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BACKGROUND: The rating result reflects not only the performance of the candidate but some extent of the examiner's preference. Examiner bias could be objective, which means it can't be changed by the examiner like gender, age, race, educational level, or professional experience. No study about examiner bias was performed in the dental education realm, especially in the orthodontic field. Therefore, this study aimed to figure out possible influencing factors in examiners from examples of the Taiwan Board of Orthodontist examination. METHODS: The examiner groups comprised 29 males and 21 females selected from the certificated Taiwan Board of Orthodontists. Every examiner would receive a series of lectures about rating standards before the exam. The score data were collected from 2009 to 2019. RESULTS: As for the univariate regression model of the Taiwan Board of Orthodontist examination, the experienced examiner with a certification of more than 15 years tends to rate more leniently, but female examiners tend to rate harsher. The scores would increase with the examiner's age in both the univariate regression model of self-prepared and assigned cases. CONCLUSION: As for the multivariate model of self-prepared exams, the elder and the examiner who work in private practice clinics tend to rate more leniently. As for the multivariate model of the assigned case exam, the score would be only affected by age. However, further studies are necessary to determine the direct relation among these factors.
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Certificación , Ortodoncistas , Masculino , Humanos , Femenino , Taiwán , Competencia ClínicaRESUMEN
BACKGROUND: Non-syndromic tooth agenesis (NSTA) is a type of ectodermal dysplasia (ED) in which patients with non-syndromic oligodontia may only affect teeth. No pathological findings were found in other tissues of the ectodermal. Herein, we report a case of a NSTA patient with severe dental anxiety and poor oral health. CASE PRESENTATION: A 5-year-old boy without systemic diseases presented as a patient with oligodontia, extensive caries, and periapical periodontitis. Molecular genetic analysis found a mutation in the Ectodysplasin A (EDA) gene, confirming the diagnosis of NSTA. CONCLUSION: Tooth agenesis (TA) is the most common ectodermal developmental abnormality in humans. Non-syndromic oligodontia patients often seek treatment in the department of stomatology. Because of their complex oral conditions, these patients should be provided with a systematic and personalized treatment plan.
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Anodoncia , Humanos , Masculino , Anodoncia/genética , Anodoncia/terapia , Preescolar , Ectodisplasinas/genética , Periodontitis Periapical/terapia , Caries Dental/terapia , MutaciónRESUMEN
Bacterial adhesion and colonization on material surfaces pose a serious problem for healthcare-associated devices. Cationic amphiphilic polymer brushes are usually used as surface coatings in antibacterial materials to endow an interface with excellent bactericidal efficiency, but they are easily contaminated, which puts a great limitation on their application. Herein, novel antibacterial copolymer brush surfaces containing geminized cationic amphiphilic polymers (pAGC8) and thermoresponsive poly(N-isopropylacrylamide) polymers (pNIPAm) have been synthesized. Surface functionalization of polymer brushes was investigated by X-ray photoelectron spectroscopy, spectroscopic ellipsometry, atomic force microscopy, and water contact angle measurements. A proportion of AGC8 and NIPAm units in copolymer brushes has been adjusted to obtain a high-efficiency bactericidal surface with minimal interference to its self-cleaning property. The killing and releasing efficiency of the optimized surface simultaneously reached up to above 80% for both Staphylococcus aureus and Escherichia coli bacteria, and the bactericidal and self-cleaning abilities are still excellent even after three kill-release cycles. Such a novel copolymer brush system provides innovative guidance for the development of high-efficiency antibacterial materials in biomedical application.
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Antibacterianos , Polímeros , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/química , Escherichia coli/química , Polímeros/química , Polímeros/farmacología , Espectroscopía de Fotoelectrones , Propiedades de SuperficieRESUMEN
AIM: Dentinal tubules serve as disease-causing channels for infiltration and penetration of bacteria and their by-products; which are regarded as the major driver of pathogenesis in pulpal inflammation and infection. In this study, we aimed to evaluate the transdentinal potential of nanoscale cetylpyridinium chloride/cholesterol (CPC/Chol) sterosomes, which are a recently developed type of cationic non-phospholipid liposomal nanocarrier; as well as their intrinsic and universal antibacterial activity. METHODOLOGY: Cetylpyridinium chloride/cholesterol sterosomes were formulated, with a hydrodynamic diameter of 134 ± 4 nm, a low polydisperse index of 0.161 ± 0.007, and a positive zeta potential of 41 ± 3 mV at pH 7.4. Transdentinal diffusion ability of sterosomes was evaluated using human dentine blocks in vitro, and Wistar rat molar teeth in vivo. The intrinsic antibacterial activities of CPC/Chol sterosomes against Enterococcus faecalis, Streptococcus mutans, Fusobacterium nucleatum, and Porphyromonas gingivalis were further examined. RESULTS: Cetylpyridinium chloride/cholesterol sterosomes successfully penetrated through the dentinal tubules, and diffused into the pulp, which could be internalized by dental pulp cells with a high efficiency. In addition, they exhibited substantial levels of intrinsic antibacterial activity against these Gram-positive and Gram-negative endodontic bacteria and their biofilms. CONCLUSIONS: Given its high penetration and diffusion ability through the dentine and pulp, great potential for multi-drug delivery, and distinct intrinsic antibacterial activity; sterosome-based nanocarriers might serve as a promising therapeutic strategy aimed at targeting various specific pathways associated with pulpal diseases. This will help determine and characterize the most appropriate prophylactic and therapeutic targets for early intervention in our future dentistry practice.
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Cetilpiridinio , Liposomas , Animales , Ratas , Humanos , Cetilpiridinio/farmacología , Ratas Wistar , Colesterol , Antibacterianos/farmacologíaRESUMEN
OBJECTIVE: This study aimed to explore the efficiency of ultrasound (US) in prenatal diagnosis and prognosis of Pierre Robin sequence (PRS) of 18 cases. STUDY DESIGN: A total of 79,305 women admitted for prenatal US examinations were recruited from January 2017 to December 2020. Eighteen cases of PRS fetuses were selected form the cohort and 40 cases of isolated micrognathia were recruited randomly as control group. All the clinical and imaging results were retrospectively reviewed. General condition, US measurements, and prognosis of fetuses were compared between groups. RESULTS: Cleft palate, glossoptosis, and micrognathia were found in all 18 fetuses with PRS by prenatal US. Compared with the isolated micrognathia group, there were no significant differences in the PRS group in examination of maternal age, gestational weeks at assessment, and gender of fetuses, but significant lower measures in inferior facial angle, jaw index, and frontal nasal-mental angle (each p < 0.05). Twelve fetuses were defined to have other associated malformations. Ear malformations were the most common associated malformations with a prevalence of 44.4% (8/18). All of the18 cases were confirmed with PRS after delivery or autopsy. Two delivered infants were found bucking easily, one baby was spitting up frequently but growth showed normal. CONCLUSION: Prenatal detection of PRS with US examination is highly efficient. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period. Prenatal detection of Pierre Robin syndrome with targeted US examination is efficient in discerning characteristics of this rare syndrome. Even with the triad of malformations, isolated PRS had good outcomes following initial stabilization and management in the neonatal period. KEY POINTS: · Prenatal diagnosis of fetal PRS is of great clinical importance.. · Micrognathia has been identified as the primary feature of PRS.. · Posterior displacement of the tongue may cause acute neonatal respiratory distress.. · Even with triad malformation, isolated PRS seemed to have good outcomes..
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Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst-initiated therapeutics. Here, a Cu-doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi-catalytic activities, including catalyzing H2 O2 to generate O2 and · OH, and consuming reduced glutathione by a Cu(II)-Cu(I) transition approach. By decorating with sonosensitizers and DSPE-PEG, the obtained CuPPy-TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor-specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress-based antitumor therapy.
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Polímeros , Pirroles , Catálisis , Línea Celular Tumoral , Peróxido de Hidrógeno/farmacología , Polímeros/farmacología , Microambiente TumoralRESUMEN
The gradually depleting fossil resources and the biosafety of bisphenol A have always restricted the green development of the traditional epoxy resin field. In this Article, biomass macromolecule lignin sulfonates are selected as the raw material instead of traditional bisphenol A to prepare lignin-based epoxy resin adhesives. Lignin sulfonates are chemically modified and combined with a cross-linking agent to form lignin-based epoxy resin adhesives with double-interpenetrating-network structures. The resulting lignin-based epoxy adhesive exhibits a maximum tensile shear strength of 11.29 MPa, which is 213% higher than the strength before chemical modification. The tensile shear strength of the adhesive is still 10.13 MPa after 12 h of immersion in water (20 °C), and its tensile shear strength is 9.30 MPa after 12 h of immersion in boiling water (100 °C). The high-temperature and high-humidity environment has no significant effect on the properties of the resulting lignin-based epoxy adhesive.
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Adhesivos , Resinas Epoxi , Adhesivos/química , Resinas Epoxi/química , Ambientes Extremos , Lignina/química , AguaRESUMEN
The objective of the proposed human-machine cooperation (HMC) workstation is to both rapidly detect calcium-based fish bones in masses of minced fish floss and visually guide operators in approaching and removing the detected fish bones by hand based on the detection of fingernails or plastic-based gloves. Because vibration is a separation mechanism that can prevent absorption or scattering in thick fish floss for UV fluorescence detection, the design of the HMC workstation included a vibration unit together with an optical box and display screens. The system was tested with commonly used fish (swordfish, salmon, tuna, and cod) representing various cooking conditions (raw meat, steam-cooked meat, and fish floss), their bones, and contaminating materials such as derived from gloves made of various types of plastic (polyvinylchloride, emulsion, and rubber) commonly used in the removal of fish bones. These aspects were each investigated using the spectrum analyzer and the optical box to obtain and analyze the fluorescence spectra and images. The filter was mounted on a charge-coupled device, and its transmission-wavelength window was based on the characteristic band for fish bones observed in the spectra. Gray-level AI algorithm was utilized to generate white marker rectangles. The vibration unit supports two mechanisms of air and downstream separation to improve the imaging screening of fish bones inside the considerable flow of fish floss. Notably, under 310 nm ultraviolet B (UVB) excitation, the fluorescence peaks of the raw fillets, steam-cooked meat, and fish floss were observed at for bands at longer wavelengths (500-600 nm), whereas those of the calcium and plastic materials occurred in shorter wavelength bands (400-500 nm). Perfect accuracy of 100% was achieved with the detection of 20 fish bones in 2 kg of fish floss, and the long test time of around 10-12 min results from the manual removal of these fish bones.
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Calcio , Vibración , Animales , Humanos , Fluorescencia , Vapor , Peces , Tecnología , PlásticosRESUMEN
This study analyzed the epidemiological and clinical features of dengue fever in Zhangshu, Jiangxi Province, in 2019 and provided evidence for the diagnosis, treatment, prevention, and control of dengue fever. A total of 718 dengue fever patients in Zhangshu in 2019 were involved. ELISA and qRT-PCR were used for pathogenic detection of dengue virus. Multiple adjuvant therapies were applied, and the condition of patients after treatment was examined. Patients were between the ages of 0.75 and 92 years old, and all of them had a fever. A total of 519 cases had fatigue, and 413 cases had generalized myalgia and bone ache; 356 cases had dry mouth, 289 cases had bitter taste, and 167 cases felt dry and bitter taste; 279 cases had rash, and 93 cases had pruritus; 587 cases had decreased leukocyte, among which, 7 cases had leukocyte lower than 1 × 10 [9]/L; 380 cases had a low platelet count, and the platelet count of 29 cases was lower than 50 × 10 [9]/L; 488 cases had increased aspartic transaminase, and 460 cases had increased alanine aminotransferase; 5 cases had a severe disease. It proved that the majority of dengue fever sufferers were adults, with the main clinical features being fever and rash and the chief injured organs being the blood system, liver, heart, and gastrointestinal tract. Besides, over 40% of patients had dry and bitter taste, and 12 cases had alopecia after discharge. It indicates that the incidence of dengue fever in Zhangshu is closely related to the sudden population flow and imported cases.
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Dengue/epidemiología , Brotes de Enfermedades , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Dengue/sangre , Dengue/etiología , Virus del Dengue/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Factores Sexuales , Adulto JovenRESUMEN
A portable biosensor has been developed based on microfluidic particle accumulation for visual quantification of copper ions. A copper-dependent DNAzyme is used to connect magnetic microparticles (MMPs) and polystyrene microparticles (PMPs), forming "MMPs-DNAzyme-PMPs." When copper ions are present, the DNAzyme is cleaved, allowing free PMPs to be released from the MMPs-DNAzyme-PMP complex. Using a capillary-flow-based microfluidic device, the MMPs-DNAzyme-PMPs are first separated by a magnetic chamber, allowing the free PMPs to continue flowing until being trapped at a particle dam with a narrowing nozzle. Therefore, as a thermometer-like display, the copper level can be visually quantified by the accumulation length of the free PMPs in the trapping microchannel. The limit of detection (LOD) is 33 nM determined by the linear range of 25-100 nM, which is 900 times lower than the prevalent standard (~30 µM) in Hong Kong. The system shows excellent selectivity (> 1000-folds) against other heavy metal ions and abilities to adapt to multiple water environmental conditions. Tests on tap water samples and three local natural water sources in Hong Kong manifest that the device can effectively monitor the quality of freshwater with >70% recovery and 26.16% RSD.
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Técnicas Biosensibles/métodos , Cobre/análisis , ADN Catalítico/química , Nanopartículas/química , Contaminantes Químicos del Agua/análisis , Agua Potable/análisis , Ácidos Nucleicos Inmovilizados/química , Dispositivos Laboratorio en un Chip , Límite de Detección , Fenómenos Magnéticos , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos , Oligodesoxirribonucleótidos/química , Poliestirenos/químicaRESUMEN
Acne vulgaris, which is mostly associated with the colonization of Cutibacterium acnes (C. acnes), is a common skin inflammatory disease in teenagers. However, over the past few years, the disease has extended beyond childhood to chronically infect approximately 40% of adults. While antibiotics have been used for several decades to treat acne lesions, antibiotic resistance is a growing crisis; thus, finding a new therapeutic target is urgently needed. Studies have shown that phage therapy may be one alternative for treating multi-drug-resistant bacterial infections. In the present study, we successfully isolated a C. acnes phage named TCUCAP1 from the skin of healthy volunteers. Morphological analysis revealed that TCUCAP1 belongs to the family Siphoviridae with an icosahedral head and a non-contractile tail. Genome analysis found that TCUCAP1 is composed of 29,547 bp with a G+C content of 53.83% and 56 predicted open reading frames (ORFs). The ORFs were associated with phage structure, packing, host lysis, DNA metabolism, and additional functions. Phage treatments applied to mice with multi-drug-resistant (MDR) C.-acnes-induced skin inflammation resulted in a significant decrease in inflammatory lesions. In addition, our attempt to formulate the phage into hydroxyethyl cellulose (HEC) cream may provide new antibacterial preparations for human infections. Our results demonstrate that TCUCAP1 displays several features that make it an ideal candidate for the control of C. acnes infections.
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Acné Vulgar/terapia , Terapia de Fagos/métodos , Propionibacterium acnes/virología , Siphoviridae/clasificación , Secuenciación Completa del Genoma/métodos , Acné Vulgar/microbiología , Animales , Composición de Base , Celulosa/química , Modelos Animales de Enfermedad , Composición de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Tamaño del Genoma , Genoma Viral , Voluntarios Sanos , Humanos , Inyecciones Intradérmicas , Ratones , Sistemas de Lectura Abierta , Filogenia , Propionibacterium acnes/fisiología , Siphoviridae/genética , Siphoviridae/aislamiento & purificación , Piel/virologíaRESUMEN
Pathogenic bacteria adhesion and formation of biofilm on the implant are the most common reasons for healthcare-associated device failure. Cationic amphiphilic polymer brushes containing covalently linked quaternary ammonium salts (QASs) are considered to be the most promising bactericidal materials, but these surfaces still suffer from incomplete bactericidal ability and serious microorganism accumulation. With this in mind, a novel kind of hierarchical surface integrating both geminized cationic amphiphilic antibacterial upper layer and zwitterionic antifouling sublayer has been developed in this study. Measurements of X-ray photoelectron spectroscopy, spectroscopic ellipsometry, atomic force microscopy, water contact angle, and surface ζ-potential were performed to investigate the surface functionalization process. The thicknesses and grafting densities of the pAGC8 upper blocks have been optimized to avert the mutual interference among different components. The optimal hierarchical surface exhibits an ultrahigh antibacterial activity and a potent self-cleaning functionality against both Staphylococcus aureus and Escherichia coli bacteria, as well as a certain protein repellence ability. Such a novel hierarchical architecture provides innovative guidance for the construction of super-antibacterial and self-cleaning brushes in many biomedical applications.
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Adhesión Bacteriana , Polímeros , Antibacterianos/farmacología , Staphylococcus aureus , Propiedades de SuperficieRESUMEN
Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Hipofaríngeas/radioterapia , Liposomas/química , MicroARNs/genética , Polietilenglicoles/química , Radioisótopos/administración & dosificación , Radioisótopos/uso terapéutico , Renio/administración & dosificación , Renio/uso terapéutico , Animales , Cápsulas , Línea Celular Tumoral , Humanos , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/patología , Ratones , Radioisótopos/química , Renio/química , Análisis de SupervivenciaRESUMEN
Periodontitis is an important inflammatory disease that often causes by periodontopathic bacteria. The present study, we tested the anti-inflammatory effects of plantamajoside on LPS-stimulated human gingival fibroblasts. Human gingival fibroblasts (HGFs) were stimulated with LPS from Porphyromonas gingivalis. Plantamajoside was administrated 1â¯h before LPS treatment. The results demonstrated that plantamajoside decreased the production of PGE2, NO, IL-6, and IL-8 in LPS-stimulated HGFs. LPS-induced NF-κB p65 and IκB phosphorylation were also suppressed by plantamajoside. Furthermore, plantamajoside inhibited LPS-induced PI3K and AKT phosphorylation. In conclusion, these results suggested that the mechanism of plantamajoside was through inhibiting PI3K/AKT signaling pathway, which lead to the inhibition of NF-κB activation and inflammatory response.
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Antiinflamatorios/farmacología , Catecoles/farmacología , Fibroblastos/efectos de los fármacos , Glucósidos/farmacología , Lipopolisacáridos/toxicidad , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Células Cultivadas , Humanos , Mediadores de Inflamación/antagonistas & inhibidores , Lipopolisacáridos/aislamiento & purificación , Porphyromonas gingivalis/químicaRESUMEN
Bacterial infection on biomaterial devices and the subsequent medical risks pose a serious problem in both human healthcare and industrial applications, resulting in a prevalence of various antimicrobial materials. Cationic amphiphilic polymer has been proposed to be a new generation of efficient antibacterial material, but the surface modified by such types of polymers still shows incomplete bactericidal ability and easily contaminated performance. With this in mind, a novel kind of geminized cationic amphiphilic polymer brush surface has been developed in this study, presenting a complete antibacterial activity, because of the synergistic biocidal effect of electrostatic and hydrophobic interactions, as well as the minimized contact area between bacteria and polymer surface. A structure self-adjustment process of polymer brush construction has been proposed, in which the mutual interference among cationic head groups can be avoided and the electrostatic repulsion and hydrophobic attraction can be balanced, in the formation of a smooth and tight surface. A self-cleaning capability of polymer surface has been performed via hydrolysis and degradation, maintaining a high antibacterial activity. Therefore, we provide a facile and possible manipulation strategy to fabricate super-antibacterial and self-cleaning surfaces in a wide range of biomedical and industrial applications.
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Antibacterianos/química , Antibacterianos/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química , Polímeros/farmacología , Escherichia coli/efectos de los fármacos , Modelos Moleculares , Conformación Molecular , Staphylococcus aureus/efectos de los fármacosRESUMEN
Zwitterionic polymers are continually suggested as promising alternatives to tune the surface/interface properties of materials in many fields because of their unique molecular structures. Tremendous efforts have been devoted to immobilizing zwitterionic polymers (polyzwitterions, PZIs) on the material surfaces. However, these efforts usually suffer from cumbersome and time-consuming procedures. Herein we report a one-step strategy to facilely achieve the bioinspired polydopamine/polyzwitterion (PDA/PZI) coatings on various substrates. It requires only 30 min to form PDA/PZI coatings by mixing oxidant, dopamine, and zwitterionic monomers, including carboxybetaine methacrylate (CBMA), sulfobetaine methacrylate (SBMA), and 2-methacryloxyethyl phosphorylcholine (MPC). These bioinspired coatings display multifunctional properties such as underwater antioil-adhesion and antifreezing thanks to their high hydrophilicity and underwater superoleophobicity. The coatings even show the antiadhesion property for crude oil with high viscosity. Therefore, the PDA/PZI-coated meshes are efficient for separating both light oil and crude oil from oil/water mixtures. All these results demonstrate that the one-step strategy is a facile approach to design and exploit the bioinspired PDA/PZI coatings for diverse applications.
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Betaína/química , Indoles/química , Metacrilatos/química , Petróleo , Fosforilcolina/análogos & derivados , Polímeros/química , Ácidos Polimetacrílicos/química , Betaína/síntesis química , Congelación , Indoles/síntesis química , Metacrilatos/síntesis química , Fosforilcolina/síntesis química , Fosforilcolina/química , Polímeros/síntesis química , Ácidos Polimetacrílicos/síntesis química , Extracción en Fase Sólida/instrumentación , Extracción en Fase Sólida/métodos , Propiedades de Superficie , Agua/químicaRESUMEN
Tissue-nonspecific alkaline phosphatase (TNAP) is an ectoenzyme crucial for bone matrix mineralization via its ability to hydrolyze extracellular inorganic pyrophosphate (ePPi), a potent mineralization inhibitor, to phosphate (Pi). By the controlled hydrolysis of ePPi, TNAP maintains the correct ratio of Pi to ePPi and therefore enables normal skeletal and dental calcification. In other areas of the body low ePPi levels lead to the development of pathological soft-tissue calcification, which can progress to a number of disorders. TNAP inhibitors have been shown to prevent these processes via an increase of ePPi. Herein we describe the use of a whole blood assay to optimize a previously described series of TNAP inhibitors resulting in 5-((5-chloro-2-methoxyphenyl)sulfonamido)nicotinamide (SBI-425), a potent, selective and oral bioavailable compound that robustly inhibits TNAP in vivo.
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Fosfatasa Alcalina/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Niacinamida/análogos & derivados , Niacinamida/química , Sulfonamidas/química , Administración Oral , Fosfatasa Alcalina/metabolismo , Animales , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacocinética , Semivida , Concentración 50 Inhibidora , Ratones , Niacinamida/metabolismo , Niacinamida/farmacocinética , Relación Estructura-Actividad , Sulfonamidas/metabolismo , Sulfonamidas/farmacocinéticaRESUMEN
BACKGROUND: Bladder cancer is a disease of the elderly that is associated with high morbidity in those treated with radical cystectomy. In this observational study of patients with bladder cancer undergoing radical cystectomy, we analyzed and compared patient-reported outcomes from those treated with Enhanced Recovery After Surgery (ERAS) methods versus those who received traditional perioperative care. METHODS: We enrolled patients who underwent radical cystectomy at a high-volume tertiary care referral center from November 2013 to December 2016, when the ERAS concept was being introduced into postoperative care at our institution. Patients reported symptom outcomes using the MD Anderson Symptom Inventory preoperatively and on postoperative days 1 to 5. Mann-Whitney U tests were used to compare symptom burden between the ERAS and traditional-care groups. General linear mixed-effects models were used for longitudinal data; linear regression models were used for multivariable analysis. RESULTS: Patients (N = 383) reported dry mouth, disturbed sleep, drowsiness, fatigue, pain, and lack of appetite as the most severe symptoms. Compared with the traditional-care group, the ERAS group had significantly less pain (est. = -0.98, P = .005), drowsiness (est. = -0.91, P = .009), dry mouth (est. = -1.21, P = .002), disturbed sleep (est. = -0.97, P = .01), and interference with functioning (est. = -0.70, P = .022) (adjusted for age, sex, surgical technique, and neoadjuvant chemotherapy status). CONCLUSIONS: These results suggest that ERAS practice significantly reduced immediate postoperative symptom burden in bladder cancer patients recovering from radical cystectomy, supporting the use of patient-reported symptom burden as an outcome measure in perioperative care.
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Cistectomía , Neoplasias de la Vejiga Urinaria/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Cistectomía/efectos adversos , Cistectomía/métodos , Cistectomía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/epidemiologíaRESUMEN
To fully deploy the potential of semiconductor nanocrystal films as low-cost electronic materials, a better understanding of the amount of dopants required to make their conductivity metallic is needed. In bulk semiconductors, the critical concentration of electrons at the metal-insulator transition is described by the Mott criterion. Here, we theoretically derive the critical concentration nc for films of heavily doped nanocrystals devoid of ligands at their surface and in direct contact with each other. In the accompanying experiments, we investigate the conduction mechanism in films of phosphorus-doped, ligand-free silicon nanocrystals. At the largest electron concentration achieved in our samples, which is half the predicted nc, we find that the localization length of hopping electrons is close to three times the nanocrystals diameter, indicating that the film approaches the metal-insulator transition.
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Conductividad Eléctrica , Nanopartículas del Metal/química , Semiconductores , Membranas Artificiales , Nanotecnología/métodos , Tamaño de la Partícula , Fósforo/química , Silicio/químicaRESUMEN
A novel fluorescent probe-based real-time reverse transcription recombinase polymerase amplification (real-time RT-RPA) assay was developed for rapid detection of highly pathogenic type 2 porcine reproductive and respiratory syndrome virus (HP-PRRSV). The sensitivity analysis showed that the detection limit of RPA was 70 copies of HP-PRRSV RNA/reaction. The real-time RT-RPA highly specific amplified HP-PRRSV with no cross-reaction with classic PRRSV, classic swine fever virus, pseudorabies virus, and foot-and-mouth disease virus. Assessment with 125 clinical samples showed that the developed real-time RT-RPA assay was well correlated with real-time RT-qPCR assays for detection of HP-PRRSV. These results suggest that the developed real-time RT-RPA assay is suitable for rapid detection of HP-PRRSV.