Cerium Dioxide Nanoparticle Exposure Improves Microvascular Dysfunction and Reduces Oxidative Stress in Spontaneously Hypertensive Rats

The elevated production of reactive oxygen species (ROS) in the vascular wall is associated with cardiovascular diseases such as hypertension. This increase in oxidative stress contributes to various mechanisms of vascular dysfunction, such as decreased nitric oxide bioavailability. Therefore, anti-oxidants are being researched to decrease the high levels of ROS, which could improve the microvascular dysfunction associated with various cardiovascular diseases. From a therapeutic perspective, cerium dioxide nanoparticles (CeO2 NP) hold great anti-oxidant potential, but their in vivo activity is unclear. Due to this potential anti-oxidant action, we hypothesize that injected CeO2 NP would decrease microvascular dysfunction and oxidative stress associated with hypertension. In order to simulate a therapeutic application, spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were intravenously injected with either saline or CeO2NP (100 μg suspended in saline). Twenty-four hours post-exposure mesenteric arteriolar reactivity was assessed via intravital microscopy. Endothelium-dependent and –independent function was assessed via acetylcholine and sodium nitroprusside. Microvascular oxidative stress was analyzed using fluorescent staining in isolated mesenteric arterioles. Finally, systemic inflammation was examined using a multiplex analysis and venular leukocyte flux was counted. Endothelium-dependent dilation was significantly decreased in the SH rats (29.68 ± 3.28%, maximal response) and this microvascular dysfunction was significantly improved following CeO2 NP exposure (43.76 ± 4.33%, maximal response). There was also an increase in oxidative stress in the SH rats, which was abolished following CeO2 NP treatment. These results provided evidence that CeO2 NP act as an anti-oxidant in vivo. There were also changes in the inflammatory profile in the WKY and SH rats. In WKY rats, IL-10 and TNF-α were increased following CeO2 NP treatment. Finally, leukocyte flux was increased in the SH rats (34 ± 4 vs. 17 ± 3 cells/min in the normotensive controls), but this activation was decreased following exposure (15 ± 2 vs. 34 ± 4 cells/min). These results indicated that CeO2 NP may alter the inflammatory response in both SH and WKY rats. Taken together, these results provide evidence that CeO2 NP act as an anti-oxidant in vivo and may improve microvascular reactivity in a model of hypertension

Impact of Difficult Airway Training on Performance of Korean Paramedic Students in Simulated Normal and Difficult Airway Scenarios: A Randomized Educational Intervention Study

Aim: Evaluate the impact of difficult airway traning on Korean paramedic students' performance during manikin-based airway management simulations. Methods: 40 Korean paramedic students with previous training in airway management and endotracheal intubation were randomly assigned to an intervention or control group. Students in the intervention group completed 16 additional hours of training using curriculum from the Difficult Airway Course<sup>™</sup>. Both groups were then tested on a series of airway management scenarios using a Laerdal SimMan<sup>®</sup> manikin. Results: All participants were able to secure the airway in a normal intubaion scenario, though the intervention group did so fasster on average (121.9 seconds vs. 161.2 seconds in the control group, p=.04). None of the students in the control group were able to secure the airway of a manikin manifesting tongue edema, shile 18 of 20 students in the intervention group sere successful. Students in both groups were equally likily to secure the airway of a manikin fitted with a cervical spine immobilization collar. Students in the intervention group were more likely to employ video laryngoscopy or use a gum elastic bougie to assist during intubaion. On average, students in the intervention group scored significantly higher on a checklist of airway management maneuvers for all three scenarios (p<.001) and reported higher confidence in their ability to manage both a normal and difficult airway (p=0.011 and p=0.003, respectively). Conclusion: Difficult airway training improves Korean paramedic students' performance on simulated airway managenent scenarios

Mycobacterium avium Infection in a C3HeB/FeJ Mouse Model

Infections caused by Mycobacterium avium complex (MAC) species are increasing worldwide, resulting in a serious public health problem. Patients with MAC lung disease face an arduous journey of a prolonged multidrug regimen that is often poorly tolerated and associated with relatively poor outcome. Identification of new animal models that demonstrate a similar pulmonary pathology as humans infected with MAC has the potential to significantly advance our understanding of nontuberculosis mycobacteria (NTM) pathogenesis as well as provide a tractable model for screening candidate compounds for therapy. One new mouse model is the C3HeB/FeJ which is similar to MAC patients in that these mice can form foci of necrosis in granulomas. In this study, we evaluated the ability of C3HeB/FeJ mice exposure to an aerosol infection of a rough strain of MAC 2285 to produce a progressive infection resulting in small necrotic foci during granuloma formation. C3HeB/FeJ mice were infected with MAC and demonstrated a progressive lung infection resulting in an increase in bacterial burden peaking around day 40, developed micronecrosis in granulomas and was associated with increased influx of CD4+ Th1, Th17, and Treg lymphocytes into the lungs. However, during chronic infection around day 50, the bacterial burden plateaued and was associated with the reduced influx of CD4+ Th1, Th17 cells, and increased numbers of Treg lymphocytes and necrotic foci during granuloma formation. These results suggest the C3HeB/FeJ MAC infection mouse model will be an important model to evaluate immune pathogenesis and compound efficacy

Education in adult basic life support training programs

The Panel on Educational Issues in Adult Basic Life Support Training Programs reviewed the characteristics of adult learners, aspects of educational theory, issues concerning barriers to learning and performing CPR, and issues concerning testing and evaluation.The panel made the following recommendations: a comprehensive evaluation of the basic life support program with the goal of improving the program design and educational tools must be initiated; adult programs must be designed to motivate laypersons to become trained in CPR, as well as to target relatives and friends of high-risk individuals; and emotional and attitudinal issues, including the student's reluctance to act in an emergency, must be addressed. Programs must incorporate information on the willingness of an individual to perform CPR; CPR programs must be simplified and focus on critical success factors; flexible educational approaches in programs are encouraged; flexible programming that addresses the needs of the allied health professional is encouraged; formal testing should be eliminated for layperson programs; and formal testing for health care providers and instructors should be continued.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30976/1/0000649.pd

The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

Effect of obesity on biodistribution of nanoparticles

[EN] Nanoparticles have specific features (lipophilicity, surface charge, composition and size). Studies regarding the biological behavior of nanoparticles in diseases such diabetics and obesity are scarce. Here, we evaluated two nanoparticles: magnetic core mesoporous silica (MSN) (58 nm) and polycaprolactone (PCL) nanoparticle (280 nm) in obese mice. Changes in the biodistribution were observed, especially considering the mononuclear phagocyte system (MPS), and the visceral fat tissue. Nonetheless, our data corroborates the influence of size in the biodistribution in obese animals, supporting that smaller nanoparticles, may show a higher tissue deposition at spleen, due the associated splenomegaly and the complications arising from this state. Finally, our study demonstrated that, in obesity, probably due the low-grade inflammatory state associated with metabolic syndrome a difference in accumulation of nanoparticles was found, with profound impact in the tissue deposition of nanoparticles.The authors would like to thank the National Scientific and Technological Research Council (CNPQ) - no. 400018/2016-0 and the Rio de Janeiro State Research Foundation (FAPERJ) - E-26/102.940/2012 for funding. Authors also gratefully acknowledge the financial support from the Ministerio de Economía y Competitividad (Project MAT2012-38429-C04-01) and the Generalitat Valenciana (project PROMETEO/2009/016) for support.Felismino, CDJ.; Helal-Neto, E.; Portilho, F.; Rocha Pinto, S.; Sancenón Galarza, F.; Martínez-Máñez, R.; Ferreira, ADA.... (2018). Effect of obesity on biodistribution of nanoparticles. Journal of Controlled Release. 281:11-18. https://doi.org/10.1016/j.jconrel.2018.05.003S111828

"Spenser's Ireland," December 1941: Scripting a Response

With reference to a vinyl record, some unpublished letters, and a series of reading scripts, this essay reconstructs the circumstances of a trip Marianne Moore made to Harvard in December 1941. Her trip to Cambridge followed closely in the wake of Roosevelt’s declaration of war, such that her reading might be considered a fresh response to the shifty rhetoric of foreign policy and to the plight of her imaginary homeland, Eire, in particular. The essay centers on Moore’s rendering of “Spenser’s Ireland,” a lyric whose complex textual condition congealed in the aftermath of Pearl Harbor into a document thick with questions, jotted afterthoughts, and a longing for political intervention. The essay’s broader purpose is to consider Moore’s revisionary habits as a species of vocal improvisation and so to offer a new angle on her emerging responsibilities as a war poet

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (~3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55–1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60–1.99), NRT gum (OR 1.60, 95% CI, 1.37–1.86) or patch (OR 1.63, 95% CI, 1.41–1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77–2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10–2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72–2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20–6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12–4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65–5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22–2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16–2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17–2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22–2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness