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Here, we describe a SERS-based vertical flow assay as a platform technology suitable for point-of-care (POC) diagnostic testing. A capture substrate is constructed from filter paper embedded with spherical gold nanoparticles (AuNPs) and functionalized with an appropriate capture antibody. The capture substrate is loaded into a filtration device and connected to a syringe to rapidly and repeatedly pass the sample through the sensor for efficient antigen binding. The antigen is then labeled with a SERS-active detection probe. We show that only a few Raman reporter molecules, exclusively located adjacent to the plasmonic capture substrate, generate detectible signals. To maximize the signal from underutilized Raman reporter molecules, we employ a secondary signal enhancing probe that undergoes antibody-directed assembly to form plasmonic core-satellites. This facile enhancement step provides a 3.5-fold increase in the signal and a detection limit of 0.23 ng/mL (1.6 pM) for human IgG. This work highlights the potential to rationally design plasmonic architectures using widely available and reproducible spherical AuNPs to achieve large SERS enhancements for highly sensitive POC diagnostics.
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Ouro , Imunoglobulina G , Nanopartículas Metálicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Ouro/química , Nanopartículas Metálicas/química , Imunoensaio/métodos , Humanos , Imunoglobulina G/imunologia , Limite de Detecção , Anticorpos/imunologia , Anticorpos/químicaRESUMO
BACKGROUND: The objective of this study is to validate the possibility of setting volumetric surgical indications by predicting permanent enophthalmos using a simplified formula. METHODS: The volume difference of bilateral orbits in a CT scan was automatically measured, and permanent enophthalmos was predicted by substituting the volume difference into a formula made using the 3-dimensional (3D) integral model. RESULTS: The predicted enophthalmos showed a strong positive correlation with the permanent enophthalmos of 52 blowout fracture patients. Analyzing CT of 768 pure blowout fracture patients, the mean predicted enophthalmos was 1.84 mm, and both the size of the fracture area and the degree of EOM herniation showed the absence of correlations. CONCLUSIONS: Through the digitized orbital volume analysis and formula using the 3D integral model, blowout fracture patients who require surgery in the early post-traumatic period can be identified with convenience and reproducibility.
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Various chimeric lysins have been developed as efficacious antibiotics against multidrug-resistant bacteria, but direct comparisons of their antibacterial activities have been difficult due to the preparation of multiple recombinant chimeric lysins. Previously, we reported an Escherichia coli cell-free expression method to better screen chimeric lysins against Staphylococcus aureus, but we still needed to increase the amounts of expressed proteins enough to be able to detect them non-isotopically for quantity comparisons. In this study, we improved the previous cell-free expression system by adding a previously reported artificial T7 terminator and reversing the different nucleotides between the T7 promoter and start codon to those of the T7 phage. The new method increased the expressed amount of chimeric lysins enough for us to detect them using Western blotting. Therefore, the qualitative comparison of activity between different chimeric lysins has become possible via the adjustment of the number of variables between samples without protein purification. We applied this method to select more active chimeric lysins derived from our previously reported chimeric lysin (ALS2). Finally, we compared the antibacterial activities of our selected chimeric lysins with reported chimeric lysins (ClyC and ClyO) and lysostaphin and determined the rank orders of antibacterial activities on different Staphylococcus aureus strains in our experimental conditions.
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Antibacterianos , Bacteriófagos , Antibacterianos/farmacologia , Staphylococcus aureus/metabolismo , Lisostafina , N-Acetil-Muramil-L-Alanina Amidase , Bacteriófagos/metabolismoRESUMO
Validating the direct photocatalytic activity of colloidal plasmonic nanoparticles is challenging due to their limited stability and needed support materials that can often contribute to the chemical reactions. Stable gold nanoparticles (AuNPs) with tunable sizes are prepared across porous polymer particles without any chemical bonds where the resulting composite particles exhibit intense surface plasmon resonances (SPRs) in the visible region. These composite particles are then tested as photocatalysts under a broadband solar-simulated light source to examine the contribution degree of photothermal heating and SPR coming from the incorporated AuNPs in the C-C bond forming homocoupling reaction. Generally, the thermal and photothermal heating are the main driving force to increase the reactivity of relatively smaller AuNPs (~ 44 nm in diameter) with a narrower SPR band. However, the SPR-induced catalytic activity is much greater for the composite particles containing larger AuNPs (~ 87 nm in diameter) with a broader SPR. As the polymer particle matrix does not influence the catalytic activity (e.g., inducing charge delocalization and/or separation), the unique SPR role of the colloidal AuNPs in the catalytic reaction is assessable under light irradiation. This study experimentally demonstrates the possibility of evaluating the direct contribution of SPRs to photocatalytic chemical reactions.
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BACKGROUND: Endobronchial ultrasound (EBUS) is widely used to diagnose lung cancer. Monitored anesthesia care (MAC) can enhance patient comfort and procedural conditions during EBUS. EBUS under MAC is usually safe but can lead to various complications. CASE: A 34-year-old male who had increased sputum for two months showed an enlarged paratracheal lymph node and planned for lymph node biopsy by EBUS. During EBUS under MAC, an unexpected oxygen saturation decline required intervention. After intubation, copious frothy fluid was suctioned from the bronchi, and oxygenation was recovered. A narrowed trachea and the EBUS bronchoscope might have resulted in upper airway obstruction, and suction performed under these conditions might have caused pulmonary edema. The patient received non-invasive ventilation and high-flow nasal cannula and recovered without complications. CONCLUSIONS: When there is an expected risk of upper airway obstruction during EBUS, careful preoperative evaluation and preparation are essential to prevent negative pressure pulmonary edema.
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Rapid, sensitive, and quantitative detection of biomarkers is needed for early diagnosis of disease and surveillance of infectious outbreaks. Here, we exploit a plasmonic syringe filter and surface-enhanced Raman spectroscopy (SERS) in the development of a rapid detection system, using human IgG as a model diagnostic biomarker. The novel assay design facilitates multiple passages of the sample and labeling solution through the detection zone enabling us to investigate and maximize sampling efficiency to the capture substrate. The vertical flow immunoassay process in this study involves the utilization of filter paper embedded with gold nanoparticles (AuNPs) to form a plasmonic substrate. Capture antibody (anti-human IgG) is then immobilized onto the prepared plasmonic paper and inserted into a vertical flow device (syringe filter holder). Sample solution is passed through the filter paper and the target antigen (human IgG) is selectively captured by the immobilized antibody to form an antibody-antigen complex. Next, functionalized AuNPs as extrinsic Raman labels (ERLs) are passed through the filter paper to label the captured biomarker molecules forming a layered structure. This sandwiched geometry enhances plasmonic coupling and SERS signal to provide highly sensitive detection of biomolecules. Systematic studies to investigate the impact of multiple infuse/withdraw cycles of the sample and labeling solutions reveal that antigen and ERL binding are maximized with 10 and 20 cycles, respectively. The optimized assay achieves a detection limit of â¼0.2 ng mL-1 for human IgG with a total assay time of less than 5 minutes, meeting the demands for rapid point of care diagnostics. Additionally, the optimized platform was implemented in the quantitative analysis of the SARS-CoV-2 nucleocapsid protein, the typical target in commercial, FDA-approved rapid antigen tests for COVID-19.
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Ouro , Nanopartículas Metálicas , Humanos , Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Biomarcadores , Imunoensaio/métodos , Antígenos , Imunoglobulina GRESUMO
The Mre11 complex (comprising Mre11, Rad50, Nbs1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain ( Mre11 ATLD1/ATLD1 ) was highly susceptible to oncogene induced breast cancer. Here we used a mammary organoid system to examine which Mre11 dependent responses are tumor suppressive. We found that Mre11 ATLD1/ATLD1 organoids exhibited an elevated interferon stimulated gene (ISG) signature and sustained changes in chromatin accessibility. This Mre11 ATLD1/ATLD1 phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation of Ifi205 in Mre11 ATLD1/ATLD1 organoids restored baseline and oncogene-induced chromatin accessibility patterns to those observed in WT . Implantation of Mre11 ATLD1/ATLD1 organoids and activation of oncogene led to aggressive metastatic breast cancer. This outcome was reversed in implanted Ifi205 -/- Mre11 ATLD1/ATLD1 organoids. These data reveal a connection between innate immune signaling and tumor suppression in mammary epithelium. Given the abundance of aberrant DNA structures that arise in the context of genome instability syndromes, the data further suggest that cancer predisposition in those contexts may be partially attributable to tonic innate immune transcriptional programs.
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BACKGROUND: COVID-19 and delayed hip surgery are well-known risk factors for thromboembolism in elderly patients. CASE: We report the case of an 88-year-old female patient with COVID-19 and pulmonary thromboembolism (PTE) who underwent delayed hip surgery 21 days after the injury. Heparinization and inferior vena cava filters were used to treat and prevent PTE. Transesophageal echocardiography and extracorporeal membrane oxygenation (ECMO) sheaths were inserted as a precaution in case of emergencies during surgery; the procedure was performed without any specific event. CONCLUSIONS: COVID-19-infected patients suffering from a hip fracture have a high risk of thromboembolism, and therefore, require utmost attention for appropriate evaluation and prevention.
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Drowsy driving is a common, but underestimated phenomenon in terms of associated risks as it often results in crashes causing fatalities and serious injuries. It is a challenging task to alert or reduce the driver's drowsy state using non-invasive techniques. In this study, a drowsiness reduction strategy has been developed and analyzed using exposure to different light colors and recording the corresponding electrical and biological brain activities. 31 subjects were examined by dividing them into 2 classes, a control group, and a healthy group. Fourteen EEG and 42 fNIRS channels were used to gather neurological data from two brain regions (prefrontal and visual cortices). Experiments shining 3 different colored lights have been carried out on them at certain times when there is a high probability to get drowsy. The results of this study show that there is a significant increase in HbO of a sleep-deprived participant when he is exposed to blue light. Similarly, the beta band of EEG also showed an increased response. However, the study found that there is no considerable increase in HbO and beta band power in the case of red and green light exposures. In addition to that, values of other physiological signals acquired such as heart rate, eye blinking, and self-reported Karolinska Sleepiness Scale scores validated the findings predicted by the electrical and biological signals. The statistical significance of the signals achieved has been tested using repeated measures ANOVA and t-tests. Correlation scores were also calculated to find the association between the changes in the data signals with the corresponding changes in the alertness level.
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Condução de Veículo , Cromoterapia , Eletroencefalografia , Fadiga , Privação do Sono , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Masculino , Eletroencefalografia/métodos , Fadiga/diagnóstico , Fadiga/etiologia , Fadiga/terapia , Sono/fisiologia , Privação do Sono/complicações , Fases do Sono/fisiologia , Vigília/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Sonolência , Cor , Fototerapia/métodos , Cromoterapia/métodos , Córtex CerebralRESUMO
Acute myeloid leukemia (AML) is a hematologic malignancy for which several epigenetic regulators have been identified as therapeutic targets. Here we report the development of cereblon-dependent degraders of IKZF2 and casein kinase 1α (CK1α), termed DEG-35 and DEG-77. We utilized a structure-guided approach to develop DEG-35 as a nanomolar degrader of IKZF2, a hematopoietic-specific transcription factor that contributes to myeloid leukemogenesis. DEG-35 possesses additional substrate specificity for the therapeutically relevant target CK1α, which was identified through unbiased proteomics and a PRISM screen assay. Degradation of IKZF2 and CK1α blocks cell growth and induces myeloid differentiation in AML cells through CK1α-p53- and IKZF2-dependent pathways. Target degradation by DEG-35 or a more soluble analog, DEG-77, delays leukemia progression in murine and human AML mouse models. Overall, we provide a strategy for multitargeted degradation of IKZF2 and CK1α to enhance efficacy against AML that may be expanded to additional targets and indications.
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Caseína Quinase Ialfa , Leucemia Mieloide Aguda , Animais , Humanos , Camundongos , Caseína Quinase Ialfa/genética , Caseína Quinase Ialfa/metabolismo , Hematopoese , Fator de Transcrição Ikaros/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Fatores de TranscriçãoRESUMO
BACKGROUND: Delayed emergence after general anesthesia may significantly affect a patient's condition. We present the case of a patient who experienced prolonged delayed recovery of consciousness, language, and motor response due to catatonia after eight hours of total elbow arthroplasty under general anesthesia. CASE: A 68-year-old woman with neuropsychiatric disorders and Parkinson's disease did not respond adequately during recovery after more than eight hours of general anesthesia. Following the operation, the patient was semi-comatose and appeared to have nonconvulsive status epilepticus upon awakening from anesthesia. However, subsequent examinations did not reveal any organic causes. The patient was subsequently diagnosed with catatonia, treated, and discharged following gradual improvement. CONCLUSIONS: Although rare, patients taking psychiatric drugs for an extended period may experience delayed emergence after prolonged general anesthesia without identifiable causes. Catatonia should be considered in the differential diagnoses of these patients.
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Catatonia , Estupor , Feminino , Humanos , Idoso , Catatonia/etiologia , Catatonia/diagnóstico , Catatonia/tratamento farmacológico , Estupor/complicações , Alta do Paciente , Anestesia Geral/efeitos adversosRESUMO
This work demonstrates the incorporation of gold nanoparticles (AuNPs) into crosslinker-free poly(N-isopropylacrylamide), PNIPAM, particles in situ and the examination of their structural and catalytic properties. The formation process of the AuNPs across the crosslinker-free PNIPAM particles are compared to that of crosslinked PNIPAM particles. Given the relatively larger free volume across the crosslinker-free polymer network, the AuNPs formed by the in situ reduction of gold ions are detectably larger and more polydisperse, but their overall integration efficiency is slightly inferior. The structural features and stability of these composite particles are also examined in basic and alcoholic solvent environments, where the crosslinker-free PNIPAM particles still offer comparable physicochemical properties to the crosslinked PNIPAM particles. Interestingly, the crosslinker-free composite particles as a colloidal catalyst display a higher reactivity toward the homocoupling of phenylboronic acid and reveal the importance of the polymer network density. As such, the capability to prepare composite particles in a controlled polymer network and reactive metal nanoparticles, as well as understanding the structure-dependent physicochemical properties, can allow for the development of highly practical catalytic systems.
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Oblique lumbar interbody fusion is a minimally invasive procedure for treating degenerative lumbar disease. Its advantages include correcting coronal and sagittal spinal alignment and indirect neural decompression. However, achieving a successful outcome is limited in some patients who need direct decompression for central canal lesions including hard stenotic lesions (endplate or facet articular osteophytes and ossification of posterior longitudinal ligaments) and sequestration of the disk. Biportal endoscopic spinal surgery is a minimally invasive technique, which directly decompresses the lesion. By taking advantage of two procedures, in a longlevel lumbar lesion, alignment correction and direct decompression can be both achieved. Herein, the authors introduce multilevel lumbar fusion through oblique lumbar interbody fusion and selective direct decompression through biportal endoscopic spinal surgery and discuss the surgical indications, surgical pitfalls, and recommendations for application. Consequently, it is regarded as a minimally invasive interbody fusion method for patients with multilevel lumbar degenerative degeneration.
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OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) on the use of noninvasive ventilation (NIV) for acute respiratory failure (ARF) in pediatric patients. DATA SOURCES: We searched PubMed, EMBASE, the Cochrane Central Register of Clinical Trials, and Clinicaltrials.gov with a last update on July 31, 2022. STUDY SELECTION: We included RCTs comparing NIV with any comparator (standard oxygen therapy and high-flow nasal cannula [HFNC]) in pediatric patients with ARF. We excluded studies performed on neonates and on chronic respiratory failure patients. DATA EXTRACTION: Baseline characteristics, intubation rate, mortality, and hospital and ICU length of stays were extracted by trained investigators. DATA SYNTHESIS: We identified 15 RCTs (2,679 patients) for the final analyses. The intubation rate was 109 of 945 (11.5%) in the NIV group, and 158 of 1,086 (14.5%) in the control group (risk ratio, 0.791; 95% CI, 0.629-0.996; p = 0.046; I2 = 0%; number needed to treat = 31). Findings were strengthened after removing studies with intervention duration shorter than an hour and after excluding studies with cross-over as rescue treatment. There was no difference in mortality, and ICU and hospital length of stays. CONCLUSIONS: In pediatric patients, NIV applied for ARF might reduce the intubation rate compared with standard oxygen therapy or HFNC. No difference in mortality was observed.
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Ventilação não Invasiva , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Recém-Nascido , Humanos , Criança , Oxigênio , Oxigenoterapia , Intubação , Síndrome do Desconforto Respiratório/terapia , Cânula , Insuficiência Respiratória/terapiaRESUMO
BACKGROUND: Although competency-based education (CBE) is becoming a popular form of medical education, it has not been used to train residents. Recently, the Korean Society of Anesthesiologists completed a pilot implementation and evaluation of a CBE program.This study aims to outline the experience. METHODS: The chief training faculty from each hospital took a one-hour online course about CBE. Emails on the seven core competencies and their evaluation were sent ahead of a pilot core competency evaluation (CCE) to residents and faculty. The pilot CCE took place in late 2021, followed by a survey. RESULTS: A total of 68 out of 84 hospitals participated in the pilot CCE. The survey response rate was 55.9% (38/68) for chief training faculty, 10.2% (91/888) for training faculty, and 30.2% (206/683) for residents. More than half of the training faculty thought that CCE was necessary for the education of residents. Residents' and training faculty's responses about CCE were generally positive, although their understanding of CCE criteria was low. More than 80% of the hospitals had a defibrillator and cardiopulmonary resuscitation manikin while the rarest piece of equipment was an ultrasound vessel model. Only defibrillators were used in more than half of the hospitals. Thoughts about CCE were related to various factors, such as length of employment, location of hospitals, and the number of residents per grade. CONCLUSIONS: This study's results may be helpful in improving resident education quality to meet the expectations of both teaching faculty and residents while establishing CBE.
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Anestesiologia , Internato e Residência , Humanos , Educação Baseada em Competências , Anestesiologia/educação , Competência Clínica , República da CoreiaRESUMO
This study reports the effects of recovered carbon black (produced in a clean and sustainable way) as a reinforcing agent on the physicochemical properties of a styrene-butadiene rubber (SBR) matrix. SBR-based composite materials are prepared with recovered green carbon black (GCB), and these are thoroughly compared to the composite materials containing conventional virgin carbon black (VCB) (produced by the incomplete combustion of petroleum products). The GCB-SBR composite materials generally show detectably inferior properties compared to the VCB-SBR composite under the same preparation conditions due to the limited functionality of the GCB filler. However, the introduction of a small amount of crosslinker, acrylate-functionalized POSS (polyhedral oligomeric silsesquioxane), into the GCB-SBR composite materials effectively enhances the overall physical properties, including the tensile strength, fracture elongation, and thermal stability. The degree of the crosslinking efficiency, thermal stability, and mechanical properties of the composite materials are optimized and thoroughly examined to demonstrate the possibility of replacing typical VCB with GCB, which can allow for upcycling the inexpensive and ecofriendly carbon black materials as effective reinforcing fillers.