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As a technique in artificial intelligence, a convolution neural network model has been utilized to extract average surface roughness from the geometric characteristics of a membrane image featuring micro- and nanostructures. For surface roughness measurement, e.g. atomic force microscopy and optical profiler, the previous methods have been performed to analyze a porous membrane surface on an interest of region with a few micrometers of the restricted area according to the depth resolution. However, an image from the scanning electron microscope, combined with the feature extraction process, provides clarity on surface roughness for multiple areas with various depth resolutions. Through image preprocessing, the geometric pattern is elucidated by amplifying the disparity in pixel intensity values between the bright and dark regions of the image. The geometric pattern of the binary image and magnitude spectrum confirmed the classification of the surface roughness of images in a categorical scatter plot. A group of cropped images from an original image is used to predict the logarithmic average surface roughness values. The model predicted 4.80 % MAPE for the test dataset. The method of extracting geometric patterns through a feature map-based CNN, combined with a statistical approach, suggests an indirect surface measurement. The process is achieved through a bundle of predicted output data, which helps reduce the randomness error of the structural characteristics. A novel feature extraction approach of CNN with statistical analysis is a valuable method for revealing hidden physical characteristics in surface geometries from irregular pixel patterns in an array of images.
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Ovarian cancer is the leading cause of gynecologic cancer death. Among the most innovative anti-cancer approaches, the genetic concept of synthetic lethality is that mutations in multiple genes work synergistically to effect cell death. Previous studies found that although vaccinia-related kinase-1 (VRK1) associates with DNA damage repair proteins, its underlying mechanisms remain unclear. Here, we found high VRK1 expression in ovarian tumors, and that VRK1 depletion can significantly promote apoptosis and cell cycle arrest. The effect of VRK1 knockdown on apoptosis was manifested by increased DNA damage, genomic instability, and apoptosis, and also blocked non-homologous end joining (NHEJ) by destabilizing DNA-PK. Further, we verified that VRK1 depletion enhanced sensitivity to a PARP inhibitor (PARPi), olaparib, promoting apoptosis through DNA damage, especially in ovarian cancer cell lines with high VRK1 expression. Proteins implicated in DNA damage responses are suitable targets for the development of new anti-cancer therapeutic strategies, and their combination could represent an alternative form of synthetic lethality. Therefore, normal protective DNA damage responses are impaired by combining olaparib with elimination of VRK1 and could be used to reduce drug dose and its associated toxicity. In summary, VRK1 represents both a potential biomarker for PARPi sensitivity, and a new DDR-associated therapeutic target, in ovarian cancer.
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Daño del ADN , Proteína Quinasa Activada por ADN , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Ováricas , Proteínas Serina-Treonina Quinasas , Femenino , Humanos , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Proteína Quinasa Activada por ADN/metabolismo , Proteína Quinasa Activada por ADN/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inestabilidad Genómica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Ftalazinas/farmacología , Piperazinas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genéticaRESUMEN
Haptic human-machine interfaces (HHMIs) combine tactile sensation and haptic feedback to allow humans to interact closely with machines and robots, providing immersive experiences and convenient lifestyles. Significant progress has been made in developing wearable sensors that accurately detect physical and electrophysiological stimuli with improved softness, functionality, reliability, and selectivity. In addition, soft actuating systems have been developed to provide high-quality haptic feedback by precisely controlling force, displacement, frequency, and spatial resolution. In this Review, we discuss the latest technological advances of soft sensors and actuators for the demonstration of wearable HHMIs. We particularly focus on highlighting material and structural approaches that enable desired sensing and feedback properties necessary for effective wearable HHMIs. Furthermore, promising practical applications of current HHMI technology in various areas such as the metaverse, robotics, and user-interactive devices are discussed in detail. Finally, this Review further concludes by discussing the outlook for next-generation HHMI technology.
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Dispositivos Electrónicos Vestibles , Humanos , Reproducibilidad de los ResultadosRESUMEN
This research presents a simple but general method to prepare water-soluble-polymer-based superabsorbent hydrogels with predefined microscale geometries and controlled swelling properties. Unlike conventional hydrogel preparation methods based on bulk solution-phase cross-linking, poly(vinyl alcohol) is homogeneously mixed with polymer-based cross-linkers in the solution phase and thermally cross-linked in the solid phase after drying; the degree of cross-linking is modulated by controlling the cross-linker concentration, pH, and/or thermal annealing conditions. After the shape definition process, cross-linked films or electrospun nanofibers are treated with sulfuric acid to weaken hydrogen bonds and introduce sulfate functionality in polymer crystallites. The resultant superabsorbent hydrogels exhibit an isotropic expansion of the predefined geometry and tunable swelling properties. Particularly, hydrogel microfibers exhibit excellent optical transparency, good biocompatibility, large porosity, and controlled cell adhesion, leading to versatile 3D cell culture scaffolds that not only support immortalized cell lines and primary neurons but also enable stiffness-modulated cell adhesion studies.
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Alpha-2-Glycoprotein 1, Zinc-binding (AZGP1, ZAG) is a secreted protein that is synthesized by adipocytes and epithelial cells; it is downregulated in several malignancies such as breast, prostate, liver and lung cancers. However, its function remains unclear in cholangiocarcinoma (CCA). Here, we evaluated the impact AZGP1 in CCA using Gene Expression Omnibus (GEO) and GEPIA. In addition, we analysed AZGP1 expression using quantitative reverse transcription PCR and western blotting. Expression of AZGP1 was nearly deficient in CCA patients and cell lines and was associated with poor prognosis. AZGP1 overexpression upregulated apoptosis markers. Co-immunoprecipitation experiments showed that AZGP1 interacts with tripartite motif-containing protein 25 (TRIM25), and tissue microarray and bioinformatic analysis showed that AZGP1 is negatively correlated with TRIM25 expression in CCA. Thereafter, TRIM25 knockdown led to AZGP1 upregulation and induced cancer cell apoptosis. TRIM25 targets AZGP1 for degradation by catalysing its ubiquitination. AZGP1 overexpression significantly suppressed tumour growth in a xenograft mouse model. This study findings suggest that AZGP1 is a potential therapeutic target or a diagnostic biomarker for treating patients with CCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Masculino , Humanos , Animales , Ratones , Colangiocarcinoma/metabolismo , Transformación Celular Neoplásica , Conductos Biliares Intrahepáticos/metabolismo , Neoplasias de los Conductos Biliares/metabolismo , Apoptosis , Línea Celular Tumoral , Proliferación Celular/genética , Proteínas de Motivos Tripartitos , Factores de Transcripción , Ubiquitina-Proteína Ligasas , Zn-alfa-2-GlicoproteínaRESUMEN
Colorectal cancer (CRC) is one of the highest mortality rates worldwide, and various studies reported to the occurrence of CRC. In particular, the Wnt/ß-catenin pathway is known to be a major factor in the progression of CRC and ß-catenin involved in the expression of its downstream target genes. We searched for TCOF1 through sliver staining to identify a new binding partner for ß-catenin and to investigate the role of the gene involved in CRC. Treacle Ribosome Biogenesis Factor 1 (TCOF1) is a nucleolar protein that regulates the transcription of ribosomal DNA (rDNA). There are many reports of genetic studies on TCOF1 mutations and defects, but its function in CRC remains unknown. We demonstrated that TCOF1 and ß-catenin expression in tissue microarray (TMA) containing 101 individual CRC and 17 adjacent normal samples. Additionally, the effects of TCOF1 knockdown or overexpression were examined proliferation, colony formation assay, western blot, and quantitative real-time PCR (qRT-PCR). TCOF1 knockdown or overexpression regulates cell proliferation about three-fold and the phosphorylation of ß-catenin, cyclin D1 expression levels. Besides, we discovered the mechanism through which TCOF1 regulates the stability of ß-catenin was involved in degradation through proteasome using ubiquitination assay. Finally, we confirmed the interaction of TCOF1 with the tankyrase inhibitor NVP-TNKS656, which destabilizes ß-catenin through in vitro and in vivo. Collectively, this study shows that significantly correlation was observed that TCOF1 and ß-catenin were risk factor for tumor progression. The stability of ß-catenin via regulating TCOF1 expression could be a potential strategy for therapeutic with CRC.
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Neoplasias Colorrectales , beta Catenina , Humanos , beta Catenina/genética , beta Catenina/metabolismo , Línea Celular Tumoral , Neoplasias Colorrectales/patología , Vía de Señalización Wnt/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismoRESUMEN
Film-type shape-configurable speakers with tunable sound directivity are in high demand for wearable electronics. Flexible, thin thermoacoustic (TA) loudspeakers-which are free from bulky vibrating diaphragms-show promise in this regard. However, configuring thin TA loudspeakers into arbitrary shapes is challenging because of their low sound pressure level (SPL) under mechanical deformations and low conformability to other surfaces. By carefully controlling the heat capacity per unit area and thermal effusivity of an MXene conductor and substrates, respectively, it fabricates an ultrathin MXene-based TA loudspeaker exhibiting high SPL output (74.5 dB at 15 kHz) and stable sound performance for 14 days. Loudspeakers with the parylene substrate, whose thickness is less than the thermal penetration depth, generated bidirectional and deformation-independent sound in bent, twisted, cylindrical, and stretched-kirigami configurations. Furthermore, it constructs parabolic and spherical versions of ultrathin, large-area (20 cm × 20 cm) MXene-based TA loudspeakers, which display sound-focusing and 3D omnidirectional-sound-generating attributes, respectively.
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The blood-brain barrier (BBB) is a selective barrier that controls the transport between the blood and neural tissue features and maintains brain homeostasis to protect the central nervous system (CNS). In vitro models can be useful to understand the role of the BBB in disease and assess the effects of drug delivery. Recently, we reported a 3D BBB model with perfusable microvasculature in a Transwell insert. It replicates several key features of the native BBB, as it showed size-selective permeability of different molecular weights of dextran, activity of the P-glycoprotein efflux pump, and functionality of receptor-mediated transcytosis (RMT), which is the most investigated pathway for the transportation of macromolecules through endothelial cells of the BBB. For quality control and permeability evaluation in commercial use, visualization and quantification of the 3D vascular lumen structures is absolutely crucial. Here, for the first time, we report a rapid, non-invasive optical coherence tomography (OCT)-based approach to quantify the microvessel network in the 3D in vitro BBB model. Briefly, we successfully obtained the 3D OCT images of the BBB model and further processed the images using three strategies: morphological imaging processing (MIP), random forest machine learning using the Trainable Weka Segmentation plugin (RF-TWS), and deep learning using pix2pix cGAN. The performance of these methods was evaluated by comparing their output images with manually selected ground truth images. It suggested that deep learning performed well on object identification of OCT images and its computation results of vessel counts and surface areas were close to the ground truth results. This study not only facilitates the permeability evaluation of the BBB model but also offers a rapid, non-invasive observational and quantitative approach for the increasing number of other 3D in vitro models.
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Barrera Hematoencefálica , Aprendizaje Profundo , Barrera Hematoencefálica/diagnóstico por imagen , Células Endoteliales , Tomografía de Coherencia Óptica , Microvasos/diagnóstico por imagen , AlgoritmosRESUMEN
BACKGROUND: Complex orbital fractures are impure orbital fractures because they involve the orbital walls and mid-facial bones. The author reported an orbital wall restoration technique in which the primary orbital wall fragments were restored to their prior position in complex orbital fractures in 2020. As a follow-up to a previous preliminary study, this study retrospectively reviewed the surgical results of complex orbital wall fractures over a 4-year period and compared the surgical outcomes by dividing them into groups with and without balloon restoration. METHODS: Data of 939 patients with facial bone fractures between August 2018 and August 2022 were reviewed. Of these, 154 had complex orbital fractures. Among them, 44 and 110 underwent reduction with and without the balloon technique respectively. Pre- and postoperative Naugle exophthalmometer (Good-Lite Co.) scales were evaluated. The orbital volume and orbital volume ratio were calculated from preoperative and 6 months postoperative computed tomography images. RESULTS: Among 154 patients with complex orbital fractures, 44 patients underwent restoration with the balloon technique, and 110 patients underwent restoration without it. The Naugle scale did not differ significantly between the two groups, but the orbital volume ratio significantly decreased by 3.32% and 2.39% in groups with and without the balloon technique and the difference in OVR was significantly greater in patients in the balloon restoration group compared with the control group. Postoperative balloon rupture occurred in six out of 44 cases (13.64%). None of the six patients with balloon rupture showed significant enophthalmos at 6 months of follow-up. CONCLUSION: The balloon rupture rate was 13.64% (6/44 cases) with marginal screw fixation, blunt screws, and extra protection with a resorbable foam dressing. Furthermore, we restored the orbital wall with primary orbital fragments using balloon support in complex orbital wall fractures.
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3D printing in a microgel-based supporting bath enables the construction of complex structures with soft and watery biomaterials but the low print resolution is usually an obstacle to its practical application in tissue engineering. Herein, high-resolution printing of a 3D collagen organ scaffold is realized by using an engineered Gellan gum (GG) microgel bath containing trisodium citrate (TSC). The introduction of TSC into the bath system not only mitigates the aggregation of GG microgels, leading to a more homogeneous bath morphology but also suppresses the diffusion of the collagen ink in the bath due to the dehydration effect of TSC, both of which contribute to the improvement of print resolution. 3D collagen organ structures such as hand, ear, and heart are successfully constructed with high shape fidelity in the developed bath. After printing, the GG and TSC can be easily removed by washing with water, and the obtained collagen product exhibits good cell affinity in a tissue scaffold application. This work offers an easy-to-operate strategy for developing a microgel bath for high-resolution printing of collagen, providing an alternative path to in vitro 3D organ construction.
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Microgeles , Ácido Cítrico , Andamios del Tejido/química , Colágeno/química , Ingeniería de Tejidos , Citratos , Impresión TridimensionalRESUMEN
Biocompatible field-effect-transistor-based biosensors have drawn attention for the development of next-generation human-friendly electronics. High-performance electronic devices must achieve low-voltage operation, long-term operational stability, and biocompatibility. Herein, we propose an electrolyte-gated thin-film transistor made of large-area solution-processed indium-gallium-zinc oxide (IGZO) semiconductors capable of directly interacting with live cells at physiological conditions. The fabricated transistors exhibit good electrical performance operating under sub-0.5 V conditions with high on-/off-current ratios (>107) and transconductance (>1.0 mS) over an extended operational lifetime. Furthermore, we verified the biocompatibility of the IGZO surface to various types of mammalian cells in terms of cell viability, proliferation, morphology, and drug responsiveness. Finally, the prolonged stable operation of electrolyte-gated transistor devices directly integrated with live cells provides the proof-of-concept for solution-processed metal oxide material-based direct cellular interfaces.
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Stretchable sound-in-displays, which can generate synchronous sound and light directly from the display without a separate speaker, allow immersive audio and visual perception even on curved surfaces. In stretchable sound-in-displays, alternating current electroluminescent (ACEL) devices have been used as light-emitting sources owing to their high brightness and stability. However, stretchable ACEL devices that use low dielectric constant (κ) materials require a high operating voltage for generating light and sound. Herein, we demonstrate a stretchable ACEL loudspeaker with a low operating voltage using stretchable high-κ dielectrics and strain-insensitive electrodes. Our device exhibits 87.7 cd/m2 of luminance and 79.70 dB of sound pressure level at an operating voltage of 120 V and 10 kHz. As the next platform of wearable devices, the suggested ACEL loudspeaker exhibits high-quality synchronous light and sound generation performance even under various types of mechanical deformation, such as finger flexion and wrist bending.
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BACKGROUND: Hydrogels have been widely used in many research fields owing to optical transparency, good biocompatibility, tunable mechanical properties, etc. Unlike typical hydrogels in the form of an unstructured bulk material, we developed aqueous dispersions of fiber-shaped hydrogel structures with high stability under ambient conditions and their application to various types of transparent soft cell culture interfaces with anisotropic nanoscale topography. METHOD: Nanofibers based on the polyvinyl alcohol and polyacrylic acid mixture were prepared by electrospinning and hydrogelified to nano-fibrous hydrogels (nFHs) after thermal crosslinking and sulfuric acid treatment. By modifying various material surfaces with positively-charged polymers, negatively-charged superabsorbent nFHs could be selectively patterned by employing micro-contact printing or horizontally aligned by applying shear force with a wired bar coater. RESULTS: The angular distribution of bar-coated nFHs was dramatically reduced to ± 20° along the applied shear direction unlike the drop-coated nFHs which exhibit random orientations. Next, various types of cells were cultured on top of transparent soft nFHs which showed good viability and attachment while their behaviors could be easily monitored by both upright and inverted optical microscopy. Particularly, neuronal lineage cells such as PC 12 cells and embryonic hippocampal neurons showed highly stretched morphology along the overall fiber orientation with aspect ratios ranging from 1 to 14. Furthermore, the resultant neurite outgrowth and migration behaviors could be effectively controlled by the horizontal orientation and the three-dimensional arrangement of underlying nFHs, respectively. CONCLUSION: We expect that surface modifications with transparent soft nFHs will be beneficial for various biological/biomedical studies such as fundamental cellular studies, neuronal/stem cell and/or organoid cultures, implantable probe/device coatings, etc.
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Although the physiological function of receptor-interacting protein kinase (RIPK) 3 has emerged as a critical mediator of programmed necrosis/necroptosis, the intracellular role it plays as an attenuator in human lungs and human bronchial epithelia remains unclear. Here, we show that the expression of RIPK3 dramatically decreased in the inflamed tissues of human lungs, and moved from the nucleus to the cytoplasm. The overexpression of RIPK3 dramatically increased F-actin formation and decreased the expression of genes for pro-inflammatory cytokines (IL-6 and IL-1ß), but not siRNA-RIPK3. Interestingly, whereas RIPK3 was bound to histone 1b without LPS stimulation, the interaction between them was disrupted after 15 min of LPS treatment. Histone methylation could not maintain the binding of RIPK3 and activated movement towards the cytoplasm. In the cytoplasm, overexpressed RIPK3 continuously attenuated pro-inflammatory cytokine gene expression by inhibiting NF-κB activation, preventing the progression of inflammation during Pseudomonas aeruginosa infection. Our data indicated that RIPK3 is critical for the regulation of the LPS-induced inflammatory microenvironment. Therefore, we suggest that RIPK3 is a potential therapeutic candidate for bacterial infection-induced pulmonary inflammation.
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Lipopolisacáridos , Pseudomonas aeruginosa , Humanos , Histonas , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Necrosis , Inflamación/metabolismo , Citocinas/metabolismoRESUMEN
Blast furnace slag (BFS) used in the road construction as base/subbase materials leads to leachate problems under poor drainage conditions. The BSF leachate is a source of high pH, sulfur, and dissolved solids which will be affected to surrounding ecosystem. A column experiment was performed to evaluate the treatment of BFS leachate by media commonly used in passive treatment systems. The treatment efficiency of column media was assessed for inorganic (gravel and limestone) and organic (peat and mushroom compost) with zero-valent iron (ZVI). Columns were dosed with experimentally generated BFS leachate and operated under residence times of 7 and 14 days. The column depths of 45 cm and 75 cm allowed for determination of the role of anoxic conditions in the transformation, precipitation, and adsorption of dissolved constituents. The organic treatments were more effective for reducing pH, TDS, sulfate, and total sulfur. Mushroom compost, with ZVI and a residence time of 14 days, was the most effective matrix for the removal of sulfate (67%), and total sulfur (72%). Peat treatments resulted in the lowest pH at 6.34; however, concentrations of Al, Fe, Mg, and Mn were elevated. Organic biofilters utilizing sulfate-reducing bacteria (SRB) and ZVI may prove to be useful for treating BFS leachate and other sources of sulfur and TDS pollution.
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Contaminantes Químicos del Agua , Reactores Biológicos , Carbonato de Calcio , Ecosistema , Hierro , Suelo , Sulfatos , Azufre , Contaminantes Químicos del Agua/análisisRESUMEN
An anatomical understanding of median nerve variation is essential for successful decompression of carpal tunnel syndrome (CTS). Although iatrogenic injury of the thenar branch after carpal tunnel release (CTR) has not been reported in many cases, it can cause serious damage to the patient. In case of rapidly progressing thenar atrophy after CTS surgery, thenar branch of median nerve injury should be suspected. Nerve conduction examination and ultrasound before surgery can be a useful tool for diagnosis.
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BACKGROUND: Personal mobility devices (PMDs) have become an increasingly popular transport modality globally. With increasing social interest in and demand for PMDs, the number of individuals visiting emergency departments with PMD-related injuries has also increased annually. This study aimed to evaluate injury patterns and treatment costs for patients treated in the department of plastic surgery in a trauma center. METHODS: In this retrospective study, data concerning patients with PMD-related injuries from January 2017 to December 2021 were reviewed. The data retrieved included age, sex, alcohol consumption, helmet use, the type of impact, onset of injury, place of first visit, type of injury, admission status, operation status, and treatment cost. Multiple linear regression analysis was performed to determine the effects of various factors on cost. RESULTS: Data were collected from 93 patients. Until 2019, the annual number of PMD-related accidents was less than 10; however, this number increased sharply in 2020. The average cost of hospitalization was USD 7,698 whereas the average cost of non-hospitalization was USD 631. Only fractures had a significant association with total cost in linear regression analysis (p < 0.001). CONCLUSION: The prevalence of PMD use and related injuries requiring plastic surgery during the study period showed significant health and financial costs both to the patients involved and to society. This cost could be reduced through stricter regulations concerning PMD use, advocating the use of protective gear, and promoting greater awareness of safety measures and of the consequences of PMD-related accidents.
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While sevoflurane and desflurane have been regarded as inhalation agents providing rapid induction and emergence, previous studies demonstrated the superiority of desflurane-anesthesia compared to sevoflurane-anesthesia in the postoperative recovery in obese and geriatric patients. We investigated whether a short-term switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia enhances patient postoperative recovery profile in non-obese patients. We randomly divide patients undergoing elective surgery (n = 60) into two groups: sevoflurane-anesthesia group (Group-S, n = 30) and sevoflurane-desflurane group (Group-SD, n = 30). In Group-S, patients received only sevoflurane-anesthesia until the end of surgery (for >2 hours). In Group-SD, sevoflurane was stopped and switched to desflurane-anesthesia before the completion of sevoflurane-anesthesia (for approximately 30 minutes). We assessed the intergroup differences in the times to get eye-opening, extubation, and a bispectral index of 80 (BIS-80). Group-SD showed significantly shorter times to get eye-opening (438 ± 101 vs. 295 ± 45 s; mean difference, 143 s; 95% confidence interval [CI], 101-183; p < 0.001), extubation (476 ± 108 vs. 312 ± 42 s; mean difference, 164 s; 95% CI, 116-220; p < 0.001), and BIS-80 (378 ± 124 vs. 265 ± 49 minutes; mean difference, 113 s; 95% CI, 58-168 p < 0.001) compared to Group-S. There was no between-group difference in postoperative nausea, vomiting, and hypoxia incidences. Our results suggested that the short-term (approximately 30 minutes) switch of sevoflurane to desflurane at the end of sevoflurane-anesthesia can facilitate the speed of postoperative patient recovery.
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Anestésicos por Inhalación , Isoflurano , Éteres Metílicos , Anciano , Periodo de Recuperación de la Anestesia , Anestesia General , Anestésicos por Inhalación/farmacología , Desflurano , Humanos , Isoflurano/farmacología , Náusea y Vómito Posoperatorios , SevofluranoRESUMEN
The blood-brain barrier (BBB), a selective barrier regulating the active and passive transport of solutes in the extracellular fluid of the central nervous system, prevents the delivery of therapeutics for brain disorders. The BBB is composed of brain microvascular endothelial cells (BMEC), pericytes and astrocytes. Current in vitro BBB models cannot reproduce the human structural complexity of the brain microvasculature, and thus their functions are not enough for drug assessments. In this study, we developed a 3D self-assembled microvascular network formed by BMEC covered by pericytes and astrocyte end feet. It exhibited perfusable microvasculature due to the presence of capillary opening ends on the bottom of the hydrogel. It also demonstrated size-selective permeation of different molecular weights of fluorescent-labeled dextran, as similarly reported for in vivo rodent brain, suggesting the same permeability with actual in vivo brain. The activity of P-glycoprotein efflux pump was confirmed using the substrate Rhodamine 123. Finally, the functionality of the receptor-mediated transcytosis, one of the main routes for drug delivery of large molecules into the brain, could be validated using transferrin receptor (TfR) with confocal imaging, competition assays and permeability assays. Efficient permeability coefficient (Pe) value of transportable anti-TfR antibody (MEM-189) was seven-fold higher than those of isotype antibody (IgG1) and low transportable anti-TfR antibody (13E4), suggesting a higher TfR transport function than previous reports. The BBB model with capillary openings could thus be a valuable tool for the screening of therapeutics that can be transported across the BBB, including those using TfR-mediated transport.
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Accurate transmission of biosignals without interference of surrounding noises is a key factor for the realization of human-machine interfaces (HMIs). We propose frequency-selective acoustic and haptic sensors for dual-mode HMIs based on triboelectric sensors with hierarchical macrodome/micropore/nanoparticle structure of ferroelectric composites. Our sensor shows a high sensitivity and linearity under a wide range of dynamic pressures and resonance frequency, which enables high acoustic frequency selectivity in a wide frequency range (145 to 9000 Hz), thus rendering noise-independent voice recognition possible. Our frequency-selective multichannel acoustic sensor array combined with an artificial neural network demonstrates over 95% accurate voice recognition for different frequency noises ranging from 100 to 8000 Hz. We demonstrate that our dual-mode sensor with linear response and frequency selectivity over a wide range of dynamic pressures facilitates the differentiation of surface texture and control of an avatar robot using both acoustic and mechanical inputs without interference from surrounding noise.