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BACKGROUND: The management of intractable secondary pneumothorax poses a considerable challenge as it is often not indicated for surgery owing to the presence of underlying disease and poor general condition. While endobronchial occlusion has been employed as a non-surgical treatment for intractable secondary pneumothorax, its effectiveness is limited by the difficulty of locating the bronchus leading to the fistula using conventional techniques. This report details a case treated with endobronchial occlusion where the combined use of transbronchoscopic oxygen insufflation and a digital chest drainage system enabled location of the bronchus responsible for a prolonged air leak, leading to the successful treatment of intractable secondary pneumothorax. CASE PRESENTATION: An 83-year-old male, previously diagnosed with chronic hypersensitivity pneumonitis and treated with long-term oxygen therapy and oral corticosteroid, was admitted due to a pneumothorax emergency. Owing to a prolonged air leak after thoracic drainage, the patient was deemed at risk of developing an intractable secondary pneumothorax. Due to his poor respiratory condition, endobronchial occlusion with silicone spigots was performed instead of surgery. The location of the bronchus leading to the fistula was unclear on CT imaging. When the bronchoscope was wedged into each subsegmental bronchus and low-flow oxygen was insufflated, a digital chest drainage system detected a significant increase of the air leak only in B5a and B5b, thus identifying the specific location of the bronchus leading to the fistula. With the occlusion of those bronchi using silicone spigots, the air leakage decreased from 200 mL/min to 20 mL/min, and the addition of an autologous blood patch enabled successful removal of the drainage tube. CONCLUSION: The combination of transbronchoscopic oxygen insufflation with a digital chest drainage system can enhance the therapeutic efficacy of endobronchial occlusion by addressing the problems encountered in conventional techniques, where the ability to identify the leaking bronchus is dependent on factors such as the amount of escaping air and the location of the fistula.
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Broncoscopía , Drenaje , Insuflación , Neumotórax , Humanos , Neumotórax/terapia , Neumotórax/cirugía , Masculino , Anciano de 80 o más Años , Drenaje/métodos , Broncoscopía/métodos , Insuflación/métodos , Oxígeno/administración & dosificación , Fístula Bronquial/cirugía , Fístula Bronquial/terapia , Tomografía Computarizada por Rayos X , Tubos Torácicos , BronquiosRESUMEN
This paper reports the facile preparation of dual stimuli-responsive gel particles that simultaneously respond to weakly acidic and reducing stimuli and the application of these gel particles as a drug delivery carrier. The dual stimuli-responsive gel particles composed of a pH-responsive polymer network cross-linked with reduction stimuli-responsive disulfide cross-links, and biocompatible poly(ethylene glycol) cross-links were prepared by soap-free emulsion polymerization. The resulting gel particles were colloidally stable at physiological ionic strength and had a diameter of approximately 200 nm with a narrow size distribution. The resulting gel particles slightly swelled in an acidic environment. On the other hand, the gel particles drastically swelled under simultaneous weakly acidic and reducing conditions because of the ionization of tertiary amino groups in the gel network and a decrease in the cross-linking density resulting from cleavage of the disulfide cross-links. When cells were treated with the gel particles, they were taken up by cells via the endocytosis pathway and distributed in the cytosol after endosomal escape by the proton sponge effect. In addition, a hydrophobic drug, doxorubicin (Dox), was loaded into the gel particles through hydrophobic interactions. Dox was released from the gel particles under weakly acidic and reducing conditions, while the Dox release was inhibited at neutral pH. The weakly acidic pH- and reduction stimuli-responsive release of Dox from gel particles was attributed to the drastic swelling of these particles. The fascinating properties of the dual stimuli-responsive gel particles suggest that they can provide a useful platform for designing intracellular drug delivery carriers.
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Doxorrubicina , Portadores de Fármacos , Doxorrubicina/toxicidad , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Concentración de Iones de Hidrógeno , MicelasRESUMEN
The usefulness of the derived neutrophil-to-lymphocyte ratio (dNLR) and its dynamics before/after durvalumab consolidation therapy to predict safety or efficacy remains unclear. We retrospectively reviewed patients with locally advanced non-small cell lung cancer treated with durvalumab consolidation therapy after chemoradiotherapy (D group) or chemoradiotherapy alone (non-D group) at multiple institutions. We investigated the association between dNLR, or its dynamics, and pneumonitis, checkpoint inhibitor-related pneumonitis (CIP), irAEs, and efficacy. Ninety-eight and fifty-six patients were enrolled in the D and non-D groups, respectively. The dNLR at baseline was significantly lower in patients who experienced irAEs or CIP than in those who did not. The low dNLR group, 28 days following durvalumab consolidation therapy (dNLR28 ≤ 3), demonstrated longer progression-free survival (PFS) and overall survival (OS) than the high dNLR group (dNLR28 > 3) (PFS, hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.22-0.88, p = 0.020; OS, HR 0.39, 95% CI 0.16-0.94, p = 0.037). Among patients with high dNLR at baseline (dNLR > 3), the dNLR28 ≤ 3 group showed longer PFS than the dNLR28 > 3 group (p = 0.010). The dNLR is a predictive factor for irAEs and CIP in patients receiving durvalumab consolidation therapy. The dNLR at 28 days after durvalumab consolidation therapy and its dynamics predict favorable outcomes.
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Anticuerpos Monoclonales , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Neoplasias Pulmonares , Linfocitos , Neutrófilos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto , Antineoplásicos Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Anciano de 80 o más AñosRESUMEN
We report a simple method for the control of electrical characteristics of planar-type metal-based single-electron transistors (SETs) using field-emission-induced electromigration. The advantages of this method are as follows: (1) the fabrication of SETs is achieved by only passing a field emission current through a nanogap and (2) the charging energy of SETs can be controlled by adjusting the magnitude of the applied current during the procedure. In order to better control the electrical properties of the SETs, we investigate the relation between control parameters of the method and electrical characteristics of the SETs. When the field-emission-induced electromigration with the preset current of 500 nA was applied to the nanogaps, current-voltage characteristics of the nanogaps displayed the suppression of electrical current at low-bias voltages known as Coulomb blockade at 16 K. In addition, Coulomb blockade voltage was clearly modulated by the gate voltage periodically at 16 K, resulting in the formation of single island in the SETs by the field-emission-induced electromigration. Furthermore, as the preset current was increased, the charging energy of the SETs was decreased with decreasing the initial gap separation of the nanogaps. These results imply that the electrical characteristics of the SETs are controllable by the preset current of the method and the initial gap separation of the nanogaps. Field-emission-induced electromigration procedure allows us to simply control electrical characteristics of planar-type metal-based SETs.
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Oxygen is essential for animals, but high concentrations of oxygen are toxic to them probably because of an increase in reactive oxygen species (ROS). Many genes are involved in the regulation of ROS, but they largely remain to be identified. To identify these genes, we employed the nematode Caenorhabditis elegans as a model organism, and systematically screened for genes that, when down-regulated by RNAi, lead to an increased sensitivity to ROS. We examined approximately 2400 genes on linkage group I and found that knock-down of 9 genes which participate in various cellular functions led to an increased sensitivity to ROS. This finding suggests an implication of a variety of cellular processes in the regulation of oxidative stress.
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Proteínas de Caenorhabditis elegans/genética , Caenorhabditis elegans/genética , Regulación de la Expresión Génica/fisiología , Estrés Oxidativo/genética , Animales , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/fisiología , Regulación hacia Abajo , Regulación de la Expresión Génica/efectos de los fármacos , Pruebas Genéticas , Carbonilación Proteica , Interferencia de ARN , Especies Reactivas de Oxígeno/farmacologíaRESUMEN
A novel technique for the integration of planar-type single-electron transistors (SETs) composed of nanogaps is presented. This technique is based on the electromigration procedure, which is caused by a field emission current. The technique is called "activation." By applying the activation to the nanogaps, SETs can be easily obtained. Furthermore, the charging energy of the SETs can be controlled by adjusting the magnitude of the applied current during the activation process. The integration of two SETs was achieved by passing a field emission current through two series-connected initial nanogaps. The current-voltage (I(D)-V(D)) curves of the simultaneously activated devices exhibited clear electrical-current suppression at a low-bias voltage at 16 K, which is known as the Coulomb blockade. The Coulomb blockade voltage of each device was also obviously modulated by the gate voltage. In addition, the two SETs, which were integrated by the activation procedure, exhibited similar electrical properties, and their charging energy decreased uniformly with increasing the preset current during the activation. These results indicate that the activation procedure allows the simple and easy integration of planar-type SETs.
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A newly investigated technique for the tuning of the tunnel resistance of nanogaps using electromigration method induced by a field emission current is presented to reduce the power consumption during the process. The method is called "activation" and is demonstrated with a current source. Planar-type initial nanogaps of Ni separated by 20-80 nm were defined on SiO2/Si substrates via electron-beam lithography and the lift-off process. Then, a bias current was applied to the initial nanogaps at room temperature, using a current source. The applied current was slowly ramped up until it reached the preset value. As a result, the process time of the current-source-based activation was 16 times shorter than activation using a voltage source. Furthermore, the tunnel resistance of the nanogaps was reduced from 100 T ohms to 70 M ohms by increasing preset current I(s) from 1 nA to 3.5 microA. Regarding the average power required for current-source-based activation, it can be successfully suppressed compared with that of voltage-source-based activation. These results imply that the current source directly and precisely tunes the field emission current passing through the nanogaps, and effectively causes the migration of atoms across the nanogaps, resulting in the successful control of the tunnel resistance of the nanogaps.
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Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1α changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34+ and c-kit+ was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.