BackgroundThe complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain.MethodsTo identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1+ neurons in both wild type mice and a mouse model of Alzheimer’s disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis.ResultsWhile C1q expression in the brain was unaffected after inactivation of C1qa in Thy-1+ neurons, the brains of C1qa FL/FL :Cx3cr1 CreERT2 mice in which C1qa was ablated in microglia were devoid of C1q with the exception of limited C1q in subsets of interneurons. Surprisingly, this loss of C1q occurred even in the absence of tamoxifen by 1 month of age, demonstrating that Cre activity is tamoxifen-independent in microglia in Cx3cr1 CreERT2/WganJ mice. C1q expression in C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice continued to decline and remained almost completely absent through aging and in AD model mice. No difference in C1q was detected in the liver or kidney from C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice relative to controls, and C1qa FL/FL : Cx3cr1 CreERT2/WganJ mice had minimal, if any, reduction in plasma C1q.ConclusionsThus, microglia, but not neurons or peripheral sources, are the dominant source of C1q in the brain. While demonstrating that the Cx3cr1 CreERT2/WganJ deleter cannot be used for adult-induced deletion of genes in microglia, the model described here enables further investigation of physiological roles of C1q in the brain and identification of therapeutic targets for the selective control of complement-mediated activities contributing to neurodegenerative disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0814-9) contains supplementary material, which is available to authorized users.
Background The human papillomavirus (HPV) vaccine is a major advancement in cancer prevention and this primary prevention tool has the potential to reduce and eliminate HPV-associated cancers; however, the safety and efficacy of vaccines in general and the HPV vaccine specifically have come under attack, particularly through the spread of misinformation on social media. The popular social media platform Instagram represents a significant source of exposure to health (mis)information; 1 in 3 US adults use Instagram. Objective The objective of this analysis was to characterize pro- and anti-HPV vaccine networks on Instagram, and to describe misinformation within the anti-HPV vaccine network. Methods From April 2018 to December 2018, we collected publicly available English-language Instagram posts containing hashtags #HPV, #HPVVaccine, or #Gardasil using Netlytic software (n=16,607). We randomly selected 10% of the sample and content analyzed relevant posts (n=580) for text, image, and social media features as well as holistic attributes (eg, sentiments, personal stories). Among antivaccine posts, we organized elements of misinformation within four broad dimensions: 1) misinformation theoretical domains, 2) vaccine debate topics, 3) evidence base, and 4) health beliefs. We conducted univariate, bivariate, and network analyses on the subsample of posts to quantify the role and position of individual posts in the network. Results Compared to provaccine posts (324/580, 55.9%), antivaccine posts (256/580, 44.1%) were more likely to originate from individuals (64.1% antivaccine vs 25.0% provaccine; P<.001) and include personal narratives (37.1% vs 25.6%; P=.003). In the antivaccine network, core misinformation characteristics included mentioning #Gardasil, purporting to reveal a lie (ie, concealment), conspiracy theories, unsubstantiated claims, and risk of vaccine injury. Information/resource posts clustered around misinformation domains including falsification, nanopublications, and vaccine-preventable disease, whereas personal narrative posts clustered around different domains of misinformation, including concealment, injury, and conspiracy theories. The most liked post (6634 likes) in our full subsample was a positive personal narrative post, created by a non-health individual; the most liked post (5604 likes) in our antivaccine subsample was an informational post created by a health individual. Conclusions Identifying characteristics of misinformation related to HPV vaccine on social media will inform targeted interventions (eg, network opinion leaders) and help sow corrective information and stories tailored to different falsehoods.
Background. With its growing popularity, inclusion of image and text, and user-friendly interface, Instagram is uniquely positioned for exploring health behaviors and sources and types of informational exposure related to the human papillomavirus (HPV) vaccine. Aims. To characterize public Instagram posts about the HPV vaccine and quantify the impact of sentiment and context on engagement via likes. Method. Using Netlytic, 3,378 publicly available English-language posts were collected using the search terms “#HPV,” “#HPVVaccine,” and “#Gardasil.” We randomly selected 1,200 posts to content analyze. Our final analytic sample included 360 posts after excluding posts whose links were no longer active ( n = 221) or that were not relevant ( n = 619). Results. A higher proportion of posts were pro-vaccine (55.8%) than anti-vaccine (42.2%). Pro-HPV vaccination posts were liked significantly less than anti-vaccination posts (24 vs. 86 likes; p < .001). More posts contained actionable information/resources (63.9%) than personal narrative elements (36.1%). Less than one in three posts (30.0%) came from health-related sources. Discussion. Pro-vaccine posts were more prevalent on Instagram, and anti-vaccine posts had higher engagement and typically included misleading information about the HPV vaccine. Personal narratives skewed toward anti-vaccine sentiments and most were produced by individual users. Pro-vaccine narratives portrayed individuals who received the vaccine, but provided limited details on vaccine experiences, starkly contrasting with the depth of details in anti-vaccine personal narrative posts. Conclusion. On Instagram, individuals and organizations have an opportunity to promote HPV vaccination by continuing to provide informational resources in addition to creating more narrative-style posts.
Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. Finally, we pilot tested the DSI among five patients with NSCLC in treatment SDM at the beginning of an office visit scheduled to discuss Treatment with an oncologist. Analyses of pilot study baseline and exit survey data showed that DSI use was associated with increased patient awareness of the alternatives’ treatment options and benefits/risks. In contrast, patient concern about treatment costs and uncertainty in treatment decision making decreased. All patients expressed a treatment preference. Future randomized controlled trials are needed to assess DSI implementation feasibility and efficacy in clinical care.
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