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Background Fine particulate matter (PM 2.5 ) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies. Methods To measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM 2.5 , in the form of concentrated ambient particles (mean: 37.8 μg/m 3 , SD 6.5), and filtered air (mean: 2.1 μg/m 3 , SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure. Results Low-level PM 2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM 2.5 concentration (37.8 μg/m 3 ) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM 2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV 1 ) and FEV 1 / forced vital capacity (FEV 1 /FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM 2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure. Conclusions This study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM 2.5 particles at levels near the PM 2.5 US NAAQS standard. Clinical trial registration information clinicaltrials.gov ; Identifier: NCT03232086 . The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

Trends in climate suggest that extreme weather events such as heat waves will become more common. High levels of the gaseous pollutant ozone are associated with elevated temperatures. Ozone has been associated with respiratory diseases as well as cardiovascular morbidity and mortality and can reduce lung function and alter systemic markers of fibrinolysis. The interaction between ozone and temperature is unclear. Sixteen healthy volunteers were exposed in a randomized crossover study to 0.3 ppm ozone and clean air for 2 hr at moderate (22°C) temperature and again at an elevated temperature (32.5°C). In each case lung function was performed and blood taken before and immediately after exposure and the next morning. Ozone exposure at 22°C resulted in a decrease in markers of fibrinolysis the next day. There was a 51.8% net decrease in PAI-1 (plasminogen activator inhibitor-1), a 12.1% net decrease in plasminogen, and a 17.8% net increase in D-dimer. These significantly differed from the response at 32.5°C, where there was a 44.9% (p = 0.002) and a 27.9% (p = 0.001) increase in PAI-1 and plasminogen, respectively, and a 12.5% (p = 0.042) decrease in D-dimer. In contrast, decrements in lung function following ozone exposure were comparable at both moderate and elevated temperatures (forced expiratory volume in 1 sec, -12.4% vs. -7.5%, p > 0.05). No changes in systemic markers of inflammation were observed for either temperature. Ozone-induced systemic but not respiratory effects varied according to temperature. Our study suggests that at moderate temperature ozone may activate the fibrinolytic pathway, while at elevated temperature ozone may impair it. These findings provide a biological basis for the interaction between temperature and ozone on mortality observed in some epidemiologic studies.

Background In-hospital mortality and discharge disposition following traumatic hip fractures previously reported in the literature, has mainly focused on a nationwide scale, which may not be reflective of unique populations. Objective Our aim was to characterize demographics, hospital disposition, and associated outcomes for patients with the most common hip fractures. Methods A retrospective study utilizing the Trauma Registry from the Texas Department of State Health Services. Patient demographics, injury characteristics, and outcomes, such as in-hospital mortality, and discharge dispositions, were collected. The data were analyzed via univariate analysis and multivariate regressions. Results There were 17,104 included patients, composed of 45% femoral neck fractures (FN) and 55% intertrochanteric fractures (IT). There were no differences in injury severity score (ISS) (9 ± 1.8) or age (77.4 ± 8 years old) between fracture types. In-hospital mortality risk was low but different among fracture types (intertrochanteric, 1.9% vs femoral neck, 1.3%, P = .004). However, when controlling for age, and ISS, intertrochanteric fractures and Hispanic patients were associated with higher mortality (P < .001, OR 1.5, 95% CI 1.1-2.0). Uninsured, and Black/African American (P = .05, OR 1.2, 95% CI 1.1-1.3) and Hispanic (P < .001, OR 1.2, 95% CI 1.1-1.3) patients were more likely to be discharged home after adjusting for age, ISS, and payment method. Conclusion Regardless of age, severity of the injury or admission hemodynamics, intertrochanteric fractures and Hispanic/Latino patients had an increased risk of in-hospital mortality. Patients who were uninsured, Hispanic, or Black were discharged home rather than to rehabilitation, regardless of age, ISS, or payment method.

Exposure to ambient particulate matter (PM) induces endothelial dysfunction, a risk factor for cardiovascular disease. Olive oil (OO) and fish oil (FO) supplements have beneficial effects on endothelial function. In this study we evaluated the potential efficacy of OO and FO in mitigating endothelial dysfunction and disruption of hemostasis caused by exposure to particulate matter (PM). Forty-two participants (58 ± 1 years of age) received either 3 g/day of OO or FO, or no supplements (naive) for 4 weeks prior to undergoing 2-hr exposures to filtered air and concentrated ambient particulate matter (CAP; mean, 253 ± 16 μg/m3). Endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery preexposure, immediately postexposure, and 20 hr postexposure. Levels of endothelin-1 and markers of fibrinolysis and inflammation were also measured. The FMD was significantly lower after CAP exposure in the naive (-19.4%; 95% CI: -36.4, -2.3 per 100 μg/m3 CAP relative to baseline; p = 0.03) and FO groups (-13.7%; 95% CI: -24.5, -2.9; p = 0.01), but not in the OO group (-7.6%; 95% CI: -21.5, 6.3; p = 0.27). Tissue plasminogen activator levels were significantly increased immediately after (11.6%; 95% CI: 0.8, 22.2; p = 0.04) and 20 hr after CAP exposure in the OO group. Endothelin-1 levels were significantly increased 20 hr after CAP exposure in the naive group only (17.1%; 95% CI: 2.2, 32.0; p = 0.03). Short-term exposure to CAP induced vascular endothelial dysfunction. OO supplementation attenuated CAP-induced reduction of FMD and changes in blood markers associated with vasoconstriction and fibrinolysis, suggesting that OO supplementation may be an efficacious intervention to protect against vascular effects of exposure to PM. Tong H, Rappold AG, Caughey M, Hinderliter AL, Bassett M, Montilla T, Case MW, Berntsen J, Bromberg PA, Cascio WE, Diaz-Sanchez D, Devlin RB, Samet JM. 2015. Dietary supplementation with olive oil or fish oil and vascular effects of concentrated ambient particulate matter exposure in human volunteers. Environ Health Perspect 123:1173-1179; http://dx.doi.org/10.1289/ehp.1408988.

To evaluate if income status affects the timing of presentation to orthopaedic care, surgical treatment, or continuity of care following a closed ankle fracture. Th is retrospective study identified 434 patients with closed ankle fractures treated with operative fixation from 2014 to 2016. Median income data were extracted using the patients' ZIP codes and data from the U.S. Census Bureau. Lower-income patients presented to the hospital and received surgical treatment significantly later than others. They were also more often uninsured and nonadherent with postoperative weightbearing precautions. Additionally, these patients less frequently sought care on the day of their injury, and they had both shorter inpatient stays and duration of overall follow-up in comparison with others. Socioeconomic status is a vital consideration for improving patient access to acute orthopaedic surgical care. Lower-income patients are more susceptible to multiple time-sensitive delays in their care, and these patients frequently encounter difficulties maintaining appropriate follow-up carex.

Exposure to low levels of chemicals indoors is often to a mixture of volatile organic compounds (VOCs). It is of interest to determine if the symptomatic and sensory responses can be attributed to a single chemical or to a mixture of chemicals. To determine if sensory or symptomatic responses differ with exposure to single or mixed VOCs, 100 female subjects participated in a 6-hr exposure study. Subjects were exposed to one of six equimolar concentrations equivalent to 24 mg/ m3 toluene, control, m-xylene, n-butyl acetate, m-xylene plus n-butyl acetate, a mixture of 21 chemicals including n-butyl acetate and m-xylene, and to the same mixture of chemicals without n-butyl acetate and m-xylene (19 chemicals). The results indicated that there was no difference in reporting of symptoms or sensory responses between the exposures. When the control group was added, some variables, primarily odor intensity and nasal irritation, attained significance.

New Media and Digital Pedagogy: Enhancing the Twenty-First-Century Classroom addresses the influence of new media on instruction, higher education, and pedagogy.The contributors specifically examine the practical and theoretical implications of new media and the influence of new media on education.

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P  =  1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains conserved among influenza subtypes. We conducted a first-in-human, randomized, open-label, phase 1 clinical trial ( NCT03186781 ) to evaluate a novel ferritin (H2HA-Ferritin) nanoparticle influenza vaccine platform. The H2 subtype has not circulated in humans since 1968. Adults born after 1968 have been exposed to only the H1 subtype of group 1 influenza viruses, which shares a conserved stem with H2. Including both H2-naive and H2-exposed adults in the trial allowed us to evaluate memory responses against the conserved stem domain in the presence or absence of pre-existing responses against the immunodominant HA head domain. Fifty healthy participants 18–70 years of age received H2HA-Ferritin intramuscularly as a single 20-μg dose ( n  = 5) or a 60-μg dose either twice in a homologous ( n  = 25) prime-boost regimen or once in a heterologous ( n  = 20) prime-boost regimen after a matched H2 DNA vaccine prime. The primary objective of this trial was to evaluate the safety and tolerability of H2HA-Ferritin either alone or in prime-boost regimens. The secondary objective was to evaluate antibody responses after vaccination. Both vaccines were safe and well tolerated, with the most common solicited symptom being mild headache after both H2HA-Ferritin ( n  = 15, 22%) and H2 DNA ( n  = 5, 25%). Exploratory analyses identified neutralizing antibody responses elicited by the H2HA-Ferritin vaccine in both H2-naive and H2-exposed populations. Furthermore, broadly neutralizing antibody responses against group 1 influenza viruses, including both seasonal H1 and avian H5 subtypes, were induced in the H2-naive population through targeting the HA stem. This ferritin nanoparticle vaccine technology represents a novel, safe and immunogenic platform with potential application for pandemic preparedness and universal influenza vaccine development. First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

β-Turns are common conformations that enable proteins to adopt globular structures, and their formation is often rate limiting for folding. β-Turn mimics, molecules that replace the i + 1 and i + 2 amino acid residues of a β-turn, are envisioned to act as folding nucleators by preorganizing the pendant polypeptide chains, thereby lowering the activation barrier for β-sheet formation. However, the crucial kinetic experiments to demonstrate that β-turn mimics can act as strong nucleators in the context of a cooperatively folding protein have not been reported. We have incorporated 6 β-turn mimics simulating varied β-turn types in place of 2 residues in an engineered β-turn 1 or β-bulge turn 1 of the Pin 1 WW domain, a three-stranded β-sheet protein. We present 2 lines of kinetic evidence that the inclusion of β-turn mimics alters β-sheet folding rates, enabling us to classify β-turn mimics into 3 categories: those that are weak nucleators but permit Pin WW folding, native-like nucleators, and strong nucleators. Strong nucleators accelerate folding relative to WW domains incorporating all α-amino acid sequences. A solution NMR structure reveals that the native Pin WW β-sheet structure is retained upon incorporating a strong E-olefin nucleator. These β-turn mimics can now be used to interrogate protein folding transition state structures and the 2 kinetic analyses presented can be used to assess the nucleation capacity of other β-turn mimics.