Healthcare professionals in research (HPiR) Facebook community: a survey of U.K. doctoral and postdoctoral healthcare professionals outside of medicine.

BACKGROUND: Healthcare professionals outside of medicine (HCPs), including nurses, midwives and allied health professionals, are increasingly involved in research for patient benefit. Their challenge is to negotiate inter-professional or professionally isolated contexts. The aims of this study were to evaluate the 'Healthcare Professionals in Research' (HPiR) Facebook group (a self-directed and confidential peer support group for doctoral and postdoctoral HCPs) including engagement, the experiences of doctoral and postdoctoral HPiR members and to identify future career challenges using an on-line survey. METHODS: The HPiR Facebook group was launched in May 2019. Five HCP Community managers (CMs) were trained in on-line platform curation, moderation and screening. An on-line survey was designed to capture data from HPiR members. A purposive sampling approach was applied. Respondents were required to be doctoral and postdoctoral HCPs and a registered member of the HPiR group. Respondents represented a range of healthcare professions, 79 % of whom had over ten years clinical experience. Membership growth and engagement was analysed. Descriptive statistics were used to present numerical data. Qualitative data were analysed thematically. RESULTS: 96 members were admitted to the group within the first month. All members were actively engaged with group content. 34/96 doctoral and postdoctoral HCPs completed the survey. Most members joined for networking (88 %) and peer support (82 %) purposes. Analysis of text responses showed difficulties in balancing a clinical academic career and highlighted the consequences of undefined clinical academic roles and pathways. CONCLUSIONS: Doctoral and postdoctoral HCPs value the opportunities that HPiR provides for peer support and connection with fellow HCPs. HPiR has the potential to strengthen research capacity, support research skill development and drive change within the clinical academic community. Clinical academic roles and pathways need to be standardised. The creation of opportunities beyond doctoral studies is a priority.

Reliability and minimal detectable change of the 'Imperial Spine' marker set for the evaluation of spinal and lower limb kinematics in adults.

OBJECTIVES: As a step towards the comprehensive evaluation of movement in patients with low back pain, the aim of this study is to design a marker set (three rigid segment spine, pelvic and lower limb model) and evaluate the reliability and minimal detectable change (MDC) of this marker set in healthy adults during gait and sit to stand (STS) tasks using three dimensional motion capture. RESULTS: The 'Imperial Spine' marker set was used to assess relative peak angles during gait and STS tasks using the minimum recommended sample size (n = 10) for reliability studies with minimum Intraclass Correlation Coefficient (ICC) of 0.70, optimum ICC 0.90 and 9 trials replicated per subject per task. Intra- and inter-tester reliability between an experienced and inexperienced user was examined. ICC, mean, standard error (SEM), Bland Altman 95% limits of agreement (LOA) and MDC were computed. ICC values demonstrated excellent intra- and inter-tester reliability in both tasks, particularly in the sagittal plane (majority ICCs > 0.80). SEM measurements were lower in gait (0.8-5.5°) than STS tasks (1°-12.6°) as were MDC values. LOA demonstrated good agreement. The 'Imperial Spine' marker set is reliable for use in healthy adults during functional tasks. Future evaluation in patients is required.

The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis.

OBJECTIVE: Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. RESULTS: Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

Endometrial Mesenchymal Stem/Stromal Cells Modulate the Macrophage Response to Implanted Polyamide/Gelatin Composite Mesh in Immunocompromised and Immunocompetent Mice.

The immunomodulatory properties of human endometrial mesenchymal stem cells (eMSC) have not been well characterised. Initial studies showed that eMSC modulated the chronic inflammatory response to a non-degradable polyamide/gelatin mesh in a xenogeneic rat skin wound repair model, but the mechanism remains unclear. In this study, we investigated the immunomodulatory effect of eMSC on the macrophage response to polyamide/gelatin composite mesh in an abdominal subcutaneous wound repair model in C57BL6 immunocompetent and NSG (NOD-Scid-IL2Rgamma null ) immunocompromised mice to determine whether responses differed in the absence of an adaptive immune system and NK cells. mCherry lentivirus-labelled eMSC persisted longer in NSG mice, inducing longer term paracrine effects. Inclusion of eMSC in the mesh reduced inflammatory cytokine (Il-1ß, Tnfα) secretion, and in C57BL6 mice reduced CCR7+ M1 macrophages surrounding the mesh on day 3 and increased M2 macrophage marker mRNA (Arg1, Mrc1, Il10) expression at days 3 and 7. In NSG mice, these effects were delayed and only observed at days 7 and 30 in comparison with controls implanted with mesh alone. These results show that the differences in the immune status in the two animals directly affect the survival of xenogeneic eMSC which leads to differences in the short-term and long-term macrophage responses to implanted meshes.

Localization of intraflagellar transport protein IFT52 identifies basal body transitional fibers as the docking site for IFT particles.

Intraflagellar transport (IFT) is a motility in which particles composed of at least 17 polypeptides move underneath the flagellar membrane. Anterograde (outward) and retrograde (inward) movements of these IFT particles are mediated by FLA10 kinesin-II and cytoplasmic dynein DHC1b, respectively. Mutations affecting IFT particle polypeptides or motors result in the inability to assemble flagella. IFT particles and the motors moving them are located principally around the basal bodies as well as in the flagella. Here, we clone the cDNA encoding one of the IFT particle proteins, IFT52, and show by immunofluorescence that while some IFT52 is in the flagella, the majority is found in two horseshoe-shaped rings around the basal bodies. Immunoelectron microscopy indicates that IFT52 is associated with the periphery of the transitional fibers, which extend from the distal portion of the basal body to the cell membrane and demarcate the entrance to the flagellar compartment. This localization suggests that the transitional fibers form a docking complex for the IFT particles destined for the flagellum. Finally, the flagellaless mutant bld1 completely lacks IFT52 due to a deletion in the gene encoding IFT52.

Creating a sustainable physician compensation plan. Serving both fee-for-service and capitated populations.

A large, integrated health system in St. Louis acquired a primary care, health maintenance organization staff model group practice with 55 physicians. Health system leadership positioned the acquired physician group to diversify and expand its fee-for-service patient base to increase revenue and support the expansive fixed cost structure of the health centers. With interim managers, the leaders developed a new physician compensation plan that put a greater portion of the physicians' compensation at risk and provided incentives for enhanced productivity in both the capitated and fee-for-service lines of business. This article explores the key characteristics, benefits and potential areas for improvement associated with the new incentive compensation model and describes the centers' improved operating performance and gains in physician productivity.

Evidence for nucleomorph to host nucleus gene transfer: light-harvesting complex proteins from cryptomonads and chlorarachniophytes.

Cryptomonads and chlorarachniophytes acquired photosynthesis independently by engulfing and retaining eukaryotic algal cells. The nucleus of the engulfed cells (known as a nucleomorph) is much reduced and encodes only a handful of the numerous essential plastid proteins normally encoded by the nucleus of chloroplast-containing organisms. In cryptomonads and chlorarachniophytes these proteins are thought to be encoded by genes in the secondary host nucleus. Genes for these proteins were potentially transferred from the nucleomorph (symbiont nucleus) to the secondary host nucleus; nucleus to nucleus intracellular gene transfers. We isolated complementary DNA clones (cDNAs) for chlorophyll-binding proteins from a cryptomonad and a chlorarachniophyte. In each organism these genes reside in the secondary host nuclei, but phylogenetic evidence, and analysis of the targeting mechanisms, suggest the genes were initially in the respective nucleomorphs (symbiont nuclei). Implications for origins of secondary endosymbiotic algae are discussed.

The secondary endosymbiont of the cryptomonad Guillardia theta contains alpha-, beta-, and gamma-tubulin genes.

Cryptomonads have acquired photosynthesis through secondary endosymbiosis: they have engulfed and retained a photosynthetic eukaryote. The remnants of this autotrophic symbiont are severely reduced, but a small volume of cytoplasm surrounding the plastid persists, along with a residual nucleus (the nucleomorph) that encodes only a few hundred genes. We characterized tubulin genes from the cryptomonad Guillardia theta. Despite the apparent absence of microtubules in the endosymbiont, we recovered genes encoding alpha-, beta-, and gamma-tubulins from the nucleomorph genome of G. theta. The presence of tubulin genes in the nucleomorph indicates that some component of the cytoskeleton is still present in the cryptomonad symbiont despite the fact that very little cytoplasm remains, no mitosis is known in the nucleomorph, and microtubules have never been observed anywhere in the symbiont. Phylogenetic analyses with nucleomorph alpha- and beta-tubulins support the origin of the cryptomonad nucleomorph from a red alga. We also characterized alpha and beta-tubulins from the host nucleus of G. theta and compared these with tubulins we isolated from two flagellates, Goniomonas truncata and Cyanophora paradoxa, previously proposed to be related to the cryptomonad host. Phylogenetic analyses support a relationship between the cryptomonad host and Goniomonas but do not support any relationship between cryptomonads and Cyanophora.

A phylogenetic assessment of the eukaryotic light-harvesting antenna proteins, with implications for plastid evolution.

The light-harvesting complexes (LHCs) are a superfamily of chlorophyll-binding proteins present in all photosynthetic eukaryotes. The Lhc genes are nuclear-encoded, yet the pigment-protein complexes are localized to the thylakoid membrane and provide a marker to follow the evolutionary paths of plastids with different pigmentation. The LHCs are divided into the chlorophyll a/b-binding proteins of the green algae, euglenoids, and higher plants and the chlorophyll a/c-binding proteins of various algal taxa. This work examines the phylogenetic position of the LHCs from three additional taxa: the rhodophytes, the cryptophytes, and the chlorarachniophytes. Phylogenetic analysis of the LHC sequences provides strong statistical support for the clustering of the rhodophyte and cryptomonad LHC sequences within the chlorophyll a/c-binding protein lineage, which includes the fucoxanthin-chlorophyll proteins (FCP) of the heterokonts and the intrinsic peridinin-chlorophyll proteins (iPCP) of the dinoflagellates. These associations suggest that plastids from the heterokonts, haptophytes, cryptomonads, and the dinoflagellate, Amphidinium, evolved from a red algal-like ancestor. The Chlorarachnion LHC is part of the chlorophyll a/b-binding protein assemblage, consistent with pigmentation, providing further evidence that its plastid evolved from a green algal secondary endosymbiosis. The Chlorarachnion LHC sequences cluster with the green algal LHCs that are predominantly associated with photosystem II (LHCII). This suggests that the green algal endosymbiont that evolved into the Chlorarachnion plastid was acquired following the emergence of distinct LHCI and LHCII complexes.

The phylogenetic position of alpha- and beta-tubulins from the Chlorarachnion host and Cercomonas (Cercozoa).

Alpha and beta-tubulin genes from Chlorarachnion and an alpha-tubulin gene from Cercomonas have been characterised. We found the Cercomonas and Chlorarachnion alpha tubulins to be closely related to one another, confirming the proposed relationship of these genera. In addition, the Chlorarachnion host and Cercomonas also appear to be more distantly related to Heterolobosea, Euglenozoa, chlorophytes, heterokonts, and alveolates. Chlorarachnion was also found to have two distinctly different types of both alpha- and beta-tubulin, one type being highly-divergent. Chlorarachnion contains a secondary endosymbiont of green algal origin, raising the possibility that one type of Chlorarachnion tubulins comes from the host and the other from the endosymbiont. Probing pulsed field-separated chromosomes showed that the highly-divergent genes are encoded by the host genome, and neither alpha- nor beta-tubulin cDNAs were found to include 5' extensions that might serve as targeting peptides. It appears that Chlorarachnion has distinct and divergent tubulin paralogues that are all derived from the host lineage. One Chlorarachnion beta-tubulin was also found to be a pseudogene, which is still expressed but aberrantly processed. Numerous unspliced introns and deletions resulting from mis-splicing are contained in the mRNAs from this gene.