Author Correction: Ecology, evolution and spillover of coronaviruses from bats.

In the past two decades, three coronaviruses with ancestral origins in bats have emerged and caused widespread outbreaks in humans, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first SARS epidemic in 2002–2003, the appreciation of bats as key hosts of zoonotic coronaviruses has advanced rapidly. More than 4,000 coronavirus sequences from 14 bat families have been identified, yet the true diversity of bat coronaviruses is probably much greater. Given that bats are the likely evolutionary source for several human coronaviruses, including strains that cause mild upper respiratory tract disease, their role in historic and future pandemics requires ongoing investigation. We review and integrate information on bat–coronavirus interactions at the molecular, tissue, host and population levels. We identify critical gaps in knowledge of bat coronaviruses, which relate to spillover and pandemic risk, including the pathways to zoonotic spillover, the infection dynamics within bat reservoir hosts, the role of prior adaptation in intermediate hosts for zoonotic transmission and the viral genotypes or traits that predict zoonotic capacity and pandemic potential. Filling these knowledge gaps may help prevent the next pandemic

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.

The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons

Reducing depression in older home care clients: design of a prospective study of a nurse-led interprofessional mental health promotion intervention

Abstract Background Very little research has been conducted in the area of depression among older home care clients using personal support services. These older adults are particularly vulnerable to depression because of decreased cognition, comorbid chronic conditions, functional limitations, lack of social support, and reduced access to health services. To date, research has focused on collaborative, nurse-led depression care programs among older adults in primary care settings. Optimal management of depression among older home care clients is not currently known. The objective of this study is to evaluate the feasibility, acceptability and effectiveness of a 6-month nurse-led, interprofessional mental health promotion intervention aimed at older home care clients with depressive symptoms using personal support services. Methods/Design This one-group pre-test post-test study aims to recruit a total of 250 long-stay (> 60 days) home care clients, 70 years or older, with depressive symptoms who are receiving personal support services through a home care program in Ontario, Canada. The nurse-led intervention is a multi-faceted 6-month program led by a Registered Nurse that involves regular home visits, monthly case conferences, and evidence-based assessment and management of depression using an interprofessional approach. The primary outcome is the change in severity of depressive symptoms from baseline to 6 months using the Centre for Epidemiological Studies in Depression Scale. Secondary outcomes include changes in the prevalence of depressive symptoms and anxiety, health-related quality of life, cognitive function, and the rate and appropriateness of depression treatment from baseline to 12 months. Changes in the costs of use of health services will be assessed from a societal perspective. Descriptive and qualitative data will be collected to examine the feasibility and acceptability of the intervention and identify barriers and facilitators to implementation. Discussion Data collection began in May 2010 and is expected to be completed by July 2012. A collaborative nurse-led strategy may provide a feasible, acceptable and effective means for improving the health of older home care clients by improving the prevention, recognition, and management of depression in this vulnerable population. The challenges involved in designing a practical, transferable and sustainable nurse-led intervention in home care are also discussed. Trial Registration ClinicalTrials.gov: NCT0140792

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Hormone therapy prescribing patterns in the United States

OBJECTIVE: We sought to examine prescribing patterns (prevalence and rates of initiation and discontinuation) for estrogen plus progestin (hormone therapy [HT] and estrogen alone [ET]) in the United States in the 2 years before the published results of Women\u27s Health Initiative\u27s (WHI) HT trial\u27s early termination and for 5 months after their release. METHODS: We conducted an observational cohort study of 169,586 women aged 40-80 years who were enrolled in 5 health maintenance organizations in the United States to estimate the prevalence of HT and ET and discontinuation and initiation rates between September 1, 1999, to June 31, 2002 (baseline), and December 31, 2002 (follow-up). We used automated pharmacy data to identify all oral and transdermal estrogen and progestin dispensed during the study period. RESULTS: The prevalence of HT declined 46% from baseline to follow-up (14.6% to 7.9%); ET use declined 28% during the same period (12.6% to 9.1%). The discontinuation of HT increased almost immediately, from 2.5% at baseline to 13.8% in October 2002. We saw an immediate decrease in HT and ET initiation rates, from 0.4% and 0.3% at baseline, respectively, to 0.2% for HT and ET at follow-up. CONCLUSION: The diffusion of the WHI HT trial results had an immediate impact on the discontinuation of HT and ET and is likely responsible for the 46% and 28% decline in the initiation of these respective therapies. Further exploration of why women continue to use HT and identification of methods for addressing reasons for continued use are indicated. LEVEL OF EVIDENCE: II-2

The impact of comorbidities on hormone use. After the 2000 release of the Women\u27s Health Initiative

OBJECTIVE: Determine the impact of fracture, coronary disease, and diabetes on changes in rates of discontinuation and initiation of estrogen therapy with (EPT) and without (ET) progestin, before (September 1, 1999 to June 30, 2002, baseline) versus 5 months after (follow-up) release of the Women\u27s Health Initiative EPT trial results (WHI). DESIGN, SETTING, AND PARTICIPANTS: Observational cohort; 169,586 women 40 to 80 years old from 5 U.S. HMOs. METHODS: We used pharmacy data to identify ET and EPT users. A woman was a user any month she filled \u3e or =1 estrogen prescription and in subsequent months based upon the number of pills/patches dispensed. We used inpatient and outpatient claims to identify fracture January 1, 1999 to June 30, 2002 and pharmacy data to identify disease-based groups of medications for diabetes and cardiovascular disease. MEASURES: EPT/ET prevalence, initiation, and discontinuation rates. RESULTS: Baseline to follow-up EPT and ET prevalence declined 45% and 22%, respectively, with no difference by comorbidity. Follow-up EPT initiation was half the baseline rate irrespective of comorbidity. Compared to baseline, follow-up EPT discontinuation rates increased among women with diabetes (relative risk [RR], 6.9; 95% confidence interval [CI], 5.6 to 8.4), cardiovascular disease (RR, 5.5; 95% CI, 4.9 to 6.2), fracture (RR, 3.8; 95% CI, 2.4 to 5.7), and no comorbidity (RR, 4.4; 95% CI, 3.9 to 4.9). The RRs for follow-up versus baseline EPT discontinuation were higher among women with diabetes (P\u3c.01) and cardiovascular disease (P\u3c.01) versus women without these comorbidities. ET discontinuation rates among these same groups were elevated 2- to 2.8-fold. CONCLUSIONS: Diabetes and cardiovascular disease were associated with higher EPT discontinuation rates post-WHI compared to women without comorbidity; comorbidity had little impact on changes in prevalence or initiation of ET/EPT after release of the WHI

Morphological and quantitative analysis of leukocytes in free-living Australian black flying foxes (Pteropus alecto).

The black flying fox (Pteropus alecto) is a natural reservoir for Hendra virus, a paramyxovirus that causes fatal infections in humans and horses in Australia. Increased excretion of Hendra virus by flying foxes has been hypothesized to be associated with physiological or energetic stress in the reservoir hosts. The objective of this study was to explore the leukocyte profiles of wild-caught P. alecto, with a focus on describing the morphology of each cell type to facilitate identification for clinical purposes and future virus spillover research. To this end, we have created an atlas of images displaying the commonly observed morphological variations across each cell type. We provide quantitative and morphological information regarding the leukocyte profiles in bats captured at two roost sites located in Redcliffe and Toowoomba, Queensland, Australia, over the course of two years. We examined the morphology of leukocytes, platelets, and erythrocytes of P. alecto using cytochemical staining and characterization of blood films through light microscopy. Leukocyte profiles were broadly consistent with previous studies of P. alecto and other Pteropus species. A small proportion of individual samples presented evidence of hemoparasitic infection or leukocyte morphological traits that are relevant for future research on bat health, including unique large granular lymphocytes. Considering hematology is done by visual inspection of blood smears, examples of the varied cell morphologies are included as a visual guide. To the best of our knowledge, this study provides the first qualitative assessment of P. alecto leukocytes, as well as the first set of published hematology reference images for this species

Data from: Land use, season, and parasitism predict metal concentrations in Australian flying fox fur

There are two .csv files in this upload. The Pteropus_metal_data_wide.csv file contains metal concentrations (reported in ng/g) measured in fur samples collected from Pteropus flying foxes (P. alecto, P. conspicillatus, P. poliocephalus). Flying foxes were captured from 2015-2018 at multiple sites across Australia. The file also contains capture information (e.g. date, location) and biological information (e.g. species, sex, age class, parasitism) for each flying fox. The Pteropus_metadata.csv file provides further details on all column names in the primary data file, including the specific metals that were quantified. Detailed information on the study methods and results can be found in the associated Science of the Total Environment publication, Land use, season, and parasitism predict metal concentrations in Australian flying fox fur by Sánchez et al