RESUMO
Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses have caused large outbreaks within avian populations on five continents, with concurrent spillover into a variety of mammalian species. Mutations associated with mammalian adaptation have been sporadically identified in avian isolates, and more frequently among mammalian isolates following infection. Reports of human infection with A(H5N1) viruses following contact with infected wildlife have been reported on multiple continents, highlighting the need for pandemic risk assessment of these viruses. In this study, the pathogenicity and transmissibility of A/Chile/25945/2023 HPAI A(H5N1) virus, a novel reassortant with four gene segments (PB1, PB2, NP, MP) from North American lineage, isolated from a severe human case in Chile, was evaluated in vitro and using the ferret model. This virus possessed a high capacity to cause fatal disease, characterized by high morbidity and extrapulmonary spread in virus-inoculated ferrets. The virus was capable of transmission to naïve contacts in a direct contact setting, with contact animals similarly exhibiting severe disease, but did not exhibit productive transmission in respiratory droplet or fomite transmission models. Our results indicate that the virus would need to acquire an airborne transmissible phenotype in mammals to potentially cause a pandemic. Nonetheless, this work warrants continuous monitoring of mammalian adaptations in avian viruses, especially in strains isolated from humans, to aid pandemic preparedness efforts.
Assuntos
Furões , Virus da Influenza A Subtipo H5N1 , Influenza Humana , Infecções por Orthomyxoviridae , Animais , Furões/virologia , Humanos , Chile , Influenza Humana/virologia , Influenza Humana/transmissão , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/transmissão , Infecções por Orthomyxoviridae/veterinária , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/patogenicidade , Virus da Influenza A Subtipo H5N1/isolamento & purificação , Virus da Influenza A Subtipo H5N1/classificação , Virus da Influenza A Subtipo H5N1/fisiologia , Vírus Reordenados/genética , Vírus Reordenados/isolamento & purificação , Vírus Reordenados/patogenicidade , Vírus Reordenados/classificação , Filogenia , Influenza Aviária/virologia , Influenza Aviária/transmissãoRESUMO
Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Biomarcadores , Criança , Humanos , ProteômicaRESUMO
Respiratory syncytial virus (RSV) infection is the main cause of lower respiratory tract infection in children. However, there is no effective treatment for RSV infection. Here, we aimed to identify potential biomarkers to aid in the treatment of RSV infection. Children in the acute and convalescence phases of RSV infection were recruited and proteomic analysis was performed to identify differentially expressed proteins (DEPs). Subsequently, promising candidate proteins were determined by functional enrichment and protein-protein interaction network analysis, and underwent further validation by western blot both in clinical and mouse model samples. Among the 79 DEPs identified in RSV patient samples, 4 proteins (BPGM, TPI1, PRDX2, and CFL1) were confirmed to be significantly upregulated during RSV infection. Functional analysis showed that BPGM and TPI1 were mainly involved in glycolysis, indicating an association between RSV infection and the glycolysis metabolic pathway. Our findings provide insights into the proteomic profile during RSV infection and indicated that BPGM, TPI1, PRDX2, and CFL1 may be potential therapeutic biomarkers or targets for the treatment of RSV infection.
Assuntos
Humanos , Criança , Vírus Sincicial Respiratório Humano , Infecções por Vírus Respiratório Sincicial , Biomarcadores , ProteômicaRESUMO
INTRODUCTION: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. OBJECTIVE: To investigate the rate and mechanism of macrolide resistance in Yantai. METHODS: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. RESULTS: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. CONCLUSIONS: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai.
INTRODUCCIÓN: Neumonía adquirida por en la comunidad (NAC) es una enfermedad responsable por un gran número de muertes y un impacto económico importante. Debido a que el diagnostico incrementó la sensibilidad, se cambió la etiología de la NAC. Adicionalmente, Mycoplasma pneumoniae es uno de los patógenos que causan la NAC. Los macrólidos y antibióticos relacionados son la primera línea de tratamiento para M. pneumoniae. La resistencia a macrólidos se aumentó en los últimos 15 años y ahora se encuentra distribuido en todo el mundo. Nosotros realizamos el primer estudio de resitencia a M. pneumoniae a los macrólidos en Yantai. Esto podría ser útil para determinar una terapia apropiada para NAC en esta población. OBJETIVO: Investigar la tasa y el mecanismo para la resitencia a los macrólidos en Yantai. MÉTODOS: Se colectaron muestras faringeas usando un hisopo. Las muestras se analizaron mediante la reacción en cadena de la polimerasa (PCR) y por cultivo para M. pneumoniae. Se uso una PCR anidad para amplificar fragmentos del gen 23S rRNA especifico con las mutaciones para M. pneumoniae. Se analizaron amplicomes por CE-SSCP para determinar la resitencia a los macrólidos. Estos resultados se confirmaron por secuenciación. Se aislaron 27 cepas de M. pneumoniae y se probaron nueve antibióticos in vitro. RESULTADOS: De 128 muestras, 27 fueron positivas para M. pneumoniae. Se determinó una resistencia a macrólidos por Mycoplasma del 100%. Los mecanismos de esta resitencia fue una mutacion punctual A2063G en la secuencia que se une directamente a los macrólidos en el dominio 23S rRNA V in vitro. El tiempo piotolítico medio para el grupo de fluoroquinolonas fue 4.7 ±2.9 d, que fue significativamente más corto que para el grupo de azitromicina: 8.2 ±4.1 d. CONCLUSIONES: Los macrólidos no son la primera linea de tratamiento para las infecciones del tracto respiratorio contra M. pneumoniae respiratory tract infections en Yantai.
Assuntos
Antibacterianos/farmacologia , Infecções Comunitárias Adquiridas/epidemiologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/epidemiologia , Adolescente , Adulto , Idoso , China/epidemiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Macrolídeos/farmacologia , Masculino , Pessoa de Meia-Idade , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/microbiologia , Mutação Puntual , Reação em Cadeia da Polimerase , Adulto JovemRESUMO
Abstract Introduction: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. Objective: To investigate the rate and mechanism of macrolide resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. Results: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. Conclusions: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai.
Resumen Introducción: Neumonía adquirida por en la comunidad (NAC) es una enfermedad responsable por un gran número de muertes y un impacto económico importante. Debido a que el diagnostico incrementó la sensibilidad, se cambió la etiología de la NAC. Adicionalmente, Mycoplasma pneumoniae es uno de los patógenos que causan la NAC. Los macrólidos y antibióticos relacionados son la primera línea de tratamiento para M. pneumoniae. La resistencia a macrólidos se aumentó en los últimos 15 años y ahora se encuentra distribuido en todo el mundo. Nosotros realizamos el primer estudio de resitencia a M. pneumoniae a los macrólidos en Yantai. Esto podría ser útil para determinar una terapia apropiada para NAC en esta población. Objetivo: Investigar la tasa y el mecanismo para la resitencia a los macrólidos en Yantai. Métodos: Se colectaron muestras faringeas usando un hisopo. Las muestras se analizaron mediante la reacción en cadena de la polimerasa (PCR) y por cultivo para M. pneumoniae. Se uso una PCR anidad para amplificar fragmentos del gen 23S rRNA especifico con las mutaciones para M. pneumoniae. Se analizaron amplicomes por CE-SSCP para determinar la resitencia a los macrólidos. Estos resultados se confirmaron por secuenciación. Se aislaron 27 cepas de M. pneumoniae y se probaron nueve antibióticos in vitro. Resultados: De 128 muestras, 27 fueron positivas para M. pneumoniae. Se determinó una resistencia a macrólidos por Mycoplasma del 100%. Los mecanismos de esta resitencia fue una mutacion punctual A2063G en la secuencia que se une directamente a los macrólidos en el dominio 23S rRNA V in vitro. El tiempo piotolítico medio para el grupo de fluoroquinolonas fue 4.7 ±2.9 d, que fue significativamente más corto que para el grupo de azitromicina: 8.2 ±4.1 d. Conclusiones: Los macrólidos no son la primera linea de tratamiento para las infecciones del tracto respiratorio contra M. pneumoniae respiratory tract infections en Yantai.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Pneumonia por Mycoplasma/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Antibacterianos/farmacologia , Mycoplasma pneumoniae/isolamento & purificação , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , China/epidemiologia , Reação em Cadeia da Polimerase , Mutação Puntual , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Macrolídeos/farmacologia , Farmacorresistência Bacteriana/genéticaRESUMO
Abstract Objective This study aimed to determine the differences in learning style preferences among bachelor degree nursing students at Central South University and associate degree nursing students at the Vocational Health School in China. Methods This study was a cross-sectional survey using the Chinese version of the VARK questionnaire to assess preferred learning styles: 159 enrolled bachelor degree nursing students and 199 enrolled associate degree nursing students completed the questionnaire with a response rate of 96.8%. Results The bachelor degree nursing students tend to prefer a multimodal learning style (58.49%), which significantly differed from that of associate degree nursing students (45.77%). The kinaesthetic modality was the predominant unimodal learning style among the bachelor degree and associate degree nursing students (18.20% and 33.67%), and the read-write modality was the least popular modality (2.5% and 4.02%). Conclusion There are both differences and similarities between the learning style preferences of bachelor degree and associate degree nursing students. Educational background is one of the most critical factors that influence the learning style preference of nursing students. This finding may be necessary and beneficial for carrying out future curricula reform. In addition, further comprehensive research should be conducted to examine the relationships between learning style preferences and academic performance, as well as learning style preferences and teaching methods.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Adulto Jovem , Estudantes de Enfermagem , Ensino , Inquéritos e Questionários , Bacharelado em Enfermagem , Aprendizagem , China , Estudos TransversaisRESUMO
OBJECTIVES: The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. METHODS: A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. RESULTS: There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. CONCLUSIONS: It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications.
Assuntos
Articulação Atlantoaxial/lesões , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Luxações Articulares/cirurgia , Procedimentos Ortopédicos/instrumentação , Adulto , Placas Ósseas , Cadáver , Desenho de Equipamento , Estudos de Viabilidade , Humanos , Imageamento Tridimensional , Fixadores Internos , Ilustração Médica , Procedimentos Ortopédicos/métodos , Valores de Referência , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. METHODS: A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. RESULTS: There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. CONCLUSIONS: It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications. .
Assuntos
Adulto , Humanos , Articulação Atlantoaxial/lesões , Parafusos Ósseos , Vértebras Cervicais/cirurgia , Luxações Articulares/cirurgia , Procedimentos Ortopédicos/instrumentação , Placas Ósseas , Cadáver , Desenho de Equipamento , Estudos de Viabilidade , Imageamento Tridimensional , Fixadores Internos , Ilustração Médica , Procedimentos Ortopédicos/métodos , Valores de Referência , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios XRESUMO
H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry.