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Deep ocean foraging northern elephant seals (Mirounga angustirostris) consume fish and squid in remote depths of the North Pacific Ocean. Contaminants bioaccumulated from prey are subsequently transferred by adult females to pups during gestation and lactation, linking pups to mercury contamination in mesopelagic food webs (200-1000 m depths). Maternal transfer of mercury to developing seal pups was related to maternal mercury contamination and was strongly correlated with maternal foraging behavior (biotelemetry and isotopes). Mercury concentrations in lanugo (hair grown in utero) were among the highest observed worldwide for young pinnipeds (geometric mean 23.01 μg/g dw, range 8.03-63.09 μg/g dw; n = 373); thus, some pups may be at an elevated risk of sub-lethal adverse health effects. Fetal mercury exposure was affected by maternal foraging geographic location and depth; mercury concentrations were highest in pups of the deepest diving, pelagic females. Moreover, pup lanugo mercury concentrations were strongly repeatable among successive pups of individual females, demonstrating relative consistency in pup mercury exposure based on maternal foraging strategies. Northern elephant seals are biosentinels of a remote deep-sea ecosystem. Our results suggest that mercury within North Pacific mesopelagic food webs may also pose an elevated risk to other mesopelagic-foraging predators and their offspring.

BackgroundCoccidioidomycosis (cocci) is an endemic fungal disease that can cause asymptomatic or post-symptomatic lung nodules which are visible on chest CT scanning. Lung nodules are common and can represent early lung cancer. Differentiating lung nodules due to cocci from those due to lung cancer can be difficult and lead to invasive and expensive evaluations.Materials and methodsWe identified 302 patients with biopsy-proven cocci or bronchogenic carcinoma seen in our multidisciplinary nodule clinic. Two experienced radiologists who were blinded to the diagnosis read the chest CT scans and identified radiographic characteristics to determine their utility in differentiating lung cancer nodules from those due to cocci.ResultsUsing univariate analysis, we identified several radiographic findings that differed between lung cancer and cocci infection. We then entered these variables along with age and gender into a multivariate model and found that age, nodule diameter, nodule cavitation, presence of satellite nodules and radiographic presence of chronic lung disease differed significantly between the two diagnoses. Three findings, cavitary nodules, satellite nodules and chronic lung disease, have sufficient discrimination to potentially be useful in clinical decision-making.ConclusionsCareful evaluation of the three obtained radiographic findings can significantly improve our ability to differentiate benign coccidioidomycosis infection from lung cancer in an endemic region for the fungal disease. Using these data may significantly reduce the cost and risk associated with distinguishing the cause of lung nodules in these patients by preventing unnecessary invasive studies.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including typical, indeterminate, and atypical appearance for COVID-19, or negative for pneumonia, adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Objective: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Results: Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. Conclusion: This study suggests which types of interventions are more effective in addressing depression in heart failure patients.

CX3CR1, one of the highest expressed genes in microglia in mice and humans, is implicated in numerous microglial functions. However, the molecular mechanisms underlying Cx3cr1 signaling are not well understood. Here, we analyzed transcriptomes of Cx3cr1-deficient microglia under varying conditions by RNA-sequencing (RNA-seq). In 2-mo-old mice, Cx3cr1 deletion resulted in the down-regulation of a subset of immune-related genes, without substantial epigenetic changes in markers of active chromatin. Surprisingly, Cx3cr1-deficient microglia from young mice exhibited a transcriptome consistent with that of aged Cx3cr1-sufficient animals, suggesting a premature aging transcriptomic signature. Immunohistochemical analysis of microglia in young and aged mice revealed that loss of Cx3cr1 modulates microglial morphology in a comparable fashion. Our results suggest that CX3CR1 may regulate microglial function in part by modulating the expression levels of a subset of inflammatory genes during chronological aging, making Cx3cr1-deficient mice useful for studying aged microglia.

ObjectivesOptimistic expectations about prognosis by surrogate decision-makers in ICUs are common, but there are few data about the causes and clinical consequences. Our objective was to determine the causes of optimistic expectations about prognosis among surrogates and whether it is associated with more use of life support at the end of life.DesignProspective, multicenter cohort study from 2009 to 2012.SettingTwelve ICUs from multiple regions of the United States.SubjectsThe surrogates and physicians of 275 incapacitated ICU patients at high risk of death.InterventionsNone.Measurements and main resultsSurrogates and physicians completed a validated instrument assessing their prognostic expectations for hospital survival. We determined the proportion of surrogates with optimistic expectations, defined as a prognostic estimate that was at least 20% more optimistic than the physician's, then determined how frequently this arose from surrogates miscomprehending the physicians' prognosis versus holding more hopeful beliefs compared with the physician. We used multivariable regression to examine whether optimistic expectations were associated with length of stay, stratified by survival status, and time to withdrawal of life support among nonsurvivors. Overall, 45% of surrogates (95% CI, 38-51%) held optimistic expectations about prognosis, which arose from a combination of misunderstanding the physician's prognostic expectations and from holding more hopeful beliefs compared with the physician. Optimistic expectations by surrogates were associated with significantly longer duration of ICU treatment among nonsurvivors before death (β coefficient = 0.44; 95% CI, 0.05-0.83; p = 0.027), corresponding to a 56% longer ICU stay. This difference was associated with a significantly longer time to withdrawal of life support among dying patients whose surrogates had optimistic prognostic expectations compared with those who did not (β coefficient = 0.61; 95% CI, 0.16-1.07; p = 0.009).ConclusionsThe prevalent optimism about prognosis among surrogates in ICUs arises both from surrogates' miscomprehension of physicians' prognostications and from surrogates holding more hopeful beliefs. This optimism is associated with longer duration of life support at the end of life.