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Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.
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Biomarcadores de Tumor , Neoplasias Encefálicas , Proteómica , Humanos , Proteómica/métodos , Biomarcadores de Tumor/líquido cefalorraquídeo , Neoplasias Encefálicas/líquido cefalorraquídeo , Neoplasias Encefálicas/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Adulto , Linfoma no Hodgkin/líquido cefalorraquídeo , Linfoma no Hodgkin/diagnósticoRESUMEN
BACKGROUND: Patients who are recovering from general anesthesia commonly exhibit symptoms such as dry lips, throat irritation, and thirst, prompting a desire to drink water in the post-anesthesia care unit (PACU). In this study, we aimed to evaluate the therapeutic effects and any potential complications of administering varying quantities of water to such patients. The primary objectives are to assess the safety and feasibility of early water intake after general anesthesia, specifically in the context of daytime surgery. METHODS: A total of 200 nongastrointestinal patients who underwent outpatient surgery were randomly assigned to four groups: Group A (drinking < 1 ml/kg), Group B (drinking 1-2 ml/kg), Group C (drinking > 2 ml/kg), and Group D (no water intake). We monitored changes in the assessment parameters before and after water consumption, as well as the incidence of post-drinking nausea and vomiting, and compared these outcomes among the four groups. RESULTS: Water intake led to a significant reduction in thirst, oropharyngeal discomfort, and pain scores and a notable increase in the gastric antrum motility index (MI), exhibiting statistical significance compared to the values before drinking (p < 0.05). Remarkably, higher water consumption correlated with enhanced gastrointestinal peristalsis. There was a significant difference in the antral MI among groups B, C, and A (p < 0.05). The occurrence of nausea and vomiting did not significantly differ among groups A, B, C, and D (p > 0.05). Early water consumption enhanced patient satisfaction with medical care, significantly varying from Group D (p < 0.05). CONCLUSION: Non-gastrointestinal surgical patients who passed pre-drinking water assessments post GA(general anesthesia)recovery could safely ingest moderate amounts of water in the PACU. Early water intake is both safe and feasible, effectively fostering swift postoperative recovery.
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Procedimientos Quirúrgicos Ambulatorios , Periodo de Recuperación de la Anestesia , Anestesia General , Agua Potable , Estudios de Factibilidad , Humanos , Anestesia General/métodos , Femenino , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Ambulatorios/métodos , Agua Potable/administración & dosificación , Adulto , Ingestión de Líquidos , Náusea y Vómito Posoperatorios/epidemiología , Sed/fisiología , AncianoRESUMEN
BACKGROUND: Pediatric asthma is a significant public health issue that impacts the quality of life of children globally. Traditional management approaches focus on symptom control and medication adherence but often overlook the comprehensive educational needs of patients and their families. A multifaceted health education approach may offer a more holistic strategy in managing pediatric asthma, especially in outpatient settings. AIM: To evaluate the efficacy of a comprehensive health education strategy in improving disease management, medication adherence, and quality of life among children with asthma in outpatient settings. METHODS: In total, 100 pediatric patients with severe asthma were enrolled from January 2021 to November 2022 and randomly allocated to a control group (n = 50) or an observation group (n = 50). The control group received standard nursing care, including basic nursing interventions and health education upon admission. In contrast, the observation group was exposed to a broad spectrum of health education methodologies, including internet-based hospital systems, social media channels, one-on-one verbal education, informational brochures, slide presentations, telephone check-ins, animated videos, and illustrated health education manuals. Data on asthma management knowledge, symptom control, quality of life [St. George's Respiratory Questionnaire (SGRQ)], treatment adherence, and nursing satisfaction were collected and analyzed. RESULTS: The scores of the observation group in knowledge areas, such as medication, home care, disease understanding, symptom management, prevention strategies, and nutritional guidance, were significantly higher than those of the control group (P < 0.05). In addition, the observation group exhibited greater symptom control, improved quality of life based on their SGRQ scores, and higher treatment adherence post-intervention (P < 0.05). Nursing satisfaction was also rated higher in the observation group across all evaluated areas (P < 0.05). CONCLUSION: Implementing a diversified health education approach in pediatric asthma management significantly enhances disease understanding, symptom management, and treatment adherence, leading to improved quality of life for affected children. These findings underscore the importance of multifaceted clinical health education in augmenting disease awareness and facilitating continuous improvements in asthma control rates, highlighting the potential benefits of incorporating comprehensive educational strategies into pediatric asthma care protocols.
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Bupivacaine (BUP) is an anesthetic commonly used in clinical practice that when used for spinal anesthesia, might exert neurotoxic effects. Thioredoxin-interacting protein (TXNIP) is a member of the α-arrestin protein superfamily that binds covalently to thioredoxin (TRX) to inhibit its function, leading to increased oxidative stress and activation of apoptosis. The role of TXNIP in BUP-induced oxidative stress and apoptosis remains to be elucidated. In this context, the present study aimed to explore the effects of TXNIP knockdown on BUP-induced oxidative stress and apoptosis in the spinal cord of rats and in PC12 cells through the transfection of adeno-associated virus-TXNIP short hairpin RNA (AAV-TXNIP shRNA) and siRNA-TXNIP, respectively. In vivo, a rat model of spinal neurotoxicity was established by intrathecally injecting rats with BUP. The BUP + TXNIP shRNA and the BUP + Control shRNA groups of rats were injected with an AAV carrying the TXNIP shRNA and the Control shRNA, respectively, into the subarachnoid space four weeks prior to BUP treatment. The Basso, Beattie & Bresnahan (BBB) locomotor rating score, % MPE of TFL, H&E staining, and Nissl staining analyses were conducted. In vitro, 0.8 mM BUP was determined by CCK-8 assay to establish a cytotoxicity model in PC12 cells. Transfection with siRNA-TXNIP was carried out to suppress TXNIP expression prior to exposing PC12 cells to BUP. The results revealed that BUP effectively induced neurological behavioral dysfunction and neuronal damage and death in the spinal cord of the rats. Similarly, BUP triggered cytotoxicity and apoptosis in PC12 cells. In addition, treated with BUP both in vitro and in vivo exhibited upregulated TXNIP expression and increased oxidative stress and apoptosis. Interestingly, TXNIP knockdown in the spinal cord of rats through transfection of AAV-TXNIP shRNA exerted a protective effect against BUP-induced spinal neurotoxicity by ameliorating behavioral and histological outcomes and promoting the survival of spinal cord neurons. Similarly, transfection with siRNA-TXNIP mitigated BUP-induced cytotoxicity in PC12 cells. In addition, TXNIP knockdown mitigated the upregulation of ROS, MDA, Bax, and cleaved caspase-3 and restored the downregulation of GSH, SOD, CAT, GPX4, and Bcl2 induced upon BUP exposure. These findings suggested that TXNIP knockdown protected against BUP-induced spinal neurotoxicity by suppressing oxidative stress and apoptosis. In summary, TXNIP could be a central signaling hub that positively regulates oxidative stress and apoptosis during neuronal damage, which renders TXNIP a promising target for treatment strategies against BUP-induced spinal neurotoxicity.
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Apoptosis , Bupivacaína , Proteínas Portadoras , Técnicas de Silenciamiento del Gen , Síndromes de Neurotoxicidad , Estrés Oxidativo , ARN Interferente Pequeño , Médula Espinal , Animales , Ratas , Apoptosis/efectos de los fármacos , Bupivacaína/toxicidad , Bupivacaína/efectos adversos , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Inyecciones Espinales , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/genética , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Células PC12 , Ratas Sprague-Dawley , ARN Interferente Pequeño/genética , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/efectos de los fármacos , Tiorredoxinas/genética , Tiorredoxinas/metabolismoRESUMEN
BACKGROUND: Single-cell RNA sequencing (scRNA-seq) measurements of gene expression show great promise for studying the cellular heterogeneity of rice roots. How precisely annotating cell identity is a major unresolved problem in plant scRNA-seq analysis due to the inherent high dimensionality and sparsity. RESULTS: To address this challenge, we present NRTPredictor, an ensemble-learning system, to predict rice root cell stage and mine biomarkers through complete model interpretability. The performance of NRTPredictor was evaluated using a test dataset, with 98.01% accuracy and 95.45% recall. With the power of interpretability provided by NRTPredictor, our model recognizes 110 marker genes partially involved in phenylpropanoid biosynthesis. Expression patterns of rice root could be mapped by the above-mentioned candidate genes, showing the superiority of NRTPredictor. Integrated analysis of scRNA and bulk RNA-seq data revealed aberrant expression of Epidermis cell subpopulations in flooding, Pi, and salt stresses. CONCLUSION: Taken together, our results demonstrate that NRTPredictor is a useful tool for automated prediction of rice root cell stage and provides a valuable resource for deciphering the rice root cellular heterogeneity and the molecular mechanisms of flooding, Pi, and salt stresses. Based on the proposed model, a free webserver has been established, which is available at https://www.cgris.net/nrtp .
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Objective: Endotracheal tubes (ETTs) are commonly associated with laryngeal injury that may be short lasting and temporary or more severe and life altering. Injury is believed to result from forces that these ETTs exert on the larynx. Here we quantify the forces of ETTs of various sizes on the laryngotracheal complex to gain a more quantitative understanding of these potential damaging forces. Here we also perform preclinical testing of a novel support device to offload these forces. Methods: Endotracheal intubation was performed on a fresh human cadaver using various ETT sizes. A strain-sensitive graphene nanosheet sensor and a commercially available force sensing resistor were secured behind the larynx, anterior to the prevertebral fascia. The forces exerted on the larynx were measured for each of the commonly used ETTs. A novel support device, ETT clip (Endo Clip), was attached to the ETTs and changes in these forces were observed. Results: Forces exerted on the laryngotracheal complex by various ETTs were observed to increase with increasing tube size. This pressure can be significantly reduced with a novel ETT clip. Conclusion: Here we demonstrate the first quantitative measurement of forces that ETTs exert on the larynx. We demonstrate a novel device that can easily clip onto an ETT reducing pressure on the laryngotracheal complex. This preclinical test paves the way for a human clinical trial. Level of evidence: 5.
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The semimetal-based photodetector possesses the intrinsic advantage of high response speed, low power consumption, and wide-range photoresponse. Here, we report the synthesis and application of 1 inch wafer-scale polycrystalline few layer 1T'-MoTe2 on the SiO2/Si substrate by employing a modified chemical vapor deposition method of predeposition of precursors. A continuous film with seamlessly stitched micrometer scale grains has been realized, and the pure 1T' phase was confirmed by Raman spectroscopy. An asymmetric metal electrode photodetector device of Pd-MoTe2-Au was designed and fabricated by using shadow mask-assisted UHV deposition. By measuring the self-powered photocurrent under the illumination of Xe lamp, we show that the device is sensitive to a wide spectra range (λ = 320-1200 nm) while maintaining high performance of the ON/OFF ratio (â¼103), responsivity (1.2 A/W), and specific detectivity (7.68 × 1012 Jones). Under 450, 648, and 850 nm pulsed laser illumination, the response time achieves tens of microsecond scale. The device shows polarized photoresponse as well. Our work may promote the potential application of a self-powered high-performance photodetector based on 1T'-MoTe2.
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Bupivacaine (BUP) has previously been shown to trigger neurotoxicity after spinal anesthesia. Further, ferroptosis has been implicated in the pathological processes associated with various central nervous system diseases. Although the impact of ferroptosis on BUP-induced neurotoxicity in the spinal cord has not been fully understood, this research aims to investigate this relationship in rats. Additionally, this study aims to determine whether ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, can provide protection against BUP-induced spinal neurotoxicity. The experimental model for BUP-induced spinal neurotoxicity involved the administration of 5% bupivacaine through intrathecal injection. Then, the rats were randomized into the Control, BUP, BUP + Fer-1, and Fer-1 groups. BBB scores, %MPE of TFL, and H&E and Nissl stainings showed that intrathecal Fer-1 administration improved functional recovery, histological outcomes, and neural survival in BUP-treated rats. Moreover, Fer-1 has been found to alleviate the BUP-induced alterations related to ferroptosis, such as mitochondrial shrinkage and disruption of cristae, while also reducing the levels of malondialdehyde (MDA), iron, and 4-hydroxynonenal (4HNE). Fer-1 also inhibits the accumulation of reactive oxygen species (ROS) and restores the normal levels of glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), and glutathione (GSH). Furthermore, double-immunofluorescence staining revealed that GPX4 is primarily localized in the neurons instead of microglia or astroglia in the spinal cord. In summary, we demonstrated that ferroptosis play a pivotal role in mediating BUP-induced spinal neurotoxicity, and Fer-1 ameliorated BUP-induced spinal neurotoxicity by reversing the underlying ferroptosis-related changes in rats.
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Ferroptosis , Síndromes de Neurotoxicidad , Animales , Ratas , Médula Espinal , Bupivacaína , GlutatiónRESUMEN
OBJECTIVES: To investigate the osteogenic effect of allograft bone (BIO-GENE) and autologous iliac crest bone graft in the alveolar cleft repair. MATERIALS AND METHODS: A total of 131 patients with congenital unilateral alveolar cleft who consulted in our hospital from January 2016 to May 2021 were selected and divided into 3 groups according to the different bone restoration materials used. Group A totaling 43 cases was the autologous bone group; group B totaling 41 cases was the BIO-GENE group; and group C totaling 47 cases was the BMP-2+BIO-GENE group. The preoperative and postoperative cone beam CT data of the same patient were imported into MIMICS 21.0 in DICOM format. The preoperative cleft volume and newly formed bone volume were calculated by 3-dimensional reconstruction to measure their osteogenic rate. RESULTS: The differences in osteogenesis rates were not statistically significant in the group B compared with the group A, and in the group C compared with the group B ( P >0.05 for both). The differences in osteogenesis rates were statistically significant in the group C compared with the group A ( P =0.003). CONCLUSIONS: Comparative studies found the allograft bone with an ideal artificial material to repair alveolar clefts has become possible. Meanwhile, the addition of BMP-2 in the allograft bone significantly increased the osteogenic rate.
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Injerto de Hueso Alveolar , Labio Leporino , Fisura del Paladar , Humanos , Fisura del Paladar/cirugía , Trasplante Óseo/métodos , Tomografía Computarizada de Haz Cónico , Osteogénesis , Aloinjertos , Injerto de Hueso Alveolar/métodosRESUMEN
Objective@# To investigate the osteogenic effect of β-tricalcium phosphate (β-TCP) and bone morphogenetic protein-2 (BMP-2) in the repair of the alveolar cleft.@*Methods @# Fifty-nine patients with unilateral alveolar cleft who visited Capital Medical University School of Stomatology from January 2016 to May 2021 were included. They were divided into three groups according to the different bone repair materials: autologous bone, β-TCP and BMP-2 +β-TCP. The preoperative and postoperative CBCT data of the patients were imported into Mimics 21.0 software. The preoperative volume of the bone defect and the new volume of bone formation were calculated by the three-dimensional reconstruction method. The osteogenesis rate was calculated to evaluate the osteogenesis effect@*Results@#The wounds in the three groups healed well after the operation, without implant material discharge, infection, dehiscence, rejection or other symptoms. Twelve months after the operation, CBCT scanning and three⁃dimensional reconstruction images of the three groups of patients showed the formation of new bone bridges in the alveolar ridge fissure area. The image density of the new bone tissue was not significantly different from that of normal bone tissue, and the continuity of the maxilla was re⁃ stored to varying degrees. The bone rate of autogenous bone was 65.00% ± 16.66%, β⁃ TCP group and BMP⁃2+ β⁃ The bone composition rate of TCP was 69.82% ± 17.60%, 71.35% ± 17.51%, respectively, and there was no significant dif⁃ ference compared with the autogenous bone group (P = 0.382, P = 0.244). The β⁃TCP and BMP⁃2+ β⁃TCP groups had no significant differences in bone rate (P = 0.789). @*Conclusion@#β⁃TCP could be used to replace autologous bone for alveolar cleft repair. The addition of BMP⁃2 to β⁃TCP did not significantly improve the osteogenesis rate.
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Insight into, and measurements of, muscle contraction during movement may help improve the assessment of muscle function, quantification of athletic performance, and understanding of muscle behavior, prior to and during rehabilitation following neuromusculoskeletal injury. A self-adhesive, elastic fabric, nanocomposite, skin-strain sensor was developed and validated for human movement monitoring. We hypothesized that skin-strain measurements from these wearables would reveal different degrees of muscle engagement during functional movements. To test this hypothesis, the strain sensing properties of the elastic fabric sensors, especially their linearity, stability, repeatability, and sensitivity, were first verified using load frame tests. Human subject tests conducted in parallel with optical motion capture confirmed that they can reliably measure tensile and compressive skin-strains across the calf and tibialis anterior. Then, a pilot study was conducted to assess the correlation of skin-strain measurements with surface electromyography (sEMG) signals. Subjects did biceps curls with different weights, and the responses of the elastic fabric sensors worn over the biceps brachii and flexor carpi radialis (i.e., forearm) were well-correlated with sEMG muscle engagement measures. These nanocomposite fabric sensors were validated for monitoring muscle engagement during functional activities and did not suffer from the motion artifacts typically observed when using sEMGs in free-living community settings.
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Nanocompuestos , Cementos de Resina , Adhesivos , Electromiografía , Humanos , Músculo Esquelético , Proyectos PilotoRESUMEN
Identification of muscle-tendon force generation properties and muscle activities from physiological measurements, e.g., motion data and raw surface electromyography (sEMG), offers opportunities to construct a subject-specific musculoskeletal (MSK) digital twin system for health condition assessment and motion prediction. While machine learning approaches with capabilities in extracting complex features and patterns from a large amount of data have been applied to motion prediction given sEMG signals, the learned data-driven mapping is black-box and may not satisfy the underlying physics and has reduced generality. In this work, we propose a feature-encoded physics-informed parameter identification neural network (FEPI-PINN) for simultaneous prediction of motion and parameter identification of human MSK systems. In this approach, features of high-dimensional noisy sEMG signals are projected onto a low-dimensional noise-filtered embedding space for the enhancement of forwarding dynamics prediction. This FEPI-PINN model can be trained to relate sEMG signals to joint motion and simultaneously identify key MSK parameters. The numerical examples demonstrate that the proposed framework can effectively identify subject-specific muscle parameters and the trained physics-informed forward-dynamics surrogate yields accurate motion predictions of elbow flexion-extension motion that are in good agreement with the measured joint motion data.
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Músculo Esquelético , Redes Neurales de la Computación , Algoritmos , Electromiografía , Humanos , Músculo Esquelético/fisiología , Física , Rango del Movimiento Articular/fisiologíaRESUMEN
Strain measurements are vital for monitoring the load-bearing capacity and safety of structures. A common approach is to affix strain gages onto structural surfaces. On the other hand, most aerospace, automotive, civil, and mechanical structures are painted and coated, often with many layers, prior to their deployment. There is an opportunity to design smart and multifunctional paints that can be directly pre-applied onto structural surfaces to serve as a sensing layer among their other layers of functional paints. Therefore, the objective of this study was to design a strain-sensitive paint that can be used for structural monitoring. Carbon nanotubes (CNT) were dispersed in paint by high-speed shear mixing, while paint thinner was employed for adjusting the formulation's viscosity and nanomaterial concentration. The study started with the design and fabrication of the CNT-based paint. Then, the nanocomposite paint's electromechanical properties and its sensitivity to applied strains were characterized. Third, the nanocomposite paint was spray-coated onto patterned substrates to form "Sensing Meshes" for distributed strain monitoring. An electrical resistance tomography (ERT) measurement strategy and algorithm were utilized for reconstructing the conductivity distribution of the Sensing Meshes, where the magnitude of conductivity (or resistivity) corresponded to the magnitude of strain, while strain directionality was determined based on the strut direction in the mesh.
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Nanocompuestos , Nanotubos de Carbono , Conductividad Eléctrica , Pintura , Prótesis e ImplantesRESUMEN
Transition metal carbides and nitrides (MXenes), as a large family of emerging two-dimensional materials, have demonstrated extraordinary performance in many fields such as electronics, optics and energy storage. However, their susceptibility to oxidation during preparation and storage in ambient air environment is undesirable for long-term and stable applications. Here, we have demonstrated that the spontaneous oxidation of Ti3C2Txcan be harnessed ingeniously to prepare Ti3C2Tx/TiO2in situformed heterojunctions. Furthermore, a self-powered ultraviolet photodetector was constructed based on the photoelectrochemical performance of Ti3C2Tx/TiO2heterojunctions. Since the highly conductive Ti3C2Txcan promote the separation and transfer of photogenerated carriers in TiO2, the prepared photodetector exhibits high responsivity (2.06 mA W-1), short rise and decay times (45 and 69 ms) and long-term stability. This work demonstrates the controllable synthesis of Ti3C2Tx/TiO2heterojunctions and provides a new promising potential of MXenes for photodetection applications.
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Periodontal disease is a chronic disease that can lead to lose teeth and even tooth loss if left untreated. Osteoporosis and periodontal disease share similar characteristics and associated factors. Current regenerative techniques for periodontal diseases are ineffective in restoring complete function and structural integrity of periodontium due to unwanted migration of cells. In this study, we applied the concept of guided tissue regeneration (GTR) and 3D fabricated gingival fibroblast cell-laden collagen/strontium-doped calcium silicate (SrCS) bi-layer scaffold for periodontal regeneration. The results revealed that the bioactive SrCS had a hydroxyapatite formation on its surface after 14 days of immersion and that SrCS could release Sr and Si ions even after 6 months of immersion. In addition, in vitro results showed that the bi-layer scaffold enhanced secretion of FGF-2, BMP-2, and VEGF from human gingival fibroblasts and increased secretion of osteogenic-related proteins ALP, BSP, and OC from WJMSCs. In vivo studies using animal osteoporotic models showed that the 3D-printed cell-laden collagen/SrCS bi-layer scaffold was able to enhance osteoporotic bone regeneration, as seen from the increased Tb.Th and BV/TV ratio and the histological stains. In conclusion, it can be seen that the bi-layer scaffolds enhanced osteogenesis and further showed that guided periodontal regeneration could be achieved using collagen/SrCS scaffolds, thus making it a potential candidate for future clinical applications.
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Testosterone (T), predominantly acting through its derivative 17ß-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2.1% sevoflurane exposure, followed by collection of trunk blood and brain tissue. Pharmacological agents, including the GABA type A receptor inhibitor bicuculline and the aromatase inhibitor formestane, were administered 30 min before sevoflurane anesthesia. Sevoflurane increased serum T levels in males only. All other effects of sevoflurane were similar in both sexes, including increases in serum levels of E2, hypothalamic mRNA levels of aromatase, estrogen receptor α (Erα) [not estrogen receptor ß (Erß)], Na+-K+-Cl- cotransporter (Nkcc1)/K+-Cl- cotransporter (Kcc2) mRNA ratio, electroencephalography-detectable seizures, and stress-like corticosterone secretion. Bicuculline and formestane alleviated these effects, except the T level increases. The ERα antagonist MPP, but not the ERß antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.
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Anestésicos por Inhalación/administración & dosificación , Encéfalo/efectos de los fármacos , Estradiol/sangre , Convulsiones/inducido químicamente , Sevoflurano/administración & dosificación , Sevoflurano/toxicidad , Testosterona/sangre , Anestésicos por Inhalación/efectos adversos , Animales , Encéfalo/fisiología , Electroencefalografía , Estrógenos/administración & dosificación , Femenino , Masculino , Ratas Sprague-Dawley , Convulsiones/fisiopatologíaRESUMEN
BACKGROUND: Neonatal exposure to sevoflurane induces neurobehavioral and neuroendocrine abnormalities in exposed male rats (generation F0) and neurobehavioral, but not neuroendocrine, abnormalities in their male, but not female, offspring (generation F1). These effects of sevoflurane are accompanied by a hypermethylated neuron-specific K-2Cl (Kcc2) Cl exporter gene in the F0 spermatozoa and the F1 male hypothalamus, while the gene's expression is reduced in the F0 and F1 hypothalamus. We investigated whether inhibition of deoxyribonucleic acid methyltransferases (DNMTs) before paternal sevoflurane exposure could alleviate the anesthetic's F0 and F1 effects. METHODS: Sprague-Dawley male rats were anesthetized with 2.1% sevoflurane for 5 hours on postnatal day (P) 5 and mated with control females on P90 to generate offspring. The nonselective DNMT inhibitor decitabine (0.5 mg/kg, intraperitoneally) was administered 30 minutes before sevoflurane exposure. The F0 and F1 male rats were evaluated in in vivo and in vitro tests in adulthood. RESULTS: Paternal exposure to sevoflurane induced impaired prepulse inhibition of the acoustic startle response and exacerbated corticosterone responses to stress in F0 males and impaired prepulse inhibition of the startle responses in F1 males. These effects were accompanied in both generations by reduced and increased expressions of hypothalamic Kcc2 and Dnmt3a/b, respectively. Decitabine deterred the effects of paternal exposure to sevoflurane in F0 and F1 males. CONCLUSIONS: These results suggest that similar decitabine-sensitive mechanisms regulating expression of multiple genes are involved in the mediation of neurobehavioral abnormalities in sires neonatally exposed to sevoflurane and in their future unexposed male offspring.
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Anestesia por Inhalación/efectos adversos , Anestésicos por Inhalación/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Decitabina/uso terapéutico , Exposición Paterna/efectos adversos , Sevoflurano/efectos adversos , Animales , Animales Recién Nacidos , Corticosterona/metabolismo , Metilasas de Modificación del ADN/antagonistas & inhibidores , Femenino , Masculino , Ratas , Ratas Sprague-Dawley , Reflejo de Sobresalto/efectos de los fármacos , Estrés Psicológico/metabolismo , Simportadores/antagonistas & inhibidores , Cotransportadores de K ClRESUMEN
BACKGROUND: Deficiencies in neurocognitive function have been found in late childhood or adolescence in patients who had prolonged and/or repeated early-life general anesthesia. Animal studies suggest that anesthetic-induced impairment in the neuron-specific K+-2Cl- (Kcc2) Cl- exporter expression, which regulates developmental maturation of GABA type A receptor (GABAAR) signaling from excitatory to inhibitory, may play a mediating role. We tested whether the DNA methyltransferase (DNMT) inhibitor decitabine ameliorates the anesthetic's adverse effects. METHODS: Sprague-Dawley male rats were injected with vehicle or decitabine 30â¯min before 2.1 % sevoflurane exposure for 5â¯h on postnatal day 5 (P5). On P19, P20, or P21, electroencephalography-detectable seizures were measured during 1â¯h of sevoflurane exposure, followed by collection of the trunk blood and brain tissue samples. Other rats were evaluated for changes in hippocampal CA1 dendrite morphology and gene expressions onâ¯≥â¯P120. RESULTS: Rats in the vehicle plus sevoflurane group responded to sevoflurane exposure on P19, P20 or P21 with electroencephalography-detectable seizures and stress-like corticosterone secretion and had altered hippocampal dendrite morphology in adulthood. These rats had expressions of Kcc2 and Dnmt genes downregulated and upregulated, respectively, in the P19 - P21 cortex and hypothalamus and theâ¯≥â¯P120 hippocampus. All measured parameters in the sevoflurane-exposed rats that were pretreated with decitabine were not different from those in the control group. CONCLUSIONS: Neonatal exposure to sevoflurane sensitizes rats to adverse effects of repeated exposure to the anesthetic. The anesthetic-caused changes in the decitabine-sensitive mechanisms may play a mediating role in the developmental effects of early-life anesthesia.
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Anestésicos por Inhalación/toxicidad , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , Decitabina/toxicidad , Hipocampo/efectos de los fármacos , Hipocampo/patología , Sevoflurano/toxicidad , Factores de Edad , Anestésicos por Inhalación/administración & dosificación , Animales , Animales Recién Nacidos , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Decitabina/administración & dosificación , Electroencefalografía/efectos de los fármacos , Electroencefalografía/métodos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/toxicidad , Hipocampo/fisiopatología , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Sevoflurano/administración & dosificaciónRESUMEN
Rational engineering of the architecture and structure of an adsorbent material is essential for high-performance adsorption. Herein, a porous nanocomposite composed of MgO and carbon species (MgO/C) with a hierarchical architecture is fabricated via the simple pyrolysis of a Mg-containing metal-organic complex. Our investigations reveal that with the unique architectural and chemical characteristics, MgO/C performs as a remarkable solid adsorbent for gas adsorption and wastewater treatment. Impressively, in CO2 uptake, it exhibits exceptionally high CO2 capture capacity, a fast sorption rate and excellent stability. Additionally, the MgO/C nanocomposite is capable of displaying extraordinary adsorption properties in the removal of Congo red (CR) from water. The maximum CR uptake capacity can even reach as high as 2937.8 mg g-1, which is the highest recorded value among all of the previously reported solid adsorbents. The work presented here is expected to give fresh inspiration for the refined design of next-generation advanced solid adsorbents for environmental remediation including CO2 abatement and water purification.
RESUMEN
BACKGROUND The effects of PPI are variable owing to the CYP2C19 polymorphisms. However, whether the polymorphisms could affect the Hp eradication efficacy of triple therapy is still not clear. The present study aimed to assess the effects of CYP2C19 gene polymorphisms on proton pump inhibitor (PPI), amoxicillin, and levofloxacin triple therapy for Helicobacter pylori (Hp) eradication. MATERIAL AND METHODS We randomly assigned 160 Hp-positive patients with chronic gastritis to 2 groups to receive either 20 mg bid omeprazole (OAL group, n=80) or 10 mg bid rabeprazole (RAL group, n=80), combined with 1000 mg bid amoxicillin and 500 mg qd levofloxacin. The 2 groups were treated for 10 days. The CYP2C19 genotypes included wild-type, M1 mutant gene (*2, the mutation of exon 5), and M2 mutant gene (*3, the mutation of exon 4) identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFIP). According to CYP2C19 genotype combinations, the patients were divided into extensive metabolizer (EM), intermediate metabolizer (IM), and poor metabolizer (PM) subgroups. The eradication efficacy of Hp was evaluated by 14C-UBT at 28 days after treatment. RESULTS The trial was completed by 155 patients. Hp eradication rates in OAL and RAL groups were 78.2% and 88.3%, respectively, on per-protocol (PP) analysis, indicating no significant difference (P>0.05). Regarding CYP2C19 genotypes, eradication rates of 60.7%, 84.2%, and 100% were obtained for EM, IM, and PM subgroups, respectively, of the OAL group. EM group eradication rates were significantly lower than IM and PM group values (P<0.05). In the RAL group, no such difference was observed (P>0.05). Hp eradication rates were significantly lower in the EM subgroup of the OAL group compared with that of the RAL group. CONCLUSIONS Hp eradication rates were higher in the RAL group than in OAL-treated patients. Interestingly, omeprazole-based therapy was significantly affected by the CYP2C19 genotype, unlike the rabeprazole-based therapy.