Assessment of glove stretch and storage temperature on fentanyl permeation: Implications for standard test methods and PPE recommendations.

The National Institute for Occupational Safety and Health recommends the use of nitrile gloves with a minimum thickness of 5.0 ± 2.0 mil [0.127 ± 0.051 millimeters] in situations where it is suspected or known that fentanyl or other illicit drugs are present. However, there is limited data available on fentanyl permeation through gloves. Current test methods used to measure fentanyl permeation do not consider the effect of glove fit and flexion. Furthermore, first responders need to have PPE readily available in the field, and storage conditions may affect the protective performance of the gloves. The objective of this study was to evaluate the effects of glove stretch and storage temperatures on glove durability and barrier performance against fentanyl. Nine nitrile glove models previously shown to be resistant to fentanyl permeation were selected for this investigation. These nine models were stretched 25% in one linear direction, to consider glove fit and flexion, and tested against fentanyl hydrochloride permeation. Additionally, four of the nine glove models were stored at 48 °C, 22 °C, and -20 °C, and evaluated for tensile strength, ultimate elongation, and puncture resistance after up to 16 wk of storage and fentanyl permeation after up to 8 wk of storage. At least one sample for six of the nine tested models had maximum permeation over the test method fail threshold when stretched. The tested storage temperatures showed no effect on glove tensile strength, ultimate elongation, and puncture resistance. The findings of this study can be used to inform PPE recommendations, with consideration to storage practices and proper sizing for first responders with potential exposure to fentanyl and other illicit drugs. The results of this study can be used to assess the need for new standard test methods to evaluate the barrier performance of gloves and shelf-life determination with consideration to glove fit.

A Control Banding Framework for Protecting the US Workforce from Aerosol Transmissible Infectious Disease Outbreaks with High Public Health Consequences.

Recent high-profile infectious disease outbreaks illustrate the importance of selecting appropriate control measures to protect a wider range of employees, other than those in healthcare settings. In such settings, where routine exposure risks are often high, control measures may be more available, routinely implemented, and studied for effectiveness. In the absence of evidence-based guidelines or established best practices for selecting appropriate control measures, employers may unduly rely on personal protective equipment (PPE) because of its wide availability and pervasiveness as a control measure, circumventing other effective options for protection. Control banding is one approach that may be used to assign job tasks into risk categories and prioritize the application of controls. This article proposes an initial control banding framework for workers at all levels of risk and incorporates a range of control options, including PPE. Using the National Institutes of Health (NIH) risk groups as a surrogate for toxicity and combining the exposure duration with the exposure likelihood, we can generate the risk of a job task to the worker.

Assessment of environmental and surgical mask contamination at a student health center - 2012-2013 influenza season.

Increased understanding of influenza transmission is critical for pandemic planning and selecting appropriate controls for healthcare personnel safety and health. The goals of this pilot study were to assess environmental contamination in different areas and at two time periods in the influenza season and to determine the feasibility of using surgical mask contamination to evaluate potential exposure to influenza virus. Bioaerosol samples were collected over 12 days (two 6-day sessions) at 12 locations within a student health center using portable two-stage bioaerosol samplers operating 8 hr each day. Surface samples were collected each morning and afternoon from common high-contact non-porous hard surfaces from rooms and locations where bioaerosol samplers were located. Surgical masks worn by participants while in contact with patients with influenza-like illness were collected. A questionnaire administered to each of the 12 participants at the end of each workday and another at the end of each workweek assessed influenza-like illness symptoms, estimated the number of influenza-like illness patient contacts, hand hygiene, and surgical mask usage. All samples were analyzed using qPCR. Over the 12 days of the study, three of the 127 (2.4%) bioaerosol samples, 2 of 483 (0.41%) surface samples, and 0 of 54 surgical masks were positive for influenza virus. For the duration of contact that occurred with an influenza patient on any of the 12 days, nurse practitioners and physicians reported contacts with influenza-like illness patients >60 min, medical assistants reported 15-44 min, and administrative staff reported <30 min. Given the limited number of bioaerosol and surface samples positive for influenza virus in the bioaerosol and surface samples, the absence of influenza virus on the surgical masks provides inconclusive evidence for the potential to use surgical masks to assess exposure to influenza viruses. Further studies are needed to determine feasibility of this approach in assessing healthcare personnel exposures. Information learned in this study can inform future field studies on influenza transmission.

Assessment of influenza virus exposure and recovery from contaminated surgical masks and N95 respirators.

Healthcare workers (HCWs) are at significantly higher risk of exposure to influenza virus during seasonal epidemics and global pandemics. During the 2009 influenza pandemic, some healthcare organizations recommended that HCWs wear respiratory protection such as filtering facepiece respirators, while others indicated that facemasks such as surgical masks (SMs) were sufficient. To assess the level of exposure a HCW may possibly encounter, the aim of this study was to (1.) evaluate if SMs and N95 respirators can serve as "personal bioaerosol samplers" for influenza virus and (2.) determine if SMs and N95 respirators contaminated by influenza laden aerosols can serve as a source of infectious virus for indirect contact transmission. This effort is part of a National Institute for Occupational Safety and Health 5-year multidisciplinary study to determine the routes of influenza transmission in healthcare settings. A coughing simulator was programmed to cough aerosol particles containing influenza virus over a wide concentration range into an aerosol exposure simulation chamber virus/L of exam room air), and a breathing simulator was used to collect virus on either a SM or N95 respirator. Extraction buffers containing nonionic and anionic detergents as well as various protein additives were used to recover influenza virus from the masks and respirators. The inclusion of 0.1% SDS resulted in maximal influenza RNA recovery (41.3%) but with a complete loss of infectivity whereas inclusion of 0.1% bovine serum albumin resulted in reduced RNA recovery (6.8%) but maximal retention of virus infectivity (17.9%). Our results show that a HCW's potential exposure to airborne influenza virus can be assessed in part through analysis of their SMs and N95 respirators, which can effectively serve as personal bioaerosol samplers.

Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?

Understanding the molecular defects underlying cardiovascular disease is necessary for the development of therapeutics. The most common method to lower circulating lipids, which reduces the incidence of cardiovascular disease, is statins, but other drugs are now entering the clinic, some of which have been approved. Nevertheless, patients cannot tolerate some of these therapeutics, the drugs are costly, and/or the treatments are approved for only rare forms of disease. Efforts to find alternative treatments have focused on other factors, such as apolipoproteinB (apoB), which transports cholesterol in the blood stream. The levels of apoB are regulated by endoplasmic reticulum (ER) associated degradation as well as by a post ER degradation pathway in model systems, and we suggest that these events provide novel therapeutic targets. We discuss first how cardiovascular disease arises and how cholesterol is regulated, and then summarize the mechanisms of action of existing treatments for cardiovascular disease. We then review the apoB biosynthetic pathway, focusing on steps that might be amenable to therapeutic interventions.

Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates.

Macrophage accumulation in atherosclerosis is directly linked to the destabilization and rupture of plaque, causing acute atherothrombotic events. Circulating monocytes enter the plaque and differentiate into macrophages, where they are activated by CD4+ T lymphocytes through CD40-CD40 ligand signalling. Here, we report the development and multiparametric evaluation of a nanoimmunotherapy that moderates CD40-CD40 ligand signalling in monocytes and macrophages by blocking the interaction between CD40 and tumour necrosis factor receptor-associated factor 6 (TRAF6). We evaluated the biodistribution characteristics of the nanoimmunotherapy in apolipoprotein E-deficient (Apoe-/-) mice and in non-human primates by in vivo positron-emission tomography imaging. In Apoe-/- mice, a 1-week nanoimmunotherapy treatment regimen achieved significant anti-inflammatory effects, which was due to the impaired migration capacity of monocytes, as established by a transcriptome analysis. The rapid reduction of plaque inflammation by the TRAF6-targeted nanoimmunotherapy and its favourable toxicity profiles in both mice and non-human primates highlights the translational potential of this strategy for the treatment of atherosclerosis.

Author Correction: Efficacy and safety assessment of a TRAF6-targeted nanoimmunotherapy in atherosclerotic mice and non-human primates.

In the version of this Article originally published, the surname of the author Edward A. Fisher was spelt incorrectly as 'Fischer'. This has now been corrected.

Regression of inflammation in atherosclerosis by the LXR agonist R211945: a noninvasive assessment and comparison with atorvastatin.

OBJECTIVES: The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945. BACKGROUND: R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control. METHODS: Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test. RESULTS: (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02). CONCLUSIONS: Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis.

Pioglitazone modulates vascular inflammation in atherosclerotic rabbits noninvasive assessment with FDG-PET-CT and dynamic contrast-enhanced MR imaging.

OBJECTIVES: We sought to determine the antiatherosclerotic properties of pioglitazone using multimethod noninvasive imaging techniques. BACKGROUND: Inflammation is an essential component of vulnerable or high-risk atheromas. Pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, possesses potent anti-inflammatory properties. We aimed to quantify noninvasively the anti-inflammatory effects of pioglitazone on atheroma using (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). METHODS: Atherosclerotic plaques were induced in the aorta of 15 New Zealand white rabbits by a combination of a hyperlipidemic diet and 2 balloon endothelial denudations. Nine rabbits continued the same diet, whereas 6 rabbits received pioglitazone (10 mg/kg orally) in addition to the diet. Twelve animals underwent (18)F-FDG-PET/CT, and 15 animals underwent DCE-MRI at baseline, 1 month, and 3 months after treatment initiation. Concomitantly, serum metabolic parameters were monitored. After imaging was completed, aortic histologic analysis and correlation analysis were performed. RESULTS: The (18)F-FDG-PET/CT imaging detected an increase in average standardized uptake value in the control group (p < 0.01), indicating progressive inflammation, whereas stable standardized uptake values were observed in the treatment group, indicating no progression. The DCE-MRI analysis detected a significant decrease in the area under the curve for the pioglitazone group (p < 0.01). Immunohistologic examination of the aortas demonstrated a significant decrease in macrophage and oxidized phospholipid immunoreactivity in the pioglitazone group (p = 0.04 and p = 0.01, respectively) with respect to control animals, underlining the imaging results. Serum metabolic parameters showed no difference between groups. Strong positive correlations between standardized uptake value and macrophage density and between area under the curve and neovessels were detected (r(2) = 0.86 and p < 0.0001, and r(2) = 0.66 and p = 0.004, respectively). CONCLUSIONS: Both (18)F-FDG-PET/CT and DCE-MRI demonstrate noninvasively the anti-inflammatory effects of pioglitazone on atheroma. Both imaging methods seem suited to monitor inflammation in atherosclerosis.