620 research outputs found

    Bacterial-epithelial contact is a key determinant of host innate immune responses to enteropathogenic and enteroaggregative escherichia coli

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    Background: Enteropathogenic (EPEC) and Enteroaggregative (EAEC) E. coli have similar, but distinct clinical symptoms and modes of pathogenesis. Nevertheless when they infect the gastrointestinal tract, it is thought that their flagellin causes IL-8 release leading to neutrophil recruitment and gastroenteritis. However, this may not be the whole story as the effect of bacterial adherence to IEC innate response(s) remains unclear. Therefore, we have characterized which bacterial motifs contribute to the innate epithelial response to EPEC and EAEC, using a range of EPEC and EAEC isogenic mutant strains. Methodology: Caco-2 and HEp-2 cell lines were exposed to prototypical EPEC strain E2348/69 or EAEC strain O42, in addition to a range of isogenic mutant strains. E69 [LPS, non-motile, non-adherent, type three secretion system (TTSS) negative, signalling negative] or O42 [non-motile, non-adherent]. IL-8 and CCL20 protein secretion was measured. Bacterial surface structures were assessed by negative staining Transmission Electron Microscopy. The Fluorescent-actin staining test was carried out to determine bacterial adherence. Results: Previous studies have reported a balance between the host pro-inflammatory response and microbial suppression of this response. In our system an overall balance towards the host pro-inflammatory response is seen with the E69 WT and to a greater extent O42 WT, which is in fit with clinical symptoms. On removal of the external EPEC structures flagella, LPS, BFP, EspA and EspC; and EAEC flagella and AAF, the host inflammatory response is reduced. However, removal of E69 lymphostatin increases the host inflammatory response suggesting involvement in the bacterial mediated anti-inflammatory response. Conclusion: Epithelial responses were due to combinations of bacterial agonists, with host-bacterial contact a key determinant of these innate responses. Host epithelial recognition was offset by the microbe's ability to down-regulate the inflammatory response. Understanding the complexity of this host-microbial balance will contribute to improved vaccine design for infectious gastroenteritis

    A qualitative exploration of the barriers and enablers to supporting informal and familial carers within community pharmacies

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    Objectives: There are approximately 5.3 million informal carers in the United Kingdom, many of whom support family in their health despite being unpaid and often unsupported. Many visit pharmacies to collect medicines and look for advice. This work explores informal carer support within community pharmacies (CP). Methods: Semi-structured video interviews exploring perspectives on the role of CP in supporting carers were conducted in autumn 2022. The study received institutional ethical approval. Interviews were audio-recorded, transcribed verbatim, and analysed using a reflexive thematic approach. Key findings: In total 25 interviews were conducted with 13 carers and 12 pharmacy staff. Three themes were identified:-What support do carers need through CP?—medicines management, navigating services, and carers health and wellbeing.-Barriers to CP better supporting carers—relationships with CP, carer needs, identification as a ‘carer’.-Enablers to CP better supporting carers—support is a team effort, and CP as a community ‘hub’. Conclusions: There is a trusted relationships between carers and pharmacy staff which can contribute to establishing pharmacies as a safe space of support, this includes medicines-specific support and navigating services, but also carer health and wellbeing support. Pharmacy staff may need to reconsider approaches to identifying and supporting carers and not just treating them as an extension of supporting a patient. In making this support accessible, relationships with pharmacy staff are important, as well as embracing CP as a ‘community hub’, although pharmacy staff may need training and information to facilitate them in this role

    Relationship Between Quality Time, Conscientiousness, and Relationship Satisfaction

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    Relationships are challenging, but can the key to relationship satisfaction boil down to understanding your partner\u27s expression of love or simply spending more time together? Quality time, one of the five love languages, has been found to be the most common love language (Mostova et al., 2022). The love language of quality time has previously been associated with higher levels of conscientiousness, a big five personality trait positively correlated with feelings of love, intimacy, and passion (Surijah & Sari, 2018; Engel et al., 2002). The purpose of the present study is to investigate the relationship between levels of conscientiousness and quality time as well as levels of conscientiousness and relationship satisfaction. In the present study, we hypothesize that there will be a positive correlation between the conscientiousness score and relationship satisfaction as well as a positive correlation between the conscientiousness score and quality time score. This study uses a correlational design where 40 undergraduate students were asked to complete the Big Five Personality inventory, the Love Language Assessment, and a relationship satisfaction survey in a randomized order. The participants were asked to take the relationship satisfaction survey regarding their current romantic relationship if they were in one, or regarding a close friend if they were not. The proposed results of this study indicate a positive correlation between a participant’s conscientiousness score and their quality time score and a positive correlation between the conscientiousness score and relationship satisfaction. The results of this study can help individuals better understand personality variables and patterns of behavior that can correlate with their romantic relationship satisfaction. This study can help individuals know what qualities to look for in a romantic partner or encourage behaviors, such as spending more time together, that may increase relationship satisfaction overall

    Further evidence for fungivory in the Lower Devonian (Lochkovian) of the Welsh Borderland, UK

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    The recent demonstrations that widespread mid-Palaeozoic Prototaxites and other nematophytes had fungal affinities indicate that terrestrial fungi were important elements in carbon cycling in the Early Devonian. Here, we provide evidence for their participation in the recycling of nutrients by early terrestrial invertebrates. Evidence is in the form of coprolites, both those associated with nematophytes or containing their fragmentary remains. Cylindrical coprolites consistently associated with fungal mats are placed in a new ichnospecies, Bacillafaex myceliorum. Their contents are granular to amorphous, suggestive of complete digestion of the ingested hyphae, with the inference of possession of chitinases in the digestive tracts of the consumers. A further single example comprises a cluster of cylindrical bodies attached to the lower surface of a Nematothallus fragment. Here, homogenisation was less complete, with traces of hyphae remaining. Terrestrial animal fossils have not been found at the locality, but scorpions, pseudoscorpions, Opiliones, mites, centipedes (carnivores) and millipedes, and Collembola (detritivores) have been recorded from the slightly younger Rhynie cherts. Studies of fungivory in extant arthropods have concentrated on Collembola and, to a lesser extent, mites, but their faecal pellets are much smaller than the fossil examples. Millipedes, based on body size and faeces of extant forms, are considered more realistic producers, but little is known about fungal feeding in these animals. Regardless of the affinities of the producers, the diversity in morphology, sizes, aggregations, and composition of nematophyte-containing examples suggests that fungivory was an important component of carbon cycling in early terrestrial ecosystems

    A novel HRAS c.466C>T p.(Phe156Leu) variant in two patients with attenuated features of Costello syndrome

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    Costello syndrome (CS) is caused by heterozygous HRAS germline mutations. Most patients share the HRAS variant p.Gly12Ser that is associated with a typical, homogeneous phenotype. Rarer pathogenic HRAS variants (e.g., p.Thr56Ile) were identified in individuals with attenuated CS phenotypes. The obvious phenotypical variability reflects different dysfunctional consequences of distinct HRAS variants. We report on two boys with the novel de novo HRAS variant c.466 C > T p.(Phe156Leu). Both had severe feeding difficulties, airway obstruction and developmental delay, which are typical findings in CS. They showed subtle facial and dermatologic features consistent with attenuated CS. They significantly differed in their musculoskeletal, cardiovascular and endocrinologic manifestations underscoring the clinical variability of individuals with identical, in particular rarer pathogenic HRAS variants. Functional studies revealed enhanced effector-binding, increased downstream signaling activation and impaired growth factor-induced signaling dynamics in cells expressing HRASPhe156Leu. Our data further illustrate the molecular and phenotypic variability of CS

    Strategies for Systems Change: Lessons Learned from the Transforming Early Educator Lead Teacher Preparation Programs Through Multi-Partner Innovation Grant Program

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    In 2021–22, The Collaborative awarded eight grants in support of partnerships between institutions of higher education (IHEs) and states/territories/tribal nations to transform their preparation programs for early educators. To support our grantees in their work, The Collaborative engaged School Readiness Consulting (SRC) to develop a learning community to foster peer learning and collective problem-solving.Two years into this work, The Collaborative and SRC provided grantees with an opportunity to reflect on their experiences through the lens of an overarching question: How have the IHEs and their partners made meaningful, systemic changes to address barriers on their campuses, in their communities, and in the field at large?This report describes the strategies grantees used for systems change, as well as their reflections on next steps and sustainability.Key insights from the report include:Grantees readily leveraged policies, practices, and resources to create immediate and measurable impacts on their institutions and their students. Strategies include centering equity in student recruitment and retention, enhancing coursework offerings and strengthening classes related to culturally relevant practices, and investing in resources driven by the actual needs of their students.In addition, grantees identified strategies to create the conditions needed to maintain progress and enable further changes to best support their students. These strategies include strengthening and creating connections, shifting power dynamics, and changing mental models
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