Post-operative immune suppression is reversible with interferon gamma and independent of IL-6 pathways

Introduction The post-operative period is characterised by increased IL-6 production and clinical features of immune suppression. In vitro anti-inflammatory actions of IL-6 are mediated through suppression of interferon gamma (IFNγ) [1]. The clinical significance of IL-6 in mediating post-operative immune suppression remains unclear. Objectives To evaluate the role of IL-6 pathways in post-operative immune suppression and the reversibility of this phenomenon. Methods Patients over 45 years old undergoing elective surgery involving the gastrointestinal tract and requiring at least an overnight hospital stay were recruited. The primary outcome was hospital-acquired infection. IL-6 and IFNγ levels were assayed using ELISA preoperatively and at 24 and 48 hours. Pooled healthy control peripheral blood mononuclear cells (PBMCs) were cultured in perioperative serum and CD14+HLA-DR (mHLA-DR) geometric mean florescent intensity (MFI) measured in the presence and absence of interferon gamma (IFNγ) and IL-6 neutralising antibody. Data were analysed with non-parametric statistics. Results 119 patients were recruited and 44 (37%) developed a post-operative infection a median of 9 (IQR 5-11) days postoperatively (Figure 1). IL-6 levels increased from baseline to 24 hours postoperatively (P < 0.0001, Figure 1A) but were then unchanged between 24 and 48 hours (P = 0.06, Figure 1B). Postoperative IL-6 levels correlated with the duration of the procedure (P = 0.009). Higher preoperative IL-6 levels were observed in patients with cancer (P = 0.02). IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with the later occurrence of infectious complications. This pattern remained similar after adjustment for baseline characteristics. Healthy donor PBMCs incubated with postoperative serum downregulated mHLA-DR MFI when compared with serum from baseline (n = 8, p = 0.008). Culturing in the presence of IFNγ 250IU (n = 4) prevented this decrease whereas culturing in the presence of IL-6 neutralising antibody 15ng/ml (n = 8) did not. Conclusions IL-6 levels increase following major surgery and are associated with an increased susceptibility to post-operative infections. Serum obtained from post-operative patients induces an immunosuppressive response through an IL-6 independent pathways which is reversible with IFNγ treatment

Herbivores at the Highest Risk of Extinction Among Mammals, Birds, and Reptiles

As a result of their extensive home ranges and slow population growth rates, predators have often been perceived to suffer higher risks of extinction than other trophic groups. Our study challenges this extinction-risk paradigm by quantitatively comparing patterns of extinction risk across different trophic groups of mammals, birds, and reptiles. We found that trophic level and body size were significant factors that influenced extinction risk in all taxa. At multiple spatial and temporal scales, herbivores, especially herbivorous reptiles and large-bodied herbivores, consistently have the highest proportions of threatened species. This observed elevated extinction risk for herbivores is ecologically consequential, given the important roles that herbivores are known to play in controlling ecosystem function

Frequency and distribution of rare electrophoretic mobility variants in a population of human newborns in Ann Arbor, Michigan

We have summarized the frequency and distribution of the rare variants encountered during the screening of 258 815 allele products, the products of 51 different loci, in 3242 predominantly Caucasian (88 %) newborns. Seventy-nine different rare variants, representing 187 occurrences, were identified. Almost 60 % (46 of 79) of the rare variants occurred as singletons while another 20 % were seen in two unrelated individuals. No rare variants were detected at 18 loci while no variants, either rare or polymorphic, were detected at 14 loci. More rare variants were identified at loci that were classified as polymorphic and also at loci where the gene products exist as a monomer. A positive relationship was observed between variant frequency, either classes or copies, and subunit molecular mass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65173/1/j.1469-1809.1987.tb01065.x.pd

How well do services for young people with long term conditions deliver features proposed to improve transition?

Background - For young people with long-term conditions, transition from child to adult-oriented health services is a critical period which, if not managed well, may lead to poor outcomes. There are features of transition services which guidance and research suggest improve outcomes. We studied nine such features, calling them ‘proposed beneficial features’: age-banded clinic; meet adult team before transfer; promotion of health self-efficacy; written transition plan; appropriate parent involvement; key worker; coordinated team; holistic life-skills training; transition manager for clinical team. We aimed to describe the extent to which service providers offer these nine features, and to compare this with young people’s reported experience of them. Methods - A longitudinal, mixed methods study followed 374 young people as their care moved from child to adult health services. Participants had type 1 diabetes, cerebral palsy or autism spectrum disorder with additional mental health difficulties. Data are reported from the first two visits, one year apart. Results - Three hundred four (81.3%) of the young people took part in the second visit (128 with diabetes, 91 with autism, 85 with cerebral palsy). Overall, the nine proposed beneficial features of transition services were poorly provided. Fewer than half of services stated they provided an age-banded clinic, written transition plan, transition manager for clinical team, a protocol for promotion of health self-efficacy, or holistic life-skills training. To varying degrees, young people reported that they had not experienced the features which services said they provided. For instance, the agreement for written transition plan, holistic life-skills training and key worker, was 30, 43 and 49% respectively. Agreement was better for appropriate parent involvement, age-banded clinic, promotion of health self-efficacy and coordinated team at 77, 77, 80 and 69% respectively. Variation in the meaning of the features as experienced by young people and families was evident from qualitative interviews and observations. Conclusions - UK services provide only some of the nine proposed beneficial features for supporting healthcare transition of young people with long term conditions. Observational studies or trials which examine the influence of features of transition services on outcomes should ensure that the experiences of young people and families are captured, and not rely on service specifications

Co-transplantation of Human Embryonic Stem Cell-derived Neural Progenitors and Schwann Cells in a Rat Spinal Cord Contusion Injury Model Elicits a Distinct Neurogenesis and Functional Recovery

Co-transplantation of neural progenitors (NPs) with Schwann cells (SCs) might be a way to overcome low rate of neuronal differentiation of NPs following transplantation in spinal cord injury (SCI) and the improvement of locomotor recovery. In this study, we initially generated NPs from human embryonic stem cells (hESCs) and investigated their potential for neuronal differentiation and functional recovery when co-cultured with SCs in vitro and co-transplanted in a rat acute model of contused SCI. Co-cultivation results revealed that the presence of SCs provided a consistent status for hESC-NPs and recharged their neural differentiation toward a predominantly neuronal fate. Following transplantation, a significant functional recovery was observed in all engrafted groups (NPs, SCs, NPs+SCs) relative to the vehicle and control groups. We also observed that animals receiving co-transplants established a better state as assessed with the BBB functional test. Immunohistofluorescence evaluation five weeks after transplantation showed invigorated neuronal differentiation and limited proliferation in the co-transplanted group when compared to the individual hESC-NPs grafted group. These findings have demonstrated that the co-transplantation of SCs with hESC-NPs could offer a synergistic effect, promoting neuronal differentiation and functional recovery

The African surgical outcomes-2 (Asos-2) pilot trial, a mixed-methods implementation study

Funding Information: The ASOS-2 Pilot Trial was supported by a grant (OPP#1161108) from the Bill & Melinda Gates Foundation.Peer reviewe

Ex Vivo

The measurement of vaccine-induced humoral and CD4+ and CD8+ cellular immune responses represents an important correlate of vaccine efficacy. Accurate and reliable assays evaluating such responses are therefore critical during the clinical development phase of vaccines. T cells play a pivotal role both in coordinating the adaptive and innate immune responses and as effectors. During the assessment of cell-mediated immunity (CMI) in subjects participating in a large-scale influenza vaccine trial, we identified the expansion of an IFN-γ-producing CD3+CD4-CD8-γδ+ T cell population in the peripheral blood of 90/610 (15%) healthy subjects. The appearance of CD3+CD4-CD8-γδ+ T cells in the blood of subjects was transient and found to be independent of the study cohort, vaccine group, subject gender and ethnicity, and ex vivo restimulation conditions. Although the function of this population and relevance to vaccination are unclear, their inclusion in the total vaccine-specific T-cell response has the potential to confound data interpretation. It is thus recommended that when evaluating the induction of IFN-γ-producing CD4+ and CD8+ immune responses following vaccination, the CD3+CD4-CD8-γδ+ T cells are either excluded or separately enumerated from the overall frequency determination

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Open Science Principles for Accelerating Trait-Based Science Across the Tree of Life

Synthesizing trait observations and knowledge across the Tree of Life remains a grand challenge for biodiversity science. Species traits are widely used in ecological and evolutionary science, and new data and methods have proliferated rapidly. Yet accessing and integrating disparate data sources remains a considerable challenge, slowing progress toward a global synthesis to integrate trait data across organisms. Trait science needs a vision for achieving global integration across all organisms. Here, we outline how the adoption of key Open Science principles—open data, open source and open methods—is transforming trait science, increasing transparency, democratizing access and accelerating global synthesis. To enhance widespread adoption of these principles, we introduce the Open Traits Network (OTN), a global, decentralized community welcoming all researchers and institutions pursuing the collaborative goal of standardizing and integrating trait data across organisms. We demonstrate how adherence to Open Science principles is key to the OTN community and outline five activities that can accelerate the synthesis of trait data across the Tree of Life, thereby facilitating rapid advances to address scientific inquiries and environmental issues. Lessons learned along the path to a global synthesis of trait data will provide a framework for addressing similarly complex data science and informatics challenges

Open Science principles for accelerating trait-based science across the Tree of Life.

Synthesizing trait observations and knowledge across the Tree of Life remains a grand challenge for biodiversity science. Species traits are widely used in ecological and evolutionary science, and new data and methods have proliferated rapidly. Yet accessing and integrating disparate data sources remains a considerable challenge, slowing progress toward a global synthesis to integrate trait data across organisms. Trait science needs a vision for achieving global integration across all organisms. Here, we outline how the adoption of key Open Science principles-open data, open source and open methods-is transforming trait science, increasing transparency, democratizing access and accelerating global synthesis. To enhance widespread adoption of these principles, we introduce the Open Traits Network (OTN), a global, decentralized community welcoming all researchers and institutions pursuing the collaborative goal of standardizing and integrating trait data across organisms. We demonstrate how adherence to Open Science principles is key to the OTN community and outline five activities that can accelerate the synthesis of trait data across the Tree of Life, thereby facilitating rapid advances to address scientific inquiries and environmental issues. Lessons learned along the path to a global synthesis of trait data will provide a framework for addressing similarly complex data science and informatics challenges