It has been two decades since the discovery of adiponectin, and today its role in insulin resistance, inflammation, and atherosclerosis are areas of major interest. Production of adiponectin is reduced in all inflammatory processes and states of insulin resistance such as obesity, type 2 diabetes mellitus, and coronary artery disease. Adiponectin regulates carbohydrate metabolism, and may also regulate vascular homeostasis by affecting important signaling pathways in endothelial cells and modulating inflammatory responses in the subendothelial space. Clinical studies have demonstrated a relationship between serum adiponectin concentrations and the activity of the renin-angiotensin-aldosterone system (RAAS), causing changes in blood pressure. Antihypertensive therapy with angiotensin II receptor blockers (ARBs) has been demonstrated to increase adiponectin levels in 3-6 months. Adiponectin has also been shown to play a role in cardiac injury in modulation of pro-survival reactions, cardiac energy metabolism, and inhibition of hypertrophic remodeling. The effects of adiponectin on the cardiovascular system are believed to be partially mediated by the activation of 5' adenosine monophosphate-activated protein kinase (AMPK) and cyclooxygenase-2 (COX-2) pathways, reducing endothelial cell apoptosis, promoting nitric oxide production, decreasing tumor necrosis factor-alpha (TNF-α) activity, and preventing atherosclerotic proliferation and smooth muscle cell migration. Further evaluation of biologically active forms of adiponectin and its receptor should help to clarify how obesity affects the cardiovascular system.
BackgroundAntibiotic resistance is a global public health threat. Water from human activities is collected at wastewater treatment plants where processes often do not sufficiently neutralize antibiotic resistant bacteria and genes, which are further shed into the local environment. This protocol outlines the steps to conduct a systematic review based on the Population, Exposure, Comparator and Outcome (PECO) framework, aiming at answering the question “Are antimicrobial-resistant enterobacteriaceae and antimicrobial resistance genes present (O) in air and water samples (P) taken either near or downstream or downwind or down-gradient from wastewater treatment plants (E), as compared to air and water samples taken either further away or upstream or upwind or up-gradient from such wastewater treatment plant (C)?” Presence of antimicrobial-resistant bacteria and genes will be quantitatively measured by extracting their prevalence or concentration, depending on the reviewed study.MethodsWe will search PubMed, EMBASE, the Cochrane database and Web of Science for original articles published from 1 Jan 2000 to 3 Sep 2018 with language restriction. Articles will undergo a relevance and a design screening process. Data from eligible articles will be extracted by two independent reviewers. Further, we will perform a risk of bias assessment using a decision matrix. We will synthesize and present results in narrative and tabular form and will perform a meta-analysis if heterogeneity of results allows it.DiscussionAntibiotic resistance in environmental samples around wastewater treatment plants may pose a risk of exposure to workers and nearby residents. Results from the systematic review outlined in this protocol will allow to estimate the extend of exposure, to inform policy making and help to design future studies.
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.
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.
We estimated the degree to which language used in the high profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched and screened for 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, three reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as None (no causal implication) in 13.8%, Weak 34.2%, Moderate 33.2%, and Strong 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers’ ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.
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