Developing a Nasal Organotypic Model to Investigate the Effects of the Nasal Microbiome on Susceptibility to Pathogens

The microbiota is essential to the functioning of the immune system. The nasal milieu secretes immune molecules that can be influenced by diverse bacteria. Hence commensals that enhance anti-viral responses may confer resistance to respiratory viral infection. Our collaborators have identified 7 microbial state types (CST) defined by indicator species in the nose and recently, through analyses of nasal immune molecules, we have categorized the nasal immune profile types into 8 groups (IPT). Although the IPTs correlated with certain CSTs, the influence of the nasal microbiome on susceptibility to respiratory pathogens is still unknown. Defining this complex relationship requires a relevant in vitro model which recapitulates key aspects of the in vivo nasal epithelium (pseudostratification, mucociliary differentiation), can sustain stable bacterial communities in a relevant environment (air-interfaced), and can support infection with respiratory pathogens (e.g., Staphylococcus aureus, influenza, SARS-CoV-2). Conventionally cultured cells lack innate protective features such as mucus and cilia and do not express physiological levels of innate immune mediators or pathogen entry receptors. These epithelial characteristics are crucial to reconstruct the complexity of microbiome-host-pathogen interactions in a controlled in vitro model. We have previously developed a nasal model capable of being infected by SARS-CoV-2, however due to variability in the source of cells, maintenance of culture consistency was difficult to achieve. Some obstacles included nonviable cells at isolation, fibroblast contaminations, and early death of differentiated cells. Hypothesis: In this study, we aim to optimize our current nasal model to provide consistent cell cultures to support bacterial co-cultures and SARS-CoV-2 infection studies

Never Give Up: Take Charge of Your Life, School, and Community Before It’s Too Late

Victor Woods will share many heartfelt life lessons learned from his journey during his middle-class upbringing with two college-educated parents—his mother, a school teacher—to a troubled childhood, which led to him to two prison terms. This session will concentrate on how Victor turned his life around and became a published author at Simon & Schuster. Victor’s life story is currently in production with Warner Bros. Studios in Hollywood. He will share his philosophy of “never giving up on yourself, students, and family members.” Victor’s message is clear: there is something special in everyone, sometimes we just have to look a little harder to find it. School systems, cities, and communities are failing because, in many instances, people have simply given up hope

Never Give Up: Take Charge of Your Life, School, and Community Before It’s Too Late

Victor Woods will share many heartfelt life lessons learned from his journey during his middle-class upbringing with two college-educated parents—his mother, a school teacher—to a troubled childhood, which led to him to two prison terms. This session will concentrate on how Victor turned his life around and became a published author at Simon & Schuster. Victor’s life story is currently in production with Warner Bros. Studios in Hollywood. He will share his philosophy of “Never Giving Up on Yourself, Students, and Family Members.” Victor’s message is clear: there’s something special in everyone, sometimes we just have to look a little harder to find it. School systems, cities, and communities are failing because, in many instances, people have simply given up hope

PROBLEMS ASSOCIATED WITH EFFECTIVE PROVISION OF INFORMATION ON AGRICULTURAL INSURANCE TO RURAL FARMERS FOR CLIMATE CHANGE ADAPTATION.

Information provision and adult literacy on Agricultural insurance is very vital in facilitating rural farmer’s change of behavior and adjustment to climate change adaptation. Majority of rural farmers in Enugu State, Nigeria is mostly illiterate, found in rural communities and are mainly dependent on rain-fed agriculture and with low level of educational development and thus require agricultural information and adult literacy on Agricultural insurance to be able to adapt to the never-ending climate change. However, there are problems facing Information provision and adult literacy on Agricultural insurance to rural farmers for climate change adaptation. This study therefore identified some of the constraints to information agents and rural farmers in Enugu State, Nigeria. A multistage sampling procedure was used in selecting five hundred and ten respondents for the study. Data collected with questionnaire and focus group discussion were analyzed using descriptive statistics. The data gathered from the focus group discussion were also analyzed qualitatively using summaries and consensus of respondents’ views. Findings from the study show that the problems include lack of rural infrastructure, illiteracy, lack of rural information centers, lack of trained extension agents etc. The study recommended that weather forecast information should be published and made available to the farmers through agricultural extension agents. Rural farmers should be educated on different insurance plans to enable them adapt easily to climate change etc

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Implementation, Validation and Profiling of a Genetic Algorithm for Molecular Conformational Optimization

Prediction of the lowest energy conformation of a protein chain is a challenging optimization problem in computational chemistry and biology. Simple lattice-based protein models have been shown to be effective representations of the characteristics of proteins important in protein folding. An effective genetic algorithm for conformational optimization of proteins represented by the hydrophobic-hydrophillic lattice model was recently published. In this work, we create a publically available implementation of this genetic optimization algorithm. Tests of our implementation show equivalent performance to that reported for the original, in terms of both optimal conformation and number of function evaluations. In addition, we test our implementation across a range of data set sizes to characterize the performance of the algorithm as chain length increases: benchmarking that is necessary for future optimization and parallelization of the algorithm

Survey of rehabilitation support for children 0-15 years in a rural part of Kenya

Abstract Purpose: Information regarding the nature, availability and distribution of rehabilitation services for children with disabilities across developing countries is scarce, and data that do exist are of variable quality. If planning and development are to progress, information about service provision is vital. The aim was to establish the scope and nature of rehabilitation support available to children with disabilities (0-15 years) and their families in rural Kenya. Method: A comprehensive sample comprising service provision in the health and special education sectors was established. Non-governmental and community-based organisations were also included. A survey of rehabilitation services was conducted through examination of service-related documentation and key informant interviews with the heads of services. Results: Rehabilitation comprised hospital-based occupational therapy, physiotherapy and orthopaedic technology; and seven special education establishments plus an education assessment resource centre. There was one non-government organisation and one community-based organisation relevant to children with disabilities. Activities focused on assessment, diagnosis and raising community awareness. Provision was challenged by inadequate staffing, resources and transport. Government funding was supplemented variously by donations and self-sufficiency initiatives. Rehabilitation approaches appeared to be informed by professional background of practitioner, rather than the needs of child. Service documentation revealed use of inconsistent recording methods. Conclusions: The data highlight the challenges of rehabilitation, demanding greater investment in personnel and their training, more material resources, improved access to the community and better recording mechanisms. Implications for Rehabilitation There needs to be greater investment in rehabilitation provision in developing countries. Consideration of community-based initiatives is required to support better access for all. In order to argue the case for improved resources, better skills and mechanisms for recording, monitoring and evaluating practice are needed

Role of macrophage sialoadhesin in host defense against the sialylated pathogen group B <em>Streptococcus</em>

ABSTRACT: Several bacterial pathogens decorate their surfaces with sialic acid (Sia) residues within cell wall components or capsular exopolysaccharides. Sialic acid expression can promote bacterial virulence by blocking complement activation or by engagement of inhibitory sialic acid-binding immunoglobulin-like lectins (Siglecs) on host leukocytes. Expressed at high levels on splenic and lymph node macrophages, sialoadhesin (Sn) is a unique Siglec with an elongated structure that lacks intracellular signaling motifs. Sialoadhesin allows macrophage to engage certain sialylated pathogens and stimulate inflammatory responses, but the in vivo significance of sialoadhesin in infection has not been shown. We demonstrate that macrophages phagocytose the sialylated pathogen group B Streptococcus (GBS) and increase bactericidal activity via sialoadhesin-sialic-acid-mediated recognition. Sialoadhesin expression on marginal zone metallophillic macrophages in the spleen trapped circulating GBS and restricted the spread of the GBS to distant organs, reducing mortality. Specific IgM antibody responses to GBS challenge were also impaired in sialoadhesin-deficient mice. Thus, sialoadhesin represents a key bridge to orchestrate innate and adaptive immune defenses against invasive sialylated bacterial pathogens. KEY MESSAGE: Sialoadhesin is critical for macrophages to phagocytose and clear GBS. Increased GBS organ dissemination in the sialoadhesin-deficient mice. Reduced anti-GBS IgM production in the sialoadhesin-deficient mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00109-014-1157-y) contains supplementary material, which is available to authorized users

implications for first line treatment recommendations

Introduction: Treatment for All recommendations have allowed access to antiretroviral (ARV) treatment for an increasing number of patients. This minimizes the transmission of infection but can potentiate the risk of transmitted (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed up in Portuguese hospitals between 2001 and 2017. Methods: In total, 11,911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutation according to the WHO surveillance list. Genotypic resistance to ARV was evaluated with Stanford HIVdb v7.0. Patterns of TDR, ADR and the prevalence of mutations over time were analyzed using logistic regression. Results and Discussion: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (p < 0.001). This was due to a significant increase in both resistance to nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleotide reverse transcriptase inhibitors (NNRTIs), from 5.6% to 6.7% (p = 0.002) and 2.9% to 8.9% (p < 0.001), respectively. TDR was associated with infection with subtype B, and with lower viral load levels (p < 0.05). The prevalence of ADR declined from 86.6% in 2001 to 51.0% in 2017 (p < 0.001), caused by decreasing drug resistance to all antiretroviral (ARV) classes (p < 0.001). Conclusions: While ADR has been decreasing since 2001, TDR has been increasing, reaching a value of 13.1% by the end of 2017. It is urgently necessary to develop public health programs to monitor the levels and patterns of TDR in newly diagnosed patients.publishersversionpublishe

Solving the Simplest Theory of Quantum Gravity

We solve what is quite likely the simplest model of quantum gravity, the worldsheet theory of an infinitely long, free bosonic string in Minkowski space. Contrary to naive expectations, this theory is non-trivial. We illustrate this by constructing its exact factorizable S-matrix. Despite its simplicity, the theory exhibits many of the salient features expected from more mature quantum gravity models, including the absence of local off-shell observables, a minimal length, a maximum achievable (Hagedorn) temperature, as well as (integrable relatives of) black holes. All these properties follow from the exact S-matrix. We show that the complete finite volume spectrum can be reconstructed analytically from this S-matrix with the help of the thermodynamic Bethe Ansatz. We argue that considered as a UV complete relativistic two-dimensional quantum field theory the model exhibits a new type of renormalization group flow behavior, "asymptotic fragility". Asymptotically fragile flows do not originate from a UV fixed point.Comment: 32+4 pages, 1 figure, v2: typos fixed, published versio