Long-Term Efficacy and Safety of RNAi-Mediated Virus Resistance in ‘HoneySweet’ Plum

Interfering RNA technology has been established as an effective strategy to protect plants against viral infection. Despite this success, interfering RNA (RNAi) has rarely been applied due to the regulatory barriers that confront genetically engineered plants and concerns over possible environmental and health risks posed by non-endogenous small RNAs. ‘HoneySweet’ was developed as a virus-resistant plum variety that is protected by an RNAi-mediated process against Sharka disease caused by the plum pox virus. ‘HoneySweet’ has been approved for cultivation in the United States but not in countries where the plum pox virus is endemic. In this study, we evaluated the long-term efficacy of virus resistance in ‘HoneySweet,’ the nature and stability of its sRNA profile, and the potential health risks of consuming ‘HoneySweet’ plums. Graft-challenged ‘HoneySweet’ trees carrying large non-transgenic infected limbs remained virus-free after more than 10 years in the field, and the viral sequences from the non-transgenic infected limbs showed no evidence of adaptation to the RNAi-based resistance. Small RNA profiling revealed that transgene-derived sRNA levels were stable across different environments and, on average, were more than 10 times lower than those present in symptom-less fruits from virus-infected trees. Comprehensive 90-day mouse feeding studies showed no adverse health impacts in mice, and there was no evidence for potential siRNA off-target pathologies predicted by comparisons of the most abundant transgene-derived sRNAs to the mouse genome. Collectively, the data confirmed that RNAi provides a highly effective, stable, and safe strategy to combat virus diseases in crop plants.

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Long-term concentrations of airborne cadmium in metropolitan cities in Korea and potential health risks

Atmospheric Environment ◽

10.1016/j.atmosenv.2011.11.019 ◽

2012 ◽

Vol 47 ◽

pp. 164-173 ◽

Cited By ~ 16

Author(s):

Atilla Mutlu ◽

Byeong-Kyu Lee ◽

Gee-Hyeong Park ◽

Bong-Gwan Yu ◽

Chi-Hyeon Lee

Keyword(s):

Health Risks ◽

Potential Health ◽

Metropolitan Cities

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Cancer potencies and margin of exposure used for comparative risk assessment of heated tobacco products and electronic cigarettes aerosols with cigarette smoke

Archives of Toxicology ◽

10.1007/s00204-020-02924-x ◽

2020 ◽

Author(s):

Gregory Rodrigo ◽

Guy Jaccard ◽

Donatien Tafin Djoko ◽

Alexandra Korneliou ◽

Marco Esposito ◽

...

Keyword(s):

Cancer Risk ◽

Health Risks ◽

Electronic Cigarettes ◽

Epidemiological Data ◽

Cancer Risks ◽

Predictive Tool ◽

Potential Health ◽

Tobacco Products ◽

Margin Of Exposure

Abstract Health risk associated with the use of combustible cigarettes is well characterized and numerous epidemiological studies have been published for many years. Since more than a decade, innovative non-combusted tobacco products have emerged like heated tobacco products (HTP) or electronic cigarettes (EC). Long-term effects of these new products on health remain, however, unknown and there is a need to characterize associated potential health risks. The time dedicated to epidemiological data generation (at least 20 to 40 years for cancer endpoint), though, is not compatible with innovative development. Surrogates need, therefore, to be developed. In this work, non-cancer and cancer risks were estimated in a range of HTP and commercial combustible cigarettes based upon their harmful and potentially harmful constituent yields in aerosols and smoke, respectively. It appears that mean lifetime cancer risk values were decreased by more than one order of magnitude when comparing HTPs and commercial cigarettes, and significantly higher margin of exposure for non-cancer risk was observed for HTPs when compared to commercial cigarettes. The same approach was applied to two commercial ECs. Similar results were also found for this category of products. Despite uncertainties related to the factors used for the calculations and methodological limitations, this approach is valuable to estimate health risks associated to the use of innovative products. Moreover, it acts as predictive tool in absence of long-term epidemiological data. Furthermore, both cancer and non-cancer risks estimated for HTPs and ECs highlight the potential of reduced risk for non-combusted products when compared to cigarette smoking.

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Long-Term Efficacy and Safety of Hizentra® in Patients with Primary Immunodeficiency in Japan, Europe, and the United States: a Review of 7 Phase 3 Trials

Journal of Clinical Immunology ◽

10.1007/s10875-018-0560-5 ◽

2018 ◽

Vol 38 (8) ◽

pp. 864-875 ◽

Cited By ~ 6

Author(s):

Stephen Jolles ◽

Mikhail A. Rojavin ◽

John-Philip Lawo ◽

Robert Nelson ◽

Richard L. Wasserman ◽

...

Keyword(s):

United States ◽

Primary Immunodeficiency ◽

The United States ◽

Efficacy And Safety ◽

Phase 3 ◽

Term Efficacy

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Exploring perceptions of fracking and environmental health in a 3-county population in South Texas

Journal of Epidemiological Research ◽

10.5430/jer.v3n1p61 ◽

2017 ◽

Vol 3 (1) ◽

pp. 61 ◽

Cited By ~ 4

Author(s):

Kristina W. Whitworth ◽

Elisabeth De LaRosa ◽

Taylor Mackay ◽

Ashley Hernandez ◽

Mary K. Martin ◽

...

Keyword(s):

Health Literacy ◽

Environmental Health ◽

Health Risks ◽

The United States ◽

South Texas ◽

Convenience Sample ◽

Potential Health ◽

Limited Knowledge ◽

Gas Drilling ◽

Environmental Health Risks

Introduction: The past decade in the United States has been marked by an unprecedented expansion of unconventional oil and gas drilling, including hydraulic fracturing (i.e., fracking). Concerns have arisen regarding potential health and environmental risks associated with the use of the fracking process. The purpose of this exploratory study was to examine community perceptions, concerns, and knowledge of environmental health issues related to fracking in three Texas counties near one of the most active shale plays in South Texas, the Eagle Ford Shale.Methods: A convenience sample of 153 adults over the age of 18 years in three rural South Texas counties completed a 46-question survey. Demographic information, perceptions of environmental health risks, and knowledge of potential environmental health effects related to fracking were obtained. A validated health literacy measure was also used to assess participants’ health literacy.Results: Participants were predominantly female (61%), white (75%), and Hispanic (62%). A majority owned land (53.6%) and had lived in their respective county for over 21 years (54%). Only 32% percent of participants had marginal or inadequate health literacy though a larger percentage of participants had limited knowledge of potential environmental health risks related to fracking.Conclusions: Approximately one third of participants had less than adequate health literacy as measured by the BRIEF. A high percentage of the population demonstrated limited knowledge regarding the potential environmental health impacts of fracking, suggesting limited environmental health literacy. Findings point to the need for environmental health specific assessments and focused environmental health promotion strategies.

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Assessing potential health risks to fish and humans using mercury concentrations in inland fish from across western Canada and the United States

The Science of The Total Environment ◽

10.1016/j.scitotenv.2016.03.031 ◽

2016 ◽

Vol 571 ◽

pp. 342-354 ◽

Cited By ~ 17

Author(s):

Jesse M. Lepak ◽

Mevin B. Hooten ◽

Collin A. Eagles-Smith ◽

Michael T. Tate ◽

Michelle A. Lutz ◽

...

Keyword(s):

United States ◽

Health Risks ◽

The United States ◽

Western Canada ◽

Potential Health

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Short interfering RNAs are Associated with Virus Resistance in a Woody Perennial Fruit Tree (Prunus domestica)

HortScience ◽

10.21273/hortsci.39.4.862d ◽

2004 ◽

Vol 39 (4) ◽

pp. 862D-862

Author(s):

Jean-Michel Hily ◽

Ralph Scorza* ◽

Michel Ravelonandro

Keyword(s):

Virus Resistance ◽

Rna Silencing ◽

Transcriptional Gene Silencing ◽

Marker Genes ◽

Plum Pox Virus ◽

Woody Perennials ◽

Woody Perennial ◽

Post Transcriptional Gene Silencing ◽

High Level ◽

Interfering Rna

We have shown that high-level resistance to plum pox virus (PPV) in transgenic plum clone C5 is based on post-transcriptional gene silencing (PTGS), otherwise termed RNA silencing (Scorza et al. Transgenic Res. 10:201-209, 2001). In order to more fully characterize RNA silencing in woody perennial crops, we investigated the production of short interfering RNA (siRNA) in transgenic plum clones C3 and C5, both of which harbor the capsid protein (CP) gene of PPV. We used as a control, plum PT-23, a clone only transformed with the two marker genes, NPTII and GUS. We show in the current report that C5 constitutively produces two classes of siRNA, the short (21-22 nucleotides) and long (≈27 nucleotides) species in the absence of PPV inoculation. Transgenic susceptible clone C3 and the control clone PT-23, when healthy, produce no siRNA. Upon infection, these clones produce only the short siRNA (21-22 nt). This siRNA production suggests that plum trees naturally respond to virus infection by initiating PTGS or PTGS-like mechanisms. This study also suggests that high-level virus resistance in woody perennials may require the production of both the short and long size classes of siRNA, as are produced by the resistant C5 plum clone.

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The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys-The Future Is Now?

Journal of Clinical Medicine ◽

10.3390/jcm8030407 ◽

2019 ◽

Vol 8 (3) ◽

pp. 407 ◽

Cited By ~ 7

Author(s):

Vedran Stefanovic

Keyword(s):

Complement Activation ◽

Atypical Hemolytic Uremic Syndrome ◽

The United States ◽

Adverse Outcomes ◽

European Medicines Agency ◽

United States Food ◽

Uremic Syndrome ◽

Number Of Publications ◽

Interfering Rna

Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring.

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Analysis of Heavy Metals in Foodstuffs and an Assessment of the Health Risks to the General Public via Consumption in Beijing, China

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16060909 ◽

2019 ◽

Vol 16 (6) ◽

pp. 909 ◽

Cited By ~ 15

Author(s):

Gang Liang ◽

Wenwen Gong ◽

Bingru Li ◽

Jimin Zuo ◽

Ligang Pan ◽

...

Keyword(s):

Heavy Metals ◽

Health Risks ◽

Toxic Metals ◽

Local Population ◽

The United States ◽

World Health ◽

Potential Health ◽

Metal Levels ◽

Local Residents ◽

Beijing China

Consumption of foodstuffs is the most likely route for human exposure to heavy metals. This study was designed to investigate the toxic metals (cadmium (Cd), lead (Pb), chromium (Cr), arsenic (As), and mercury (Hg)) concentrations in different foodstuffs (cereals, vegetables, fruits, fish, and meat) and then estimate the potential health risks of toxic metals via consumption to the local residents in Beijing, China. Most of the selected toxic metal levels in the foodstuffs were lower than the maximum allowable concentrations of Pb, Cr, Cd, As, and Hg for Chinese foodstuffs recommended in the China National Food Safety Standard. The health risks associated with the toxic metals Pb, Cr, Cd, As, and Hg were assessed based on the target hazard quotients (THQs) proposed by the United States Environmental Protection Agency (US EPA). The THQ values of the foodstuffs varied and were 0.03–0.29 for Cr, 0.02–0.23 for Pb, 0.01–0.33 for Cd, 0.01–0.06 for As, and 0.00–0.04 for Hg, not exceeding the maximum level of 1. The total THQ (TTHQ) values were 0.88 for vegetables, 0.57 for cereals, 0.46 for meat, 0.32 for fish, and 0.07 for fruits. This indicates that the risk contribution from vegetable intake (38.8%) was significant in comparison to that from other foodstuffs. The TTHQ values were 0.96 for Cr, 0.54 for Pb, 0.50 for Cd, 0.19 for As, and 0.09 for Hg, suggesting that Cr was a major risk contributor (41.7%) for the local residents of Beijing, which should attract great attention. However, the THQ/TTHQ values were all below 1, suggesting no health risks to the local population through consumption. Furthermore, dietary weekly intakes (WIs) were also calculated and the values were all lower than the proposed limit of Provisional Tolerable Weekly Intakes (PTWI) established by the the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). This suggests no additional health risks as well as consistency with the THQ results.

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