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Characterization of reactive intermediates in C-H functionalization is challenging due to the fleeting lifetimes of these species. Synthetic photochemistry provides a strategy to generate post-turnover-limiting-step intermediates in catalysis under cryogenic conditions that enable characterization. We have a long-standing interest in the structure and reactivity of Rh2 nitrene intermediates, which are implicated as transient intermediates in Rh2-catalyzed C-H amination. Previously, we demonstrated that Rh2 complexes bearing organic azide ligands can serve as solid-state and in crystallo photoprecursors in the synthesis of transient Rh2 nitrenoids. Complementary solution-phase experiments have not been available due to the weak binding of most organic azides to Rh2 complexes. Furthermore, the volatility of the N2 that is evolved during in crystallo nitrene synthesis from these precursors has prevented the in crystallo observation of C-H functionalization from lattice-confined nitrenes. Motivated by these challenges, here we describe the synthesis and photochemistry of nonclassical nitrene precursors based on sulfilimine ligands. Sulfilimines bind to Rh2 carboxylate complexes more tightly than the corresponding azides, which has enabled the full solid-state and solution-phase characterization of these new complexes. The higher binding affinity of sulfilimine ligands as compared with organic azides has enabled both solution-phase and solid-state nitrene photochemistry. Cryogenic photochemical studies of Rh2 sulfilimine complexes confined within polystyrene thin films demonstrate that sulfilimine photochemistry can be accomplished at low temperature but that C-H amination is rapid at temperatures compatible with NâS photoactivation. The potential of these structures to serve as platforms for multistep in crystallo cascades is discussed.
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In this work, we investigated the effect of hole transporting poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) interfacing with Mn-doped CdS/ZnS quantum dots (QDs) deposited on an indium tin oxide (ITO) substrate on the photoemission of upconverted hot electrons under weak continuous wave photoexcitation in a vacuum. Among the various factors that can influence the photoemission of the upconverted hot electrons, we studied the role of PEDOT:PSS in facilitating the hole transfer from QDs and altering the energy of photoemitted hot electrons. Compared to hot electrons emitted from QDs deposited directly on the ITO substrate, the addition of the PEDOT:PSS layer between the QD and ITO layers increased the energy of the photoemitted hot electrons. The increased energy of the photoemitted hot electrons is attributed in part to the reduced steady-state positive charge on the QDs under continuous photoexcitation, which reduces the energy required to eject the electron from the conduction band.
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Hot electrons play a crucial role in enhancing the efficiency of photon-to-current conversion or photocatalytic reactions. In semiconductor nanocrystals, energetic hot electrons capable of photoemission can be generated via the upconversion process involving the dopant-originated intermediate state, currently known only in Mn-doped cadmium chalcogenide quantum dots. Here, we report that Mn-doped CsPbBr3 nanocrystals are an excellent platform for generating hot electrons via upconversion that can benefit from various desirable exciton properties and the structural diversity of metal halide perovskites (MHPs). Two-dimensional Mn-doped CsPbBr3 nanoplatelets are particularly advantageous for hot electron upconversion due to the strong exciton-dopant interaction mediating the upconversion process. Furthermore, nanoplatelets reveal evidence for the hot electron upconversion via long-lived dark excitons in addition to bright excitons that may enhance the upconversion efficiency. This study establishes the feasibility of hot electron upconversion in MHP hosts and demonstrates the potential merits of two-dimensional MHP nanocrystals in the upconversion process.
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In this study, the performance of machine learning in classifying parotid gland tumors based on diffusion-related features obtained from the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland was evaluated. Seventy-eight patients participated in this study and underwent magnetic resonance diffusion-weighted imaging. Three regions of interest, including the parotid gland tumor, the peritumor parotid gland, and the contralateral parotid gland, were manually contoured for 92 tumors, including 20 malignant tumors (MTs), 42 Warthin tumors (WTs), and 30 pleomorphic adenomas (PMAs). We recorded multiple apparent diffusion coefficient (ADC) features and applied a machine-learning method with the features to classify the three types of tumors. With only mean ADC of tumors, the area under the curve of the classification model was 0.63, 0.85, and 0.87 for MTs, WTs, and PMAs, respectively. The performance metrics were improved to 0.81, 0.89, and 0.92, respectively, with multiple features. Apart from the ADC features of parotid gland tumor, the features of the peritumor and contralateral parotid glands proved advantageous for tumor classification. Combining machine learning and multiple features provides excellent discrimination of tumor types and can be a practical tool in the clinical diagnosis of parotid gland tumors.
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Imagen de Difusión por Resonancia Magnética/métodos , Aprendizaje Automático , Neoplasias de la Parótida/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Susac syndrome is a rare disease presenting with a classic triad of symptoms. These are sensorineural hearing loss, encephalopathy, and branch retinal artery occlusions. Initial presentation is usually headache and symptoms of encephalopathy. Hearing loss is unusual in the early stages but, when it does present, can often lead to a misdiagnosis of sudden sensorineural hearing loss. Hence, neurological and retinal examinations are essential to an accurate diagnosis. In this study, we aimed to raise awareness of Susac syndrome among physicians and facilitate recognition of its manifestation, especially in those patients presenting with hearing loss alone. Identifying Susac syndrome that presents as sudden sensorineural hearing loss can be challenging but a number of case reviews have been reported in recent years and treatment guidelines are available.
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Encefalopatías , Pérdida Auditiva Súbita , Oclusión de la Arteria Retiniana , Síndrome de Susac , Pérdida Auditiva Súbita/diagnóstico , Pérdida Auditiva Súbita/etiología , Humanos , Imagen por Resonancia Magnética , Síndrome de Susac/complicaciones , Síndrome de Susac/diagnósticoRESUMEN
Microimplant-assisted rapid palatal expansion (MARPE) has been demonstrated successfully in maxillary expansion in late adolescence and adulthood. The maxillary advancement accompanied by expansion is frequently anticipated, which is beneficial for the treatment of class III malocclusion. Airway volume increase can also be noted in some cases from the measurement of cone beam computerized tomography (CBCT) after expansion. The objective of this case report is to demonstrate the feasibility of applying MARPE on late adolescence patients with maxillary transverse deficiency and to present the changes in transverse and anteroposterior dimensions as well as the volume increase in velopharyngeal airway after MARPE. A 15-year-old female presented class III skeletal pattern. She had maxillary transverse deficiency with moderate crowding and posterior/anterior crossbites. Maxillary Skeletal Expander (MSE; Biomaterials Korea Inc.) type-2 was used as a MARPE device in this case. After four weeks of maxillary expansion, a significant amount of expansion was achieved and the anterior crossbite was spontaneously corrected. Fixed appliance treatment was commenced four weeks after MARPE with 0.022-slot preadjusted brackets (MBT prescription). Temporary anchorage devices (TADs) were placed over the mandibular buccal shelves for posterior teeth distalization and crowding relief. After 25 months of treatment, the facial profile was improved with maxillary advancement (SNA: 83° to 83.5°) and mandibular backward rotation (SNB: 83° to 82°; SN-MP: 34.5° to 35°). In this case, MARPE not only engenders significant transverse correction but also aids in anteroposterior change. The treatment effects of maxillary advancement and mandibular backward rotation can lead to a more esthetic profile in skeletal class III cases.
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Maloclusión de Angle Clase III , Maloclusión , Adolescente , Adulto , Femenino , Humanos , Maloclusión/terapia , Maloclusión de Angle Clase III/terapia , Maxilar , Diseño de Aparato Ortodóncico , Técnica de Expansión PalatinaRESUMEN
Background and Objectives: Tuberculous pleurisy is a common extrapulmonary TB that poses a health threat. However, diagnosis of TB pleurisy is challenging because of the low positivity rate of pleural effusion mycobacterial culture and difficulty in retrieval of optimal pleural tissue. This study aimed to investigate the efficacy of mycobacterial culture from pleural tissue, obtained by forceps biopsy through medical pleuroscopy, in the diagnosis of TB pleurisy. Materials and Methods: This study retrospectively enrolled 68 TB pleurisy patients. Among them, 46 patients received semi-rigid pleuroscopy from April 2016 to March 2021 in a tertiary hospital. We analyzed the mycobacterial culture from pleural tissue obtained by forceps biopsy. Results: The average age of the study participants was 62.8 years, and 64.7% of them were men. In the pleuroscopic group, the sensitivity of positive Mycobacterium tuberculosis (M. TB) cultures for sputum, pleural effusion, and pleural tissue were 35.7% (15/42), 34.8% (16/46), and 78.3% (18/23), respectively. High sensitivities of M. TB culture from pleural tissue were up to 94.4% and 91.7% when pleural characteristic patterns showed adhesion lesions and both adhesion lesions and presence of micronodules, respectively. Conclusions: M. TB culture from pleural tissue should be considered a routine test when facing unknown pleural effusion during pleuroscopic examination.
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Mycobacterium tuberculosis , Derrame Pleural , Pleuresia , Tuberculosis Pleural , Biopsia/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Derrame Pleural/diagnóstico , Derrame Pleural/etiología , Estudios Retrospectivos , Tuberculosis Pleural/diagnóstico , Tuberculosis Pleural/microbiología , Tuberculosis Pleural/patologíaRESUMEN
Roselle (Hibiscus sabdariffa L.) plants, whose calyces are used for production of beverages or jams, are mainly cultivated in Taitung County of eastern Taiwan. Since 2016, large crown galls were observed on the roselle plants in the commercial plantations at Taimali and Jinfong Townships of Taitung County. A follow-up survey in July and August of 2017 revealed spreading of this disease to the neighboring areas including Beinan and Dawu Townships. Disease incidence was estimated to be 0.6-10%. Galls of varying sizes (2-15 cm in diameter) were usually found on the roots and crowns of the roselle plants, starting with small swellings at the infection sites. Galls were light-colored, and smooth and tender in texture at the early stage, but later turned dark-colored, and appeared rough and woody. In some cases, adventitious roots extruding from the larger crown galls could be seen. Isolation of the causal agent was performed by quadrantally streaking bacterial suspension made from surface-sterilized, macerated galls on trypticase soy agar (TSA). After incubating at 28°C for 5 days, single colonies were transferred onto new TSA plates for further cultivation at 28°C. Finally, circular, convex, viscous and milky white colonies with smooth surface similar to colony morphology of Agrobacterium tumefaciens C58 were obtained for further identification. First, all six candidate isolates (TZ-1, TL1-2, TL2-1, TD1-1, TD1-24 and TD2-1) were identified as Agrobacterium spp. using the partial sequences of the 16S rRNA gene (accession numbers MW205820 to MW205825 in the GenBank database). The selected isolates also showed some biochemical and physiological characteristics similar to A. tumefaciens, including oxidase positive, growth at 35°C and in 2% NaCl, and alkalinity from litmus milk. Moreover, they were tested negative for utilization of citrate and acid production on potato dextrose agar (PDA) supplemented with calcium carbonate. Under a transmission electron microscope, the bacterium was rod-shaped and possessed peritrichous flagella. By means of multiplex PCR using primers designed for differentiation of Agrobacterium rubi, Agrobacterium vitis and Agrobacterium biovars 1 and 2, a 184 bp product was detected in all six isolates, indicating that they all belong to Agrobacterium biovar 1. Furthermore, the recA allele of each isolate was PCR amplified using primers F2898/F2899, and recA sequence analysis assigned all six isolates to A. tumefaciens genomospecies G7 (GenBank accession numbers MZ570905-MZ570910). Pathogenicity assay was carried out by inoculating the stems of 2-week-old roselle seedlings through wounds made with a sterile needle with bacteria on it. The inoculated seedlings were kept in plastic bags to maintain high humidity. Symptoms similar to those observed in the field developed at the inoculation sites after 7 days, and Koch's postulates were fulfilled when the bacteria re-isolated from the galls were also identified as A. tumefaciens genomospecies G7 using recA gene sequence analysis. To our knowledge, this is the first report of crown gall disease caused by A. tumefaciens on Hibiscus sabdariffa in Taiwan. This disease may potentially damage the roselle industry if no action is taken to stop its spreading. Identification of the causal agent of roselle crown gall disease could help us further investigate its ecology and develop integrated pest management strategies for prevention of this disease in the future.
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Primary thyroid lymphoma (PTL) is a rare disease which responds well to rituximab-based chemotherapy. Here, we describe a case who was diagnosed through core needle biopsy as having diffuse large B-cell lymphoma in the right lobe of thyroid gland. Positron emission tomography computed tomography (PET-CT) revealed no other foci of hot spots, so PTL was considered. She was treated with rituximab plus bendamustine for three cycles, and color Doppler ultrasound revealed significant reduction of blood flow signals in the tumor but no significant decrease of its size (<25% extent). Then, the chemotherapy regimen was adjusted to rituximab, cyclophosphamide, vincristine, prednisone (R-COP), and complete remission was noted on ultrasound and PET-CT after three cycles of R-COP treatment. This case is reported to tell that color Doppler ultrasound, in addition to PET-CT, is useful to evaluate chemotherapeutic effect on PTLs.
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The aim of this study was to evaluate the imaging quality and diagnostic performance of fast spin echo diffusion-weighted imaging with periodically rotated overlapping parallel lines with enhanced reconstruction (FSE-PROP-DWI) in distinguishing parotid pleomorphic adenoma (PMA) from Warthin tumor (WT). This retrospective study enrolled 44 parotid gland tumors from 34 patients, including 15 PMAs and 29 WTs with waived written informed consent. All participants underwent 1.5 T diffusion-weighted imaging including FSE-PROP-DWI and single-shot echo-planar diffusion-weighted imaging (SS-EP-DWI). After imaging resizing and registration among T2WI, FSE-PROP-DWI and SS-EP-DWI, imaging distortion was quantitatively analyzed by using the Dice coefficient. Signal-to-noise ratio and contrast-to-noise ratio were qualitatively evaluated. The mean apparent diffusion coefficient (ADC) of parotid gland tumors was calculated. Wilcoxon signed-rank test was used for paired comparison between FSE-PROP-DWI versus SS-EP-DWI. Mann-Whitney U test was used for independent group comparison between PMAs versus WTs. Diagnostic performance was evaluated by receiver operating characteristics curve analysis. P < 0.05 was considered statistically significant. The Dice coefficient was statistically significantly higher on FSE-PROP-DWI than SS-EP-DWI for both tumors (P < 0.005). Mean ADC was statistically significantly higher in PMAs than WTs on both FSE-PROP-DWI and SS-EP-DWI (P < 0.005). FSE-PROP-DWI and SS-EP-DWI successfully distinguished PMAs from WTs with an AUC of 0.880 and 0.945, respectively (P < 0.05). Sensitivity, specificity, positive predictive value, negative predictive value and accuracy in diagnosing PMAs were 100%, 69.0%, 62.5%, 100% and 79.5% for FSE-PROP-DWI, and 100%, 82.8%, 75%, 100% and 88.6% for SS-EP-DWI, respectively. FSE-PROP-DWI is useful to distinguish parotid PMAs from WTs with less distortion of tumors but lower AUC than SS-EP-DWI.
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Adenolinfoma/diagnóstico por imagen , Adenolinfoma/diagnóstico , Adenoma Pleomórfico/diagnóstico por imagen , Adenoma Pleomórfico/diagnóstico , Imagen de Difusión por Resonancia Magnética , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Neoplasias de las Glándulas Salivales/diagnóstico , Diagnóstico Diferencial , Humanos , Procesamiento de Imagen Asistido por Computador , Curva ROC , Procesamiento de Señales Asistido por Computador , Relación Señal-RuidoRESUMEN
PURPOSE: The role of brain FDG-PET in patients with lung cancer and brain metastases remains unclear. Here, we sought to determine the prognostic significance of whole-body PET/CT plus brain PET/MR in predicting the time to neurological progression (nTTP) and overall survival (OS) in this patient group. METHODS: Of 802 patients with non-small cell lung cancer who underwent primary staging by a single-day protocol of whole-body PET/CT plus brain PET/MR, 72 cases with adenocarcinoma and brain metastases were enrolled for a prognostic analysis of OS. On the basis of the available follow-up brain status, only 52 patients were eligible for prognostic analysis of nTTP. Metastatic brain tumors were identified on post-contrast MR imaging, and the tumor-to-brain ratio (TBR) was measured on PET images. RESULTS: Multivariate analysis revealed that FDG-PET findings and eligibility for initial treatment with targeted therapy were significant independent predictors of nTTP and OS. A new index, termed the molecular imaging prognostic (MIP) score, was proposed to define three disease classes. MIP scores were significant predictors of both nTTP and OS (P < 0.001). Pre-existing prognostic indices such as Lung-molGPA scores were significant predictors of OS but did not predict nTTP. CONCLUSIONS: When staging is performed with whole-body PET/CT plus brain PET/MR, our new prognostic index may be helpful to stratify the outcomes of patients with lung adenocarcinoma and brain metastases. The superior prognostic power of this index for nTTP might be used to select appropriate patients for intracranial control and thereby achieve better quality of life.
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Adenocarcinoma del Pulmón/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Encéfalo/diagnóstico por imagen , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Imagen de Cuerpo EnteroRESUMEN
Influenza-associated acute encephalopathy (IAE) is more prevalent in children than in adults and often results in neurological sequelae or even death. Diagnosis of IAE is difficult as clinical presentation varies significantly and the influenza virus is rarely detected in cerebrospinal fluid. Moreover, seizures in adults due to influenza infection are rare. Herein, we describe the case of an adult presenting with both acute encephalitis and seizures. A 38-year-old female was admitted to the emergency department with acute respiratory symptoms and fever, followed by quick progression to stupor within 24â¯h. A rapid antigen test was influenza A-positive, and polymerase chain reaction of nasal secretions confirmed the H3N2 subtype. Brain magnetic resonance imaging showed bilateral water restriction lesions at the thalamus and the cerebellum and an electroencephalogram showed frequent episodic generalized sharp-and-slow waves over the bilateral frontal region. Based on the neuroimaging and laboratory findings, we diagnosed the patient with adult influenza A (H3N2)-related encephalitis complicated by seizure. Treatment with oseltamivir and anticonvulsants led to complete neurologic recovery by day 14. This report describes two unusual neurological manifestations of influenza A, i.e., encephalitis and seizures, in an adult. We emphasize that, in adults presenting with acute viral encephalitis, clinicians should consider influenza infection as part of the differential diagnosis, and that typical neuroimaging in conjunction with laboratory detection of influenza virus and/or intrathecal antibody production suggestive of IAE, may help establish an accurate diagnosis.
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Encefalitis Viral/virología , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/diagnóstico , Enfermedad Aguda , Adulto , Anticonvulsivantes/administración & dosificación , Antivirales/administración & dosificación , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Diagnóstico Diferencial , Encefalitis Viral/complicaciones , Encefalitis Viral/diagnóstico , Encefalitis Viral/tratamiento farmacológico , Femenino , Humanos , Gripe Humana/complicaciones , Gripe Humana/tratamiento farmacológico , Gripe Humana/virología , Levetiracetam/administración & dosificación , Imagen por Resonancia Magnética , Oseltamivir/administración & dosificación , Convulsiones/tratamiento farmacológico , Convulsiones/etiologíaRESUMEN
Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi-square). We conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down-regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1 in MPM is warranted.
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Proteínas Adaptadoras Transductoras de Señales/genética , Antígeno B7-H1/genética , Neoplasias Pulmonares/genética , Mesotelioma/genética , Fosfoproteínas/genética , Neoplasias Pleurales/genética , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Mesotelioma/patología , Mesotelioma Maligno , Fosfoproteínas/antagonistas & inhibidores , Neoplasias Pleurales/patología , Transducción de Señal/genética , Factores de Transcripción , Proteínas Señalizadoras YAPRESUMEN
OBJECTIVE: The objective of this article is to propose a Warthin tumor (WT) score to distinguish WTs from other parotid tumors. MATERIALS AND METHODS: The study included 78 patients with 92 histologically proven parotid tumors, including 42 WTs, 30 pleomorphic adenomas (PMAs), and 20 carcinomas. Echo-planar DW images were acquired. The WT score, which comprised the mean apparent diffusion coefficient (ADCM) and the SD of the ADC (ADCSD) of tumors, patient age, and patient sex, was used to predict WTs. The diagnostic performance of the WT score was evaluated using ROC analyses. Statistical significance was denoted by p < 0.05. RESULTS: With the use of optimized criteria, including an ADCM less than or equal to 1.016 × 10-3 mm2/s (WT score, 1), an ADCSD less than or equal to 0.1171 × 10-3 mm2/s (WT score, 1), patient age older than 49 years (WT score, 1), and male sex (WT score, 1), a WT score greater than 2 had a sensitivity, specificity, positive negative value, negative predictive value, and accuracy of 85.7%, 100.0%, 100.0%, 89.3%, and 93.4%, respectively. CONCLUSION: The WT score allows parotid WTs to be distinguished from PMAs and carcinomas with high accuracy.
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Adenolinfoma/diagnóstico por imagen , Adenoma Pleomórfico/diagnóstico por imagen , Carcinoma/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar , Neoplasias de la Parótida/diagnóstico por imagen , Adenolinfoma/patología , Adenoma Pleomórfico/patología , Adenoma Pleomórfico/cirugía , Biopsia con Aguja Gruesa , Carcinoma/patología , Carcinoma/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/cirugía , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Mechanical ventilation (MV) used in patients with acute respiratory distress syndrome (ARDS) can increase lung inflammation and pulmonary fibrogenesis. Src is crucial in mediating the transforming growth factor (TGF)-ß1-induced epithelial-mesenchymal transition (EMT) during the fibroproliferative phase of ARDS. Nintedanib, a multitargeted tyrosine kinase inhibitor that directly blocks Src, has been approved for the treatment of idiopathic pulmonary fibrosis. The mechanisms regulating interactions among MV, EMT and Src remain unclear. In this study, we suggested hypothesized that nintedanib can suppress MV-augmented bleomycin-induced EMT and pulmonary fibrosis by inhibiting the Src pathway. Five days after administrating bleomycin to mimic acute lung injury (ALI), C57BL/6 mice, either wild-type or Src-deficient were exposed to low tidal volume (VT ) (6 ml/kg) or high VT (30 ml/kg) MV with room air for 5 hrs. Oral nintedanib was administered once daily in doses of 30, 60 and 100 mg/kg for 5 days before MV. Non-ventilated mice were used as control groups. Following bleomycin exposure in wild-type mice, high VT MV induced substantial increases in microvascular permeability, TGF-ß1, malondialdehyde, Masson's trichrome staining, collagen 1a1 gene expression, EMT (identified by colocalization of increased staining of α-smooth muscle actin and decreased staining of E-cadherin) and alveolar epithelial apoptosis (P < 0.05). Oral nintedanib, which simulated genetic downregulation of Src signalling using Src-deficient mice, dampened the MV-augmented profibrotic mediators, EMT profile, epithelial apoptotic cell death and pathologic fibrotic scores (P < 0.05). Our data indicate that nintedanib reduces high VT MV-augmented EMT and pulmonary fibrosis after bleomycin-induced ALI, partly by inhibiting the Src pathway.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Indoles/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Lesión Pulmonar Inducida por Ventilación Mecánica/tratamiento farmacológico , Familia-src Quinasas/antagonistas & inhibidores , Actinas/genética , Actinas/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Administración Oral , Animales , Bleomicina/toxicidad , Cadherinas/genética , Cadherinas/metabolismo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Cadena alfa 1 del Colágeno Tipo I , Modelos Animales de Enfermedad , Esquema de Medicación , Transición Epitelial-Mesenquimal/genética , Regulación de la Expresión Génica , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Respiración Artificial/efectos adversos , Transducción de Señal , Volumen de Ventilación Pulmonar , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/etiología , Lesión Pulmonar Inducida por Ventilación Mecánica/genética , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Familia-src Quinasas/deficiencia , Familia-src Quinasas/genéticaRESUMEN
BACKGROUND: The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the early diagnosis of this heterogeneous and fatal disease becomes critical. METHODS: We retrospectively reviewed the characteristics of genetically confirmed ATTR Ala97Ser patients at a tertiary referral medical center. RESULTS: Eight patients from 7 different families were enrolled (61.7 ± 5.5 years). Gastrointestinal symptoms, dyspnea or chest tightness, rather than sensory symptoms, were the initial symptoms in two patients (2/7 = 29%). Body weight loss (3/7 = 43%), muscle wasting (4/7 = 57%), or dysphagia (3/7 = 43%) were the consecutive symptoms. Orthostatic symptoms including orthostatic hypotension (7/7 = 100%), dizziness (6/7 = 86%) and syncope (5/7 = 71%) tended to develop in the late phase of the disease. Autonomic dysfunction was conspicuous. Cardiographic findings included a combination of ventricular wall thickening and pericardial effusion (7/7 = 100%), a granular sparkling appearance of the ventricular myocardium (4/7 = 57%), or conduction abnormalities (5/7 = 71%). CONCLUSIONS: This study broadens the recognition of the initial signs and symptoms, including cardiographic findings and longitudinal manifestations in Taiwanese individuals with ATTR Ala97Ser mutation. These manifestations should prompt doctors to perform further studies and make an early diagnosis.
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Amiloidosis/genética , Prealbúmina/genética , Anciano , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Estudios Retrospectivos , TaiwánRESUMEN
INTRODUCTION: Fracture impaction is a surgical technique used to support the fractured humerus with locking plate or intramedullary nail when treating proximal humeral fractures. However, few studies have investigated the mechanical difference between fracture impaction with locking plate and with intramedullary nail. The mechanism of fracture impaction to increase stability is still unclear. The aim of this study was to use numerical methods to compare the biomechanical effect of treating proximal humeral fracture. METHODS: Six different humerus models, including intact and fractured humeri with various fixation patterns were used in this study. Fracture impaction was simulated by moving the distal fragment of the humeral shift upwards directly until touching the inferior surface of the proximal fragment. We also considered both poor- and normal-quality bone in the simulation. RESULTS: Results confirmed that fracture impaction increases fracture stabilityand decreases peak stress in both implant and bone. Also, fracture impaction and plating with medial shift of the humeral shaft provides the highest stability. The metallic implant shared loading with the bone in the impacted models, while implants sustained all the loading alone in the nonimpacted models. CONCLUSIONS: Based on the results, the technique of fracture impaction is suggested for both nail and plate to reduce stresses on bone and implants and to increase structural stability. Furthermore, impaction with medial shift of the humeral shaft with plate is found to achieve the highest stability when treating proximal humeral fractures.
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Clavos Ortopédicos/efectos adversos , Placas Óseas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Fracturas del Hombro/cirugía , Fenómenos Biomecánicos , Simulación por Computador , Fijación Intramedular de Fracturas/efectos adversos , HumanosRESUMEN
We propose a short- and long-range corrected (SLC) hybrid scheme employing 100% Hartree-Fock exchange at both zero and infinite interelectronic distances, wherein three SLC hybrid density functionals with the D3 dispersion corrections (SLC-LDA-D3, SLC-PBE-D3, and SLC-B97-D3) are developed. SLC-PBE-D3 and SLC-B97-D3 are shown to be accurate for a very diverse range of applications, such as core ionization and excitation energies, thermochemistry, kinetics, noncovalent interactions, dissociation of symmetric radical cations, vertical ionization potentials, vertical electron affinities, fundamental gaps, and valence, Rydberg, and long-range charge-transfer excitation energies. Relative to ωB97X-D, SLC-B97-D3 provides significant improvement for core ionization and excitation energies and noticeable improvement for the self-interaction, asymptote, energy-gap, and charge-transfer problems, while performing similarly for thermochemistry, kinetics, and noncovalent interactions.
RESUMEN
PURPOSE: Distal femur fractures adjacent to total knee arthroplasty are a rare yet complex problem. Recently, extramedullary locking plate and retrograde intramedullary nail fixations have become popular options, but the complication rates associated with these procedures are 15-20 %. Modified fixations were assessed in an effort to reduce complications from unstable periprosthetic fractures. METHODS: Using experimental and finite element methods, this study compared the construct behaviours of a locking plate, a retrograde intramedullary nail, and their modifications (a spiral-blade supplemented in an intramedullary nail or a locking plate/allograft hybrid) when subjected to various fracture types, locations, loading conditions, and bony strength. The implanted models were used to assess construct stiffness, fracture micromotion, and implant stress under different osteoporotic conditions. Finally, we collected 40 cases for radiological analysis to indicate the appropriate procedure for treating periprosthetic fractures following total knee arthroplasty. RESULTS: Regardless of the fracture type, femoral constructs fixed with a conventional or spiral-blade supplemented intramedullary nail exhibited higher axial but lower torsional stiffness than those fixed with a locking plate. Torsional deformation occurred if the lower-positioned fracture had no medial support. The locking plate/allograft construct exhibited the highest stiffness and the least micromotion. A review of 40 clinical cases confirmed the above findings regarding the locking plate/allograft construct. CONCLUSION: The spiral-blade supplement of retrograde intramedullary nail and locking plate/allograft modified constructs significantly stabilizes the unstable fractured gaps. The locking plate/allograft is recommended for the periprosthetic fractures with deficient bone stock and severe osteoporosis to improve alignment and healing potentials.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Fracturas del Fémur/cirugía , Fijación Interna de Fracturas/métodos , Fracturas Periprotésicas/cirugía , Clavos Ortopédicos , Placas Óseas , Simulación por Computador , Fracturas del Fémur/etiología , Análisis de Elementos Finitos , Humanos , Ensayo de Materiales , Modelos BiológicosRESUMEN
BACKGROUND: Although Sjögren's syndrome has been known to complicate with white matter lesions, encephalopathy, or stroke, reports of cerebral venous sinus thrombosis due to Sjögren's syndrome with atypical antibodies are rare. CASE REPORT: A 50-year-old woman was admitted to our neurological ward with nausea and vomiting following acute onset of severe headache in the left occipital region. Brain computed tomography revealed no abnormalities. The patient was fully conscious, with normal cognitive functioning, but exhibited unsteady tandem gait. Both magnetic resonance venography and computed tomography venography suggested left transverse sinus blockage. Intravenous enoxaparin, followed by oral warfarin, was initiated as treatment for cerebral venous sinus thrombosis. After investigation, Sjögren's syndrome was diagnosed and lupus anticoagulant antibody test was positive. The patient was treated with hydroxychloroquine, and appeared fully recovered at the 6-month follow-up, with no clinical or radiological signs of relapse. CONCLUSION: This case reports the relationship between cerebral venous sinus thrombosis and Sjögren's syndrome. It is necessary to screen autoimmune disorders in patients with cerebral venous sinus thrombosis that present with no common risk factors of venous thrombosis in order to prevent inappropriate management, and potentially adverse outcomes.