Biology subjects

Osborne, S.

Publications and source records attributed to Osborne, S..

4 recordsLinked to original sources

bioRxiv2023

Age-Associated Weaker Immunity to Coronaviruses is Characteristic of Children that Develop Multisystem Inflammatory Syndrome following SARS-CoV-2 Infection

We analyzed the antibody and cytokine responses of twenty-three patients with multisystem inflammatory syndrome of children (MIS-C) that appeared with a three-to-six-week delay following a mild or asymptomatic SARS-CoV-2 infection. These responses were compared to healthy convalescent pediatric COVID-19 patients approximately twenty-eight days after the onset of symptoms. Both groups had strong IgG responses to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, but the MIS-C patients had weaker antibody responses to certain epitopes in the SARS-CoV-2 S and N proteins and to the S and N proteins of endemic human coronaviruses (HCoV) compared to pediatric convalescent COVID patients. HCoV antibody reactivity was correlated with age. In contrast, MIS-C patients had elevated serum levels of several proinflammatory cytokines compared to convalescent COVID patients, including interleukins IL-6, IL-8, IL-18 and chemokines CCL2, CCL8, CXCL5, CXCL9 and CXCL10 as well as tumor necrosis factor alpha and interferon gamma. Moreover, many cytokine responses of MIS-C patients were positively correlated with antibody responses to the SARS-CoV-2 S, N, membrane and ORF3a proteins while pediatric convalescent COVID patient cytokine responses were more often negatively correlated with antibody responses to the S, N and ORF3a proteins of SARS-CoV-2.

immunology↗

bioRxiv2023

KinCytE- a Kinase to Cytokine Explorer to Identify Molecular Regulators and Potential Therapeutic Opportunities

Cytokines and chemokines are secreted proteins that regulate various biological processes, such as inflammation, immune response, and cell differentiation. Therefore, disruption of signaling pathways involving these proteins has been linked to a range of diseases, including cancer. However, targeting individual cytokines, chemokines, or their receptors is challenging due to their regulatory redundancy and incomplete understanding of their signaling networks. To transform these difficult-to-drug targets into a pharmacologically manageable class, we developed a web-based platform called KinCytE. This platform was designed to link the effects of kinase inhibitors, a well-established class of drugs, with cytokine and chemokine release and signaling networks. The resulting KinCytE platform enables users to investigate protein kinases that regulate specific cytokines or chemokines, generate a ranked list of FDA-approved kinase inhibitors that affect cytokine/chemokine activity, and explore and visualize cytokine signaling network thus facilitating drugging this challenging target class. KinCytE is freely accessible via https://atlas.fredhutch.org/kincyte.

systems biology↗

bioRxiv2019

The effectiveness and cost effectiveness of a hospital avoidance program in a residential aged care facility

BackgroundResidential aged care facility residents experience high rates of hospital admissions which are stressful, costly and often preventable.\n\nDesignProspective pre-post cohort study and decision model analysis\n\nInterventionA decision-support tool was implemented to enable nursing staff to detect, refer and quickly respond to early signals of a deteriorating resident. Advanced clinical skills training, new diagnostic equipment and guided support from clinical lead nurses and nurse practitioners was provided to support nursing staff in the delivery of appropriate sub-acute care.\n\nOutcome measuresRate of hospital admissions; length of stay; incremental cost per QALY; net monetary benefit.\n\nResultsThe hospital avoidance program was associated with a 19% reduction in annual hospital admissions and a 31% reduction in the average length of stay. When modelled in a cohort of 1,000 residents the program resulted in a total of 1,606 fewer hospital bed days per annum. This contributed to a total cost saving of $2.6 million and 0.62 incremental QALYs gained per 1,000 residents. The program had a positive net monetary benefit and was considered cost-effective, even when the willingness to pay for health care gains was set to zero. A probabilistic sensitivity analysis estimated that there was an 86% probability that the program was cost-effective after taking the uncertainty of the model inputs into account.\n\nConclusionsThis study provides compelling evidence for the effectiveness and cost-effectiveness of a RACF nurse led sub-acute care program in preventing unnecessary hospital admissions.

epidemiology↗

bioRxiv2017

Microbial Community Assembly And Metabolite Profile Of The Gut Microbiome In Extremely Low Birthweight Infants

The assembly and development of the gut microbiome in infants has important consequences for immediate and long-term health. Preterm infants represent an abnormal case for bacterial colonization because of early exposure to bacteria and frequent use of antibiotics. To better understand the assembly of the gut microbiota in preterm infants, fecal samples were collected from 32 very low birthweight preterm infants over the first six weeks of life. Infant health outcomes included healthy, late-onset sepsis, and necrotizing enterocolitis (NEC). We characterized the bacterial composition by 16S rRNA gene sequencing and metabolome by untargeted gas chromatography mass spectrometry. Preterm infant fecal samples lacked beneficial Bifidobacterium and were dominated by Enterobacteriaceae, Enterococcus, and Staphylococcus due to the near uniform antibiotic administration. Most of the variance between the microbial community compositions could be attributed to which baby the sample came from (Permanova R2=0.48, p<0.001), while clinical status (healthy, NEC, or late-onset sepsis), and overlapping time in the NICU did not explain a significant amount of variation in bacterial composition. Fecal metabolomes were also found to be unique to the individual (Permanova R2=0.43, p<0.001) and weakly associated with bacterial composition (Mantel statistic r = 0.23 {+/-} 0.05 (p = 0.03 {+/-} 0.03). No measured metabolites were found to be associated with necrotizing enterocolitis, late-onset sepsis or a healthy outcome. Overall, preterm infants gut microbial communities were personalized and reflected antibiotic usage.\n\nImportancePreterm infants face health problems likely related to microbial exposures including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from thirty-two preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found the preterm infant microbiome and metabolome were both personalized, and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangling the health consequences of the preterm infant microbiome.

microbiology↗