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Introduction. Helicobacter pylori infection is a major global health concern, linked to the development of various gastrointestinal diseases, including gastric cancer. To study the pathogenesis of H. pylori and develop effective intervention strategies, appropriate animal pathogen models that closely mimic human infection are essential.Gap statement. This study focuses on the understudied hpEastAsia genotype in Southeast Asia, a region marked by a high H. pylori infection rate. No mouse-adapted model strains has been reported previously. Moreover, it recognizes the urgent requirement for vaccines in developing countries, where overuse of antimicrobials is fuelling the emergence of resistance.Aim. This study aims to establish a novel mouse-adapted H. pylori model specific to the hpEastAsia genotype prevalent in Southeast Asia, focusing on comparative genomic and histopathological analysis of pathogens coupled with vaccine preclinical studies.Methodology. We collected and sequenced the whole genome of clinical strains of H. pylori from infected patients in Vietnam and performed comparative genomic analyses of H. pylori strains in Southeast Asia. In parallel, we conducted preclinical studies to assess the pathogenicity of the mouse-adapted H. pylori strain and the protective effect of a new spore-vectored vaccine candidate on male Mlac:ICR mice and the host immune response in a female C57BL/6 mouse model.Results. Genome sequencing and comparison revealed unique and common genetic signatures, antimicrobial resistance genes and virulence factors in strains HP22 and HP34; and supported clarithromycin-resistant HP34 as a representation of the hpEastAsia genotype in Vietnam and Southeast Asia. HP34-infected mice exhibited gastric inflammation, epithelial erosion and dysplastic changes that closely resembled the pathology observed in human H. pylori infection. Furthermore, comprehensive immunological characterization demonstrated a robust host immune response, including both mucosal and systemic immune responses. Oral vaccination with candidate vaccine formulations elicited a significant reduction in bacterial colonization in the model.Conclusion. Our findings demonstrate the successful development of a novel mouse-adapted H. pylori model for the hpEastAsia genotype in Vietnam and Southeast Asia. Our research highlights the distinctive genotype and pathogenicity of clinical H. pylori strains in the region, laying the foundation for targeted interventions to address this global health burden.
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Infecciones por Helicobacter , Helicobacter pylori , Vacunas , Humanos , Masculino , Femenino , Ratones , Animales , Infecciones por Helicobacter/microbiología , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Genotipo , Genómica , Asia Sudoriental/epidemiologíaRESUMEN
BACKGROUND: Helicobacter pylori infection remains a major public health threat leading to gastrointestinal illness and increased risk of gastric cancer. Mostly affecting populations in developing countries no vaccines are yet available and the disease is controlled by antimicrobials which, in turn, are driving the emergence of AMR. MATERIALS AND METHODS: We have engineered spores of Bacillus subtilis to display putative H. pylori protective antigens, urease subunit A (UreA) and subunit B (UreB) on the spore surface. Following oral dosing of mice with these spores, we evaluated immunity and colonization in animals challenged with H. pylori. RESULTS: Oral immunization with spores expressing either UreA or UreB showed antigen-specific mucosal responses (fecal sIgA) including seroconversion and hyperimmunity. Following challenge, colonization by H. pylori was significantly reduced by up to 1-log. CONCLUSIONS: This study demonstrates the utility of bacterial spores for mucosal vaccination to H. pylori infection. The heat stability and robustness of Bacillus spores coupled with their existing use as probiotics make them an attractive solution for either protection against H. pylori infection or potentially for therapy and control of active infection.
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Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Infecciones por Helicobacter/prevención & control , Vacunas Bacterianas , Ureasa/genética , Inmunización , Vacunación , Antígenos Bacterianos/genética , Esporas , Ratones Endogámicos BALB C , Anticuerpos AntibacterianosRESUMEN
Of the blue carbon sinks, mangroves have one of the highest organic matter (OM) storage capacities in their soil due to low mineralization processes resulting from waterlogging. However, mangroves are disappearing worldwide because of demographic increases. In addition to the loss of CO2 fixation, mangrove clearing can strongly affect soil characteristics and C storage. The objectives of the present study were to quantify the evolution of soil quality, carbon stocks and carbon fluxes after mangrove clearing. Sediment cores to assess physico-chemical properties were collected and in situ CO2 fluxes were measured at the soil-air interface in a mangrove of Northern Vietnam. We compared a Kandelia candel mangrove forest with a nearby zone that had been cleared two years before the study. Significant decrease of clay content and an increase in bulk density for the upper 35cm in the cleared zone were observed. Soil organic carbon (OC) content in the upper 35cm decreased by >65% two years after clearing. The quantity and the quality of the carbon changed, with lower carbon to nitrogen ratios, indicating a more decomposed OM, a higher content of dissolved organic carbon, and a higher content of inorganic carbon (three times higher). This highlights the efficiency of mineralization processes following clearing. Due to the rapid decrease in the soil carbon content, CO2 fluxes at sediment interface were >50% lower in the cleared zone. Taking into account carbonate precipitation after OC mineralization, the mangrove soil lost ~10MgOCha-1yr-1 mostly as CO2 to the atmosphere and possibly as dissolved forms towards adjacent ecosystems. The impacts on the carbon cycle of mangrove clearing as shown by the switch from a C sink to a C source highlight the importance of maintaining these ecosystems, particularly in a context of climate change.
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BACKGROUND: In Australia, 61.5 % of children aged 3-4 attend Early Childhood Education and Care (ECEC) programs. Children's experiences within these programs vary widely and impact directly on educational wellbeing and social development. Research has shown that higher quality programs enhance children's learning and developmental outcomes, foster social participation and have long-lasting effects on their productivity as adults. Quality matters, yet we do not know what components of ECEC result in a quality program. Effective Early Educational Experiences (E4Kids) is a 5-year longitudinal study designed to identify and assess the impact of mainstream ECEC programs and program components on children's learning, development, social inclusion and well-being. E4Kids sets out to measure quality ECEC; identify components that add value and positively impact children's outcomes; evaluate the effects of child, family, community and environment characteristics on programs; and provide evidence on how best to invest in ECEC. METHODS/DESIGN: E4Kids follows a sample of 2,494 children who have experienced a variety of approved care programs (long day care, kindergarten, family day care and occasional care), as well as 157 children who have not accessed such programs. Children are tracked to the first point of National Assessment Program - Literacy and Numeracy (NAPLAN) testing at Year 3. The study presents a multi-level design in which ECEC programs were sampled from two states - Queensland and Victoria - then randomly sampled from two greater metropolitan regions and two regional and remote locations. Parents, centre directors, educators and carers complete questionnaires to provide information on demographics and children's progress. Data collected also include the make-up and organisation of ECEC programs and schools children attended. The quality of adult-child interactions is directly assessed using the Classroom Assessment Scoring System (CLASS) and direct testing of children's cognitive abilities and achievements is undertaken over 3 years and linked with NAPLAN scores. DISCUSSION: Findings from the E4Kids study have the potential to influence the quality of ECEC available in Australia by providing up-to-date evidence on the impact of ECEC programs and program components to inform future policy decisions and research.
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Cuidado del Niño , Intervención Educativa Precoz , Australia , Desarrollo Infantil , Preescolar , Femenino , Humanos , Aprendizaje , Estudios Longitudinales , Masculino , Evaluación de Programas y Proyectos de Salud , Calidad de Vida , Conducta Social , Encuestas y CuestionariosRESUMEN
The attitudes of parents and students towards schooling are often considered to be important factors associated with students' educational outcomes. This article presents the process of constructing and calibrating two scales to measure the attitudes of students and parents in Vietnam, and then linking these two scales to compare the two groups. A set of items that covered both development and opportunity aspects of education was designed. After the items were trialled, a final version of 13 items was compiled. The two scales yielded scores that were shown to have logical, face, content and construct validity.