , ApoptosisRESUMEN
Environmentally friendly and non-toxic polylactic acid (PLA) foam has shown great application prospects in heat preservation, adsorption and other fields. However, it is still challenging to prepare high-expansion PLA foam. Herein, a cooling batch foaming process under supercritical CO2 (sc-CO2), based on pre-melted non-crystalline state, was proposed to prepare PLA foams with high expansion ratio. The CO2 dissolved in the polymer melt will lower the crystallization temperature of PLA. Due to the lack of crystallization, the foaming temperature of PLA can be reduced, which increases the CO2 saturation and helps foam. When foaming is triggered before crystallization, ultrahigh expansion foam can be produced. Based on pre-melting treatment, the maximum expansion ratio of PLA has reached 59.7-fold. At the same time, an open-pore structure is produced by this method, which can selectively absorb oil from water. In addition, the adsorption capacity of CCl4 reaches 15 g/g, and there is no significant attenuation in 20 adsorption-desorption cycles. This work provides a green, solvent-free method to prepare biodegradable oil-adsorbing foam.
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Petróleo , Poliésteres/química , Agua/químicaRESUMEN
Objective:To research the differences of sensory organization testing in maintaining postural stability between patients with type 2 diabetes mellitus and patients with peripheral vertigo using computerized posturography. Methods:Participants were divided into the control group ï¼52 casesï¼, the type 2 diabetes mellitus group ï¼T2DMï¼ ï¼45 casesï¼, and the peripheral vertigo group ï¼PVï¼ ï¼47 casesï¼. All participants were examined under six conditions by computerized posturography: The sensory organization test, a part of computerized dynamic posturography, was used to assess the abilities of vision, somatosensory and vestibular systems in maintaining postural stability. Results:The scores of statokinesiogram ï¼SKGï¼ of the T2DM group in condition 1 ï¼standing on static platform with eye openï¼, condition 4ï¼standing on foam platform with eyes openï¼ and condition 6ï¼standing on foam platform with servo-controlled visionï¼ were significantly greater than that in the vertigo group ï¼P<0.01ï¼. The visual scores in the T2DM group were lower than those of the PV groupï¼P<0.01ï¼ in the anteroposterior and lateral directions. Conclusion:Patients with type 2 diabetes and peripheral vertigo have a decreased ability to maintain balance in the upright position. Patients with type 2 diabetes have a poorer ability to maintain balance with visual systems than patients with peripheral vertigo.