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Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.
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Envelhecimento , Bleomicina , Células Endoteliais , Lesão Pulmonar , Pulmão , Fibrose Pulmonar , Animais , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Envelhecimento/patologia , Bleomicina/toxicidade , Humanos , Camundongos , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/genética , Pulmão/patologia , Pulmão/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , Receptor trkB/metabolismo , Receptor trkB/genética , Camundongos Endogâmicos C57BL , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas de Sinalização YAP/metabolismo , Masculino , Análise de Célula Única , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Feminino , Modelos Animais de DoençasRESUMO
Recent advancements in nanomaterials have enabled the application of nanotechnology to the development of cutting-edge sensing and actuating devices. For instance, nanostructures' collective and predictable responses to various stimuli can be monitored to determine the physical environment of the nanomaterial, such as temperature or applied pressure. To achieve optimal sensing and actuation capabilities, the nanostructures should be controllable. However, current applications are limited by inherent challenges in controlling nanostructures that counteract many sensing mechanisms that are reliant on their area or spacing. This work presents a technique utilizing the piezo-magnetoelectric properties of nanoparticles to enable strain sensing and actuation in a flexible and wearable patch. The alignment of nanoparticles has been achieved using demagnetization fields with computational simulations confirming device characteristics under various types of deformation followed by experimental demonstrations. The device exhibits favorable piezoelectric performance, hydrophobicity, and body motion-sensing capabilities, as well as machine learning-powered touch-sensing/actuating features.
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RET fusion is an oncogenic driver in 1-2 % of patients with non-small cell lung cancer (NSCLC). Although RET-positive tumors have been treated with multikinase inhibitors such as vandetanib or RET-selective inhibitors, ultimately resistance to them develops. Here we established vandetanib resistance (VR) clones from LC-2/ad cells harboring CCDC6-RET fusion and explored the molecular mechanism of the resistance. Each VR clone had a distinct phenotype, implying they had acquired resistance via different mechanisms. Consistently, whole exome-seq and RNA-seq revealed that the VR clones had unique mutational signatures and expression profiles, and shared only a few common remarkable events. AXL and IGF-1R were activated as bypass pathway in different VR clones, and sensitive to a combination of RET and AXL inhibitors or IGF-1R inhibitors, respectively. SMARCA4 loss was also found in a particular VR clone and 55 % of post-TKI lung tumor tissues, being correlated with higher sensitivity to SMARCA4/SMARCA2 dual inhibition and shorter PFS after subsequent treatments. Finally, we detected an increased number of damaged mitochondria in one VR clone, which conferred sensitivity to mitochondrial electron transfer chain inhibitors. Increased mitochondria were also observed in post-TKI biopsy specimens in 13/20 cases of NSCLC, suggesting a potential strategy targeting mitochondria to treat resistant tumors. Our data propose new promising therapeutic options to combat resistance to RET inhibitors in NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares , Mitocôndrias , Piperidinas , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-ret , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas Proto-Oncogênicas c-ret/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas de Fusão Oncogênica/antagonistas & inibidores , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Helicases/antagonistas & inibidores , Proteínas do CitoesqueletoRESUMO
BACKGROUND Ketamine, a compelling candidate for neuropathic pain management, has attracted interest for its potential to elevate brain-derived neurotrophic factor (BDNF) levels. We aimed to assess the effects of intrathecally administered ketamine on the cerebrospinal fluid (CSF) levels of BDNF(c-BDNF) and allodynia in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS Forty-five rats were divided into 3 groups: sham operation (Group S), untreated TBI (Group T), and ketamine-treated TBI (Group K), with 15 rats in each group. Rats were anesthetized, and their skulls were secured in a stereotactic frame before undergoing craniotomy. A controlled cortical impact (CCI) was induced, followed by injection of ketamine (3.41 µg/g) into the CSF in Group K. In Group T, no drug was injected after CCI delivery. On postoperative days (POD) 1, 7, and 14, the 50% mechanical withdrawal threshold (50% MWT) and c-BDNF levels were assessed. RESULTS Groups T and K exhibited a significantly lower 50% MWT than Group S on POD 1(6.6 [5.7, 8.7] g, 10.0 [6.8, 11.6] g, and 18.7 [11.6, 18.7] g, respectively; P<0.001). The c-BDNF levels in Group K were significantly higher than those in Groups S and T on POD 1 (18.9 [16.1, 23.0] pg/ml, 7.3 [6.0, 8.8] pg/ml, and 11.0 [10.6, 12.3] pg/ml, respectively; P=0.006). CONCLUSIONS Intrathecal ketamine administration did not exhibit anti-allodynic effects following mild TBI. c-BDNF level is a promising potential indicator for predicting the expression of allodynia after mild TBI.
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Concussão Encefálica , Ketamina , Ratos , Animais , Hiperalgesia/tratamento farmacológico , Ketamina/farmacologia , Ketamina/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos Sprague-DawleyRESUMO
BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO2), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO2 and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.
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Obesidade , Doenças Vasculares , Adulto , Humanos , Anestesia Geral , Índice de Massa Corporal , Capilares , Microcirculação , Estudos Observacionais como AssuntoRESUMO
Alzheimer's disease (AD) is the most common age-related progressive neurodegenerative disorder. The accumulation of amyloid beta-peptide is a neuropathological marker of AD. While melatonin is recognized to have protective effects on aging and neurodegenerative disorders, the therapeutic effect of melatonin on calcineurin in AD is poorly understood. In this study, we examined the effect and underlying molecular mechanisms of melatonin treatment on amyloid beta-mediated neurotoxicity in neuroblastoma cells. Melatonin treatment decreased calcineurin and autophagy in neuroblastoma cells. Electron microscopy images showed that melatonin inhibited amyloid beta-induced autophagic vacuoles. The increase in the amyloid beta-induced apoptosis rate was observed more in PrPC-expressing ZW cells than in PrPC-silencing Zpl cells. Taken together, the results suggest that by mitigating the effect of calcineurin and autophagy flux activation, melatonin could also rescue amyloid beta-induced neurotoxic effects. These findings may be relevant to therapy for neurodegenerative diseases, including AD.
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BACKGROUND: Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that affects the nervous system and triggers inflammation in the brain. METHODS: Melatonin is used as a sleep-inducing agent in neurophysiology and may serve as a protective agent against neurological and neurodegenerative diseases. Herein, we investigated the effects of melatonin and the critical roles of the serine/threonine protein phosphatase calcineurin during JEV infection in SK-N-SH neuroblastoma cells. RESULTS: Melatonin treatment decreased JEV replication and JEV-mediated neurotoxicity. Calcineurin activity was increased by JEV infection and inhibited by melatonin treatment. Through calcineurin regulation, melatonin decreased the JEV-mediated neuroinflammatory response and attenuated JEV-induced autophagy. CONCLUSIONS: Calcineurin inactivation has a protective effect in JEV-infected neuronal cells, and melatonin is a novel resource for the development of anti-JEV agents.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Melatonina , Animais , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Calcineurina/farmacologia , Melatonina/farmacologia , AutofagiaRESUMO
Flaviviruses are a major cause of viral diseases worldwide, for which effective treatments have yet to be discovered. The prion protein (PrPc) is abundantly expressed in brain cells and has been shown to play a variety of roles, including neuroprotection, cell homeostasis, and regulation of cellular signaling. However, it is still unclear whether PrPc can protect against flaviviruses. In this study, we investigated the role of PrPc in regulating autophagy flux and its potential antiviral activity during Japanese encephalitis virus (JEV) infection. Our in vivo experiment showed that JEV was more lethal to the PrPc knocked out mice which was further supported by histological analysis, western blot and rtPCR results from infected mice brain samples. Role of PrPc against viral propagation in vitro was verified through cell survival study, protein expression and RNA replication analysis, and adenoviral vector assay by overexpressing PrPc. Further analysis indicated that after virus entry, PrPc inhibited autophagic flux that prevented JEV replication inside the host cell. Our results from in vivo and in vitro investigations demonstrate that prion protein effectively inhibited JEV propagation by regulating autophagy flux which is used by JEV to release its genetic material and replication after entering the host cell, suggesting that prion protein may be a promising therapeutic target for flavivirus infection.
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Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Animais , Camundongos , Proteínas Priônicas/genética , Proteínas Priônicas/farmacologia , Linhagem Celular , Antivirais/farmacologia , Antivirais/uso terapêutico , Replicação ViralRESUMO
Magnetic domain wall (DW)-based logic devices offer numerous opportunities for emerging electronics applications allowing superior performance characteristics such as fast motion, high density, and nonvolatility to process information. However, these devices rely on an external magnetic field, which limits their implementation; this is particularly problematic in large-scale applications. Multiferroic systems consisting of a piezoelectric substrate coupled with ferromagnets provide a potential solution that provides the possibility of controlling magnetization through an electric field via magnetoelastic coupling. Strain-induced magnetization anisotropy tilting can influence the DW motion in a controllable way. We demonstrate a method to perform all-electrical logic operations using such a system. Ferromagnetic coupling between neighboring magnetic domains induced by the electric-field-controlled strain has been exploited to promote noncollinear spin alignment, which is used for realizing essential building blocks, including DW generation, propagation, and pinning, in all implementations of Boolean logic, which will pave the way for scalable memory-in-logic applications.
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BACKGROUND: Pyruvate dehydrogenase complex (PDHC) deficiency is a rare mitochondrial disorder caused by a genetic mutation affecting the activity of the PDHC enzyme, which plays a major role in the tricarboxylic cycle. Few cases of surgery or anesthesia have been reported. Moreover, there is no recommended anesthetic method. CASE: A 24-month-old child with a PDHC deficiency presented to the emergency room with respiratory failure, mental decline, systemic cyanosis, and lactic acidosis. During hospitalization period, the patient presented with pneumothorax, pneumoperitoneum, and multiple air pockets in the heart. Two surgeries were performed under general anesthesia using an inhalational anesthetic agent. The patient was discharged with home ventilation. CONCLUSIONS: Anesthesiologists should be wary of multiple factors when administering anesthesia to patients with PDHC deficiency, including airway abnormalities, acid-base imbalance, intraoperative fluid management, selection of appropriate anesthetics, and monitoring of lactic acid levels.
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BACKGROUND: We investigated the effects of sevoflurane exposure on the expression of matrix metalloproteinase (MMP), expression and ablation of natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins 1-3 and major histocompatibility complex class I chain-related molecules A/B), and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells. METHODS: Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 µM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and -2 and the concentration of soluble NKG2D ligands were analyzed using western blotting and enzyme-linked immunosorbent assays, respectively. RESULTS: Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells but did not affect the expression of MMP-1 or -2 or the concentration of soluble NKG2D ligands in the MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, P = 0.040, and P = 0.040, respectively). CONCLUSIONS: Our results demonstrate that sevoflurane exposure attenuates NK cell-mediated cytotoxicity in breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.
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Neoplasias da Mama , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Feminino , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Sevoflurano , Ligantes , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Células Matadoras Naturais/metabolismoRESUMO
BACKGROUND Robot-assisted radical prostatectomy (RARP) is becoming an increasingly common method for treatment of prostate cancer. This study aimed to compare outcomes of estimated blood loss and postoperative pain, determined by patient-controlled analgesia (PCA), between RARP and standard laparoscopic radical -prostatectomy (LRP). MATERIAL AND METHODS We enrolled 57 patients who had localized prostate cancer (28 patients in RARP, 29 patients in LRP). Primary outcomes were estimated blood loss (EBL) measured by gravimetric method for gauze and visual estimation for suction bottle, and PCA bolus count that the bolus doses were injected at the 1st, the 6th, the 24th, and the 48th hour after the operation. We recorded anesthesia and operation time, pneumoperitoneum duration, vital signs, fluid volume, and remifentanil use. Using the numeric rating scale (NRS), adverse effects were checked at the 1st, the 6th, the 24th, and the 48th hour and patient satisfaction was assessed at the 48th hour after the operation. RESULTS Anesthesia time, operation time, and gas insufflation time were longer (P=0.001, P=0.003, P=0.021), and patient-controlled analgesia (PCA) bolus counts at the 1st hour after the operation and volumes of administered crystalloid and remifentanil were higher in the RARP group than in the LRP group (P=0.013, P=0.011, P=0.031). There were no significant differences in EBL. CONCLUSIONS The RARP group required longer anesthetic time and more analgesics during the acute postoperative period compared to the LRP group. Regarding anesthesia, LRP is as good a surgical procedure as RARP until the operation time and the number of ports are reduced.
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Laparoscopia , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Masculino , Humanos , Remifentanil , Resultado do Tratamento , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Laparoscopia/métodosRESUMO
OBJECTIVES: To compare the analgesic efficacies of erector spinae plane (ESP) block and thoracic epidural analgesia (TEA) in video-assisted thoracic surgery (VATS). METHODS: Sixty patients undergoing VATS received patient-controlled TEA with a basal rate of 3 ml/hour (h), a bolus of 3 ml (Group E), or ESP block with programmed intermittent bolus infusions of 15 mL/3 h and a bolus of 5 ml (Group ES) for 2 postoperative days. The primary outcome was to compare pain scores at rest 24 h postoperatively between the 2 groups. Secondary outcomes included NRS score for 48 h, procedural time, dermatomal spread, use of rescue medication, adverse events, and patient satisfaction. RESULTS: Patients with continuous ESP block had a higher NRS score than those with TEA but no statistical difference at a specific time. The dermatomal spread was more extensive in the TEA group than in the ESP block group (p=0.016); cumulative morphine consumption was higher in the ESP block group (p=0.047). The incidence of overall adverse events in the TEA group was higher than in the ESP block group (p=0.045). CONCLUSION: Erector spinae plane block may be inferior to TEA for analgesia following VATS, but it could have tolerable analgesia and a better side effect profile than TEA. Therefore, it could be an alternative to TEA as a component of multimodal analgesia.
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Analgesia Epidural , Bloqueio Nervoso , Humanos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Anestésicos Locais/uso terapêutico , Estudos Prospectivos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Ultrassonografia de IntervençãoRESUMO
Mesenchymal cells in the lung are crucial during development, but also contribute to the pathogenesis of fibrotic disorders, including idiopathic pulmonary fibrosis (IPF), the most common and deadly form of fibrotic interstitial lung diseases. Originally thought to behave as supporting cells for the lung epithelium and endothelium with a singular function of producing basement membrane, mesenchymal cells encompass a variety of cell types, including resident fibroblasts, lipofibroblasts, myofibroblasts, smooth muscle cells, and pericytes, which all occupy different anatomic locations and exhibit diverse homeostatic functions in the lung. During injury, each of these subtypes demonstrate remarkable plasticity and undergo varying capacity to proliferate and differentiate into activated myofibroblasts. Therefore, these cells secrete high levels of extracellular matrix (ECM) proteins and inflammatory cytokines, which contribute to tissue repair, or in pathologic situations, scarring and fibrosis. Whereas epithelial damage is considered the initial trigger that leads to lung injury, lung mesenchymal cells are recognized as the ultimate effector of fibrosis and attempts to better understand the different functions and actions of each mesenchymal cell subtype will lead to a better understanding of why fibrosis develops and how to better target it for future therapy. This review summarizes current findings related to various lung mesenchymal cells as well as signaling pathways, and their contribution to the pathogenesis of pulmonary fibrosis.
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Fibrose Pulmonar Idiopática , Células-Tronco Mesenquimais , Fibrose Pulmonar , Humanos , Pulmão/metabolismo , Fibrose , Fibrose Pulmonar/metabolismo , Células-Tronco Mesenquimais/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fibroblastos/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/patologiaRESUMO
Lung regeneration deteriorates with aging leading to increased susceptibility to pathologic conditions, including fibrosis. Here, we investigated bleomycin-induced lung injury responses in young and aged mice at single-cell resolution to gain insights into the cellular and molecular contributions of aging to fibrosis. Analysis of 52,542 cells in young (8 weeks) and aged (72 weeks) mice identified 15 cellular clusters, many of which exhibited distinct injury responses that associated with age. We identified Pdgfra + alveolar fibroblasts as a major source of collagen expression following bleomycin challenge, with those from aged lungs exhibiting a more persistent activation compared to young ones. We also observed age-associated transcriptional abnormalities affecting lung progenitor cells, including ATII pneumocytes and general capillary (gCap) endothelial cells (ECs). Transcriptional analysis combined with lineage tracing identified a sub-population of gCap ECs marked by the expression of Tropomyosin Receptor Kinase B (TrkB) that appeared in bleomycin-injured lungs and accumulated with aging. This newly emerged TrkB + EC population expressed common gCap EC markers but also exhibited a distinct gene expression signature associated with aberrant YAP/TAZ signaling, mitochondrial dysfunction, and hypoxia. Finally, we defined ACKR1 + venous ECs that exclusively emerged in injured lungs of aged animals and were closely associated with areas of collagen deposition and inflammation. Immunostaining and FACS analysis of human IPF lungs demonstrated that ACKR1 + venous ECs were dominant cells within the fibrotic regions and accumulated in areas of myofibroblast aggregation. Together, these data provide high-resolution insights into the impact of aging on lung cell adaptability to injury responses.
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Histological analysis is considered to be the gold standard method of evaluating osseointegration around a bone-implant. However, this method requires invasive specimen preparation and is capable of representing only one plane. By comparison, micro-computed tomography (µCT) is a fast and convenient method that offers three-dimensional information but is hampered by problems related to resolution and artifacts, making it a supplementary method for osseointegration analysis. To verify the reliability of µCT for osseointegration evaluation, this animal model study compared bone-to-implant contact (BIC) ratios obtained by the gold standard histomorphometric method with those obtained by the µCT method, using a rabbit tibia implant model. A sandblasted, large-grit, acid-etched (SLA) implant and a machined surface implant were inserted into each tibia of two rabbits (giving eight implants in total). Bone-implant specimens were analyzed using µCT with a spiral scan technique (SkyScan 1275) and histological sections were prepared thereafter. Three-dimensional (3D) reconstructed µCT data and four two-dimensional (2D) µCT sections, including one section corresponding to the histologic section and three additional sections rotated 45°, 90°, and 135°, were used to calculate the BIC ratio. The Pearson's test was used for correlation analysis at a significance level of 0.05. The histomorphometric BIC and the 2D-µCT BIC showed strong correlation (r = 0.762, P = 0.046), whereas the histomorphometric BIC and 3D-µCT BIC did not (r = -0.375, P = 0.385). However, the mean BIC value of three or four 2D-µCT sections showed a strong correlation with the 3D-µCT BIC (three sections: r = 0.781, P = 0.038; four sections: r = 0.804, P = 0.029). The results of this animal model study indicate that µCT can be used to complement the histomorphometric method in bone-implant interface analyses. With the limitations of this study, 3D-µCT analysis may even have a superior aspect in that it eliminates random variables that arise as a consequence of the selected cutting direction.
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Interface Osso-Implante , Implantes Dentários , Animais , Interface Osso-Implante/diagnóstico por imagem , Implantação Dentária Endóssea , Osseointegração , Próteses e Implantes , Coelhos , Reprodutibilidade dos Testes , Propriedades de Superfície , Titânio , Microtomografia por Raio-XRESUMO
OBJECTIVES: To review reports false-positive Xpert results in an emergency room and trauma center. METHODS: Patients' data with false-positive Xpert results from November 2020 to February 2022 at Pusan National University Hospital, Busan, Republic of Korea, were extracted from the electronic medical records. RESULTS: The positive predictive value of Xpert was 40%. Of the 12 patients with false-positive results, 5 (41.7%) were re-positives (such as, patients recovered from coronavirus disease-19 [COVID-19]), and 4 (33.3%) had head or facial trauma. Two out of 4 head or facial trauma cases had documented sample contamination with blood. CONCLUSION: We found a high incidence of false-positive Xpert results among patients who recovered from COVID-19 and those with head or facial injury. Careful history taking for COVID-19 and physical examination of the sample collection site is essential before Xpert analysis.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Centros de TraumatologiaRESUMO
Analog arithmetic operations are the most fundamental mathematical operations used in image and signal processing as well as artificial intelligence (AI). In-memory computing (IMC) offers a high performance and energy-efficient computing paradigm. To date, in-memory analog arithmetic operations with emerging nonvolatile devices are usually implemented using discrete components, which limits the scalability and blocks large scale integration. Here, a prototypical implementation of in-memory analog arithmetic operations (summation, subtraction and multiplication) is experimentally demonstrated, based on in-memory electrical current sensing units using spin-orbit torque (SOT) devices. The proposed structures for analog arithmetic operations are smaller than the state-of-the-art complementary metal oxide semiconductor (CMOS) counterparts by several orders of magnitude. Moreover, data to be processed and computing results can be locally stored, or the analog computing can be done in the nonvolatile SOT devices, which are exploited to experimentally implement the image edge detection and signal amplitude modulation with a simple structure. Furthermore, an artificial neural network (ANN) with SOT devices based synapses is constructed to realize pattern recognition with high accuracy of ≈95%.
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BACKGROUND: Microcirculatory disturbances are typically most severe during cardiopulmonary bypass (CPB), which occurs during cardiac surgeries. If microvascular reactivity compensates for microcirculatory disturbances during CPB, tissue hypoxemia can be minimized. The primary aim of this study was to assess whether microvascular reactivity during CPB could predict major adverse events (MAE) after cardiac surgery. METHODS: This prospective observational study included 115 patients who underwent elective on-pump cardiac surgeries. A vascular occlusion test (VOT) with near-infrared spectroscopy was performed five times for each patient: before the induction of general anesthesia, 30 min after the induction of general anesthesia, 30 min after applying CPB, 10 min after protamine injection, and post-sternal closure. The postoperative MAE was recorded. The area under the receiver operating characteristic (AUROC) curve analysis was performed for the prediction of MAE using the recovery slope. RESULTS: Of the 109 patients, MAE occurred in 32 (29.4%). The AUROC curve for the recovery slope during CPB was 0.701 (P < 0.001; 95% CI [0.606, 0.785]). If the recovery slope during CPB was < 1.08%/s, MAE were predicted with a sensitivity of 62.5% and specificity of 72.7%. CONCLUSIONS: Our study demonstrated that the recovery slope of the VOT during CPB could predict MAE after cardiac surgery. These results support the idea that disturbances in microcirculation induced by CPB can predict the development of poor clinical outcomes, thereby demonstrating the potential role of microvascular reactivity as an early predictor of MAE after cardiac surgery.
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Procedimentos Cirúrgicos Cardíacos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Humanos , Microcirculação , Estudos Prospectivos , Espectroscopia de Luz Próxima ao Infravermelho/métodosRESUMO
BACKGROUND: Laparoscopic hepatectomy has recently become popular because it results in less bleeding than open hepatectomy. However, CO2 embolism occurs more frequently. Most CO2 embolisms during laparoscopic surgery are self-resolving and non-symptomatic; however, severe CO2 embolism may cause hypotension, cyanosis, arrhythmia, and cardiovascular collapse. In particular, paradoxical CO2 embolisms are highly likely to cause neurological deficits. We report a case of paradoxical CO2 embolism found on transesophageal echocardiography (TEE) during laparoscopic hepatectomy, although the patient had no intracardiac shunt. CASE SUMMARY: A 71-year-old man was admitted for laparoscopic left hemihepatectomy. During left hepatic vein ligation, the inferior vena cava was accidentally torn. We observed a sudden drop in oxygen saturation to 85%, decrease in systolic blood pressure (SBP) below 90 mmHg, and reduction in end-tidal CO2 to 24 mmHg. A "mill-wheel" murmur was auscultated over the precordium. The fraction of inspired oxygen was increased to 100% with 5 cmH2O of positive end-expiratory pressure (PEEP) and hyperventilation was maintained. Norepinephrine infusion was increased to maintain SBP above 90 mmHg. A TEE probe was inserted, revealing gas bubbles in the right side of the heart, left atrium, left ventricle, and ascending aorta. The surgeon reduced the pneumoperitoneum pressure from 17 to 14 mmHg and repaired the damaged vessel laparoscopically. Thereafter, the patient's hemodynamic status stabilized. The patient was transferred to the intensive care unit, recovering well without complications. CONCLUSION: TEE monitoring is important to quickly determine the presence and extent of embolism in patients undergoing laparoscopic hepatectomy.