Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

Background: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro–ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.<p></p> Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.<p></p> Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.<p></p> Results: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.<p></p> Conclusions: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting

Alcohol Consumption is associated with Increased CEA Levels in Male Patients with Stage IV Colorectal Cancer- A Single-Institution Retrospective Analysis

Introduction: Alcohol use is an independent risk factor for liver metastasis, a major cause of morbidity and mortality in colorectal cancer (CRC) patients. Serum CEA level is an established prognostic indicator in CRC, yet the correlation with behavioral factors such as alcohol use remains to be defined. In a single-center review, we evaluated alcohol use, gender, and CEA levels in predicting advanced disease in CRC patients. Methods: Retrospective analysis of UNMC patients diagnosed with CRC as the primary cancer between 2012-2019, stages I-IV, and age \u3e19 with documentation of alcohol use. Univariable statistics were performed using Chi-Square and non-parametric tests. Associations between stage, gender, and alcohol use (some vs. none) and the log-transformed CEA outcome (either initial or rate of change) were assessed using linear regressions. Results: Alcohol use was found to be reported in 333 of 1243 CRC patients. The cohort was comprised of 192 male and 141 female subjects. Elevated CEA levels at CRC diagnosis were associated with increased all-cause mortality (33.0% for CEA \u3e 3.4ng/ml vs 10.4% for CEA \u3c 3.4ng/ml). Model analysis found that stage IV male alcohol users showed an increase in serial CEA levels compared to males who did not use alcohol, but this pattern was not observed among stage IV females. Conclusions: Males with a history of alcohol use may be at risk for advanced CRC disease suggesting the utility of serial serum CEA monitoring in these patients. A detailed alcohol use history should be obtained in all patients with CRC as it has prognostic value and may allow for early intervention. This analysis was limited by missing alcohol use data for the majority (73.2%) of CRC patients evaluated. A prospective study is warranted to define the implications of alcohol use and risk of CRC liver metastasis

An Electrochemical Study of Frustrated Lewis Pairs: A Metal-free Route to Hydrogen Oxidation

[Image: see text] Frustrated Lewis pairs have found many applications in the heterolytic activation of H(2) and subsequent hydrogenation of small molecules through delivery of the resulting proton and hydride equivalents. Herein, we describe how H(2) can be preactivated using classical frustrated Lewis pair chemistry and combined with in situ nonaqueous electrochemical oxidation of the resulting borohydride. Our approach allows hydrogen to be cleanly converted into two protons and two electrons in situ, and reduces the potential (the required energetic driving force) for nonaqueous H(2) oxidation by 610 mV (117.7 kJ mol(–1)). This significant energy reduction opens routes to the development of nonaqueous hydrogen energy technology

Relationship of homestead food production with night blindness among children below 5 years of age in Bangladesh

Abstract Objective To examine the relationship between homestead food production and night blindness among pre-school children in rural Bangladesh in the presence of a national vitamin A supplementation programme. Design A cross-sectional study. Setting A population-based sample of six rural divisions of Bangladesh assessed in the Bangladesh Nutrition Surveillance Project 2001-2005. Subjects A total of 158 898 children aged 12-59 months. Results The prevalence rates of night blindness in children among those who did and did not receive vitamin A capsules in the last 6 months were 0·07 % and 0·13 %, respectively. Given the known effect of vitamin A supplementation on night blindness, the analysis was stratified by children's receipt of vitamin A capsules in the last 6 months. Among children who did not receive vitamin A capsules in the last 6 months, the lack of a home garden was associated with increased odds of night blindness (OR = 3·16, 95 % CI 1·76, 5·68; P = 0·0001). Among children who received vitamin A capsules in the last 6 months, the lack of a home garden was not associated with night blindness (OR = 1·28, 95 % CI 0·71, 2·31; P = 0·4). Conclusions Homestead food production confers a protective effect against night blindness among pre-school children who missed vitamin A supplementation in rural Banglades

Gattini 2010: Cutting Edge Science at the Bottom of the World

The high altitude Antarctic sites of Dome A and the South Pole offer intriguing locations for future large scale optical astronomical Observatories. The Gattini project was created to measure the optical sky brightness, large area cloud cover and aurora of the winter-time sky above such high altitude Antarctic sites. The Gattini-DomeA camera was installed on the PLATO instrument module as part of the Chinese-led traverse to the highest point on the Antarctic plateau in January 2008. This single automated wide field camera contains a suite of Bessel photometric filters (B, V, R) and a long-pass red filter for the detection and monitoring of OH emission. We have in hand one complete winter-time dataset (2009) from the camera that was recently returned in April 2010. The Gattini-South Pole UV camera is a wide-field optical camera that in 2011 will measure for the first time the UV properties of the winter-time sky above the South Pole dark sector. This unique dataset will consist of frequent images taken in both broadband U and B filters in addition to high resolution (R similar to 5000) long slit spectroscopy over a narrow bandwidth of the central field. The camera is a proof of concept for the 2m-class Antarctic Cosmic Web Imager telescope, a dedicated experiment to directly detect and map the redshifted lyman alpha fluorescence or Cosmic Web emission we believe possible due to the unique geographical qualities of the site. We present the current status of both projects

Chemical characteristics of air from differing source regions during the Pacific Exploratory Mission‐Tropics A (PEM‐Tropics A)

Ten‐day backward trajectories are used to determine the origins of air parcels arriving at airborne DC‐8 chemical measurement sites during NASA\u27s Pacific Exploratory Mission‐Tropics A (PEM‐T) that was conducted during August‐October 1996. Those sites at which the air had a common geographical origin and transport history are grouped together, and statistical measures of chemical characteristics are computed. Temporal changes in potential temperature are used to determine whether trajectories experience a significant convective influence during the 10‐day period. Those trajectories that do not experience a significant convective influence are divided into four geographical categories depending on their origins and paths. Air parcels originating over Africa and South America are characterized by enhanced mixing ratios of O3, CO, HNO3, and PAN. The backward trajectories travel at high altitudes (∼10–11 km), covering long distances due to strong upper‐tropospheric westerly winds. The observed enhancement of combustion‐related species is attributed to biomass burning from distant sources to the west, extending even to South America. The relatively large value of Be‐7 probably is due either to less efficient removal of aerosols from upper tropospheric air or to small stratospheric contributions. Aged marine parcels are found to have relatively small concentrations of burning‐related species. Although these trajectories arrive at a wide range of aircraft altitudes, they do not pass over a land mass during the preceding 10‐day period. Air passing over Australia but no other land mass exhibits a combustion signature; however, photochemical product species such as O3 and PAN are less enhanced than in the long‐range transport category. These trajectories travel shorter distances and are at lower altitudes (∼5–8 km) than those reaching Africa and/or South America. The combustion influence on these parcels is attributed to biomass burning emissions injected over Australia. That burning is less widespread than in Africa and South America. Finally, trajectories originating over Southeast Asia appear to receive a weak combustion influence. However, compared to Africa and South America, Southeast Asia has a relatively small incidence of biomass burning. There is little combustion input from Australia due to the high transport altitudes compared to the lower heights of the convection. The Southeast Asian parcels exhibit the greatest NOx to ∑NOi ratio of any category, perhaps due to lightning. Parcels experiencing a significant convective influence also are examined. Most of these parcels pass through widespread, persistent convection along either the South Pacific Convergence Zone or Intertropical Convergence Zone approximately 5 days prior to arriving at the aircraft locations. Thus the category mostly represents marine convection. Mixing ratios of peroxides and acids in the convective category are found to be smaller than in parcels not experiencing convection. Small mixing ratios of Be‐7 and Pb‐210 suggest particle removal by precipitation

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR