Effectiveness of Conventional Digital Fundus Photography-Based Teleretinal Screening for Diabetic Retinopathy and Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: This American Academy of Ophthalmology Ophthalmic Technology Assessment aims to assess the effectiveness of conventional teleretinal screening (TS) in detecting diabetic retinopathy (DR) and diabetic macular edema (DME). METHODS: A literature search of the PubMed database was conducted most recently in July 2023 to identify data published between 2006 and 2023 on any of the following elements related to TS effectiveness: (1) the accuracy of TS in detecting DR or DME compared with traditional ophthalmic screening with dilated fundus examination or 7-standard field Early Treatment Diabetic Retinopathy Study photography, (2) the impact of TS on DR screening compliance rates or other patient behaviors, and (3) cost-effectiveness and patient satisfaction of TS compared with traditional DR screening. Identified studies then were rated based on the Oxford Centre for Evidence-Based Medicine grading system. RESULTS: Eight level I studies, 14 level II studies, and 2 level III studies were identified in total. Although cross-study comparison is challenging because of differences in reference standards and grading methods, TS demonstrated acceptable sensitivity and good specificity in detecting DR; moderate to good agreement between TS and reference-standard DR grading was observed. Performance of TS was not as robust in detecting DME, although the number of studies evaluating DME specifically was limited. Two level I studies, 5 level II studies, and 1 level III study supported that TS had a positive impact on overall DR screening compliance, even increasing it by more than 2-fold in one study. Studies assessing cost-effectiveness and patient satisfaction were not graded formally, but they generally showed that TS was cost-effective and preferred by patients over traditional surveillance. CONCLUSIONS: Conventional TS is an effective approach to DR screening not only for its accuracy in detecting referable-level disease, but also for improving screening compliance in a cost-effective manner that may be preferred by patients. Further research is needed to elucidate the ideal approach of TS that may involve integration of artificial intelligence or other imaging technologies in the future. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Treatment of Noninfectious Uveitic Macular Edema with Periocular and Intraocular Corticosteroid Therapies: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the effectiveness and complications of periocular and intraocular corticosteroid therapies for noninfectious uveitic macular edema. METHODS: A literature search of the PubMed database was conducted last in December 2021 and a post-assessment search was conducted in March 2023. The searches were limited to articles published in English and no date restrictions were imposed. The combined searches yielded 739 citations; 53 articles were selected for inclusion because the studies (1) evaluated periocular corticosteroid injection, intraocular corticosteroid injection or implant, suprachoroidal corticosteroid injection, or a combination thereof for uveitic macular edema; (2) had outcomes that included visual acuity (VA) or macular edema assessed clinically or imaged by OCT or fluorescein angiography; and (3) included more than 20 patients. RESULTS: This assessment reviewed 23 articles that provided level I or level II evidence from 18 studies on the use of periocular, suprachoroidal, and intravitreal triamcinolone acetonide injections and intravitreal dexamethasone and fluocinolone acetonide implants or inserts in noninfectious uveitic macular edema. These reports consistently demonstrated that all investigated periocular and intraocular corticosteroid therapies improved VA, macular structure, or both. One comparative study showed that intravitreal triamcinolone acetonide injection and the dexamethasone intravitreal implant had effectiveness superior to that of periocular triamcinolone acetonide injection for these outcomes. As a group, the studies highlighted the potential for these therapies to elevate intraocular pressure and to accelerate cataract formation. CONCLUSIONS: The published literature provides high-quality evidence that periocular and intraocular corticosteroid therapies are effective and safe for the treatment of noninfectious uveitic macular edema. However, information on the relative effectiveness and complication rates across the different therapies is limited. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effects of tumor necrosis factor-α and interleukin-1ß on human retinal endothelial cells.

Uveitis, or intraocular inflammation, is a potentially blinding condition that mostly affects the working-age population. The cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß, play a role in the pathogenesis of non-infectious uveitis and have been linked to the breakdown of the inner blood-retinal barrier, composed mainly of retinal endothelial cells, leading to macular oedema and vascular leakage. However, the effects of TNF-α and IL-1ß on human retinal endothelial function are not fully understood. In this work, we investigated the impact of TNF-α and IL-1ß on several aspects of human retinal endothelial cell biology. Through a real-time biosensor, the impact of TNF-α and IL-1ß on formation of a retinal endothelial cell barrier was analyzed. Changes in junctional components were assessed via RT-qPCR and immunolabelling. Cell survival, necrosis and apoptosis were appraised via cell proliferation and flow cytometric studies. Tumor necrosis factor-α and IL-1ß impaired the electrical resistance of the retinal endothelial cell barrier, while the addition of a potentially barrier-impairing cytokine, IL-6, did not enhance the effect of TNF-α and IL-1ß. Level of the gene transcript encoding zonula occludens (ZO)-1 was diminished, while ZO-1 protein configuration was changed by TNF-α and IL-1ß. Both cytokines affected human retinal endothelial cell proliferation and viability, while only TNF-α increased rates of necrosis. These results indicate that TNF-α and IL-1ß are important drivers of retinal endothelial dysfunction in non-infectious uveitis, suggesting that targeting these cytokines is critical when treating complications of uveitis, such as macular oedema and vascular leakage.

Characterisation of social media conversations on syphilis: an unobtrusive observational study.

BACKGROUND: Conversations around disease conducted through social media provide a means for capturing public perspectives that may be useful in considering public health approaches. Syphilis is a sexually transmitted disease that is re-emerging. We sought to characterise online discourse on syphilis using data collected from the social media platform, Twitter. METHODS: We extracted English-language tweets containing the word 'syphilis' posted on Twitter in 2019. Tweet identification number and URL, date and time of posting, number of retweets and likes, and the author's screen name, username and biographical statement were included in the dataset. A systematically sampled 10% subset of the data was subjected to qualitative analysis, involving categorisation on content. All tweets assigned to the category of medical resource were assessed for clinical accuracy. The engagement ratio for each category was calculated as (retweets+likes):tweets. RESULTS: In 2019, 111,388 tweets mentioning syphilis were posted by 69,921 authors. The most frequent content category - totalling 5370 tweets (48%) - was a joke. Of 1762 tweets (16%) categorised as a medical resource, 1484 (84%) were medically correct and 240 (14%) were medically incorrect; for 38 (2%), medical accuracy could not be judged from the information posted. Tweets categorised as personal experiences had the highest engagement ratio at approximately 19:1. Medical resource tweets had an engagement ratio of approximately 7:1. CONCLUSIONS: We found medical information about syphilis was limited on Twitter. As tweets about personal experiences generate high engagement, coupling an experience with information may provide opportunity for public health education.

The influence of human activity on predator-prey spatiotemporal overlap.

Despite growing evidence of widespread impacts of humans on animal behaviour, our understanding of how humans reshape species interactions remains limited. Here, we present a framework that draws on key concepts from behavioural and community ecology to outline four primary pathways by which humans can alter predator-prey spatiotemporal overlap. We suggest that predator-prey dyads can exhibit similar or opposite responses to human activity with distinct outcomes for predator diet, predation rates, population demography and trophic cascades. We demonstrate how to assess these behavioural response pathways with hypothesis testing, using temporal activity data for 178 predator-prey dyads from published camera trap studies on terrestrial mammals. We found evidence for each of the proposed pathways, revealing multiple patterns of human influence on predator-prey activity and overlap. Our framework and case study highlight current challenges, gaps, and advances in linking human activity to animal behaviour change and predator-prey dynamics. By using a hypothesis-driven approach to estimate the potential for altered species interactions, researchers can anticipate the ecological consequences of human activities on whole communities.

Selective Transcription Factor Blockade Reduces Human Retinal Endothelial Cell Expression of Intercellular Adhesion Molecule-1 and Leukocyte Binding.

The interaction between leukocytes and cytokine-activated retinal endothelium is an initiating step in non-infectious uveitis involving the posterior eye, mediated by cell adhesion molecules. However, because cell adhesion molecules are required for immune surveillance, therapeutic interventions would ideally be employed indirectly. Using 28 primary human retinal endothelial cell isolates, this study sought to identify transcription factor targets for reducing levels of the key retinal endothelial cell adhesion molecule, intercellular adhesion molecule (ICAM)-1, and limiting leukocyte binding to the retinal endothelium. Five candidate transcription factors-C2CD4B, EGR3, FOSB, IRF1, and JUNB-were identified by differential expression analysis of a transcriptome generated from IL-1ß- or TNF-α-stimulated human retinal endothelial cells, interpreted in the context of the published literature. Further filtering involved molecular studies: of the five candidates, C2CD4B and IRF1 consistently demonstrated extended induction in IL-1ß- or TNF-α-activated retinal endothelial cells and demonstrated a significant decrease in both ICAM-1 transcript and ICAM-1 membrane-bound protein expression by cytokine-activated retinal endothelial cells following treatment with small interfering RNA. RNA interference of C2CD4B or IRF1 significantly reduced leukocyte binding in a majority of human retinal endothelial cell isolates stimulated by IL-1ß or TNF-α. Our observations suggest that the transcription factors C2CD4B and IRF1 may be potential drug targets for limiting leukocyte-retinal endothelial cell interactions in non-infectious uveitis involving the posterior eye.

A skewed literature: Few studies evaluate the contribution of predation-risk effects to natural field patterns.

A narrative in ecology is that prey modify traits to reduce predation risk, and the trait modification has costs large enough to cause ensuing demographic, trophic and ecosystem consequences, with implications for conservation, management and agriculture. But ecology has a long history of emphasising that quantifying the importance of an ecological process ultimately requires evidence linking a process to unmanipulated field patterns. We suspected that such process-linked-to-pattern (PLP) studies were poorly represented in the predation risk literature, which conflicts with the confidence often given to the importance of risk effects. We reviewed 29 years of the ecological literature which revealed that there are well over 4000 articles on risk effects. Of those, 349 studies examined risk effects on prey fitness measures or abundance (i.e., non-consumptive effects) of which only 26 were PLP studies, while 275 studies examined effects on other interacting species (i.e., trait-mediated indirect effects) of which only 35 were PLP studies. PLP studies were narrowly focused taxonomically and included only three that examined unmanipulated patterns of prey abundance. Before concluding a widespread and influential role of predation-risk effects, more attention must be given to linking the process of risk effects to unmanipulated patterns observed across diverse ecosystems.

Cascading effects of a disease outbreak in a remote protected area.

Disease outbreaks induced by humans increasingly threaten wildlife communities worldwide. Like predators, pathogens can be key top-down forces in ecosystems, initiating trophic cascades that may alter food webs. An outbreak of mange in a remote Andean protected area caused a dramatic population decline in a mammalian herbivore (the vicuña), creating conditions to test the cascading effects of disease on the ecological community. By comparing a suite of ecological measurements to pre-disease baseline records, we demonstrate that mange restructured tightly linked trophic interactions previously driven by a mammalian predator (the puma). Following the mange outbreak, scavenger (Andean condor) occurrence in the ecosystem declined sharply and plant biomass and cover increased dramatically in predation refuges where herbivory was historically concentrated. The evidence shows that a disease-induced trophic cascade, mediated by vicuña density, could supplant the predator-induced trophic cascade, mediated by vicuña behaviour, thereby transforming the Andean ecosystem.

Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

Social media and ophthalmology: A review.

Social media is being widely used across ophthalmology. Its communication tools have been employed more often by ophthalmologists in private practice than academia, although academic institutions may be more impactful influencers. There are opportunities to promote ophthalmic services and to augment traditional clinical care. Social media provides a medium to disseminate peer-reviewed literature in ophthalmology, and to expand conference experiences. It is used for teaching ophthalmology at medical schools and attracting medical students into ophthalmology training, and for research in ophthalmology. Important considerations when using social media include the required time commitment and the public nature of interactions. The high level of misinformation in medical social media remains a challenge for both ophthalmologists and their patients, and the ophthalmologist can play an active role in addressing the issue. This review considers the role that social media is playing in ophthalmology today, including impact on ophthalmic practice, applications in ophthalmic education and training, and patient-focused networking.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 1: Guidelines for Initiating Antitubercular Therapy in Tubercular Choroiditis.

TOPIC: An international, expert-led consensus initiative organized by the Collaborative Ocular Tuberculosis Study (COTS), along with the International Ocular Inflammation Society and the International Uveitis Study Group, systematically developed evidence- and experience-based recommendations for the treatment of tubercular choroiditis. CLINICAL RELEVANCE: The diagnosis and management of tubercular uveitis (TBU) pose a significant challenge. Current guidelines and literature are insufficient to guide physicians regarding the initiation of antitubercular therapy (ATT) in patients with TBU. METHODS: An international expert steering subcommittee of the COTS group identified clinical questions and conducted a systematic review of the published literature on the use of ATT for tubercular choroiditis. Using an interactive online questionnaire, guided by background knowledge from published literature, 81 global experts (including ophthalmologists, pulmonologists, and infectious disease physicians) generated preliminary consensus statements for initiating ATT in tubercular choroiditis, using Oxford levels of medical evidence. In total, 162 statements were identified regarding when to initiate ATT in patients with tubercular serpiginous-like choroiditis, tuberculoma, and tubercular focal or multifocal choroiditis. The COTS group members met in November 2018 to refine these statements by a 2-step modified Delphi process. RESULTS: Seventy consensus statements addressed the initiation of ATT in the 3 subtypes of tubercular choroiditis, and in addition, 10 consensus statements were developed regarding the use of adjunctive therapy in tubercular choroiditis. Experts agreed on initiating ATT in tubercular choroiditis in the presence of positive results for any 1 of the positive immunologic tests along with radiologic features suggestive of tuberculosis. For tubercular serpiginous-like choroiditis and tuberculoma, positive results from even 1 positive immunologic test were considered sufficient to recommend ATT, even if there were no radiologic features suggestive of tuberculosis. DISCUSSION: Consensus guidelines were developed to guide the initiation of ATT in patients with tubercular choroiditis, based on the published literature, expert opinion, and practical experience, to bridge the gap between clinical need and available medical evidence.

Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis-Report 2: Guidelines for Initiating Antitubercular Therapy in Anterior Uveitis, Intermediate Uveitis, Panuveitis, and Retinal Vasculitis.

TOPIC: The Collaborative Ocular Tuberculosis Study (COTS), supported by the International Ocular Inflammation Society, International Uveitis Study Group, and Foster Ocular Immunological Society, set up an international, expert-led consensus project to develop evidence- and experience-based guidelines for the management of tubercular uveitis (TBU). CLINICAL RELEVANCE: The absence of international agreement on the use of antitubercular therapy (ATT) in patients with TBU contributes to a significant heterogeneity in the approach to the management of this condition. METHODS: Consensus statements for the initiation of ATT in TBU were generated using a 2-step modified Delphi technique. In Delphi step 1, a smart web-based survey based on background evidence from published literature was prepared to collect the opinion of 81 international experts on the use of ATT in different clinical scenarios. The survey included 324 questions related to tubercular anterior uveitis (TAU), tubercular intermediate uveitis (TIU), tubercular panuveitis (TPU), and tubercular retinal vasculitis (TRV) administered by the experts, after which the COTS group met in November 2019 for a systematic and critical discussion of the statements in accordance with the second round of the modified Delphi process. RESULTS: Forty-four consensus statements on the initiation of ATT in TAU, TIU, TPU, and TRV were obtained, based on ocular phenotypes suggestive of TBU and corroborative evidence of tuberculosis, provided by several combinations of immunologic and radiologic test results. Experts agreed on initiating ATT in recurrent TAU, TIU, TPU, and active TRV depending on the TB endemicity. In the presence of positive results for any 1 of the immunologic tests along with radiologic features suggestive of past evidence of tuberculosis infection. In patients with a first episode of TAU, consensus to initiate ATT was reached only if both immunologic and radiologic test results were positive. DISCUSSION: The COTS consensus guidelines were generated based on the evidence from published literature, specialists' opinions, and logic construction to address the initiation of ATT in TBU. The guidelines also should inform public policy by adding specific types of TBU to the list of conditions that should be treated as tuberculosis.

Recommendations for the management of childhood juvenile idiopathic arthritis-type chronic anterior uveitis.

IMPORTANCE: Australian- and New Zealand-based, uveitis-specialized ophthalmologists have produced recommendations for the management of juvenile idiopathic arthritis (JIA)-type chronic anterior uveitis. BACKGROUND: Historically, the visual prognosis of JIA-type chronic anterior uveitis has been poor. New medical advances are likely to improve outcomes, but recently published guidelines are tailored for ophthalmic care in Europe and the United States. DESIGN: This work involved a consensus survey and a panel meeting. PARTICIPANTS: The Australian and New Zealand JIA-Uveitis Working Group (29 ophthalmologists) participated in the work. METHODS: The Delphi technique was used to achieve consensus. MAIN OUTCOME MEASURES: This work yielded consensus statements. RESULTS: The Working Group achieved consensus around 18 statements related to clinical evaluation, use of topical and regional corticosteroids, use of systemic corticosteroid and non-corticosteroid immunomodulatory drugs, and management of secondary cataract and glaucoma in childhood JIA-type uveitis. CONCLUSIONS AND RELEVANCE: Recommendations of the Australian and New Zealand JIA-Uveitis Working Group provide current and regionally applicable advice for managing chronic anterior uveitis in children with JIA.

Dengue virus infects the mouse eye following systemic or intracranial infection and induces inflammatory responses.

Dengue virus (DENV) infection is associated with clinical ocular presentations and here DENV infection of the eye was assessed in mice. In an AG129 mouse model of antibody-dependent enhancement of DENV infection, DENV RNA was detected in the eye and vascular changes were present in the retinae. Intraocular CD8 and IFN-γ mRNA were increased in mice born to DENV-naïve, but not DENV-immune mothers, while TNF-α mRNA was induced and significantly higher in mice born to DENV-immune than DENV-naïve mothers. DENV RNA was detected in the eye following intracranial DENV infection and CD8 mRNA but not IFN-γ nor TNF-α were induced. In all models, viperin was increased following DENV infection. Thus, DENV in the circulation or the brain can infect the eye and stimulate innate immune responses, with induction of viperin as one response that consistently occurs in multiple DENV eye-infection models in both an IFN-dependent and independent manner.

Zooming in on mechanistic predator-prey ecology: Integrating camera traps with experimental methods to reveal the drivers of ecological interactions.

Camera trap technology has galvanized the study of predator-prey ecology in wild animal communities by expanding the scale and diversity of predator-prey interactions that can be analysed. While observational data from systematic camera arrays have informed inferences on the spatiotemporal outcomes of predator-prey interactions, the capacity for observational studies to identify mechanistic drivers of species interactions is limited. Experimental study designs that utilize camera traps uniquely allow for testing hypothesized mechanisms that drive predator and prey behaviour, incorporating environmental realism not possible in the laboratory while benefiting from the distinct capacity of camera traps to generate large datasets from multiple species with minimal observer interference. However, such pairings of camera traps with experimental methods remain underutilized. We review recent advances in the experimental application of camera traps to investigate fundamental mechanisms underlying predator-prey ecology and present a conceptual guide for designing experimental camera trap studies. Only 9% of camera trap studies on predator-prey ecology in our review use experimental methods, but the application of experimental approaches is increasing. To illustrate the utility of camera trap-based experiments using a case study, we propose a study design that integrates observational and experimental techniques to test a perennial question in predator-prey ecology: how prey balance foraging and safety, as formalized by the risk allocation hypothesis. We discuss applications of camera trap-based experiments to evaluate the diversity of anthropogenic influences on wildlife communities globally. Finally, we review challenges to conducting experimental camera trap studies. Experimental camera trap studies have already begun to play an important role in understanding the predator-prey ecology of free-living animals, and such methods will become increasingly critical to quantifying drivers of community interactions in a rapidly changing world. We recommend increased application of experimental methods in the study of predator and prey responses to humans, synanthropic and invasive species, and other anthropogenic disturbances.

Intraocular chemotherapy for vitreoretinal lymphoma: A review.

Vitreoretinal lymphomas are rare ocular cancers, and the subset of primary central nervous system lymphomas that are based in the posterior eye. These tumours are challenging to treat, and today management generally involves a multispecialty team coordinating a treatment protocol that may include intraocular chemotherapy, ocular irradiation, systemic chemotherapy and/or autologous stem cell transplantation. The ophthalmologist has specific responsibility for the intraocular chemotherapy, which is delivered to the eye by intravitreal injection. The most commonly injected drugs are methotrexate-an anti-metabolite-and rituximab-an anti-human B cell monoclonal antibody. A range of intraocular chemotherapy treatment schedules have been described in the medical literature, although to date there have been no randomized clinical trials of these schedules. In this article, we review the development and current status of intraocular chemotherapy for vitreoretinal lymphoma.

Using CRISPR/Cas9 genome editing in tomato to create a gibberellin-responsive dominant dwarf DELLA allele.

The tomato PROCERA gene encodes a DELLA protein, and loss-of-function mutations derepress growth. We used CRISPR/Cas9 and a single guide RNAs (sgRNA) to target mutations to the PROCERA DELLA domain, and recovered several loss-of-function mutations and a dominant dwarf mutation that carries a deletion of one amino acid in the DELLA domain. This is the first report of a dominant dwarf PROCERA allele. This allele retains partial responsiveness to exogenously applied gibberellin. Heterozygotes show an intermediate phenotype at the seedling stage, but adult heterozygotes are as dwarfed as homozygotes.

Dengue Virus Induces Increased Activity of the Complement Alternative Pathway in Infected Cells.

Severe dengue virus (DENV) infection is associated with overactivity of the complement alternative pathway (AP) in patient studies. Here, the molecular changes in components of the AP during DENV infection in vitro were investigated. mRNA for factor H (FH), a major negative regulator of the AP, was significantly increased in DENV-infected endothelial cells (EC) and macrophages, but, in contrast, production of extracellular FH protein was not. This discord was not seen for the AP activator factor B (FB), with DENV induction of both FB mRNA and protein, nor was it seen with Toll-like receptor 3 or 4 stimulation of EC and macrophages, which induces both FH and FB mRNA and protein. Surface-bound and intracellular FH protein was, however, induced by DENV, but only in DENV antigen-positive cells, while in two other DENV-susceptible immortalized cell lines (ARPE-19 and human retinal endothelial cells), FH protein was induced both intracellularly and extracellularly by DENV infection. Regardless of the cell type, there was an imbalance in AP components and an increase in markers of complement AP activity associated with DENV-infected cells, with lower FH relative to FB protein, an increased ability to promote AP-mediated lytic activity, and increased deposition of complement component C3b on the surface of DENV-infected cells. For EC in particular, these changes are predicted to result in higher complement activity in the local cellular microenvironment, with the potential to induce functional changes that may result in increased vascular permeability, a hallmark of dengue disease.IMPORTANCE Dengue virus (DENV) is a significant human viral pathogen with a global medical and economic impact. DENV may cause serious and life-threatening disease, with increased vascular permeability and plasma leakage. The pathogenic mechanisms underlying these features remain unclear; however, overactivity of the complement alternative pathway has been suggested to play a role. In this study, we investigate the molecular events that may be responsible for this observed alternative pathway overactivity and provide novel findings of changes in the complement system in response to DENV infection in primary cell types that are a major target for DENV infection (macrophages) and pathogenesis (endothelial cells) in vivo Our results suggest a new dimension of cellular events that may influence endothelial cell barrier function during DENV infection that could expand strategies for developing therapeutics to prevent or control DENV-mediated vascular disease.

Scavenging in the Anthropocene: Human impact drives vertebrate scavenger species richness at a global scale.

Understanding the distribution of biodiversity across the Earth is one of the most challenging questions in biology. Much research has been directed at explaining the species latitudinal pattern showing that communities are richer in tropical areas; however, despite decades of research, a general consensus has not yet emerged. In addition, global biodiversity patterns are being rapidly altered by human activities. Here, we aim to describe large-scale patterns of species richness and diversity in terrestrial vertebrate scavenger (carrion-consuming) assemblages, which provide key ecosystem functions and services. We used a worldwide dataset comprising 43 sites, where vertebrate scavenger assemblages were identified using 2,485 carcasses monitored between 1991 and 2018. First, we evaluated how scavenger richness (number of species) and diversity (Shannon diversity index) varied among seasons (cold vs. warm, wet vs. dry). Then, we studied the potential effects of human impact and a set of macroecological variables related to climatic conditions on the scavenger assemblages. Vertebrate scavenger richness ranged from species-poor to species rich assemblages (4-30 species). Both scavenger richness and diversity also showed some seasonal variation. However, in general, climatic variables did not drive latitudinal patterns, as scavenger richness and diversity were not affected by temperature or rainfall. Rainfall seasonality slightly increased the number of species in the community, but its effect was weak. Instead, the human impact index included in our study was the main predictor of scavenger richness. Scavenger assemblages in highly human-impacted areas sustained the smallest number of scavenger species, suggesting human activity may be overriding other macroecological processes in shaping scavenger communities. Our results highlight the effect of human impact at a global scale. As species-rich assemblages tend to be more functional, we warn about possible reductions in ecosystem functions and the services provided by scavengers in human-dominated landscapes in the Anthropocene.

Integrating temporal refugia into landscapes of fear: prey exploit predator downtimes to forage in risky places.

The landscape of fear is an important driver of prey space use. However, prey can navigate the landscape of fear by exploiting temporal refuges from predation risk. We hypothesized that diel patterns of predator and prey movement and space use would be inversely correlated due to temporal constraints on predator habitat domain. Specifically, we evaluated habitat selection and activity of the vicuña and its only predator, the puma, during three diel periods: day, dawn/dusk, and night. Pumas selected the same habitats regardless of diel period-vegetated and rugged areas that feature stalking cover for pumas-but increased their activity levels during dawn/dusk and night when they benefit from reduced detection by prey. Vicuñas avoided areas selected by pumas and reduced activity at night, but selected vegetated areas and increased activity by day and dawn/dusk. Vicuña habitat selection and movement strategies appeared to reduce the risk of encountering pumas; movement rates of pumas and vicuñas were negatively correlated across the diel cycle, and habitat selection was negatively correlated during dawn/dusk and night. Our study shows that an ambush predator's temporal activity and space use patterns interact to create diel refugia and shape the antipredator behaviors of its prey. Importantly, it is likely the very nature of ambush predators' static habitat specificity that makes predator activity important to temporally varying perceptions of risk. Prey which depend on risky habitats for foraging appear to mitigate risk by feeding when they can more easily detect predators and when predators are least active.