Global and cell type-specific immunological hallmarks of severe dengue progression identified via a systems immunology approach.

Severe dengue (SD) is a major cause of morbidity and mortality. To define dengue virus (DENV) target cells and immunological hallmarks of SD progression in children's blood, we integrated two single-cell approaches capturing cellular and viral elements: virus-inclusive single-cell RNA sequencing (viscRNA-Seq 2) and targeted proteomics with secretome analysis and functional assays. Beyond myeloid cells, in natural infection, B cells harbor replicating DENV capable of infecting permissive cells. Alterations in cell type abundance, gene and protein expression and secretion as well as cell-cell communications point towards increased immune cell migration and inflammation in SD progressors. Concurrently, antigen-presenting cells from SD progressors demonstrate intact uptake yet impaired interferon response and antigen processing and presentation signatures, which are partly modulated by DENV. Increased activation, regulation and exhaustion of effector responses and expansion of HLA-DR-expressing adaptive-like NK cells also characterize SD progressors. These findings reveal DENV target cells in human blood and provide insight into SD pathogenesis beyond antibody-mediated enhancement.

A Randomized, Double-Blind, Phase 3 Safety and Efficacy Study of Ridinilazole Versus Vancomycin for Treatment of Clostridioides difficile Infection: Clinical Outcomes With Microbiome and Metabolome Correlates of Response.

BACKGROUND: Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI. METHODS: In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs. RESULTS: Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (∼3.5-fold), and increased the resistome. CONCLUSIONS: Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.

In defense of children's brain: reshuffling the laboratory toolbox for the diagnosis of congenital toxoplasmosis.

For decades, an immunosorbent agglutination assay (ISAGA) has been considered the gold standard method for the detection of Toxoplasma gondii-specific IgM in infants for the diagnosis of congenital toxoplasmosis (CT). The Toxoplasma IgM ISAGA was consistently reported as having superior sensitivity. Unfortunately, the commercial kit for the detection of Toxoplasma IgM ISAGA will no longer be available in 2024 and alternatives will only be available at a handful of reference laboratories as in-house or laboratory-developed tests. In a recent study, S. Arkhis, C. Rouges, N. Dahane, H. Guegan, et al. (J Clin Microbiol 62:e01222-23, 2024, https://doi.org/10.1128/jcm.01222-23), reported that the performance of the PLATELIA Toxo IgM was comparable to that of the ISAGA method for the diagnosis of CT. A second study revealing similar results supports the PLATELIA Toxo IgM as the new gold standard for the detection of T. gondii-specific IgM in infants. Although the laboratory toolbox for CT diagnosis has been reshuffled successfully, it is by universally implementing all available serological and molecular tools at the earliest possible time during gestation that we can best defend children's brain from the potential harm caused by trans-placentally transmitted T. gondii.

Intraspecific diversity loss in a predator species alters prey community structure and ecosystem functions.

Loss in intraspecific diversity can alter ecosystem functions, but the underlying mechanisms are still elusive, and intraspecific biodiversity-ecosystem function (iBEF) relationships have been restrained to primary producers. Here, we manipulated genetic and functional richness of a fish consumer (Phoxinus phoxinus) to test whether iBEF relationships exist in consumer species and whether they are more likely sustained by genetic or functional richness. We found that both genotypic and functional richness affected ecosystem functioning, either independently or interactively. Loss in genotypic richness reduced benthic invertebrate diversity consistently across functional richness treatments, whereas it reduced zooplankton diversity only when functional richness was high. Finally, losses in genotypic and functional richness altered functions (decomposition) through trophic cascades. We concluded that iBEF relationships lead to substantial top-down effects on entire food chains. The loss of genotypic richness impacted ecological properties as much as the loss of functional richness, probably because it sustains "cryptic" functional diversity.

Phytoplankton biodiversity is more important for ecosystem functioning in highly variable thermal environments.

The 21st century has seen an acceleration of anthropogenic climate change and biodiversity loss, with both stressors deemed to affect ecosystem functioning. However, we know little about the interactive effects of both stressors and in particular about the interaction of increased climatic variability and biodiversity loss on ecosystem functioning. This should be remedied because larger climatic variability is one of the main features of climate change. Here, we demonstrated that temperature fluctuations led to changes in the importance of biodiversity for ecosystem functioning. We used microcosm communities of different phytoplankton species richness and exposed them to a constant, mild, and severe temperature-fluctuating environment. Wider temperature fluctuations led to steeper biodiversity-ecosystem functioning slopes, meaning that species loss had a stronger negative effect on ecosystem functioning in more fluctuating environments. For severe temperature fluctuations, the slope increased through time due to a decrease of the productivity of species-poor communities over time. We developed a theoretical competition model to better understand our experimental results and showed that larger differences in thermal tolerances across species led to steeper biodiversity-ecosystem functioning slopes. Species-rich communities maintained their ecosystem functioning with increased fluctuation as they contained species able to resist the thermally fluctuating environments, while this was on average not the case in species-poor communities. Our results highlight the importance of biodiversity for maintaining ecosystem functions and services in the context of increased climatic variability under climate change.

Imaging biomarkers and radiomics in pediatric oncology: a view from the PRIMAGE (PRedictive In silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers) project.

This review paper presents the practical development of imaging biomarkers in the scope of the PRIMAGE (PRedictive In silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers) project, as a noninvasive and reliable way to improve the diagnosis and prognosis in pediatric oncology. The PRIMAGE project is a European multi-center research initiative that focuses on developing medical imaging-derived artificial intelligence (AI) solutions designed to enhance overall management and decision-making for two types of pediatric cancer: neuroblastoma and diffuse intrinsic pontine glioma. To allow this, the PRIMAGE project has created an open-cloud platform that combines imaging, clinical, and molecular data together with AI models developed from this data, creating a comprehensive decision support environment for clinicians managing patients with these two cancers. In order to achieve this, a standardized data processing and analysis workflow was implemented to generate robust and reliable predictions for different clinical endpoints. Magnetic resonance (MR) image harmonization and registration was performed as part of the workflow. Subsequently, an automated tool for the detection and segmentation of tumors was trained and internally validated. The Dice similarity coefficient obtained for the independent validation dataset was 0.997, indicating compatibility with the manual segmentation variability. Following this, radiomics and deep features were extracted and correlated with clinical endpoints. Finally, reproducible and relevant imaging quantitative features were integrated with clinical and molecular data to enrich both the predictive models and a set of visual analytics tools, making the PRIMAGE platform a complete clinical decision aid system. In order to ensure the advancement of research in this field and to foster engagement with the wider research community, the PRIMAGE data repository and platform are currently being integrated into the European Federation for Cancer Images (EUCAIM), which is the largest European cancer imaging research infrastructure created to date.

A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%-2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high-throughput sequencing. We found no consistent group-specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.

Predicting effects of multiple interacting global change drivers across trophic levels.

Global change encompasses many co-occurring anthropogenic drivers, which can act synergistically or antagonistically on ecological systems. Predicting how different global change drivers simultaneously contribute to observed biodiversity change is a key challenge for ecology and conservation. However, we lack the mechanistic understanding of how multiple global change drivers influence the vital rates of multiple interacting species. We propose that reaction norms, the relationships between a driver and vital rates like growth, mortality, and consumption, provide insights to the underlying mechanisms of community responses to multiple drivers. Understanding how multiple drivers interact to affect demographic rates using a reaction-norm perspective can improve our ability to make predictions of interactions at higher levels of organization-that is, community and food web. Building on the framework of consumer-resource interactions and widely studied thermal performance curves, we illustrate how joint driver impacts can be scaled up from the population to the community level. A simple proof-of-concept model demonstrates how reaction norms of vital rates predict the prevalence of driver interactions at the community level. A literature search suggests that our proposed approach is not yet used in multiple driver research. We outline how realistic response surfaces (i.e., multidimensional reaction norms) can be inferred by parametric and nonparametric approaches. Response surfaces have the potential to strengthen our understanding of how multiple drivers affect communities as well as improve our ability to predict when interactive effects emerge, two of the major challenges of ecology today.

Clinical Outcomes of Medical Management Options for Chronic Anal Fissures in a Long-Term Follow-up: Systematic Review and Meta-Analysis.

BACKGROUND: Topical treatments and botulinum toxin injections are valid options for the management of patients with chronic anal fissures (CAF), but little is known about the efficacy of these techniques in long-term follow-up. The aim of this meta-analysis was to evaluate the effectiveness, given to clinical outcomes, of medical treatments with calcium antagonists, nitroglycerin, and botulinum toxin on CAF treatment in adults. METHOD: A systemic review and meta-analysis developed according to PRISMA [PLoS Med. 2009 Jul 21;6(7):e1000100; BMJ. 2010 Mar 23;340:c332] and registered in PROSPERO (Registration number: CRD42020120386). A systematic literature search was conducted through MEDLINE, EMBASE, Web of Science, and Cochrane Library databases. Randomized control trials that compared medical treatment were identified; publications had to have a clinical definition of CAF with at least one of the following signs or symptoms: visible sphincter fibers at the base of the fissure, anal papillae, sentinel piles, and indurated margins. The symptoms had to be chronic for at least 4 weeks. Data were independently extracted for each study, and a meta-analysis was drawn using fixed- and random-effects models. RESULTS: 17 randomized trials met the inclusion criteria. Diltiazem showed a superior effect compared with glycerin (RR = 1.16 [95% CI = 1.05-1.30]; I2 = 18%) and with fewer adverse effects (RR = 0.13 [95% CI = 0.04-0.042]; I2 = 87%). Similar results were evidenced with the use of nifedipine compared with lidocaine (RR = 4.53 [95% CI = 2.99-6.86]; I2 = 28%). Botulinum toxin did not show statistically significant differences compared to glycerin (RR = 0.81 [95% CI = 0.02-29.36]; I2 = 93%) or isosorbide dinitrate (RR = 1.45 [95% CI = 0.32-6.54]; I2 = 85%). Regarding recurrence, nifedipine was superior to lidocaine (RR = 0.18 [95% CI = 0.08-0.44]; I2 = 31%). CONCLUSIONS: Calcium channel blockers performed well regarding the healing of CAF when compared to others in long-term follow-up. The superiority of botulinum toxin was not evidenced compared to topical treatments. More studies are needed to better assess recurrence rates.

On near-redundancy and identifiability of parametric hazard regression models under censoring.

We study parametric inference on a rich class of hazard regression models in the presence of right-censoring. Previous literature has reported some inferential challenges, such as multimodal or flat likelihood surfaces, in this class of models for some particular data sets. We formalize the study of these inferential problems by linking them to the concepts of near-redundancy and practical nonidentifiability of parameters. We show that the maximum likelihood estimators of the parameters in this class of models are consistent and asymptotically normal. Thus, the inferential problems in this class of models are related to the finite-sample scenario, where it is difficult to distinguish between the fitted model and a nested nonidentifiable (i.e., parameter-redundant) model. We propose a method for detecting near-redundancy, based on distances between probability distributions. We also employ methods used in other areas for detecting practical nonidentifiability and near-redundancy, including the inspection of the profile likelihood function and the Hessian method. For cases where inferential problems are detected, we discuss alternatives such as using model selection tools to identify simpler models that do not exhibit these inferential problems, increasing the sample size, or extending the follow-up time. We illustrate the performance of the proposed methods through a simulation study. Our simulation study reveals a link between the presence of near-redundancy and practical nonidentifiability. Two illustrative applications using real data, with and without inferential problems, are presented.

Treated and highly diluted, but wastewater still impacts diversity and energy fluxes of freshwater food webs.

Wastewater treatment plants (WWTPs) have greatly improved water quality globally. However, treated effluents still contain a complex cocktail of pollutants whose environmental effects might go unnoticed, masked by additional stressors in the receiving waters or by spatiotemporal variability. We conducted a BACI (Before-After/Control-Impact) ecosystem manipulation experiment, where we diverted part of the effluent of a large tertiary WWTP into a small, unpolluted stream to assess the effects of a well-treated and highly diluted effluent on riverine diversity and food web dynamics. We sampled basal food resources, benthic invertebrates and fish to search for changes on the structure and energy transfer of the food web with the effluent. Although effluent toxicity was low, it reduced diversity, increased primary production and herbivory, and reduced energy fluxes associated to terrestrial inputs. Altogether, the effluent decreased total energy fluxes in stream food webs, showing that treated wastewater can lead to important ecosystem-level changes, affecting the structure and functioning of stream communities even at high dilution rates. The present study shows that current procedures to treat wastewater can still affect freshwater ecosystems and highlights the need for further efforts to treat polluted waters to conserve aquatic food webs.

Plasma Microbial Cell-free DNA Next-generation Sequencing in the Diagnosis and Management of Febrile Neutropenia.

BACKGROUND: Standard testing fails to identify a pathogen in most patients with febrile neutropenia (FN). We evaluated the ability of the Karius microbial cell-free DNA sequencing test (KT) to identify infectious etiologies of FN and its impact on antimicrobial management. METHODS: This prospective study (ClinicalTrials.gov; NCT02912117) enrolled and analyzed 55 patients with FN. Up to 5 blood samples were collected per subject within 24 hours of fever onset (T1) and every 2 to 3 days. KT results were compared with blood culture (BC) and standard microbiological testing (SMT) results. RESULTS: Positive agreement was defined as KT identification of ≥1 isolate also detected by BC. At T1, positive and negative agreement were 90% (9/10) and 31% (14/45), respectively; 61% of KT detections were polymicrobial. Clinical adjudication by 3 independent infectious diseases specialists categorized Karius results as: unlikely to cause FN (N = 0); definite (N = 12): KT identified ≥1 organism also found by SMT within 7 days; probable (N = 19): KT result was compatible with a clinical diagnosis; possible (N = 10): KT result was consistent with infection but not considered a common cause of FN. Definite, probable, and possible cases were deemed true positives. Following adjudication, KT sensitivity and specificity were 85% (41/48) and 100% (14/14), respectively. Calculated time to diagnosis was generally shorter with KT (87%). Adjudicators determined real-time KT results could have allowed early optimization of antimicrobials in 47% of patients, by addition of antibacterials (20%) (mostly against anaerobes [12.7%]), antivirals (14.5%), and/or antifungals (3.6%); and antimicrobial narrowing in 27.3% of cases. CLINICAL TRIALS REGISTRATION: NCT02912117. CONCLUSION: KT shows promise in the diagnosis and treatment optimization of FN.

Data-driven speciation tree prior for better species divergence times in calibration-poor molecular phylogenies.

MOTIVATION: Precise time calibrations needed to estimate ages of species divergence are not always available due to fossil records' incompleteness. Consequently, clock calibrations available for Bayesian dating analyses can be few and diffused, i.e. phylogenies are calibration-poor, impeding reliable inference of the timetree of life. We examined the role of speciation birth-death (BD) tree prior on Bayesian node age estimates in calibration-poor phylogenies and tested the usefulness of an informative, data-driven tree prior to enhancing the accuracy and precision of estimated times. RESULTS: We present a simple method to estimate parameters of the BD tree prior from the molecular phylogeny for use in Bayesian dating analyses. The use of a data-driven birth-death (ddBD) tree prior leads to improvement in Bayesian node age estimates for calibration-poor phylogenies. We show that the ddBD tree prior, along with only a few well-constrained calibrations, can produce excellent node ages and credibility intervals, whereas the use of an uninformative, uniform (flat) tree prior may require more calibrations. Relaxed clock dating with ddBD tree prior also produced better results than a flat tree prior when using diffused node calibrations. We also suggest using ddBD tree priors to improve the detection of outliers and influential calibrations in cross-validation analyses.These results have practical applications because the ddBD tree prior reduces the number of well-constrained calibrations necessary to obtain reliable node age estimates. This would help address key impediments in building the grand timetree of life, revealing the process of speciation and elucidating the dynamics of biological diversification. AVAILABILITY AND IMPLEMENTATION: An R module for computing the ddBD tree prior, simulated datasets and empirical datasets are available at https://github.com/cathyqqtao/ddBD-tree-prior.

Proinflammatory cytokines levels in sepsis and healthy volunteers, and tumor necrosis factor-alpha associated sepsis mortality: A systematic review and meta-analysis.

BACKGROUND: Sepsis is a global health challenge associated with significant morbidity and mortality. Detrimental sepsis effects are attributed to excessive inflammation or a "cytokine storm." However, anti-inflammation therapies have failed to lower sepsis mortality. We aim to characterize levels of key inflammatory cytokines in patients with sepsis and compare levels with those in healthy individuals and relate tumor necrosis factor (TNF) α levels to patient characteristics and outcomes. METHODS: We performed a systematic review and meta-analysis. Medline, Embase, Cochrane Library, and Web of Science Core Collection databases were searched between 1985 and May 2020. Analysis was restricted to studies in English. We included randomized controlled trials (RCTs), controlled trials, cohort studies, case series, and cross-sectional studies that reported mean levels of cytokines in the circulation thought to be relevant for sepsis pathogenesis. We also evaluated concentrations of these cytokines in healthy individuals. The Quality in Prognosis Studies tool was used to assess the methodological quality of included studies. We extracted summary data from published reports. Data analyses were performed using a random-effects model to estimate pooled odds ratios (OR) with 95% confidence intervals for cytokine levels and mortality. This systematic review is registered in PROSPERO (CRD42020179800). FINDINGS: We identified 3654 records, and 104 studies were included with a total of 3250 participants. The pooled estimated mean TNFα concentration in sepsis patients was 58.4 pg/ml (95% Confidence Interval or CI 39.8-85.8 pg/ml), and in healthy individuals was 5.5 pg/ml (95% CI 3.8-8.0 pg/ml). Pooled estimate means for IL-1ß and IFN-γ in sepsis patients were 21.8 pg/ml and 63.3 pg/ml, respectively. Elevated TNFα concentrations associated with increased 28-day sepsis mortality (p = 0.001). In subgroup analyses, we did not detect an association between TNFα levels and sepsis source, sepsis severity, or sequential organ failure assessment (SOFA) score. A TNF-α cutoff level ≥14.7 pg/ml separated sepsis patients from healthy individuals with a sensitivity of 82.6%, a specificity of 91.7%, and a likelihood ratio of 9.9. INTERPRETATION: Sepsis mean TNFα concentration is increased approximately 10-fold compared to mean concentration in healthy individuals, and TNFα associated with sepsis mortality but not sepsis severity. The concept that elevated cytokines cause sepsis should be revisited in the context of these data. FUNDING: None.

Water diversion and pollution interactively shape freshwater food webs through bottom-up mechanisms.

Water diversion and pollution are two pervasive stressors in river ecosystems that often co-occur. Individual effects of both stressors on basal resources available to stream communities have been described, with diversion reducing detritus standing stocks and pollution increasing biomass of primary producers. However, interactive effects of both stressors on the structure and trophic basis of food webs remain unknown. We hypothesized that the interaction between both stressors increases the contribution of the green pathway in stream food webs. Given the key role of the high-quality, but less abundant, primary producers, we also hypothesized an increase in food web complexity with larger trophic diversity in the presence of water diversion and pollution. To test these hypotheses, we selected four rivers in a range of pollution subject to similar water diversion schemes, and we compared food webs upstream and downstream of the diversion. We characterized food webs by means of stable isotope analysis. Both stressors directly changed the availability of basal resources, with water diversion affecting the brown food web by decreasing detritus stocks, and pollution enhancing the green food web by promoting biofilm production. The propagation of the effects at the base of the food web to higher trophic levels differed between stressors. Water diversion had little effect on the structure of food webs, but pollution increased food chain length and trophic diversity, and reduced trophic redundancy. The effects at higher trophic levels were exacerbated when combining both stressors, as the relative contribution of biofilm to the stock of basal resources increased even further. Overall, we conclude that moderate pollution increases food web complexity and that the interaction with water abstraction seems to amplify this effect. Our study shows the importance of assessing the interaction between stressors to create predictive tools for a proper management of ecosystems.

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.

Oral hygiene prior to cardiac surgery to prevent infections: Randomized clinical trial.

CONTEXT: It is not clear if an oral hygiene protocol to control biofilm applied before cardiac surgery can reduce infection rates. OBJECTIVE: We aim to verify the effectiveness of an oral hygiene protocol in reducing postoperative infections when compared to usual practices, in patients admitted to a cardiology unit, prior to cardiac surgery. DESIGN, SETTING AND PARTICIPANTS: Randomized, blind, controlled clinical trial, with 107 participants who expected to undergo cardiac surgery, randomized into two groups: Experimental Group (EG) standardized oral hygiene protocol (54) and Control Group (CG), usual practices performed in patients admitted (53). INTERVENTION: a standardized oral hygiene protocol, 1 day before surgery: professional prophylaxis with a portable ultrasound device, tooth brushing and flossing plus a 0.12% chlorhexidine gluconate solution (0.12% CHX) mouth rinsing. When applicable, removable prostheses cleaning. PRIMARY OUTCOME: the presence of infection. RESULTS: The occurrence of postoperative infection was higher in CG = 7 (13.2%) than in EG = 5 (9.3%); but no statistical difference was found between protocols (p = 0.518). The length of stayed from surgery to discharge presented a statistical difference (p = 0.047; RR = 4.9; CI = 1.01-24.33); the percentage of postoperative infection was almost five times higher in those participants who stayed 11 or more days. CONCLUSION: The standardized oral hygiene protocol with mechanical and chemical cleaning, 1 day before cardiac surgery, was not more effective than the usual practices performed regarding the reduction of postoperative infections. Other interventions regarding oral hygiene procedures before cardiac surgery must be studied to contribute to the reduction of adverse post-surgical events. CLINICAL TRIAL REGISTRATION: Site Ensaclinicos.gov.br number U1111-1214-2862. DESCRIPTORS: Healthcare Associated Infections, Cardiovascular Diseases, Periodontal Diseases, Dental Biofilm, Cardiovascular Surgery.

Toxoplasmosis Outbreak Associated With Toxoplasma gondii-Contaminated Venison-High Attack Rate, Unusual Clinical Presentation, and Atypical Genotype.

BACKGROUND: During 2017, in response to a physician's report, the Wisconsin Department of Health Services, Division of Public Health, began investigating an outbreak of febrile illness among attendees of a retreat where never frozen, intentionally undercooked, locally harvested venison was served. Preliminary testing tentatively identified the illness as toxoplasmosis. METHODS: Confirmatory human serology panels and testing of the venison to confirm and categorize the presence and type of Toxoplasma gondii were completed by French and American national reference laboratories. All 12 retreat attendees were interviewed; medical records were reviewed. RESULTS: All attendees were male; median age was 51 years (range: 22-75). After a median incubation period of 7 days, 9 (82%) of 11 exposed persons experienced illness lasting a median of 12 days. All 9 sought outpatient healthcare for symptoms including fever, chills, sweats, and headache (100%) and ocular disturbances (33%). Testing confirmed the illness as toxoplasmosis and venison as the infection source. Multiple laboratory results were atypical for toxoplasmosis, including transaminitis (86%), lymphocytopenia (88%), thrombocytopenia (38%), and leukopenia (63%). One exposed but asymptomatic person was seronegative; the other had immunity from prior infection. The T. gondii strain was identified as closely related to an atypical genotype (haplogroup 12, polymerase chain reaction restriction fragment length polymorphism genotype 5) common in North American wildlife but with previously uncharacterized human clinical manifestations. CONCLUSIONS: The T. gondii strain contaminating the venison might explain the unusual clinical presentations. In North America, clinicians and venison consumers should be aware of risk for severe or unusual presentations of acute toxoplasmosis after consuming undercooked game meat.

Theory of temperature-dependent consumer-resource interactions.

Changes in temperature affect consumer-resource interactions, which underpin the functioning of ecosystems. However, existing studies report contrasting predictions regarding the impacts of warming on biological rates and community dynamics. To improve prediction accuracy and comparability, we develop an approach that combines sensitivity analysis and aggregate parameters. The former determines which biological parameters impact the community most strongly. The use of aggregate parameters (i.e., maximal energetic efficiency, ρ, and interaction strength, κ), that combine multiple biological parameters, increases explanatory power and reduces the complexity of theoretical analyses. We illustrate the approach using empirically derived thermal dependence curves of biological rates and applying it to consumer-resource biomass ratio and community stability. Based on our analyses, we generate four predictions: (1) resource growth rate regulates biomass distributions at mild temperatures, (2) interaction strength alone determines the thermal boundaries of the community, (3) warming destabilises dynamics at low and mild temperatures only and (4) interactions strength must decrease faster than maximal energetic efficiency for warming to stabilise dynamics. We argue for the potential benefits of directly working with the aggregate parameters to increase the accuracy of predictions on warming impacts on food webs and promote cross-system comparisons.