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Objective: The objective of this study was to determine the implementation, clinical barriers, and unmet needs of repetitive transcranial magnetic stimulation (rTMS) and neuro-navigation systems for stroke rehabilitation. Design: We employed a nationwide survey via Google Forms (web and mobile) consisting of 36 questions across rTMS and neuro-navigation systems, focusing on their implementation, perceptions, and unmet needs in stroke recovery. The survey targeted physiatrists registered in the Korean Society for Neuro-rehabilitation and in rehabilitation hospitals in South Korea. Results: Of 1,129 surveys distributed, 122 responses were analyzed. Most respondents acknowledged the effectiveness of rTMS in treating post-stroke impairments; however, they highlighted significant unmet needs in standardized treatment protocols, guidelines, education, device usability, and insurance coverage. Unmet needs for neuro-navigation were also identified; only 7.4% of respondents currently used such systems, despite acknowledging their potential to enhance treatment accuracy. Seventy percent of respondents identified lack of prescription coverage, time and errors in preparation, and device cost as barriers to clinical adoption of neuro-navigation systems. Conclusion: Despite recognition of the potential of rTMS in stroke rehabilitation, there is a considerable gap between research evidence and clinical practice. Addressing these challenges, establishing standardized protocols, and advancing accessible neuro-navigation systems could significantly enhance the clinical application of rTMS, offering a more personalized, effective treatment modality for stroke recovery.
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The number of individuals with underlying medical conditions has been increasing steadily. These individuals are relatively vulnerable to harmful external factors. But it has not been proven that the effects of hazardous chemicals may differ depending on their physicochemical properties. This study determines the toxic effects of two chemicals with high indoor exposure risk and different physicochemical properties on an underlying disease model. A pulmonary arterial hypertension (PAH) model was constructed by a single subcutaneous injection of monocrotaline (MCT; 60â¯mg/kg) into Sprague-Dawley rats. After three weeks, formaldehyde (FA; 2.5â¯mg/kg) and polyhexamethylene guanidine (PHMG; 0.05â¯mg/kg) were administered once via intratracheal instillation, and rats were necropsied one week later. Exposure to FA and PHMG affected organ weight and the Fulton and toxicity indices in rats induced with PAH. FA promoted bronchial injury and aggravated PAH, while PHMG only induced alveolar injury. Additionally, the differentially expressed genes were altered following exposure to FA and PHMG, as were the associated diseases (cardiovascular disease and pulmonary fibrosis, respectively). In conclusion, inhaled chemicals with different physicochemical properties can cause damage to organs, such as the lungs and heart, and can aggravate underlying diseases. This study elucidates indoor inhaled exposure-induced toxicities and alerts patients with pre-existing diseases to the harmful chemicals.
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INTRODUCTION: This paper presents a camera sheath that can be assembled to various minimally invasive surgical instruments and provide the localized view of the instrument tip. MATERIAL AND METHODS: The advanced transformable head structure (ATHS) that overcomes the trade-off between the camera resolution and the instrument size is designed for the sheath. Design solutions to maintain the alignment between the camera's line of sight and the instrument tip direction during the transformation of the ATHS are derived and applied to the prototype of the sheath. RESULTS: The design solution ensured proper alignment between the line of sight and the tip direction. The prototype was used with the curved micro-debrider blades in simulated functional endoscopic sinus surgery (FESS). Deep regions of the sinus that were not observable with the conventional endoscopes was accessed and observed using the prototype. CONCLUSIONS: The presented camera sheath allows the delivery of the instrument and camera to the surgical site with minimal increase in port size. It may be applied to various surgeries to reduce invasiveness and provide additional visual information to the surgeons.
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BACKGROUND: The present study aimed to evaluate the long-term oncological and obstetric outcomes following the loop electrosurgical excision procedure (LEEP) in patients with cervical intraepithelial neoplasia (CIN) and investigate the risk factors for recurrence and preterm birth. METHODS: This retrospective cohort study included patients who underwent LEEP for CIN 2-3 between 2011 and 2019. Demographic information, histopathological findings, postoperative cytology, and human papillomavirus (HPV) status were collected and analyzed. The Cox proportional hazards model and Kaplan-Meier curves with the log-rank test were used for risk factor analysis. RESULTS: A total of 385 patients treated with the LEEP were analyzed. Treatment failure, including recurrence or residual disease following surgery, was observed in 13.5% of the patients. Positive surgical margins and postoperative HPV detection were independent risk factors for CIN1 + recurrence or residual disease (HR 1.948 [95%CI 1.020-3.720], p = 0.043, and HR 6.848 [95%CI 3.652-12.840], p-value < 0.001, respectively). Thirty-one patients subsequently delivered after LEEP, and the duration between LEEP and delivery was significantly associated with preterm-related complications, such as a short cervix, preterm labor, and preterm premature rupture of the membrane (p = 0.009). However, only a history of preterm birth was associated with preterm delivery. CONCLUSIONS: Positive HPV status after LEEP and margin status were identified as independent risk factors for treatment failure in patients with CIN who underwent LEEP. However, combining these two factors did not improve the prediction accuracy for recurrence.
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Infecciones por Papillomavirus , Nacimiento Prematuro , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Embarazo , Femenino , Recién Nacido , Humanos , Estudios Retrospectivos , Márgenes de Escisión , Virus del Papiloma Humano , Electrocirugia/métodos , Infecciones por Papillomavirus/complicaciones , Nacimiento Prematuro/epidemiología , Displasia del Cuello del Útero/patología , Recurrencia Local de Neoplasia/cirugíaRESUMEN
Deep endometriosis (DE) is endometriotic tissue that invades the peritoneum by >5 mm. Surgery is the treatment of choice for symptomatic DE, and laparoscopic surgery is preferred over laparotomy due to better vision and postoperative pain. In this review, we aimed to collect and summarize recent literature on DE surgery and share laparoscopic procedures for rectovaginal and bowel endometriosis.
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Cigarette smoke induces an inflammatory response in the lungs by recruiting inflammatory cells, leading to lung diseases such as lung cancer, chronic obstructive pulmonary disease, and pulmonary fibrosis. Existing inhalation exposure methods for assessing the adverse effects of cigarette smoke require expensive equipment and are labor-intensive. Therefore, we attempted to develop a novel method to assess these adverse effects using intratracheal instillation (ITI) of whole cigarette smoke condensate (WCSC). The WCSC (0, 5, 10, or 20 mg/mL) was administered by ITI once daily for 6 or 12 days using an automatic video instillator. Repeated WCSC ITI increased the lung weight, and monocyte chemoattractant protein-1 (MCP-1), neutrophil, and lymphocyte levels within bronchoalveolar lavage fluid compared to the control. In the histopathological analysis of the lung tissue, a mild inflammatory response was observed in the 6 and 12 days 20 mg/mL WCSC exposure groups. The genome-wide RNA-seq expression patterns revealed that inflammatory and immune response-related genes, such as the chemokine signaling pathway, Th1/Th2 cell differentiation, and cytokine-cytokine receptor interaction, were employed following WCSC exposure. In addition, MCP-1 was time-dependent and increased in the 10 mg/mL exposure group compared to the control group. These results suggested that the WCSC might induce the potential pulmonary inflammatory response. Furthermore, we proposed that ITI may be a rapid and effective method of evaluating the adverse effects of WCSC within a short exposure period (less than 2 weeks), and it can be used to evaluate cigarette inhalation toxicity studies as an alternative method.
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Fumar Cigarrillos , Enfermedades Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Ratas , Animales , Pulmón , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedades Pulmonares/patología , Líquido del Lavado BronquioalveolarRESUMEN
The ß-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA.
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Lateral flow assays (LFAs) have emerged as indispensable tools for point-of-care testing during the pandemic era. However, the interpretation of results through unassisted visual inspection by untrained individuals poses inherent limitations. In our study, we propose a novel approach that combines computer vision (CV) and lightweight machine learning (ML) to overcome these limitations and significantly enhance the performance of LFAs. By incorporating CV-assisted analysis into the LFA assay, we achieved a remarkable three-fold improvement in analytical sensitivity for detecting Influenza A and for SARS-CoV-2 detection. The obtained R2 values reached approximately 0.95, respectively, demonstrating the effectiveness of our approach. Moreover, the integration of CV techniques with LFAs resulted in a substantial amplification of the colorimetric signal specifically for COVID-19 positive patient samples. Our proposed approach, which incorporates a simple machine learning algorithm, provides substantial enhancements in assay sensitivity, improving diagnostic efficacy and accessibility of point-of-care testing without requiring significant additional resources. Moreover, the simplicity of the machine learning algorithm enables its standalone use on a mobile phone, further enhancing its practicality for point-of-care testing.
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COVID-19 , Gripe Humana , Humanos , SARS-CoV-2 , Gripe Humana/diagnóstico , COVID-19/diagnóstico , Algoritmos , Bioensayo , Prueba de COVID-19RESUMEN
The ongoing coronavirus disease 2019 (COVID-19) pandemic demands rapid and straightforward diagnostic tools to prevent early-stage viral transmission. Although nasopharyngeal swabs are a widely used patient sample collection method for diagnosing COVID-19, using these samples for diagnosis without RNA extraction increases the risk of obtaining false-positive and -negative results. Thus, multiple purification steps are necessary, which are time-consuming, generate significant waste, and result in substantial sample loss. To address these issues, we developed surface-modified polymerase chain reaction (PCR) tubes using the tertiary aminated polymer poly(2-dimethylaminomethylstyrene) (pDMAMS) via initiated chemical vapor deposition. Introducing the clinical samples into the pDMAMS-coated tubes resulted in approximately 100% RNA capture efficiency within 25 min, which occurred through electrostatic interactions between the positively charged pDMAMS surface and the negatively charged RNA. The captured RNA is then detected via chamber digital PCR, enabling a sensitive, accurate, and rapid diagnosis. Our platform provides a simple and efficient RNA extraction and detection strategy that allows detection from 22 nasopharyngeal swabs and 21 saliva specimens with 0% false negatives. The proposed method can facilitate the diagnosis of COVID-19 and contribute to the prevention of early-stage transmission.
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COVID-19 , Humanos , COVID-19/diagnóstico , Prueba de COVID-19 , Reacción en Cadena de la Polimerasa , Polímeros , ARNRESUMEN
Digital enzyme linked immunosorbent assays (ELISA) can be used to detect various antigens such as spike (S) or nucleocapsid (N) proteins of SARS-CoV-2, with much higher sensitivity compared to that achievable using conventional antigen tests. However, the use of microbeads and oil for compartmentalization in these assays limits their user-friendliness and causes loss of assay information due to the loss of beads during the process. To improve the sensitivity of antigen test, here, we developed an oil- and bead-free single molecule counting assay, with rolling circle amplification (RCA) on a substrate. With RCA, the signal is localized at the captured region of an antigen, and the signal from a single antigen molecule can be visualized using the same immune-reaction procedures as in the conventional ELISA. Substrate-based single molecule assay was theoretically evaluated for kd value, and the concentration of capture and detection antibodies. As a feasibility test, biotin-conjugated primer and mouse IgG conjugates were detected even at femto-molar concentrations with this digital immuno-RCA. Using this method, we detected the N protein of SARS-CoV-2 with a limit of detection less than 1 pg/mL more than 100-fold improvement compared to the detection using conventional ELISA. Furthermore, testing of saliva samples from COVID-19 patients and healthy controls (n = 50) indicated the applicability of the proposed method for detection of SARS-CoV-2 with 99.5% specificity and 90.9% sensitivity.
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Técnicas Biosensibles , COVID-19 , Animales , Ratones , SARS-CoV-2 , COVID-19/diagnóstico , Saliva , Ensayo de Inmunoadsorción Enzimática/métodos , Antígenos , Sensibilidad y Especificidad , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. OBJECTIVES: We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. METHODS: Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. RESULTS: After exposure to CA and NaOCl, body weight loss was observed but recovered. Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. CONCLUSIONS: The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.
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Pulmón , Hipoclorito de Sodio , Masculino , Ratas , Femenino , Animales , Ratas Sprague-Dawley , Hipoclorito de Sodio/toxicidadRESUMEN
Since many lateral flow assays (LFA) are tested daily, the improvement in accuracy can greatly impact individual patient care and public health. However, current self-testing for COVID-19 detection suffers from low accuracy, mainly due to the LFA sensitivity and reading ambiguities. Here, we present deep learning-assisted smartphone-based LFA (SMARTAI-LFA) diagnostics to provide accurate decisions with higher sensitivity. Combining clinical data learning and two-step algorithms enables a cradle-free on-site assay with higher accuracy than the untrained individuals and human experts via blind tests of clinical data (n = 1500). We acquired 98% accuracy across 135 smartphone application-based clinical tests with different users/smartphones. Furthermore, with more low-titer tests, we observed that the accuracy of SMARTAI-LFA was maintained at over 99% while there was a significant decrease in human accuracy, indicating the reliable performance of SMARTAI-LFA. We envision a smartphone-based SMARTAI-LFA that allows continuously enhanced performance by adding clinical tests and satisfies the new criterion for digitalized real-time diagnostics.
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COVID-19 , Aprendizaje Profundo , Humanos , Teléfono Inteligente , Prueba de COVID-19 , AlgoritmosRESUMEN
Highly sensitive rapid testing for COVID-19 is essential for minimizing virus transmission, especially before the onset of symptoms and in asymptomatic cases. Here, we report bioengineered enrichment tools for lateral flow assays (LFAs) with enhanced sensitivity and specificity (BEETLES2), achieving enrichment of SARS-CoV-2 viruses, nucleocapsid (N) proteins and immunoglobulin G (IgG) with 3-minute operation. The limit of detection is improved up to 20-fold. We apply this method to clinical samples, including 83% with either intermediate (35%) or low viral loads (48%), collected from 62 individuals (n = 42 for positive and n = 20 for healthy controls). We observe diagnostic sensitivity, specificity, and accuracy of 88.1%, 100%, and 91.9%, respectively, compared with commercial LFAs alone achieving 14.29%, 100%, and 41.94%, respectively. BEETLES2, with permselectivity and tunability, can enrich the SARS-CoV-2 virus, N proteins, and IgG in the nasopharyngeal/oropharyngeal swab, saliva, and blood serum, enabling reliable and sensitive point-of-care testing, facilitating fast early diagnosis.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Sensibilidad y Especificidad , Reacción en Cadena de la Polimerasa , Inmunoglobulina GRESUMEN
BACKGROUND: Nivolumab is an immune checkpoint inhibitor that targets the programmed cell death-1 protein and is effective in treating advanced cancer. However, it is also associated with various immune-related neurological complications, including myasthenia gravis, Guillain-Barré syndrome, and demyelinating polyneuropathy. These complications can easily mimic other neurological diseases and have greatly varying therapeutic approaches depending on the underlying pathophysiology. CASE PRESENTATION: Here, we report a case of nivolumab-induced demyelinating peripheral polyneuropathy involving the brachial plexus in a patient with Hodgkin lymphoma. Approximately 7 months after nivolumab treatment, the patient experienced muscle weakness with a tightness and tingling sensation in the right forearm. Electrodiagnostic studies showed features of demyelinating peripheral neuropathy with right brachial plexopathy. Magnetic resonance imaging revealed thickening with a diffuse enhancement of both brachial plexuses. The patient was eventually diagnosed with nivolumab-induced demyelinating polyneuropathy involving the brachial plexus. Oral steroid therapy improved motor weakness and sensory abnormalities without aggravation. CONCLUSION: Our study indicates the possibility of nivolumab-induced neuropathies in cases involving muscle weakness with sensory abnormalities of the upper extremity following nivolumab administration in patients with advanced cancer. Comprehensive electrodiagnostic studies and magnetic resonance imaging are helpful in the differential diagnosis of other neurological diseases. Appropriate diagnostic and therapeutic approaches may prevent further neurological deterioration.
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Neuropatías del Plexo Braquial , Síndrome de Guillain-Barré , Enfermedad de Hodgkin , Humanos , Nivolumab/efectos adversos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/complicaciones , Síndrome de Guillain-Barré/complicaciones , Neuropatías del Plexo Braquial/inducido químicamente , Neuropatías del Plexo Braquial/diagnóstico , Neuropatías del Plexo Braquial/complicaciones , Debilidad Muscular/complicacionesRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The high human-to-human transmission and rapid evolution of SARS-CoV-2 have resulted in a worldwide pandemic. To contain SARS-CoV-2, it is essential to efficiently control the transmission of the virus through the early diagnosis of infected individuals, including asymptomatic people. Therefore, a rapid and accurate assay is vital for the early diagnosis of SARS-CoV-2 in suspected individuals. In this study, we developed a colorimetric lateral flow immunoassay (LFIA) in which a CBP31-BC linker was used to immobilize antibodies on a cellulose membrane in an oriented manner. The developed LFIA enabled sensitive detection of cultured SARS-CoV-2 in 15 min with a detection limit of 5 × 104 copies/mL. The clinical performance of the LFIA for detecting SARS-CoV-2 was evaluated using 19 clinical samples validated by reverse transcription-polymerase chain reaction (RT-PCR). The LFIA detected all the positive and negative samples accurately, corresponding to 100% accuracy. Importantly, patient samples with low viral loads were accurately identified. Thus, the proposed method can provide a useful platform for rapid and accurate point-of-care testing of SARS-CoV-2 in infected individuals to efficiently control the COVID-19 pandemic.
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A simple, affordable point of care test (POCT) is necessary for on-site detection of coronavirus disease 2019 (COVID-19). The lateral flow assay (LFA) has great potential for use in POCT mainly because of factors such as low time consumption, low cost, and ease of use. However, it lacks sensitivity and limits of detection (LOD), which are essential for early diagnostics. In this study, we proposed a non-powered preconcentrator (NPP) based on nanoelectrokinetics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Antigen (Ag) lateral flow assay. The non-powered preconcentrator is composed of glass fiber-based composite paper and ion permselective material, and it can be simply operated by force balancing gravitational, capillary, and depletion-induced forces. The proposed approach helps enrich the SARS-CoV-2 viral nucleocapsid (N) proteins based on a 10-min operation, and it improved the LOD by up to 10-fold. The corresponding virus enrichment, which was evaluated using the reverse-transcriptase polymerase chain reaction (RT-PCR), revealed an improvement in ΔCt values > 3. We successfully demonstrated the enhancement of the NPP-assisted LFA, we extended to applying it to clinical samples. Further, we demonstrated an affordable, easy-to-implement form of LFA by simply designing NPP directly on the LFA buffer tube.
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Técnicas Biosensibles , COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Prueba de COVID-19 , Límite de Detección , Sensibilidad y EspecificidadRESUMEN
Sodium dichloroisocyanurate-96% (NaDCC) is commonly used to treat drinking water, industrial water, and wastewater. However, exposure to NaDCC by inhalation can have toxic pulmonary effects in humans. In the present study, we evaluated the potential toxicity of NaDCC following a 90-day inhalation toxicity study in Sprague-Dawley/Crl:CD (SD) rats. The animals were exposed to 0.4, 2.0, or 10.0 mg/m3 NaDCC for 90 days. In addition, male and female rats from the 10.0 mg/m3 group were set up as the recovery group for 14 days. The bronchoalveolar lavage fluid showed a concentration-dependent increase in the total cell count, with a significant increase in neutrophils in both the sexes in the 10.0 mg/m3 group compared to the negative control group. In the 10.0 mg/m3 group, lung organ weight was significantly increased among the female rats. Histopathological examination showed eosinophilic droplets in the olfactory/respiratory epithelium, mucous cell hyperplasia, atrophy/degeneration of the tracheal branches, and wall thickening of the alveolar ducts in the nasal cavity of both sexes in the 10.0 mg/m3 group. The adverse effects of NaDCC exposure were observed to decrease during the 14-day recovery period in both sexes. Based on pathological observations, the "no observed adverse effect concentration (NOAEC)" of inhaled NaDCC was 2.0 mg/m3 for both sexes. These results are expected to provide a scientific basis for inhalation toxicity data of NaDCC.
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Exposición por Inhalación , Pulmón , Humanos , Ratas , Animales , Masculino , Femenino , Ratas Sprague-Dawley , Administración por Inhalación , Líquido del Lavado Bronquioalveolar , Exposición por Inhalación/efectos adversosRESUMEN
Cigarette smoke (CS) substances are known to induce diverse ailments such as cancer, decreased immunity, and lung diseases. Although some studies have been actively conducted to evaluate cigarette toxicity, the current animal exposure methods, that is, exposure of 28- or 90-days, require considerable research cost and lead to obscure results of the CS effects. In a previous study, we compared the effects of CS in a rat model of bleomycin (BLM) and lipopolysaccharide (LPS) induced lung disease. We determined that compared to the LPS-induced rat model, the BLM-induced rat model was more sensitive to alterations in secreting cytokines and total cell number. In the current study, we further confirmed the time-point of effective inhalation exposure by CS in the BLM-induced lung injury rat model. Using an automatic video instillator, rats were administered a single dose of 2.5 mg/kg BLM (day 1), and subsequently exposed to CS via inhalation (nose-only) 4 h/day, for 1, 2, 3, and 4 weeks. The bronchoalveolar lavage fluid (BALF) was obtained from the right lung lobes, total cell numbers were counted, and chemokine and cytokine expressions were evaluated using Enzyme-Linked Immunosorbent Assay. For the 1-week exposure, we observed a greater increase of neutrophils in the BLM + CS 300 µg/L group than in the BLM or CS 300 µg/L groups. Exposure of CS in the BLM-induced lung injury rat model enhanced the secretions of chemokines and cytokines, such as CCL2/MCP-1, CXCL2/MIP-2 and TNF-α, at 1 week. Immunohistochemistry and Hematoxylin and Eosin staining of lungs at 1-2 weeks after exposure clearly confirmed this tendency in the increased levels of CCL2/MCP-1 and TNF-α. Taken together, these results indicate that the rat model of BLM-induced lung injury is more sensitive to CS exposure than other rat models, and may be an appropriate model to evaluate the effect of CS exposure at 1-2 weeks.
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Fumar Cigarrillos , Lesión Pulmonar , Animales , Bleomicina/toxicidad , Líquido del Lavado Bronquioalveolar/química , Fumar Cigarrillos/efectos adversos , Pulmón , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/metabolismo , RatasRESUMEN
The histogenesis of pleomorphic adenoma (PA) of the salivary glands remains controversial. PAs are characterized by the transition of epithelial cells to spindled mesenchymal cells, known as epithelial-mesenchymal transition (EMT). The present study aimed to identify a major EMT-inducing transcription factor (EMT-TF) in PAs. Real-time PCR analysis of SNAIL, SLUG, ZEB1, and TWIST1 demonstrated that only SLUG was significantly upregulated in normal salivary glands and PAs. Combined in situ hybridization for SLUG and multiplex immunohistochemistry for CK19 and P63 revealed that SLUG was specifically expressed in the myoepithelial cells of normal salivary glands. In PAs, SLUG was expressed in neoplastic myoepithelial cells and stromal cells but not in the luminal cells lining the inner layers of tumor glands. SLUG expression showed no correlation with PLAG1 expression, and in vitro experiments demonstrated that PLAG1 suppression in primary cultured PA cells or PLAG1 overexpression in HEK 293 T cells did not affect SLUG levels, indicating that PLAG1 was not involved in the upregulation of SLUG in PAs. The suppression of SLUG expression in cultured PA cells resulted in a morphology change to a less elongated shape and attenuated tumor growth. In addition, SLUG downregulation led to increased E-cadherin and decreased N-cadherin and vimentin expression levels along with decreased migratory activity in cultured PA cells. These findings suggest that SLUG is a major TF that can induce EMT in PAs. In summary, SLUG is specifically and highly expressed in the myoepithelial cells and stromal cells of PAs and is a key regulator of EMT in PAs.
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Adenoma Pleomórfico , Factores de Transcripción de la Familia Snail , Adenoma Pleomórfico/química , Adenoma Pleomórfico/genética , Adenoma Pleomórfico/metabolismo , Transición Epitelial-Mesenquimal , Células HEK293 , Humanos , Inmunohistoquímica , Factores de Transcripción de la Familia Snail/genética , Factores de Transcripción de la Familia Snail/metabolismoRESUMEN
Recently, as air pollution and particulate matter worsen, the importance of a platform that can monitor the air environment is emerging. Especially, among air pollutants, nitrogen dioxide (NO2) is a toxic gas that can not only generate secondary particulate matter, but can also derive numerous toxic gases. To detect such NO2 gas at low concentration, we fabricated a GNWs/NiO-WO3/GNWs heterostructure-based gas sensor using microwave plasma-enhanced chemical vapor deposition (MPECVD) and sputter, and we confirmed the NO2 detection characteristics between 10 and 50 ppm at room temperature. The morphology and carbon lattice characteristics of the sensing layer were investigated using field emission scanning electron microscopy (FESEM) and Raman spectroscopy. In the gas detection measurement, the resistance negative change according to the NO2 gas concentration was recorded. Moreover, it reacted even at low concentrations such as 5-7 ppm, and showed excellent recovery characteristics of more than 98%. Furthermore, it also showed a change in which the reactivity decreased with respect to humidity of 33% and 66%.