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Influenza A virus causes numerous deaths and infections worldwide annually. Therefore, we have considered nanobodies as a potential treatment for patients with severe cases of influenza. We developed a nanobody that was expected to have protective efficacy against the A/California/04/2009 (CA/04; pandemic 2009 flu strain) and evaluated its therapeutic efficacy against CA/04 in mice experiments. This nanobody was derived from the immunization of the alpaca, and the inactivated CA/04 virus was used as an immunogen. We successfully generated a nanobody library through bio-panning, phage ELISA, and Bio-layer interferometry. Moreover, we confirmed that administering nanobodies after lethal doses of CA/04 reduced viral replication in the lungs and influenza-induced clinical signs in mice. These research findings will help to develop nanobodies as viral therapeutics for CA/04 and other infectious viruses.
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Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Anticuerpos de Dominio Único , Animales , Anticuerpos de Dominio Único/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Ratones , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/tratamiento farmacológico , Infecciones por Orthomyxoviridae/virología , Femenino , Ratones Endogámicos BALB C , Camélidos del Nuevo Mundo/inmunología , Pulmón/inmunología , Pulmón/virología , Pulmón/efectos de los fármacos , Pulmón/patología , Anticuerpos Antivirales/inmunología , Replicación Viral/efectos de los fármacosRESUMEN
The various strains of influenza virus cause respiratory symptoms in humans every year and annual vaccinations are recommended. Due to its RNA-type genes and segmented state, it belongs to a virus that mutates frequently with antigenic drift and shift, giving rise to various strains. Each year, the World Health Organization identifies the epidemic strains and operates a global surveillance system to suggest the viral composition for the influenza vaccine. Influenza viruses, which have multiple viral strains, are produced in the format of multivalent vaccine. However, the multivalent vaccine has a possibility of causing immune interference by introducing multiple strain-specific antigens in a single injection. Therefore, evaluating immune interference phenomena is essential when assessing multivalent vaccines. In this study, the protective ability and immunogenicity of multivalent and monovalent vaccines were evaluated in mice to assess immune interference in the multivalent vaccine. Monovalent and multivalent vaccines were manufactured using the latest strain of the 2022-2023 seasonal influenza virus selected by the World Health Organization. The protective abilities of both types of vaccines were tested through hemagglutination inhibition test. The immunogenicity of multivalent and monovalent vaccines were tested through enzyme-linked immunosorbent assay to measure the cellular and humoral immunity expression rates. As a result of the protective ability and immunogenicity test, higher level of virus neutralizing ability and greater amount of antibodies in both IgG1 and IgG2 were confirmed in the multivalent vaccine. No immune interference was found to affect the protective capacity and immune responses of the multivalent vaccines.
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The infection status of zoonotic trematode metacercariae (ZTM) was investigated in total 568 freshwater fishes (19 species) from the irrigation canal of Togyo-jeosuji (Reservoir) in Cheorwon-gun, Gangwon-do, the Republic of Korea for 3 years (2018-2020). All fishes were examined using the artificial digestion method. The metacercariae of Clonorchis sinensis (CsMc) were detected in 180 (43.8%) out of 411 fish of positive species, and their infection intensity was 38 per fish infected (PFI). Especially, in 2 fish species, i.e., Pseudorasbora parva and Puntungia herzi, the prevalence was 82.1% and 31.3%, and the infection intensity with CsMc was 88 and 290 PFI, respectively. Metagonimus spp. metacercariae (MsMc) were found in 403 (74.1%) out of 544 fish of positive species, and their infection intensity was 62 PFI. In the pale chub, Zacco platypus, the prevalence of MsMc was 98.6%, and their infection intensity was 144 PFI. Centrocestus armatus metacercariae were detected in 171 (38.9%) out of 440 fish of positive species, and their infection intensity was 1,844 PFI. Echinostoma spp. metacercariae were found in 94 (19.6%) out of 479 fish of positive species, and their infection intensity was 3 PFI. Metorchis orientalis metacercariae were detected in 43 (29.3%) out of 147 fish of positive species, and their infection intensity was 4 PFI. By the present study, it has been confirmed that some species of ZTM, including CsMc and MsMc, are prevalent in fishes from the irrigation canal of Togyo-jeosuji in Cheorwon-gun, Gangwon-do, Korea.
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Enfermedades de los Peces , Trematodos , Infecciones por Trematodos , Animales , Enfermedades de los Peces/epidemiología , Peces , Metacercarias , República de Corea/epidemiología , Infecciones por Trematodos/epidemiología , Infecciones por Trematodos/veterinariaRESUMEN
Background: Monitoring and evaluation is vital in the quest to improve the quality of care and to reduce the morbidity and mortality of neonates in a resource-limited setting. Databases offer several advantages such as data on large cohorts of neonates and from multiple centres. Aim: To establish a minimal dataset neonatal database in Kigali, Rwanda and to assess the quality and timing of the data entry process. Secondary objectives were to describe survival rates and associated risk factors. Methods: A cross-sectional, observational study was undertaken at a tertiary hospital in Kigali, Rwanda. The Rwanda Neonatal Data Collection Form was designed specifically for the database, based on the Vermont-Oxford Network neonatal data-collection tool with locally relevant amendments. All admitted neonates were enrolled during the study period of 2011-2017 with ongoing data-collection. Infants were recruited and data collected prospectively and cross-checked retrospectively with the inclusion of basic data on neonates who were not initially recruited prospectively. Results: 3391 analysable cases were recruited: 1420 prospective and 1971 retrospective cases. Prospective data collection peaked at 90%. Data entry was not always complete with data-points left blank with only 21% having adequate data available (0-25% missing). All-cause mortality during the study period was 16% and annual mortality ranged from 12% to 24%. On multivariate analysis, place of birth (AOR 2.17), small-for-gestational-age (AOR 2.05) and gestational age were all positively associated with survival. Conclusions: An academic setting in a low- or middle-income country can create and maintain a neonatal database without funding and produce a wealth of actionable results. Throughout the process, there were considerable challenges which must be addressed if such a database is to be optimised, maintained and created in other clinical sites. Abbreviations: CHUK: Centre Hospitalier et Universitaire de Kigali (University Teaching Hospital of Kigali); CPAP: continuous positive airway pressure; HCP: Healthcare professional; HRH, Human Resources for Health Programme; LMIC: low- and middle-income countries; MeSH: Medical subject headings; MoH: Ministry of Health; NAR: Newborn admission record; QI: Quality improvement; REDCap: Research electronic data capture; RNDB: Rwanda neonatal database; RNDCF: Rwanda neonatal data collecion form; SGA: Small for gestational age; STROBE: Strengthening the reporting of observational studies in epidemiology; VON: The Vermont-Oxford Network.
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Bases de Datos Factuales , Mortalidad Infantil/tendencias , Estudios Transversales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de Riesgo , Rwanda , Análisis de Supervivencia , Centros de Atención TerciariaRESUMEN
Super-resolution (SR) has become more vital, because of its capability to generate high-quality ultra-high definition (UHD) high-resolution (HR) images from low-resolution (LR) input images. Conventional SR methods entail high computational complexity, which makes them difficult to be implemented for up-scaling of full-high-definition input images into UHD-resolution images. Nevertheless, our previous super-interpolation (SI) method showed a good compromise between Peak-Signal-to-Noise Ratio (PSNR) performances and computational complexity. However, since SI only utilizes simple linear mappings, it may fail to precisely reconstruct HR patches with complex texture. In this paper, we present a novel SR method, which inherits the large-to-small patch conversion scheme from SI but uses global regression based on local linear mappings (GLM). Thus, our new SR method is called GLM-SI. In GLM-SI, each LR input patch is divided into 25 overlapped subpatches. Next, based on the local properties of these subpatches, 25 different local linear mappings are applied to the current LR input patch to generate 25 HR patch candidates, which are then regressed into one final HR patch using a global regressor. The local linear mappings are learned cluster-wise in our off-line training phase. The main contribution of this paper is as follows: Previously, linear-mapping-based conventional SR methods, including SI only used one simple yet coarse linear mapping to each patch to reconstruct its HR version. On the contrary, for each LR input patch, our GLM-SI is the first to apply a combination of multiple local linear mappings, where each local linear mapping is found according to local properties of the current LR patch. Therefore, it can better approximate nonlinear LR-to-HR mappings for HR patches with complex texture. Experiment results show that the proposed GLM-SI method outperforms most of the state-of-the-art methods, and shows comparable PSNR performance with much lower computational complexity when compared with a super-resolution method based on convolutional neural nets (SRCNN15). Compared with the previous SI method that is limited with a scale factor of 2, GLM-SI shows superior performance with average 0.79 dB higher in PSNR, and can be used for scale factors of 3 or higher.
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Transparent conducting oxide (TCO) is widely used for the application of flat panel display like liquid crystal displays and plasma display panel. It is also applied in the field of touch panel, solar cell electrode, low-emissivity glass, defrost window, and anti-static material. Fluorine-doped tin oxide (FTO) thin films were fabricated by spray pyrolysis of ethanol-added FTO precursor solutions. FTO thin film by spray pyrolysis is very much investigated and normally formed at high temperature, about 500 degrees C. However, these days, flexible electronics draw many attentions in the field of IT industry and the research for flexible transparent conducting thin film is also required. In the industrial field, indium-tin oxide (ITO) film on polymer substrate is widely used for touch panel and displays. In this study, we investigated the possibility of FTO thin film formation at relatively low temperature of 250 degrees C. We found out that the control of volume of input precursor and exhaust gases could make it possible to form FTO thin film with a relatively low electrical resistance, less than 100 Ohm/sq and high optical transmittance about 88%.
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To produce supplementary cementitious materials from electric arc furnace (EAF) slags, FeO was reduced using a two-stage reduction process that included an Al-dross reduction reaction followed by direct carbon reduction. A decrease in FeO was observed on tapping after the first-stage reduction, and further reduction with a stirred carbon rod in the second-stage reduction resulted in final FeO content below 5wt%, which is compatible with cement clinker applications. The reduced electric arc furnace slags (REAFS) mixed with cement at a unit ratio exhibited physical properties comparable to those of commercialized ground granulated blast furnace slags (GGBFS). Confocal laser scanning microscopy (CLSM) was used to obtain fundamental information on the cooling characteristics and conditions required to obtain amorphous REAFS. REAFS can be applied in cement mixtures to achieve the hydraulic properties needed for commercial use.
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Materiales de Construcción/análisis , Incineración , Residuos Industriales/análisisRESUMEN
In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P < .001 and P < .001, respectively) but not during the clarithromycin phase (P = .099 and P = .090, respectively). Exposure to sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo.
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Depresores del Apetito/farmacocinética , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Claritromicina/farmacología , Ciclobutanos/farmacocinética , Inhibidores del Citocromo P-450 CYP3A , Oxidorreductasas N-Desmetilantes/antagonistas & inhibidores , Ticlopidina/análogos & derivados , Adulto , Depresores del Apetito/química , Hidrocarburo de Aril Hidroxilasas/genética , Clopidogrel , Estudios Cruzados , Ciclobutanos/sangre , Ciclobutanos/química , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP3A , Genotipo , Humanos , Masculino , Microsomas/metabolismo , Oxidorreductasas N-Desmetilantes/genética , Polimorfismo Genético , Estereoisomerismo , Ticlopidina/farmacología , Adulto JovenRESUMEN
PURPOSE: A high rate of sustained viral response (SVR) in Koreans with chronic hepatitis C (CHC) is related to a favorable IL28B genotype. We compared two dosing strategies for peginterferon alfa-2a in Koreans with CHC and defined the combined effect of polymorphisms and dosing on the virological response. METHODS: A total of 178 treatment-naïve patients with CHC genotype 1 were prospectively enrolled. All patients were randomly assigned to treatment with one of two peginterferon alfa-2a regimens: 180 µg per week for 48 weeks (full-dose group) or 180 µg per week during the first 12 weeks followed by 135 µg per week for the next 36 weeks (dose-reduction group). Polymorphisms related to IL28B, ITPA, C20orf194 and SLC29A1 were studied. RESULTS: SVR rates did not differ between the full-dose and dose-reduction groups (56.5 and 51.2 %, respectively, p = 0.474). The frequency of additional reductions of the peginterferon dose because of adverse events was higher in the full-dose group than in the dose-reduction group. SVR rates in patients homozygous for the IL28B major allele were higher than those in patients for the other IL28B alleles. For patients with unfavorable IL28B genotypes, SVR was less likely to be achieved in the dose-reduction group than in the full-dose group. CONCLUSIONS: In Koreans with HCV genotype 1, the virological response to treatment did not differ between a full dose and reduced dose (≥80 % of full dose) of peginterferon alfa-2a. However, in the patients with unfavorable IL28B genotypes, the full-dose treatment of peginterferon alfa-2a may be beneficial.
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OBJECTIVES: In the present study, we aimed to examine the anti-atopic properties of bile from the cat fish, Silurus asotus, to determine its possible use as a pharmaceutical product. METHODS: The anti-atopic activities of cat fish bile were examined in a non-cell antioxidant, in-vitro assay (splenocytes and mast cells) and a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like mouse model. RESULTS: The results of these experiments revealed that Silurus asotus bile (SAB) scavenges radicals and protects proteins from superoxide attacks, suggesting that SAB suppresses the T helper (Th) type 2-skewed immune response. Th1/Th2 mRNA cytokines (interleukin (IL)-2, interferon (IFN)-γ and IL-4) from mouse splenocytes were effectively inhibited, and the release of ß-hexosaminidase in RBL-2H3 mast cells was significantly suppressed by SAB. These results were supported by screening the Th1/Th2 cytokine mRNAs (IL-2, IFN-γ and IL-4) from lymph nodes in DNCB-treated mice. More dramatic results were observed in the histological changes at higher SAB concentrations (5%) compared to the therapeutic control, visualized using hematoxylin-eosin (H&E) staining. CONCLUSIONS: The results presented in this study suggest that SAB may provide functional advantages with regard to treating atopic dermatitis because of its antioxidant and immune-suppressive effects.
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Antioxidantes/uso terapéutico , Bilis , Productos Biológicos/uso terapéutico , Bagres , Dermatitis Atópica/terapia , Piel/efectos de los fármacos , Linfocitos T/metabolismo , Animales , Antioxidantes/farmacología , Productos Biológicos/farmacología , Terapias Complementarias , Citocinas/antagonistas & inhibidores , Citocinas/genética , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Dinitroclorobenceno , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/metabolismo , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Ratones Endogámicos BALB C , Carbonilación Proteica/efectos de los fármacos , ARN Mensajero/metabolismo , Piel/patología , Bazo/citología , Bazo/efectos de los fármacos , Bazo/metabolismo , Superóxidos/metabolismo , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th2/efectos de los fármacos , Células Th2/metabolismo , beta-N-Acetilhexosaminidasas/antagonistas & inhibidoresRESUMEN
Acne is a typical condition of adolescence and is caused by multi-factorial events including hormonal, microbiological and immunological mechanisms. Although there has been much debate about the direct involvement of bacteria, Propionibacterium acnes is now believed to contribute to the inflammatory stages of the condition, and thus initiate the inflamed lesion. The present study examined the anti-acne properties of the Selaginella involvens extract (SIE) in cell models. Primarily, SIE was not found to be cytotoxic under 50 microg/mL, and revealed the inhibitory effect on both nitric oxide (NO) production and iNOS/IL-1beta expression as well as the NO scavenging effect. The IL-1alpha and IL-8 cytokines, triggering the inflammatory acne response, were also inhibited in keratinocytes when stimulated with viable P. acnes. Furthermore, SIE was found to have an antioxidant effect in a dose-dependent manner in the hydroxyl radical-mediated oxidation test. Finally, it was found that SIE has non-antibiotic antimicrobial activity at a dose greater than 100 microg/mL on P. acnes. In conclusion, SIE may be a safe non-antibiotic anti-acne source in the therapeutic application of the treatment of acne development by reducing the chance of non-specific initiation and augmentation phase of the inflammatory response.