Historical Comparison of Perfluorooctanesulfonate, Perfluorooctanoate, and Other Fluorochemicals in Human Blood

The purpose of this investigation was to determine whether there has been a change in the human blood concentration of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and five other fluorochemicals since 1974. Blood samples were collected in 1974 (serum) and 1989 (plasma) from volunteer participants of a large community health study. The study included a total of 356 samples (178 from each time period). These samples were analyzed by high-pressure liquid chromatography/tandem mass spectrometry methods. The median 1974 and 1989 fluorochemical concentrations, respectively, were as follows: PFOS, 29.5 ng/mL vs. 34.7 ng/mL; PFOA, 2.3 ng/mL vs. 5.6 ng/mL; perfluorohexanesulfonate (PFHS), 1.6 ng/mL vs. 2.4 ng/mL; and N-ethyl perfluorooctanesulfonamidoacetate (PFOSAA), less than the lower limit of quantitation (LLOQ; 1.6 ng/mL, vs. 3.4 ng/mL). For N-methyl perfluorooctanesulfonamidoacetate (M570), perfluorooctanesulfonamide, and perfluorooctanesulfonamidoacetate, median serum concentrations in both years were less than the LLOQ values (1.0, 1.0, and 2.5 ng/mL, respectively). Statistical analysis of 58 paired samples indicated that serum concentrations of PFOS, PFOSAA, PFOA, PFHS, and M570 were significantly (p < 0.001) higher in 1989 than in 1974. The data from 1989 were then compared with geometric mean fluorochemical concentrations of serum samples collected in 2001 from 108 American Red Cross adult blood donors from the same region. Except for M570, there were no statistically significant (p < 0.05) geometric mean fluorochemical concentration differences between the 1989 and 2001 samples. In conclusion, based on this study population, PFOS and other serum fluorochemical concentrations have increased between 1974 and 1989. Comparison with other regional data collected in 2001 did not suggest a continued increase in concentrations since 1989

Association between Serum Perfluorooctanoic Acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey

addresses: Epidemiology and Public Health Group, eninsula Medical School, Exeter, United Kingdom.notes: PMCID: PMC2866686types: Journal Article'Reproduced with permission from Environmental Health Perspectives'Copyright © 2010 National Institute of Environmental Health SciencesPerfluorooctanoic acid (PFOA, also known as C8) and perfluorooctane sulfonate (PFOS) are stable compounds with many industrial and consumer uses. Their persistence in the environment plus toxicity in animal models has raised concern over low-level chronic exposure effects on human health

Time to tweak the TTO: results from a comparison of alternative specifications of the TTO

Abstract This article examines the effect that different specifications of the time trade-off (TTO) valuation task may have on values for EQ-5D-5L health states. The new variants of the TTO, namely lead-time TTO and lag-time TTO, along with the classic approach to TTO were compared using two durations for the health states (15 and 20 years). The study tested whether these methods yield comparable health-state values. TTO tasks were administered online. It was found that lag-time TTO produced lower values than lead-time TTO and that the difference was larger in the longer time frame. Classic TTO values most resembled those of the lag-time TTO in a 20-year time frame in terms of mean absolute difference. The relative importance of different domains of health was systematically affected by the duration of the health state. In the tasks with a 10-year health-state duration, anxiety/ depression had the largest negative impact on health-state values; in the tasks with a 5-year duration, the pain/discomfort domain had the largest negative impact

Sacrocolpopexy without concomitant posterior repair improves posterior compartment defects

The aim of this study is to determine posterior compartment topography 1-year after sacrocolpopexy (SC). Women who had SC without concomitant anterior or posterior repairs for symptomatic pelvic organ prolapse (POP) were included. Vaginal topography was assessed at baseline and 1-year postoperatively using POP quantification (POPQ). At baseline, 24% had stage IV POP, 68% stage III, and 8% stage II. One year after surgery, 75% had stage 0/I POP, 24% stage II, and 1% stage III. 112 (75%) were objectively cured (stage 0 or I POP). Anterior compartment was the most common site of POP persistence or recurrence (Ba ≥ stage II in 23 women) followed by posterior compartment (Bp ≥ stage II in 12 women) and apex (C ≥ stage II in 2 women). In 1-year follow-up, SC without concomitant posterior repair restores posterior vaginal topography in the majority of women with undergoing SC

Effects of intranasal TNFα on granulocyte recruitment and activity in healthy subjects and patients with allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>TNFα may contribute to the pathophysiology of airway inflammation. For example, we have recently shown that nasal administration of TNFα produces late phase co-appearance of granulocyte and plasma exudation markers on the mucosal surface. The objective of the present study was to examine indices of granulocyte presence and activity in response to intranasal TNFα challenge.</p> <p>Methods</p> <p>Healthy subjects and patients with allergic rhinitis (examined out of season) were subjected to nasal challenge with TNFα (10 μg) in a sham-controlled and crossover design. Nasal lavages were carried out prior to and 24 hours post challenge. Nasal biopsies were obtained post challenge. Nasal lavage fluid levels of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were analyzed as indices of neutrophil and eosinophil activity. Moreover, IL-8 and α₂-macroglobulin were analyzed as markers of pro-inflammatory cytokine production and plasma exudation. Nasal biopsy numbers of neutrophils and eosinophils were monitored.</p> <p>Results</p> <p>Nasal lavage fluid levels of MPO recorded 24 hours post TNFα challenge were increased in healthy subjects (p = 0.0081) and in patients with allergic rhinitis (p = 0.0081) (<it>c.f</it>. sham challenge). Similarly, α₂-macroglobulin was increased in healthy subjects (p = 0.014) and in patients with allergic rhinitis (p = 0.0034). Lavage fluid levels of ECP and IL-8 were not affected by TNFα challenge. TNFα increased the numbers of subepithelial neutrophils (p = 0.0021), but not the numbers of eosinophils.</p> <p>Conclusion</p> <p>TNFα produces a nasal inflammatory response in humans that is characterised by late phase (i.e., 24 hours post challenge) neutrophil activity and plasma exudation.</p

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Development of FRET Assay into Quantitative and High-throughput Screening Technology Platforms for Protein–Protein Interactions

Förster resonance energy transfer (FRET) technology has been widely used in biological and biomedical research and is a very powerful tool in elucidating protein interactions in many cellular processes. Ubiquitination and SUMOylation are multi-step cascade reactions, involving multiple enzymes and protein–protein interactions. Here we report the development of dissociation constant (Kd) determination for protein–protein interaction and cell-based high-throughput screening (HTS) assay in SUMOylation cascade using FRET technology. These developments are based on steady state and high efficiency of fluorescent energy transfer between CyPet and YPet fused with SUMO1 and Ubc9, respectively. The developments in theoretical and experimental procedures for protein interaction Kd determination and cell-based HTS provide novel tools in affinity measurement and protein interaction inhibitor screening. The Kd determined by FRET between SUMO1 and Ubc9 is compatible with those determined with other traditional approaches, such as isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR). The FRET-based HTS is pioneer in cell-based HTS. Both Kd determination and cell-based HTS, carried out in 384-well plate format, provide powerful tools for large-scale and high-throughput applications

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (2.5 hour). ETHICS AND DISSEMINATION Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER CRD42018090261