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Background and objective: A range of diagnostic criteria are applied for the heterogenous patient group with fatigue or postviral fatigue syndromes with or without Post Exertional Malaise (PEM). We explored whether DePaul Symptom Questionnaires (DSQ) based symptoms reported in an open online survey called MECOV, served to identify more homogenous sub-groups. Method: Patients living in Norway were invited to participate in an open online survey in 2022. The questionnaire covered diagnostic history, SARS-CoV-2, general health, RAND-36 and DSQ symptoms, treatments and background information. Results: 2362 patients responded to the survey. 1904 respondents had Fatigue or Postviral disease. 1026 fulfilled CCC criteria with multi-dimensional PEM and 14 h recovery period or ICC criteria for ME. 384 fulfilled IOM/NICE or CCC criteria with only less rigid PEM, while 494 respondents fulfilled only broad fatigue and Fukuda criteria. Self-reported health status, number of treatments tried, and reported effect of activity-based treatments varied significantly across the three groups. Conclusion: DSQ symptom-based survey diagnoses served to identify more homogenous subgroups of patients with Fatigue or Postviral diseases (ME and CFS) and may serve as a valid supplement to standard medical examinations. Symptoms, treatment, management strategies and further research may gain from being tailored to the three sub-groups. [ABSTRACT FROM AUTHOR]

A series of lidar measurements has been performed at the Vidsel Test Range, Vidsel, situated in the inland of the very northern part of Sweden, as a part of an assessment of reducing the laser hazard distance using atmospheric attenuation within the calculations of nominal ocular hazard distance (NOHD). The question was “How low is the atmospheric attenuation as function of height in this area, using a wavelength of 1064 nm?” The work included building a ground based backscatter lidar, performing a series of measurements and analyzing the results. The measurements were performed during June to November, 2014, with the objective to measure at clear air and good weather situations. The lidar measurements at 1064 nm showed a very low atmospheric attenuation as a function of height to altitudes of at least 10 km at several occasions. The lowest limit of backscatter coefficient possible to measure with this instrument is 0.3·10-7 m-1 sr-1. Assuming a lidar ratio varying between 30 – 100 sr, this was leading to an extinction coefficient of about 0.9 - 3·10-6 m-1. The atmospheric attenuation reduces the laser hazard distance with about 50 – 56 % depending on the lidar ratio. A recommendation is to monitor the atmospheric attenuation at the occasions when the method to the reduced laser hazard distance using atmospheric attenuation is used.

Communicating the scientific consensus that human-caused climate change is real increases climate change beliefs, worry and support for public action in the United States. In this preregistered experiment, we tested two scientific consensus messages, a classic message on the reality of human-caused climate change and an updated message additionally emphasizing scientific agreement that climate change is a crisis. Across online convenience samples from 27 countries (n = 10,527), the classic message substantially reduces misperceptions (d = 0.47, 95% CI (0.41, 0.52)) and slightly increases climate change beliefs (from d = 0.06, 95% CI (0.01, 0.11) to d = 0.10, 95% CI (0.04, 0.15)) and worry (d = 0.05, 95% CI (-0.01, 0.10)) but not support for public action directly. The updated message is equally effective but provides no added value. Both messages are more effective for audiences with lower message familiarity and higher misperceptions, including those with lower trust in climate scientists and right-leaning ideologies. Overall, scientific consensus messaging is an effective, non-polarizing tool for changing misperceptions, beliefs and worry across different audiences., (© 2024. The Author(s).)

Recurrent pericarditis poses a significant challenge to patients and clinicians given its high morbidity and health care burden. Since the last iteration of European Society of Cardiology Guidelines in 2015, further insights have been gained into the pathophysiology, multimodality imaging assessment, and treatment of this condition. The purpose of this review is to discuss each of these aspects and highlight the role of imaging-guided therapy and interleukin-1 inhibitors in autoinflammatory phenotypes that together have transformed the care of these patients. Although future investigations are needed to optimize diagnostic surveillance and timing of therapy, recent evidence points at an encouraging paradigm shift in the treatment of recurrent pericarditis., Competing Interests: This work was supported by 10.13039/100007312Cleveland Clinic Foundation. Dr Klein has received research funding from 10.13039/100016492Kiniksa Pharmaceuticals, Ltd and Cardiol Therapeutics; and has served on scientific advisory boards for 10.13039/100016492Kiniksa Pharmaceuticals, Ltd, Cardiol Therapeutics, and 10.13039/100004319Pfizer, Inc. Dr Cremer has received research grants from Kiniksa Pharmaceutics and Novartis, and is on advisory boards for Kiniksa Pharmaceutics and Swedish Orphan Biovitrum. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

In patients with cardiac amyloidosis, pericardial involvement is common, with up to half of patients presenting with pericardial effusions. The pathophysiological mechanisms of pericardial pathology in cardiac amyloidosis include chronic elevations in right-sided filling pressures, myocardial and pericardial inflammation due to cytotoxic effects of amyloid deposits, and renal involvement with subsequent uremia and hypoalbuminemia. The pericardial effusions are typically small; however, several cases of life-threatening cardiac tamponade with hemorrhagic effusions have been described as a presenting clinical scenario. Constrictive pericarditis can also occur due to amyloidosis and its identification presents a clinical challenge in patients with cardiac amyloidosis who concurrently manifest signs of restrictive cardiomyopathy. Multimodality imaging, including echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging, is useful in the evaluation and management of this patient population. The recognition of pericardial effusion is important in the risk stratification of patients with cardiac amyloidosis as its presence confers a poor prognosis. However, specific treatment aimed at the effusions themselves is seldom indicated. Cardiac tamponade and constrictive pericarditis may necessitate pericardiocentesis and pericardiectomy, respectively., Competing Interests: Declaration of competing interest Dr. Klein reports serving on the advisory boards for Sobi and Pfizer. The other authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care., Methods: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function., Results: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543)., Conclusions: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units., Clinical Relevance Statement: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT., Key Points: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contrast media did not have an increased incidence of acute kidney injury or persistent decline in renal function. • A more clearly defined risk of iodine contrast media helps guide clinical decisions whether to perform contrast-enhanced CTs or not., (© 2023. The Author(s).)

Background: Sarcopenia refers to a reduction in skeletal muscle mass and strength. Despite the known association between single-slice muscle measurements on lumbar computed tomography and poor outcomes in various clinical settings, studies using thoracic muscle measurements on cardiac magnetic resonance imaging (CMR) have been limited., Methods: Patients undergoing surgical aortic valve replacement (SAVR) between 2010 and 2020 were included if they were ≥ 50 years of age with preoperative CMR. Manual unilateral pectoralis major and minor skeletal muscle area measurements were made at the carina and normalized for body size by height to obtain skeletal muscle index (SMI). Sarcopenia was defined as the lowest sex-stratified SMI tertile and higher-risk as the highest fiftieth percentile Society of Thoracic Surgeons' (STS) mortality score., Results: A total of 133 patients were included, 35 (26.3%) females. The average age was 64 ± 9 years, with most Caucasian (93.2%). Compared to non-sarcopenic patients, sarcopenic patients were older with lower body mass index. During a median follow-up of 27.3 (7.6-60.4) months, 10 (22.2%) deaths occurred in the sarcopenic group and 8 (9.1%) in the non-sarcopenic group (p = 0.039 by log-rank test). On subgroup analysis (66 patients), higher-risk sarcopenic patients had 10 (37.0%) deaths compared to 8 (20.5%) in higher-risk non-sarcopenic patients (p = 0.011 by log-rank test)., Conclusions: Simple unilateral pectoralis muscle measurements on preoperative CMR can be used as an adjunct to traditional risk scores for predicting mortality post-SAVR., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The optimal timing for administering antihypertensive medications remains a topic of debate. This review examines the effectiveness of nighttime vs daytime administration of antihypertensive medications in controlling blood pressure (BP). The MAPEC and Hygia trials suggest that nighttime dosing achieves better BP control and significantly lowers cardiovascular events. However, concerns about methodology and generalizability have been raised. In contrast, the HARMONY and TIME trials found no significant difference in BP control nor cardiovascular outcomes between daytime and nighttime dosing. Current research suggests that the timing of antihypertensive medication administration may not be a crucial factor. Therefore, the decision about the timing of antihypertensive medications administration should be individualized, taking into account patient preference and clinical context, in order to promote consistent compliance., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Urban wastewater treatment plants harbor a large collection of antibiotic resistant enteric bacteria. It is therefore reasonable to hypothesize that workers at such plants would possess a more diverse set of resistant enteric bacteria, compared to the general population. To address this hypothesis, we have compared the fecal microbiome and resistome of 87 workers at wastewater treatment plants (WWTPs) from Romania and the Netherlands to those of 87 control individuals, using shotgun metagenomics. Controlling for potential confounders, neither the total antibiotic resistance gene (ARG) abundance, nor the overall bacterial composition were significantly different between the two groups. If anything, the ARG richness was slightly lower in WWTP workers, and in a stratified analysis the total ARG abundance was significantly lower in Dutch workers compared to Dutch control participants. We identified country of residence, together with recent antibiotic intake in the Dutch population, as the largest contributing factors to the total abundance of ARGs. A striking side-finding was that sex was associated with carriage of disinfectant resistance genes, with women in both Romania and the Netherlands having significantly higher abundance compared to men. A follow up investigation including an additional 313 publicly available samples from healthy individuals from three additional countries showed that the difference was significant for three genes conferring resistance to chemicals commonly used in cosmetics and cleaning products. We therefore hypothesize that the use of cosmetics and, possibly, cleaning products leads to higher abundance of disinfectant resistance genes in the microbiome of the users. Altogether, this study shows that working at a WWTP does not lead to a higher abundance or diversity of ARGs and no large shifts in the overall gut microbial composition in comparison to participants not working at a WWTP. Instead, other factors such as country of residence, recent antibiotic intake and sex seem to play a larger role., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use., Aim: To examine whether snus users eat unhealthier than never tobacco users., Methods: A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models., Results: In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake consisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40])., Conclusion: We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder., Competing Interests: None to declare. The current study was supported by grants from the Norrbotten County Council (to Viktor Oskarsson). The funder had no role in the study design, data collection, analysis or interpretation of data, or preparation of the manuscript., (© 2023 Fanny Berglund et al.)

Objective: Chylopericardium (CPE) is a rare condition associated with accumulation of triglyceride-rich chylous fluid in the pericardial cavity. Due to minimal information on CPE within the literature, we conducted a systematic review of all published CPE cases to understand its clinical characteristics, management and outcomes., Methods: We performed a literature search and identified cases of patients with CPE from 1946 until May 2021 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified relevant articles for pooled analyses of clinical, diagnostic and outcome data., Results: A total of 95 articles with 98 patients were identified. Patient demographics demonstrated male predominance (55%), with a mean age of 37±15 years. Time from symptom onset to diagnosis was 5 (Q1 4.5, Q3 14) days, with 74% of patients symptomatic on presentation. Idiopathic CPE (60%) was the most common aetiology. Cardiac tamponade secondary to CPE was seen in 38% of cases. Pericardial fluid analysis was required in 94% of cases. Lymphangiography identified the leakage site in 59% of patients. Medical therapy (total parenteral nutrition, medium-chain triglycerides or octreotide) was undertaken in 63% of cases. In our cohort, 32% progressed towards surgical intervention. During a median follow-up of 180 (Q1 180, Q3 377) days, CPE recurred in 16% of cases. Of the patients with recurrence, 10% were rehospitalised., Conclusion: CPE tends to develop in younger patients and may cause serious complications. Many patients fail medical therapy, thereby requiring surgical intervention. Although overall mortality is low, associated morbidities warrant close follow-up and possible reintervention and hospitalisations., Competing Interests: Competing interests: ALK: research grant and scientific advisory board for Kiniksa Pharmaceuticals, research grant and scientific advisory board for Cardiol Therapeutics, and scientific advisory board for Pfizer., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Antibiotic resistance is a growing threat to human health, caused in part by pathogens accumulating antibiotic resistance genes (ARGs) through horizontal gene transfer. New ARGs are typically not recognized until they have become widely disseminated, which limits our ability to reduce their spread. In this study, we use large-scale computational screening of bacterial genomes to identify previously undiscovered mobile ARGs in pathogens. From ~1 million genomes, we predict 1,071,815 genes encoding 34,053 unique aminoglycoside-modifying enzymes (AMEs). These cluster into 7,612 families (<70% amino acid identity) of which 88 are previously described. Fifty new AME families are associated with mobile genetic elements and pathogenic hosts. From these, 24 of 28 experimentally tested AMEs confer resistance to aminoglycoside(s) in Escherichia coli, with 17 providing resistance above clinical breakpoints. This study greatly expands the range of clinically relevant aminoglycoside resistance determinants and demonstrates that computational methods enable early discovery of potentially emerging ARGs., (© 2023. Springer Nature Limited.)

Antibiotics are an essential tool of modern medicine, contributing to significantly decreasing mortality and morbidity rates from infectious diseases. However, persistent misuse of these drugs has accelerated the evolution of antibiotic resistance, negatively impacting clinical practice. The environment contributes to both the evolution and transmission of resistance. From all anthropically polluted aquatic environments, wastewater treatment plants (WWTPs) are probably the main reservoirs of resistant pathogens. They should be regarded as critical control points for preventing or reducing the release of antibiotics, antibiotic-resistant bacteria (ARB), and antibiotic-resistance genes (ARGs) into the natural environment. This review focuses on the fate of the pathogens Enterococcus faecium , Staphylococcus aureus , Clostridium difficile , Acinetobacter baumannii , Pseudomonas aeruginosa , and Enterobacteriaceae spp. (ESCAPE) in WWTPs. All ESCAPE pathogen species, including high-risk clones and resistance determinants to last-resort antibiotics such as carbapenems, colistin, and multi-drug resistance platforms, were detected in wastewater. The whole genome sequencing studies demonstrate the clonal relationships and dissemination of Gram-negative ESCAPE species into the wastewater via hospital effluents and the enrichment of virulence and resistance determinants of S. aureus and enterococci in WWTPs. Therefore, the efficiency of different wastewater treatment processes regarding the removal of clinically relevant ARB species and ARGs, as well as the influence of water quality factors on their performance, should be explored and monitored, along with the development of more effective treatments and appropriate indicators (ESCAPE bacteria and/or ARGs). This knowledge will allow the development of quality standards for point sources and effluents to consolidate the WWTP barrier role against the environmental and public health AR threats., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Marutescu, Popa, Gheorghe-Barbu, Barbu, Rodríguez-Molina, Berglund, Blaak, Flach, Kemper, Spießberger, Wengenroth, Larsson, Nowak, Radon, de Roda Husman, Wieser, Schmitt, Pircalabioru Gradisteanu, Vrancianu and Chifiriuc.)

The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where such initial mobilization events of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes., (© 2023. The Author(s).)

Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention., (© 2022. The Author(s).)

Antibiotic resistance (AR) is currently a major threat to global health, calling for a One Health approach to be properly understood, monitored, tackled, and managed. Potential risk factors for AR are often studied in specific high-risk populations, but are still poorly understood in the general population. Our aim was to explore, describe, and characterize potential risk factors for carriage of Extended-Spectrum Beta-Lactamase-resistant Escherichia coli (ESBL-EC) in a large sample of European individuals aged between 16 and 67 years recruited from the general population in Southern Germany, the Netherlands, and Romania. Questionnaire and stool sample collection for this cross-sectional study took place from September 2018 to March 2020. Selected cultures of participants' stool samples were analyzed for detection of ESBL-EC. A total of 1183 participants were included in the analyses: 333 from Germany, 689 from the Netherlands, and 161 from Romania. Travels to Northern Africa (adjusted Odds Ratio, aOR 4.03, 95% Confidence Interval, CI 1.67-9.68), Sub-Saharan Africa (aOR 4.60, 95% CI 1.60-13.26), and Asia (aOR 4.08, 95% CI 1.97-8.43) were identified as independent risk factors for carriage of ESBL-EC. Therefore, travel to these regions should continue to be routinely asked about by clinical practitioners as possible risk factors when considering antibiotic therapy.

Summary: Comparing genomic loci of a given bacterial gene across strains and species can provide insights into their evolution, including information on e.g. acquired mobility, the degree of conservation between different taxa or indications of horizontal gene transfer events. While thousands of bacterial genomes are available to date, there is no software that facilitates comparisons of individual gene loci for a large number of genomes. GEnView (Genetic Environment View) is a Python-based pipeline for the comparative analysis of gene-loci in a large number of bacterial genomes, providing users with automated, taxon-selective access to the >800.000 genomes and plasmids currently available in the NCBI Assembly and RefSeq databases, and is able to process local genomes that are not deposited at NCBI, enabling searches for genomic sequences and to analyze their genetic environments through the interactive visualization and extensive metadata files created by GEnView., Availability and Implementation: GEnView is implemented in Python 3. Instructions for download and usage can be found at https://github.com/EbmeyerSt/GEnView under GLP3., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

Macrolides are broad-spectrum antibiotics used to treat a range of infections. Resistance to macrolides is often conferred by mobile resistance genes encoding Erm methyltransferases or Mph phosphotransferases. New erm and mph genes keep being discovered in clinical settings but their origins remain unknown, as is the type of macrolide resistance genes that will appear in the future. In this study, we used optimized hidden Markov models to characterize the macrolide resistome. Over 16 terabases of genomic and metagenomic data, representing a large taxonomic diversity (11 030 species) and diverse environments (1944 metagenomic samples), were searched for the presence of erm and mph genes. From this data, we predicted 28 340 macrolide resistance genes encoding 2892 unique protein sequences, which were clustered into 663 gene families (<70 % amino acid identity), of which 619 (94 %) were previously uncharacterized. This included six new resistance gene families, which were located on mobile genetic elements in pathogens. The function of ten predicted new resistance genes were experimentally validated in Escherichia coli using a growth assay. Among the ten tested genes, seven conferred increased resistance to erythromycin, with five genes additionally conferring increased resistance to azithromycin, showing that our models can be used to predict new functional resistance genes. Our analysis also showed that macrolide resistance genes have diverse origins and have transferred horizontally over large phylogenetic distances into human pathogens. This study expands the known macrolide resistome more than ten-fold, provides insights into its evolution, and demonstrates how computational screening can identify new resistance genes before they become a significant clinical problem.

To investigate whether wastewater treatment plant (WWTP) workers and residents living in close proximity to a WWTP have elevated carriage rates of ESBL-producing Enterobacterales, as compared to the general population. From 2018 to 2020, we carried out a cross-sectional study in Germany, the Netherlands, and Romania among WWTP workers (N = 344), nearby residents (living ≤ 300 m away from WWTPs; N = 431) and distant residents (living ≥ 1000 m away = reference group; N = 1165). We collected information on potential confounders via questionnaire. Culture of participants' stool samples was performed with ChromID®-ESBL agar plates and species identification with MALDI-TOF-MS. We used logistic regression to estimate the odds ratio (OR) for carrying ESBL-producing E. coli (ESBL-EC). Sensitivity analyses included stratification by country and interaction models using country as secondary exposure. Prevalence of ESBL-EC was 11% (workers), 29% (nearby residents), and 7% (distant residents), and higher in Romania (28%) than in Germany (7%) and the Netherlands (6%). Models stratified by country showed that within the Romanian population, WWTP workers are about twice as likely (aOR = 2.34, 95% CI: 1.22-4.50) and nearby residents about three times as likely (aOR = 3.17, 95% CI: 1.80-5.59) to be ESBL-EC carriers, when compared with distant residents. In stratified analyses by country, we found an increased risk for carriage of ESBL-EC in Romanian workers and nearby residents. This effect was higher for nearby residents than for workers, which suggests that, for nearby residents, factors other than the local WWTP could contribute to the increased carriage., (© 2021. The Author(s).)

Systemic autoimmune diseases are an important cause of pericardial involvement and contribute to up to ∼22% cases of pericarditis with a known aetiology. The underlying mechanism for pericardial involvement varies with each systemic disease and leads to a poor understanding of its management. Multimodality imaging establishes the diagnosis and determines the type and extent of pericardial involvement. In this review, we elaborate upon various pericardial syndromes associated with different systemic autoimmune and autoinflammatory diseases and the multitude of imaging modalities that can be used to further characterize autoimmune pericardial involvement. Lastly, these forms of pericarditis have a greater likelihood of recurrence, and clinicians need to understand their unique treatment approaches to improve patient outcomes., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Antibiotic resistance has become a serious global health threat. Wastewater treatment plants may become unintentional collection points for bacteria resistant to antimicrobials. Little is known about the transmission of antibiotic resistance from wastewater treatment plants to humans, most importantly to wastewater treatment plant workers and residents living in the vicinity. We aim to deliver precise information about the methods used in the AWARE (Antibiotic Resistance in Wastewater: Transmission Risks for Employees and Residents around Wastewater Treatment Plants) study. Within the AWARE study, we gathered data on the prevalence of two antibiotic resistance phenotypes, ESBL-producing E. coli and carbapenemase-producing Enterobacteriaceae , as well as on their corresponding antibiotic resistance genes isolated from air, water, and sewage samples taken from inside and outside of different wastewater treatment plants in Germany, the Netherlands, and Romania. Additionally, we analysed stool samples of wastewater treatment plant workers, nearby residents, and members of a comparison group living ≥1000 m away from the closest WWTP. To our knowledge, this is the first study investigating the potential spread of ESBL-producing E. coli , carbapenemase-producing Enterobacteriaceae , and antibiotic resistance genes from WWTPs to workers, the environment, and nearby residents. Quantifying the contribution of different wastewater treatment processes to the removal efficiency of ESBL-producing E. coli , carbapenemase-producing Enterobacteriaceae , and antibiotic resistance genes will provide us with evidence-based support for possible mitigation strategies.

Background: Metallo-β-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available β-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles., Objectives: To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history., Methods: We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees., Results: We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported., Conclusions: Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1-B1.5 and B3.1-B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Heart failure with preserved ejection fraction (HFpEF) affects half of all patients with heart failure. While previously neglected, the right ventricle (RV) has sparked interest in recent years as a means for better understanding this condition and as a potential therapeutic target.Right ventricular dysfunction (RVD) is present in 4%-50% of patients with HFpEF. The RV is intimately connected to the pulmonary circulation, and pulmonary hypertension is commonly implicated in the pathophysiology of RVD. The development of RVD in HFpEF may also be driven by comorbidities, such as chronic obstructive pulmonary disease, obesity, obstructive sleep apnoea and atrial fibrillation. The evaluation of RVD is particularly challenging due to anatomical and structural factors, as well as unique physiological characteristics of this chamber like load and interventricular dependency. Fractional area change, tricuspid annular plane systolic excursion and tricuspid annular systolic velocity are commonly used measurements of RV function. Speckle tracking echocardiography and cardiac magnetic resonance (CMR) are also gaining attention as important tools for the assessment of RV structure, fibre deformation and systolic performance. Further research is needed to confirm the utility and prognostic significance of RV [ 18 F]fluorodeoxyglucose (FDG) positron emission tomography imaging as FDG accumulation is suggested to increase with progressive RVD. Targeted pharmacotherapy with phosphodiesterase inhibitors, guanylate-cyclase stimulators, nitrates and inhaled inorganic nitrites have yet to demonstrate improvement in RVD, compelling the need for evaluation and discovery of novel pharmacological interventions for this entity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment. Surveillance data also provides an overview of geographical and temporal changes that are invaluable for guiding interventions. Still, due to limited infrastructure and resources, clinical surveillance data is lacking in many parts of the world. Given that sewage is largely made up of human fecal bacteria from many people, sewage epidemiology could provide a cost-efficient strategy to partly fill the current gap in clinical surveillance of antibiotic resistance. Here we explored the potential of sewage metagenomic data to assess clinical antibiotic resistance prevalence using environmental and clinical surveillance data from across the world. The sewage resistome correlated to clinical surveillance data of invasive Escherichia coli isolates, but none of several tested approaches provided a sufficient resolution for clear discrimination between resistance towards different classes of antibiotics. However, in combination with socioeconomic data, the overall clinical resistance situation could be predicted with good precision. We conclude that analyses of bacterial genes in sewage could contribute to informing management of antibiotic resistance.

Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70 % amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria . This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.