RESUMEN
OBJECTIVES: Adolescents and young adults are the main target population for human papillomavirus (HPV). The study aimed to investigate school students' HPV vaccination intentions and explore the contributing factors from a socio-ecological perspective. DESIGN: A questionnaire survey was conducted in three secondary schools and three colleges in China. SAMPLE: A total of 1756 students aged 14-22 years participated in this study. Among the 1756 participants, 182 students have received the HPV vaccine. For the remaining 1574 students, we analyzed their HPV vaccination intentions and the influencing factors. MEASUREMENTS: Survey items for sociodemographics, knowledge and awareness of HPV, sexual intercourse and sexual knowledge, subjective socioeconomic status, self-efficacy, eHealth literacy, perceived social support from family, and the availability of HPV vaccine information were measured. RESULTS: Only 182 (10.4%) had received the HPV vaccine among the 1756 participants. Among the remaining 1574 students, the majority of the students (1403, 89.1%) were willing to receive the HPV vaccine. Binary logistic regression analysis showed that students who were female, had lower self-efficacy, scored higher on sexual knowledge, believed vaccination preventing related diseases, worried about side effects after vaccination, thought oneself at risk of contracting HPV, had higher family support, knew the availability of the HPV vaccine in Mainland China from healthcare institutions, and with family residence in rural areas were more willing to receive the HPV vaccine. CONCLUSIONS: Students had high HPV vaccination intentions while had low vaccination rate. Intrapersonal, interpersonal and institutional or community factors predicted HPV vaccination intention. Public health nurses in communities and schools could target the modifiable factors to promote students' HPV vaccine uptake.
Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto Joven , Adolescente , Masculino , Intención , Infecciones por Papillomavirus/prevención & control , Estudios Transversales , Neoplasias del Cuello Uterino/prevención & control , Aceptación de la Atención de Salud , Vacunas contra Papillomavirus/uso terapéutico , China , Encuestas y Cuestionarios , Vacunación , Virus del Papiloma Humano , Conocimientos, Actitudes y Práctica en SaludRESUMEN
Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased ß-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.
RESUMEN
To investigate the intracellular mechanisms of seven Trp-containing peptides in clinically isolated multidrug-resistant Pseudomonas aeruginosa (MRPA0108). The results showed that the Trp-containing peptides had high antibacterial activity against the MRPA0108 strain, with minimal inhibitory concentration (MIC) values ranging from 6.25 to 25 µM. The peptides rapidly and completely killed the MRPA0108 at a concentration of 16 × MIC at 60-90 min. The Trp-containing peptides were found to penetrate the bacterial cell membrane and accumulate in the cells. A DNA gel retardation assay indicated that the peptides were able to bind with the genomic DNA of MRPA0108 cells; L5W exhibited a stronger DNA binding ability than that of the other peptides, and the ratio of peptide to DNA was 0.62/1. Next, the UV absorption spectrum of the DNA indicated that L5W interacted with the MRPA0108 genomic DNA and intercalated into the groove of the DNA molecule, resulting in loosening of the double-helical structure of the originally contracted DNA and leading to the occurrence of a hyperchromic effect. The circular dichroism spectrum suggested that I1W and L5W associated with the DNA via a trench combination mode resulting from the compact structure of the DNA double helix and reduction in ππ accumulation between base pairs. Furthermore, real-time quantitative PCR demonstrated that the Trp-containing peptides could downregulate the expression of DNA replication-initiating genes in MRPA0108 cells. MRPA0108 DNA may be a potential active target for the antimicrobial activity of Trp-containing peptides.
Asunto(s)
ADN/metabolismo , Diseño de Fármacos , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Triptófano , Pruebas de Sensibilidad Microbiana , Proteínas Citotóxicas Formadoras de Poros/metabolismoRESUMEN
Nosocomial infections caused by Pseudomonas aeruginosa are difficult to treat due to the low permeability of its outer membrane as well as to its remarkable ability to acquire further resistance to antibiotics. Chensinin-1b exhibited antibacterial activity against the tested multiple-drug-resistant bacteria with a MIC ranging between 1.56 and 50µM, except E. cloacae strain 0320 (MREC0320), P. fluorescens strain 0322 (MRPF0322) and E. aerogenes strain 0320 (MREA0320). However, the MIC (25µM) of chensinin-1b to multiple-drug-resistant P. aeruginosa strain (MRPA 0108) was 16-fold higher than that observed to P. aeruginosa susceptible strain CGMCC 1.860 (PA1860). Chensinin-1b was able to disturb the integration of the cytoplasmic membrane of PA1860 and MRPA0108 cells similarly, but the outer membrane permeability of MRPA0108 cells was significantly lower. This low permeability was associated with increased expression of lipopolysaccharide (LPS) in the outer membrane and a decrease in negatively charged phospholipids in the outer membrane leaflet. In addition, the biofilm of MRPA0108 was responsible for the reduced susceptibility to chensinin-1b. A higher concentration of chensinin-1b (12.5µM) was required to maximally inhibit the formation of MRPA0108 biofilm. Notably, chensinin-1b inhibited the formation of MRPA0108 biofilm at concentrations below its MIC value by down-regulating the level of PelA, algD, and PslA gene transcription. Importantly, chensinin-1b had a significant antibacterial effect against MRPA0108 in vivo. Administration of chensinin-1b to mice infected with MRPA 0108 significantly increased survival by 50-70%. Moreover, chensinin-1b reduced the production of pro-inflammatory mediators and correspondingly reduced lung and liver tissue damage in the mouse model of septic shock induced by MRPA 0108. Collectively, these results suggest that chensinin-1b could be an effective antibiotic against multiple-drug-resistant bacterial strains.