Myocarditis and dilated cardiomyopathy (DCM) are often caused by viral infections and occur more frequently in men than in women, but the reasons for the sex difference remain unclear. The aim of this study was to assess whether gene changes in the heart during coxsackievirus B3 (CVB3) myocarditis in male and female BALB/c mice predicted worse DCM in males. Although myocarditis (P = 4.2 × 10(-5)) and cardiac dilation (P = 0.008) were worse in males, there was no difference in viral replication in the heart. Fibrotic remodeling genes, such as tissue inhibitor of metalloproteinase (TIMP)-1 and serpin A 3n, were upregulated in males during myocarditis rather than during DCM. Using gonadectomy and testosterone replacement, we showed that testosterone increased cardiac TIMP-1 (P = 0.04), serpin A 3n (P = 0.007), and matrix metalloproteinase (MMP)-8 (P = 0.04) during myocarditis. Testosterone increased IL-1β levels in the heart (P = 0.02), a cytokine known to regulate cardiovascular remodeling, and IL-1β in turn increased cardiac serpin A 3n mRNA (P = 0.005). We found that 39 of 118 (33%) genes identified in acute DCM patients were significantly altered in the heart during CVB3 myocarditis in mice, including serpin A 3n (3.3-fold change, P = 0.0001). Recombinant serpin A 3n treatment induced cardiac fibrosis during CVB3 myocarditis (P = 0.0008) while decreasing MMP-3 (P = 0.04) and MMP-9 (P = 0.03) levels in the heart. Thus, serpin A 3n was identified as a gene associated with fibrotic cardiac remodeling and progression to DCM in male myocarditis patients and mice.
Hydrologic and irrigation regimes mediate the timing of selenium (Se) mobilization to rivers, but the extent to which patterns in Se uptake and trophic transfer through recipient food webs reflect the temporal variation in Se delivery is unknown. We investigated Se mobilization, partitioning, and trophic transfer along approximately 60 river miles of the selenium-impaired segment of the Lower Gunnison River (Colorado, USA) during six sampling trips between June 2015 and October 2016. We found temporal patterns in Se partitioning and trophic transfer to be independent of those in dissolved Se concentrations and that the recipient food web sustained elevated Se concentrations from earlier periods of high Se mobilization. Using an ecosystem-scale Se accumulation model tailored to the Lower Gunnison River, we predicted that the endangered Razorback Sucker (Xyrauchen texanus) and Colorado Pikeminnow (Ptychocheilus lucius) achieve whole-body Se concentrations exceeding aquatic life protection criteria during periods of high runoff and irrigation activity (April–August) that coincide with susceptible phases of reproduction and early-life development. The results of this study challenge assumptions about Se trophodynamics in fast-flowing waters and introduce important considerations for the management of Se risks for biota in river ecosystems.
Per- and poly-fluoroalkyl substances (PFAS) are a large group of man-made chemicals that repel oil, stains, grease, and water and are fire resistant. PFAS are known to be persistent in the environment and bioaccumulate in human and animal tissue, soil, and water. To mitigate human exposure to these chemicals, PFAS analysis by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) was used to monitor their presence in the environment. This study focused on analyzing oysters harvested from coastal New England for 14 PFAS. The validated method addressed in this study utilized a quick, easy, cheap, effective, rugged, and safe (QuEChERS) approach using various sorbents and showed that the combination of primary secondary amine/graphitized carbon black (PSA/GCB) provided the most effective sample clean-up prior to analysis. The recoveries for the targeted analysis ranged from 61% to 116.3% with relative standard deviations from 2.4% to 13.3% at the 125.0 ng mL−1 analyte level. The method detection limits were from 0.33 ng g−1 to 6.75 ng g−1. In a targeted analysis of five unknown samples, two samples had a detectable level of the legacy compound, perfluorooctanesulfonic acid (PFOS).
Objective. To analyze our five-year experience with a telephone helpline service for patients suffering from chronic rheumatic diseases and provide the patients' perspective derived from a dedicated survey. Methods. A telephone service (contact center) was set up in the rheumatology unit at Sapienza University of Rome, Italy, in September 2007. It is managed by operators from a medical service society who collect the patients'calls. Daily reports with medical issues are transmitted to the physicians who are supposed to call back shortly. A year after the institution of the contact center, a questionnaire was administered to a group of patients to address the level of satisfaction. Results. A total of 39,076 calls were registered between September 2007 and August 2012. Each month, an average of 20% of the calls were made by patients referring to our rheumatology unit for the first time and an average of 68.5% patients phoned to request medical consultation. Demographic analysis demonstrated a prevalence of middle-aged female patients. The majority of patients filling in the questionnaire declared an intention to use it again in the future. Furthermore, 85.7% of callers reported full satisfaction with respect to the responses received to their requests. Conclusions. A telephone helpline may provide extra-clinical advice and support for patients with rheumatic diseases. Although these services cannot replace clinical appointments, they should be encouraged both to assure patients easy access to medical counseling and to optimize the daily clinical workload of physicians.
Abstract Coal, as one of the most economic and abundant energy sources, remains the leading fuel for producing electricity worldwide. Yet, burning coal produces more global warming CO 2 relative to all other fossil fuels, and it is a major contributor to atmospheric particulate matter known to have a deleterious respiratory and cardiovascular impact in humans, especially in China and India. Here we have discovered that burning coal also produces large quantities of otherwise rare Magnéli phases (Ti x O 2 x –1 with 4 ≤ x ≤ 9) from TiO 2 minerals naturally present in coal. This provides a new tracer for tracking solid-state emissions worldwide from industrial coal-burning. In its first toxicity testing, we have also shown that nanoscale Magnéli phases have potential toxicity pathways that are not photoactive like TiO 2 phases, but instead seem to be biologically active without photostimulation. In the future, these phases should be thoroughly tested for their toxicity in the human lung.
